阅读说明：本技术 治疗和预防皮肤屏障破坏的方法和组合物 (Methods and compositions for treating and preventing skin barrier disruption ) 是由 舒拉米特·里希特·达扬 于 2019-02-04 设计创作，主要内容包括：本发明提供了用于治疗或减弱和/或预防受试者的皮肤屏障破坏、皮肤损伤和皮肤病症的组合物和方法。本发明的溶致液晶组合物包括相变材料中的至少一种和至少一种角质层组分。(The present invention provides compositions and methods for treating or attenuating and/or preventing skin barrier disruption, skin damage and skin conditions in a subject. The lyotropic liquid crystal composition of the present invention comprises at least one of the phase change materials and at least one stratum corneum component.)

1. A lyotropic liquid crystal composition comprising:

a. at least one Phase Change Material (PCM); and

b. at least one Stratum Corneum (SC) component,

for topical administration to treat, attenuate or prevent skin barrier disruption in mammals.

2. The composition of claim 1, wherein the lyotropic liquid crystal composition is in a phase selected from the group consisting of hexagonal phase, lamellar phase, cubic phase, reverse topology lyotropic phase, and any combination thereof.

3. The composition according to claim 1, wherein the Phase Change Material (PCM) is a paraffin hydrocarbon, a fatty acid, a hydrate of a fatty acid salt, a hydrate of a phospholipid fatty acid salt, polyethylene glycol (PEG), a polyol, a mineral oil, a hygroscopic material, a hydrate of an inorganic salt, and a combination of a fatty acid and sodium acetate trihydrate.

4. The composition according to claim 1, wherein the Stratum Corneum (SC) component is selected from the group consisting of phospholipids, cholesterol, free fatty acids, squalane, n-alkanes, triglycerides, ceramides, keratinocyte-derived components, proteins, keratin, and keratin-derived components.

5. The composition of claim 1, further comprising at least one amphiphilic compound, a surfactant and a solvent selected from the group consisting of water, an aqueous phase or a non-aqueous phase.

6. The composition of claim 1, further comprising at least one additive selected from the group consisting of: vitamins, sunscreens, diglycerides, triglycerides, antibiotics, antifungal agents, citric acid, insect repellents, analgesics, active cosmetic ingredients, polyols, disinfectants, astringents, herbal extracts, fruit extracts, antiseptics, pigments, thermotropic liquid crystal pigments, oils, etheric oils, fragrances, perfumes, anesthetics, abrasives, and emulsifiers.

7. The composition of claim 1, further comprising a drug.

8. The composition according to claim 1, for cosmetic use.

9. The composition of claim 1, which is a soap, a soap-based composition, a skin care fire suppressant or a skin care fire suppressant-based composition.

10. The composition of claim 1, wherein the skin barrier disruption is selected from dermal injury, topical injury, skin condition, skin energy disruption, skin ailments, skin allergies, skin discomfort, skin hypopigmentation, skin perturbations, superficial burns, deep local burns, deep burns, blisters, congestion, local pain, local wounds, dermal inflammation and scarring following acute or chronic injury, and acute or chronic skin irritation.

11. The composition of claim 10, wherein the acute or chronic skin irritation is selected from irritation following thermal skin injury, insect bites, abrasion, radiation, laser, exposure to extreme cold, acne, wrinkles, nursing breast skin injury, skin abrasion, and skin dryness.

12. The composition of claim 1, wherein the composition is suitable for preventing skin barrier disruption selected from dermal medical procedures, veterinary dermal procedures, medical hygiene preparations, soaps, fungal or pest-destroying preparations.

13. The composition of claim 1, wherein the topical administration is selected from the group consisting of applying directly onto a skin barrier disruption with or without a dressing or onto a fabric wipe, tissue, silicon pad, band-aid or bandage, applying as a soap, painting or spraying the composition.

14. A method for treating, attenuating or preventing skin barrier disruption in a mammal, the method comprising administering the composition of claim 1 to the skin barrier disruption.

15. A method of reducing scarring of an area of skin following a skin barrier disruption, the method comprising applying the composition of claim 1 to a topical area of skin in the vicinity of the skin barrier disruption.

16. A process for producing the lyotropic liquid crystal composition of claim 1, comprising:

(a) hydrolyzing and/or saponifying and/or dissolving at least one PCM component and at least one SC component to produce an amphiphilic product;

(b) hydrating the amphiphilic product; and optionally

(c) Adding at least one additive.

17. The method of claim 16, wherein the PCM is a fatty acid salt hydrate or a phospholipid fatty acid salt hydrate.

18. The lyotropic liquid crystal composition according to any of claims 1 to 13, for use in the treatment, attenuation or prevention of skin barrier disruption in a mammal.

Technical Field

The present invention relates generally to methods of treating and preventing localized injury, and more particularly to methods of producing compositions for treating and protecting against skin barrier disruption, skin damage, and skin conditions.

Background

Our skin is the largest organ of the human body and it has a number of key functions. Due to the existence of the skin barrier, the skin regulates the body temperature, prevents the body fluid loss caused by evaporation and has the function of resisting infection. It also contains sensory receptors that provide important information about the environment.

The skin barrier is actually the Stratum Corneum (SC), which is the outermost layer of the epidermis. The stratum corneum functions to form a barrier to protect the underlying tissues from infection, dehydration, chemicals and mechanical stress. This layer consists of dead or non-dividing keratinocytes, called keratinocytes, mainly keratin embedded in the Liquid Crystal (LC) phase of a lipid matrix consisting of phospholipids/ceramides, cholesterol and fatty acids.

The liquid crystalline phase of the stratum corneum itself enables the skin to protect the body homeostasis. With environmental or internal temperature changes and thermal or any dynamic vibration of the molecules, the constituents of the stratum corneum undergo "thermotropic phase changes" and may change the liquid crystal phase slightly to a series of mesophases, causing water loss (by transpiration cooling) or being in a specular state (by preventing water loss and maintaining body temperature). The cooling process, for example, involves removing internal energy from the system. Thus, the horny layer itself functions as a Phase Change Material (PCM) due to its liquid crystal state, has the ability to change phase with kinetic or thermal energy changes, and may cause latent heat, heat radiation, absorption, or maintenance.

Burns are an injury-mediated skin condition that disrupts the "skin barrier" to disrupt the stratum corneum, which is caused by any energy (including heat, radiation, laser, radiation, very low temperature, electrical or mechanical abrasion), abrasion, and friction applied to the skin. The chemical may also be the source of a burn that is caused solely by chemically mediated disruption of the stratum corneum. Thermal, UV or other radiation damage damages the skin through similar pathophysiological processes. Skin inflammation and dehydration also cause heating of the skin layers, resulting in a breakdown of the skin barrier. Disruption of the skin barrier may also cause inflammation (e.g., insect bites, dermatitis) and dehydration (e.g., xerosis).

Although deep skin may be destroyed immediately after severe injury, in most cases the stratum corneum/"skin barrier" is destroyed first. The deeper layers of the skin may then be involved due to the "domino effect" resulting from the breakdown of the skin barrier.

The severity of the burn condition or the burn condition outcome is a function of the intensity and duration (e.g., energy) of the injury. For example, the temperature of the heat source and/or its duration on the skin will determine the severity of the burn. Three major burn severity categories are: shallow second (first level), deep second (second level) and full layer (third level).

Heat-mediated, mechanical-mediated, radiation-mediated, laser-mediated and other damage-mediated skin damage triggers the "domino effect" and a series of wound progression events, as summarized in table 1 below:

TABLE 1

If the burn is allowed to progress to the metabolic and inflammatory stages described above, the risk of complications (mainly due to fluid loss and infection) will increase exponentially. Complications associated with burns can still occur despite the use of existing early burn treatments, even the low-intensity treatment of moderate burns, costing $ 200,000 or more per treatment if complications occur.

Although there is no accurate statistical data on how many people have experienced a burn (in any form), we do know that at least 600 million patients worldwide each year seek treatment for burns, which makes burns a heavy burden on the medical system. In 2015 there were 486,000 patients who received hospital and emergency room treatment for burns in the united states alone, with the vast majority of burns occurring at home or at work. Of these, 50,000 people require hospitalization and treatment, costing over $ 104 million.

