Composition and method for preparing film and application thereof
阅读说明：本技术 制备薄膜的组合物和方法及其应用 (Composition and method for preparing film and application thereof ) 是由 刘超 约翰·J·朗德 于 2019-03-14 设计创作，主要内容包括：在一些实施例中,本发明所述的成膜组合物包含脂肪族多异氰酸酯、脂肪族多官能亲核试剂、增链剂、第一溶剂、以及第二溶剂,其中所述第一溶剂的蒸发速率和所述第二溶剂的蒸发速率在彼此的150％以内,所述百分比以较大值为准。在一些实施例中,本发明描述了在基底上成膜的方法,所述方法包括使多异氰酸酯与多元醇结合形成聚氨酯预聚物、使聚氨酯预聚物与增链剂结合形成聚合物；并且将所述聚合物施加到所述基底上。(In some embodiments, the film-forming composition of the present disclosure comprises an aliphatic polyisocyanate, an aliphatic multifunctional nucleophile, a chain extender, a first solvent, and a second solvent, wherein the evaporation rate of the first solvent and the evaporation rate of the second solvent are within 150% of each other, the percentages being relative to the greater. In some embodiments, the present disclosure describes a method of forming a film on a substrate, the method comprising combining a polyisocyanate with a polyol to form a polyurethane prepolymer, combining the polyurethane prepolymer with a chain extender to form a polymer; and applying the polymer to the substrate.)
1. A film-forming composition comprising:
an aliphatic polyisocyanate;
an aliphatic multifunctional nucleophile;
a chain extender;
a first solvent;
and a second solvent, wherein the first solvent is a water-soluble solvent,
wherein the evaporation rate of the first solvent and the evaporation rate of the second solvent are within 150% of each other, the percentages being subject to a greater value.
2. The composition of claim 1, wherein the polyisocyanate and the multifunctional nucleophile are capable of combining to form a prepolymer.
3. The composition of claim 2 wherein said chain extender is capable of combining with said prepolymer to form a film-forming polymer solution.
4. The composition of claim 1, wherein the ratio of isocyanate groups of the polyisocyanate to the total of hydroxyl and amino groups of the multifunctional nucleophile and chain extender is from 1.5:1 to 1: 1.
5. The composition of claim 1, wherein the first solvent, second solvent, or both are antimicrobial solvents.
6. The composition of claim 5, wherein the antimicrobial solvent comprises ethanol, propanol, isopropanol, butanol, isobutanol, or any combination thereof.
7. The composition of claim 1, wherein the evaporation rate of the first solvent and the evaporation rate of the second solvent are in the range of 50% to 1500% of the evaporation rate of n-butyl acetate.
8. The composition of claim 1, wherein the mixture of the first solvent and the second solvent has a polarity index of 1 to 7 or a dielectric constant of 2 to 30.
9. The composition of claim 1, wherein the total vapor pressure of the mixture of the first solvent and the second solvent is from 4 to 70mmHg, according to raoult's law.
10. The composition of claim 1, wherein the first solvent and the second solvent comprise water, acetone, ethanol, butanone, ethanol, isopropanol, methyl acetate, ethyl acetate, butyl acetate, methyl propyl acetate, methyl isobutyl ketone, tetrahydrofuran, N-methylcyclohexanone, siloxane, linear alkanes, branched alkanes, cyclic alkanes, or any combination thereof, and further wherein the first solvent is different from the second solvent.
11. The composition of claim 1, wherein the polyisocyanate comprises Hexamethylene Diisocyanate (HDI), isophorone diisocyanate (IPDI), bis (4-isocyanatocyclohexyl) methane, Butane Diisocyanate (BDI), lysine diisocyanate, lysine triisocyanate, tris (6-isocyanatohexyl) isocyanurate, or any combination thereof.
12. The composition of claim 1, wherein the aliphatic polyfunctional nucleophile comprises a polyol, a polyamine, a thiol, or any combination thereof.
13. The composition of claim 1, wherein the chain extender is an aliphatic, a siloxane, or an ether.
14. The composition of claim 13, wherein the aliphatic, siloxane, and ether are a polyamine, a polyol, or any combination thereof.
15. The composition of claim 12, wherein the aliphatic polyamine comprises ethylenediamine, butanediamine, pentanediamine, hexamethylenediamine, isophoronediamine, piperazine, or any combination thereof.
16. The composition of claim 1, wherein a film formed from the composition has an average thickness of 20 to 250 micrometers.
17. The composition of claim 1, further comprising an additive comprising an antimicrobial agent, a growth factor, a peptide, a therapeutic agent, a biorenewable agent, a cosmetic agent, a metallic antioxidant, or any combination thereof.
18. A method of forming a film on a substrate, the method comprising:
combining a polyisocyanate with a polyol to form a polyurethane prepolymer;
combining the polyurethane prepolymer with a chain extender to form a polymer; and is
Applying the polymer to the substrate.
19. The method of claim 18, wherein the prepolymer and/or the polymer is formed in a mixture of a first solvent and a second solvent.
20. The method of claim 19, wherein the evaporation rate of the first solvent and the evaporation rate of the second solvent are within 150% of each other, the percentages being based on the greater; or within 50% to 1500% of the evaporation rate of n-butyl acetate.
21. The method of claim 19, wherein the mixture of the first solvent and the second solvent has a polarity index of 1 to 7 or a dielectric constant of 2 to 30.
22. The method of claim 19, wherein the total vapor pressure of the mixture of the first solvent and the second solvent is from 4 to 70mmHg, according to raoult's law.
23. The method of claim 19, wherein the first solvent and the second solvent comprise water, acetone, ethanol, butanone, propanol, isopropanol, butanol, isobutanol, methyl acetate, ethyl acetate, butyl acetate, methyl propyl acetate, methyl isobutyl ketone, tetrahydrofuran, N-methylcyclohexanone, siloxane, linear alkane, branched alkane, cycloalkane, or any combination thereof,
wherein the first solvent is different from the second solvent.
24. The method of claim 19, further comprising applying the first solvent and the second solvent mixture to the substrate.
25. The method of claim 24, wherein the first solvent and the second solvent mixture comprise the polymer.
26. The method of claim 24, wherein the first and second solvent mixtures are antimicrobial solvents capable of sterilizing the surface of the substrate.
27. The method of claim 18, wherein the polyisocyanate is an aliphatic polyisocyanate.
28. The method of claim 27, wherein the polyisocyanate comprises Hexamethylene Diisocyanate (HDI), isophorone diisocyanate (IPDI), bis (4-isocyanatocyclohexyl) methane, Butane Diisocyanate (BDI), lysine diisocyanate, lysine triisocyanate, tris (6-isocyanatohexyl) isocyanurate, or any combination thereof.
29. The method of claim 18, wherein the chain extender comprises:
an aliphatic polyamine comprising ethylenediamine, butanediamine, pentanediamine, hexamethylenediamine, isophoronediamine, piperazine, or any combination thereof;
an ether comprising an amino terminated polypropylene glycol, an amino terminated polyethylene glycol, or a combination thereof; or
A combination of the aliphatic polyamine and the ether.
