JP5637548B2 - Exfoliating composition - Google Patents

Description

  The present invention relates to a exfoliating composition useful for the treatment of wolfome or octopus.

  Wonome is characterized by a thickening of the stratum corneum that is frequently pressed and rubbed against the skin, and if this stratum corneum is further thickened and continues to be subjected to strong compression, this thickened stratum corneum is now wedge-shaped. Instead, it gives a painful women when stimulated.

  Conventionally, a keratin exfoliation method using keratin softening and dissolving action of salicylic acid has been generally used for the treatment of keratinized skin such as urchin, octopus, wart and soy bean. The Japanese pharmacopoeia also contains salicylic acid adhesive bandages, which are generally applied to the affected area.

  For the purpose of keratin dissolution and softening, salicylic acid, urea, enzymes, reducing agents such as thioglycolic acid, cysteine, cysteamine, and pharmaceutically acceptable salts thereof are used. However, in the case of salicylic acid, the skin horny skin is strongly corroded at a concentration effective for softening of urchin or octopus, so that normal skin may be corroded or the entire affected area that has become white may become thickened and difficult to peel off. is there.

  In addition, when a reducing agent such as thioglycolic acid or cysteamine is used, the disulfide bond of the cystine residue in the keratin keratin protein structure is cleaved to generate free thiol and mercaptide groups on the cysteine residue. It can be softened temporarily. However, the disulfide bond that has been cleaved over time is oxidized to form a new disulfide bond in the protein structure, so that the stratum corneum of the affected area is cured again, and when the affected area is loaded, the stratum corneum becomes even harder. Therefore, it is difficult to easily peel off the cured keratin.

  Therefore, in order to enable intensive administration of a liquid drug to the affected area, a method has been proposed in which a through-hole is provided in a pad attached to the affected area, and the salicylic acid collodion solution is administered to the affected area via the through-hole. (Patent Document 1).

  On the other hand, woome and octopus are affected by external stimuli because the affected part protrudes from the skin surface. To remove the pain, a patch containing a local anesthetic (Patent Document 2) or a patch There has also been proposed an improvement related to the structure of the adhesive bandage in which a recess is provided in the recess and a detachable fitting member is fitted in the recess (Patent Document 3).

  As keratin softeners other than salicylic acid, alkaline protease (Patent Document 4), liquid saturated α-hydroxy fatty acid (Patent Document 5), and cyanoacrylate (Patent Document 6) have been proposed. Both are treatment methods by exfoliating the stratum corneum.

  In addition, a method of combining activated keratin protein as an activated protein with a salt of thioglycolic acid as a reducing agent and sodium pernitrate as an oxidizing agent (Patent Document 7), a thin film-forming protein and a reduced protein for the purpose of promoting healing and blocking odor A method of combining agents (Patent Document 8) has also been proposed.

  Furthermore, a method using a salt of salicylic acid, urea or thioglycolic acid as an activator for a local heat generating device (Patent Document 9), and a method using a similar activator for an exothermic dressing (Patent Document 10) have also been proposed. .

  However, these conventional methods are still not fully satisfactory in terms of rapid effect and pain relief, and further provision of new therapeutic agents is desired.

JP-A-6-319768 JP-A-6-72880 JP 2005-230494 A Japanese Patent Publication No. 4-53498 JP-T 8-500603 JP 2006-56860 A Japanese National Patent Publication No. 3-506024 Japanese translation of PCT publication No. 5-503071 Special table 2003-504117 gazette JP-T-2004-510454

  It is an object of the present invention to provide a useful new exfoliating composition which exhibits an effective exfoliating action in the treatment of urchin or octopus and has less adverse effects on the skin such as skin irritation and on the stability of the preparation.

