External use ingredients

Abstract

To provide compositions for external use that have viscosity different from the conventional feel and contain a heparinoid and placenta extract, in which temporal coloring is suppressed, so as to solve the problems of temporal coloring and poor formulation stability when blended with a water-soluble thickener and stored.SOLUTION: We have found that a composition for external use containing a heparinoid, placenta extract, and a specific thickener can solve the above problems. That is, the present invention is a composition for external use that contains (a) a heparinoid, (b) placenta extract, and (c) at least one thickener selected from the group consisting of hydroxyethyl cellulose, xanthan gum, Tremella fuciformis polysaccharide, carboxyvinyl polymer, hydroxypropyl methylcellulose, pullulan, sodium chondroitin sulfate, gellan gum, sodium carboxymethyl dextran, polyacrylate crosspolymer 11, polyethylene glycol, (Na acrylate / Na acryloyl dimethyl taurine) copolymer, and hydrophobized hydroxypropyl methylcellulose. Furthermore, when a polyhydric alcohol is added, it has a higher improvement effect.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a composition for external use containing a heparinoid and a placenta extract. [Background technology]

[0002] Heparinoids are a type of acidic mucopolysaccharides, and are incorporated into topical preparations such as medicines and quasi-drugs because of their wide range of effects, including moisturizing and anti-inflammatory effects on the skin, promoting blood flow, and treating and preventing scars and keloids. Various studies have been conducted to improve the effects of heparinoids. For example, it is known that by combining heparinoids with betaines, the heparinoids' effect of enhancing keratin moisture retention and the moisturizing effect of betaines act synergistically, resulting in a significant improvement and prevention effect on rough skin (Patent Document 1). While the usefulness of heparinoids for the skin has been shown in this way, it is known that poor usability is an issue when heparinoids are incorporated into topical preparations, and it has been reported that the usability can be improved by incorporating hyaluronic acid oligosaccharides (Patent Document 2). Heparinoids are also used to treat xerosis and atopic dermatitis. Heparinoids are composed mainly of polysulfated polysaccharides and therefore cause some irritation to the skin. However, since the skin of patients with xerosis or atopic dermatitis is hypersensitive to irritation, preparations that minimize this irritation are being developed (Patent Document 3).

[0003] Placental extract is an extract extracted from the placenta of mammals such as pigs, cows, horses, humans, or sheep. Placental tissue of mammals is rich in amino acids, active peptides, vitamins, minerals, sugars, enzymes, nucleic acids, etc., which are nutrients essential for fetal growth, and the extract extracted from the placenta of the mammals is called placental extract. The placental extract has effects such as cell proliferation, improvement of immunity, improvement of blood pressure, antioxidant effect, anti-inflammatory effect, analgesic effect, and blood coagulation inhibition effect, and is used as a raw material for cosmetics such as whitening cosmetics, dietary supplements such as fatigue recovery drinks, and pharmaceuticals such as anti-aging drugs (Patent Document 4).

[0004] In general, the viscosity of external compositions applied to the skin, such as cosmetics, is adjusted according to the purpose and use, and various thickeners are used according to the formulation. As the thickener, specifically, water-soluble polymers such as carboxyvinyl polymer, xanthan gum, cellulose, guar gum, alginic acid, polyacrylic acid, polyvinyl alcohol, acrylates / alkyl acrylate (C10-30) crosspolymer, etc. are often used. By using these according to the purpose and changing the blending amount, blending components, etc., it is possible to prepare low-viscosity formulations such as the thickness of lotions to solid gel-like ones such as hair tics (Patent Document 5). In addition, formulations such as viscous cosmetics are often used because they have a thick appearance, a rich feeling during use, a moisturizing feeling, etc., and therefore improve the marketability (Patent Document 6).

[0005] Adriace (registered trademark) Active Lotion, a cosmetic product containing heparinoids and placenta extract, was released in May 2019. However, no topical composition containing heparinoids, placenta extract, and a water-soluble thickener is known, and there have been no reports on how adding a water-soluble thickener to a topical composition containing heparinoids and placenta extract affects the formulation. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] JP 2000-143486 A [Patent Document 2] JP 2017-66060 A [Patent Document 3] JP 2015-203029 A [Patent Document 4] JP 2011-160742 A [Patent Document 5] JP 2017-36217 A [Patent Document 6] JP 2014-185118 A Summary of the Invention [Problem to be solved by the invention]

[0007] In order to provide a topical composition with a different viscosity from conventional compositions, the present inventors mixed a water-soluble thickener into a topical composition containing a heparinoid and placenta extract and stored it, but found that the composition became discolored over time and the stability of the formulation was poor. The discoloration of the formulation is undesirable from the viewpoints of formulation stability and marketability.

[0008] The present invention has been made in consideration of the above-mentioned circumstances, and an object of the present invention is to provide a composition for external use which contains a heparinoid and a placenta extract and is suppressed from discoloring over time. [Means for solving the problem]

[0009] As a result of intensive research into solving the above problems, the present inventors have found that a composition for external use containing a heparinoid, a placenta extract, and a specific thickener can solve the above problems. Furthermore, they have found that the inclusion of a polyhydric alcohol provides a higher improvement effect, and have thus completed the present invention.

[0010] That is, the present invention provides: (1) A composition for external use, comprising (a) a heparinoid, (b) a placenta extract, and (c) at least one thickener selected from the group consisting of hydroxyethyl cellulose, xanthan gum, Tremella fuciformis polysaccharide, carboxyvinyl polymer, hydroxypropyl methylcellulose, pullulan, sodium chondroitin sulfate, gellan gum, sodium carboxymethyl dextran, polyacrylate crosspolymer 11, polyethylene glycol, (sodium acrylate / sodium acryloyldimethyltaurate) copolymer, and hydrophobized hydroxypropyl methylcellulose; (2) The composition for external use according to (1), further comprising (d) a polyhydric alcohol. (3) (d) The composition for external use according to (2), wherein the polyhydric alcohol is at least one selected from the group consisting of 1,2-pentanediol, glycerin, diglycerin, 1,3-butylene glycol, dipropylene glycol, and 1,2-propanediol; (4) The composition for external use according to any one of (1) to (3), which has a viscosity of 1 mPa s or more at 20°C. (5) The composition for external use according to any one of (1) to (4), further comprising (e) water. (6) The composition for external use according to any one of (1) to (5), which has a dosage form of a lotion, cream, emulsion, gel, or pack. (7) The composition for external use according to any one of (1) to (6), which is a cosmetic, a quasi-drug, or a pharmaceutical. Includes: Effect of the Invention

[0011] According to the present invention, it is possible to provide a composition for external use which contains a heparinoid, a placenta extract, and a specific thickener, and which has excellent formulation stability and suppresses discoloration. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] The components used in the topical composition of the present invention may be of the same quality as those normally used in pharmaceuticals, quasi-drugs, or cosmetics.

[0013] The content of the heparinoid in the composition for external use of the present invention is preferably 0.001 to 10 w / w%, more preferably 0.01 to 1.0 w / w%.

[0014] The placenta extract in the composition for external use of the present invention may be derived from, for example, human, cow, pig, horse, sheep, etc., and is preferably from pig. In addition, a commercially available product (e.g., Biocatalyzer Placenta APF (SW) (M-PE-APF)) may be used as a placenta extract. The content of the placenta extract of the present invention in the composition for external use of the present invention is preferably 0.001 to 10 w / w%, more preferably 0.01 to 1.0 w / w%.

[0015] The specific thickeners of the present invention are hydroxyethyl cellulose, xanthan gum, Tremella fuciformis polysaccharide, carboxyvinyl polymer, hydroxypropyl methylcellulose, pullulan, sodium chondroitin sulfate, gellan gum, sodium carboxymethyl dextran, polyacrylate crosspolymer 11, polyethylene glycol, (Na acrylate / Na acryloyldimethyl taurate) copolymer, and hydrophobized hydroxypropyl methylcellulose. One or more types of thickeners can be used. In addition, each of the above components may be one type or two or more types.

[0016] The content of the hydroxyethyl cellulose in the topical composition of the present invention is preferably from 0.001 to 20 w / w %, more preferably from 0.01 to 10 w / w %.

[0017] The content of the xanthan gum in the topical composition of the present invention is preferably 0.001 to 20 w / w%, and more preferably 0.01 to 10 w / w%.

[0018] The Tremella fuciformis polysaccharide of the present invention can be extracted from the fruit body of Tremella fuciformis Berk. of the Tremella family with water or a mixture of water and a water-soluble solvent. Commercially available products include Tremoist-TP (trade name) and Tremoist-SL (trade name) sold by Nippon Fine Chemical Co., Ltd. The Tremella fuciformis polysaccharide content in the topical composition of the present invention is preferably 0.001 to 20 w / w%, more preferably 0.01 to 10 w / w%.

[0019] The content of the carboxyvinyl polymer of the present invention in the topical composition of the present invention is preferably 0.001 to 20 w / w%, more preferably 0.01 to 10 w / w%. If necessary, the pH can be adjusted to achieve a further thickening effect.

[0020] The content of the hydroxypropyl methylcellulose in the topical composition of the present invention is preferably from 0.001 to 20 w / w %, and more preferably from 0.01 to 10 w / w %.

[0021] The content of pullulan in the composition for external use of the present invention is preferably 0.001 to 20 w / w%, more preferably 0.01 to 10 w / w%.

[0022] The content of sodium chondroitin sulfate in the topical composition of the present invention is preferably 0.001 to 20 w / w%, and more preferably 0.01 to 10 w / w%.

[0023] The content of the gellan gum of the present invention in the topical composition of the present invention is preferably 0.001 to 20 w / w%, and more preferably 0.01 to 10 w / w%.

[0024] The content of carboxymethyldextran sodium in the topical composition of the present invention is preferably 0.001 to 20 w / w%, more preferably 0.01 to 10 w / w%.

[0025] The content of the polyacrylate crosspolymer 11 of the present invention in the topical composition of the present invention is preferably 0.001 to 20 w / w%, more preferably 0.01 to 10 w / w%. As a commercially available product, for example, Aristflex Velvet (product name) sold by Clariant Japan Co., Ltd. can be used.

[0026] The content of the polyethylene glycol of the present invention in the topical composition of the present invention is preferably 0.001 to 20 w / w%, more preferably 0.01 to 10 w / w%. Commercially available products that can be used include, for example, PEG#1000 (trade name) and PEG#4000P (trade name) sold by NOF Corporation.

[0027] The content of the (sodium acrylate / sodium acryloyldimethyltaurate) copolymer of the present invention in the topical composition of the present invention is preferably 0.001 to 20 w / w%, more preferably 0.01 to 10 w / w%. As a commercially available product, for example, SIMULGEL EG (product name) manufactured by SEPPIC SA and sold by Seiwa Kasei Co., Ltd. can be used.

[0028] The content of the hydrophobized hydroxypropyl methylcellulose of the present invention in the topical composition of the present invention is preferably 0.001 to 20 w / w%, more preferably 0.01 to 10 w / w%. As for commercially available products, for example, Sangelose 90L (trade name) and Sangelose 60L (trade name) sold by Daido Chemical Industry Co., Ltd. can be used.

[0029] The topical composition of the present invention is more preferably made to contain a polyhydric alcohol in terms of the coloring suppression effect of the present invention. Examples of the polyhydric alcohol of the present invention include 1,2-pentanediol, glycerin, diglycerin, 1,3-butylene glycol, dipropylene glycol, and 1,2-propanediol. The content of component (d) in the topical composition of the present invention is preferably 0.01 to 30 w / w%, more preferably 0.1 to 20 w / w%.

[0030] The composition for external use of the present invention preferably contains water. The content of water in the composition for external use of the present invention is preferably 1 to 99.99 w / w%, more preferably 20 to 99.9 w / w%, even more preferably 50 to 99.5 w / w%, and even more preferably 60.0 to 98.0 w / w%.

[0031] The viscosity of the topical composition of the present invention is preferably from 1 mPa·s to 10,000 Pa·s (B-type viscometer) at 20°C. More preferably, it is from 3 mPa·s to 1,000 Pa·s (B-type viscometer). In the present application, a B-type viscometer (TVB-25L / TOKI SANGYO CO., LTD.) is used, and the conditions are set in accordance with the instruction manual for this device, and the viscosity is measured at 20°C.

[0032] In addition to the above-mentioned components, the composition for external use of the present invention may be appropriately blended with various components used in ordinary cosmetics, quasi-drugs, pharmaceuticals, etc., within the scope of not impairing the effects of the present invention. For example, pH adjusters (potassium hydroxide, sodium hydroxide, citric acid, sodium citrate, etc.), fragrances, refreshing agents (menthol, peppermint oil, camphor, etc.), anti-inflammatory agents (salicylic acid, glycyrrhizic acid or its salts, glycyrrhetinic acid, allantoin, etc.), bactericides (chlorhexidine gluconate, isopropylmethylphenol, etc.), preservatives (parabens (methylparaben, butylparaben, propylparaben, etc.), benzoic acid or its salts, phenoxyethanol, etc.), moisturizers (hyaluronic acid or its salts, amino acids (L-serine, L-proline, L-hydroxyproline, glycine, etc.), lipidure, sorbitol, maltitol, etc.), extracts of various animals and plants (Coptis chinensis, Phellodendron bark, seaweed, Peony root, licorice, rosemary, sage, etc.), vitamins (retinol palmitate, ascorbic acid, thiamine nitrate, cyanocobalamin, biotin, riboflavin, nicotinamide, etc.), antioxidants (dibutylhydroxytoluene, tocopherol, sodium edetate, ascorbic acid, isopropyl gallate, etc.), solubilizing agents (various vegetable oils, various animal oils, alkyl glyceryl ethers, hydrocarbons, etc.), metabolic activators, adhesives, etc.

[0033] The amounts of these components added are not particularly limited and can be appropriately determined taking into consideration the feel when used, etc.

[0034] The composition for external use of the present invention can be used for applications such as cosmetics, quasi-drugs, and pharmaceuticals. The form of the topical composition of the present invention is not particularly limited as long as it is a formulation that can be applied to the skin. Specific formulations include lotions, creams, milky lotions, gels, packs, etc. The topical composition of the present invention may be a W / O or O / W type emulsion formulation, of which O / W type emulsion formulations are preferred. The topical composition of the present invention can be prepared by a conventional method depending on the dosage form. EXAMPLES

[0035] The present invention will be described in detail below with reference to examples and comparative examples, but the present invention is not limited to the following examples. In the examples and comparative examples, all numerical values ​​mean mass%. The blending amount of the thickener in Comparative Example 3 and Example 12 is described as the amount as a premix raw material.

[0036] (Method of preparing a composition for external use) According to the formulations shown in Tables 1 to 3 below, a heparinoid, placenta extract, a thickener, and a polyhydric alcohol were uniformly mixed with purified water to obtain compositions for external use in Examples 1 to 21 and Comparative Examples 1 to 5. The viscosity of the final composition was measured using a B-type viscometer (TVB-25L / Toki Sangyo Co., Ltd.) at a rotation speed of 60 rpm, rotor No. 1, and a set time of 1 min.