The current state-of-the-art burn care treatments aim at cooling the affected area and increasing the hydration of water/hydrogel-or alcohol-based formulations, to prevent contamination and infections (e.g. silver-based formulations), to reduce pain and support wound healing by analgesics/anesthetics (e.g. enzymes and cell-based formulations), until now known involving a number of different treatment regimes for each stage of the chain reaction after the initial injury. From daily care to hospitalization, it requires a range of professionals including surgeons, dermatologists, psychologists, occupational therapists, and the like.

In the case of more severe burns, repair therapy typically involves the destruction of a portion of the damaged epithelial layer, including the excision of the blister (bulla) and the removal of adherent necrotic (dead) tissue and eschar (debridement). These treatments are associated with a number of complications due to the loss of the epithelial barrier and can cause irreparable scarring. If they are not effective, it may be necessary to replace irreparable damaged skin by transplantation and skin substitutes.

A large number of burn patients die due to infection, dehydration, lack of healing and sepsis. In addition, many burn patients develop disabling wounds and scars years after the initial burn. Additionally or alternatively, the patient may be disfigured and require plastic surgery.

Accordingly, it is an object of the present invention to provide a topical composition for preventing, treating, reducing and/or attenuating skin barrier disruption in a subject.

It is another object of the present invention to provide pharmaceutical compositions and/or pharmaceutical "carriers" for use in treating subjects suffering from skin barrier disruption.

Disclosure of Invention

In one aspect, the present invention provides a lyotropic liquid crystal composition comprising: (a) at least one Phase Change Material (PCM); and (b) at least one Stratum Corneum (SC) component for topical administration to treat, reduce, or prevent skin barrier disruption in a mammal.

In some embodiments, the lyotropic liquid crystal composition is in a phase selected from the group consisting of: hexagonal phase, lamellar phase, cubic phase, inverse topological lyotropic phase, and any combination thereof.

In some embodiments, the Phase Change Material (PCM) is a paraffin hydrocarbon, a fatty acid salt hydrate, a phospholipid fatty acid salt hydrate, polyethylene glycol (PEG), a polyol, a mineral oil, a hygroscopic material, an inorganic salt hydrate, and a combination of a fatty acid and sodium acetate trihydrate.

In some embodiments, the Stratum Corneum (SC) component is selected from the group consisting of phospholipids, cholesterol, free fatty acids, squalane, n-alkanes, triglycerides, ceramides, keratinocyte-derived components, proteins, keratins, and keratin-derived components.

In some embodiments, the composition further comprises at least one amphiphilic compound, a surfactant, and a solvent selected from water, an aqueous phase, or a non-aqueous phase.

In some embodiments, the composition further comprises at least one additive selected from the group consisting of: vitamins, sunscreens, diglycerides, triglycerides, antibiotics, antifungal agents, citric acid, insect repellents, analgesics, active cosmetic ingredients, polyols, disinfectants, astringents, herbal extracts, fruit extracts, antiseptics, pigments, thermotropic liquid crystal pigments, oils, etheric oils, fragrances, perfumes, anesthetics, abrasives, and emulsifiers.

In another embodiment, the composition further comprises a drug.

In another embodiment, the present invention provides a composition for cosmetic use.

In some other embodiments, the compositions of the present invention are soaps, soap-based compositions, skin care and fire suppression agents, or skin care and fire suppression agent-based compositions.

In some embodiments, the skin barrier disruption according to the present invention is selected from dermal injury, topical injury, skin disorder, skin energy disruption, skin ailments, skin allergies, skin discomfort, skin hypopigmentation, skin perturbations, superficial burns, deep local burns, deep burns, blisters, congestion, local pain, local wounds, dermal inflammation and scarring following acute or chronic injury, and acute or chronic skin irritation. The acute or chronic skin irritation is selected from the group consisting of irritation after thermal skin injury, insect bites, abrasions, radiation, laser, exposure to extreme cold, acne, wrinkles, nursing breast skin injury, skin abrasion, and skin dryness.

In some embodiments, the composition is suitable for preventing a skin barrier disruption selected from dermal medical procedures, veterinary dermal procedures, medical hygiene preparations, soaps, preparations that disrupt fungi or pests.

In some embodiments, the topical administration is selected from the group consisting of application directly onto the skin barrier disruption with or without a dressing or onto a fabric wipe, tissue, silicon pad, band-aid or bandage, application as a soap, application or spraying of the composition.

In another aspect, the present invention provides a method for treating, reducing or preventing skin barrier disruption in a mammal, the method comprising administering to the skin barrier disruption a composition comprising: (a) at least one Phase Change Material (PCM); and (b) at least one Stratum Corneum (SC) component.

In another aspect, the present invention provides a method of reducing scarring of an area of skin following a skin barrier disruption, the method comprising applying to a topical area of skin in the vicinity of the skin barrier disruption a composition comprising: (a) at least one Phase Change Material (PCM); and (b) at least one Stratum Corneum (SC) component.

In another aspect, the present invention provides a process for producing a lyotropic liquid crystal composition according to the present invention, said process comprising: (a) hydrolyzing and/or saponifying and/or dissolving at least one PCM component and at least one SC component to produce an amphiphilic product; (b) hydrating the amphiphilic product; and optionally (c) adding at least one additive. According to a particular embodiment, the PCM is a fatty acid salt hydrate or a phospholipid fatty acid salt hydrate.

In another aspect, the present invention provides a lyotropic liquid crystal composition comprising (a) at least one Phase Change Material (PCM); and (b) at least one Stratum Corneum (SC) component for use in treating, reducing, or preventing skin barrier disruption in a mammal.

Drawings

The present invention will now be described in connection with certain preferred embodiments with reference to the following illustrative figures so that the invention may be more fully understood.

With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of the preferred embodiments of the present invention only, and are presented in the cause of providing what is believed to be the most useful and readily understood description of the principles and conceptual aspects of the invention. In this regard, no attempt is made to show structural details of the present invention in more detail than is necessary for the fundamental understanding of the present invention, the description taken with the drawings making apparent to those skilled in the art how the several forms of the present invention may be embodied in practice.

In the drawings:

fig. 1A is a simplified block diagram of damage-induced damage to the skin barrier and repair mechanisms according to an embodiment of the present invention.

Fig. 1B is a simplified schematic flow diagram of an outlined method for preparing a dermal administration formulation according to an embodiment of the invention.

Fig. 2A is an image of a 300mm brass rod applied under sterile conditions to a dermal back burn injury tool of a 3 month old pig. Burn spots on skin are marked as: no formulation (no treatment) was administered (N1, N2, N3), control-treatment silver-based Silverol (S1, S2, S3) was administered, and a-formulation according to an embodiment of the invention (D1, D2, D3) was administered;

fig. 2B is a graphical representation of temperature measurements (° c) of the dermal back spots at 9 on a 3 month old pig before (control) and 1 hour, 3 hours, 24 hours, and 72 hours after burn injury: no formulation ("untreated"), control silver-based treatment ("Silverol") and composition of the invention ("composition a");

fig. 3A is an image of dermal back burn injury on a 3 month old pig after 15 days: no formulation administered (no treatment) (N2); administering a control silver-based treatment Silverol (S1); and applying an a-formulation according to an embodiment of the invention (D1).

Fig. 3B is a graphical representation of 18 dermal back burn lesions on two 3 month old pigs 15 days later: no formulation "no treatment" was administered, a control silver-based treatment "Silverol" was administered, and an "a-formulation" according to an embodiment of the invention was administered.

Fig. 4A is an image of dermal back burn injury on 3 months old pigs after 18 days: no formulation administered (no treatment) (N1, N2, N3); administering a control silver-based treatment Silverol (S1, S2, S3); and applying an a-formulation (D1, D2, D3) according to an embodiment of the invention.

Fig. 4B is an image of dermal back burn injury on a 3 month old pig after 24 days with application of formula a according to an embodiment of the invention (D2) with skin ruler on the injury spot and detached eschar (right hand side).

