External composition

Abstract

The present invention provides a composition for external use that enhances the effect of heparinoids, which are expensive and have limitations on the amount that can be used. [Solution] A composition for external use containing 0.01 to 0.3 mass % of a heparinoid and 0.1 to 2 mass % of dextran sulfate sodium.

Description

[Technical field]

[0001] The present invention relates to a composition for external use containing a heparinoid and dextran sulfate sodium. [Background technology]

[0002] Mucopolysaccharides (also called sulfate polysaccharides) such as hyaluronic acid, heparinoids, chondroitin sulfate, and dextran sulfate have moisturizing, blood circulation promoting, and anti-inflammatory effects, and therefore have traditionally been used as active ingredients in topical pharmaceutical preparations. In recent years, they have also become increasingly popular as active ingredients in quasi-drugs.

[0003] Among mucopolysaccharides, heparinoids are particularly expensive, and their content is limited to 0.3% by mass or less in pharmaceuticals and 0.1% by mass or less in quasi-drugs, meaning that the content cannot be increased even if one wishes to maximize the effects of the heparinoids.

[0004] Meanwhile, numerous techniques for utilizing mucopolysaccharides in quasi-drugs have been known to date. For example, Patent Document 1 discloses a pore contracting agent containing as an active ingredient one or more sulfate polysaccharides selected from the group consisting of dextran sulfate, fucoidan, chondroitin sulfate, heparin, and carrageenan. Patent Document 2 discloses a liquid oily composition containing (A) one or more mucopolysaccharides selected from hyaluronic acid, heparinoids, chondroitin sulfate, dextran sulfate, and salts thereof, (B) liquid oil, (C) a nonionic surfactant, and (D) one or more selected from (D1) phospholipids and (D2) sterols.

[0005] However, all of these techniques are related to new uses or new dosage forms of mucopolysaccharides, and are not techniques capable of enhancing the effects of mucopolysaccharides, particularly heparinoids, even within the range of the blend amount. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] JP 2000-169322 A [Patent Document 2] JP 2021-116306 A Summary of the Invention [Problem to be solved by the invention]

[0007] An object of the present invention is to provide a composition for external use that enhances the effect of heparinoids, which are expensive and have limitations on the amount that can be used. [Means for solving the problem]

[0008] As a result of intensive research into solving the above-mentioned problems, the inventors discovered that a topical composition containing a heparinoid and dextran sulfate sodium in a specific mass range can solve the above-mentioned problems, and thus completed the present invention.

[0009] That is, the present invention is as follows. (1) A composition for external use, comprising 0.01 to 0.3% by mass of a heparinoid and 0.1 to 2% by mass of dextran sodium sulfate. (2) The composition for external use described in (1), which contains a heparinoid and dextran sulfate sodium in a mass ratio of 1:5 to 15. (3) The composition for external use described in (1) or (2) for moisturizing purposes. (4) The topical composition according to (1) or (2), which is used to improve skin firmness. Effect of the Invention

[0010] The composition for external use of the present invention is an excellent one in which the moisturizing effect and skin firming improving effect of the heparinoid are synergistically achieved by using the heparinoid in combination with dextran sulfate sodium. [Brief description of the drawings]

[0011] [Figure 1] FIG. 2 is a graph showing the results of measuring the moisture content of the stratum corneum in the moisturizing effect confirmation test of Example 1. [Diagram 2] FIG. 2 is a graph showing the results of measuring the moisture content of the stratum corneum in the moisturizing effect confirmation test of Example 1. [Diagram 3] FIG. 2 is a diagram showing the results of skin viscoelasticity measurement in a firmness improvement effect confirmation test in Example 1. [Figure 4] FIG. 2 is a diagram showing the results of skin viscoelasticity measurement in a firmness improvement effect confirmation test in Example 1. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] The composition for external use of the present invention contains 0.01 to 0.3% by mass of a heparinoid and 0.1 to 2% by mass of dextran sodium sulfate.

[0013] The heparinoid used in the topical composition of the present invention is a general term for glycosaminoglycans in which uronic acid and glucosamine are alternately 1,4-bonded, and has the same action as heparin, and is also called heparinoid. The heparinoid used in the topical composition of the present invention may be, for example, any of plant, animal, and synthetic oligosaccharides and sulfated polysaccharides, but animal-derived substances extracted from animal organs are preferred. The physical properties of the heparinoid are not particularly limited, but for example, those with a molecular weight of 10,000 to 40,000 are preferred, and those with a molecular weight of 25,000 to 35,000 are more preferred. The molecular weight is a value measured by size exclusion chromatography using pullulan as a standard substance.

[0014] A preferred example of the heparinoid used in the topical composition of the present invention is one that complies with the Japanese Pharmacopoeia's non-prescription drug standards. Commercially available products of such heparinoids include, for example, heparinoids (API Co., Ltd.).

[0015] The content of the heparinoid in the composition for external use of the present invention is 0.01 to 0.3% by mass, and preferably 0.05 to 0.2% by mass.

[0016] The dextran sulfate sodium used in the topical composition of the present invention is a sodium salt of a sulfate ester of dextran. Examples of the dextran sulfate sodium used in the topical composition of the present invention include fermentation semi-synthetic products obtained by sulfate esterification and sodium salting of dextran obtained from dextran-producing bacteria. The physical properties of the dextran sulfate sodium are not particularly limited, but for example, a molecular weight of 1,000 to 3,000 is preferred. The molecular weight is a value measured by size exclusion chromatography.

[0017] Dextran sulfate sodium used in the topical composition of the present invention is preferably used in ordinary cosmetics, medicines, and quasi-drugs. Examples of commercially available dextran sulfate sodium include dextran sulfate sodium (product name: DST-H, Meito Sangyo Co., Ltd.).

[0018] The content of dextran sodium sulfate in the topical composition of the present invention is 0.1 to 2% by mass, preferably 0.5 to 1.0% by mass.

[0019] In the topical composition of the present invention, the mass ratio of the heparinoid to dextran sulfate sodium is not particularly limited, but is preferably 1:5-15, and more preferably 1:5-10.

[0020] In addition, in the topical composition of the present invention, it is preferable that the mucopolysaccharides contain a heparin-like substance and dextran sodium sulfate, and it is more preferable that the mucopolysaccharides contain only a heparin-like substance and dextran sodium sulfate, and that the mucopolysaccharides do not contain any other mucopolysaccharides.

[0021] In addition to the above-mentioned essential components, the topical composition of the present invention is preferably made to contain other components according to various dosage forms.For example, if the dosage form is liquid, such other components include bases such as water, butylene glycol, glycerin, dipropylene glycol, sorbitol, oil, etc., chelating agents such as EDTA, pH adjusters such as citric acid and sodium citrate, thickeners such as xanthan gum, preservatives such as ethylhexylglycerin, parabens, and phenoxyethanol, surfactants such as nonionic surfactants, anionic surfactants, cationic surfactants, and amphoteric surfactants, vitamins such as vitamin A and vitamin E, ultraviolet absorbers such as benzyl paramethoxycinnamate, moisturizers such as sugars, and plant extracts such as aloe extract.These other components can be contained in the topical composition of the present invention in an appropriate amount according to various dosage forms.

[0022] The dosage form of the topical composition of the present invention is not particularly limited, and examples thereof include known dosage forms of topical agents such as liquid, gel, sherbet, milky lotion, cream, ointment, solid paste, paste, solid, powder, etc. Preferred dosage forms of the topical composition of the present invention include liquid, milky lotion, cream, etc.

[0023] The topical composition of the present invention can be prepared by known methods for preparing topical agents, except that it contains a heparinoid and dextran sulfate sodium.

[0024] The topical composition of the present invention described above contains specific amounts of a heparinoid and dextran sulfate sodium, and thus has excellent moisturizing effects and skin firmness improving effects, and can be used for various skin care purposes, but is particularly preferably used for moisturizing and improving skin firmness.

[0025] Furthermore, the topical composition of the present invention is suppressed from being sticky or slimy when applied, providing an excellent feel when used.

[0026] When such a topical composition of the present invention is used for various skin care purposes, for example, an appropriate amount may be applied to the subject's skin three times a day, in the morning, afternoon and evening, or twice a day, in the morning and evening. EXAMPLES

[0027] The present invention will be described in detail below by way of examples of the present invention, but the present invention is not limited to these examples in any way.

[0028] Example 1 Preparation of topical composition (liquid): A test was conducted to compare the moisturizing effects of using either a heparinoid (API Co., Ltd., molecular weight approximately 30,000) or dextran sodium sulfate (product name: DST-H (molecular weight approximately 2,000), Meito Sangyo Co., Ltd.) alone with a combination of both. Samples were prepared using 0.1% heparinoid alone (formulation 2), 1% dextran sodium sulfate alone (formulation 3), and a combination of heparinoid and dextran sodium sulfate (half the amount of each used alone; formulation 4). Formulation 1, which did not contain either heparinoid or dextran sodium sulfate, served as the control. The compositions of formulations 1 to 6 are shown in Table 1.

[0029] [Table 1]

[0030] <Moisturizing effect confirmation test> Under conditions of room temperature 22°C and relative humidity 50%, 50μL of each sample was applied to the inside of the forearm of the subject, and the moisture content of the keratin was measured every 15 minutes for 60 minutes after application using a keratin moisture meter (Corneometer CM825: manufactured by Courage+Khazaka) according to the manual. The relative values ​​plotted with the moisture content of the keratin before application set at 100% are shown below (Figure 1). The moisture content of the keratin was also measured in the same way for sodium hyaluronate (HA) (manufactured by SperaNexus Co., Ltd.), both when used alone (Formulation Example 5) and when used in combination with a heparinoid (Formulation Example 6) (Figure 2).

[0031] As shown in Figure 1, the moisture content of the stratum corneum was higher when half the amount of each was used in combination compared to when either a heparinoid or dextran sulfate sodium was used alone, confirming that the combined use of a heparinoid and dextran sulfate sodium provides a synergistic moisturizing effect.

[0032] In contrast, sodium hyaluronate, which is listed as a mucopolysaccharide along with heparinoids and sodium dextran sulfate in prior art (2), had almost no effect when used alone, and no enhancing effect was observed when used in combination with heparinoids (Figure 2).

[0033] <Test to confirm the effect of improving firmness> For the samples of formulations 1 to 4, skin viscoelasticity was measured using a skin viscoelasticity measuring probe (Cutomerter CT580-2 (probe diameter 2 mm): manufactured by Courage+Khazaka) according to the manual. 50 μL of each sample was applied to the inside of the forearm of the subject, and 15 minutes after application, the probe was attached to the skin and sucked for 2 seconds, then released (negative pressure was released). The skin deformation was plotted to evaluate the viscoelasticity. R2 is the result of Ua (final return after negative pressure release) / Uf (maximum suction height) (Figure 3), and R7 is the result of Ur (instantaneous return after negative pressure release) / UF (maximum suction height) (Figure 4).

[0034] As shown in Figures 3 and 4, skin viscoelasticity was higher when half the amount of each was used in combination compared to when either a heparinoid or dextran sulfate sodium was used alone, confirming that the combined use of a heparinoid and dextran sulfate sodium showed a synergistic effect in improving skin firmness.

[0035] Furthermore, when a heparinoid and dextran sulfate sodium were used in combination, the sticky and slimy feeling upon application was suppressed, providing an excellent feel when used.

[0036] Example 2 Preparation of external composition (milky lotion): The following ingredients were mixed and emulsified according to a conventional method to prepare a composition for external use (lotion type). (component) (mass%) Heparinoid 0.2 Dextran Sodium Sulfate 1.0 Nonionic Surfactant 2.0 Polyhydric alcohol 5.0 Higher Alcohol 2.0 Ester oil 6.0 Liquid Paraffin 2.0 Purified water remainder

[0037] This emulsion-like composition for external use can exert the same effects as those of Example 1.

[0038] Example 3 Preparation of topical composition (cream): The following ingredients were mixed and emulsified according to a conventional method to prepare a composition for external use (cream-like). (component) (mass%) Heparinoid 0.3 Dextran Sodium Sulfate 2.0 Nonionic Surfactant 3.0 Polyhydric alcohol 10.0 Higher alcohol 4.0 Ester oil 8.0 Liquid Paraffin 4.0 Purified water remainder

[0039] This cream-type composition for external use can exert the same effects as those of Example 1. [Industrial Applicability]

[0040] The topical composition of the present invention has excellent moisturizing effects, firmness improving effects, etc., and can be used for various skin care purposes.

Claims

1. A composition for external use, characterized by containing 0.01 to 0.3 mass% of a heparinoid substance having a molecular weight of 10,000 to 40,000 and 0.1 to 2 mass% of dextran sodium sulfate having a molecular weight of 1,000 to 3,000.

2. 2. The composition for external use according to claim 1, which contains a heparinoid and dextran sulfate sodium in a mass ratio of 1:5-15.

3. 3. The composition for external use according to claim 1 or 2, which is for moisturizing purposes.

4. 3. The composition for external use according to claim 1 or 2, which is used to improve skin firmness.

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