30. The method of claim 18, further comprising applying an additive to the substrate, the additive comprising an antimicrobial agent, a growth factor, a peptide, a therapeutic agent, a biorenewable agent, a cosmetic agent, a dye, a metallic antioxidant, or any combination thereof.
31. A method of coating a biological tissue surface, the method comprising:
applying the composition of claim 1 on a surface of the biological tissue.
Technical Field
The present invention relates generally to polymeric films and, more particularly, to peelable polymeric films.
Background
Films and film compositions are used in a variety of industries. For example, various films have been used in the healthcare industry as protective layers for exposed surfaces, such as the dermis layer of human or animal skin, or devices with delicate mechanics. For healthcare applications, the ideal skin-covering film will conform to the complex contours of the skin, remain adherent for long periods of time, exhibit similar stretch and strain characteristics to the natural dermal layers, promote transpiration, and be non-toxic. Various film dressings have been used, each of which attempts to satisfy all of the above-described ideal conditions of the film. However, these conventional films suffer from a number of disadvantages. For example, many conventional films use adhesive-coated polymer films on a removable substrate. The polymer film is removed from the substrate and the adhesive coated surface is then applied to the skin of a person. However, the polymer film tends to wrinkle and adhere to itself during application, and thus becomes unusable. While increasing the thickness of the polymer film sometimes alleviates some of these problems, increased thickness often results in polymer films that do not conform to the contours of the skin, do not feel like natural skin, and have reduced transpiration. In addition, because conventional polymer films are prefabricated and applied to a substrate, the polymer films must be manufactured in a variety of different sizes to accommodate different sized application surfaces and locations.
Thus, there is a need for polymer films with improved properties.
Disclosure of Invention
In one aspect, the present disclosure describes films and film compositions that, in some embodiments, can provide one or more advantages over existing films and film compositions. For example, in some embodiments, the films of the present disclosure may exhibit desirable elastic, peelable, and/or durable physical properties. The films can be used in many different fields including human healthcare, industrial equipment, veterinary, cosmetic, art, cinematographic and sports industries. In some embodiments, the film-forming composition of the present disclosure comprises an aliphatic polyisocyanate, an aliphatic multifunctional nucleophile, a chain extender, and a solvent. In some embodiments, the present disclosure describes compositions comprising a film comprising a polymer formed from the reaction product of an aliphatic polyisocyanate, an aliphatic multifunctional nucleophile and a chain extender. In some cases, the ratio of isocyanate groups of the polyisocyanate to the total of hydroxyl and amino groups of the multifunctional nucleophile and chain extender is from 1.5:1 to 1: 1. In some cases, the polyisocyanate and the multifunctional nucleophile may be combined to form a prepolymer. The chain extender described herein can be combined with a prepolymer to form a polymer.
In some cases, the solvent of the present invention comprises a first solvent and a second solvent. The evaporation rate of the first solvent and the evaporation rate of the second solvent are within 150% of each other, the percentages being based on the greater value; and/or, in some cases, between 50% and 1500% of the n-butyl acetate evaporation rate. In some cases, the mixture of the first solvent and the second solvent may have a polarity index of 1 to 7 and/or a dielectric constant of 2 to 30. Further, according to raoult's law, the total vapor pressure of the mixture of the first solvent and the second solvent is 4 to 70mmHg in some cases.
In some embodiments, solvents (such as the first and second solvents described herein) may include water, acetone, ethanol, methyl ethyl ketone, ethanol, isopropanol, methyl acetate, ethyl acetate, butyl acetate, methyl propyl acetate, methyl isobutyl ketone, tetrahydrofuran, N-methylcyclohexanone, siloxanes, linear alkanes, branched alkanes, cyclic alkanes, or any combination thereof. In some cases, the first solvent is different from the second solvent.
The polyisocyanate of the present invention may include Hexamethylene Diisocyanate (HDI), isophorone diisocyanate (IPDI), bis (4-isocyanatocyclohexyl) methane, Butane Diisocyanate (BDI), lysine diisocyanate, lysine triisocyanate, tris (6-isocyanatohexyl) isocyanurate or any combination thereof.
The multifunctional nucleophile of the present invention may comprise a polyol, a polyamine, a thiol, or any combination thereof.
In some embodiments, the chain extender of the present invention is an aliphatic, silicone, or ether. In some cases, the aliphatic, siloxane, and ether are a polyamine, a polyol, or any combination thereof. The aliphatic polyamine may include ethylenediamine, butanediamine, pentanediamine, hexamethylenediamine, isophoronediamine, piperazine, or any combination thereof.
In some cases, the films of the present invention have an average thickness of 20 to 250 micrometers.
In some embodiments, the solvent of the present invention may be an antimicrobial solvent. For example, in some cases, the antimicrobial solvent can include ethanol, propanol, isopropanol, butanol, isobutanol, or any combination thereof.
In some cases, the films or compositions of the present invention may comprise an additive comprising an antimicrobial agent, a growth factor, a peptide, a therapeutic agent, a biorenewable agent, a cosmetic agent, a metallic antioxidant, or any combination thereof.
In another aspect, the disclosure describes methods of forming thin films on a substrate, which in some embodiments may provide one or more advantages over other methods of forming thin films on a substrate. For example, in some embodiments, the film-forming methods described herein are simple, efficient, stretchable, inexpensive, reproducible, biocompatible, and/or have desirable physical properties.
In some embodiments, a method of forming a film on a substrate includes applying a polyisocyanate, a multifunctional nucleophile and a chain extender to a substrate. In some cases, the polyisocyanate and the multifunctional nucleophile are first combined to form a prepolymer, then a chain extender is combined with the formed prepolymer to produce a film-forming polymer, and the film-forming polymer is applied to a substrate.
In some embodiments, a method of forming a film on a substrate includes combining a polyisocyanate and a polyol to form a polyurethane prepolymer; mixing the polyurethane prepolymer with a chain extender to form a polymer; and applying the polymer to the substrate.
In some cases, the prepolymers and/or polymers of the present invention are formed in a mixture of a first solvent and a second solvent, where the first solvent is different from the second solvent. For example, in some cases, the first solvent and the second solvent mixture may comprise a prepolymer and/or a polymer.
In some cases, a solvent, such as the first solvent and the second solvent, comprises water, acetone, ethanol, butanone, propanol, isopropanol, butanol, isobutanol, methyl acetate, ethyl acetate, butyl acetate, methyl propyl acetate, methyl isobutyl ketone, tetrahydrofuran, N-methylcyclohexanone, siloxane, linear alkane, branched alkane, cycloalkane, or any combination thereof.
In some cases, the evaporation rate of the first solvent and the evaporation rate of the second solvent are within 150% of each other, the percentages being based on the greater value; or within 50% to 1500% of the evaporation rate of n-butyl acetate. In some cases, the mixture of the first solvent and the second solvent has a polarity index of 1 to 7 or a dielectric constant of 2 to 30. Further, in some cases, the total vapor pressure of the mixture of the first solvent and the second solvent is 4 to 70mmHg according to raoult's law.