[0037] (Coloring evaluation) Each of the compositions for external use in Examples 1 to 21 and Comparative Examples 1 to 5 was filled into a 30 mL screw tube and stored at 65° C. for 2 weeks. The stored product was transferred to a 20 mL centrifuge tube and centrifuged at 2000 rpm for 10 minutes to remove impurities. The absorbance of the sample was measured at a wavelength of 400 nm to evaluate coloration.

[0038] [Table 1]

[0039] [Table 2]

[0040] [Table 3]

[0041] As is clear from the results of Tables 1 to 3, the compositions for external use containing a thickener selected from the group consisting of heparinoids, placenta extract, and acrylates / alkyl acrylate (C10-30) crosspolymer, cationic guar gum, or acrylates copolymer, were significantly discolored over time (Comparative Examples 1 to 3). On the other hand, the compositions of Examples 1 to 13 containing xanthan gum, hydroxyethyl cellulose, tremella fuciformis polysaccharide, carboxyvinyl polymer, hydroxypropyl methylcellulose, pullulan, sodium chondroitin sulfate, gellan gum, sodium carboxymethyl dextran, polyacrylate crosspolymer 11, polyethylene glycol, (Na acrylate / Na acryloyldimethyl taurate) copolymer, or hydrophobized hydroxypropyl methylcellulose were able to suppress discoloration over time compared to Comparative Examples 1 to 3. In addition, the compositions of Examples 14 to 19 containing polyhydric alcohol in the formulation of Example 4 were confirmed to further suppress discoloration. Furthermore, even when the concentrations of heparinoids and placenta extract were 0.01% and 0.1%, discoloration was suppressed in Examples 20 and 21, which contained a carboxyvinyl polymer, compared to Comparison Examples 4 and 5, which contained an acrylates / alkyl acrylate (C10-30) crosspolymer.

[0042] (Prescription example)

[0043] [Table 4]

[0044] *1: An example of a composition containing 2-methacryloyloxyethyl phosphorylcholine-stearyl methacrylate copolymer is the product name "Lipidure-NR" (manufactured by NOF Corporation). [Industrial Applicability]

[0045] According to the present invention, it is possible to provide a composition for external use which contains a heparinoid, placenta extract, and a thickener and has excellent formulation stability.

Claims

1. The composition contains (a) a heparinoid, (b) a placenta extract, and (c) at least one thickener selected from the group consisting of hydroxyethyl cellulose, xanthan gum, Tremella fuciformis polysaccharide, carboxyvinyl polymer, hydroxypropyl methylcellulose, pullulan, sodium chondroitin sulfate, gellan gum, sodium carboxymethyl dextran, polyacrylate crosspolymer 11, polyethylene glycol, (sodium acrylate / sodium acryloyldimethyltaurate) copolymer, and hydrophobized hydroxypropyl methylcellulose; A composition for external use that is not a hair growth promoting composition and contains vitamin E nicotinate, ethinyl estradiol, ecdysteroid, Chorei extract, Poria columbine extract, Crataegus crenata extract, Sandalwood extract, or minoxidil, The composition for external use is characterized in that the contents of (a) a heparinoid, (b) a placenta extract, and (c) a thickener in the composition for external use are 0.01 to 1.0 w / w%, 0.01 to 1.0 w / w%, and 0.001 to 20 w / w%, respectively.

2. The composition for external use according to claim 1, further comprising (d) a polyhydric alcohol.

3. The composition for external use according to claim 2, wherein the polyhydric alcohol (d) is at least one selected from the group consisting of 1,2-pentanediol, glycerin, diglycerin, 1,3-butylene glycol, dipropylene glycol, and 1,2-propanediol.

4. The composition for external use according to any one of claims 1 to 3, having a viscosity of 1 mPa·s or more at 20°C.

5. The composition for external use according to any one of claims 1 to 4, further comprising (e) water.

6. The composition for external use according to any one of claims 1 to 5, which is in the form of a lotion, cream, emulsion, gel, or pack.

7. The composition for external use according to any one of claims 1 to 6, which is a cosmetic, a quasi-drug, or a pharmaceutical.

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