阅读说明：本技术 制备聚合物胶囊的方法 (Method for preparing polymer capsules ) 是由 劳尔·罗德里戈-戈麦斯 特奥多尔·贝雷斯库博戈莫洛夫 于 2020-04-17 设计创作，主要内容包括：本发明提供了一种用于制备具有被聚合物壳包围的芯的胶囊的方法,该方法可包括：通过使分散相通过膜中的多个孔从该膜的第一侧到该膜的第二侧并进入连续相来将该分散相的小滴分散在该连续相中,同时使该连续相流过膜的第二侧并且机械地移动膜。该分散相可包含聚合物前体、抗溶剂和有益剂,并且该连续相包含水。该方法还可包括在足以引发该聚合物前体在该分散相的小滴内聚合的条件下将该分散相的小滴的分散体掺混在该连续相中,以及使该聚合物前体聚合以形成该壳。(The present invention provides a method for preparing a capsule having a core surrounded by a polymeric shell, which may comprise: dispersing droplets of the dispersed phase in the continuous phase by passing the dispersed phase through a plurality of pores in the film from the first side of the film to the second side of the film and into the continuous phase while flowing the continuous phase through the second side of the film and mechanically moving the film. The dispersed phase may comprise a polymer precursor, an anti-solvent, and a benefit agent, and the continuous phase comprises water. The method can also include blending a dispersion of droplets of the dispersed phase in the continuous phase under conditions sufficient to initiate polymerization of the polymer precursor within the droplets of the dispersed phase, and polymerizing the polymer precursor to form the shell.)

1. A method of making a capsule comprising a core surrounded by a polymeric shell, the method comprising:

dispersing droplets of a dispersed phase in a continuous phase by passing the dispersed phase through a plurality of pores in a film from a first side of the film to a second side of the film and into the continuous phase while flowing the continuous phase through the second side of the film and mechanically moving the film, wherein the dispersed phase comprises a polymer precursor and a benefit agent and the continuous phase comprises water and the dispersed phase forms as droplets of the dispersed phase upon exiting the plurality of pores on the second side of the film; and

exposing a dispersion of the droplets of the dispersed phase in the continuous phase to conditions sufficient to initiate polymerization of the polymer precursor within the droplets of the dispersed phase, wherein the polymer precursor becomes insoluble in the dispersed phase and migrates to an interface between the dispersed phase and the continuous phase, wherein:

the benefit agent remains in the core after polymerization,

a stabilizer system is present in at least one of the dispersed phase or the continuous phase,

at least one of the dispersed phase or the continuous phase comprises an initiator, and

the polymer precursor is soluble in the dispersed phase and comprises at least one multifunctional ethylenically unsaturated monomer.

2. The method of claim 1, wherein the at least one multifunctional ethylenically unsaturated monomer has at least three functional groups.

3. The method of claim 1, wherein the at least one multifunctional ethylenically unsaturated monomer is a multifunctional ethylenically unsaturated (meth) acrylate monomer.

4. The method of claim 3, wherein the at least one multifunctional ethylenically unsaturated (meth) acrylate monomer has at least three functional groups.

5. The method of any one of claims 1 to 4, wherein the polymer precursor comprises a combination of ethylenically unsaturated monomers.

6. The method of any one of claims 1 to 5, wherein the polymer precursor comprises a combination of one or more ethylenically unsaturated monomers and one or more ethylenically unsaturated monomers comprising one or more other functional groups selected from the group consisting of amines, amides, alcohols, thiols, sulfonic acids, and carboxylic acids.

7. The method of any one of claims 1 to 6, wherein the polymer precursor is a hexafunctional aromatic urethane acrylate.

8. The method of any preceding claim, wherein the stabilizer system comprises a primary stabilizer present in the continuous phase.

9. The method of claim 8, wherein the primary stabilizer is present in an amount of from about 51 wt% to about 100 wt%, based on the total weight of the stabilizer system.

10. The method of claim 8 or 9, wherein the primary stabilizer comprises an amphiphilic nonionic stabilizer that is soluble or dispersible in the continuous phase.

11. The method of claim 10, wherein the primary stabilizer is one or more of the following: polysaccharides, pyrrolidone-based polymers, natural source gums, polyalkylene glycol ethers; alkyl phenols, aliphatic alcohols, condensation products of fatty acids and alkylene oxides, ethoxylated alkyl phenols, ethoxylated aryl phenols, ethoxylated polyaryl phenols, carboxylic esters solubilized with polyols, polyvinyl alcohols, polyvinyl acetates, copolymers of polyvinyl alcohol and polyvinyl acetate, polyacrylamides, poly (N-isopropylacrylamide), poly (hydroxypropyl 2-methacrylate), poly (2-ethyl-2-oxazoline), polyalkyleneimines, poly (2-isopropenyl-2-oxazoline-co-methyl methacrylate), poly (methyl vinyl ether), polyvinyl alcohol-co-ethylene, and acetate modified polyvinyl alcohols.

12. The method of claim 11, wherein the primary stabilizer is a polyvinyl alcohol having a degree of hydrolysis of less than 95%.

13. The method of any one of claims 8 to 12, wherein the stabilizer system further comprises a trace amount of a protective colloid present in the continuous phase, wherein the trace amount of protective colloid comprises one or more of a low molecular weight nonionic surfactant, a cationic stabilizer, and an anionic stabilizer.

14. The method of any preceding claim, wherein the benefit agent comprises one or more of: perfume compositions, perfume raw materials, sanitizers, disinfectants, antiviral agents, fabric fresheners and freshness maintenance agents, chlorine bleach odor control agents, dye fixatives, dyes, optical brighteners, color restoration/restoration agents, enzymes, defoamers, fabric comfort agents, skin care agents, lubricants, waxes, hydrocarbons, malodor reduction agents, odor control materials, fertilizers, nutrients, and herbicides.

15. The method according to claim 14, wherein the benefit agent comprises a perfume composition, preferably wherein the perfume composition comprises a combination of perfume raw materials comprising by weight based on the total weight of the perfume composition: (1) from about 2.5% to about 30% of a first perfume raw material characterized by a logP of less than 3.0 and a boiling point of less than 250 ℃; (2) from about 5% to about 30% of a second perfume raw material characterized by a logP of less than or equal to 3.0 and a boiling point of greater than or equal to 250 ℃; (3) from about 35% to about 60% of a third perfume raw material characterized by having a logP greater than 3.0 and a boiling point less than 250 ℃; and (4) from about 10% to about 45% of a fourth perfume raw material characterized by having a logP greater than 3.0 and a boiling point greater than 250 ℃.

Technical Field

The present disclosure relates to capsules for the transfer and triggered release of beneficial agents and methods of making the same, and more particularly to capsules having narrow capsule sizes and/or burst strength distributions.

Background

Encapsulation is a process of encapsulating a liquid droplet, solid particle, or gas within a solid shell. The core material is then mechanically separated from the surrounding environment (Jyothi et al, Journal of Microencapsis, 2010,27, 187-. Encapsulation technology has received attention from various scientific fields and has found widespread commercial use in various industries. In general, the capsule is capable of one or more of the following: (i) providing stability of the formulation or material by mechanical separation of incompatible components, (ii) protecting the core material from the surrounding environment, (iii) masking or hiding undesirable properties of the active ingredient, (iv) controlling or triggering the release of the active ingredient at a specific time or to a specific location. All of these attributes may allow for increased shelf life of various products and stabilization of active ingredients in liquid formulations, as well as customized delivery of encapsulated formulations, which may improve efficacy and/or efficiency.

Encapsulation can be found in areas such as medicine, personal care, textiles, food, coatings, fabric care, home care, construction, and agriculture. In addition, the main challenge facing the practical commercial application of encapsulation technology is the need to retain the encapsulated active completely within the capsule throughout the supply chain until controlled or triggered release of the core material is applied (Thompson et al, Journal of Colloid and Interface Science,2015,447, 217-228).

Disclosure of Invention

According to an embodiment, a method of making a capsule comprising a core surrounded by a polymeric shell may comprise: the droplets of the dispersed phase are dispersed in the continuous phase by passing the dispersed phase through a plurality of pores in the film from the first side of the film to the second side of the film and into the continuous phase while flowing the continuous phase through the second side of the film and mechanically moving the film. The dispersed phase may comprise a polymer precursor, a processing aid, and a benefit agent, and the continuous phase comprises water. In this method, the dispersed phase is formed as droplets of the dispersed phase upon exiting the plurality of pores on the second side of the film. The method can further include exposing the dispersion of droplets of the dispersed phase to the continuous phase under conditions sufficient to initiate polymerization of the polymer precursor within the droplets of the dispersed phase. The polymer precursor becomes insoluble in the dispersed phase and migrates to the interface between the dispersed phase and the continuous phase, while the benefit agent remains in the core after polymerization. In embodiments, the stabilizer system is present in at least one of the dispersed phase and the continuous phase, at least one of the dispersed phase and the continuous phase comprising an initiator. In embodiments, the polymer precursor is soluble in the dispersed phase and comprises a multifunctional ethylenically unsaturated monomer.

According to embodiments, the population of capsules may comprise a plurality of capsules, each capsule may comprise a core comprising a benefit agent and a polymeric shell surrounding the core. The population of capsules can have a percent delta burst strength of about 15% to about 230% and a shell thickness of 20nm to 400 nm.

According to embodiments, the population of capsules may comprise a plurality of capsules, each capsule may comprise a core comprising a benefit agent and a polymeric shell surrounding the core. The population of capsules may have a number population diameter coefficient of variation of 10% to 100% and the capsules have an average shell thickness of 20nm to 400 nm.

According to embodiments, one or more capsules may comprise a core comprising a benefit agent, and a polymeric shell surrounding the core. In embodiments, the capsules may have an average weight core to shell ratio of greater than about 90: 10. In embodiments, the capsules may have an average weight core to shell ratio of about 95: 5. In embodiments, the capsules may have an average effective volume core-shell ratio of greater than about 90: 10. In embodiments, the capsules may have an average effective volume core-shell ratio of greater than about 95: 5.

Drawings

While the specification concludes with claims particularly pointing out and distinctly claiming the subject matter presented herein, it is believed that the disclosure herein will be more fully understood from the following description taken in conjunction with the accompanying drawings. Some of these figures may have been simplified by the omission of selected elements in order to more clearly show other elements. Such omissions of elements in certain figures do not necessarily indicate the presence or absence of particular elements in any of the exemplary embodiments, unless explicitly stated to the contrary in the corresponding written description. The figures are not drawn to scale.

Fig. 1 is a schematic illustration of an embodiment of a cylindrical membrane device for use in a process according to an embodiment of the present disclosure;

FIG. 2 is a schematic illustration of a membrane having a plurality of pores in the membrane for use in a method according to an embodiment of the present disclosure;

fig. 3A is a photograph of a membrane having a plurality of pores in the membrane for use in a method according to an embodiment of the present disclosure;

FIG. 3B is an enlarged photograph of the film of FIG. 3A;

fig. 4A is an optical microscope image of a population of capsules according to an embodiment of the present disclosure;

fig. 4B is an optical microscope image of a population of capsules according to an embodiment of the present disclosure;

fig. 5A is a cryo-scanning electron microscope image of a capsule according to an embodiment of the present disclosure, showing the capsule having a diameter of 24.2 μm (white arrows indicate the two end points of the diameter measurement);

FIG. 5B is a cryo-scanning electron microscope image of the capsule of FIG. 5A showing the capsule's shell thickness at 218nm (white arrows indicate the two end points of the shell thickness measurement);

fig. 6A is a cryo-scanning electron microscope image of a capsule according to an embodiment of the present disclosure, showing the capsule diameter of 17.6 μm (white arrows indicate the two end points of the diameter measurement);

FIG. 6B is a cryo-scanning electron microscope image of the capsule of FIG. 6A showing the capsule's shell thickness of 169nm (white arrows indicate the two end points of the shell thickness measurement);

fig. 7A is a cryo-scanning electron microscope image of a capsule according to an embodiment of the present disclosure, showing the capsule having a diameter of 22.3 μm (white arrows indicate the two end points of the diameter measurement);

FIG. 7B is a cryo-scanning electron microscope image of the capsule of FIG. 7A showing the capsule's shell thickness of 150nm (white arrows indicate the two end points of the shell thickness measurement);

fig. 8A is a cryo-scanning electron microscope image of a capsule according to an embodiment of the present disclosure, showing the capsule having a diameter of 27.1 μm (white arrows indicate the two end points of the diameter measurement);

FIG. 8B is a cryo-scanning electron microscope image of the capsule of FIG. 8A showing the capsule's shell thickness of 161nm (white arrows indicate the two end points of the shell thickness measurement);

fig. 9A is a cryo-scanning electron microscope image of a capsule according to an embodiment of the present disclosure, showing the capsule diameter at 23.8 μm (white arrows indicate the two end points of the diameter measurement);

FIG. 9B is a cryo-scanning electron microscope image of the capsule of FIG. 9A showing the capsule's shell thickness of 186nm (white arrows indicate the two end points of the shell thickness measurement);

fig. 10A is a cryo-scanning electron microscope image of a capsule according to an embodiment of the present disclosure, showing the capsule having a diameter of 12.4 μm (white arrows indicate the two end points of the diameter measurement);

FIG. 10B is a cryo-scanning electron microscope image of the capsule of FIG. 10A showing the capsule's shell thickness of 185nm (white arrows indicate the two end points of the shell thickness measurement);

fig. 11A is a comparative example of an optical microscope image of a population of capsules not according to an embodiment of the present disclosure;

fig. 11B is a comparative example of an optical microscope image of a population of capsules not according to an embodiment of the present disclosure;

fig. 12A is a cryo-scanning electron microscope image of capsules prepared according to a conventional batch process as described in the comparative example, showing the capsule diameter of 4.58 μm (white arrows indicate the two end points of the diameter measurement);

FIG. 12B is a cryo-scanning electron microscope image of the capsule of FIG. 12A showing the capsule's shell thickness of 86.8nm (white arrows indicate the two end points of the shell thickness measurement);

fig. 13A is a cryo-scanning electron microscope image of capsules prepared by conventional batch processing according to a comparative example, showing that the diameter of the capsules is 7.40 μm (white arrows indicate both end points of the diameter measurement);

FIG. 13B is a cryo-scanning electron microscope image of the capsule of FIG. 13A showing the capsule's shell thickness of 123nm (white arrows indicate the two end points of the shell thickness measurement);

fig. 14A is a cryo-scanning electron microscope image of capsules prepared by conventional batch processing according to a comparative example, showing that the diameter of the capsules is 20.3 μm (white arrows indicate both end points of the diameter measurement);