Fig. 4C is a graphical representation of diameter measurements (in millimeters) of dermal back burn lesions at 18 on pigs grown 3 months after 15 days, 18 days, and 24 days compared to day 0: no formulation "no treatment" was administered, a control silver-based treatment "Silverol" was administered, and an "a-formulation" according to an embodiment of the invention was administered.

Fig. 5 is an optical microscope image and camera photograph (inset) of a skin section of a 3 month old burn injury of the dermis back on a pig after 18 days compared to day 0: no formulation "no treatment" was administered, a control silver-based treatment "Silverol" was administered, and an "a-formulation" according to an embodiment of the invention was administered.

Fig. 6A is an image of dermal UV damage on the shoulder of an 11 year old boy. Images were taken after a period of 4 days of UV damage without application (control) of a composition according to an embodiment of the invention.

Fig. 6B is an image of dermal UV damage on the shoulder of an 11 year old boy. Images were taken after a period of 46 hours following application of a composition according to an embodiment of the present invention.

Fig. 7A is an image of a subject suffering from a dermal heat (scald by boiling oil) injury on an arm of a 48 year old female after injury and 5 hours of application of a composition according to an embodiment of the invention;

fig. 7B is an image of a dermal heat (boiling oil scald) lesion on an arm of a 48 year old female after a period of 4 days after application of a composition according to an embodiment of the present invention.

Fig. 7C is an image of a dermal heat (boiling oil scald) lesion on an arm of a 48 year old female after a period of 7 days after application of a composition according to an embodiment of the present invention.

Fig. 8A is an image of xeroderma on the arm of an 85 year old woman without any composition applied (control).

Fig. 8B is an image of xeroderma on the arms of a 85 year old woman after a period of 2 weeks after administration of a composition according to an embodiment of the present invention.

Fig. 8C is an image of xeroderma on the arms of a 85 year old female after a period of 4 weeks after administration of a composition according to an embodiment of the present invention.

Fig. 9 is a graph of the relative degree of blistering, hyperemia, and pain (in percent) in untreated subjects (n ═ 18) and subjects treated with topical compositions according to embodiments of the present invention.

Like reference numerals refer to like parts throughout the drawings.

Detailed Description

In one aspect, the present invention provides a lyotropic liquid crystal composition comprising: (a) at least one Phase Change Material (PCM); and (b) at least one Stratum Corneum (SC) component for treating, reducing, or preventing skin barrier disruption in a mammal.

Phase Change Materials (PCMs) are well known for their ability to absorb and accumulate heat while changing from a solid (crystalline) to a liquid, and subsequently release this latent heat while returning to the solid (crystalline) phase as they cool. The peculiarity of PCMs is that during this phase change the temperature of the PCM itself remains almost constant, as does the space around them.

High concentrations of fatty acid salts, fatty acid salt hydrates, surfactants, amphiphilic compounds or molecules, etc., crystallize as lamellar mesophases and hexagonal mesophases and other mesophases of liquid crystalline structure, which mimic the stratum corneum, skin barrier and membranes in biological systems.

Liquid crystals are characterized by optically anisotropic compounds between a crystalline/solid phase and an isotropic liquid phase with mobility, but an average structural order relative to each other along the molecular axis, resembling a solid, transmitting polarized light under static conditions (birefringence). In other words, liquid crystals have liquid-like fluidity, but molecules are oriented in a crystal-like manner. Many compounds are known to form liquid crystalline mesophases. They may be natural or synthetic polymeric amphiphilic or non-amphiphilic liquid crystals or low molecular weight, e.g. organic surface active amphiphilic liquid crystals. The range of the liquid crystal mesophase is influenced by temperature changes (thermotropic liquid crystals) or by changes in the solvent concentration (lyotropic liquid crystals). At low concentrations, for example, amphiphilic compounds or molecules form an isotropic phase. However, as its concentration in the solvent increases, a liquid crystal phase is gradually formed in the isotropic phase until a homogeneous and anisotropic liquid crystal is obtained. The concentration increase that occurs after the addition or after the evaporation/drying process will further result in a mixture of liquid crystals (lyotropic crystals) and crystalline phases until complete crystallization. These are examples of endothermic phase transitions. After rehydration/solvent absorption, an exothermic process occurs. These effects of enthalpy are in some cases similar to PCM.

Thus, the term "lyotropic liquid crystal" refers to an intermediate phase formed by dissolving or emulsifying amphiphilic molecules in a suitable solvent under suitable concentration, temperature and pressure conditions. Mixtures of high soap concentrations in water are examples of lyotropic liquid crystals. The amphiphilic molecule or compound includes a hydrophilic head group (which may be ionic or non-ionic) attached to a hydrophobic group. Lyotropic liquid crystals have an additional degree of freedom, even if they are capable of inducing concentrations of a plurality of different phases. As the concentration of amphiphilic molecules increases, several different types of lyotropic liquid crystal structures appear in solution. Each of these different types has a different degree of molecular order in the solvent matrix. The lyotropic liquid crystals according to the present invention may form structures of hexagonal phase, lamellar phase, cubic phase, inverse topological lyotropic phase or any combination thereof. Thus, in some embodiments of the invention, liquid crystal phases are selected, but are not limited to hexagonal phases, lamellar phases, cubic phases, inverse topological lyotropic phases, and combinations thereof.

To preliminarily mimic the skin barrier and stratum corneum (e.g., lamellar liquid crystals), fatty acids, fatty acid salts, fatty acid salt hydrates, liquid crystal-forming materials, and/or lipids require minimal water content for stability, and can also be used as carriers for PCMs or PCMs that are easily dispersed upon phase change. Below this water concentration, liquid crystals are formed. Additionally, the PCM and/or the stratum corneum may be formulated to form a liquid crystal phase and/or be part of and/or intercalated into a liquid crystal forming material.

The direct beneficial effect of PCMs in the Liquid Crystal (LC) mesophase on skin barrier disruption, such as burned skin, skin irritation, wounds, and other skin conditions, appears to be related to cooling, both through the endothermic phase change and through the supporting skin barrier.

Accordingly, in one aspect, the present invention provides a lyotropic liquid crystal composition comprising: (a) at least one Phase Change Material (PCM); (b) at least one Stratum Corneum (SC) component for use in treating, attenuating or preventing skin barrier disruption in a mammal.

In some embodiments, the lyotropic liquid crystal composition of the present invention comprises 10% to 60% w/w water, based on the total weight of the composition.

In some embodiments, the present invention provides a composition for treating, or attenuating, or preventing and/or protecting against a skin barrier disruption (e.g., topical damage) to a systemic local area of a mammalian body, particularly the skin. The compositions, including at least one phase change material and at least one stratum corneum component, are adapted to absorb and transfer energy (e.g., heat) from an area of skin in order to treat skin barrier disruption and protect against damage.

Thus, according to an embodiment of the present invention, there is provided a composition for topical administration for treating or attenuating and/or protecting against dermal damage on a localized area of mammalian skin, the composition comprising (a) at least one Phase Change Material (PCM); and (b) at least one Stratum Corneum (SC) component; wherein the composition is adapted to absorb energy (heat) from a localized area to treat or attenuate and/or protect against dermal damage.

According to some embodiments, the composition comprises one PCM, two PCMs or up to 20 PCMs, in particular, at least one PCM selected from the group of 5 PCMs as defined herein.

According to some embodiments, the composition comprises one Stratum Corneum (SC) component, two Stratum Corneum (SC) components, or up to 20 Stratum Corneum (SC) components. According to particular embodiments, the composition includes five, six, or seven Stratum Corneum (SC) components.

It should be noted that in some cases, the Stratum Corneum (SC) component may be used as a Phase Change Material (PCM). In this case, the composition of the invention comprises only a single active compound, which acts both as a Stratum Corneum (SC) component and as a Phase Change Material (PCM), and is capable of providing a composition with the desired properties.

The PCM may be characterized by the absorption or release of 50-200J/g of heat during solid-solid (solid-liquid crystal) and solid-liquid phase transitions.

