WO2013122994A1

WO2013122994A1 - Skin care product

Info

Publication number: WO2013122994A1
Application number: PCT/US2013/025857
Authority: WO
Inventors: Peter Lassen; Jan Renneberg
Original assignee: Larore Llc
Priority date: 2012-02-14
Filing date: 2013-02-13
Publication date: 2013-08-22

Abstract

Herein is disclosed a topological composition that includes a biphasic mixture of an exfoliant and an antioxidant; the biphasic mixture comprising a water phase and an oil phase, preferably wherein the biphasic mixture is an oil-in-water emulsion; wherein the water phase includes the exfoliant; and the oil phase comprises the antioxidant.

Description

SKIN CARE PRODUCT

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This disclosure claims the benefit of priority to US Provisional Patent

Application 61/598,520 filed 14 February, 2012 the disclosure of which is incorporated herein in its entirety.

FIELD OF THE DISCLOSURE

[0002] The disclosure is a composition based upon proteolytic enzymes and antioxidants. In some circumstances the disclosure relates to a skin and hair care product for human use, to be used daily or in a treatment regime to rejuvenate skin and inhibit growth or regrowth of unwanted hair, accelerating the normal turnover of skin cells, revitalizing new skin cells and inhibit new growth of hair, smoothening and weakening existing hair growth. In other circumstances the disclosure relates to a treatment product for damaged skin and wounds to be used daily to remove damaged tissue and cells and increase the speed of healing by reducing risk of local infection and vitalizing and enhancing growth of new cells.

BACKGROUND

[0003] Proteolytic enzymes hydrolyze or break down proteins easing digestion or just removal of the protein material. The human body uses the enzymes to make the food absorbable - this means their function is outsite the body. There are several good reasons for this; primarily the proteolytic enzymes cannot harm living organisms / cells (The

Resistance of living Organism to Digestion by Pepsin or Trypsin, J. H. Northrop, Lab.

Rockefeller Ins. Med. Res., 1926). Only if the proteolytic enzymes is introduced into a cell (by injection or a disruption of the cell membrane, the proteolytic enzyme can hurt or kill the cell by destroying the cell proteins (The Resistance of living Organism to Digestion by Pepsin or Trypsin, J. H. Northrop, Lab. Rockefeller Ins. Med. Res., 1926 ).

[0004] Hair growth inhibitors have been available for many years and when used properly may function to prevent or minimize a regrowth of hair that has been removed previously by shaving, waxing or by a prior use of a depilatory composition. Examples of products that have been used for inhibiting the growth or regrowth of unwanted hair are disclosed in: US Patent No. 5,378,455; US Patent No. 5,648,394; US Patent No. 7,041 ,658 and US Patent No. 7,488,499. [0005] The use of thiol-based depilatory agents, for removal of unwanted body and facial hair is well established in the art (see eg. US 4,941 ,885; US 4,631 ,064; US 4,618,344). These agents react by reducing hair's protein disulfide bonds to sulfhydryl anions, thereby allowing easy removal of the weakened hairs when washed or wiped away. The combination of thiol compounds with high pH's results in ionized thiols and increased penetration of a reactant. Similarly, urea or other nitrogen-containing substances have been found to accelerate the action of the thiol-component in hair removal. These prior art hair growth inhibitors typically function to affect the root area of the hair by a chemical reaction that is intended to prevent or inhibit a regrowth of hair at the root. Prior art hair growth inhibiting solutions generally are not permanent and require periodic application of the solution.

However, there is a concern that the prior art compositions that are effective at preventing regrowth of hair at the root also are damaging or irritating to skin, particularly when used daily or as part of a continuing regime. Decreasing the frequency of application may avoid or reduce skin irritation, but also may adversely affect the intended hair regrowth inhibiting function of the composition. Similarly, decreasing the concentration of the chemicals that react with the hair roots can avoid or reduce skin irritation, but again may limit the effectiveness of the composition for inhibiting hair regrowth.

[0006] Another approach to avoid un-wanted hair is the development of hair growth inhibitors which act on the hair follicle.

[0007] Hair grows from the hair follicle. The total number of hair follicles for an adult human is estimated at 5 million with 1 million on the head of which 100,000 alone cover the scalp. In humans, the only external regions of skin devoid of hair follicles are the palms of the hands and soles of the feet. The basic hair follicle structure remains essentially the same throughout the range of mammalian species with modifications for specialized functions.

[0008] The hair follicle can be recognized as a separate entity within the skin with formation and maintenance based on interaction between dermal and epidermal

components. The hair follicle is an epithelial structure which undergoes growth cycles throughout adult life. The growth of the hair follicle down into the dermis forming a layered structure with a pigmented shaft is known as the anagen phase whereas a regression phase is known as the catagen phase in which the hair follicle shortens an a part of the hair follicle undergoes programmed cell death known as apoptosis. Also, a hair follicle rest phase has been characterize and named the telogen phase (Seiberg et al. 1997. Dev. Dynamics 208, 553-564. Trypsin-induced follicular papilla apoptosis in delayed hair growth and

pigmentation). [0009] Examples of proteolytic enzymes are trypsin, chymotrypsin, ficin and papain.