In some embodiments, the methods of the present disclosure further comprise applying a solvent or solvent mixture to the substrate. In some cases, the solvent or solvent mixture may be an antimicrobial solvent that sterilizes the substrate surface.
In some embodiments, the polyisocyanate described in the process of the present invention is an aliphatic polyisocyanate. For example, the polyisocyanate may include Hexamethylene Diisocyanate (HDI), isophorone diisocyanate (IPDI), bis (4-isocyanatocyclohexyl) methane, Butane Diisocyanate (BDI), lysine diisocyanate, lysine triisocyanate, tris (6-isocyanatohexyl) isocyanurate, or any combination thereof.
In some cases, the multifunctional nucleophile is aliphatic and comprises a polyol, a polyamine, a thiol, or any combination thereof.
In some cases, the chain extender comprises an aliphatic polyamine, an ether, or a combination of the aliphatic polyamine and the ether; the aliphatic polyamine comprises ethylenediamine, butanediamine, pentanediamine, hexamethylenediamine, isophoronediamine, piperazine or any combination thereof; the ether comprises an amino terminated polypropylene glycol, an amino terminated polyethylene glycol, or a combination thereof.
In some embodiments, the methods of the present disclosure may further comprise applying an additive to the substrate, the additive comprising an antimicrobial agent, a growth factor, a peptide, a therapeutic agent, a biorenewable agent, a cosmetic agent, a dye, a metallic antioxidant, or any combination thereof.
In another aspect, a method of coating a surface of a biological tissue comprises applying a composition of the present invention to the surface of the biological tissue.
These and other embodiments are described in more detail in the detailed description and examples that follow.
Drawings
FIG. 1 is a photograph of an exemplary film applied to human skin.
Fig. 2 is a photograph of the film of fig. 1 peeled from the skin.
FIG. 3 is a photograph of an exemplary film applied to a nail.
Fig. 4 is a photograph of the film of fig. 3 peeled from the nail.
Fig. 5 is a contrast image with no detachment from the exemplary film.
FIG. 6A is an exemplary film,
FIG. 6B is the exemplary film of FIG. 6A,
FIG. 6C is the exemplary film of FIG. 6A,
FIG. 6D shows the exemplary film of FIG. 6A,
FIG. 7 is a view showing the human skin removed from FIG. 6AExemplary films and
FIG. 8 is a stretched photograph of the exemplary film of FIG. 7 after removal from human skin.
Fig. 9 is a photograph of an exemplary film applied to human skin using two different solvents.
Detailed Description
The described embodiments of the invention may be understood more readily by reference to the following detailed description, drawings and examples and their previous and following description. The elements, devices, and methods described herein, however, are not limited to the specific embodiments presented in the detailed description, drawings, and examples. It is to be understood that these embodiments are merely illustrative of the principles of the invention. Many modifications and adaptations will be apparent to those skilled in the art without departing from the spirit and scope of the present invention.
Moreover, all ranges disclosed herein are to be understood to encompass any and all subranges subsumed therein. For example, a stated range of "1.0 to 10.0" should be considered to include any and all subranges beginning with a minimum value of 1.0 or more and ending with a maximum value of 10.0 or less, e.g., 1.0 to 5.3, or 4.7 to 10.0, or 3.6 to 7.9.
All ranges disclosed herein are to be understood to encompass the endpoints of such ranges, unless expressly stated otherwise. For example, a range of "between 5 and 10", "5 and 10", or "5-10" should generally be inclusive of the
Further, when the phrase "at most" is used in connection with an amount or quantity, it is to be understood that the amount is at least a detectable amount or quantity. For example, a material present in an amount of "up to" a specified amount can range from a detectable amount up to and including the specified amount.
All molecular weights recited herein are weight average molecular weights unless specifically stated otherwise.
Throughout this disclosure, the terms "film," "polymeric film," and "film" are used interchangeably and, unless otherwise specifically indicated, should be construed to have the same meaning.
Thin film coatings can be used in a variety of applications, including electronics, displays, semiconductors, medical implants and surgical tools, human/animal tissue, and many others. In the biomedical field, biocompatible thin film coatings are used to protect devices and tissues from contaminants such as bacteria and dust, to provide a physical barrier and protection, to prevent water loss and to promote wound healing, and the like.
Depending on the application, thin film coatings are desired to improve appearance and wear resistance, reduce wear between sliding parts, and increase lubricity. It is generally believed that the functional coating imparts a bacterial barrier, antimicrobial, and anti-fouling effect to the coated device and biological tissue.
Thin film coatings on human skin are particularly challenging. Human skin is a complex living material consisting of three layers, epidermis, dermis and stratum corneum. The epidermis layer consists of partially keratinized cells, which gradually dehydrate upon migration to the outer surface, thereby forming the Stratum Corneum (SC). The stratum corneum consists of a biphasic thin layer of 10-20 cells with an average thickness between 25-200nm, depending on the body part. The stratum corneum is often referred to as a "brick and mortar" structure because it includes a "brick" area (corneocytes) surrounded by a "mortar" of fatty acids, ceramides, cholesterol, and water. The surface of the stratum corneum is covered with a mixture of the skin surface lipid membrane (SSLF), sebum of sebaceous glands and lipids secreted by keratinocytes. It is well known that the stratum corneum plays an important role in the hydration and adhesion properties of the skin. However, the stratum corneum is considered to be a dead but highly dynamic structure, while SSLF is constantly renewing and the liquid molecules in SSLF are in a fast reorientation mode. The complex composition and dynamic properties of the SC and SSLF layers, as well as the soft and elastic properties of the skin and the constant stretching and recovery movements of the skin during human movement, present significant challenges for identifying ideal film-forming solutions for application to the skin.
The skin coating materials or products of today are usually either applied or coatedA liquid formulation sprayed on the skin to form a film layer. For example,
Thus, while many skin mimicking films have been proposed, each of these films does not mimic and accommodate the complexity of the external structure and dynamic components of the skin.
Thus, in contrast to current films, the ideal film preparation solution is one that can be easily applied to the skin without detachment and that can quickly form a film. An ideal film may in some cases have sufficient skin adhesion strength to adhere to the skin for at least 2 to 3 days without edge curl, while still maintaining the peel ability of the intact film like a conventional bandage for easy removal when needed. To prevent penetration of dust or microorganisms prior to peeling the film, it is highly desirable to maintain the integrity of the film. In some cases, an ideal film may provide good protection as a conventional bandage, but for aesthetic purposes it is transparent without the formation of cracks. In addition, in many cases, the ideal film will be biocompatible without concern for toxicity. In some cases, the ideal film will mechanically conform to the natural skin and be breathable to promote rapid healing of the wound.