FIG. 14B is a cryo-scanning electron microscope image of the capsule of FIG. 14A showing the capsule's shell thickness of 131nm (white arrows indicate the two end points of the shell thickness measurement);

fig. 15A is a cryo-scanning electron microscope image of capsules prepared by conventional batch processing according to a comparative example, showing that the diameter of the capsules is 27.5 μm (white arrows indicate both end points of the diameter measurement);

FIG. 15B is a cryo-scanning electron microscope image of the capsule of FIG. 15A showing the capsule's shell thickness of 123nm (white arrows indicate the two end points of the shell thickness measurement);

fig. 16A is a cryo-scanning electron microscope image of capsules prepared by conventional batch processing according to a comparative example, showing that the diameter of the capsules is 26.9 μm (white arrows indicate both end points of the diameter measurement);

FIG. 16B is a cryo-scanning electron microscope image of the capsule of FIG. 16A showing the capsule's shell thickness of 160nm (white arrows indicate the two end points of the shell thickness measurement);

fig. 17A is a cryo-scanning electron microscope image of capsules prepared by conventional batch processing according to a comparative example, showing that the diameter of the capsules is 2.61 μm (white arrows indicate both end points of the diameter measurement);

FIG. 17B is a cryo-scanning electron microscope image of the capsule of FIG. 17A showing the capsule's shell thickness of 70.6nm (white arrows indicate the two end points of the shell thickness measurement);

fig. 18A is an optical microscope image of a population of capsules not in accordance with an embodiment of the present disclosure;

fig. 18B is an optical microscope image of a population of capsules not in accordance with an embodiment of the present disclosure;

fig. 19A is a cryo-scanning electron microscope image of capsules prepared by conventional batch processing according to a comparative example, showing that the diameter of the capsules is 6.56 μm (white arrows indicate both end points of the diameter measurement);

FIG. 19B is a cryo-scanning electron microscope image of the capsule of FIG. 19A showing the capsule's shell thickness of 126nm (white arrows indicate the two end points of the shell thickness measurement);

fig. 20A is a cryo-scanning electron microscope image of capsules prepared by conventional batch processing according to a comparative example, showing the capsules having a diameter of 22.7 μm (white arrows indicate both end points of the diameter measurement);

FIG. 20B is a cryo-scanning electron microscope image of the capsule of FIG. 20A showing the capsule's shell thickness of 92.3nm (white arrows indicate the two end points of the shell thickness measurement);

fig. 21A is a cryo-scanning electron microscope image of capsules prepared by conventional batch processing according to a comparative example, showing that the diameter of the capsules is 32.0 μm (white arrows indicate both end points of the diameter measurement);

FIG. 21B is a cryo-scanning electron microscope image of the capsule of FIG. 21A showing the capsule's shell thickness of 85.2nm (white arrows indicate the two end points of the shell thickness measurement);

fig. 22A is a cryo-scanning electron microscope image of capsules prepared by conventional batch processing according to a comparative example, showing that the diameter of the capsules is 4.62 μm (white arrows indicate both end points of the diameter measurement);

FIG. 22B is a cryo-scanning electron microscope image of the capsule of FIG. 22A showing the capsule's shell thickness at 110nm (white arrows indicate the two end points of the shell thickness measurement);

fig. 23A is a cryo-scanning electron microscope image of capsules prepared by conventional batch processing according to a comparative example, showing the diameter of the capsules as 24.4 μm (white arrows indicate both end points of the diameter measurement);

FIG. 23B is a cryo-scanning electron microscope image of the capsule of FIG. 23A showing the capsule's shell thickness of 169nm (white arrows indicate the two end points of the shell thickness measurement);

fig. 24A is a cryo-scanning electron microscope image of capsules prepared by conventional batch processing according to a comparative example, showing that the diameter of the capsules is 10.6 μm (white arrows indicate both end points of the diameter measurement); and is

Fig. 24B is a cryo-scanning electron microscope image of the capsule of fig. 24A showing the capsule's shell thickness of 153nm (white arrows indicate the two end points of the shell thickness measurement).

Detailed Description

Provided herein are capsules having a polymeric shell surrounding a core and methods of making the capsules. Capsules according to embodiments of the present disclosure may include a benefit agent. In embodiments, the capsule may be incorporated into a formulated product to release the benefit agent upon rupture of the capsule. Various formulated products having capsules are known in the art, and capsules according to the present disclosure may be used in any such product. Examples include, but are not limited to, laundry detergents, hand soaps, cleaning products, lotions, fabric enhancers, skin care products, beauty care products, and other cosmetic products.

In various embodiments, capsules having a narrow capsule size distribution are produced. In various embodiments, the capsules can have a percent delta burst strength of 15% to 230% (as discussed in more detail below) and a shell thickness of about 20nm to about 400 nm. In various embodiments, the capsules have an average diameter greater than 1 μm. In embodiments, each capsule has a diameter greater than 1 μm. In various embodiments, the capsules can have a number population diameter coefficient of variation of 10% to 100% and an average shell thickness of about 20nm to about 400 nm. In embodiments, the capsules may have an average weight core to shell ratio of greater than about 90: 10. In embodiments, the capsules may have an average weight core to shell ratio of about 95: 5. In embodiments, the capsules may have an average effective volume core-shell ratio of greater than about 90: 10. In embodiments, the capsules may have an average effective volume core-shell ratio of greater than about 95: 5.

In embodiments, the capsules may have a percent delta burst strength of 15% to 350%, as discussed in more detail below. In embodiments, the capsules may have a percent delta burst strength of 15% to 230%, as discussed in more detail below. In any embodiment, the capsule may have a shell thickness of about 20nm to about 400 nm. In any embodiment, the capsules can have a number population diameter coefficient of variation of about 10% to about 100%.

In embodiments, the population of capsules can include a percent delta burst strength of from about 15% to about 230% and a shell thickness of from about 20nm to about 400 nm. In embodiments, a population of capsules may comprise a number population coefficient of variation of diameters from about 10% to about 100% and a shell thickness from about 20nm to about 400 nm. In embodiments, the population of capsules may have a percent delta burst strength of from about 15% to about 230%, as discussed in more detail below. In embodiments, a population of capsules may have a shell thickness of about 20nm to about 400 nm. In embodiments, a population of capsules may have a number population diameter coefficient of variation of about 10% to about 100%.

The foregoing represents exemplary embodiments of combinations of capsule characteristics. These and various additional features are described in further detail below. It should be understood herein that other combinations of such features are contemplated herein, and may be any one or more of such features described in the following paragraphs that may be used in various combinations.

In various embodiments, the capsules are provided as a single capsule, a portion of a population of capsules, or a portion of any suitable number of multiple capsules. References herein to individual capsule characteristics, parameters and characteristics are to be understood as applicable to a plurality of capsules or groups of capsules. It is understood herein that such features and associated values may be averages of a plurality of capsules or capsule populations unless otherwise specified herein.

In any of the embodiments herein, the core may comprise a benefit agent. In various embodiments, the core may be a liquid.

In embodiments, the capsule or population of capsules may have an average weight core to shell ratio of at least about 80:20, 85:15, 90:10, 95:5, 98:2, 99:1, 99.5:0.5, 99.9:0.1, or 99.99: 0.01. For example, the capsule or population of capsules may have an average weight core-shell ratio of 80:20, 85:15, 90:10, 95:5, 98:2, 99:1, 99.5:0.5, 99.9:0.1, or 99.99: 0.01. In embodiments, the population of capsules may have an average weight core-shell ratio of about 80:20 to about 99.9:0.1, or about 90:10 to about 99.9:0.1, or about 95:5 to about 99.99:0.01, or about 97:3 to about 99.99:0.01, or about 95:5 to about 99.5: 0.5. In embodiments, the entire population of capsules may have an average weight core to shell ratio of at least 80:20, or at least 90:10, or at least 95:5, or at least 97: 3. As used herein, core-shell weight ratio refers to the weight percent ratio based on the total weight of the core material and the shell material of the capsule.

In embodiments, the capsule or population of capsules may have an average effective volume core-shell ratio of at least 80:20, 85:15, 90:10, 95:5, 98:2, 99:1, 99.5:0.5, 99.9:0.1, or 99.99: 0.01. For example, the capsule or population of capsules may have an average effective volume core-shell ratio of 80:20, 85:15, 90:10, 95:5, 98:2, 99:1, 99.5:0.5, 99.9:0.1, or 99.99: 0.01. In embodiments, the population of capsules may have an average effective volume core-shell ratio of about 80:20 to about 99.9:0.1, or about 90:10 to about 99.9:0.1, or about 95:5 to about 99.99:0.01, or about 97:3 to about 99.99:0.01, or about 95:5 to about 99.5: 0.5. In embodiments, the entire population of capsules may have an average effective volume core-shell ratio based on the mass balance of core material to shell material of at least 80:20, or at least 90:10, or at least 95:5, or at least 97: 3. The calculation of the average effective volume core-shell ratio is detailed below.

A high core-shell material ratio (by weight or volume) can advantageously result in highly efficient capsules with a high content of benefit agent per capsule. In embodiments, this may allow for a high loading of benefit agent in a formulated product with capsules and/or allow for a smaller amount of capsules to be used in the formulated product. In embodiments, capsules having a high core-to-shell material ratio may advantageously require less shell material, which in various embodiments is a non-functional material. Smaller masses of such non-functional materials reduce waste, can reduce cost by reducing the amount of precursor needed, and can improve environmental impact by reducing the amount of organic precursor material needed.

In embodiments, the capsule or population of capsules may have a percent delta burst strength of from about 10% to about 500%, or from about 10% to about 350%, or from about 10% to about 230%, from about 15% to about 350%, from about 15% to about 230%, from about 50% to about 350%, from about 50% to about 230%, from about 15% to about 200%, from about 30% to about 200%. For example, a population of capsules may have a percentage delta burst strength of about 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 110%, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190%, 200%, 210%, 220%, 230%, 240%, 250%, 300%, 350%, 400%, or 500%. Percent delta burst strength can be calculated using the following formula:

wherein FS represents the rupture strength, and d_iThe FS at (b) is the FS of the capsules at percentile "i" of the volume size distribution. Delta burst strength can be measured by the delta burst strength test method described further below, and d₅、d₅₀And d₉₀The measurement can be as follows.

A percent delta burst strength of about 15% to about 230% can be beneficial in ensuring that the capsules properly and more uniformly release the benefit agent in the formulated product at the desired time. For example, in embodiments, the formulated product may be a fabric care product, a laundry detergent, a soap, a dishwashing aid, a cleaning product, or a skin care product or a hair care product, and capsules having a percent delta burst strength of from about 15% to about 230% may beneficially ensure that substantially all of the capsules release the benefit agent at the targeted stage of consumer use of the product.

In embodiments, the capsule may have a d of from about 0.2MPa to about 30MPa, or from about 0.4MPa to about 10MPa, or from about 0.6MPa to about 5MPa, or even from about 0.8MPa to about 4MPa₅₀The breaking strength (absolute breaking strength at the median size of the population). E.g. d₅₀The fracture strength of (A) can be about 0.2MPa, 0.3MPa, 0.4MPa, 0.5MPa, 0.6MPa, 0.7MPa, 0.8MPa, 0.9MPa, 1MPa, 1.5MPa, 2MPa, 2.5MPa, 3MPa, 3.5MPa, 4MPa, 4.5MPa, 5MPa, 6MPa, 7MPa, 8MPa, 9MPa, 10MPa, 11MPa, 12MPa, 13MPa, 14MPa, 15MPa, 16MPa, 17MPa, 18MPa, 19MPa, 20MPa, 25MPa, or 30 MPa.

In embodiments, the capsules may have a diameter greater than 1 μm. In embodiments, the capsules or population of capsules may have an average diameter greater than 1 μm. In embodiments, the capsules or population of capsules may have a median diameter greater than 1 μm. In any of the preceding embodiments, the reference diameter may be greater than or equal to 1 μm, 2 μm, 3 μm, 4 μm, 5 μm, 10 μm, 15 μm, 20 μm, or 25 μm. In any of the preceding embodiments, actual, average, d₅₀Or other reference diameters may be about 1 μm to 100 μm, or 1 μm to 80 μm, or 1 μm to 65 μm, or 1 μm to 50 μm, or 5 μm to 80 μm, or 10 μm to 65 μm, or 15 μm to 65 μm, or 20 μm to 60 μm. For example, the reference diameter can be about 1 μm, 2 μm, 3 μm, 4 μm, 5 μm, 10 μm, 15 μm, 20 μm, 25 μm, 30 μm, 35 μm, 40 μm, 50 μm, 55 μm, 60 μm, 65 μm, 70 μm, 75 μm, 80 μm, 85 μm, 90 μm, 95 μm, or 100 μm. In embodiments, the entire population of capsules may have a diameter greater than 1 μm, 2 μm, 3 μm, 4 μm, 5 μm, or 10 μm. In embodiments, the entire population of capsules can include 1 μm to 80 μm, 3 μm to 80 μmA diameter of 80 μm, or 5 μm to 65 μm, or 10 μm to 65 μm, 15 μm to 65 μm. For example, the capsules herein can have a diameter within the aforementioned ranges, as shown, for example, by the frozen SEM images shown in fig. 5A, 6A, 7A, 8A, 9A, and 10A.

In embodiments, the capsule may have a coefficient of variation of diameter ("CoV") based on volume percentage (or volume weighted size distribution) of less than 50%, or less than 45%, or less than 40%, or less than 35%. For example, the capsule diameter CoV is from about 20% to about 50%, or from about 25% to about 40%, or from about 20% to about 45%, or from about 30% to about 40%, on a volume percent basis. The diameter CoV based on volume percentage is calculated by the following formula:

wherein

Wherein:

coefficient of variation of CoVv-volume weighted size distribution

σ_vStandard deviation of volume weighted size distribution

μ_vDistribution mean of the volume-weighted size distribution

d_iDiameter in fraction i: (>1um)

x_i,vThe frequency in the fraction i (corresponding to the diameter i) of the volume weighted size distribution.

In embodiments, the capsules may have a coefficient of diameter (number population coefficient of variation in diameter) on a number percentage basis of about 1% to about 150%, or about 1% to about 100%, or about 10% to about 80%, or about 25% to about 100%, or about 25% to about 75%. For example, a capsule may have a coefficient of variation in diameter on a number percentage basis of about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, 100%, or 150%. The number population diameter coefficient of variation can be calculated by the following formula:

wherein

Wherein:

coefficient of variation of CoVn-number weighted size distribution

σ_n-standard deviation of the number weighted size distribution

μ_nDistribution average of the number weighted size distribution

d_iDiameter in fraction i: (>1um)

x_i,nThe frequency in the fraction i (corresponding to the diameter i) of the number weighted size distribution

μ_nDistribution mean of the number distribution

x_i,nFrequency in the fraction i (corresponding to the diameter i) of the number distribution

n_i-number of capsules in fraction i

The relationship between the number and the volume weighted size distribution frequency is represented by the following equation:

wherein the coefficients are as defined above.

Core

In any of the embodiments disclosed herein, the capsule may comprise a benefit agent in the core. In embodiments, the benefit agent may include one or more perfume compositions, perfume raw materials, silicone oils, waxes, hydrocarbons, higher fatty acids, essential oils, lipids, skin cooling agents, vitamins, sunscreens, antioxidants, glycerin, catalysts, bleach encapsulates, silica encapsulates, malodor reduction agents, odor control materials, chelating agents, antistatic agents, emollients, agricultural materials (such as pesticides, insecticides, nutrients, herbicides, fungal control agents, insect and moth repellents), colorants, antioxidants, chelating agents, base agents, drape and morphology control agents, smoothing agents, wrinkle control agents, sanitizers, disinfectants, microbe control agents, mold control agents, antiviral agents, desiccants, soil repellents, detergents, fabric fresheners and refreshment agents, chlorine bleach odor control agents, and/or odor control agents, Dye fixatives, dye transfer inhibitors, color retention agents, optical brighteners, color restoration/restoration agents, anti-fading agents, whiteness enhancers, anti-abrasion agents, fabric integrity agents, anti-wear agents, anti-pilling agents, defoamers, ultraviolet light protection agents, light fade inhibitors, anti-allergic agents, enzymes, water repellents, fabric comfort agents, anti-shrinkage agents, anti-stretch agents, stretch-recovery agents, other structuring agents (such as phase change materials, self-healing materials, skin care agents, glycerin, and natural actives), antimicrobial actives, antiperspirant actives, cationic polymers and dyes, food and feed additives (such as antioxidants, probiotics, and food and beverage colorants). In embodiments, the benefit agent may include one or more of the following: perfume compositions, perfume raw materials, sanitizers, disinfectants, antiviral agents, fabric fresheners and freshness maintenance agents, chlorine bleach odor control agents, dye fixatives, dyes, optical brighteners, color restoration/restoration agents, enzymes, defoamers, fabric comfort agents, skin care agents, lubricants, waxes, hydrocarbons, malodor reduction agents, odor control materials, fertilizers, nutrients, and herbicides.

In embodiments, the benefit agent may comprise a perfume or perfume composition. In embodiments, the perfume composition may comprise one or more of the following: perfume raw materials, essential oils, malodor reducing agents, and odor controlling agents.

In various embodiments, the perfume composition may comprise one or more perfume raw materials. In an embodiment, the perfume composition may comprise a combination of the following by weight, based on the total weight of the perfume composition: (1) from about 2.5% to about 30%, or from about 5% to about 30%, of a perfume raw material characterized by a logP of less than 3.0 and a boiling point of less than 250 ℃; (2) from about 5% to about 30%, or from about 7% to about 25%, of a perfume raw material characterized by a logP of less than or equal to 3.0 and a boiling point of greater than or equal to 250 ℃; (3) from about 35% to about 60%, or from about 40% to about 55%, of perfume raw materials characterized by having a logP greater than 3.0 and a boiling point less than 250 ℃; and (4) from about 10% to about 45%, or from about 12% to about 40%, of a perfume raw material characterized by having a logP greater than 3.0 and a boiling point greater than 250 ℃.

The log value (logP) of the octanol/water partition coefficient of each perfume raw material in the tested perfume compositions was calculated. logP of individual perfume raw materials was calculated using the Consensus logP calculation model version 14.02(Linux) or equivalent available from Advanced Chemistry Development Inc (ACD/Labs) (Toronto, Canada) to provide dimensionless logP values. The Consensus logP calculation model of ACD/Labs is part of the ACD/Labs model suite, and more details are provided below in the logarithmic octanol/water partition coefficient (logP) test method.

In embodiments, the perfume raw material may be one or more of the following:

the malodor reduction agent may be selected from the group consisting of antimicrobial materials, enzyme inhibitors, reactive aldehydes, masking fragrance raw materials and masking accords, and binding polymers (e.g., polyethylene imine).

In embodiments, the perfume raw materials may be present in an amount from about 10% to 100% by total weight of the perfume composition, or from about 15% to about 95%, or from about 20% to about 90%, or from about 30% to about 90%, or from about 20% to 100% by total weight of the perfume composition. In embodiments, the perfume raw material may be present in an amount of about 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 100% by total weight of the perfume composition.

In embodiments, the perfume composition may comprise from about 2.5% to 30%, or from about 5% to 30%, or from about 7% to 30%, or from about 10% to 25%, by weight based on the total weight of the perfume composition, of perfume raw materials characterized by having a logP of less than 3.0 and a boiling point of less than 250 ℃.

In embodiments, the perfume composition may comprise from about 5% to 30%, or from about 7% to 25%, or from about 10% to 25%, by weight based on the total weight of the perfume composition, of perfume raw materials characterized by having a logP of less than or equal to 3.0 and a boiling point of greater than or equal to 250 ℃.

In embodiments, the perfume composition may comprise from about 35% to 60%, or from about 40% to 55%, or from about 45% to 55%, by weight based on the total weight of the perfume composition, of perfume raw materials characterized by having a logP greater than 3.0 and a boiling point less than 250 ℃.

In embodiments, the perfume composition may comprise from about 10% to 45%, or from 12% to 40%, or from 15% to 35%, or from 15% to 40%, by weight based on the total weight of the perfume composition, of perfume raw materials characterized by having a logP greater than 3.0 and a boiling point greater than 250 ℃.

In embodiments, the benefit agent may be present in an amount of about 10 wt% or more based on the total weight of the core. In embodiments, the perfume composition may be present in an amount of about 10 wt% or more based on the total weight of the core. For example, the perfume composition may be present in an amount of about 20 wt% or more, or about 30% or more, or about 40% or more, or about 45% or more, or about 50% or more, or about 60% or more, or about 70% or more, or about 80% or more, or about 90% or more, or 100%, based on the total weight of the core.

In embodiments, the benefit agent may have a logP value greater than or equal to 1. In embodiments, the benefit agent may have a logP value of 1 to 5, or 1 to 4, or 1 to 3, or 1 to 2. For example, the benefit agent may have a logP value of about 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, or 5.

In embodiments, the core may further comprise additional components, such as excipients, carriers, diluents, and other agents. In embodiments, the benefit agent may be mixed with an oil. Non-limiting examples of oils include isopropyl myristate, C₄-C₂₄Mono-, di-, and tri-esters of fatty acids, castor oil, mineral oil, soybean oil, hexadecanoic acid, methyl ester isododecane, isoparaffinic oils, polydimethylsiloxane, brominated vegetable oils, and combinations thereof. The capsules may also have different ratios of oil to benefit agent in order to produce different capsule populations that may have different bloom patterns. Such populations may also incorporate different flavor oils in order to prepare populations of capsules exhibiting different bloom patterns and different flavor experiences. Other non-limiting examples of oils are disclosed in U.S. patent application 2011/0268802 and are hereby incorporated by reference. In embodiments, the oil mixed with the benefit agent may include isopropyl myristate.

Shell

In any of the embodiments disclosed herein, the capsule shell can be a polymeric shell and can comprise greater than 90% polymeric material, or greater than 95% polymeric material, or greater than 98% polymeric material, or greater than 99% polymeric material. In embodiments, the polymeric shell may comprise one or more of a homopolymer, a copolymer, and a crosslinked polymer. In embodiments, the polymeric shell may comprise a copolymer and a cross-linked polymer. In embodiments, the polymeric shell may be made by simple and/or complex coacervation. In embodiments, the polymeric shell may comprise one or more of a polyacrylate, a polymethacrylate, an aminoplast such as melamine formaldehyde, a polyurea, a polyurethane, a polyamide, a polyvinyl alcohol, chitosan, gelatin, a polysaccharide, or a gum. In embodiments, the polymeric shell comprises a poly (meth) acrylate. As used herein, the term "poly (meth) acrylate" may be a polyacrylate, a polymethacrylate, or a combination thereof.

In embodiments, the capsule may have a shell thickness or average shell thickness of from about 1nm to about 1000nm, or from about 1nm to about 800nm, or from about 1nm to about 500nm, or from about 5nm to about 400nm, or from about 10nm to about 500nm, or from about 10nm to about 400nm, or from about 20nm to about 500nm, or from about 20nm to about 400nm, or from about 50nm to about 350 nm. For example, the shell thickness or average shell thickness can be about 1nm, 5nm, 10nm, 20nm, 30nm, 40nm, 50nm, 60nm, 70nm, 80nm, 90nm, 100nm, 150nm, 200nm, 250nm, 300nm, 350nm, 400nm, 450nm, 500nm, 600nm, 700nm, 800nm, 900nm, or 1000 nm. In embodiments, the entire population of capsules may have a shell thickness of less than 1000nm, or less than 800nm, or less than 600nm, or less than 400nm, or less than 350 nm. Fig. 5B, 6B, 7B, 8B, 9B, and 10B illustrate capsules having a shell thickness as described herein, according to embodiments of the present disclosure.

In various embodiments, the capsules and methods of making capsules allow for reduced shell thicknesses. For example, the capsule may have a thickness of about 20nm to about 400 nm. In various embodiments, capsules having a shell thickness of about 20nm to about 400nm can minimize permeation of benefit agents during shelf life while maintaining sufficient burst strengthAnd a desired release profile to maintain functionality of the formulated product. For example, in such embodiments, the capsules can have a median population (d) of from about 0.2MPa to about 30MPa, or from about 0.4MPa to about 10MPa, or from about 0.6MPa to about 5MPa, or from about 0.8MPa to about 4MPa₅₀) Absolute rupture strength of (d). In such embodiments, the reduced shell thickness may beneficially allow for a reduction in the amount of polymer precursor material required compared to conventional capsules, which may reduce cost and may reduce environmental impact through increased activity and more efficient formulation.

In embodiments, the capsule may have a delta burst strength of from about 15% to about 230% and a shell thickness of from about 20nm to about 400 nm. Such a combination may be advantageous, allowing for uniform and timely release of the benefit agent in the formulated product, as well as reducing the polymer material required, which reduces the cost of preparing the capsules and is more sustainable.

In embodiments, the capsules may have a number population diameter coefficient of variation of about 10% to about 100% and an average shell thickness of about 20nm to about 400 nm.

In embodiments, the capsules can have a number population diameter coefficient of variation of about 10% to about 100%, a delta burst strength of about 15% to about 230%, and an average shell thickness of about 20nm to about 400 nm.

In embodiments, the capsules may have an average effective volume core-shell ratio of core material to shell material of greater than or equal to about 95:5 capsules, a delta burst strength of from about 15% to about 230%, and a shell thickness of from about 20nm to about 400 nm. In embodiments, the capsules can have an average effective volume core-shell ratio of greater than or equal to about 95:5, a number population diameter coefficient of variation of about 10% to about 100%, and an average shell thickness of about 20nm to about 400 nm. In embodiments, the capsules can have an average effective volume core-shell ratio of greater than or equal to about 95:5, a number population diameter coefficient of variation of about 10% to about 100%, a delta burst strength of about 15% to about 230%, and an average shell thickness of about 20nm to about 400 nm. In various embodiments, the capsules can have a number population diameter CoV of about 10% to about 100%. It is believed that such covs may allow for improved release properties and enable the formulation of capsules into the final product. In various embodiments, the capsules can have a delta burst strength of from about 15% to about 230%. Without intending to be bound thereby, it is believed that the narrow delta rupture strength may be associated with improved and uniform rupture of the capsules. In various embodiments, the capsules can have a shell thickness of about 20nm to about 400nm and an average effective volume core-shell ratio of greater than or equal to about 95: 5. In such embodiments, less polymeric material may be required to make the shell, which may reduce waste and environmental impact, without sacrificing stability and mechanical resistance of the capsule.

Preparation method

According to embodiments, a method of making a capsule having a core surrounded by a polymeric shell may comprise emulsifying using a membrane. In various embodiments, the capsules may be prepared by coacervation or solvent extraction methods. In various embodiments, the method of making the capsule may comprise dispersing droplets of the dispersed phase in the continuous phase by passing the dispersed phase through a plurality of pores in the film. In embodiments, the method may include passing the dispersed phase through the membrane from the first side of the membrane to the second side of the membrane and into the continuous phase flowing through the second side of the membrane. Upon exiting the plurality of pores on the second side of the film, the dispersed phase is formed into droplets of the dispersed phase. In embodiments, the membrane may be mechanically moved while the dispersed phase is passed through the membrane to create a shear force on the second side of the membrane to cause it to exit the membrane and disperse into the flowing continuous phase.

In embodiments, the dispersed phase may comprise a polymer precursor and a benefit agent. In embodiments, the method can further comprise subjecting the dispersed phase emulsion in the continuous phase to conditions sufficient to initiate polymerization of the polymer precursor within the droplets of the dispersed phase. For the particular polymer precursor present in the dispersed phase, suitable polymerization conditions can be selected as known in the art. Without intending to be bound by theory, it is believed that upon initiation of polymerization, the polymer becomes insoluble in the dispersed phase and migrates within the droplet to the interface between the dispersed phase and the continuous phase, thereby defining the capsule shell.

In embodiments, the method may use a polymerization process to form the capsules, wherein the shell is formed by the precursor polymerizing within the core material and migrating to the interface to surround the core. In particular, the method may include the dispersed phase droplets comprising a soluble polymer precursor that becomes insoluble after polymerization and migrates to the interface between the dispersed and continuous phases, thereby forming a capsule shell surrounding a core that, after complete polymerization, comprises the remaining components of the dispersed phase, such as the benefit agent.

A high core-shell material ratio (by weight or volume) can advantageously result in highly efficient capsules with a high content of benefit agent per capsule. The highest proportion of cores in the capsules is achieved by making so-called core-shell capsules. Moreover, in this type of capsule morphology, a protective barrier is formed over the entire core surface, which may be very relevant in some cases. Core-shell capsules are spherical structures in which the capsule shell is present only on spheres formed by the core in the core of the capsule. To achieve this core-shell structure, the wall material precursor is carefully selected to be able to reach the core sphere surface during capsule formation. Without being bound by theory, the capsule wall material precursor is initially soluble in the capsule core, and once the capsule formation reaction is triggered, it may begin to become increasingly insoluble and will attempt to detach from the core solution. Once at the core surface, it is insoluble in the continuous phase. Proper balance of surface energy in a core/continuous phase/capsule material three-phase system can be critical to the formation of a thin film at the core/continuous phase interface. In other words, the final capsule wall material should have the following properties: insolubility in the core, insolubility in the continuous phase, film-forming ability, and appropriate surface energy to produce a film between the core and the continuous phase.

If the wall material does not have the ability to form a thin film on the core sphere, the type of capsule formed is a matrix capsule. In matrix capsules, the "core" active is distributed as "particles" or droplets within the spheres of wall material. The core to shell ratio is typically below 80:20 and even below 60:40 or 50: 50. Thus, the matrix type of the capsule is a less efficient encapsulation morphology (capsules for active delivery are less efficient and the protection of the core active is incomplete). Higher amounts of wall material may trap the core material within the capsule wall. Furthermore, the materials used to form the matrix capsules do not require extensive selection rules.

In embodiments, the dispersed phase may comprise one or more of a polymer precursor, a processing aid, and a benefit agent. In embodiments, the polymer precursor may include one or more monomers and oligomers, including mixtures of monomers and oligomers. In embodiments, the polymer precursor is soluble in the dispersed phase. In embodiments, the polymer precursor is multifunctional. As used herein, the term "multifunctional" refers to having more than one reactive chemical functional group. For example, the reactive chemical functional group F may be a carbon-carbon double bond (i.e., an ethylenically unsaturated group) or a carboxylic acid. In embodiments, the polymer precursor may have any desired number of functional groups F. For example, the polymer precursor may comprise two, three, four, five, six, seven, eight, nine, ten, eleven, or twelve functional groups F. In embodiments, the polymer precursor may comprise a monomer or oligomer comprising at least one ethylenically unsaturated group. In embodiments, the polymer precursor may include at least one multifunctional ethylenically unsaturated monomer having at least three functional groups. In embodiments, the polymer precursor may include a combination of ethylenically unsaturated monomers. In embodiments, the polymer precursor may comprise a combination of one or more ethylenically unsaturated monomers with one or more ethylenically unsaturated monomers comprising one or more other functional groups. In embodiments, the polymer precursor may comprise a combination of at least one ethylenically unsaturated monomer having one or more other functional groups (such as amino, amide, alcohol, thiol, sulfonic acid, and/or carboxylic acid functional groups) and one or more polymer precursors comprising at least one ethylenically unsaturated unmodified monomer. In embodiments, the polymer precursor may comprise a combination of one or more ethylenically unsaturated monomers and one or more monomers comprising one or more other functional groups selected from amine, amide, alcohol, thiol, sulfonic acid, and carboxylic acid functional groups.

In embodiments, the polymer precursor may comprise one or more of the amine monomers selected from the group consisting of: aminoalkyl acrylates, alkylaminoalkyl acrylates, dialkylaminoalkyl acrylates, aminoalkyl methacrylates, alkylaminoalkyl methacrylates, dialkylaminoalkyl methacrylates, t-butylaminoethyl methacrylate, diethylaminoethyl methacrylate, dimethylaminoethyl methacrylate, and dipropylaminoethyl methacrylate; styrenes, allyls, ethylenes, glycidyl ethers, epoxies, and a variety of multifunctional monomers or multifunctional oligomers. In embodiments, the polymer precursor may include one or more acrylates. For example, the polymer precursor may include one or more of methacrylate, ethyl acrylate, propyl acrylate, and butyl acrylate. In embodiments, the polymer precursor is one or more ethylenically unsaturated monomers or oligomers. In various embodiments, the ethylenically unsaturated monomer or oligomer is multifunctional. In embodiments, the multifunctional ethylenically unsaturated monomer or oligomer is a multifunctional ethylenically unsaturated (meth) acrylate monomer or oligomer. In embodiments, the multifunctional ethylenically unsaturated monomer or oligomer may be one or more of a multifunctional urethane acrylate, a pentaerythritol acrylate, and a polypentaerythritol acrylate. In embodiments, the multifunctional ethylenically unsaturated monomer or oligomer may comprise two, three, four, five, six, seven, eight, nine, ten, eleven, or twelve functional groups. In embodiments, the multifunctional ethylenically unsaturated monomer or oligomer may comprise at least three functional groups. In embodiments, the multifunctional ethylenically unsaturated monomer or oligomer may comprise at least four functional groups. In embodiments, the multifunctional ethylenically unsaturated monomer or oligomer may comprise at least five functional groups. The multifunctional monomer or oligomer may exhibit improved crosslinking. Without intending to be bound by theory, it is believed that the double bonds of the multifunctional monomer serve as a crosslinking agent in polymerization, such as free radical polymerization, and thus the higher the number of double bonds, i.e., the more functional the monomer, the higher the crosslinking density.

In embodiments, the polymer precursor may include a multifunctional urethane acrylate. For example, the polymer precursor may include one or more of the following: CN975 (hexafunctional aromatic urethane acrylate),248 (aliphatic urethane diacrylate diluted with 12% 1, 6-hexanediol diacrylate, MW 1200g/mol), CN9001 (aliphatic urethane acrylate), Incorez 701(Incorez Ltd, 1050 g/eq), CN9001NS (Sartomer Co. USA, functionality 2, MW 2813g/mol), Laromer LR 8987, Laromer LR 8765 and Laromer LR 9000(BASF, difunctional), aliphatic PUA (Tianjin, China, MW 3000g/mol), ether urethane diacrylate oligomers (Wuxi Tianjiao-saite Co.), AR-12[88](Etnal Chemical, Taiwan, China, epoxy acrylate, difunctional), SM6020, EB2002 (waterborne resin, functionality 2), PUA CN972(Sartomer Co., MW 3500g/mol), Bayhydrol UV 2282(Sayer Material Science, waterborne PUA), Genomer 4269 and Ganomer 6043(Rahn USA, aliphatic urethane polyester acrylate), OAK-27(Ciba Geigy Co., PUA), Ebecryl @270(UCB, aliphatic, functionality 2 and MW 1500), difunctional urethane acrylate oligomers, such as Exothane 8, Exothane 10 and Exano 26 (Estech, USA),1290(UCB, aliphatic urethane hexaacrylate),220(UCB, aromatic urethane hexaacrylate),830(UCB, polyester hexaacrylate) and8301(UCB, aliphatic urethane hexaacrylate). In embodiments, the polymer precursor may include one or more of the following: melamine, polyacrylamide, silicone, polystyrene, polyurea, polyurethane, polyacrylate-based material, gelatin, styrene maleic anhydride, polyamide, aromatic alcohol, polyvinyl alcohol, resorcinol-based material, polyisocyanate-basedEster materials, acetals (such as 1,3, 5-triol-benzene-glutaraldehyde and 1,3, 5-triol-benzene melamine), starch, cellulose acetate phthalate, and gums. In embodiments, the polymer precursor may comprise a polyacrylate or polymethacrylate precursor having at least three functional groups.

For example, the polymer precursor may be one or more of the following: hexafunctional aromatic urethane acrylate oligomers, such as CN975,8301. Pentaerythritol tri-tetraacrylate, pentaerythritol triacrylate, dipentaerythritol pentaacrylate, and dipentaerythritol hexaacrylate. In embodiments, the polymer precursor may be one or more of the following compounds:

in embodiments, the polymer precursor may include one or more of the compounds in table 1 below.

TABLE 1

In embodiments, the polymer precursor may include one or more of the following: methyl Methacrylate (MMA), Ethyl Methacrylate (EMA), Methyl Acrylate (MA), 2-ethylhexyl acrylate, di (ethylene glycol) ethyl ether acrylate (DEGEEA), Butyl Acrylate (BA), trimethylolpropane triacrylate (TMPTA), tripropylene glycol diacrylate (TPGDA), acrylonitrile, ethyl acrylate, 2-hydroxy acrylate (2-HBA), 2-hydroxyethyl acrylate (2-HEA), 2-hydroxypropyl acrylate (2-HPA), 2- (2-ethoxy) ethyl acrylate (EOEA), lauryl methacrylate, styrene, isobornyl acrylate (iBOA), stearyl acrylate, dipentaerythritol pentaacrylate (DPHPA), vinyl methacrylate, Photomer 4003 (ethoxylated (4) nonylphenol acrylate) and Photomer 8061 (propoxylated (3) nonylphenol ether acrylate), Bisphenol a Bis (2-hydroxy-3-methacryloxypropyl) ether (Bis-GMA), 1, 6-hexanediol diacrylate (HDDA), heptadecafluorodecyl methacrylate, Glycidyl Methacrylate (GMA), tetrafluoropropyl 2,2,3, 3-acrylate (TFPA), dipentaerythritol penta/hexaacrylate (DPHPA), trimethylolpropane triacrylate (TMPTA), triethylene glycol dimethacrylate (TEGDMA), phenoxyethyl 2-acrylate, trifluoroethyl 2,2, 2-methacrylate, dimethylaminoethyl N, N' -methacrylate (DMAEMA), pentaerythritol tetraacrylate (PETEA), triallyl cyanurate, triallyl isocyanurate, and N-acryloyl-morpholine (AMCO).

In embodiments, the polymer precursor may be present in the dispersed phase in an amount of from about 0.01 wt% to about 30 wt% based on the total weight of the dispersed phase or from about 0.01 wt% to about 20 wt%, or from about 0.05 wt% to about 20 wt%, or from about 0.1 wt% to about 15 wt%, or from about 0.5 wt% to about 15 wt%, or from about 1 wt% to about 15 wt%, or from about 5 wt% to about 15 wt%, or from about 0.05 wt% to about 15 wt%, or from about 0.1 wt% to about 10 wt%, or from about 0.1 wt% to about 5 wt%, or from about 0.1 wt% to about 2 wt% based on the total weight of the dispersed phase. For example, the polymer precursor can be present in an amount of about 0.01, 0.05, 0.1, 0.5, 1,2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13, 14, or 15 weight percent based on the total weight of the dispersed phase.

In embodiments, the polymer precursor may comprise a primary monomer and a secondary monomer, wherein the primary monomer is present in an amount of at least 51% and the secondary monomer is present in an amount of no more than 49% based on the total weight of the polymer precursor. In embodiments, the secondary monomer may include one or more monomers or combinations of oligomers provided in any suitable ratio to achieve a total secondary monomer content of up to 49% based on the total weight of the polymer precursor. In embodiments, the primary monomer is an ethylenically unsaturated monomer or oligomer, and the secondary monomer is any one or more ethylenically unsaturated monomers having different functional groups (such as amino, amide, alcohol, thiol, sulfonic acid, and/or carboxylic acid functional groups).

In embodiments, the continuous phase may be free or substantially free of polymer precursors. As used herein, the term "substantially free of polymer precursors" means that the continuous phase comprises 1 wt% or less of polymer precursors based on the total weight of the continuous and dispersed phases.

In embodiments, the polymer precursors contained in the dispersed phase polymerize to form about 50% or more of the shell, 75% or more of the shell, 90% or more of the shell, or about 95% or more of the shell, or about 96% or more of the shell, or about 97% or more of the shell, or about 98% of the polymer by weight of the shell.

In embodiments, the method of making the capsules may include a stabilizer system in one or both of the dispersed and continuous phases. In embodiments, the stabilizer system may be present in an amount of about 0.01 wt% to about 30 wt%, based on the total weight of the continuous phase, or in an amount of about 0.1 wt% to about 25 wt%, or about 0.5 wt% to about 20 wt%, or about 1 wt% to about 20 wt%, or about 0.5 wt% to about 10 wt%, based on the total weight of the continuous phase. For example, the stabilizer system may be present in an amount of about 0.1, 0.2, 0.3, 0.4, 0.5, 1,2, 3, 4, 5, 6, 7, 8, 9, or 10 weight percent. In embodiments, the aqueous polyvinyl alcohol solution can have a viscosity of about 2cP to 200cP, or about 5cP to 180cP, or about 10cP to about 150 cP. For example, the polyvinyl alcohol can have a viscosity of about 2cP, 3cP, 4cP, 5cP, 10cP, 15cP, 20cP, 25cP, 30cP, 40cP, 50cP, 60cP, 70cP, 80cP, 90cP, 100cP, 110cP, 120cP, 130cP, 140cP, 150cP, 160cP, 170cP, 180cP, 190cP, or 200 cP.

In embodiments, the stabilizer system may comprise a primary stabilizer present in the continuous phase. In embodiments, the primary stabilizer may be present in an amount of from about 51 wt% to about 100 wt%, based on the total weight of the stabilizer system. In embodiments, the primary stabilizer may include an amphiphilic nonionic stabilizer that is soluble or dispersible in the continuous phase. In embodiments, the primary stabilizer may include one or more of the following: polysaccharides, acrylic acid-based stabilizers, pyrrolidone-based polymers, natural source gums, polyalkylene glycol ethers; alkylphenol, condensation products of aliphatic alcohols or fatty acids with alkylene oxides, ethoxylated alkylphenol, ethoxylated arylphenol, ethoxylated polyarylphenol, carboxylic esters solubilized with polyols, polyvinyl alcohol, polyvinyl acetate, copolymers of polyvinyl alcohol and polyvinyl acetate, polyacrylamide, poly (N-isopropylacrylamide), poly (hydroxypropyl 2-methacrylate), poly (2-ethyl-2-oxazoline), polyalkyleneimine, poly (2-isopropenyl-2-oxazoline-co-methyl methacrylate), poly (methyl vinyl ether), polyvinyl alcohol-co-ethylene, and acetate modified polyvinyl alcohol. In embodiments, the primary stabilizer may include polyvinyl alcohol. In embodiments, the polyvinyl alcohol may have a degree of hydrolysis of 50% to 99.9%. In embodiments, the polyvinyl alcohol may have a degree of hydrolysis of less than 95%. In embodiments, the polyvinyl alcohol may have a degree of hydrolysis of 50% to 95%, or 60% to 95%, or 70% to 95%, or 75% to 95%. For example, the degree of hydrolysis may be 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%.

In embodiments, selection of a stabilizing system as described herein may beneficially help stabilize droplets at the surface of the film, which in turn may provide more uniform droplet size, as well as low coefficient of variation or capsule size, low percent delta burst strength, and also serve to adjust the average size of the distribution. In embodiments, a primary stabilizer, such as polyvinyl alcohol, may be used to stabilize the emulsion at the interface between the dispersed phase droplets and the continuous phase, and to help prevent or reduce droplet coalescence. In embodiments, the stabilizer system may help provide an emulsion having a number population diameter coefficient of variation of from about 10% to about 100%.

In embodiments, the stabilizer system further comprises one or more minor amounts of a stabilizer. Combinations of two or more types of surfactants may be used in embodiments to address the kinetic and thermodynamic stability of the emulsion. In embodiments, the stabilizer system includes a minor amount of stabilizer in an amount of about 0% to about 49% by weight based on the total weight of the stabilizer system. For example, the minor stabilizer may be present in an amount of 0%, 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, or 49% of the total weight of the stabilizer system. In embodiments, the minor stabilizer may comprise a minor amount of a protective colloid present in the continuous phase. In embodiments, the minor amount of protective colloid may include one or more of a low molecular weight surfactant, a cationic stabilizer, and an anionic stabilizer. In embodiments, the micro-stabilizer may comprise a low molecular weight surfactant, wherein the low molecular weight surfactant may comprise one or more short chain ethylene oxide/propylene oxide copolymers and alkyl sulfates. In embodiments, the ethylene oxide/propylene oxide copolymer has a molecular weight less than or equal to 3500 g/mol. In embodiments, the ethylene oxide/propylene oxide copolymer has an ethylene oxide to propylene oxide ratio of about 0.7: 1.4. In embodiments, the ethylene oxide/propylene oxide copolymer has a degree of branching of less than 30%.

According to embodiments, the method may utilize a membrane having any desired shape. For example, the membrane may have a circular, square, oval, rectangular cross-sectional shape. The cross-section of the membrane is a cross-section through a plane parallel to the direction of flow of the dispersed phase through the membrane. In embodiments, the membrane may be planar. In embodiments, the membrane may be cylindrical, for example as shown in fig. 1.

In embodiments, the membrane may be mechanically moved in one or more directions. For example, the membrane may oscillate, pivot, vibrate or pulse.

In embodiments, the film may be moved in a direction perpendicular to the direction in which the dispersed phase exits the film.

In embodiments, the movement of the membrane may be performed at a rotational frequency of about 5Hz to about 100Hz, or about 10Hz to about 70 Hz. For example, the rotational frequency may be about 5Hz, 10Hz, 15Hz, 20Hz, 25Hz, 30Hz, 35Hz, 40Hz, 45Hz, 50Hz, 60Hz, 70Hz, 80Hz, 90Hz, or 100 Hz.

In embodiments, the film may have an amplitude of motion of about 0.1mm to about 30mm, or about 1mm to about 20mm, or about 1mm to about 10 mm. For example, the membrane may have an amplitude of motion of about 0.1mm, 0.5mm, 1mm, 2mm, 3mm, 4mm, 5mm, 6mm, 7mm, 8mm, 9mm, 10mm, 15mm, 20mm, 25mm, or 30 mm.

In embodiments, the film may have a thickness of from about 1 μm to about 1000 μm, or from about 5 μm to about 500 μm, or from about 10 μm to about 500 μm, or from about 20 μm to about 200 μm. For example, the film can have a thickness of about 10 μm, 15 μm, 20 μm, 25 μm, 30 μm, 40 μm, 50 μm, 60 μm, 70 μm, 80 μm, 90 μm, 100 μm, 110 μm, 120 μm, 130 μm, 140 μm, 150 μm, or 200 μm.

In embodiments, the membrane may be made of one or more of a metal, a ceramic material, silicon or silicon oxide, and a polymeric material. In embodiments, the membrane is substantially metallic or entirely metallic. According to another embodiment, the membrane is a chemically resistant metal, such as nickel or steel.

Referring to fig. 2-3B, in an embodiment, the membrane has a plurality of pores or pores. The pores or voids may have any suitable size, density and arrangement on the surface of the membrane. In embodiments, the pores or pores may have an average diameter of about 0.1 μm to about 50 μm, or about 0.1 μm to about 35 μm, or about 0.5 μm to about 30 μm, or about 0.5 μm to about 20 μm, or about 1 μm to about 20 μm, or about 4 μm to about 20 μm. For example, the plurality of pores or pores in the membrane may have an average diameter of about 0.1 μm, 0.5 μm, 1 μm, 2 μm, 3 μm, 4 μm, 5 μm, 6 μm, 7 μm, 8 μm, 9 μm, 10 μm, 15 μm, 20 μm, 25 μm, 30 μm, 35 μm, 40 μm, 45 μm, 50 μm. The plurality of pores or apertures may be randomly dispersed throughout the surface of the film, or may be arranged in a specified pattern across the surface of the film. For example, the membrane may include a plurality of pores in a circular, rectangular, square, triangular, pentagonal, hexagonal, or octagonal array.

The exemplary film pattern shown in fig. 2 includes a pore diameter of 5 μm, with a spacing between adjacent pores of 75 μm, as measured by the distance between the centers of adjacent pores. The example of fig. 2 shows a hexagonal array. Any suitable membrane may be used, including commercially available membranes. Table 1 below provides some exemplary membrane characteristics that may be used in embodiments of the present disclosure.

TABLE 1

Pore diameter (d)p，μm)	Distance between pores (L, μm)	Open area (%)	L/dp *
				5	75	0.4	15
7	40	2.8	5.7
				4.64	75	0.35	16.2
2.5	40	0.35	16
				17.6	75	5	4.3
9.4	40	5	4.3

*L/d_pThe distance between the pores divided by the diameter of the pores

In fig. 2, the percent open area may be calculated as:

wherein the total area calculation is dependent on the shape of the membrane.

In embodiments, rectangular sections of the film may be used to calculate the percent open area, assuming the spacing and size of the holes through the remaining surface of the film are regular. In such embodiments, the cross-section of the holes within the rectangle is used, and the total area is represented by the area of the rectangle. For example, the% open area of a membrane having a pore size of 7 μm can be calculated as follows:

open area (2 × pore section) 2 (pi/4) (d)_p) 77 μm [ where d_p＝7μm]

Total area 75 μmx130 μm 9750 μm rectangular area

Open area% (% open area/total area) (% open area) (% total area)

In embodiments, the plurality of pores or adjacent ones of the pores in the membrane may be spaced apart by an average distance of from about 5 μm to about 500 μm, or from about 10 μm to about 250 μm, or from about 10 μm to about 200 μm between the centers of each pore or pore. For example, the plurality of pores or pores in the membrane can have a distance between the centers of each pore of about 5 μm, 10 μm, 20 μm, 30 μm, 40 μm, 50 μm, 60 μm, 70 μm, 75 μm, 80 μm, 90 μm, 100 μm, 110 μm, 120 μm, 130 μm, 140 μm, 150 μm, 160 μm, 170 μm, 180 μm, 190 μm, 200 μm, 210 μm, 220 μm, 230 μm, 240 μm, or 250 μm. In embodiments, the plurality of pores or adjacent ones of the pores in the film may have an irregular or random spacing, or alternatively the spacing may be uniform or patterned.

In embodiments, one or both of the first and second sides of the membrane may have an open area of about 0.01% to about 20%, or about 0.1% to about 10%, or about 0.2% to about 10%, or about 0.3% to about 5%. For example, the film can have an open area of about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, or 20% of the film side surface area. In embodiments, the apertures may be conical or otherwise tapered such that the openings on the first side are different in size than the openings on the second side, thereby creating different open areas on the first and second sides. For example, the aperture may have a larger opening on the first side and a smaller opening on the second side. In embodiments, the aperture may have a smaller opening on the first side and taper to a larger opening on the second side.

In embodiments, the dispersed phase may be about 1m³/m²h to about 500m³/m²h. Or about 1m³/m²h to about 300m³/m²h. Or about 2m³/m²h to about 200m³/m²h. Or about 5m³/m²h to about 150m³/m²h、5m³/m²h to about 100m³/m²h passes through a plurality of pores in the membrane. For example, the dispersed phase may be 1m³/m²h、2m³/m²h、3m³/m²h、4m³/m²h、5m³/m²h、6m³/m²h、7m³/m²h、8m³/m²h、9m³/m²h、10m³/m²h、20m³/m²h、30m³/m²h、40m³/m²h、50m³/m²h、60m³/m²h、70m³/m²h、80m³/m²h、90m³/m²h、100m³/m²h、150m³/m²h、200m³/m²h、250m³/m²h、300m³/m²h、350m³/m²h、400m³/m²h、450m³/m²h or 500m³/m²The flux rate of h passes through a plurality of pores in the membrane. As described herein, flux is calculated by the following equation:

wherein, # pores is the number of pores, and D_{Pores of}The diameter of the pores in the membrane.

The flow rate of the continuous phase may be adjusted in conjunction with the flow rate of the dispersed phase to obtain a desired concentration of the dispersed phase in the continuous phase.

It has been advantageously found that the concentration by weight of the dispersed phase in the continuous phase can be controlled as a function of the ratio of the flow rate of the dispersed phase through the plurality of pores in the membrane to the flow rate of the continuous phase through the second side of the membrane. Advantageously, the methods of the present disclosure can allow for precise control of the concentration of the dispersed phase in the continuous phase. This may advantageously allow a high concentration of dispersed phase to be incorporated into the continuous phase while making the necessary controls to prevent overloading of the continuous phase and to avoid a concentration at which droplets of dispersed phase start to coalesce. In embodiments, the ratio of the continuous phase flow rate to the dispersed phase flow rate may be 0.1:1, 0.5:1, 1:1, 1.2:1, 1.5:1, 1.8:1, 2:1, 2.5:1, 3:1, 4:1, or 5: 1. As mentioned above, the choice of the stabilizer system may also allow to prevent or limit droplet coalescence while allowing a high concentration of the dispersed phase in the continuous phase. This is advantageous in achieving a high concentration of emulsion while maintaining a narrow capsule size distribution.

According to embodiments, the concentration of the dispersed phase in the continuous phase may be from about 1% to about 70% by weight, or from about 5% to about 60%, or from about 20% to about 60%, or from about 30% to about 60%, or from about 40% to about 60%, based on the weight of the dispersed phase divided by the total weight of the emulsion. Advantageously, the methods herein can have a concentration of the dispersed phase in the continuous phase of about 30% or more (e.g., about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, or 60%). In embodiments, the concentration of the dispersed phase in the continuous phase may be up to about 60% while maintaining limited coalescence such that the number population diameter CoV in the emulsion is less than or equal to 100%. In embodiments, the resulting emulsion may have a concentration of the dispersed phase in the continuous phase of greater than or equal to 40%, or greater than or equal to 50%, while maintaining a number population diameter CoV in the emulsion of less than or equal to 100%. In embodiments, high concentrations of the dispersed phase in the continuous phase may be achieved by having: (1) high flux of the dispersed phase through the membrane, (2) a tuned stabilizer system, and (3) high shear stress at the membrane surface.

Having a high flux of the dispersed phase in the membrane can be beneficial to obtain a high concentration of the dispersed phase in the continuous phase, because the higher the velocity of the dispersed phase, the more the dispersed phase reaches the surface of the membrane, thereby increasing the frequency of droplet formation and, therefore, the total concentration of the dispersed phase in the continuous phase. Having a tuned stabilizer system can be advantageous because the stabilizer system can stabilize droplets of the dispersed phase and reduce the rate of coalescence of the dispersed phase droplets and increase the rate of mass transfer. Increasing the mass transfer rate may be advantageous to avoid coalescence and achieve a narrow size distribution, since new molecules of the stabilizer system have to reach the surface of the film at the same time as the droplets are formed. Increasing the mass transfer rate can facilitate transport of dispersed phase droplets away from the surface of the film where new droplets are formed, to avoid further coalescence and reduce the local concentration of the dispersed phase near the film. However, having a high concentration of the stabilizer system in the emulsion increases the viscosity of the overall emulsion. Having an increased emulsion viscosity may slow the mass transport of the stabilizer molecules and droplets of the dispersed phase through the continuous phase, resulting in a higher rate of coalescence of the dispersed phase. Thus, there is a need to adjust the stabilizer system to have sufficient concentration in the emulsion to achieve this advantage without negatively impacting the emulsion by increasing the viscosity too much. Having high shear stress at the film surface may be advantageous because increased shear stress reduces the droplet size of the dispersed phase, which facilitates movement of the droplets of the dispersed phase from the film surface.

In embodiments, table 2 shows the minimum and maximum values related to the concentration of the dispersed phase in the continuous phase. τ can be calculated using the following equation:

wherein:

τ_maxfor peak shear events during oscillation (maximum shear stress)

Rho-density of continuous phase

Viscosity of the mu-continuous phase

a-amplitude of oscillation

f-oscillation frequency

TABLE 2

The methods also include initiating polymerization of the polymer precursor within the droplets of the dispersed phase. Various initiation methods can be used as known in the art and selected based on the monomers to be polymerized. By way of example, initiating polymerization of the polymer precursor can include methods involving one or more of free radical, pyrolysis, photolysis, redox reactions, persulfates, ionizing radiation, electrolysis, or ultrasonic treatment. In embodiments, initiating polymerization of the polymer precursor may include heating a dispersion of dispersed phase droplets in a continuous phase. In embodiments, initiating polymerization of the polymer precursor can include exposing a dispersion of dispersed phase droplets in the continuous phase to ultraviolet radiation. In embodiments, initiating polymerization may include activating an initiator present in one or both of the dispersed phase and the continuous phase. In embodiments, the initiator may be one or more of a thermally activated initiator, a photo-activated initiator, a redox activated initiator, and an electrochemically activated initiator.

In embodiments, the initiator may comprise a free radical initiator, wherein the free radical initiator may be one or more of a peroxy initiator, an azo initiator, a peroxide, and a compound such as 2,2' -azobismethylbutyronitrile, dibenzoyl peroxide, and the like. More specifically and without limitation, the radical initiator may be selected from the group of initiators comprising: azo or peroxy initiators, such as peroxides, dialkyl peroxides, alkyl peroxides, peroxy esters, peroxy carbonates, peroxy ketones and peroxy dicarbonates, 2 '-azobis (isobutyronitrile), 2' -azobis (2, 4-dimethylvaleronitrile), 2 '-azobis (2-methylpropionitrile), 2' -azobis (2-methylbutyronitrile), 1 '-azobis (cyclohexanecarbonitrile), 1' -azobis (cyanocyclohexane), benzoyl peroxide, decanoyl peroxide; lauroyl peroxide; benzoyl peroxide, di (n-propyl) peroxydicarbonate, di (sec-butyl) peroxydicarbonate, di (2-ethylhexyl) peroxydicarbonate, 1-dimethyl-3-hydroxybutyl peroxyneodecanoate, a-cumyl peroxyneoheptanoate, tert-amyl peroxyneodecanoate, tert-butyl peroxyneodecanoate, tert-amyl peroxypivalate, tert-butyl peroxypivalate, 2, 5-dimethyl-2, 5-di (2-ethylhexanoylperoxy) hexane, tert-amyl peroxy-2-ethylhexanoate, tert-butyl peroxyacetate, di-tert-amyl peroxyacetate, tert-butyl peroxide, di-tert-amyl peroxide, 2, 5-dimethyl-2, 5-di- (tert-butylperoxy) -3-hexyne, Cumene hydroperoxide, 1-di- (tert-butylperoxy) -3,3, 5-trimethyl-cyclohexane, 1-di- (tert-butylperoxy) -cyclohexane, 1-di- (tert-pentylperoxy) -cyclohexane, ethyl-3, 3-di- (tert-butylperoxy) -butyrate, tert-amyl perbenzoate, tert-butyl perbenzoate, ethyl-3, 3-di- (tert-pentylperoxy) -butyrate, and the like.

In embodiments, the initiator may comprise a thermal initiator. In embodiments, the thermal initiator may have a bond dissociation energy of 100kJ/mol to about 170 kJ/mol. The thermal initiator may comprise one or more of the following: peroxides such as acyl peroxide, acetyl peroxide, and benzoyl peroxide; azo compounds such as 2,2 '-azobisisobutyronitrile, 2' -azobis (2, 4-dimethylvaleronitrile), 4 '-azobis (4-cyanovaleric acid) and 1,1' -azobis (cyclohexanecarbonitrile); and disulfides.

In embodiments, the initiator may comprise a redox initiator, such as a combination of an inorganic reducing agent and an inorganic oxidizing agent. For example, reducing agents such as peroxodisulfates, HSO₃ ^-、SO₃ ^2-、S-₂O₃ ^2-、S₂O₅ ^2-Or alcohols having a source of oxidant, such as Fe²⁺、Ag⁺、Cu²⁺、Fe³⁺、ClO₃ ^-、H₂O₂、Ce⁴⁺、V⁵⁺、Cr⁶⁺Or Mn³⁺。

In embodiments, the initiator may include one or more photochemical initiators, such as benzophenone; acetophenone; benzil; benzaldehyde; o-chlorobenzaldehyde; xanthone; a thioxanthone; 9, 10-anthraquinone; 1-hydroxycyclohexyl phenyl ketone; 2, 2-diethoxyacetophenone; dimethoxy phenylacetophenone; methyldiethanolamine; dimethylaminobenzoic acid salt; 2-hydroxy-2-methyl-1-phenylpropan-1-one; 2, 2-di-sec-butoxyacetophenone; 2, 2-dimethoxy-1, 2-diphenylethan-1-one; dimethoxy ketal; and phenylglyoxal 2,2' -diethoxyacetophenone, hydroxycyclohexylphenylketone, α -hydroxyketone, α -aminoketone, α -naphthylcarbonyl compound and β -naphthylcarbonyl compound, benzoin ethers (such as benzoin methyl ether), benzil ketals (such as benzil dimethyl ketal), acetophenone, fluorenone, 2-hydroxy-2-methyl-l-phenylpropan-1-one. Such UV initiators are commercially available, for example Irgacure 184, Irgacure 369, Irgacure LEX 201, Irgacure 819, Irgacure 2959Darocur 4265 or Degacure 1173 from Ciba, or visible light initiators: irgacure 784 and camphorquinone (Genocure CQ). In embodiments, the initiator may be a thermal initiator as described in patent publication WO 2011084141a 1.

In embodiments, the initiator may comprise one or more of 2,2' -azobis (2, 4-dimethylvaleronitrile), 2' -azobis (2-methylbutyronitrile), 4' -azobis (4-cyanovaleric acid), 2' -azobis [ N- (2-hydroxyethyl) -2-methylpropionamide ], 1' -azobis (cyclohexane-1-carbonitrile). Commercially available initiators, such as Vazo initiators, generally indicate the decomposition temperature of the initiator. In embodiments, initiators having decomposition points of about 50 ℃ or higher may be selected. In embodiments, the initiator is selected to stagger the decomposition temperatures of the various steps (pre-polymerization of the capsule shell material, shell formation, and hardening or polymerization). For example, the first initiator in the dispersed phase may decompose at 55 ℃ to facilitate prepolymer formation; the second initiator may decompose at 60 ℃ to aid in the formation of the shell material. Optionally, the third initiator may decompose at 65 ℃ to facilitate polymerization of the capsule shell material.

In embodiments, the total amount of initiator may be present in the dispersed phase in an amount of from about 0.001 wt% to about 5 wt%, or from about 0.01 wt% to about 4 wt%, or from about 0.1 wt% to about 2 wt%, based on the total weight of the dispersed phase. For example, the total amount of initiator may be present in the dispersed phase in an amount of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 2,3, 4, or 5 wt%.

In embodiments, the continuous phase may be substantially free of initiator. In embodiments, the total amount of initiator may be present in the continuous phase in an amount of from about 0% to about 3%, or from about 0.01% to about 2%. For example, the total amount of initiator may be present in the continuous phase in an amount of about 0.1 wt%, 0.2 wt%, 0.3 wt%, 0.4 wt%, 0.5 wt%, 0.6 wt%, 0.7 wt%, 0.8 wt%, 0.9 wt%, 1 wt%, 1.1 wt%, 1.2 wt%, 1.3 wt%, 1.4 wt%, 1.5 wt%, 2 wt%, 3 wt%.

In embodiments, the dispersed phase may further comprise an inhibitor. In embodiments, the inhibitor may be one or more of oxygen, quinone, sodium nitrite. In embodiments, an inhibitor may be included to delay or prevent polymerization of the polymer precursor to form the capsule shell. The inhibitor may inhibit polymerization until certain conditions are met, such as until the inhibitor is consumed by the system over time, or may intentionally trigger polymerization despite changes in conditions to place the inhibitor in the dispersed phase or to overcome the effect of the inhibitor by the addition of one or more second compounds. Inhibitors may be advantageous for a variety of reasons, including controlling the capsule formation process and/or avoiding inadvertent premature polymerization before the dispersed phase is completely dispersed in the continuous phase.

In embodiments, the continuous phase may comprise a phase transfer catalyst to improve the effectiveness of the initiator in that phase. The phase transfer catalyst material may include, for example, one or more of quaternary ammonium salts and phosphonium salts, crown ethers, and cryptands.

In embodiments, and without intending to be bound by theory, it is believed that as the polymer precursor begins to polymerize, the resulting polymer becomes insoluble in the dispersed phase and further migrates to the interface between the dispersed phase and the continuous phase.

In any of the embodiments disclosed herein, the capsule may comprise a benefit agent in the core. In embodiments, the benefit agent may include one or more perfume compositions, perfume raw materials, silicone oils, waxes, hydrocarbons, higher fatty acids, essential oils, lipids, skin cooling agents, vitamins, sunscreens, antioxidants, glycerin, catalysts, bleach encapsulates, silica encapsulates, malodor reduction agents, odor control materials, chelating agents, antistatic agents, emollients, agricultural materials (such as pesticides, insecticides, nutrients, herbicides, fungal control agents, insect and moth repellents), colorants, antioxidants, chelating agents, base agents, drape and morphology control agents, smoothing agents, wrinkle control agents, sanitizers, disinfectants, microbe control agents, mold control agents, antiviral agents, desiccants, soil repellents, detergents, fabric fresheners and refreshment agents, chlorine bleach odor control agents, and/or odor control agents, Dye fixatives, dye transfer inhibitors, color retention agents, optical brighteners, color restoration/restoration agents, anti-fading agents, whiteness enhancers, anti-abrasion agents, fabric integrity agents, anti-wear agents, anti-pilling agents, defoamers, ultraviolet light protection agents, light fade inhibitors, anti-allergic agents, enzymes, water repellents, fabric comfort agents, anti-shrinkage agents, anti-stretch agents, stretch-recovery agents, other structuring agents (such as phase change materials, self-healing materials, skin care agents, glycerin, and natural actives), antimicrobial actives, antiperspirant actives, cationic polymers and dyes, food and feed additives (such as antioxidants, probiotics, and food and beverage colorants). In embodiments, the benefit agent may include one or more of the following: perfume compositions, perfume raw materials, sanitizers, disinfectants, antiviral agents, fabric fresheners and freshness maintenance agents, chlorine bleach odor control agents, dye fixatives, dyes, optical brighteners, color restoration/restoration agents, enzymes, defoamers, fabric comfort agents, skin care agents, lubricants, waxes, hydrocarbons, malodor reduction agents, odor control materials, fertilizers, nutrients, and herbicides.

In embodiments, the benefit agent may comprise a perfume or perfume composition. In embodiments, the perfume composition may comprise one or more of the following: perfume raw materials, essential oils, malodor reducing agents, and odor controlling agents.

The malodor reduction agent may be selected from the group consisting of antimicrobial materials, enzyme inhibitors, reactive aldehydes, masking fragrance raw materials and masking accords, and binding polymers (e.g., polyethylene imine). In embodiments, the dispersed phase may further comprise additional components, such as excipients, carriers, diluents, and other agents. In embodiments, the benefit agent may be mixed with an oil. In embodiments, the oil mixed with the benefit agent may include isopropyl myristate.

In embodiments, the dispersed phase may further comprise a processing aid. In embodiments, the processing aid may include one or more of a carrier, an aggregation inhibiting material, a deposition aid, and a particulate suspension polymer. Non-limiting examples of aggregation inhibiting materials include salts that can have a charge shielding effect around the capsule, such as magnesium chloride, calcium chloride, magnesium bromide, magnesium sulfate, and mixtures thereof. Non-limiting examples of particle-suspending polymers include: polymers such as xanthan gum, carrageenan, guar gum, shellac, alginates, chitosan; cellulosic materials such as carboxymethyl cellulose, hydroxypropyl methyl cellulose, cationically charged cellulosic materials; polyacrylic acid; polyvinyl alcohol; hydrogenated castor oil; ethylene glycol distearate; and mixtures thereof.

According to an embodiment, the capsules may be produced according to the methods described herein.

Test method

When the encapsulated active is incorporated into a product, the sample formulation for analysis should produce an aqueous suspension of non-aggregated particles for analysis that does not alter the initial size distribution. For example, representative formulations may include those described in WO2018169531A1, pages 31-34, the disclosure of which is incorporated herein.

Capsule size and distribution testing method

The capsule size distribution was determined by Single Particle Optical Sensing (SPOS), also known as Optical Particle Counting (OPC), using an AccuSizer 780AD instrument and accompanying software CW788 version 1.82(Particle Sizing Systems, Santa Barbara, California, u.s.a.) or equivalent. The instrument is configured with the following conditions and options: flow rate 1 ml/sec; lower size threshold 0.50 μm; sensor model LE400-05 or equivalent; opening after automatic dilution; collecting time is 60 seconds; the number of channels is 512; the volume of the vessel fluid is 50 ml; maximum coincidence 9200. The measurement is started by flushing the sensor with water to a cold state until the background count is less than 100. Samples in suspension of the delivery capsules were introduced and the density of the capsules was adjusted with DI water by automatic dilution as required to obtain a capsule count of at least 9200/ml. The suspension was analyzed over a period of 60 seconds. The size range used is 1um to 493.3 μm. Thus, the volume distribution and the number distribution are calculated as shown and described above.

From the cumulative volume distribution, a percentile 5 (d) is also calculated₅)、50(d₅₀) And 90 (d)₉₀) Is determined by the cumulative volume distribution, where the j percentage of the volume is cumulative)。

Delta rupture strength test method

To measure the Δ burst strength, three different measurements were made: i) volume weighted capsule size distribution; ii) the diameter of 10 individual capsules within each of the 3 specified size ranges, and; iii) the rupture force of the same 30 individual capsules.

a.) volume weighted capsule size distribution was determined by Single Particle Optical Sensing (SPOS), also known as Optical Particle Counting (OPC), using an AccuSizer 780AD instrument and accompanying software CW788 version 1.82(Particle Sizing Systems, Santa Barbara, California, u.s.a.) or equivalent. The instrument is configured with the following conditions and options: flow rate 1 ml/sec; lower size threshold 0.50 μm; sensor model LE400-05 or equivalent; opening after automatic dilution; collecting time is 60 seconds; the number of channels is 512; the volume of the vessel fluid is 50 ml; maximum coincidence 9200. The measurement is started by flushing the sensor with water to a cold state until the background count is less than 100. Samples in suspension of the delivery capsules were introduced and the density of the capsules was adjusted with DI water by automatic dilution as required to obtain a capsule count of at least 9200/ml. The suspension was analyzed over a period of 60 seconds. The resulting volume weighted PSD data is plotted and recorded and the values of the median, 5 th percentile and 90 th percentile are determined.

b.) the diameter and rupture force values (also known as burst force values) of each capsule were measured by a custom computer controlled micromanipulator system having a lens and camera capable of imaging the delivered capsule, and having a fine flat end probe connected to a load cell (such as model 403A from Aurora Scientific Inc. (Canada) or equivalent, as described in: zhang, Z et al (1999) "Mechanical string of single microcapsules determined by a novel microprocessing technology," J.Microfootprint, Vol.16, No. 1, page 117-.

c.) a drop of the delivery capsule suspension was placed on a glass microscope slide and dried under ambient conditions for several minutes to remove water and obtain a sparse monolayer of individual capsules on the dried slide. The concentration of capsules in the suspension is adjusted as needed to obtain the appropriate capsule density on the slide. More than one slide preparation may be required.

d.) the slide is then placed on the sample holding stage of the micromanipulation instrument. Thirty benefit delivery capsules on the slide are selected for measurement such that ten capsules are selected within each of three pre-sized bands. Each size band refers to the capsule diameter derived from the volume weighted PSD generated by the Accusizer. The three size bands of capsules are: median diameter +/-2 μm; the 5 th percentile diameter +/-2 μm; and 90 th percentile diameter +/-2 μm. The capsules that developed deflation, leakage or damage were excluded from the selection process and no measurements were taken.

e.) for each of the 30 selected capsules, the diameter of the capsule was measured from the image on the micromanipulator and recorded. The same capsule was then compressed between two flat surfaces (i.e., a flat end force probe and a glass microscope slide) at a rate of 2 μm per second until the capsule broke. During the compression step, probe forces are continuously measured and recorded by the data acquisition system of the micromanipulation instrument.

f.) calculating the cross-sectional area (π r) of each of the selected capsules using the measured diameter and assuming spherical capsules²Where r is the radius of the capsule prior to compression). The rupture force of each selected capsule was determined from the recorded force probe measurements, as shown in the following documents: zhang, Z et al (1999) "Mechanical string of single microorganisms determined by a novel microorganism modulation technique," J.Micromodulation, Vol.16, No. 1, page 117-.

g.) the rupture strength of each of the 30 capsules was calculated by dividing the rupture force (in newtons) by the calculated cross-sectional area of the respective capsule.

Using the recorded data, the delta burst strength was calculated

Wherein d is_iThe FS iodine at (b) is the FS of the capsule at percentile i of the volume size distribution.

Shell thickness measurement test method

Capsule shell thickness in nanometers was measured for 20 benefit agent containing delivery capsules using a cryofracture cryo-scanning electron microscope (FF cryoSEM) at magnification between 50000 and 150000 times. Samples were prepared by flash-chilling small volume suspensions of frozen capsules or finished products. Flash freezing can be achieved by immersion in liquid ethane, or by using devices such as 706802EM Pact type high pressure freezers (Leica Microsystems and Wetzlar, Germany) or equivalents. The frozen samples were fractured at-120 ℃ and then cooled to below-160 ℃ and lightly sputter coated with gold/palladium. These steps may be accomplished using low temperature production equipment such as those from Gatan Inc (Pleasanton, CA, USA) or equivalents. The frozen, fractured and coated samples are then transferred to a suitable cryoSEM microscope such as Hitachi S-5200SEM/STEM (Hitachi High Technologies, Tokyo, Japan) or equivalent at-170 ℃ or lower. In Hitachi S-5200, imaging was performed with 3.0KV accelerating voltage and 5 μ A to 20 μ A tip emission current.

Images of the fractured shells were taken in the form of cross-sectional views of 20 beneficial delivery capsules selected in a random manner that was not biased by their size to form representative samples exhibiting a distribution of capsule sizes. The shell thickness of each of the 20 capsules was measured using calibrated microscope software by drawing a measurement line perpendicular to the tangent to the outer surface of the capsule wall. 20 individual shell thickness measurements were recorded and used to calculate the average thickness, and the percentage of capsules having the selected shell thickness.

The diameter of the 20 cross-section capsules was also measured using calibrated microscope software by drawing a measurement line perpendicular to the capsule cross-section.

Effective volume core-shell ratio assessment

The effective volume core-shell ratio value is determined as follows, depending on the average shell thickness as measured by the shell thickness test method. The effective volume core-shell ratio of the capsules whose average shell thickness was measured was calculated by the following formula:

where the thickness is the thickness of the shell of a single capsule and Dcaps is the diameter of the cross-sectional capsule.

The results of 20 independent effective volume core-shell ratio calculations were recorded and used to calculate the average effective volume core-shell ratio.

This ratio can be converted to a core-shell ratio score value by calculating the core weight percent using the following equation:

and the shell percentage may be calculated based on the following formula:

100-% shell ═ core.

Logarithmic (logP) test method for octanol/water partition coefficient

The log value (logP) of the octanol/water partition coefficient of each Perfume Raw Material (PRM) in the tested perfume mixtures was calculated. logP (logP) of a single PRM was calculated using the Consensus logP calculation model version 14.02(Linux) or equivalent available from Advanced Chemistry Development Inc. (ACD/Labs) (Toronto, Canada)_i) To provide a dimensionless logP value. The Consensus log P Computational Model of ACD/Labs is part of the ACD/Labs Model suite.

The individual logP of each PRM was recorded to calculate the average logP of the perfume composition by using the following formula:

wherein x_iIs the weight% of PRM in the perfume composition.

Examples

While particular embodiments of the present disclosure have been illustrated and described, it would be obvious to those skilled in the art that various other changes and modifications can be made without departing from the spirit and scope of the disclosure. It is therefore intended to cover in the appended claims all such changes and modifications that are within the scope of this disclosure. In each of the following examples 1-7, the membrane utilized is shown in fig. 1.

Comparison of capsules prepared according to the present disclosure with conventional batch processing

Example 1

Referring to fig. 4A-10B, a capsule according to the present disclosure is prepared. The following method was used. A first oil solution, which is an initiator solution, was formed by mixing aromatic oil (44.85 wt%), isopropyl myristate (54.2 wt%), 2 '-azobis (2, 4-dimethylvaleronitrile) (Vazo 52, 0.58 wt%), and 2,2' -azobis (2-methylbutyronitrile) (Vazo-670.38 wt%) at 20 ℃. A second oil solution, which was a monomer solution, was formed by mixing aromatic oil (81.34 wt.%) and Sartomer CN975 (hexafunctional aromatic urethane acrylate oligomer, 18.66 wt.%) at 20 ℃. The first and second oil solutions were then pumped using two gear pumps (ISMATEC, micropump 0.32ml/rev) at a 1:1 weight ratio to form the dispersed phase before entering the membrane shaft.

A continuous phase (aqueous solution) comprising an aqueous solution of seviol 540(1.78 wt%), NaOH (0.07 wt%), and 4,4' -azobis (4-cyanovaleric acid) (Vazo 68WSP, 0.37 wt%) was prepared. The continuous phase was pumped across the second surface of the membrane by using a Tuthill GDS pump.

Emulsification was performed using a vibrating membrane emulsification device. The membrane device included a laser drilled membrane with a stainless steel membrane (supplied by Micropore) laser welded and mounted vertically on the membrane shaft. The membrane has pores with a diameter of 7 μm, wherein the pores are arranged in a hexagonal array and adjacent pores are spaced apart by a distance of 40 μm, as measured from pore center to pore center. A membrane shaft is inserted into the membrane housing and coupled to the oscillation motor. The continuous phase is pumped into the gap between the membrane shaft and the housing. The dispersed phase is injected from the top of the membrane axis towards the back portion of the membrane. The dispersed phase permeates through the pores of the membrane to the continuous phase, thereby forming an emulsion that exits the emulsion chamber to be collected in a collection vessel.

The flux of the dispersed phase through the membrane was 24.9m³/(m²And adjusting the mass flow rate of the continuous phase to achieve a ratio of the continuous phase to the dispersed phase of 1.5.Two flow rates were measured by using a Coriolis mass flowmeter (Bronkhorst, m14) placed between the pump and the membrane device. The membrane axis was oscillated at a frequency of 30Hz and an oscillation amplitude of 12.9 mm.

Once a liter of the emulsion was collected in the jacketed vessel, polymerization was initiated to form capsules. The polymerization was initiated by gently mixing the emulsion at 200rpm and the temperature was raised to 60 ℃ over a 15 minute ramp cycle. The temperature was then maintained at 60 ℃ for 45 minutes. The temperature was then raised to 75 ℃ over a 30 minute ramp cycle, followed by a 4 hour hold at 75 ℃. Finally the temperature was raised to 90 ℃ over a 30 minute ramp cycle and held at 90 ℃ for 8 hours. The batch was then allowed to cool to room temperature.

Comparative example 1

Batch process

Referring to fig. 11A-17B, capsules prepared by a conventional batch process are shown. These capsules were prepared by the following method. An oil solution (dispersed phase) was prepared by mixing aromatic oil (63.09 wt%), isopropyl myristate (27.1 wt%), Vazo 52(0.29 wt%) and Vazo-67(0.19 wt%), Sartomer CN975 (hexafunctional aromatic urethane acrylate oligomer, 9.33 wt%) at 20 ℃.

An aqueous solution (continuous phase) was prepared by mixing Selvol 540 polyvinyl alcohol (1.78 wt%), NaOH (0.07 wt%), and Vazo-68WSP (0.37 wt%).

The dispersed phase and the continuous phase were mixed at a ratio of the continuous phase to the dispersed phase of 1.5 and 1100rpm for 30 minutes with a 4-pitched blade stirrer having a diameter of 5cm, to obtain an emulsion.

Once the emulsion was complete, it was transferred to a jacketed vessel and gently mixed at 200rpm and its temperature was raised to 60 ℃ over 15 minutes. The temperature was then maintained at 60 ℃ for 45 minutes, raised to 75 ℃ over 30 minutes, maintained at 75 ℃ for 4 hours, heated to 90 ℃ over 30 minutes, and maintained at 90 ℃ for 8 hours. The batch was then allowed to cool to room temperature.

Comparative example 2

Batch process

Referring to fig. 18A to 24B, the capsules are prepared according to a conventional batch method. A first oil solution was prepared by mixing the aromatic oil (61.86 wt%), isopropyl myristate (37.48 wt%), Vazo-52(0.40 wt%) and Vazo-67(0.26 wt%) in a temperature controlled steel jacketed reactor at 35 c with mixing at 1000rpm (4 tips, 2 inch diameter, beveled blades) and a nitrogen blanket applied at 100 cc/min. The oil solution was heated to 75 ℃ over a 45 minute ramp, held at 75 ℃ for 45 minutes, and cooled to 60 ℃ over a 75 minute ramp.

A second oil solution was prepared by mixing aromatic oil (64.77 wt%), t-butylaminoethyl methacrylate (0.86 wt%), carboxyethyl 2-acrylate (0.69 wt%), and Sartomer CN975(33.68 wt%) (hexafunctional aromatic urethane acrylate oligomer), and then added to the first oil solution when the first oil solution reached 60 ℃. The ratio of the first oil solution to the second oil solution was 2.6: 1. The combined oil solutions represent the dispersed phase and are kept at 60 ℃ for a further 10 minutes.

Separately, the continuous phase was prepared as an aqueous solution comprising an aqueous solution of Selvol 540(1.78 wt%), NaOH (0.07 wt%), and Vazo 68WSP (0.37 wt%).

The continuous phase and the dispersed phase were mixed at 1100rpm for 30 minutes at 60 deg.C (with a stirrer having a diameter of 5 cm) to emulsify the dispersed phase into the continuous phase. The ratio of continuous phase to dispersed phase was 1.5. After emulsification was complete, mixing was continued with an anchoring mixer at 200 rpm. The batch was held at 60 ℃ for 45 minutes, then the temperature was raised to 75 ℃ over a ramp period of 30 minutes, held at 75 ℃ for 4 hours, then finally heated to 90 ℃ over a ramp period of 30 minutes and held at 90 ℃ for 8 hours to polymerize the capsule shells. The batch was then allowed to cool to room temperature.

EXAMPLES results summarization

As shown by a comparison of fig. 4A to 10B to fig. 11A to 24B, the capsule of example 1 has a narrower capsule distribution. Table 3 provides various parameters of the resulting capsules including average diameter, coefficient of diameter variation expressed as volume percent and number percent, delta burst strength percent, average wall thickness (nm), average effective ratio of core volume percent to shell volume percent. As shown in table 3, the capsules according to the present disclosure have a lower number population diameter CoV, and a lower percentage of delta burst strength compared to the batch process. Based on these results, it is believed that capsules according to the present disclosure will have improved performance to reliably and more uniformly release the benefit agent (when part of the formulated product).

TABLE 3

Additional embodiments of capsules prepared by the method according to the present disclosure

Example 2

A first oil solution, which is an initiator solution, was formed by mixing aromatic oil (57.95 wt%), isopropyl myristate (41.39 wt%), 2 '-azobis (2, 4-dimethylvaleronitrile) (Vazo 52, 0.40 wt%) and 2,2' -azobis (2-methylbutyronitrile) (Vazo-670.26 wt%) at 20 ℃. The resulting solution was a clear liquid.

A second oil solution, which was a monomer solution, was formed by mixing aromatic oil (64.77 wt%), t-butylaminoethyl methacrylate (0.86 wt%), carboxyethyl 2-acrylate (0.69 wt%), and Sartomer CN975 (hexafunctional aromatic urethane acrylate oligomer, 33.68 wt%). The second solution is then added to the first oil solution. The ratio of the first oil solution to the second oil solution was 2.60:1 by total weight. The combined oils were mixed at 25 ℃ for a further 10 minutes to form the dispersed phase.

The continuous phase was an aqueous solution containing sevol 540(5 wt%), NaOH (0.07 wt%), and 4,4' -azobis (4-cyanovaleric acid) (0.37 wt%).

Emulsification was performed by using a vibrating membrane emulsification device supplied by Micropore. The membrane device consists of a laser drilled membrane (stainless steel membrane laser welded and mounted vertically on the membrane shaft). A membrane shaft is inserted into the membrane housing and coupled to the oscillation motor. The continuous phase was pumped into the gap between the membrane shaft and the housing using a gear pump (ISMATEC, micropump 0.32 ml/rev). The dispersed phase was injected from the top of the membrane shaft towards the back part of the membrane using a gear pump (ISMATEC, micropump 0.017 ml/rev). The dispersed phase permeates through the pores of the membrane to the continuous phase injected using a gear pump (ISMATEC, micropump 0.32ml/rev), moving up to a collection vessel. The membrane had pores with a diameter of 7 μm, wherein the pores were arranged in a hexagonal array and adjacent pores were spaced apart by 75 μm as measured by the distance between the centers of the pores.

The flux of the dispersed phase through the membrane was 2.2m³/(m²And adjusting the mass flow rate of the continuous phase to achieve a ratio of continuous to dispersed phase of 2.2. Two flow rates were measured by using a Coriolis mass flowmeter (Bronkhorst, m14) placed between the pump and the membrane device. The membrane axis was oscillated at a frequency of 30Hz and an oscillation amplitude of 3 mm. Once a liter of the emulsion was collected in the jacketed vessel, it was gently mixed at 200rpm and its temperature was raised to 60 ℃ over 15 minutes. The temperature was then maintained at 60 ℃ for 45 minutes, raised to 75 ℃ over 30 minutes, maintained at 75 ℃ for 4 hours, heated to 90 ℃ over 30 minutes, and maintained at 90 ℃ for 8 hours. The batch was then allowed to cool to room temperature.

The average volume size of the obtained capsule population was 28.3 μm, and the capsules had a diameter coefficient of variation based on volume percentage of 20.4%.

Example 3

A first oil solution, which is an initiator solution, was formed by mixing aromatic oil (44.85 wt%), isopropyl myristate (54.2 wt%), 2 '-azobis (2, 4-dimethylvaleronitrile) (Vazo 52, 0.58 wt%), and 2,2' -azobis (2-methylbutyronitrile) (Vazo-670.38 wt%) at 20 ℃. A second oil solution, which was a monomer solution, was formed by mixing aromatic oil (81.34 wt.%) and Sartomer CN975 (hexafunctional aromatic urethane acrylate oligomer, 18.66 wt.%) at 20 ℃. The first and second oil solutions were then pumped using two gear pumps (ISMATEC, micropump 0.32ml/rev) at a 1:1 weight ratio to form the dispersed phase before entering the membrane shaft.

A continuous phase (aqueous solution) comprising an aqueous solution of seviol 540(1.78 wt%), NaOH (0.07 wt%), and 4,4' -azobis (4-cyanovaleric acid) (Vazo 68WSP, 0.37 wt%) was prepared. The continuous phase was pumped across the second surface of the membrane by using a Tuthill GDS pump.

Emulsification was performed using a vibrating membrane emulsification device. The membrane device included a laser drilled membrane with a stainless steel membrane (supplied by Micropore) laser welded and mounted vertically on the membrane shaft. The membrane has pores with a diameter of 7 μm, wherein the pores are arranged in a hexagonal array and adjacent pores are spaced apart by a distance of 40 μm, as measured from pore center to pore center. A membrane shaft is inserted into the membrane housing and coupled to the oscillation motor. The continuous phase is pumped into the gap between the membrane shaft and the housing. The dispersed phase is injected from the top of the membrane axis towards the back portion of the membrane. The dispersed phase permeates through the pores of the membrane to the continuous phase, thereby forming an emulsion that exits the emulsion chamber to be collected in a collection vessel.

The flux of the dispersed phase through the membrane was 24.9m³/(m²And adjusting the mass flow rate of the continuous phase to achieve a ratio of the continuous phase to the dispersed phase of 1.5. Two flow rates were measured by using a Coriolis mass flowmeter (Bronkhorst, m14) placed between the pump and the membrane device. The membrane axis was oscillated at a frequency of 30Hz and an oscillation amplitude of 12.9 mm.

Once a liter of the emulsion was collected in the jacketed vessel, polymerization was initiated to form capsules. The polymerization was initiated by gently mixing the emulsion at 200rpm and the temperature was raised to 60 ℃ over a 15 minute ramp cycle. The temperature was then maintained at 60 ℃ for 45 minutes. The temperature was then raised to 75 ℃ over a 30 minute ramp cycle, followed by a 4 hour hold at 75 ℃. Finally the temperature was raised to 90 ℃ over a 30 minute ramp cycle and held at 90 ℃ for 8 hours. The batch was then allowed to cool to room temperature.

The resulting capsules had an average volume size of 24.9 μm and the capsules had a diameter coefficient of variation based on volume percent of 23%.

Example 4

An oil solution was prepared by mixing aromatic oil (97.19 wt%), t-butylaminoethyl methacrylate (0.07 wt%), 2-carboxyethyl acrylate (0.06 wt%), and Sartomer CN975 (hexafunctional aromatic urethane acrylate oligomer, 2.68 wt%) at 20 ℃. The resulting solution was a clear liquid. Then, 2 '-azobis (2, 4-dimethylvaleronitrile) (Vazo 52, 0.41 wt%) and 2,2' -azobis (2-methylbutyronitrile) (Vazo-670.27 wt%) were added, and the resulting liquids were mixed at 20 ℃. The resulting mixture remained as a clear liquid. Finally, isopropyl myristate (29.89 wt%) was added. The combined oils were mixed at 25 ℃ for a further 10 minutes to form the dispersed phase.

The continuous phase was prepared as an aqueous solution comprising an aqueous solution of seviol 540(2 wt%), NaOH (0.07 wt%), and 4,4' -azobis (4-cyanovaleric acid) (0.37 wt%).

Emulsification was performed by using a vibrating membrane emulsification device supplied by Micropore. The membrane device consists of a laser drilled membrane (stainless steel membrane laser welded and mounted vertically on the membrane shaft). A membrane shaft is inserted into the membrane housing and coupled to the oscillation motor. The gap between the membrane shaft and the housing is where the continuous phase is pumped. The dispersed phase was injected from the top of the membrane shaft toward the back portion of the membrane by using a gear pump (ISMATEC, micropump 0.017 ml/rev). The dispersed phase permeates through the pores of the membrane to the continuous phase injected using a gear pump (ISMATEC, micropump 0.32ml/rev), moving up to a collection vessel.

The flux of the dispersed phase through the membrane was 65.6m³/(m²And adjusting the mass flow rate of the continuous phase to achieve a ratio of the continuous phase to the dispersed phase of 1.5. Two flow rates were measured by using a Coriolis mass flowmeter (Bronkhorst, m14) placed between the pump and the membrane device. The membrane axis was oscillated at a frequency of 30Hz and an oscillation amplitude of 3 mm.

Once a liter of the emulsion was collected in the jacketed vessel, it was gently mixed at 200rpm and its temperature was raised to 60 ℃ over 15 minutes. The temperature was then maintained at 60 ℃ for 45 minutes, raised to 75 ℃ over 30 minutes, maintained at 75 ℃ for 4 hours, heated to 90 ℃ over 30 minutes, and maintained at 90 ℃ for 8 hours. The batch was then allowed to cool to room temperature.

The average volume size of the obtained capsule population was 28.8um, and the capsules had a diameter coefficient of variation based on volume percentage of 22.7%.

Example 5

An oil solution was prepared by mixing aromatic oil (92.97 wt%), t-butylaminoethyl methacrylate (0.17 wt%), carboxyethyl 2-acrylate (0.14 wt%) and Sartomer CN975 (hexafunctional aromatic urethane acrylate oligomer, 6.72 wt%) at 20 ℃. The resulting solution was a clear liquid. Then, 2 '-azobis (2, 4-dimethylvaleronitrile) (Vazo 52, 0.41 wt%) and 2,2' -azobis (2-methylbutyronitrile) (Vazo-670.27 wt%) were added, and the resulting liquids were mixed at 20 ℃. The resulting solution remained as a clear liquid. Finally, isopropyl myristate (29.89 wt%) was added and mixed for an additional 10 minutes at 25 ℃ to form the dispersed phase.

The continuous phase was formed as an aqueous solution comprising an aqueous solution of seviol 540(2 wt%), NaOH (0.07 wt%), and 4,4' -azobis (4-cyanovaleric acid) (0.37 wt%).

Emulsification was performed by using a vibrating membrane emulsification device supplied by Micropore. The membrane device comprises a laser drilled membrane (stainless steel membrane laser welded and mounted vertically on the membrane shaft). A membrane shaft is inserted into the membrane housing and coupled to the oscillation motor. The continuous phase was pumped into the gap between the membrane shaft and the housing using a gear pump (ISMATEC, micropump 0.32 ml/rev). The dispersed phase was injected from the top of the membrane shaft towards the back part of the membrane using a gear pump (ISMATEC, micropump 0.017 ml/rev). The dispersed phase permeates through the pores of the membrane to the continuous phase injected using a gear pump (ISMATEC, micropump 0.32ml/rev), moving up to a collection vessel. The membrane had pores with a diameter of 7 μm arranged in a hexagonal array with adjacent pores spaced apart by 75 μm as measured by the distance between the centers of the pores.

The flux of the dispersed phase through the membrane was 2.2m³/(m²And adjusting the mass flow rate of the continuous phase to achieve a ratio of continuous to dispersed phase of 2.2. Two flow rates were measured by using a Coriolis mass flowmeter (Bronkhorst, m14) placed between the pump and the membrane device.

Once a liter of the emulsion was collected in the jacketed vessel, it was gently mixed at 200rpm and its temperature was raised to 60 ℃ over 15 minutes. The temperature was then maintained at 60 ℃ for 45 minutes, raised to 75 ℃ over 30 minutes, maintained at 75 ℃ for 4 hours, heated to 90 ℃ over 30 minutes, and maintained at 90 ℃ for 8 hours. The batch was then allowed to cool to room temperature.

The average volume size of the obtained capsule population was 24.0um, and the capsules had a diameter coefficient of variation based on volume percentage of 18.7%.

Example 6

The oil solution was prepared by mixing aromatic oil (96 wt%) and Sartomer CN975 (hexafunctional aromatic urethane acrylate oligomer, 4 wt%) at 20 ℃ to obtain a clear liquid.

Separately, a second oil solution was prepared by mixing the perfume oil (39.84%), isopropyl myristate (60 wt%), and 2,2' -azobis (2-methylbutyronitrile) (Vazo-670.16 wt%) at 20 ℃ to obtain a clear liquid.

The two oil solutions were pumped in a 1:1 weight ratio using two gear pumps (ISMATEC, micropump 0.32ml/rev) to form the dispersed phase upon mixing before entering the membrane shaft.

An aqueous solution (continuous phase) was prepared by mixing seviol 540(2 wt%), NaOH (0.07 wt%), and 4,4' -azobis (4-cyanovaleric acid) (0.37 wt%) in water. The continuous phase was pumped using a Tuthill GDS pump.

Emulsification was performed by using a vibrating membrane emulsification device. The membrane device consists of a laser drilled membrane (stainless steel membrane (supplied by Micropore) laser welded and mounted vertically on the membrane shaft). A membrane shaft is inserted into the membrane housing and coupled to the oscillation motor. The gap between the membrane shaft and the housing is where the continuous phase is pumped. The dispersed phase is injected from the top of the membrane axis towards the back portion of the membrane. The dispersed phase permeates through the pores of the membrane to the continuous phase, thereby forming an emulsion that exits the emulsion chamber and is collected in a collection vessel.

The membrane comprises a hexagonal array of pores with a diameter of 7 μm and the distance between the centers of the pores is 40 μm.

The flux of the dispersed phase through the membrane was 85.4m³/(m²And adjusting the mass flow rate of the continuous phase to achieve a ratio of the continuous phase to the dispersed phase of 1.5. Two flow rates were measured by using a Coriolis mass flowmeter (Bronkhorst, m14) placed between the pump and the membrane device. The membrane axis was oscillated at a frequency of 30Hz and an oscillation amplitude of 12.9 mm.

Once a liter of the emulsion was collected in the jacketed vessel, it was gently mixed at 200rpm and its temperature was raised to 60 ℃ over 15 minutes. The temperature was then maintained at 60 ℃ for 45 minutes, raised to 75 ℃ over 30 minutes, maintained at 75 ℃ for 4 hours, heated to 90 ℃ over 30 minutes, and maintained at 90 ℃ for 8 hours. The batch was then allowed to cool to room temperature.

The average volume size of the obtained capsule population was 53.1 μm, and the capsules had a diameter coefficient of variation based on volume percentage of 38.4%.

Example 7

An oil solution was prepared by mixing aromatic oil (96.26 wt%) and Sartomer CN975 (hexafunctional aromatic urethane acrylate oligomer, 3.74 wt%) at 20 ℃ to obtain a clear liquid.

Separately, a second oil solution was prepared by mixing the perfume oil (39.29%), isopropyl myristate (59.78 wt%), and 2,2' -azobis (2-methylbutyronitrile) (Vazo-670.94 wt%) at 20 ℃ to obtain a clear liquid.

The two oil solutions were pumped in a 1:1 weight ratio using two gear pumps (ISMATEC, micropump 0.32ml/rev) to form the dispersed phase upon mixing before entering the membrane shaft.

An aqueous solution (continuous phase) comprising an aqueous solution of seviol 540(2 wt%), NaOH (0.07 wt%), and 4,4' -azobis (4-cyanovaleric acid) (0.37 wt%) was prepared. The continuous phase was pumped using a Tuthill GDS pump.

Emulsification was performed by using a vibrating membrane emulsification device. The membrane device consists of a laser drilled membrane (stainless steel membrane (supplied by Micropore) laser welded and mounted vertically on the membrane shaft). A membrane shaft is inserted into the membrane housing and coupled to the oscillation motor. The gap between the membrane shaft and the housing is where the continuous phase is pumped. The dispersed phase is injected from the top of the membrane axis towards the back portion of the membrane. The dispersed phase permeates through the pores of the membrane to the continuous phase, thereby forming an emulsion that exits the emulsion chamber to be collected in a collection vessel.

The membrane comprises pores with a diameter of 7um in a hexagonal array and the distance between the centers of the pores is 40 um.

Flux of the dispersed phase through the membrane was 26.7m³/(m²And adjusting the mass flow rate of the continuous phase to achieve a ratio of the continuous phase to the dispersed phase of 1.5. Two flow rates were measured by using a Coriolis mass flowmeter (Bronkhorst, m14) placed between the pump and the membrane device. The membrane axis was oscillated at a frequency of 30Hz and an oscillation amplitude of 12.9 mm.

Once a liter of the emulsion was collected in the jacketed vessel, it was gently mixed at 200rpm and its temperature was raised to 60 ℃ over 15 minutes. The temperature was then maintained at 60 ℃ for 45 minutes, raised to 75 ℃ over 30 minutes, maintained at 75 ℃ for 4 hours, heated to 90 ℃ over 30 minutes, and maintained at 90 ℃ for 8 hours. The batch was then allowed to cool to room temperature.

The average volume size of the obtained capsule population was 27.7 μm, and the capsules had a diameter coefficient of variation based on volume percentage of 16.1%.

Example 8

An oil solution was prepared by mixing the fragrance oil (44.86 wt%), isopropyl myristate (54.95 wt%), Vazo 52(0.11 wt%), and Vazo 67(0.07 wt%) at Room Temperature (RT) until the mixture was homogeneous.

A second oil solution was prepared by mixing aromatic oil (96 wt%) and Sartomer CN975 (hexafunctional aromatic urethane acrylate oligomer, 4.00 wt%) at room temperature until the mixture was homogeneous.

An aqueous solution (continuous phase) was prepared by adding Selvol 540(2 wt%) to Reverse Osmosis (RO) water and heating to 90 ℃ for 4 hours with stirring and then cooling to room temperature.

The membrane device consisted of a laser drilled membrane (stainless steel membrane laser welded and mounted vertically on a membrane manifold) that was introduced into the emulsion chamber and coupled to an oscillating motor. The gap between the membrane manifold and the housing is where the continuous phase is pumped. The dispersed phase is injected from the top of the membrane manifold and distributed toward the back portion of the membrane. The dispersed phase permeates through the pores of the membrane to the continuous phase, thereby forming an emulsion that exits the emulsion chamber to be collected in a collection vessel.

The membrane comprises a hexagonal array of pores with a diameter of 7 μm and the distance between the centers of the pores is 40 μm.

The oscillatory displacement was 8mm and the frequency was 36 Hz. The two oil phases were mixed in-line using a static mixer at a ratio of 53.5: 46.5. The flux of the dispersed phase through the membrane was 37.4m³/(m²Membrane opening area h). The mass flow rate of the continuous phase was adjusted to achieve a ratio of continuous to dispersed phase of 1.5.

One kilogram of the emulsion was collected in a jacketed vessel and mixed using a paddle and overhead mechanical stirrer at 50 rpm. The temperature was raised to 60 ℃ at 2.5 ℃/min and held for 45 minutes. The temperature was then raised to 75 ℃ at 0.5 ℃/min and held for 240 minutes. The temperature was then raised to 90 ℃ at 0.5 ℃/min and held for 480 minutes. Finally, the batch was cooled to room temperature while maintaining stirring.

The final product is a suspension of encapsulated perfume capsules in a PVOH solution. Additional components such as stabilizers and/or preservatives may be added as desired.

The average volume size of the obtained capsule population was 29.7 μm, and the capsules had a diameter coefficient of variation based on volume percentage of 31.3%.

The dimensions and values disclosed herein are not to be understood as being strictly limited to the exact numerical values recited. Rather, unless otherwise specified, each such dimension is intended to mean both the recited value and a functionally equivalent range surrounding that value. For example, a dimension disclosed as "40 mm" is intended to mean "about 40 mm".

Each document cited herein, including any cross referenced or related patent or patent application and any patent application or patent to which this application claims priority or its benefits, is hereby incorporated by reference in its entirety unless expressly excluded or otherwise limited. The citation of any document is not an admission that it is prior art with any disclosure of the invention or the claims herein or that it alone, or in combination with any one or more of the references, teaches, suggests or discloses any such invention. Further, to the extent that any meaning or definition of a term in this document conflicts with any meaning or definition of the same term in a document incorporated by reference, the meaning or definition assigned to that term in this document shall govern.

While particular embodiments of the present invention have been illustrated and described, it would be obvious to those skilled in the art that various other changes and modifications can be made without departing from the spirit and scope of the invention. It is therefore intended to cover in the appended claims all such changes and modifications that are within the scope of this invention.