JP2016130224A - External composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an external composition having improved stability of allantoin and/or derivatives thereof, and having excellent storage stability.SOLUTION: An external composition uses (A) allantoin and/or a derivative thereof and (B) a heparin analog in combination with each other, thereby improving the stability of allantoin and/or a derivative thereof.SELECTED DRAWING: None

Description

  The present invention relates to a composition for external use in which the stability of allantoin and / or a derivative thereof is improved and the storage stability is excellent.

  Allantoin and its derivatives have an anti-inflammatory action, a cell activation action, a necrotic tissue removal action, a new normal skin tissue promotion action, and the like, and are used in compositions for external use. However, allantoin and its derivatives are liable to be decomposed and precipitated in the composition for external use and have the disadvantage of poor stability (see, for example, Non-Patent Document 1).

  Thus, various preparation techniques for improving the stability of allantoin and / or its derivatives in external compositions have been studied. For example, U.S. Patent No. 6,057,031 discloses a composition comprising an oil-in-water emulsion comprising (a) allantoin and (b) at least one anionic or nonionic emulsifier that is substantially hydrophilic and water soluble. Discloses that the stability of allantoin can be improved by setting the pH to about 3.0 to about 6.0. Patent Document 2 contains a combination of (i) allantoin and / or a related substance thereof, (ii) panthenol and / or a panthenol related substance, and (iii) diphenhydramine or a salt thereof in an external preparation for skin. It is disclosed that the stability of allantoin and / or its related substances is improved.

  However, the conventional formulation technology for stabilizing allantoin and / or its derivatives cannot deal with the diversified formulation of external compositions in recent years due to restrictions on formulation. Therefore, development of a new formulation technique for stabilizing allantoin and / or its derivatives is required.

  On the other hand, heparin-like substances are known to have moisturizing action, blood flow increasing action, and the like, and are used in compositions for external use. In addition, glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof have anti-inflammatory action, anti-allergic action, and the like, and are used in compositions for external use. However, the effect of these drugs on the stability of allantoin and / or its derivatives has not been clarified.

Shinya Yamamoto et al., Identification of allantoin stability and its degradation products, Pharmaceutical Journal, 113 (7), 515-524, 1993.

JP-T-2004-513068 JP 2006-335676 A

  An object of the present invention is to provide a composition for external use in which the stability of allantoin and / or a derivative thereof is improved and the storage stability is excellent.

  The present inventor conducted intensive studies to solve the above-mentioned problems. As a result, (A) allantoin and / or a derivative thereof and (B) a heparin-like substance are used in combination to stabilize allantoin and / or a derivative thereof. It was found that the performance is improved. Furthermore, the present inventor combined (A) allantoin and / or a derivative thereof, and (B) a heparin analog, (C) glycyrrhizic acid, glycyrrhetinic acid, a derivative thereof, and / or a salt thereof in combination. It has been found that the stability of allantoin and / or its derivatives can be further improved by blending. The present invention has been completed by further studies based on these findings.

That is, this invention provides the invention of the aspect hung up below.
Item 1. An external composition comprising (A) at least one selected from the group consisting of allantoin and derivatives thereof, and (B) a heparin-like substance.
Item 2. Item 2. The composition for external use according to Item 1, further comprising (C) at least one selected from the group consisting of glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof.
Item 3. Item 3. The external composition according to Item 1 or 2, wherein the content of the component (A) is 0.01 to 5% by weight.
Item 4. Item 4. The external composition according to any one of Items 1 to 3, wherein the content of the component (B) is 0.01 to 5% by weight.
Item 5. Item 5. The external composition according to any one of Items 2 to 4, wherein the content of the component (C) is 0.01 to 10% by weight.
Item 6. Item 6. The external composition according to any one of Items 1 to 5, wherein the pH is 4 to 7.
Item 7. A method for stabilizing allantoin and / or a derivative thereof, wherein in a composition for external use, (B) a heparin-like substance is allowed to coexist with at least one selected from the group consisting of (A) allantoin and a derivative thereof.
Item 8. Item 8. The stabilization method according to Item 7, wherein in the composition for external use, (C) at least one selected from the group consisting of glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof coexists.
Item 9. A stabilizer used for stabilizing an external composition containing at least one selected from the group consisting of allantoin and derivatives thereof,
A stabilizer comprising a heparin-like substance.
Item 10. A stabilizer used for stabilizing an external composition containing at least one selected from the group consisting of allantoin and derivatives thereof,
A stabilizer comprising: (B) a heparin-like substance; and (C) at least one selected from the group consisting of glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof.