According to some embodiments, the PCM is a single compound or a mixture of compounds selected from the group consisting of: paraffinic hydrocarbons, non-paraffinic compounds, hygroscopic materials and eutectic PCM compounds.

Paraffinic hydrocarbons include mineral oil products, typically made from n-alkanes CH₃-(CH₂)_n-CH₃Or more usually from n.gtoreq.16 (C)_nH_2n+2) The linear chain of (1). As the chain length increases, so does the heat of fusion (HoF) or latent heat, which tends to increase with the number of carbon atoms making up the chain. Paraffin is safe, reliable, predictable, and non-corrosive. Paraffin waxes are usually mixtures of different alkanes.

Non-paraffinic compounds include fatty acids, salt hydrates, glycols and polyols.

Fatty Acids (FA) are characterized by the chemical formula CH₃(CH₂)_2nCOOH。

The fatty acid eutectic mixture has better thermal reliability, and the fatty acid binary and ternary eutectic mixtures have lower phase transition temperatures relative to the corresponding single fatty acid. The fatty acid eutectic mixture includes a higher monocarboxylic acid having from about 12 to about 22 and from 8 to 25 carbon atoms. Saturated or unsaturated, substituted or unsubstituted fatty acids or combinations thereof are useful. The melting points of saturated fatty acids increase gradually with their molecular weight.

The salt hydrate being an alloy AB of salt and water_nH₂O, such as fatty acid salt hydrate, and inorganic salt hydrate M_nH₂O, e.g. copper salt hydrate.

Notably, the fatty acids can form salts upon neutralization with, for example, a base (e.g., zinc oxide, metal hydroxides such as sodium hydroxide, magnesium hydroxide, aluminum hydroxide).

The glycols, commonly known as polyethylene glycols (PEGs), are represented by the general formula HO-CH₂-(CH₂-O-CH₂-)n-CH₂-OH. Glycols are soluble in water and organic compounds. As the average Molecular Weight (MW) of the compound increases, the melting temperature HoF increases.

Polyols and some specific polyalcohol amine derivatives are PCM, which is characterized by a lower enthalpy of fusion. Nevertheless, they are still capable of releasing and absorbing large amounts of heat during solid-solid or liquid crystal mesophase transitions. For example, PEG undergoes a phase transition in the temperature range of 15 ℃ to 60 ℃.

The moisture absorbent material can absorb and release water while absorbing or releasing heat. For example cellulose, keratin.

The eutectic PCM may be a combination of PCM, e.g. a combination of a fatty acid and sodium acetate trihydrate.

Thus, the Phase Change Material (PCM) according to the present invention may be paraffin, fatty acid salt hydrate, phospholipid fatty acid salt hydrate, polyethylene glycol (PEG), polyol, mineral oil, hygroscopic material, inorganic salt hydrate, and a combination of fatty acid and sodium acetate trihydrate.

According to some embodiments, the compositions of the present invention comprise a hydrate of a fatty acid salt, which is an organic salt hydrate, capable of absorbing well over 200kJ/kg of heat. The PCM optionally further comprises a paraffin oil having a thermal conductivity of 10 to 400W/m x k.

One compound or a mixture of two or more compounds may be used as PCM component in the composition of the present invention.

According to some embodiments of the invention, the at least one PCM is present in the composition in a concentration of 0-90 wt%, more particularly 50-70 wt%.

According to some other embodiments, the Stratum Corneum (SC) component is a single compound or a mixture of compounds selected from the group consisting of: lipids, glycerides, fatty acids, squalene, squalane, phytosqualene, sterols (such as phytosterols, cholesterol, lanolin, etc.), keratinocyte-derived ingredients, proteins, keratin, and keratin-derived ingredients. The Stratum Corneum (SC) component comprises:

-non-polar lipids: from sterols/wax esters, such as beeswax and/or n-alkanes.

-a phospholipid: hydrogenated or hydroxylated lecithin, phytosphingosine, ceramides, sphingosine, dihydrosphingosine and phytosphingosine and mixtures thereof. In terms of oxidative stability, phospholipids having an iodine value of about 20, hydrogenated or hydroxylated, are preferred. Phytosphingosine is important even at levels as low as 1 wt% in the lipid layer of the stratum corneum because of its antimicrobial activity. In addition, phytosphingosine is a precursor of ceramides.

Triglycerides, such as fats or oils (e.g. palm, coconut, olive, neem, pomegranate, avocado and all others present).

-Fatty Acids (FA) and Free Fatty Acids (FFA) -carboxylic acids. Saturated or unsaturated fatty acids containing 8 to 25 carbon atoms or combinations thereof (e.g., myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, arachidic acid, and all others present) are used. Higher monocarboxylic acids having preferably from about 12 to about 22 carbon atoms. Saturated or unsaturated, substituted or unsubstituted fatty acids.

One stratum corneum compound or a mixture of two or more compounds may be used as a stratum corneum component in the compositions of the invention.

In the SC component, the composition may comprise sphingolipid(s) and/or phospholipid(s) and/or phosphatidylcholine, such as lecithin and/or ceramide(s) (0-90%, particularly 15-25%), sterols such as phytosterol(s), lanolin, cholesterol (0-90%, particularly 10-20%), wax esters such as beeswax, carnauba wax (0-90%, particularly 4-8%), alkenes such as n-alkanes such as camellia wax/oil (0-90%, particularly 2-7%), squalene and/or plant squalene (squalane) (0-90%, particularly 4-8%), free fatty acid(s) (FFA) (0-90%, particularly 0.01-15%).

In some embodiments, the composition may comprise free fatty acid(s) (FFA) as follows: stearic acid (e.g., 9.9%), myristic acid (e.g., 3.8%), arachidic acid (e.g., 0.3%), linoleic acid (e.g., 12.5%), palmitic acid (e.g., 36.8%), palmitoleic acid (e.g., 3.6%), oleic acid (e.g., 33.1%). Other FFAs may also be included.

Thus, the Stratum Corneum (SC) component of the present invention may be selected from phospholipids, cholesterol, free fatty acids, squalane, n-alkanes, triglycerides, ceramides, keratinocyte-derived components, proteins, keratin, and keratin-derived components.

According to some embodiments of the invention, the at least one Stratum Corneum (SC) component is present in the composition at a concentration of 0-90%, more specifically 50-70%, by weight.

According to some embodiments, the composition of the invention further comprises at least one additive selected from the group consisting of: drugs, vitamins (e.g., vitamins A, C, D, E and K), sunscreens, diglycerides, triglycerides, antibiotics, antifungal agents, citric acid, lactic acid, insect repellents, analgesics, active cosmetic ingredients, polyols, disinfectants, astringents, herbal extracts, fruit extracts, antiseptics, pigments, thermotropic liquid crystal pigments, lipids, oils, etheric oils, fragrances, perfumes, anesthetics, abrasives, and emulsifiers.

Thus, the compositions of the present invention may include a variety of drugs, such as triethanolamine, triethanolamine/sodium alginate; anti-inflammatory agents such as steroids; up to 2.5% hydrocortisone; an antihistamine; 0.1-3% of coal tar and benzoyl peroxide; 0.1% -3% antibacterial/antifungal agent (e.g., a silver-based component such as 0.1-2% silver sulfadiazine or 0.1-2% bifonazole); miconazole nitrate in an amount of 0.3-2%, etc.; 3, 4-dibromo and 3,4', 5-tribromosalicylanilides (3,4di-and 3,4',5 tri-bromosalicylanilides); 4,4' -dichloro-3 (trifluoromethyl) carbanilide; 3,4,4' -trichlorocarbanilide and mixtures thereof; sialic acid and glycolic acid; analgesics, such as lidocaine; and a therapeutic enzyme.

The compositions of the present invention may include alternative/talc whitening materials, antistatic and skin conditioning agents, hyaluronic acid compounds, collagen, milk extracts such as skim milk, herbal materials, humectants, antioxidants and fillers, clays, honey, astringents such as zinc oxide, zinc glycerolate, zinc chloride, magnetic particles, minerals, gold particles, sodium chloride, chelating agents such as pentasodium pentetate, pentetate.