Topical trypsin treatment of mice following depilation has been shown to induce apoptosis in the follicular papillae which results in delay in hair growth (Seiberg et al. 1997). WO

98/02134 describes the use of a trypsin-containing composition using as pharmaceutical vehicle non-ionic liposomes consisting of glycerol dilaurate, cholesterol-like compounds and fatty acid ethers. Mice are after wax-depilation treated with the composition and hair growth is effectively delayed and apoptosis at the follicular papillae is observed.

[0010] In EP 0622069, papain and chymotrypsin are used in a composition for permanent hair depilation. The proteolytic enzymes are stored in powder form in the presence of lactose. In a liquid solution, the enzyme activity is stabilized by the use of dithiotreitol, ethylene glycol, and ethylenediaminotetraacetic acid (EDTA). The solution is buffered to a suitable pH according to the proteolytic enzyme present in the solution.

Immediately before use, the enzyme is dissolved in the liquid. The depilatory activity will be retained for 7 days when the enzyme-containing solution is stored at 2-6°C and for 4 weeks if kept at -15 to -20°C. The enzyme- containing liquid is supplied by ionophoresis.

[0011] Another approach for suppressing hair growth is presented in US 6,375,948 in which plant extracts from the family Juniperus or malts-from cereals are the major active compound. Proteolytic enzymes such as papain, chymotrypsin, bromelain, ficin, pancreatin, pepsin or trypsin may or may not be added in the composition. A number of components usually employed for cosmetics selected from the groups of oils, ethanols, thickeners, emulsifiers, humectants, colors, and perfumes etc. are also included in the composition. The hair growth inhibitor is applied to the skin of mice following shaving of a selected area of the mice. One application per day was repeated for 4 weeks.

[0012] WO 97/44005 describes a depilatory preparation that is applied to the skin by spreading. The preparation comprises proteolytic enzymes such as chymotrypsin or papain solubilized in a microemulsion. The microemulsion contains an inert organic agent and droplets of water in which the proteolytic enzymes are present. The water droplets are dispersed in the organic phase by use of lecithin as a surfactant. The organic phase is kept separate from the enzyme-containing water until use. Just prior to use, the enzyme solution and the organic phase are mixed by gentle shaking to product the active depilatory preparation. The depilatory action persists for 1-3 days if stored at 2-6°C.

SUMMARY

[0013] One embodiment of the herein described invention is a topological composition comprising a biphasic mixture of an exfoliant and an antioxidant; the biphasic mixture comprising a water phase and an oil phase, preferably wherein the biphasic mixture is an oil-in-water emulsion; wherein the water phase includes the exfoliant; and the oil phase comprises the antioxidant.

BREIF DESCRIPTION OF THE FIGURES

[0014] For a more complete understanding of the disclosure, reference should be made to the following detailed description and accompanying drawing figures wherein:

[0015] Figure 1 is a photograph showing the skin surface before exfoliation depicting a thick layer of cell debris, upon the living skin, composed of fibroblast cells and collagen connective tissue interspersed with blood vessels, sweat glands and sensory nerves;

[0016] Figure 2 is a photograph showing the skin surface after exfoliation depicting the reduction and disappeared layer of cell debris leaving the skin composed of fibroblast cells and collagen connective tissue interspersed with blood vessels, sweat glands and sensory nerves exposed;

[0017] Figure 3 is a photograph showing a hair in the main differentiated layers in a mature anagen hair follicle;

[0018] Figure 4 is a photograph showing the destroyed hair follicle after treatment with the herein described compositions, the hair follicle penetrates the dermal layer of the skin and is composed of fibroblast cells and collagen connective tissue interspersed with blood vessels, sweat glands and sensory nerves, the bulb region sits just above the subcutaneous (adipose fat) tissue layer;

[0019] Figure 5 is a photograph of a chin region before treatment showing dark and thick hairs;

[0020] Figure 6 is a photograph of an upper lip region before treatment showing dark and thick hairs;

[0021] Figure 7 is a photograph of the chin and upper lip regions after treatment with the herein described composition, the dark and thick hairs are gone;

[0022] Figure 8 is a photograph of a bikini line after 10 treatments and a year since last treatment; and

[0023] Figure 9 is a photograph of a bikini line after three treatments, showing areas which have been treated compared to untreated areas without treatment.

[0024] While specific embodiments are illustrated in the figures, with the

understanding that the disclosure is intended to be illustrative, these embodiments are not intended to limit the disclosure described and illustrated herein. DETAILED DESCRIPTION

[0025] This disclosure describes a preparation that is applied to the skin by spreading. The preparation has been made in view of the above-identified problems.

[0026] Besides the proteolytic enzymes the preparation contains antioxidants in order to avoid skin irritation and stabilize and rejuvenate the skin after the treatment with proteolytic enzymes.

[0027] It is another object of the disclosure to provide a hair growth or regrowth inhibiting composition that functions to rejuvenate skin this is done by using addition of antioxidant from these plants: Syzygium Myrtoideae, Citrus Aurantium, Picrorhiza, Arnica Montana, Punica Granatum and Acetylacetyl Acid.

[0028] Besides the proteolytic enzymes the preparation contains antioxidants in order to stabilize and rejuvenate the skin after the treatment with proteolytic enzymes.

[0029] An antioxidant is a molecule capable of slowing or preventing the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons from a substance to an oxidizing agent. Oxidation reactions can produce free radicals, which start chain reactions that damage cells. Antioxidants terminate these chain reactions by removing free radical intermediates, and inhibit other oxidation reactions by being oxidized themselves. As a result, antioxidants are often reducing agents such as thiols, ascorbic acid or polyphenols. The natural oxidants are often used in food, cosmetics and medicine. The term antioxidant originally was used to refer specifically to a chemical that prevented the consumption of oxygen. In the late 19th and early 20th century, extensive study was devoted to the uses of antioxidants in important industrial processes, such as the prevention of metal corrosion, the vulcanization of rubber, and the polymerization of fuels in the fouling of internal combustion engines. Early research on the role of antioxidants in biology focused on their use in preventing the oxidation of unsaturated fats, which is the cause of rancidity. Antioxidant activity could be measured simply by placing the fat in a closed container with oxygen and measuring the rate of oxygen consumption. However, it was the identification of vitamins A, C, and E as antioxidants that revolutionized the field and led to the realization of the importance of antioxidants in the biochemistry of living organisms. The possible mechanisms of action of antioxidants were first explored when it was recognized that a substance with anti-oxidative activity is likely to be one that is itself readily oxidized. Research into how vitamin E prevents the process of lipid peroxidation led to the identification of antioxidants as reducing agents that prevent oxidative reactions, often by scavenging reactive oxygen species before they can damage cells. [0030] The antioxidants are in this disclosure used are nature's own antiinflammatory substances, with specific focus on: Clove, Citrus Aurantium extract, Ancotil, Arnica and Acetylacetyl Acid.

[0031] Accordingly, it is an object of the disclosure to provide a hair growth or regrowth inhibiting composition that avoids skin irritation even when used daily or in a continuing treatment regime.

[0032] It is another object of the disclosure to provide a hair growth or regrowth inhibiting composition that functions to rejuvenate skin.

[0033] A further object of the disclosure is to provide a skin care product that functions to remove cell material from the skin surface, while simultaneously inhibiting a regrowth of hair at the site of the application.

[0034] Still a further object of the disclosure is to provide a method for

simultaneously removing cell material and hair from skin surface and rejuvenating the underlying skin and inhibiting a growth or regrowth of hair as part of a daily application or a specified treatment regime.

[0035] Yet another object of the disclosure is to provide a care product used daily that functions to remove debris and cell material from the surface of skin and wound, while simultaneously vitalizing the cells building the skin and preventing local infection and further inflammation at the site of application.

[0036] The disclosure relates to a skin and hair care product for human to rejuvenate both damaged and undamaged skin and inhibit the growth or regrowth of hair. The composition comprises proteolytic enzymes enhancing removal of dead material and preparing for the strengthening of new skin cells through the natural antioxidant supported in the composition. The composition may be delivered in a cream, gel, foam, liquid or spray form and can be applied daily or in a specified treatment regime.

[0037] The proteolytic enzymes may include at least one of a chymotrypsin, trypsin, papain, and ficin. In this regard, chymotrypsin is a digestive enzyme that is synthesized in the pancreas of mammals. Trypsin is a related enzyme. Papain is an enzyme that can be obtained from the papaya. Ficin is an enzyme obtained from fig sap.

[0038] The natural antioxidants of the composition of the subject disclosure may be extracted from citrus aurantium, Clove, Picrorhiza root, Arnica or pomegranate. In this regard, citrus aurantium is derived from bitter orange, such as Seville orange. Cloves are the aromatic dried flower buds from the Syzygium Myrtoideae tree. Picrorhiza is a plant indigenous to the Himalayan Mountains. Arnica as an extract from Arnica Montana.

Pomegranate extract is derived from the fruits from the tree Punica Granatum.

[0039] The above-described proteolytic enzymes and the above-described antioxidants have been used previously in medical products, food supplements and topical products. However, the advantages obtained by their combination when applied topically previously were unknown. More particularly, the above-described combination of specified proteolytic enzymes and natural antioxidants were not known to have the advantageous effects of rejuvenating skin and inhibiting regrowth of unwanted hair when applied daily or in a treatment regimen.

[0040] Enzyme activity determined by the quantity of substrate transformed or product formed per unit time. The reaction rate that is measured depends on a number of experimental conditions such as temperature, pH, ionic strength, and the presence or absence of inhibitors or activators. It is only under the conditions specified in the prescribed assay procedure that enzyme units are defined.

[0041] The biological biopolymeric substrates (proteins, polysaccharides, antioxidants present, oil emulsions) often have a molecular complexity and the fact that the potential number of bonds susceptible to hydrolysis is not known and frequently varies over the time course of the assay makes a Good Standardization Practice necessary. The international Commission on Enzymes F.I. P. calculates the potency in terms of the F.I. P. - standard using a unitage expressed in "International F.I. P. -units.

[0042] The activity of a given enzyme is thus influenced by a number of parameters such as chemical and physical conditions as described above. The enzyme activity is also influenced by the action the enzyme itself, a process known as self-degradation, self- destruction or self-digestion. Loss of enzyme activity may thus be due to any of the reasons listed.

[0043] The present disclosure relates to a use of a system for the preparation of a daily treatment regime to rejuvenate skin and inhibit hair growth or regrowth of unwanted hair. The preparation comprises at least one enzyme, at least one solvent, and at least one antioxidant agent as described herein. In a preferred embodiment of the disclosure the enzyme, solvent and antioxidant are mixed.

[0044] The problem with prior art compositions is among others that proteolytic enzymes when stored in a solvent are degraded. Furthermore, some prior art compositions need to be mixed immediately before use in order to be effective. Thus, the prior art compositions have limitations in the practical use, in particular not practical to use by the consumer at home. [0045] The present disclosure offers a composition that may be stored at room temperature for a prolonged period of time without degrading the enzymes and/or antioxidants, thereby facilitating the use of the composition. Accordingly, the composition according to the disclosure may be used both by specialists and by the normal consumer, since the product is easy to apply and requires no special storage conditions.

[0046] The advantages by the present disclosure have been obtained by using both incorporation into the composition an agent capable of reducing the water activity of the composition, whereby self-degradation of the enzyme is reduced or even absent and by using an encapsulation technique. It has previously been shown (EP 1 673 057 B1 , ) that when glycerol constitutes about 67 percent of the composition the water activity is reduced to about 0.7. Furthermore, increasing amounts of glycerol will reduce the water activity so that a glycerol concentration of 96.5% will have a water activity below 0.07.

[0047] The degradation reduced by the water activity reducing agent is primarily the self-degradation known to occur in enzymes dissolved in a solvent.

[0048] The water activity reducing agent may be any agent capable of reducing the water activity, in particular an agent capable of reducing the water activity to a value below 0.3 when measured according to the assay as described herein.

[0049] In a preferred embodiment the water activity reducing agent may be selected from the propylene glycol, glycerine, sorbitol, saccharose, and saline, or a combination thereof.

[0050] The water activity reducing agent is present in an amount sufficient to provide the water activity reducing effect in combination with the encapsulation.

[0051] The encapsulation should preferably be based upon use of water, pentylen glycol, glycerin and capryl glycol.

[0052] Accordingly, it is preferred that the water activity reducing agent constitutes at least 10 percent by weight of the composition, such as at least 20 percent by weight of the composition, at least 30 percent by weight of the composition, at least 35 percent by weight of the composition, at least 40 percent by weight of the composition, at least 45 percent by weight of the composition, at least 50 percent by weight of the composition.

[0053] The water activity reducing agent combined with the encapsulation as described above is able to prolong the storage time of proteolytic enzyme and antioxidants, as the reduction of water activity will prevent self-destruction of the proteolytic enzyme and the encapsulation will both prevent self-destreduction and reduce the oxidation of the composition. It is desirable for the consumer herself that both enzyme and antioxidants are active upon storage for a long period of time. In a preferred embodiment of the disclosure the storage time of the proteolytic enzyme and antioxidant-containing composition at room temperature is at least 24 months, such as at least 12 months, at least 6 months, at least 3 months, at least 2 months, at least 1 month, at least 3 weeks.

[0054] In order to promote the penetration of the composition into the hair follicle and to reduce potential inflammation brought about by the composition, a preferred embodiment according to the disclosure is to include, at least one penetration-promoting, antiinflammatory agent. In a further preferred embodiment the penetration-promoting, anfi- inflammatory agent is selected from the group of salicylates, and even more preferred the penetration-promoting, anti-inflammatory agent is diethylamine salicylate.

[0055] In a second further preferred embodiment according to the disclosure the penetration-promoting, anfi-inflammatory agent is selected from the group of Arnica extracts, and even more preferred the penetration-promoting, anti-inflammatory agent is extract from Arnica Montana.

[0056] In a third further preferred embodiment according to the disclosure the penetration-promoting, anfi-inflammatory agent is selected from the group of Apocynin extracts, and even more preferred the penetration-promoting, anti-inflammatory agent is extract from Picrorhiza Kurroa.

[0057] In a fourth further preferred embodiment according to the disclosure the penetration-promoting, anfi-inflammatory agent is selected from the group of Citrus extracts, and even more preferred the penetration-promoting, anti-inflammatory agent is extract from Citrus Aurantium.

[0058] In a fifth further preferred embodiment according to the disclosure the penetration-promoting, anfi-inflammatory agent is selected from the group of Clove extracts, and even more preferred the penetration-promoting, anesthetic anti-inflammatory agent is extract from flowers from Syzygium Myrtoideae.

[0059] It is preferred that the penetration-promoting, anti-inflammatory agent constitutes at least 0.01 percent by weight of the composition, such as at least 0.1 percent by weight, such as at least 1 percent by weight, such as at least 2 percent by weight of the composition.

[0060] Furthermore, it is preferred that the penetration-promoting, anti-inflammatory agent constitutes at most 5 percent of the composition, such as at most 4 percent of the composition, such as at most 3 percent of the composition. [0061] In order to avoid bacterial growth and the like of the composition, a preferred embodiment is to include at least one preservative agent, and even more preferred to Include citric acid.

[0062] It is preferred that the preservative agent constitutes at least 0.1 percent by weight of the composition of the system, such as at least 0.3 percent by weight, such as at least 0.5 percent by weight, such as at least 0.8 percent by weight, such as at least 0.9 percent by weight of the composition.

[0063] Furthermore, it is preferred that the preservative agent constitutes at most 3 percent by weight of the composition, such as at most 2 percent by weight, such as at most 1.5 percent by weight, such as at most 1 .25 percent by weight, such as at most 1 .5 percent by weight of the composition.

[0064] In a more preferred embodiment the preservative agent constitutes from 0.5 to 1 .5 percent of the second composition of the second component of the system, such as about 1 percent of the second composition of the system, in particular when the preservative agent is citric acid.

[0065] The composition according to the disclosure comprises at least two enzymes, wherein the enzymes are present in order to hydrolyze or break down proteins on the skin as well as in the hair follicle.

[0066] The enzymes of the composition may be any suitable enzyme, it is however preferred that the enzyme is a proteolytic enzyme.

[0067] In one embodiment of the disclosure the enzymes are selected from the group of proteases, such as trypsin, Chymotrypsin, papain and ficin.

[0068] In a preferred embodiment the enzymes are selected from the group of enzymes consisting of trypsin, chymotrypsin, and papain,

[0069] In a more preferred embodiment the at least one enzyme is an enzyme selected from the group of enzymes consisting of trypsin and chymotrypsin.

[0070] In a further preferred embodiment the enzyme(s) is/are selected from the group of enzymes consisting of trypsin, or papain. Also preferred is the selection of at least one enzyme from ficin or papain.

[0071] It is preferred that the enzyme constitutes at least 1 .0 percent by weight of the composition, such as at least 1 .5 percent by weight of the composition, such as at least 2.0 percent by weight of the composition. [0072] Furthermore, it is preferred that the enzyme constitutes at most 10 percent by weight of the composition. More preferably the enzyme constitutes at most 7.5 percent by weight of the composition, such as at most 6 percent by weight of the composition, such as at most 5 percent by weight of the composition, such as at most 4 percent by weight of the composition.

[0073] In a more preferred embodiment the enzyme constitutes from 2.0 to 3.0 percent by weight of the composition, such as preferably about 2.5 percent by weight of the composition, in particular when the enzyme is trypsin.

[0074] In another preferred embodiment the enzyme as described above has an activity of at least 50 F.I. P. units per gram of the composition, such as at least 100 F.I. P. units per gram of the composition, such as at least 150 F.I. P. units per gram of the composition, such as at least 175 F.I. P. units per gram of the composition, such as at least 200 F.I. P. units per gram of the composition, such as at least 225 F.I. P. units per gram of the composition, such as at least 250 F.I. P. units per gram of the composition.

[0075] Furthermore, it is preferred that the enzyme has an activity of at most 350

F.I. P. units per gram of the composition. More preferably the enzyme has an activity of at most 300 F.I. P. units per gram of the composition, such as 275 F.I. P. units per gram of the composition, 250 F.I. P. units per gram of the composition, such as 225 F.I. P. units per gram of the composition.

[0076] In a more preferred embodiment the enzyme has an activity from 150 to 250

F.I. P. units per gram of the composition, such as preferably about 200 F.I. P. units per gram of the composition, in particular when the enzyme is trypsin.

[0077] The enzyme of the composition according to the disclosure is dissolved in a solvent. The solvent may be any suitable solvent. In a preferred embodiment the solvent is water.

[0078] In order to reduce the water activity of the composition as much as possible it is desirable to only include, as little as possible of the solvent. Accordingly, it is preferred that the solvent and the enzyme constitutes at the most 20 percent by weight of the composition. More preferably the solvent and the enzyme constitute at the most 15 percent by weight of the composition, such as at the most 10 percent by weight of the composition, such as at the most 5 percent by weight of the composition, such as at the most 3 percent by weight of the composition. In particular, the solvent and the enzyme constitute about 2.9 percent per weight of the composition. [0079] The solvent of the composition according to the disclosure may be cross- bound by a polymer. The polymer may be any suitable polymer. In a preferred embodiment the polymer comprises acrylic acid monomers. In an even more preferred embodiment the polymer is an acrylic acid polymer. More preferably, the polymer is selected from carbomers such carboxymethylene resins, polyacrylic acid, C10-C30 alkyl propenoate, polymer with propenoic acid, butenoic acid and/or alkyl propenoates, product with propenyl sucrose ether or propenyl 2,2-dihydroxymethyl-1 .3-propanediol. In another preferred embodiment the polymer is a combination of the polymers described. In an even more preferred embodiment the polymer is Sepigel 305.

[0080] In order to cross-bind the solvent of the composition as effectively as desirable, it is preferred that the polymer constitutes at least 0.05 percent by weight of the composition, such as at least 0.1 percent by weight of the composition, at least 0.15 percent by weight of the composition, at least 0.2 percent by weight of the composition, at least 0.25 percent by weight of the composition, at least 0.275. percent by weight of the composition, at least 0.3 percent by weight of the composition.

[0081] Furthermore, it is preferred that the polymer constitutes at most 3 percent by weight of the composition. More preferably, the polymer constitutes such as at most 2 percent by weight of the composition, such as at most 1 percent by weight of the

composition, such as at most 0.5 percent by weight of the composition, such as at most 0.4 percent by weight of the composition.

[0082] In a more preferred embodiment the polymer constitutes from 0.15 to 0.25 percent by weight of the composition, such as preferably about 0.2 percent by weight of the composition, in particular when the polymer is Sepigel 305 (Seppic , New Jersey).

[0083] The polymer according to the disclosure may be neutralized by a neutralizing agent if relevant. The neutralizing agent may be any suitable neutralizing agent, capable of neutralizing the polymer in question. In a preferred embodiment the neutralizing agent is diisopropanolamine.

[0084] In order to neutralize the polymer of the composition as effectively as desirable, it is preferred that the neutralizing agent constitutes at least 0.1 percent by weight of the composition, such as at least 0.2 percent by weight of the composition, at least 0.3 percent by weight of the composition, at least 0.35 percent by weight of the composition, at least 0.4 percent by weight of the composition.

[0085] Furthermore, it is preferred that the neutralizing agent constitutes at most 2 percent by weight of the composition. [0086] More preferably, the polymer constitutes such as at most 1 percent by weight of the composition, at most 0.5 percent by weight of the composition, at most 0.45 percent by weight of the composition.

[0087] In a more preferred embodiment the neutralizing agent constitutes from 0.35 to 0.45 percent by weight of the composition, such as preferably about 0.4 percent by weight of the composition, in particular when the neutralizing agent is diisopropanolamine.

[0088] One embodiment is a topological composition comprising a biphasic mixture of an exfoliant and an antioxidant; the biphasic mixture comprising a water phase and an oil phase, preferably wherein the biphasic mixture is an oil-in-water emulsion; wherein the water phase includes the exfoliant; and the oil phase comprises the antioxidant. The exfoliant can be selected from the group consisting of trypsin, chymotrypsin, papain, ficin, and a mixture thereof; more preferably wherein the exfoliant is a combination of trypsin and chymotrypsin or wherein the exfoliant is papain; even more preferably wherein the exfoliant is selected from the group consisting of CAS No. 03-07-9004; CAS No. 9001-33-6, CAN No. 9001-73-4, 02-07-9002, and a mixture thereof. In one example, the water phase includes a plurality of exfoliants and the oil phase includes a single antioxidant. In another example the water phase can further include an enzyme-activity-reducing agent; preferably wherein the enzyme-reducing agent is selected from the group consisting of glycerine, sorbitol, saccharose, saline, and a mixture thereof. In still another example, the topological composition can include at least 1 wt.%, or 2 wt.% of the exfoliant; preferably wherein the topological composition comprises at most 10 wt.%, 7.5 wt.%, 6 wt.%, 5 wt.%, 4 wt.%, or 3 wt.% of the exfoliant. In a still further example, the exfoliant can have an activity of at least 50 FlP/g, 100 FlP/g, 150 FlP/g, 175 FlP/g, 200 FlP/g, 225 FlP/g, 250 FlP/g of the topological composition; preferably where the exfoliant has an activity of at most 350 FlP/g, 300 FlP/g, 275 FlP/g, 250 FlP/g, or 225 FlP/g of the topological composition. In a preferred example, at least one of the exfoliants is trypsin and the trypsin has an activity of about 200 FlP/g of the topological composition; wherein the topological composition comprises about 2 wt.% trypsin.

[0089] The topological composition can include an antioxidant is selected from the group consisting of citrus bioflavonoids, clove bioflavonoids, pomegranate bioflavonoids, arnica bioflavonoids, apocynin bioflavonoids, and salicylates; preferably, wherein the antioxidant is selected from the group consisting of citrus bioflavonoids, pomegranate bioflavonoids, arnica bioflavonoids, and apocynin bioflavonoids; wherein bioflavonoid antioxidants are extracts from a respective plant matter; and more preferably wherein the antioxidants are selected from the group consisting of CAS No. 498-02-2, CAS No. 94-07-5, CAS No. 8000-34-8, CAS No. 476-66-4, and CAS No. 69-72-7. In one example, the antioxidant is a polymer supported antioxidant; preferably wherein the polymer supported antioxidant is a reaction product of the antioxidant and an acrylate polymer or a cellulosic polymer; preferably wherein the acrylate polymer is selected from the group of acrylic acid polymers, acrylic acid copolymers, methacrylate polymers, methacrylate copolymers, acrylonitrile polymers, acrylonitrile copolymers, polyvinyl alcohol polymer, a polyvinyl alcohol acrylic acid copolymer, and a mixture thereof. In another example, the topological composition comprises at least 0.01 wt.%, 0.1 wt.%, 1 wt.%, or 2 wt.% of the antioxidant; preferably wherein the topological composition comprises at most 5 wt.%, 4 wt.%, , or 3 wt.% of the antioxidant.

[0090] Preferably, the topological composition, when applied to skin, induces apoptosis in follicular papillae and delays hair regrowth. More preferably, the topological composition, when applied to skin, prevents inflammation and/or oxidation of the skin caused by exfoliation.

[0091] In yet another example, the topological composition includes a preservative agent; preferably wherein the topological composition comprises at least 0.1 wt.%, 0.3 wt.%, 0.5 wt.%, 0.8 wt.% or 0.9 wt.% of the preservative agent; preferably wherein the topological composition comprises at most 3 wt.%, 2 wt.%, 1 .5 wt.%, or 1 .25 wt.% of the preservative agent; more preferably where in the preservative agent is citric acid.

EXAMPLES

[0092] By way of example and not limitation, the following examples are illustrative of various embodiments of the present disclosure and further illustrate experimental testing conducted.

[0093] In the three preferred embodiments below are the active components in bold and italic, the range for enzymes is 0.2-2% and for the antioxidants 0.01 -0.8 %.

Example 1

Ingredients %

Glycerin 48,510

Water 47,835

Chymotrypsin, Papain, Trypsin 1,000

Carbomer 0,900

Salicylic acid 0,800

Sodium Benzoate 0,500 Sodium Hydroxide 0,290

Apocynin 0,100

Triethanolamine 0,065

Total 100

Example of alternative formulation, as lotion.

Ingredients %

Aqua 65,730

Paraffinum Liquidum 8,000

PEG-6 Stearate, Glycolstearate, PEG-32 Stearate 7,000

Glycerin 5,000

Capryl/capric Triglyceride 3,000

Glyceryl Stearate 2,300

Isopropyl Palmitate 2,000

Corn strach modified 2,000

Trypsin/Chym otrypsin 1,000

Phenoxyethanol + 0,800

Sodium Benzoate 0,400

Citric acid 0,370

Aqua, Hydrolyzed Keratin 0, 100

Prolylen Glycol, Aqua, Hyreolyzed silk, paraben 0, 100

Tetrasodium iminodisuccinate 0,200

Citrus bioflavonoids 0,200

Parfume 1 ,800

Total 100 Example 3

[0095] Example of alternative formulation, as cream /exfoliator

Ingredients %

Water 63,470

Glycerin 5,000

Caprylic/Capric Triglylceride 5,000

Octyl Palmitate 5,000

Jojoba Esters 5,000

Cetyl Alcohol 4,500

Polysorbate 60 3,000

Stearyl Alcohol 2,500

Sorbitan stearate 2,000

Chymotryppsin, Papain 2,000

Titanium Dioxide 1 ,000

Phenoxyethanol & Caprylyl Glycol & Ethylhexylglycerin & Hexylene

Glycol 1 ,000

Treithanolamine 0,200

Carbomer 0, 100

Allantoin 0, 100

Arnica 0,100

Disodium EDTA 0,030

Total 100

Example 4

[0096] Measurement of activity and effect of storage in vitro, one of these test should be used:

• Protease Colorimetric, Zigma, down to 2 μg/ml (Trypsine)

• Protease Fluorescent, Zigma, down to 0.5 μg/ml (Trypsine)

• Benzonase® Properties, protease assay, Zigma, down to 1 μg/ml (Trypsine).

[0097] It should be understood that various changes and modifications to the presently preferred embodiments described herein will be apparent to those skilled in the art. Such changes and modifications can be made without departing from the spirit and scope of the present subject matter and without diminishing its intended advantages. It is therefore intended that such changes and modifications be covered by the appended claims.

Claims

WHAT IS CLAIMED:

1. A topological composition comprising a biphasic mixture of an exfoliant and an antioxidant;

the biphasic mixture comprising a water phase and an oil phase, preferably wherein the biphasic mixture is an oil-in-water emulsion;

wherein the water phase includes the exfoliant; and

the oil phase comprises the antioxidant.

2. The topological composition of claim 1 , wherein the exfoliant is selected from the group consisting of trypsin, chymotrypsin, papain, ficin, and a mixture thereof; more preferably wherein the exfoliant is a combination of trypsin and chymotrypsin or wherein the exfoliant is papain; even more preferably wherein the exfoliant is selected from the group consisting of CAS No. 03-07-9004; CAS No. 9001 -33-6, CAN No. 9001 -73-4, 02-07-9002, and a mixture thereof.

3. The topological composition of any one of the preceding claims wherein the water phase includes a plurality of exfoliants and the oil phase includes a single antioxidant.

4. The topological composition of any one of the preceding claims wherein the water phase further includes an enzyme-activity-reducing agent; preferably wherein the enzyme-reducing agent is selected from the group consisting of glycerine, sorbitol, saccharose, saline, and a mixture thereof.

5. The topological composition of any one of the preceding claims wherein the topological composition comprises at least 1 wt.%, or 2 wt.% of the exfoliant; preferably wherein the topological composition comprises at most 10 wt.%, 7.5 wt.%, 6 wt.%, 5 wt.%, 4 wt.%, or 3 wt.% of the exfoliant.

6. The topological composition of any one of the preceding claims wherein the exfoliant has an activity of at least 50 FlP/g, 100 FlP/g, 150 FlP/g, 175 FlP/g, 200 FlP/g, 225 FlP/g, 250 FlP/g of the topological composition; preferably where the exfoliant has an activity of at most 350 FlP/g, 300 FlP/g, 275 FlP/g, 250 FlP/g, or 225 FlP/g of the topological composition.

7. The topological composition of any one of the preceding claims wherein at least one of the exfoliants is trypsin and the trypsin has an activity of about 200 FlP/g of the topological composition; wherein the topological composition comprises about 2 wt.% trypsin.

8. The topological composition of any one of the preceding claims wherein the antioxidant is selected from the group consisting of citrus bioflavonoids, clove bioflavonoids, pomegranate bioflavonoids, arnica bioflavonoids, apocynin bioflavonoids, and salicylates;

preferably, wherein the antioxidant is selected from the group consisting of citrus bioflavonoids, pomegranate bioflavonoids, arnica bioflavonoids, and apocynin bioflavonoids; wherein bioflavonoid antioxidants are extracts from a respective plant matter; and more preferably wherein the antioxidants are selected from the group consisting of CAS No. 498-02-2, CAS No. 94-07-5, CAS No. 8000-34-8, CAS No. 476-66-4, and CAS No. 69-72-7.

9. The topological composition of any one of the preceding claims wherein the antioxidant is a polymer supported antioxidant; preferably wherein the polymer supported antioxidant is a reaction product of the antioxidant and an acrylate polymer or a cellulosic polymer; preferably wherein the acrylate polymer is selected from the group of acrylic acid polymers, acrylic acid copolymers, methacrylate polymers, methacrylate copolymers, acrylonitrile polymers, acrylonitrile copolymers, polyvinyl alcohol polymer, a polyvinyl alcohol acrylic acid copolymer, and a mixture thereof.

10. The topological composition of any one of the preceding claims wherein the topological composition comprises at least 0.01 wt.%, 0.1 wt.%, 1 wt.%, or 2 wt.% of the antioxidant; preferably wherein the topological composition comprises at most 5 wt.%, 4 wt.%, , or 3 wt.% of the antioxidant.

1 1 . The topological composition of any one of the preceding claims wherein the topological composition, when applied to skin, induces apoptosis in follicular papillae and delays hair regrowth.

12. The topological composition of any one of the preceding claims wherein the topological composition, when applied to skin, prevents inflammation and/or oxidation of the skin caused by exfoliation.

13. The topological composition of any one of the preceding claims further comprising a preservative agent; preferably wherein the topological composition comprises at least 0.1 wt.%, 0.3 wt.%, 0.5 wt.%, 0.8 wt.% or 0.9 wt.% of the preservative agent; preferably wherein the topological composition comprises at most 3 wt.%, 2 wt.%, 1 .5 wt.%, or 1.25 wt.% of the preservative agent; more preferably where in the preservative agent is citric acid.