JP7615564B2 - External Composition - Google Patents

Description

Article 30, paragraph 2 of the Patent Act applies (1) September 20, 2019 Website: https://www.catalog-taisho.com/2900.php (2) May 18, 2020 Website: https://www.taisho-direct.jp/products/detail/ADYLM-00-L2F000X (3) October 1 and 23, 2019 Website: https://taisho-beauty.jp/TB/shop/g/gTB9999-10/ (4) August 27, 2019 Website: https://www. taisho. co. jp/company/news/2019/20190827000229. (5) December 7, 2019 - December 15, 2019 Samples distributed at the 1st floor atrium of KITTE Marunouchi (6) October 24, 2019 Samples distributed at Laguna Veil Atelier Shibuya (7) December 16, 2019 Samples distributed at Laguna Veil Atelier Shibuya (8) December 20, 2019 Samples mailed to customers (9) January 31, 2020 - May 15, 2020 Samples included with purchasers of Taisho Pharmaceutical products (10) January 31, 2020 - May 15, 2020 Samples included with regular purchasers of the Moist Care Set, a Taisho Pharmaceutical product (11) March 23, 2020 - April 23, 2020 Samples included with purchasers of Oisix

The present invention relates to a composition for external use that contains a heparinoid and a placenta extract.

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 when heparinoids are incorporated into topical preparations, poor usability is an issue, 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 mainly composed of polysulfated polysaccharides, which can cause some irritation to the skin, but 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).

Placenta extract is an extract extracted from the placenta of mammals such as pigs, cows, horses, humans, or sheep. Mammalian placental tissue is rich in amino acids, active peptides, vitamins, minerals, sugars, enzymes, nucleic acids, and other nutrients essential for fetal growth, and the extract extracted from the placenta of such mammals is called placenta extract. The placenta extract has benefits such as cell proliferation, immune system improvement, blood pressure improvement, 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).

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 depending on the formulation. Specifically, water-soluble polymers such as carboxyvinyl polymer, xanthan gum, cellulose, guar gum, alginic acid, polyacrylic acid, polyvinyl alcohol, and acrylates/alkyl acrylate (C10-30) crosspolymer are often used as the thickener. By using these according to the purpose and changing the blending amount and blending components, it is possible to prepare low-viscosity formulations such as the thickness of lotions to solid gels such as hair tics (Patent Document 5). In addition, formulations such as viscous cosmetics are often used as they have improved marketability due to their excellent thick appearance, rich feeling during use, and moisturizing feeling (Patent Document 6).

Adraise (registered trademark) Active Lotion was released in May 2019 as a cosmetic product containing a heparinoid and placenta extract. However, no topical composition containing a heparinoid, 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 a heparinoid and placenta extract affects the formulation.

JP 2000-143486 A JP 2017-66060 A JP 2015-203029 A JP 2011-160742 A JP 2017-36217 A JP 2014-185118 A

In order to provide a topical composition with a different viscosity from previous compositions, the present inventors mixed a water-soluble thickener into a topical composition containing a heparinoid and placenta extract and stored it, but discovered a new problem in that coloring occurred over time and the stability of the formulation was poor. Coloring of the formulation is undesirable from the standpoint of formulation stability and marketability.

The present invention was made in consideration of the above-mentioned circumstances, and its purpose is to provide a composition for external use that contains a heparinoid and placenta extract and suppresses discoloration over time.

The inventors conducted extensive research to solve the above problems and discovered that a topical composition containing a heparinoid, placenta extract, and a specific thickener can solve the above problems. They also discovered that adding a polyhydric alcohol provides a greater improvement, which led to the completion of the present invention.

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) 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), having 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 is in the 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:

The present invention makes it possible to provide a topical composition that contains a heparinoid, placenta extract, and a specific thickener, suppresses discoloration, and has excellent formulation stability.