  According to the present invention, the stability of allantoin and / or its derivative is improved by using (A) allantoin and / or its derivative in combination with (B) heparin-like substance. Even after storage, the medicinal effects of allantoin and / or derivatives thereof can be effectively exhibited. Further, according to the present invention, in addition to (A) allantoin and / or a derivative thereof, and (B) a heparin analog, (C) glycyrrhizic acid, glycyrrhetinic acid, a derivative thereof, and / or a salt thereof are combined. The stability of allantoin and / or its derivatives is drastically improved, so that it is possible to provide an externally useful composition that is extremely useful in practice.

1. Composition for External Use The composition for external use of the present invention comprises at least one selected from the group consisting of allantoin and derivatives thereof (hereinafter sometimes referred to as component (A)), and heparin-like substance (hereinafter referred to as (B) It may be described as a component). Hereinafter, the external composition of the present invention will be described in detail.

Component (A) The composition for external use of the present invention contains at least one selected from the group consisting of allantoin and derivatives thereof as the component (A). Allantoin and / or its derivatives have the disadvantage of poor stability, but according to the present invention, the stability of allantoin and / or its derivatives is improved by adding the component (B) described later. be able to.

  Allantoin is a compound also called 5-ureidohydantoin, and is a known drug known to have anti-inflammatory action, antipruritic action and the like.

  The allantoin derivative is not particularly limited as long as it is pharmaceutically acceptable, and specific examples include allantoin chlorohydroxyaluminum and allantoinhydroxyaluminum. These allantoin derivatives may be used alone or in combination of two or more.

  In the external composition of the present invention, as the component (A), one type may be selected from allantoin and derivatives thereof, or two or more types may be used in combination. Among these components (A), allantoin is preferably used from the viewpoint of improving stability more effectively.

  In the external composition of the present invention, the content of the component (A) may be appropriately set according to the medicinal effect to be provided in the external composition, for example, 0.01 to 5% by weight, preferably 0.05-3 weight%, More preferably, it is 0.05-2 weight%, More preferably, 0.1-2 weight% is mentioned.

Component (B) The composition for external use of the present invention contains a heparin-like substance as component (B). As described above, by using a combination of allantoin and / or a derivative thereof and a heparin-like substance, it is possible to improve the stability of the allantoin and / or the derivative thereof and to provide excellent storage stability.

  A heparin-like substance is a polysulfated mucopolysaccharide such as chondroitin polysulfate, and is a known drug known to have a moisturizing action, a blood flow increasing action, and the like.

  The origin of the heparin-like substance used in the present invention is not particularly limited. For example, it is obtained by polysulfating mucopolysaccharides, tissues of edible animals (for example, tracheal cartilage such as cattle and pigs) And the like extracted from the lung including In the composition for external use of the present invention, as the heparin-like substance, a heparin-like substance included in the Japanese Pharmacopoeia pharmaceutical standards is preferably used.

  In the composition for external use of the present invention, the content of the component (B) may be appropriately set within a range in which the stability of allantoin and / or a derivative thereof can be improved. Specifically, 0.01 to 5 % By weight, preferably 0.05 to 3% by weight, more preferably 0.1 to 1% by weight.

  Further, in the composition for external use of the present invention, the ratio of the component (A) and the component (B) may be appropriately set within the range satisfying the above-mentioned content, but per 100 parts by weight of the component (A) ( Component B) is 0.3 to 10000 parts by weight, preferably 2.5 to 6000 parts by weight, and more preferably 5 to 1000 parts by weight.

(C) Component In addition to the components (A) and (B), the composition for external use of the present invention further contains glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and / or salts thereof as the component (C). May be. As described above, by further containing the component (C), it is possible to further improve the stability of allantoin and / or a derivative thereof, and dramatically increase the storage stability thereof.