(First invention)
The structure of the 1st invention of this application for solving the said subject is a keratin exfoliation composition characterized by containing the following (A) component and (B) component.
(A) Component: Disulfide bond cleaving agent (B) Component: Organic amine or salt thereof (second invention)
The constitution of the second invention of the present application is a keratin exfoliation composition in which the component (A) according to the first invention is at least one reducing agent of thioglycolic acid or a salt thereof, or cysteamine or a salt thereof.
(Third invention)
The configuration of the third invention of the present application is a keratin exfoliating composition in which the component (B) according to the first invention is guanidine or a salt thereof.
(Fourth invention)
The constitution of the fourth invention of the present application is a keratin exfoliating composition in which the component (B) according to the third invention is guanidine carbonate or guanidine hydroxide.
(Fifth invention)
The structure of this-application 5th invention is a keratin exfoliation composition in which the keratin exfoliation composition concerning the above-mentioned 1st-4th invention corresponds to one or more items of the following (1) or (2).
(1) The blending amount of the component (A) is in the range of 1 to 50 parts by weight.
(2) The compounding quantity of the said (B) component exists in the range of 0.5-30 weight part.
(Sixth invention)
The constitution of the sixth invention of the present application is a therapeutic agent for urchin or octopus containing the exfoliating composition according to any of the first to fifth inventions.
(Seventh invention)
The constitution of the seventh invention of the present application is a method for exfoliating horned or octopus keratin using the exfoliating composition according to any of the first to fifth inventions.

The present inventors have conducted intensive research on a method that prevents rebonding after cleavage of a disulfide bond by a disulfide bond cleaving agent, for example, a reducing agent such as thioglycolic acid or cysteamine, and can exfoliate while maintaining the softened state of the affected skin. went.
As a result, it has been found that by containing an organic amine such as guanidine or a salt thereof in the disulfide bond cleaving agent, the keratin hardening of the affected area can be prevented and the keratin of the affected area can be easily detached while maintaining the softened state.

That is, in the case of only the disulfide bond cleaving agent, the disulfide bond is once broken and then the disulfide bond is re-bonded by oxidation, so that the affected part is cured again. When the affected area is further loaded, a wider range becomes harder than before, and the exfoliation of the stratum corneum becomes difficult, and it is necessary to process it by scraping with a blade.
In contrast, when an organic amine or a salt thereof, such as guanidine or a salt thereof, is combined, guanidine interrupts hydrogen bonds that maintain the higher-order structure of the protein, and changes the protein structure into a random coil shape. It is presumed that the state is stabilized and further swelled by hydrogen bonding with water, the skin degeneration by the reducing agent is stabilized, and the softened state can be maintained. As a result, it is considered that the thiol group generated by cleavage of the disulfide bond can be prevented from returning to the disulfide bond again by oxidation, and the keratin of the affected area can be easily peeled off.

  Keratin exfoliation comprising (A) a disulfide bond cleaving agent of the present invention such as thioglycolic acid or a salt thereof, at least one reducing agent of cysteamine or a salt thereof, and (B) an organic amine or a salt thereof such as a guanidine or a salt thereof. The composition can maintain the state in which the disulfide bond of cystine contained in the keratin protein of the skin is cut off against keratinized skin such as urchin and octopus, so that it is not necessary to scrape urchin or octopus and softens it. It can be easily peeled off.

  Furthermore, by using the exfoliating composition of the present invention, healthy exfoliation can be recovered under the affected part of the exfoliated urchin or octopus, and furthermore, the core of the urnome can be removed by repeating the exfoliation. It can be completely cured against a stubborn wolf or octopus that repeats recurrence.

  Hereinafter, the present invention will be described in more detail.

(Disulfide bond cleaving agent)
As an example of the disulfide bond cleaving agent used in the present invention, thioglycolic acid can be used. The thioglycolic acid HSCH ₂ COOX (X = H) corresponds to the INCI name THIOGLYCOLIC ACID and includes those described on page 240 of the Quasi-drug Raw Material Standard 2006 (published by Yakuji Nippo). Acid "is available from Sasaki Chemical Co., Ltd.

The salt is a thioglycolic acid monoethanolamine salt (X = NH ₃ C ₂ H ₄ OH) (INCI name ETHANOLAMINE THIOGLYCOLATE) described on page 239 of the Quasi-drug Raw Material Standard 2006, thiol described on page 241. Examples include ammonium glycolate (X = NH ₄ ) (INCI name AMMONIUM THIOGLYCOLATE). For example, “50% thioglycolic acid monoethanolamine solution” and “50% ammonium thioglycolate solution” are available from Sasaki Chemical Co., Ltd. It can be obtained.

  Furthermore, calcium thioglycolate (X = 1 / 2Ca) (INCI name CALCIUM THIOGLYCOLATE) is mentioned, for example, "calcium thioglycolate trihydrate" can be obtained from Merck & Co., Inc.