The composition of the invention may comprise an adjuvant selected from the group consisting of: water-miscible or water-soluble sunscreens or UV protectors such as benzyl salicylate; antioxidants such as pentaerythritol tetrakis (di-tert-butyl-4-hydroxy) phenylpropionate; insect repellents such as citronellol; a chemical repellant; a viscosity modifier; d-panthenol; hydrolyzed collagen; animal proteins and any mixtures thereof.

According to some embodiments of the invention, the at least one additive is present in the composition or formulation in a concentration of 0-30%, 1-20%, 2-15%, 3-10% by weight, based on the total weight of the composition.

According to some embodiments of the invention, the composition further comprises at least one solvent or hydrating agent. In some cases, the hydrating agent is water, such as double distilled water.

According to some embodiments of the invention, the at least one solvent or hydrating agent is water, which is present in the composition at a concentration of 10-60%, specifically 20-40%, more specifically 30%, by weight.

The solvent or hydrating agent may further comprise a pH adjusting agent, such as an acid or base. In some embodiments, the base comprises sodium hydroxide and an acid, lactic acid.

A composition for topical administration to treat and/or prevent skin barrier disruption, the composition comprising:

at least 40, 50, 60, 70, 80 or 90% w/w of at least one or a combination of the following: saturated or unsaturated fats, fat derivatives, lipids, lipid derivatives, fatty acids, saturated or unsaturated fatty acids, fatty acid salt hydrates, fatty acid esters, fatty acid derivatives, fatty acid salts, basic metal fatty acids, basic metal fatty acid salts, basic metal fatty acid salt derivatives, acidic metal fatty acids, acidic metal fatty acid salts, acidic metal fatty acid salt derivatives, sterols, glycerides, amphiphilic lipids, homo-and/or iso-triglycerides, diglycerides, monoglycerides, triacylglycerols, non-polar lipids, glycerophosphates, glycerophospholipids, phosphatidic acids, phosphatidic acid derivatives, phosphatidylcholines (also known as lecithins), phosphatidylethanolamines (also known as cephalins), phosphatidylserines, phosphatidylinositols, phospholipids, sphingolipids, plasmalogens, sterols, sterol esters, prenol lipids, Polyprenol, prenyl alcohol ester, alkane, protein, liposome and hygroscopic material. Lipids comprise a group of naturally occurring molecules including fats, waxes, sterols, phytosterols, fat soluble vitamins (e.g., vitamins A, C, D, E and K),

lipids can be broadly defined by scientists as hydrophobic or amphiphilic small molecules; the amphiphile of some lipids allows them to form structures such as vesicles, multilamellar/unilamellar liposomes, liquid crystals or membranes in aqueous and non-aqueous solvents. Biolipids are derived in whole or in part from two different types of biochemical subunits or "building blocks": ketoacyl and isoprene groups. Using this approach, lipids can be divided into eight classes: fatty acids, glycerolipids, glycerophospholipids, sphingolipids, glycolipids and polyketides (derived from the condensation of ketoacyl subunits), sterol lipids and prenol lipids (derived from the condensation of isoprene subunits).

Although the term "lipid" is sometimes used as a synonym for fat, fat is a subgroup of lipids known as triglycerides. Lipids also include molecules such as fatty acids and their derivatives (including triglycerides, diglycerides, monoglycerides, and phospholipids), and other sterol-containing metabolites such as cholesterol.

In some embodiments, the present invention provides a lyotropic liquid crystal topical composition for treating, reducing, or preventing a skin barrier disruption, such as dermal damage, the formulation or composition comprising:

a. optionally 40, 50, 60, 70, 80 or 90% of amphiphilic molecules that have relatively no or little impairment of skin barrier function;

b. optionally less than 60, 50, 40, 30 or 20, 10% w/w of at least one of a liquid phase or a non-aqueous solvent carrier selected from water, a hydrocarbon or mixtures thereof;

c. optionally, at least one PCM or combination of PCMs, in a concentration of 0-90%, selected from organic and/or inorganic Phase Change Materials (PCMs) and fillers such as fatty acid(s), mineral oil(s) such as paraffin, polyethylene glycol (PEG) such as PEG10 and hygroscopic materials such as cellulose, keratin;

d. optionally, at least one of stabilizers, emollients, waxes, antiseptics, antifungal agents, antibiotics, analgesics, anti-inflammatories, insect repellents, moisturizers, anesthetics, minerals, herbs, fruits, and derivatives thereof, fillers, additives, skin refreshers, and fragrances, whitening agents, at a concentration of less than 15% w/w;

e. optionally 0-4% of an antibacterial agent such as 3, 4-dibromosalicylanilide and 3,4', 5-tribromosalicylanilide; 4,4' -dichloro-3 (trifluoromethyl) carbanilide; 3,4,4' -trichlorocarbanilide and mixtures thereof;

f. optionally 10% to 60% of a solvent such as water, hydrocarbons, propylene glycol, glycerol, mixtures thereof, non-aqueous solvents, with or without herb(s) and/or fruit(s) and/or tree(s) and/or flower(s) extract(s), tincture(s), fusogenic agent(s) such as meant, aloe, chamomile, Centella asiatica (Centella asiatica) and the like, plant and/or animal milk, honey;

g. optionally, a protein, an amphiphilic protein, a ceramide, an amino acid;

h. optionally, skin components, stratum corneum components, skin barrier components and mimics and the like;

i. optionally, alkanes and normal alkanes;

j. optionally, an aerosol propellant; and

k. optionally foaming/frothing chemical or mechanical factors, hydrocarbons, surfactants, liquid crystals.

The compositions of the present invention may comprise PCM component(s) (PEG, mineral oil, FFA, etc.) mixed with SC component(s) (cholesterol, squalane, n-alkanes, triglycerides, phospholipids, etc.) in aqueous or non-aqueous media emulsified with preservatives, pigments, analgesics, etc.

The compositions of the present invention may comprise PCM component(s) (PEG, mineral oil, FFA, etc.) in combination with a SC component (cholesterol, squalane, n-alkanes, triglycerides, phospholipids, etc.) in an aqueous or non-aqueous medium emulsified with, for example, lecithin, in combination with xanthan gum liquid crystals, hygroscopic materials, saponified hygroscopic materials, preservatives, pigments, analgesics, etc.

According to some other embodiments of the invention, the PCM component (PEG, mineral oil, FFA, etc.) mixed with the SC component (cholesterol, squalane, n-alkanes, triglycerides, phospholipids, keratin) is added to FA salts purchased and/or derived from neutralization and/or saponification processes and partly from PCM and/or SC components. The mixture is further diffused with an aqueous or non-aqueous medium, which can also be absorbed into the FA salt by capillary forces, and then rehydrated to form a liquid crystalline mesophase. PCM and/or SC components may be further added. A lyotropic liquid crystal phase is obtained which can be emulsified together with xanthan gum liquid crystal emulsion and combined with preservatives, any drug classes, humectants, pigments, analgesics and combinations thereof.

According to some other embodiments of the invention, the composition comprises lecithin (18%), lanolin (14%), beeswax (6%), olefins such as n-alkanes (3.7%), squalane (6.5%), free fatty acids (19.3%), stearic acid (9.9%), myristic acid (3.8%), arachidic acid (0.3%), linoleic acid (12.5%), palmitic acid (36.8%), palmitoleic acid (3.6%), oleic acid (33.1%), zinc oxide (0.5%), peppermint tincture (6%), organic Phase Change Materials (PCMs) -PEG-10 (3%), paraffin (2%) and liquid crystal xanthan gum (20%).

Some aspects of the invention provide a pharmaceutical composition for reducing the risk of a mammalian subject suffering from skin damage.

Some aspects of the invention provide pharmaceutical compositions for protecting a mammalian subject from skin damage.

Some other aspects of the invention provide pharmaceutical compositions for treating a mammalian subject suffering from skin damage.

Some other embodiments of the present invention provide compositions and methods for treating, preventing, reducing and/or attenuating skin barrier disruption in a mammalian subject.