  Glycyrrhizic acid is a known drug known to have an anti-inflammatory action, an antiallergic action, and the like.

  The derivative of glycyrrhizic acid is not particularly limited as long as it is pharmaceutically acceptable, and specific examples include methyl glycyrrhizinate and stearyl glycyrrhizinate. These glycyrrhizic acid derivatives may be used alone or in combination of two or more.

  The salt of glycyrrhizic acid and its derivative is not particularly limited as long as it is pharmacologically acceptable, and specific examples include alkali metal salts such as sodium salt, potassium salt, dipotassium salt; ammonium salt and the like. It is done. These salts of glycyrrhizic acid and its derivatives may be used alone or in combination of two or more.

  Glycyrrhetinic acid is a known drug known to have an anti-inflammatory action, an antiallergic action and the like.

  The derivative of glycyrrhetinic acid is not particularly limited as long as it is pharmaceutically acceptable, and specific examples include pyridoxine glycyrrhetinate, stearyl glycyrrhetinate, glyceryl glycyrrhetinate, monoglucuronide glycyrrhetinate, and the like. These derivatives of glycyrrhetinic acid may be used singly or in combination of two or more.

  In the composition for external use of the present invention, as the component (C), one kind may be selected from glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof, and two or more kinds may be used in combination. May be used. Among these (C) components, from the viewpoint of further improving the stability of allantoin and / or derivatives thereof, preferably glycyrrhizic acid and salts thereof, more preferably glycyrrhizic acid salts, particularly preferably Examples include alkali metal salts of glycyrrhizic acid.

  In the composition for external use of the present invention, the content of the component (C) is not particularly limited, but for example 0.01 to 10% by weight, preferably 0.05 to 5% by weight, more preferably 0.05 to 3%. % By weight, particularly preferably 0.1 to 3% by weight.

  Further, in the composition for external use of the present invention, the ratio of the component (A) and the component (C) may be appropriately set within a range that satisfies the above-described content, but per 100 parts by weight of the component (A), Component C) is 0.2 to 100,000 parts by weight, preferably 1.7 to 10,000 parts by weight, more preferably 2.5 to 6000 parts by weight, and particularly preferably 5 to 3000 parts.

Composition for external use of the water present invention, in order to prepare the desired formulation, may contain water. Allantoin and / or a derivative thereof show a tendency to decrease in stability in the presence of water. However, according to the composition for external use of the present invention, the stability of allantoin and / or a derivative thereof caused in the presence of water. Can be effectively suppressed.

  In the composition for external use of the present invention, the water content is appropriately set according to the formulation form and the like, but is, for example, 0.5 to 99% by weight, preferably 10 to 90% by weight, and more preferably 30%. -90 weight%, Most preferably, 50-85 weight% is mentioned.

Other Components The composition for external use of the present invention may contain other pharmacological components as necessary in addition to the components described above. Such a pharmacological component is not particularly limited as long as it can be used in a composition for external use. , Mepipacaine, chloroprocaine, proparacaine, meprilucaine or salts thereof, orthocaine, oxesazein, oxypolyentoxydecane, funnel extract, percamin ase, tesitdecitine, etc., anti-inflammatory agents (indomethacin, felbinac, diclofenac sodium, loxoprofen sodium, etc.), skin protection Agents (colodion, castor oil, etc.), blood circulation promoting components (nonyl acid vanillylamide, nicotinic acid benzyl ester, capsaicin, pepper extract, etc.), cooling agents (menthol) Camphor), vitamins (vitamin A, vitamin E, etc.), mucopolysaccharides (sodium chondroitin sulfate, glucosamine, etc.) and the like.

