JP7271927B2 - external composition - Google Patents

Description

TECHNICAL FIELD The present invention relates to an external composition containing a heparinoid and having excellent formulation stability.

Heparin-like substances are a type of acidic mucopolysaccharide, and have a wide range of effects such as moisturizing effects on the skin, anti-inflammatory effects, blood flow promotion, and treatment and prevention of scars and keloids. included in the formulation. Conventionally, various studies have been conducted to improve the effects of heparin analogues. For example, by using betaines in combination with heparin analogues, the action of heparin analogues, such as enhancement of stratum corneum moisture retention, and the moisturizing action of betaine synergize. It is known that it acts effectively and exhibits a remarkable improvement and prevention effect against rough skin (Patent Document 1). In this way, while usefulness to the skin has been shown, it is known that when a heparin analogue is incorporated into an external preparation, the poor feeling of use becomes a problem. It is reported that the feeling of use can be improved (Patent Document 2). Heparin analogues are also used for the treatment of xerosis and atopic dermatitis. Since heparin-like substances are mainly composed of polysulfated polysaccharides, they cause some irritation to the skin. Development of formulations that minimize irritation is underway (Patent Document 3).

JP-A-2000-143486 JP 2017-66060 A JP 2015-203029 A

When the present inventors prepared and stored a composition for external use containing a heparin analogue, they found that the coloration and odor of the composition changed over time, and that the stability of the formulation was poor. To date, there have been no reports on problems such as changes in coloration and odor over time in formulations containing heparinoids. Changes in coloration and odor of formulations are undesirable from the standpoint of formulation stability and marketability, and means for preventing these problems are desired.

An object of the present invention is to provide an external composition containing a heparinoid and having excellent formulation stability.

As a result of intensive studies to solve the above problems, the present inventors found that the above problems can be solved by adding a placenta extract and an electrolyte to an external composition containing a heparinoid and water. I have perfected my invention.

That is, the present invention
(1) A composition for external use comprising (a) a heparinoid, (b) a placenta extract, (c) an inorganic electrolyte, and (d) water;
(2) (c) The composition for external use according to (1), wherein the inorganic electrolyte is at least one selected from the group consisting of sodium salts, magnesium salts, calcium salts, and potassium salts;
(3) (c) The composition for external use according to (1) or (2), wherein the inorganic electrolyte is at least one selected from the group consisting of sodium chloride, magnesium chloride, calcium chloride, potassium chloride, and magnesium sulfate. thing,
(4) The composition for external use according to any one of (1) to (3), wherein the dosage form is lotion, cream, milky lotion, gel, or pack;
(5) The external composition according to any one of (1) to (4), which is a cosmetic, quasi-drug, or pharmaceutical.

INDUSTRIAL APPLICABILITY According to the present invention, it has become possible to provide a composition for external use containing a heparinoid and having excellent formulation stability.

For each component used in the composition for external use of the present invention, those having the quality normally used in pharmaceuticals, quasi-drugs, or cosmetics can be appropriately used.

The content of the heparin analogue in the composition for external use of the present invention is preferably 0.01 to 5 w/w%, more preferably 0.1 to 0.5 w/w%.
The origin of the placenta extract in the composition for external use of the present invention includes, for example, human, bovine, porcine, horse, and sheep, preferably porcine. In addition, commercially available placenta extracts (eg, biocatalyst placenta APF (SW) (M-PE-APF)) may be used.

The content of the placenta extract of the present invention is preferably 0.01 to 5 w/w%, more preferably 0.1 to 0.5 w/w%, in the topical composition of the present invention. Also, it is preferably 0.001 to 500 parts by mass, more preferably 0.01 to 50 parts by mass, based on 1 part by mass of the heparinoid.
The electrolyte in the present invention includes sodium chloride, magnesium chloride, calcium chloride, potassium chloride, magnesium sulfate and the like, among which sodium chloride, magnesium chloride, calcium chloride and magnesium sulfate are particularly preferred. The electrolyte content in the composition for external use of the present invention is preferably 0.01 to 10 w/w%, more preferably 0.1 to 5 w/w%. Also, it is preferably 0.001 to 1000 parts by mass, more preferably 0.01 to 500 parts by mass, based on 1 part by mass of the heparinoid.

The composition for external use of the present invention contains water. The content of water in the topical composition of the present invention is preferably 1 to 99.9 w/w%, more preferably 50 to 99.9 w/w%.

In addition to the above components, the composition for external use of the present invention can appropriately contain various components used in ordinary cosmetics, quasi-drugs, pharmaceuticals, etc., as long as the effects of the present invention are not impaired. For example, pH adjusters (citric acid, sodium citrate, etc.), fragrances, cooling agents (menthol, peppermint oil, camphor, etc.), anti-inflammatory agents (salicylic acid, glycyrrhizic acid or its salts, glycyrrhetinic acid, allantoin, etc.), sterilization agents (chlorhexidine gluconate, isopropylmethylphenol, etc.), preservatives (parabens (methylparaben, butylparaben, propylparaben, etc.), benzoic acid or its salts, phenoxyethanol, etc.), moisturizing agents (hyaluronic acid or its salts, chondroitin sulfate, Polyhydric alcohols (glycerin, diglycerin, 1,3-butylene glycol, propylene glycol, 1,2-pentanediol, etc.), amino acids (L-serine, L-proline, L-hydroxyproline, etc.), etc.), various animals and plants ( Coptis, Phellodendron bark, seaweed, botanpi, licorice, rosemary, sage, etc.) extract, vitamins (retinol palmitate, ascorbic acid, thiamine nitrate, cyanocobalamin, biotin, riboflavin, nicotinamide, etc.), antioxidant (dibutyl) Hydroxytoluene, tocopherol, sodium edetate, ascorbic acid, isopropyl gallate, etc.), solubilizers (various vegetable oils, various animal oils, alkylglyceryl ethers, hydrocarbons, etc.), metabolic activators, gelling agents (water-soluble polymers ( carboxyvinyl polymer, hydroxyethylcellulose, hydroxypropylmethylcellulose, etc.), oily gelling agents (inulin stearate, dextrin palmitate, etc.), adhesives, and the like.

The amount of these components to be added is not particularly limited, and can be appropriately determined in consideration of the feeling of use and the like.

The composition for external use of the present invention can be used for applications such as cosmetics, quasi-drugs, and pharmaceuticals.

The composition for external use in the present invention is a composition for external use containing water as component (d).

The form of the composition for external use of the present invention is not particularly limited as long as it is a dosage form that can be applied to the skin. Specific dosage forms include lotions, creams, milky lotions, gels, packs, bath salts and the like. Among these dosage forms, lotions and creams are particularly preferred.

The composition for external use of the present invention can be produced by a conventional method depending on the dosage form.

EXAMPLES The present invention will be described in detail below with reference to Examples, Comparative Examples and Test Examples, but the present invention is not limited to the following examples. In addition, in the examples and comparative examples, all the numerical values mean % by mass.

(Method for preparing composition for external use)
According to the formulations shown in Tables 1 and 2 below, a heparinoid, placenta extract (Biocatalyst placenta APF (SW) (M-PE-APF) manufactured by BIODELL BIOCHEMICAL SA), and electrolytes are uniformly dissolved in purified water. Then, external compositions of Examples 1-8 and Comparative Examples 1-5 were obtained.

(Test Example 1: Evaluation of odor)
5 mL of each external composition of Examples 1 to 7 and Comparative Examples 1 to 4 was filled in a 10 mL screw tube and stored at 65° C. for 2 weeks, and three panelists confirmed the change in odor immediately after preparation by sensory evaluation. bottom.
(Odor evaluation criteria)
○: No change in odor ×: Change in odor (with unpleasant odor)

As is clear from the results in Table 1, the topical composition containing the heparinoid produced an unpleasant odor over time (Comparative Examples 1, 3 and 4). The composition for external use containing the heparin analogue and the placenta extract also developed an unpleasant odor over time (Comparative Example 2). On the other hand, the composition for external use containing the heparin analogue, the placenta extract and the electrolyte inhibited the change in odor over time (Examples 1 to 7).

(Test Example 2: Evaluation of coloring)
5 mL of each of the external compositions of Examples 1 to 5 and 8 and Comparative Examples 1 and 5 was filled in a 10 mL screw tube and stored at 65° C. for 2 weeks. Absorbance was measured at a wavelength of 400 nm immediately after preparation and stored at 65° C. for 2 weeks to evaluate coloration.

The composition for external use containing only the heparin analogue was remarkably colored over time (Comparative Examples 1 and 5). On the other hand, as shown in Examples 1 to 5 and 8, when the placenta extract and the electrolyte were blended together, coloration over time could be suppressed as compared with each comparative example.
(prescription example)
According to the formulation shown in Table 3 below, each component was uniformly dissolved in water to obtain a composition for external use. In addition, all numerical values in Formulation Example 1 below mean % by mass.

*1: The 2-methacryloyloxyethylphosphorylcholine/stearyl methacrylate copolymer-containing composition used was trade name “Lipidure-NR” (manufactured by NOF Corporation).
*2: Ascorbyl tetra-2-hexyldecanoate-containing composition used the product name “SBG-24” (manufactured by Yamakawa Trading Co., Ltd.).

INDUSTRIAL APPLICABILITY According to the present invention, it has become possible to provide a composition for external use containing a heparinoid and having excellent formulation stability.

Claims (4)

Characterized by containing (a) a heparin-like substance, (b) placenta extract, (c) an inorganic electrolyte that is at least one selected from the group consisting of sodium salts, magnesium salts, and calcium salts , and (d) water A composition for external use. (a) a heparin analogue, (b) placenta extract, (c) an inorganic electrolyte that is at least one selected from the group consisting of sodium chloride, magnesium chloride, calcium chloride, potassium chloride, and magnesium sulfate , and (d) A composition for external use, characterized by containing water. 3. The composition for external use according to claim 1 or 2 , wherein the dosage form is lotion, cream, emulsion, gel or pack. The external composition according to any one of claims 1 to 3 , which is a cosmetic, quasi-drug, or pharmaceutical.