Moreover, cysteamine hydrochloride can be used as an example of the disulfide bond cleaving agent used in the present invention. Cysteamine hydrochloride HSCH ₂ CH ₂ NH ₂ .HCL corresponds to the INCI name CYSTEAMINE HCL. For example, “50% cysteamine hydrochloride” can be obtained from Sasaki Chemical Co., Ltd.

(Organic amine or its salt)
Guanidine can be used as an example of the organic amine or salt thereof used in the present invention. Guanidine H ₂ NC (: NH) NH ₂ or a salt thereof H ₂ NC (: NH) NH ₂ .X is guanidine carbonate (INCI name GUANIDINE CARBONATE) or hydrochloric acid described on page 1067 of the quasi-drug raw material standard 2006 Guanidine (INCI name GUANIDINE HCL) is mentioned. For example, “guanidine carbonate” (X = 1 / 2H ₂ CO ₃ ) is obtained from Merck Ltd., and “guanidine HCl” (X = HCl) is obtained from Corallen CPP. Can do.

The external preparation for keratin softening of the present invention may be any dosage form as long as it is usually applied for external use, and (A) a disulfide bond cleaving agent such as thioglycolic acid or a salt thereof, cysteamine or At least one reducing agent of the salt, and (B) an organic amine or a salt thereof, for example, guanidine or a salt thereof as an essential component, an emulsifier and an emulsion stabilizer that are usually used in the manufacture of pharmaceuticals, quasi drugs and cosmetics , Thickeners, suspending agents, preservatives, antioxidants, pH adjusters, skin protectants or other additives, various ointments, lotions, oil-in-water creams, in oil Water-type creams, liquids, waxes, pastes, gels, patches, sprays, aerosols, colloidal suspensions and the like can be used.
Moreover, it can be set as a patch by mixing the above-mentioned essential component with the base of the polymer compound or a mixture thereof, making it uniform and spreading and molding on a support or a liner.

Although the compounding quantity of the keratin peeling composition of this invention cannot be prescribed | regulated uniformly by the kind and use of an external preparation, a disulfide bond cutting agent is 1-50 weight part as a total amount, Preferably it is 2-20 weight part. When the amount is less than 1 part by weight, the disulfide bond cannot be cleaved sufficiently, and the affected part is not softened. When the amount exceeds 50 parts by weight, the irritation is too strong and inflammation occurs.
On the other hand, the total amount of the organic amine or a salt thereof is 0.5 to 30 parts by weight, preferably 1 to 15 parts by weight. When the amount is less than 0.5 parts by weight, it is difficult to maintain the softened state, and when it exceeds 30 parts by weight, it is difficult to process in a pharmaceutical manner.

  The exfoliating composition of the present invention is applied topically in a manner effective to soften the affected area of urchin or octopus. In general, the drug is continuously used once or twice a day, or 2 to 3 times a week, and is applied to the affected area until it is sufficiently softened so that the urchin or octopus is easily peeled off.

  Examples of the present invention will be described below. The technical scope of the present invention is not limited by these examples.

Example 1 Cream (Prescription)
Ingredient (parts by weight)
50% cysteamine hydrochloride 30.0
Strong ammonia water 0.35
70% monoethanolamine 12.5
Guanidine carbonate 3.0
Sodium hydroxide 1.0
Edetate disodium 0.1
l-Menthol 3.0
Carboxyvinyl polymer 1.0
Cetanol 2.5
Behenyl alcohol 2.0
Squalane 1.0
Polyoxyethylene cetyl ether 2.0
1,3-butylene glycol 2.0
Purified water remaining

  Prepare a cream according to the general rules for preparations in Japan and the cream section. That is, components from 50% cysteamine hydrochloride to disodium edetate described in the above table were dissolved in an appropriate amount of purified water to obtain a composition for external use. Separately, components from cetanol to 1,3-butylene glycol are dissolved by heating and emulsified by adding 10% by mass of purified water to an oil phase maintained at 80 ° C., cooled to around 50 ° C. Carboxyvinyl polymer swollen in purified water was added. The composition for external use was added thereto, and further l-menthol was added and mixed uniformly to obtain the cream of Example 1.

(Usage example 1a)
The cream of Example 1 was applied to the affected area of wort and left as it was for about 20 minutes. When the state of women was examined, the hard keratin was relatively softened, and the upper keratin was able to be peeled off. By repeating application twice a day in the morning and evening, the pain disappeared in 2 to 3 days, and after 1 week, most of the hard part was easily detached, and normal skin was observed under the exfoliated keratin.