  Moreover, in order to make the external composition of this invention into a desired formulation form, in addition to the component mentioned above, the base material and the additive may be contained as needed. Such bases and additives are not particularly limited as long as they are pharmaceutically acceptable. For example, lower alcohols (ethanol, isopropanol, etc.), polyhydric alcohols (glycerin, propylene glycol, dipropylene glycol, Aqueous bases such as 1,3-butylene glycol; animal and vegetable oils (olive oil, safflower oil, soybean oil, camellia oil, corn oil, rapeseed oil, sunflower oil, cottonseed oil, peanut oil, lard, squalane, fish oil, etc.), Mineral oil (liquid paraffin, paraffin, gelled hydrocarbon, petrolatum, etc.), waxes and waxes (beeswax, carnauba wax, candelilla wax, ceresin, rice wax, microcrystalline wax, etc.), fatty acid alkyl ester, fatty acid (stearic acid) Oleic acid, palmitic acid, Helic acid, linoleic acid, lanolin, etc.), fatty acid ester (isopropyl myristate, isopropyl adipate, diethyl sebacate, isopropyl sebacate, cetyl palmitate, isopropyl palmitate, ethyl linoleate, ethyl oleate, etc.), higher alcohol ( Stearyl alcohol, cetanol, behenyl alcohol, myristyl alcohol, oleyl alcohol, hexadecyl alcohol, lanolin alcohol, etc.), cholesterol, glyceryl tri-2-ethylhexanoate, cetyl 2-ethylhexanoate, silicone oil (dimethylpolysiloxane, cyclic silicone, etc.) Oily bases such as POE (10-50 mol) phytosterol ether, POE (10-50 mol) dihydrocholesterol ether, POE (10-10 mol) 0 mol) 2-octyldodecyl ether, POE (10-50 mol) decyl tetradecyl ether, POE (10-50 mol) oleyl ether, POE (2-50 mol) cetyl ether, POE (5-50 mol) behenyl ether Polyoxyethylene alkyl ethers such as POE (5-30 mol) polyoxypropylene (5-30 mol) 2-decyltetradecyl ether, POE (10-50 mol) polyoxypropylene (2-30 mol) cetyl ether, These phosphates and phosphates (such as POE cetyl ether sodium phosphate), POE (20 to 60 mol) sorbitan monooleate, POE (10 to 60 mol) sorbitan monoisostearate, POE (10 to 80 mol) glyceryl Monoisostearate, POE (10-30 mol G) Glyceryl monostearate, POE (20 to 100 mol) / polyoxypropylene modified silicone, POE / alkyl modified silicone, polyethylene glycol monolaurate, polyethylene glycol monopalmitate, polyethylene glycol monostearate, polyethylene glycol dilaurate, di Polyethylene glycol palmitate, polyethylene glycol distearate, polyethylene glycol dioleate, polyethylene glycol diricinoleate, polyoxyethylene hydrogenated castor oil (5 to 100), polysorbate (20 to 85), glycerin fatty acid ester (glyceryl monostearate, etc.) , Surfactants such as hydrogenated soybean phospholipid and hydrogenated lanolin alcohol; refreshing agents (menthol, camphor, Neol, mint water, mint oil, etc.), preservatives (paraoxybenzoic acid esters such as methylparaben and propylparaben, benzoic acid, sodium benzoate, sorbic acid, etc.) Farnesol, etc.), coloring agents (tar pigments (brown 201, blue 201, yellow 4, yellow 403, etc.), cacao pigments, chlorophyll, aluminum oxide, etc.), thickeners (carboxyvinyl polymer, hypromellose, polyvinylpyrrolidone) , Sodium alginate, ethyl cellulose, sodium carboxymethyl cellulose, xanthan gum, carrageenan, etc.), pH adjuster (phosphoric acid, hydrochloric acid, citric acid, sodium citrate, succinic acid, tartaric acid, sodium hydroxide, potassium hydroxide, triethanolamine) Triisopropanolamine, etc.), wetting agents (dl-pyrrolidone carboxylate solution, D-sorbitol solution, macrogol, glycerin, etc.), stabilizers (dibutylhydroxytoluene, butylhydroxyanisole, sodium edetate, sodium metaphosphate, L -Arginine, L-aspartic acid, DL-alanine, glycine, sodium erythorbate, propyl gallate, sodium sulfite, sulfur dioxide, chlorogenic acid, catechin, rosemary extract, etc.), antioxidant, ultraviolet absorber, chelating agent , Additives such as adhesives, buffers, solubilizers, solubilizers, preservatives, and the like.

pH
The pH of the composition for external use of the present invention may be within a range where it can be applied transdermally, but usually 3 to 9, preferably from the viewpoint of further improving the stability of allantoin and / or its derivatives. Is 4 to 8, more preferably 4 to 7, and particularly preferably 4 to 6.