Skin barrier disruption according to the present invention is dermal injury, topical injury, skin disorder, skin energy disruption, skin ailments, skin allergies, skin discomfort, skin hypopigmentation, skin perturbations, superficial burns, topical deep burns, blisters, congestion, topical pain, topical wounds, dermal inflammation, scarring following acute or chronic injury, and acute or chronic skin irritation involving skin barrier disruption. Acute or chronic skin irritation is irritation following thermal skin injury, insect bites, abrasion, radiation, laser injury, exposure to extreme cold temperatures, acne, wrinkles, nursing breast skin injury, dry skin, and skin abrasion caused by exercise, physical activity, obesity, or military activity.

In some embodiments of the invention, methods and compositions for burn treatment are provided.

In some embodiments of the present invention, methods and compositions are provided for treating chronic skin conditions involving disruption of the skin barrier.

In some other embodiments of the present invention, methods and compositions are provided for treating, preventing and/or attenuating blisters, congestion, pain, wound progression and scarring that are complicated by acute injury to mammalian skin.

In some other embodiments of the present invention, methods and compositions are provided for preventing, treating and/or attenuating blisters, congestion, pain, wound progression, inflammation and scarring that are complicated by chronic damage to mammalian skin.

In some other embodiments of the present invention, methods and compositions are provided for treating, attenuating and/or protecting against superficial and/or partial deep and/or deep burns of mammalian skin.

In other embodiments of the present invention, methods and compositions are provided for preventing a skin barrier disruption selected from dermal medical procedures, veterinary dermal procedures, medical hygiene preparations, preparations for disrupting fungi or pests.

In some embodiments of the present invention, methods and compositions are provided for use as an additional or primary component in artificial skin and skin supplement compositions.

Some embodiments of the present invention provide methods and compositions for use as "carrier" materials for drugs, anesthetics, analgesics, hydration-promoting materials, collagen, urea, hyaluronic acid, UV protectants, insect repellents, antifungal agents, antibiotics, depilatory compounds, antiperspirants, hair growth compounds, and the like.

Some embodiments of the present invention provide methods and compositions for cosmetic use.

Some embodiments of the present invention provide methods and compositions for cosmetic use.

Some embodiments of the invention provide a topical composition that is a rescue treatment for treating a skin barrier disruption in a subject. Such emergency treatment is sufficient to treat skin barrier disruption (i.e., burns) without any further medical surgery or treatment.

In one embodiment of the invention, the composition is a soap.

In one embodiment of the invention, the composition is a soap, a soap-based composition, a skin care fire suppressant or a skin care fire suppressant-based composition.

The mammalian subject according to the invention may be a human or an animal.

Furthermore, according to some embodiments of the present invention, the composition is suitable for direct application, spreading or spraying on the skin to treat or attenuate and/or prevent skin barrier disruption (i.e., skin damage).

Thus, the compositions of the present invention are suitable for application, and/or painting, and/or spraying and/or placement on the area surrounding the skin and/or dermal lesions to treat and/or protect against said dermal lesions, as a liquid crystal based emulsion, liquid crystal soap, liquid crystal based paste, liquid crystal based foam/mousse, liquid crystal based cream or liquid crystal based lotion, with or without a dressing.

Other embodiments of the present invention provide a medical device comprising a composition for treating, attenuating, preventing and/or inhibiting irritation of skin barrier disruption such as: wounds following thermal injury, mechanical injury, radiation injury, laser injury, insect bites, abrasion, extreme low temperature injury, acne, wrinkles, dry skin and/or chronic skin conditions involving disruption of the skin barrier,

medical devices according to the present invention include medical dressings, bandages, tissue wipes, tissues, silicon pads and bandages that may be applied to the skin to treat skin barrier breakdown.

Thus, according to an embodiment of the present invention, there is provided a method of treating or attenuating and/or preventing skin barrier disruption (e.g. dermal damage) in a subject, the method comprising administering a composition as described herein to an area of skin in the vicinity of the skin barrier disruption, thereby treating and/or attenuating and/or preventing the skin barrier disruption by reducing damage to the stratum corneum structure.

Additionally, according to one embodiment of the present invention, the composition is suitable for repairing the stratum corneum structure.

Furthermore, in accordance with another embodiment of the present invention, the composition provides precursors or stratum corneum structural elements to repair stratum corneum structure.

Still further, according to an embodiment of the present invention, the composition is adapted to regenerate stratum corneum structural elements.

Additionally, according to embodiments of the present invention, the compositions are adapted to mimic the structure and/or function of the stratum corneum.

Importantly, according to embodiments of the present invention, the composition prevents or reduces scarring of the area of skin near the skin barrier disruption.

In addition, according to embodiments of the present invention, the composition induces healing of an area of skin with compromised skin barrier in a shorter period of time than an untreated area of skin.

In another embodiment, the composition prevents wound progression.

Additionally, according to embodiments of the present invention, the composition induces the exfoliation of eschar from necrotic (dead) skin areas.

In another aspect, the present invention provides a lyotropic liquid crystal composition as detailed herein for use in the treatment, attenuation or prevention of skin barrier disruption in a mammal.

Fig. 1A shows a simplified block diagram of damage to the skin barrier caused by injury and the repair mechanism of the present invention. The figure depicts the process of skin burn or other skin injury, application of the composition of the present invention and subsequent skin repair.

700-injury (heat/abrasion/UV/laser/radiation treatment/inflammation/insect bite/extreme cold etc.) (710), resulting (712) in energy impingement on and in the skin (714), further resulting (716), (718) acute phase (720), which involves damage to different skin layers like Stratum Corneum (SC) on epidermis (722) and dermis (724). Damage to these skin layers results (726), (728) in disruption of the skin barrier (732) and a shift from the acute to the chronic phase (730) that is linear in intensity and/or duration of damage. Typically, this stage progresses to a chronic stage involving pain, congestion, blistering and cell necrosis (736). Disruption of the skin barrier is known to trigger (735) chronic conditions such as psoriasis, xerosis, atopic dermatitis, acne, etc. (738). Chronic conditions and the chronic phase of injury-mediated damage may lead to (731), (729) the evolution (733) of open and chronic wounds.

Conversely, when the skin is exposed (739) to a "formulation", which is a formulation or composition of the invention, as described herein (751), it involves a phase change material mechanism (741) and a stratum corneum recovery mechanism (761), which neutralizes the effects of damage (740), (750), (760) while immobilizing the skin barrier by absorbing heat (energy) (742) from the skin, which is further released (762) from the formulation. The mechanism modulates the energy absorbed by the skin and leads to skin regeneration (752) in a "biomimetic" mechanism (753), where (754) a remission of wound progression is achieved (737).

Without being bound by any particular theory, it is believed that the mechanism is based on a Phase Change Material (PCM) in combination with a material intended to mimic the stratum corneum-skin barrier. In this way, it can act as normal skin and can support (766) skin grafts and artificial skin (767).

The compositions of the invention themselves undergo a phase change from liquid crystal to lamellar crystals upon application to the skin, and a class of liquid bandages further promotes the breakdown of pathophysiological processes by absorbing heat (positive enthalpy) from the skin. During further phase transitions, heat is released from the formulation or composition (negative enthalpy), and the damage is neutralized (740), (750), and (760). Thus, there is an "exit" (770) from the chronic phase to the acute phase and from the acute phase to normal skin function.

In another aspect, the present application provides a method of making the composition of the present invention.

Fig. 1B is a simplified schematic flow diagram of an overview of the steps for preparing a composition for topical administration according to an embodiment of the present invention.

800 is a simplified schematic of parallel or alternative steps to obtain a product consisting of phase change material(s) (PCM/s) (100) and Stratum Corneum (SC) component (200). They are combined to obtain a composition in Liquid Crystal (LC) phase, comprising one or more PCM (111, 112) and/or one or more SC components (222, 212), which can be directly finished (500) to obtain the final product (555).

More specifically, the present invention provides a method of preparing a composition for dermal administration, the method comprising combining PCM/s and/or SC components to form a lyotropic Liquid Crystal (LC) mesophase.