(Usage example 1b)
The cream of Example 1 was applied to the affected area of the wort with the core that was semitransparently cured inside, and left as it was for about 20 minutes. When the hard core was moved, the core portion was removed from the surrounding hard skin and the pain disappeared. Furthermore, by repeating the application twice a day in the morning and evening, most of the hard part was easily detached after 5 days, and normal skin was observed under the exfoliated keratin.

(Example 2) Cream (prescription)
Ingredient (parts by weight)
50% ammonium thioglycolate solution 30.0
Strong ammonia water 0.35
70% monoethanolamine 12.5
Guanidine carbonate 3.0
Sodium hydroxide 1.0
Edetate disodium 0.1
l-Menthol 3.0
Carboxyvinyl polymer 1.0
Cetanol 2.5
Behenyl alcohol 2.0
Squalane 1.0
Polyoxyethylene cetyl ether 2.0
1,3-butylene glycol 2.0
Purified water remaining

  A cream of Example 2 is obtained in the same manner as in Example 1 except that 30.0 parts by weight of 50% cysteamine hydrochloride is replaced with 50% ammonium thioglycolate solution.

(Usage example 2)
The cream of Example 2 was applied to the affected area of the octopus that was formed extensively on the side of the foot, and left for about 20 minutes to soften the upper stratum corneum and partly peeled off. By repeating the application once a day, the pain disappeared after the second application, and the hard part gradually peeled and disappeared, and normal skin could be recovered.

(Example 3) Cream (prescription)
Ingredient (parts by weight)
50% cysteamine hydrochloride 16.0
Strong ammonia water 0.2
70% monoethanolamine 12.0
Guanidine carbonate 3.0
Sodium hydroxide 1.0
Edetate disodium 0.1
l-Menthol 3.0
Carboxyvinyl polymer 1.0
Cetanol 2.5
Behenyl alcohol 2.0
Polyoxyethylene cetyl ether 2.0
1,3-butylene glycol 2.0
Purified water remaining

  Prepare a cream according to the general rules for preparations in Japan and the cream section. That is, components from 50% cysteamine hydrochloride to disodium edetate described in the above table were dissolved in an appropriate amount of purified water to obtain a composition for external use. Separately, components from cetanol to 1,3-butylene glycol are dissolved by heating and emulsified by adding 10% by mass of purified water to an oil phase maintained at 80 ° C., cooled to around 50 ° C. Carboxyvinyl polymer swollen in purified water was added. The composition for external use was added thereto, and further l-menthol was added and mixed uniformly to obtain the cream of Example 3.

(Example 4) Cream (prescription)
Ingredient (parts by weight)
50% ammonium thioglycolate solution 10.0
Strong ammonia water 0.2
70% monoethanolamine 12.0
Guanidine carbonate 3.0
Sodium hydroxide 1.0
Edetate disodium 0.1
l-Menthol 3.0
Carboxyvinyl polymer 1.0
Cetanol 2.5
Behenyl alcohol 2.0
Polyoxyethylene cetyl ether 2.0
1,3-butylene glycol 2.0
Purified water remaining

  A cream of Example 4 is obtained in the same manner as in Example 3 except that 16.0 parts by weight of 50% cysteamine hydrochloride is replaced with 10 parts by weight of 50% ammonium thioglycolate solution.

(Example 5) Patch (Prescription)
Ingredient (parts by weight)
50% cysteamine hydrochloride 30.0
Strong ammonia water 0.35
70% monoethanolamine 12.5
Guanidine hydroxide 3.0
Sodium hydroxide 1.0
Edetate disodium 0.1
l-Menthol 3.0
Carboxyvinyl polymer 1.0
Sorbitol 15.0
Sodium polyacrylate 7.0
Sodium carboxymethylcellulose 2.5
Titanium oxide 1.0
Aluminum hydroxide 0.1
Glycerin 12.0
Purified water remaining

  Prepare the patch according to the “JP” General Rules for Preparations and Patches. That is, components from 50% cysteamine hydrochloride to disodium edetate described in the above table were dissolved in an appropriate amount of purified water to obtain a composition for external use. Separately, add sorbitol to the carboxyvinyl polymer swollen in the remaining amount of purified water, stir and dissolve, and add a mixture of sodium polyacrylate to aluminum hydroxide in the above table to glycerin. Kneaded. A pre-prepared composition for external use was added thereto, and further l-menthol was added and mixed uniformly to obtain a patch composition. This was coated on a non-woven fabric so as to have a thickness of about 0.8 mm, and then a silicone-treated release paper was bonded to the surface of the plaster and cut into a desired shape to obtain a patch of Example 5.

(Example 6) Patch (prescription)
Ingredient (parts by weight)
50% ammonium thioglycolate solution 30.0
Strong ammonia water 0.35
70% monoethanolamine 12.5
Guanidine carbonate 3.0
Sodium hydroxide 1.0
Edetate disodium 0.1
l-Menthol 3.0
Carboxyvinyl polymer 1.0
Sorbitol 15.0
Sodium polyacrylate 7.0
Sodium carboxymethylcellulose 2.5
Titanium oxide 1.0
Aluminum hydroxide 0.1
Glycerin 12.0
Purified water remaining

  A patch of Example 4 is obtained in the same manner as in Example 6 except that 30.0 parts by weight of 50% cysteamine hydrochloride is replaced with 50% ammonium thioglycolate solution.

(Example 7) A patch with a pad The patch composition of Example 5 was poured into a concave portion of an annular pad fixed to a bandage to obtain a patch with a pad of Example 7.

Comparative Example 1 Cream (Prescription)
Ingredient (parts by weight)
50% cysteamine hydrochloride 30.0
Strong ammonia water 0.35
70% monoethanolamine 12.5
Sodium hydroxide 1.0
Edetate disodium 0.1
l-Menthol 3.0
Carboxyvinyl polymer 1.0
Cetanol 2.5
Behenyl alcohol 2.0
Squalane 1.0
Polyoxyethylene cetyl ether 2.0
1,3-butylene glycol 2.0
Purified water remaining

  Prepare a cream according to the general rules for preparations in Japan and the cream section. That is, components from 50% cysteamine hydrochloride to disodium edetate described in the above table were dissolved in an appropriate amount of purified water to obtain a composition for external use. Separately, components from cetanol to 1,3-butylene glycol are dissolved by heating and emulsified by adding 10% by mass of purified water to an oil phase maintained at 80 ° C., cooled to around 50 ° C. Carboxyvinyl polymer swollen in purified water was added. The composition for external use was added thereto, and further l-menthol was added and mixed uniformly to obtain the cream of Comparative Example 1.

  The cream of Comparative Example 1 was applied to the affected area of wort and left as it was for about 20 minutes. Upon examination of the condition of the women, the hard keratin became relatively soft immediately after application, but gradually became harder and pain remained. Further, by repeating the application twice a day in the morning and evening, the coated part became hard rubber, and the hardened keratin after one week could be scraped off with a blade. Although the pain was gradually reduced, the pain remained in the core.

(Comparative Example 2) Salicylic acid ointment (prescription)
component
Salicylic acid 100g
10g camphor
Vegetable oil 10mL
Simple ointment 650g
180g beeswax
Medicinal soap 50g

  After heating and dissolving simple ointment, beeswax, vegetable oil and medicinal soap, they are half-cooled, added to this is a mixture of salicylic acid and camphor with about 20 mL of ethanol, and stirred until it begins to harden. The lithic acid ointment of Comparative Example 2 An agent was obtained.

The salicylic acid ointment of Comparative Example 2 was applied to the affected area of wort and left as it was for about 30 minutes. Examination of the condition of the women showed that there was no particular change in the hard keratin, but after that it gradually became white and soft, but pain remained.

Claims (3)

A therapeutic agent for urchin or octopus comprising the following components (A) and (B):
(A) Component: Thioglycolic acid or a salt thereof, or at least one reducing agent of cysteamine or a salt thereof (B) Component: Guanidine or a salt thereof The therapeutic agent for urchin or octopus according to claim 1, wherein the component (B) is guanidine carbonate or guanidine hydroxide. The horneous or octopus therapeutic agent according to claim 1, wherein the exfoliating composition corresponds to one or more of the following (1) or (2).
(1) The compounding quantity of the said (A) component exists in the range of 1-50 weight part.
(2) The compounding quantity of the said (B) component exists in the range of 0.5-30 weight part.