Traditionally, solvent systems used in polyurethane and/or poly (urethane-urea) based films have been specifically designed to address the solubility problem of the polymer component of the film. However, as described in the present invention, it has been unexpectedly found that the mechanical properties of the ideal film are highly dependent not only on the particular combination of polymer components, but also on the solvent used. In particular, it has been found that the physical properties of films having the same or similar polymer composition can vary significantly depending on the solvent system used, and that solubility is not the only factor to consider when selecting a solvent system. For example, as described in more detail herein, when different solvent systems are used with the same polymer composition, the physical properties of the same or similar polyurethane and/or poly (urethane-urea) -based films will be different. By selecting a solvent system having a particular evaporation rate, dielectric constant, vapor pressure, and/or polarity index, as described herein, the mechanical properties, including adhesion properties, of the resulting film can be controlled. It has been found that a particular solvent system not only controls the appropriate solvent evaporation rate, film formation rate and viscosity of the film forming solution to avoid rapid release from the skin, but also controls the morphology of the film, such as the final mechanical properties, aesthetics (such as transparency and crack formation) and/or surface finish of the resulting film.
Thus, the present invention discloses the use of a particular film of a combination of polymer and solvent system to prepare a composition that exhibits unexpectedly and surprisingly superior film mechanical properties as compared to other films having similar polymer components but different solvent systems.
I.Film compositions
Films and film compositions are described that, in some embodiments, may provide one or more advantages over existing films and film compositions. In some embodiments, for example, the films of the present invention may be formed in situ on a surface and exhibit desirable elastic, peelable, and/or durable physical properties, such as being applicable to the skin without "peeling off" and being rapidly formable during application. In some cases, the film compositions of the present invention may be applied to the skin as a liquid bandage that cures to form a film on the skin. In some cases, the films of the present invention have sufficient skin adhesion strength to adhere to the skin for at least 2 to 3 days without edge curl, while still maintaining the peel ability of the intact film like conventional bandages for easy removal when needed. Furthermore, in some cases, the films of the present invention can provide a good protective feel like conventional bandages, but are transparent without cracks. In addition, the films of the present invention can exhibit desirable biocompatibility, e.g., being non-cytotoxic, implant compatible, non-pyrogenic, non-irritating, non-sensitizing, forming a microbial barrier, and/or low systemic toxicity. In some embodiments, the films of the present invention exhibit desirable metal oxidation resistance and material coating properties.
In some embodiments, the film-forming composition comprises a polyisocyanate, a multifunctional nucleophile, a chain extender, and a solvent. In some embodiments, a composition comprises a film comprising a polymer formed from the reaction product of a polyisocyanate, a multifunctional nucleophile and a chain extender. The polyisocyanate and the polyfunctional nucleophile may be combined to form a prepolymer and the chain extender may be combined with the prepolymer to form the film. The ratio of isocyanate groups of the polyisocyanate to the total of hydroxyl and amino groups of the multifunctional nucleophile and the chain extender may be 1.5:1, 1.45:1, 1.4:1, 1.35:1, 1.3:1, 1.25:1, 1.2:1, 1.15:1, or 1: 1.
In some embodiments, the polyisocyanates of the present invention comprise aliphatic, olefinic or aromatic polyisocyanates. The polyisocyanate can have 2, 3, 4, 5, 6 or more isocyanate groups. In an embodiment, the polyisocyanate is a diisocyanate. For example, the polyisocyanate may include Hexamethylene Diisocyanate (HDI), isophorone diisocyanate (IPDI), bis (4-isocyanatocyclohexyl) methane, Butane Diisocyanate (BDI), lysine diisocyanate, lysine triisocyanate, tris (6-isocyanatohexyl) isocyanurate, or any combination thereof. However, other polyisocyanates not inconsistent with the objectives of the present disclosure are also contemplated.
In some embodiments, the multifunctional nucleophiles of the present invention are multifunctional protic nucleophiles. The multifunctional protic nucleophile may comprise a polyol, a polyamine, or a thiol.
The polyol of the present invention is a compound containing two or more hydroxyl groups. In some embodiments, the polyol is an oligomer or polymer having a plurality of terminal hydroxyl groups. For example, the polyol of the present invention may comprise poly (e-caprolactone) (e-PCL) glycol, polylactic acid (PLA) glycol, poly (lactic-co-glycolic) glycol, polybutylene succinate (PBS), polybutylene adipate (PBA), polyethylene glycol (PEG), polypropylene glycol (PPG), polytetramethylene ether glycol (poly-THF), hydroxy-terminated Polydimethylsiloxane (PDMS), or any combination thereof. However, other polyols not inconsistent with the objectives of the present disclosure are also contemplated.
In some cases, the polyol of the present invention may have a weight average molecular weight of 200-10,000, 200-8,000, 200-6,000, 200-4,000, 200-2,000, 200-1000, 200-500, 300-10,000, 400-10,000, 500-10,000, 600-10,000, 700-10,000, 800-10,000, 900-10,000, 1,000-10,000, 2,000-10,000, 3,000-10,000, 4,000-10,000, 5,000-10,000, 6,000-10,000, 7,000-10,000, 8,000-10,000, 500-8,000, 1,000-6,000-4,000.
The polyamines of the present invention are compounds containing two or more primary or secondary amino groups. In some embodiments, the polyamine is an oligomer or polymer having a plurality of terminal amino groups. For example, the polyamine can include polyethylene glycol (PEG) diamine, polypropylene glycol (PPG) diamine, amino-terminated Polydimethylsiloxane (PDMS), or any combination thereof. However, other polyamines not inconsistent with the objectives of the present disclosure are also contemplated.
The polyamine may have a weight average molecular weight of 200-10,000, 200-8,000, 200-6,000, 200-4,000, 200-2,000, 200-1000, 200-500, 300-10,000, 400-10,000, 500-10,000, 600-10,000, 700-10,000, 800-10,000, 900-10,000, 1,000-10,000, 2,000-10,000, 3,000-10,000, 4,000-10,000, 5,000-10,000, 6,000-10,000, 7,000-10,000, 8,000-10,000, 500-8,000, 1,000-6,000 or 2,000-4,000.
The thiol of the present invention is a compound containing two or more mercapto groups. In some embodiments, the thiol is an oligomer or polymer having a plurality of terminal thiol groups. For example, the thiol may include polyethylene glycol (PEG) thiol, polypropylene glycol (PPG) thiol, thiol-terminated Polydimethylsiloxane (PDMS), or any combination thereof. However, other thiols not inconsistent with the objectives of the present disclosure are also contemplated.
The weight average molecular weight of the mercaptan is 200-10,000, 200-8,000, 200-6,000, 200-4,000, 200-2,000, 200-1000, 200-500, 300-10,000, 400-10,000, 500-10,000, 600-10,000, 700-10,000, 800-10,000, 900-10,000, 1,000-10,000, 2,000-10,000, 3,000-10,000, 4,000-10,000, 5,000-10,000, 6,000-10,000, 7,000-10,000, 8,000-10,000, 500-8,000, 1,000-6,000 or 2,000-4,000.