The PCM or PCM product (mixture of PCMs) is added to the vessel/reactor together with the SC component or mixture of SC components, optionally with other lipid(s) such as Fatty Methyl Ester (FME). These materials are preferably melted and mixed. In the mixer, melting (30-85 ℃) is better performed with continuous stirring and mixing to make the material pourable ("flowable" mixture) until complete homogenization is achieved. Mixing can be performed manually (i.e., using a hand-operated implement, a hand mixer with or without a propeller), or using mechanical equipment suitable for home, institutional, or industrial food or cosmetic preparation. Dough kneaders, commonly referred to as kneaders, are useful. Other suitable mixing devices include "planetary" mixers and hobart mixers. An extruder that provides a shearing operation during mixing (e.g., a Sigma mixer with an extruder) may be used. The mixer may be provided with a jacketed bowl for heating and cooling.

The mixture of PCM and SC components may then be neutralized and/or saponified with a base. The "base" can be an alkali metal, alkaline earth metal or transition metal or their compounds such as oxides, hydroxides, carbonates, sulfates and chlorides, and can be used for alkali metal salt production (e.g. NaOH) in DDW, tinctures, extracts, plant milk, animal milk, oils, etc. Although not required, saponification can be carried out in a batch reactor, but only after the addition of one or more soluble bases according to the saponification number, as is known in the art (e.g., squalane SAP NaOH: 0.1340, lecithin SAP: 0.110-0.140).

Typically, the alkali metal salt consists of metal and acid moieties supplied as a solvent or solution in oil. They may be represented by the general formula (RCOO) xM, wherein R is an aliphatic or alicyclic group and M is a metal having a valence x. In the case of neutral salts, x is equal to the valence of the metal M. The acid salt (ratio of acid equivalents to metal equivalents greater than 1) contains the free acid, while the neutral salt contains no free acid.

Alkali metal salts are soluble, sparingly soluble or insoluble. The choice of the source of metal ions and fatty acid depends on the type of process and methods known in the art. Metal salts, in this case preferably fatty acid salts, typically include those of sodium, aluminium, barium, cadmium, calcium, cobalt, copper, iron, lead, lithium, magnesium, manganese, potassium, nickel, zinc and zirconium. Important fields of application for metal salts include lubricants and gel thickeners, emulsifiers, water repellents and fungicides. Suitable alkali metal cations are potassium and sodium cations. Suitable salt counterions include alkali metal, alkaline earth metal, ammonium, alkyl or hydroxyalkyl ammonium cations and mixtures thereof. It may also be desirable to have a small amount of sulfate present. These salts may be selected from the group consisting of bisulfite, sulfoxylate, metabisulfite, sulfite, and mixtures thereof.

A hydrated salt or saponified material of about 60-80% salt with 40-20% water (preferably 70:30) is obtained. The 70:30 hydrated salt is referred to as the "pure"/"smectic"/"lamellar" phase during saponification.

Such mixtures form lamellar Liquid Crystals (LC) in very low concentrations of lipid-containing water/solvent, as in the stratum corneum structure.

Thus, according to a specific embodiment, the composition consists of a base (e.g. sodium) -FA-salt in the lyotropic liquid crystalline phase, depending on its concentration in the solvent.

The solvent may be water, a hydrocarbon or a mixture thereof, an aqueous or non-aqueous phase (10-60%, specifically 20-40%, more specifically 30%), the presence or absence of herb(s) and/or fruit(s) and/or tree(s) and/or flower(s) extract(s), tincture(s), fusogenic agent(s) such as mint, aloe, chamomile, centella asiatica etc., plant and/or animal milk, honey.

The hydrated salt may then be further mixed with one or more additives including: various classes of drugs, for example triethanolamine, triethanolamine/sodium alginate, anti-inflammatory drugs such as steroids, hydrocortisone, antihistamines, coal tar, benzoyl peroxide, antimicrobial/antifungal agents (e.g., silver-based components such as silver sulfadiazine or bifonazole, miconazole nitrate, etc.). 3, 4-dibromo-salicylanilide and 3,4', 5-tribromosalicylanilide; 4,4' -dichloro-3 (trifluoromethyl) carbanilide; 3,4,4' -trichlorocarbanilide and mixtures thereof; sialic acid and glycolic acid. Analgesics, such as lidocaine, therapeutic enzymes, conventional preservatives, perfumes and conventional dyes, pigments and thermal pigments, substitute/talc and whitening materials, antistatic and skin conditioning agents, milk extracts such as skim milk. Other additives may be; herbal materials, moisturizers, antioxidants and fillers, clays, honey, astringents such as zinc oxide, zinc glycerolate. Zinc chloride, magnetic particles, minerals, gold particles, sodium chloride, chelating agents such as pentetate, pentetate. An adjuvant selected from the group consisting of: water-miscible or water-soluble sunscreens or UV-protectants such as benzyl salicylate, antioxidants such as pentaerythritol tetrakis (di-tert-butyl-4-hydroxy) phenylpropionate, insect repellents such as citronellol, chemical repellents, viscosity modifiers, D-panthenol, hydrolysed collagen or animal proteins and mixtures thereof and the like.

Additional PCM(s) and/or SC components or mixtures thereof may be added at this stage.

The lyotropic liquid crystalline phase, e.g. lamellar phase, of the obtained product is determined, for example, by bipolar microscopy and/or NMR and/or X-ray. Briefly, the Liquid Crystal (LC) mesophase in the product is determined, for example, in a polarizing optical microscope with microscope (nikon ECLIPSE 200). For sample preparation, a small amount of product was smeared on a microscope slide and then quickly covered with a cover slip. The sample was pressed with a finger to make it as thin as possible. One 40 x objective lens and 10 40 x oculars were used with crossed polarizers in the bright field to detect birefringence. Micrographs were taken under a polarizing microscope. To produce the lamellar phase liquid crystal composition of the present invention, for example, the concentration of the amphiphilic lipid is selected to selectively form lamellar liquid crystals.

Generally, when the concentration of the amphiphilic lipid is 50 to 85 mass%, a single-phase region of lamellar liquid crystal often occurs. Therefore, it is preferable to produce the lamellar liquid crystal in such a concentration range. More specifically, the concentration-temperature range of the single-phase region in which lamellar liquid crystals are produced depends on the type of amphiphilic lipid. Thus, the concentration may be selected based on the "concentration-temperature dependent phase diagram" of the amphiphilic lipid/water system. More precisely, such temperatures can be determined according to conventional techniques involving the preparation of phase diagrams.

The liquid crystal phase can be "fine tuned" by an evaporation/rehydration "loop" if desired. The LC mesophase product is then further finished.

In some embodiments, the present invention provides a method of preparing a composition for dermal administration, the method comprising combining PCM(s) and/or SC component(s) with a material that is in or forms a Liquid Crystal (LC) mesophase.

The PCM or PCM product (mixture of PCMs), and the SC component or mixture of SC components, and optionally several additives and/or any other lipids, may be combined with at least one liquid crystal forming material (LC-FM). LC-FM and its products can be for example polysaccharides (e.g. xanthan gum) or oily gels in solvents (preferably about 50% and 15-35% water respectively), sodium alginate based on alginic acid, etc. Surfactants which form lamellar liquid crystals directly from aqueous solutions are, for example, lecithin, oligo-ethylene glycol-alkyl-ethers, monoglycerides and the like. The LC-FM forming the lamellar liquid crystal may be: basic fatty acid salt(s), egg lecithin, soybean lecithin, digalactosyldiacylglycerol, diglucosyldiacylglycerol, maltosylphytantether, dialkyldimethylammonium chloride and a phospholipid to which a polyoxyethylene chain is added, potassium oleate, an amphiphilic lipid forming a type I micelle or a type I hexagonal liquid crystal, and a surfactant. An amphiphilic lipid (curvature-modifying lipid) is used as the curvature-regulating substance.

The optimal amount of curvature-regulating substance to be added can be easily determined by the person skilled in the art based on the phase diagram of the three-component system amphiphilic lipid/curvature-regulating substance/water. For example, such a curvature-regulating substance is preferably used in an amount of 20 to 85 mass%, and more preferably 50 to 70 mass% of the total amount of the curvature-regulating substance and the amphiphilic lipid.

The formulation or composition components are initially mixed and ground in a grinding mixer (e.g., a cooled roll mill) and then further refined by extrusion for a period of about 8 to 15 minutes. The refined mixture is then hydrated by gradually adding a solvent (e.g. DDW, tincture, extract, vegetable milk, animal milk, oil) in the kneading system under continuous stirring (at 60-95 ℃ for about 60min) and then returned to room temperature or at room temperature for about 24 hours. Other additives including PCM and/or SC and/or mixtures thereof and/or lipids may be added to the LC-FM mixture.

A liquid crystal product (e.g., FA-salt hydrate) with intercalated additives and SC and PCM should be obtained with about 40-90% salt and 10-60% solvent hydration, preferably an aqueous solvent. According to a particular embodiment, the liquid crystal product contains 70% salt and 30% H₂And O. A solvent (water, hydrocarbon or mixtures thereof or non-aqueous solvent) is then added to the mixture and gentle mixing is continued until homogenization. In the case of the formulation or composition, it is also possible to use a liquid crystal mixed with some isotropic solution or some gel.

The lyotropic Liquid Crystalline (LC) phase, e.g. lamellar and/or hexagonal phase, of the product is determined. The mesophases may range from hexagonal, lamellar, cubic and inverse topology lyotropic phases and any mixtures or combinations thereof. The liquid crystal phase can be "fine tuned" by an evaporation/rehydration "loop" if desired. The lyotropic liquid crystal mesophase product is then further finished.

According to an embodiment of the invention, the method for preparing a composition for topical application further comprises a finishing with a final stage.

Accordingly, as detailed above, the present invention provides a process for producing a lyotropic liquid crystal composition, said process comprising:

(a) hydrolysing and/or dissolving and/or saponifying the at least one PCM and the at least one SC component to produce a product (optionally amphiphilic);

(b) hydrating the product (optionally amphiphilic); and optionally

(c) Adding at least one additive.

According to one embodiment of the invention, the PCM is a fatty acid salt hydrate or a phospholipid fatty acid salt hydrate.

The liquid crystal composition obtained according to the process of the present invention may be present at the interface of the foam, emulsion or dispersion. That is, they may be present at the interface of a liquid/liquid system (emulsion), a solid/liquid system (dispersion), or a gas/liquid or gas/solid system (foam). The compositions of the present invention may be poured directly into dispensers, canisters, bags, cases, bottles or tubes, or directly into creams, ointments, pastes or any topical "cream bases". The composition can then be spread on a fabric dressing (e.g. gaussians), a "woundplast", or made directly into a lotion and lotion or encapsulation, then combined in a lotion or cream, ointment, paste, and dispensed in a dispenser to obtain the product composition.

Thus, the composition of the invention may be applied, painted or sprayed directly onto the skin barrier disruption to be treated or onto a tissue wipe, tissue, silicon pad, wound patch or bandage to be applied to the skin barrier disruption, with or without a dressing.

As used herein, the term "emulsion" refers to liquid crystal-based emulsions and/or liquid crystal-based gel emulsions. Typically, emulsions comprise an oil phase, an aqueous phase, and other components. The emulsion of the composition of the present invention comprises an oil phase which may comprise the PCM and SC components together with oil(s) and alkyl polyglycoside emulsifiers and an aqueous phase which may comprise deionized water and/or water based solutions and humectants (e.g. cetyl alcohol, dimethicone, etc.), hydrocarbons or mixtures thereof. Mixing and homogenization of the aqueous phase may be carried out, for example, in F25 Ultraturrax at 13,000rpm for 3 minutes.

The composition of the present invention is a lyotropic liquid crystal microemulsion obtained by reducing the water content of the composition to 10-60%.

Encapsulation of the composition may be performed as previously described and detailed by those skilled in the art.

The foaming/mousse of the composition can be carried out in a conventional manner by using a foaming agent or by mechanical foaming. The foam may be formed directly from a pure liquid crystal formulation or composition. The foam may also be formed from a liquid comprising a liquid crystal formulation. If a blowing agent is used, it may be any of the conventional blowing agents that release gases such as nitrogen, carbon dioxide. Alternatively, the blowing agent may be one that decomposes by reaction with another component in the emulsion to release non-condensable gases as a reaction product.

If mechanical foaming is used, this can be done by using conventional whipping equipment or by pumping the emulsion through a foaming head of conventional type. As is known in the art, a suitable propellant such as carbon dioxide, propane/butane/isobutylene is mixed with dimethyl ether or nitrogen at a pressure of 40-60psi or higher, dispensed as a mousse and charged into a pressure tank to obtain a product composition.

The blowing agent used in the practice of the present invention may be comprised of one or more of the following-mentioned materials, however, the composition includes liquid crystal materials and/or alkali metal salts which are known per se as blowing agents and foam stabilizers. If desired, the blowing agent may include one or more foam stabilizers or boosters, such as methylcellulose, polyvinyl alcohol, aliphatic alcohols having from 10 to 16 carbon atoms, condensation products of ethylene oxide with aliphatic alcohols, alkylaryl polyethoxyethanol alcohols, alkali metal alkylaryl sulfonates, alkali metal salts of sulfonated alkylaryl polyethoxyethanol alcohols, colloidal silica, and alkali metal salts of water-soluble polyacrylates.

Blowing agents useful in the practice of the present invention include alkyl sulfates of alkali metals wherein the alkyl group has from 12 to 14 carbon atoms, such as sodium lauryl sulfate, alkali metal salts of the sulfated condensation products of ethylene oxide with aliphatic alcohols having from 10 to 18 carbon atoms, alkali metal salts of esters of α -sulfo-substituted fatty acids having from 10 to 16 carbon atoms, palmitic acidOr alkali metal salts of unsaturated fatty acids having more than 14 carbon atoms (such as oleic or linoleic acid); an alkali metal salt of an amphoteric surfactant of the general formula RRNR "COOH wherein R is an alkyl group having 10 to 18 carbon atoms, R is hydrogen or an alkyl group having no more than 12 carbon atoms, and R" is a divalent aliphatic hydrocarbon group having 1 up to carbon atoms; alkali metal salts of esters of sulfoacetic acid with aliphatic alcohols having from 18 carbon atoms; alkali metal salts of alkyl isethionic acids wherein the alkyl group has 10 to 18 carbon atoms; alkali metal salts of amides of sulfo-substituted fatty acids having 10 to 16 carbon atoms; tetra alkali metal salts of N- (1, 2-dicarboxyethyl) N-alkyl sulfosuccinamic acid; di-alkali metal salts of N-alkyl sulfosuccinamic acid; alkali metal salts of N-methyltaurine of fatty acids having from 10 to 14 carbon atoms; amphoteric surfactants having the general formula HO CHzCOOM, wherein R is an alkyl group having 10 to 18 carbon atoms, R' is H, Na or CH COOM, and M is Na or an organic base; and having the general formula HO C_zEL_zSO_aAn amphoteric surfactant of C, wherein R is an alkyl group having 10 to 18 carbon atoms, and M is Na or an organic base.

Typical topical "cream bases" include cetyl alcohol, methyl paraben, propyl paraben propylene glycol, purified water, sodium lauryl sulfate and stearyl alcohol, as well as ointments, mineral oil and white petrolatum.

Thus, the product according to the invention may be a foam/mousse in a pressure can, a paste, a cream, an ointment, a lotion, a solution, a soap, an emulsion, a dressing additive, a liquid bandage, "roll-on", with or without encapsulated particles. They may also be incorporated into cosmetics (e.g., foundations, eye makeup, pigmented or unpigmented lip care, such as lipsticks, and the like), as well as any formulation or composition that supports the aesthetics of the healing and/or protection and/or treatment system. Suitable products may be in the form of ointments or salves, creams, lotions, gels, foams, mousses, sprays, or medicinal dressings or bandages that must be applied directly to the skin or affected area and maintained in systemic contact with the skin and integuments.