Formulation Form The dosage form of the composition for external use of the present invention is not particularly limited as long as it can be applied transdermally, and may be any of liquid, solid, semi-solid (gel, ointment, paste), etc. Also good.

  In addition, the preparation form of the external composition of the present invention may be any preparation form such as a skin external medicine, a cosmetic, a skin cleanser and the like. As a preparation form of the composition for external use of the present invention, specifically, a skin external medicine such as a cream, lotion, gel, emulsion, liquid, patch, aerosol, ointment, pack, etc .; ointment, cream And cosmetics such as emulsions, lotions, lotions, packs and gels; skin cleansing agents such as body shampoos, hair shampoos and rinses. Among these preparation forms, preferably a topical medicine for skin, more preferably a cream, a lotion, a gel, an emulsion, a pack, and particularly preferably a cream or an emulsion.

  In the prior art, in oil-in-water creams and oil-in-water emulsions, particularly oil-in-water creams, the tendency of allantoin and / or its derivatives to decrease is significant. According to the composition, allantoin and / or a derivative thereof can be stably maintained even in such a preparation form. In view of the effects of the present invention, oil-in-water type creams and oil-in-water type emulsions, particularly preferably oil-in-water type creams, are preferable examples of the preparation form of the external composition of the present invention. Can be mentioned. Oil-in-water creams and oil-in-water emulsions are composed of an aqueous phase containing water and other aqueous components, oily bases, and other oily components from among the aforementioned bases and additives. It can manufacture by mixing with the oil phase containing etc. and performing a well-known emulsification process.

Use The composition for external use of the present invention can exhibit anti-inflammatory action and antipruritic action based on the component (A), moisturizing action and blood flow increase action based on the component (B), etc. Increased blood flow, keratosis of elbows, knees, heels, and ankles, rough fingers, cracks and tears on limbs, dry skin, dry skin of children, excluding sores, and after bruises and sprains It can be applied to the skin for purposes such as dry / muscular pain / joint pain, dry skin with itching (dry skin of the elderly and adults, dry skin of children), and bruises.

  In addition, when the composition for external use of the present invention contains the component (C), in addition to the anti-inflammatory action and antiallergic action based on the component (C), the components (A) to (C) Can be used together to prevent or treat hypertrophic scars and / or keloids, such as discoloration (redness, dullness), pulling (stretching), lump, reduced elasticity, etc. It can also be used for improvement purposes.

2. Method for Stabilizing Allantoin and / or its Derivative The stabilizing method of the present invention is a method for stabilizing allantoin and / or its derivative, and is selected from the group consisting of (A) allantoin and its derivative in an external composition. (B) a heparin-like substance coexists with at least one selected from the above. In the stabilization method of the present invention, allantoin and / or a derivative thereof can be stabilized by allowing (C) glycyrrhizic acid, glycyrrhetinic acid, a derivative thereof, and / or a salt thereof to coexist in the composition for external use. It is possible to further improve the performance.

  The types, contents, ratios, and the like of the components (A) to (C) used in the stabilization method of the present invention are as described in the column of “1. Composition for external use”. Further, in the stabilization method of the present invention, the other components added to the external composition, the preparation form of the external composition, the use of the external composition, etc. are also described in the section of “1. External composition”. It is as follows.

3. Stabilizer for Allantoin and / or its Derivative Stabilizer of the present invention is a stabilizer used for stabilizing an external composition containing at least one selected from the group consisting of allantoin and its derivative. And containing a heparin-like substance. Furthermore, the stabilizer of the present invention is a stabilizer used to stabilize an external composition containing at least one selected from the group consisting of allantoin and derivatives thereof, and comprises (B) heparin It contains at least one selected from the group consisting of similar substances and (C) glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof. These stabilizers are used as an additive for improving the stability of allantoin and / or its derivative and enhancing the storage stability of the externally used composition in an external composition containing allantoin and / or its derivative. The

  The types of allantoin and / or derivatives thereof, the type of component (B), the type of component (C), the content thereof, the ratio thereof, etc. used in the stabilizer of the present invention are described in “1. It is as described in the column of “External composition”. In the stabilizer of the present invention, other components to be added to the external composition, the preparation form of the external composition, the use of the external composition, etc. are also as described in the column of “1. External composition”. It is.