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

The content of the heparinoid in the topical composition of the present invention is preferably 0.001 to 10 w/w%, and more preferably 0.01 to 1.0 w/w%.

The placenta extract in the topical composition of the present invention may originate from, for example, human, bovine, porcine, equine, or ovine sources, with porcine being preferred. Commercially available products (e.g., Biocatalyzer Placenta APF (SW) (M-PE-APF)) may also be used as placenta extract. The content of the placenta extract of the present invention in the topical composition of the present invention is preferably 0.001 to 10 w/w%, more preferably 0.01 to 1.0 w/w%.

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, (sodium acrylate/sodium 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.

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

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

The Tremella fuciformis polysaccharide of the present invention can be extracted from the fruiting 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%.

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%, and more preferably 0.01 to 10 w/w%. If necessary, the pH can be adjusted to achieve a further thickening effect.

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

The content of pullulan in the topical composition of the present invention is preferably 0.001 to 20 w/w%, more preferably 0.01 to 10 w/w%.

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

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

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%.

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%, and more preferably 0.01 to 10 w/w%. If it is a commercially available product, for example, Aristflex Velvet (product name) sold by Clariant Japan Co., Ltd. can be used.

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%, and 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.

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%, and more preferably 0.01 to 10 w/w%. If it is a commercially available product, for example, SIMULGEL EG (product name) manufactured by SEPPIC S.A. and sold by Seiwa Kasei Co., Ltd. can be used.

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%. Commercially available products that can be used include, for example, Sangelose 90L (trade name) and Sangelose 60L (trade name) sold by Daido Chemical Industry Co., Ltd.

The topical composition of the present invention is more preferable in terms of the coloring suppression effect of the present invention if it contains a polyhydric alcohol. 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%, and more preferably 0.1 to 20 w/w%.

The topical composition of the present invention preferably contains water. The content of water in the topical composition 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%.

The viscosity of the topical composition of the present invention is preferably 1 mPa·s or more and 10,000 Pa·s or less (B-type viscometer) at 20°C. More preferably, it is 3 mPa·s or more and 1,000 Pa·s or less (B-type viscometer). In this 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.

In addition to the above-mentioned components, the topical composition 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, glyceryl stearate, etc.), glyceryl stearate, ... lysine, lipidure, sorbitol, maltitol, etc.), extracts of various plants and animals (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.

There are no particular restrictions on the amounts of these ingredients added, and they can be determined appropriately while taking into consideration the feel when used, etc.

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 an O/W type emulsion formulation is preferred.
The topical composition of the present invention can be prepared by a conventional method depending on the dosage form.

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

(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 compositions 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.

(Evaluation of Coloration)
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 products were transferred to 20 mL centrifuge tubes and centrifuged at 2000 rpm for 10 minutes to remove impurities. The absorbance of the samples was measured at a wavelength of 400 nm to evaluate coloration.

As is clear from the results of Tables 1 to 3, the compositions for external use containing a heparinoid, placenta extract, and a thickener selected from the group consisting of 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, (sodium acrylate/sodium acryloyldimethyltaurate) 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, which contained a 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 carboxyvinyl polymer, compared to Comparative Examples 4 and 5, which contained acrylates/alkyl acrylate (C10-30) crosspolymer.

(Prescription example)

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

The present invention makes it possible to provide a topical composition with excellent formulation stability by incorporating a heparinoid, placenta extract, and a thickener.

Claims (7)

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 . The topical composition according to claim 1, further comprising (d) a polyhydric alcohol. The topical composition according to claim 2, wherein (d) 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. The composition for external use according to any one of claims 1 to 3, which has a viscosity of 1 mPa·s or more at 20°C. The composition for external use according to any one of claims 1 to 4 further contains (e) water. The composition for external use according to any one of claims 1 to 5, which is in the form of a lotion, cream, milky lotion, gel, or pack. The composition for external use according to any one of claims 1 to 6, which is a cosmetic, a quasi-drug, or a pharmaceutical.