The chain extender of the present invention is typically a reactive crosslinker that can be used to modify the reaction product produced between the polyisocyanate and the polyfunctional nucleophile. In some cases, the chain extender may be an aliphatic, a siloxane, an ether, or any combination thereof. In some embodiments, the aliphatic, silicone, and ether chain extenders are polyamines, polyols, or any combination thereof. For example,the aliphatic polyamine chain extender may include ethylenediamine, butanediamine, pentanediamine, hexamethylenediamine, isophoronediamine, piperazine, or any combination thereof. The ether chain extender may comprise an amino terminated polypropylene glycol (e.g.
In some embodiments, the solvent of the present invention comprises water, acetone, ethanol, butanone, ethanol, isopropanol, methyl acetate, ethyl acetate, butyl acetate, methyl propyl acetate, methyl isobutyl ketone, tetrahydrofuran, N-methylcyclohexanone, siloxane, linear alkane, branched alkane, cycloalkane, or any combination thereof. For example, the linear, branched and cyclic alkanes may include linear, branched or cyclic alkanes such as propane, butane, pentane, hexane, heptane or octane. Examples of siloxanes include hexamethyldisiloxane, octamethyltrisiloxane, hexamethylcyclotrisiloxane, octamethylcyclotetrasiloxane, or any combination thereof. However, the solvents described are merely exemplary, and other solvents not inconsistent with the objectives of the present disclosure are also contemplated.
In some embodiments, the solvent of the present invention is an antimicrobial solvent comprising ethanol, propanol, isopropanol, butanol, isobutanol, or any combination thereof. The antimicrobial solvent may be used as the sole solvent or in combination with one or more solvents. Generally, when a film is applied to a surface of a biological tissue (e.g., skin), the antimicrobial solvent can sterilize the surface of the biological tissue as the film is formed in situ on the surface. However, these antimicrobial solvents are merely exemplary, and other antimicrobial solvents not inconsistent with the objectives of the present disclosure are also contemplated. In some embodiments, the solvent described herein can comprise a first solvent and a second solvent. The first solvent and the second solvent may be selected from the solvents described herein to form a constant evaporative mixing rate that allows the components of the film to remain solvated until the reaction of the film components is complete without premature evaporation of the solvents. In some cases, the first solvent and the second solvent may be selected from the solvents described herein to form a constant evaporation mixture rate, which allows the one or more polymers in solution to form a uniform film without premature precipitation of the one or more polymers prior to evaporation of the solvent. While not being bound by theory, the evaporation rate of the drying process can be controlled theoretically by selecting a first solvent and a second solvent that are chemically different. For example, the solvent combination may include alcohols and ketones, alcohols and hydrocarbons, alcohols and acetates, alcohols and esters, acetates, halogenated hydrocarbons, and the like. In some embodiments, the evaporation rate is such that the film composition can be dried into a film within 10 minutes, within 8 minutes, within 6 minutes, within 5 minutes, within 4 minutes, within 2 minutes, and within less than 1 minute. In some embodiments, the solvent evaporation rate is 50-500% (or 0.5-5 times) or 50-500mmHg g/mol of n-butyl acetate as described by Hofmann in industrial and engineering chemistry (Vol.24, No.2, 135-140), the entire contents of which are incorporated herein by reference. As described by Hofmann, the rate of evaporation of a liquid is not proportional to the boiling point of the liquid. Furthermore, in this case, the evaporation rate of the solvent is 50-400%, 50-300%, 50-250%, 50-200%, 50-150%, 50-125%, 50-100%, 50-75%, 75-500%, 100-500%, 150-500%, 200-500%, 250-500%, 300-500%, 350-500%, 400-500%, 100-400%, 150-350% or 200-300% of the evaporation rate of n-butyl acetate described by Hofmann.
In some embodiments, the evaporation rate of the first solvent and the evaporation rate of the second solvent are within 150% of each other, the percentages being based on the greater value. In some cases, the evaporation rates of the first solvent and the second solvent are within 75%, 100%, 115%, 130%, 145%, 160%, 185%, or 200% of each other, the percentages being by greater value. For example, in certain embodiments, the first solvent comprises Ethanol (EAL) and the second solvent comprises Ethyl Acetate (EAC). The Evaporation Rate (ER), as described in Hofmann, can be calculated by equation 1:
evaporation rate ═ vapor pressure molecular weight/11 (equation 1)
Ethanol (EAL) ER 43.7mmHg × 46.07g/mol/11 183.02mmHg g/mol; ethyl Acetate (EAC) has ER 73.91mmHg × 88.11g/mol/11 389.95mmHg g/mol. Thus, the evaporation rates of both solvents are within 150% of each other and within 50% to 1500% of this parameter for n-butyl acetate (ER of n-butyl acetate is 100mmHg g/mol at 20 ℃).
In some embodiments, the mixture of the first solvent and the second solvent may have a polarity index of 1 to 7. In some cases, the polarity index is 2 to 6 or 3 to 5. In some examples, the polarity index is 1, 2, 3, 4, 5, 6, or 7. The polarity index of the mixture may be calculated according to
wherein, P'iIs a polar exponential weighting factor for the solvent I,
P＝(5.2)(0.3)+(4.4)(0.7)＝4.64
in some embodiments, the mixture of the first solvent and the second solvent may have a dielectric constant of 2 to 30. In some cases, the mixture has a dielectric constant of 5 to 25, 10 to 20, 12 to 18, 5 to 15, 5, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, or 30. The dielectric constant value of the mixture can be calculated by multiplying the volume fraction of each solvent by its dielectric constant and summing, as shown in equation 3:
A+B＝fAδA+fBδB+.. (Eq.3)
Where A and B are the solvents in the mixture, f is the volume fraction of each solvent, and δ is the dielectric constant of each solvent. For example, for a mixture of ethanol (δ ═ 24.5) and ethyl acetate (δ ═ 6.02), the dielectric constant of the EAL/EAC (3:7) mixture can be calculated as follows:
the EAL/EAC (3:7) ratio 24.5 × 0.3+6.02 × 0.7 ═ 11.56
Raoult's law states that the partial vapor pressure of each component in an ideal liquid mixture is equal to the Vapor Pressure (VP) of the pure component multiplied by its mole fraction in the mixture. In some embodiments, the total vapor pressure of the mixture of the first solvent and the second solvent is from 4 to 80mmHg, according to raoult's law. In some cases, the total vapor pressure of the mixture of the first solvent and the second solvent is from 10 to 40mmHg, 20 to 30mmHg, 15 to 30mmHg, 4mmHg, 8mmHg, 10mmHg, 15mmHg, 20mmHg, 25mmHg, 30mmHg, 35mmHg, 40mmHg, 45mmHg, 50mmHg, 55mmHg, 60mmHg, 75mmHg, or 80mmHg, according to raoult's law. For example, the molar ratio of EAL (VP: 43.7mmHg) to EAC (VP: 73.91mmHg) was 3:7, the molar ratio of EAL was 0.273, and the molar ratio of EAC was 0.727. Then the total vapor pressure of EAL/EAC is 43.7 0.273+73.91 0.727 65.66 mmHg.
In some embodiments, the films of the present disclosure are elastomeric and have a strain rate (e.g., elongation at break) of 100% to 1200%. For example, the strain at break of the film may be at least greater than 100%, greater than 200%, greater than 300%, greater than 400%, greater than 500%, or greater than 600%. The elastic nature of the film helps the film to remain adhered to the flexible surface. For example, when the membrane is placed on the skin of a human or animal, the membrane may stretch and bend with the skin, allowing the membrane to flexibly mimic the movement of the skin. In addition, the elastic properties of the film impart the ability to peel the film from the substrate surface, as seen below in fig. 1-4.
The thickness of the films of the present invention may vary depending on the application. For example, in some embodiments, the average thickness of the film is 20 to 300 microns. In other embodiments, the average thickness of the film is 20 to 50 microns, 20 to 100 microns, 20 to 150 microns, 20 to 200 microns, or 20 to 250 microns.
In some embodiments, the films of the present disclosure may have a thickness of 200 to 600g/m2Water vapor transmission rate per day. In other embodiments, the water vapor transmission rate of the membrane is 200 to 400g/m2300 to 500 g/m/day2400 to 600 g/m/day2500 to 600 g/m/day2200 g/m/day2300 g/m/day2400 g/m/day2500 g/m/day2A day, or 600g/m2The day is. The water vapor transmission rate of the membrane can be determined according to ASTM standard test method E96/E96M-15, described in more detail below in example 4. In some instances, for substrates such as human or animal skin, the water vapor transmission rate of the membrane may allow perspiration to evaporate from the skin and be released through the membrane into the atmosphere, rather than being trapped between the skin and the membrane.
Young's modulus (e.g. elastic modulus) is a mechanical property of an elastic solid material, young's modulus defining the relationship between stress (force per unit area) and strain (proportional deformation) in the material. In some embodiments, the films of the present disclosure have a young's modulus of 3 to 20 MPa. In other embodiments, the film has a young's modulus of 4 to 18MPa, 6 to 16MPa, 8 to 14MPa, 10 to 12MPa, 5 to 17MPa, 7 to 15MPa, 9 to 13MPa, 3 to 10MPa, 10 to 15MPa, 15 to 20MPa, 3MPa, 4MPa, 5MPa, 6MPa, 7MPa, 8MPa, 9MPa, 10MPa, 11MPa, 12MPa, 13MPa, 14MPa, 15MPa, 16MPa, 17MPa, 18MPa, 19MPa, or 20 MPa. The Young's modulus value of the film may be determined according to ASTM Standard test method D882, which is described in more detail in example 6 below.
Tensile strength at break is the ability of a material to resist breaking under tension. In some embodiments, the film has a tensile strength of 10 to 60 MPa. In other embodiments, the film has a tensile strength of 10 to 50MPa, 10 to 40MPa, 10 to 30MPa, 10 to 20MPa, 20 to 60MPa, 30 to 60MPa, 40 to 60MPa, 50 to 60MPa, 20 to 50MPa, 30 to 40MPa, 10MPa, 15MPa, 20MPa, 25MPa, 30MPa, 35MPa, 40MPa, 45MPa, 50MPa, 55MPa, or 60 MPa. Tensile strength values for the films can be determined according to ASTM standard test method D882, described in more detail in example 6 below.
In some embodiments, the films of the present invention have a molecular weight of 1.0 × 104g/mol to 5.0X 105g/mol. In other embodiments, the molecular weight of the membrane is 5.0 × 104g/mol to 5.0X 105g/mol、1.0×105g/mol to 5.0X 105g/mol、2.5×105g/mol to 5.0X 105g/mol。
ISO10993 sets forth a series of standards for assessing biocompatibility of medical devices. In some embodiments, the films of the present invention are non-cytotoxic, implant compatible, non-pyrogenic, non-irritating, non-sensitizing, non-displaying systemic toxicity, or any combination thereof, according to a set of standards described in ISO 10993. Specific examples of such films that meet one or more of the series of standards set forth in ISO10993 are described in more detail below in examples 10-14.
In some embodiments, the film of the present invention may form a microbial barrier when disposed on a substrate surface. The microbial barrier refers to a membrane that forms a barrier that prevents, excludes, or reduces the penetration of microorganisms. The microbial penetration may be in one direction or in both directions. For example, the microbial penetration may be through the membrane from the substrate surface in an outward direction away from the substrate surface, or may be through the membrane from an outer surface of the membrane in an inward direction toward the substrate surface. In some embodiments, the membrane may form a microbial barrier that may prevent 80% to 100%, 90% -100%, 80%, 90%, or 100% penetration of microorganisms.
In some embodiments, the film-forming compositions and films of the present disclosure contain additives. Exemplary additives contain antimicrobial agents, growth factors, peptides, therapeutic agents, anti-inflammatory agents, analgesic agents, biorenewable agents, cosmetic agents, metal antioxidants, or any combination thereof. For example, the antimicrobial agent may comprise an antibiotic, antifungal agent, or other pharmaceutically acceptable antimicrobial agent. Exemplary cosmetic agents include colorants or dyes, such as mica, iron oxide, manganese violet, zinc oxide, or other known cosmetic dyes or pigments to match the film to the substrate (e.g., a flesh-colored dye for matching human skin tone). Exemplary growth factors include Vascular Endothelial Growth Factor (VEGF), Platelet Derived Growth Factor (PDGF), neurotrophins, Keratinocyte Growth Factor (KGF), insulin-like growth factor (IGF), Fibroblast Growth Factor (FGF), Epidermal Growth Factor (EGF), angiogenin, erythropoietin, or any known growth factor that can be incorporated into a film for wound treatment. Exemplary peptides include MG53, RGD, rggdfv, RGDs or any known peptide that can be incorporated into a membrane for wound therapy.
II.Method for forming film
In another aspect, the present disclosure describes methods of forming a film on a substrate, which in some embodiments may provide one or more advantages over other methods of forming a film on a substrate. For example, in some embodiments, the methods of forming films described herein are simple, efficient, stretchable, inexpensive, reproducible, compatible with biological tissue, and/or have desirable physical properties. In particular, the film-forming methods of the present invention can allow the film to be formed in situ (e.g., "in situ") on a substrate such as skin.
In some embodiments, a method of forming a film on a surface of a substrate comprises applying a polyisocyanate, a multifunctional nucleophile and a chain extender to the substrate. In some embodiments, the polyisocyanate and the multifunctional nucleophile are first combined to form a prepolymer, and the chain extender is subsequently combined with the prepolymer. Each of the polyisocyanate, the multifunctional nucleophile and the chain extender may be applied to the surface of the substrate, either singularly or in combination with a solvent. In some embodiments, the polyisocyanate, the polyfunctional nucleophile and the chain extender may be formulated together and reacted in preferably one or more solvents to produce a film-forming polymer solution before the polymer solution is applied to a substrate to form a film.
In some embodiments, the methods described herein may further comprise applying an additive to a surface of the substrate. The additive may be applied to the surface of the substrate at any step of the process. In some cases, the additive may be combined with one or more of the polyisocyanate, the multifunctional nucleophile, the chain extender, or the final polymer solution and applied to the surface of the substrate. In a non-limiting example, when the additive is an antibiotic, the antibiotic can be combined with the polyisocyanate or the multifunctional nucleophile and applied to the substrate in the form of a composition containing the same. In this example, the introduction of the antibiotic in the resulting prepolymer matrix precedes the addition of the chain extender. In another non-limiting example, the antibiotic can be combined with the chain extender and then incorporated into the resulting polymer matrix that forms the film. In another non-limiting example, the antibiotic can be combined with the final polymer solution and then incorporated into a film formed on the substrate. In yet another non-limiting example, an antibiotic may be applied directly onto the surface of the substrate and the resulting film formed over the antibiotic, effectively forming an antibiotic layer between the substrate and the film.
The film composition may be applied to the surface of the substrate in various formulations, such as liquids, creams, lotions, emulsions, or other formulations. The method may be accomplished by applying each component with an applicator (e.g., a brush) or by hand. Each component may also be applied by spraying or aerosol, or by dipping the substrate into each component.
The characteristics and types of the polyisocyanate, the polyfunctional nucleophile, the chain extender, the optional solvent, and the optional additives should be understood to be consistent with the description of each of the ingredients previously discussed in the part I-film compositions of the present invention.
Exemplary applications of the film
The films and methods of forming films on substrates described herein can be used in many different fields, including the human healthcare, industrial equipment, veterinary, cosmetic, art, motion picture production, and sports industries. For each of the following exemplary applications of the film, it should be understood that each of the examples is for the purpose of illustrating various aspects of the invention and does not limit the scope of the invention as defined by the claims.
In one example, such as in the healthcare and cosmetic fields, the film may be applied to a prosthetic device using the film compositions and methods described herein such that the prosthetic device obtains a film coating. The film may include additives, such as colorants, dyes, or pigments, such that the film visually resembles a particular skin tone.
In another example, the film of the present invention may be applied to a robotic device or a holding tool using a spray coating system. In some cases, the sprayed film may provide enhanced grip, aesthetic effects, or human-like features. The film may be coated with several coats and may be replenished as wear occurs. Exemplary robotic instruments may include those used for picking fruit, assembling precision hardware, or performing robotic medical procedures.
In another example, the films of the present invention can be used to protect the mammary glands of dairy animals from pathogenic contamination by forming a teat sealant on the teats of the animals to reduce the incidence of mastitis in the animals.
The film of the invention can be used for coating a humanoid robot or an accompanying doll, so that the humanoid robot or the accompanying doll is more vivid, comfortable or natural. This includes robots, simulated robots, or automated machines built for social, commercial, and industrial use. Although the film is typically used to form a skin-like film, the film may also be used to mask or protect the exterior or sensitive parts of the mechanics of the humanoid robot.
Another industrial application of the films of the present invention is as a water or air barrier covering the surface of a metal part to reduce the exposure of the surface to water or oxygen, reduce the formation of rust (e.g., metal oxidation), and extend the useful life of the material. For example, the metal part may be part of a ship that is often exposed to highly oxidizing conditions. In some cases, the oxidation resistance of the film may be enhanced by including a metallic antioxidant as previously described.
The films of the present invention may have various applications involving biological tissues of humans and animals. For example, the film may mimic the skin and be applied to damaged skin with minor cuts, tears, abrasions, burns, blisters and closed surgical incisions and cuts to protect these sites from external bacteria and dirt, and to relieve pain and itching by covering nerve endings. The films may also be used to protect or soothe the skin from problems such as dryness, itching, blistering or peeling of patients receiving radiation therapy and who are unable to tolerate conventional bandages, tapes or skin protectants. The film may fall off naturally over time or peel off of the skin when needed, and may be recoated as a new film or reused before the original film falls off or peels off. In another example, the film of the present invention may be applied to the chest of a long distance runner to provide a barrier that reduces friction between the chest and clothing, thereby preventing chafing and irritation.
In yet another example, a membrane according to the present invention may be applied to a catheter percutaneous access site to protect or seal the catheter. The membrane may also be applied to the surface of the dermal skin region adjacent to the catheter port. After insertion of the catheter, a protective tape is applied to the real skin surface protected by the membrane. After physical removal of the protective, i.e. adhesive tape, the film prevents the dermal skin of the subject from being damaged.
The film of the present invention may be applied to the skin fold of an obese individual for a period of time, e.g., up to 24 hours. The membrane acts as a barrier between the contact points of the individual portions of the skin fold, reducing friction and keeping the real skin area dry and comfortable until the membrane falls off naturally or is subsequently removed with soap and water.
The films of the present invention can be applied to the outer real skin areas of a joint, such as the elbow, and minimize abrasions that may occur during athletic or athletic activities.
The film of the present invention can be applied to the border of a stoma to prevent irritation and sensitization of healthy tissue that may be infected by a stoma leak.
The films of the present invention can be applied to the thighs and buttocks of elderly or mobility impaired individuals to reduce irritation and abrasion that can accompany urinary incontinence.
The films of the present invention are useful as surgical dustless covers and microbial sealants during surgery, where they may be applied by a physician. The applied film may mask the flora of the patient's real skin, reducing the likelihood that the flora will enter the surgical incision and cause infectious complications.
The films of the present invention can be applied to the foot of a diabetic patient to enhance the mechanical strength of the natural skin, reduce the rate of ulcer formation and prevent the formation of painful sores.
The films of the present invention may be applied to areas of the skin that are prone to develop or have developed pressure sores or pressure sores to prevent or reduce ulcers, pus-like fluid, pain and swelling.
In another example, the film of the present invention may be applied to the forearm of an individual to form a barrier that prevents wear.
In another example, the films of the present invention may be applied to open ulcers on livestock with foot-and-mouth disease. Spot-checks on livestock identify blistering individuals who may cause and spread infection. The film may be applied to the wound to reduce further spread of disease.
Some of the embodiments of the invention described are further illustrated in the following non-limiting examples.
Example 1
Synthesis of
The polymer formulation was synthesized using the monomer isophorone diisocyanate/piperazine/polycaprolactone diol at a molar ratio of 2/1/1 in a glass reactor equipped with a dry nitrogen/vacuum line, a controlled heating device, and a stirring mechanism. Isophorone diisocyanate was slowly added to the dried polycaprolactone diol at 45 ℃ and reacted in acetone solvent until the desired isocyanate content was reached. The mixture may also be reacted in other skin compatible solvents including acetone, ethanol, tetrahydrofuran, isopropanol, methyl acetate, ethyl acetate, n-butyl acetate, isobutyl acetate or mixtures of solvents until the desired isocyanate content is achieved. Piperazine was then added dropwise to the mixture at room temperature and additional solvent or solvent mixture was added to form a clear and viscous polymer solution.
Example 2
Synthesis of
The polymer formulation was synthesized using the monomer isophorone diisocyanate/polycaprolactone diol/polyethylene glycol/isophorone diamine/at a molar ratio of 2.4/0.2/1.2/1 in a glass reactor equipped with a dry nitrogen/vacuum line, a controlled heating device, and a stirring mechanism. Isophorone diisocyanate was slowly added to the dried polycaprolactone diol/polyethylene glycol mixture at 45 ℃ and reacted in different solvents compatible with the skin, including acetone, ethanol, tetrahydrofuran, isopropanol, methyl acetate, ethyl acetate, n-butyl acetate, isobutyl acetate and mixtures thereof, until the desired isocyanate content was reached. Isophorone diamine is then added dropwise to the reactor at room temperature, and additional solvent or solvent mixture is added to form a clear and viscous polymer solution.
Example 3
Film drying time
The film formulation prepared according to example 1 was coated on a glass slide at 35 ℃ to evaluate the drying time. All samples showed rapid drying within 2 minutes, which resulted in a clear, uniform film. Table 1 lists the average drying times for different polymer concentrations.
TABLE 1 average drying time of films prepared in example 1 at different concentrations
Example 4
Water vapor transmission rate of film
The ability of water vapor to pass through the films of the present invention was measured as the water vapor transmission rate (WVT) according to ASTM standard test method E96/E96M-15. WVT was evaluated for polymer formulations prepared according to examples 1 and 2 and determined to be 545.6 g/(day) (m), respectively2) And 657.0 g/(day) (m)2) Water vapor transmission rate to human skin of 240-1920 g/(day) (m)2) And (4) the equivalent.
Example 5
Water absorption and contact angle
The performance of the films of the invention under humid conditions was evaluated by measuring the contact angle, surface energy and water absorption. The films prepared from the formulations of examples 1 and 2 exhibited the ability to form hydrophobic and water-resistant films and exhibited low water absorption, as shown in table 2.
TABLE 2 Performance of the films under humid conditions
Example 6
Mechanical Properties
The mechanical properties of the film formulations prepared according to example 1 were evaluated according to the standard method ASTM D882 and are shown in table 3.
TABLE 3 mechanical Properties of the films
The above-described mechanical properties show that the film formulations prepared according to example 1 are capable of forming elastic and flexible but tough polymer films.
Example 7
In situ film formation on skin
The film compositions prepared according to examples 1 and 2 were applied to human skin including forearms, legs and knuckles. The thickness of the formed transparent film is 20-120 μm during curing, and the curing time is within 2 minutes. As shown in fig. 1-4, the resulting film is flexible and peelable from a person's skin and nails. These films were observed to remain on the skin for more than 2 days without edge curl. No crack formation was observed. The film remained intact on the skin, and no edge curl was observed after bathing or swimming.
The film peeled from the nail in fig. 4 was observed to be transparent, and the film peeled from the skin in fig. 2 was observed to be opaque. While not wishing to be bound by theory, it is believed that during film formation, the solvent system in the film forming solution may be dissolving/clearing the Skin Surface Lipid Film (SSLF), a mixture of sebum from sebaceous glands and lipids secreted by keratinocytes to promote firm adhesion to the skin. Thus, sebum and lipids on the film in fig. 2 may cause the opacity phenomenon.
Example 8
Bacterial barrier
A study was conducted to evaluate the ability of the film formulations prepared according to example 1 to act as protective barriers against microbial penetration. The formulation was brushed on an agar plate and allowed to form a polymer film in situ. Each of the five (5) clinically relevant microorganisms listed below was deposited directly on the formed film. The dishes are then incubated under conditions conducive to the growth of these microorganisms. On
Example 9
Antibacterial agent
An antimicrobial study according to the united states pharmacopeia, chapter 51, antimicrobial efficacy test was conducted to evaluate the antimicrobial performance of the formulations prepared according to examples 1 and 2. Five (5) microorganisms listed in example 6 were used to examine the samples. Both example 1 and example 2 exhibit antibacterial properties against all five microorganisms under the usp chapter 51 standard.
Further studies were conducted to evaluate the antimicrobial properties of the example 1 formulation over multiple uses. The preparation was repeatedly examined daily for a period of 10 days using 5 microorganisms each at a concentration of
Example 10
Cytotoxicity
According to standard ISO 10993-5: in vitro cytotoxicity test, the cytotoxicity of the preparation prepared according to example 1 was evaluated. Two experiments were performed, agarose overlay and direct contact using mouse fibroblasts. In both tests, the formulation was rated as non-toxic.
Example 11
Skin irritation and allergy
According to standard ISO 10993-10: irritation and skin allergy tests the formulations prepared according to example 1 were evaluated for skin irritation and sensitization. Buehler skin sensitization tests were performed on albino guinea pigs to assess the effect of the formulation on any allergic reactions such as erythema and edema. Each study showed that the formulation did not cause any sensitization reaction.
The formulation was additionally applied directly to shaved rabbits to assess the potential for skin irritation. The primary irritation index of the formulation was scored as 0.2, indicating negligible irritation response.
Example 12
Subcutaneous implantation
Testing according to standard ISO 10993-6: local response test after implantation, the local response of the preparation prepared according to example 1 was evaluated when it was in direct contact with the live subcutaneous tissue of rabbits. Subcutaneous implantation was performed with the formulation scored by histopathological analysis, with a irritation score of 0.0, indicating that the formulation was non-irritant.
Example 13
Acute toxicity
According to standard ISO 10993-11: systemic toxicity was tested and the short-term systemic toxic effect of the formulation prepared according to example 1 on mice was evaluated. No sign of toxicity was observed in any of the mice treated with the formulation, indicating that the formulation was non-toxic.
Example 14
Sub-chronic toxicity
A two-week subchronic toxicity study was conducted in rats according to the same ISO standard method as in example 13 to evaluate the effect of the example 1 formulation on long-term systemic toxicity. Clinical observations, histopathological analysis, hematology, coagulation, clinical chemistry and autopsy were performed in this study. The formulation was determined to be negative for any signs of systemic toxicity.
Example 15
And (3) comparing data: detachment during application
The formulation prepared according to example 1 (film 1) and commercially available
Example 16
And (3) comparing data: film cracking and peeling
The formulation prepared according to example 1 (film 1), commercially available
FIG. 6A shows a
FIG. 6B shows the
FIG. 6C is the exemplary film of FIG. 6A taken 18 hours after application to human skin,
Fig. 6D shows the skin of a person after being applied to the skin of the person 24Exemplary film of FIG. 6A taken after,
FIG. 7 is the exemplary film of FIG. 6A after removal from human skin
Thus, the
Example 17
And (3) comparing data: solvent effect
The formulation prepared according to example 1 (film 1) was varied in that two different solvent systems were used to illustrate the effect of different solvents on the adhesion of the film to the skin.
A
In fig. 9, the
Fig. 9 illustrates that the adhesion and other mechanical properties of the film are determined by the compounding of the different components, rather than by the polymer composition of the film alone.
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