  EXAMPLES The present invention will be described more specifically with reference to the following examples, but the present invention is not limited to these examples.

Test Example 1: Evaluation of Allantoin Stability in Creams Creams (Examples 1 to 3 and Comparative Example 1) having the formulations shown in Table 1 were prepared. Specifically, an aqueous phase in which a predetermined amount of an aqueous phase component shown in Table 1 is mixed and an oil phase in which a predetermined amount of an oil phase component shown in Table 1 is mixed are prepared, and the aqueous phase and the oil phase are heated. The oil-in-water type cream was prepared by mixing the mixture in the prepared state, emulsifying, and cooling.

  The obtained cream was stored in a container (made of glass) and stored for 7 days in a light-shielding environment at a temperature of 50 ° C. The amount of allantoin contained in each cream before and after storage was quantified by HPLC, and the reduction ratio of allantoin after storage was calculated according to the following formula.

  The obtained results are shown in Table 1. From this result, when no heparin-like substance is contained (comparative example), allantoin has reached a weight loss ratio of 7.2% by storage at 50 ° C. for 7 days, but allantoin and heparin-like substance are used in combination. As a result (Examples 1 to 3), the weight loss ratio of allantoin was effectively reduced, and the stability of allantoin was improved. In particular, when allantoin was combined with a heparin-like substance and dipotassium glycyrrhizinate (Example 2), the stability of allantoin was dramatically improved.

Test Example 2: Evaluation of Allantoin Stability in Emulsion An emulsion (Example 4) having the formulation shown in Table 2 was prepared. Specifically, an aqueous phase in which a predetermined amount of an aqueous phase component shown in Table 2 is mixed and an oil phase in which a predetermined amount of an oil phase component shown in Table 2 is mixed are prepared, and the aqueous phase and the oil phase are heated. The mixture was mixed, emulsified, and then cooled to prepare an oil-in-water emulsion.

  The obtained emulsion was placed in a container and stored for 11 days in a light-shielding environment at a temperature of 50 ° C. The amount of allantoin contained in each emulsion before and after storage was quantified by HPLC, and the weight loss ratio of allantoin after storage was calculated according to the calculation formula shown in Test Example 1.

  The obtained results are shown in Table 2. Also from this result, it was confirmed that the stability of allantoin can be significantly improved by combining a heparin analog and dipotassium glycyrrhizinate together with allantoin.

Formulation Examples Oil-in-water creams (Formulation Examples 1 to 13) having the composition shown in Table 3, oil-in-water emulsions (Formulation Examples 14 to 23) shown in Table 4, and lotions (Formulation Example 24) shown in Table 5 -32) were prepared. All of these preparations have a formulation that does not include (B) a heparin analog and (C) at least one selected from the group consisting of glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof. In comparison, the allantoin stability effect is demonstrated.

Claims (9)

  An external composition comprising (A) at least one selected from the group consisting of allantoin and derivatives thereof, and (B) a heparin-like substance.   The composition for external use according to claim 1, further comprising (C) at least one selected from the group consisting of glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof.   The external composition according to claim 1 or 2, wherein the content of the component (A) is 0.01 to 5% by weight.   The composition for external use in any one of Claims 1-3 whose content of the said (B) component is 0.01-5 weight%.   The composition for external use in any one of Claims 2-4 whose content of the said (C) component is 0.01 to 10 weight%.   A method for stabilizing allantoin and / or a derivative thereof, wherein in a composition for external use, (B) a heparin-like substance is allowed to coexist with at least one selected from the group consisting of (A) allantoin and a derivative thereof.   The stabilization method according to claim 6, wherein in the composition for external use, at least one selected from the group consisting of (C) glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof is coexisted. A stabilizer used for stabilizing an external composition containing at least one selected from the group consisting of allantoin and derivatives thereof,
A stabilizer comprising a heparin-like substance. A stabilizer used for stabilizing an external composition containing at least one selected from the group consisting of allantoin and derivatives thereof,
A stabilizer comprising: (B) a heparin-like substance; and (C) at least one selected from the group consisting of glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof.