External composition

Abstract

To provide an external composition that enhances action of an expensive heparin analog with a limited amount of use.SOLUTION: An external composition contains a heparin analog by 0.01 to 0.3 mass% and sodium dextran sulfate by 0.1 to 2 mass%.SELECTED DRAWING: Figure 1

Description

[Technical Field]

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

[0002] Mucopolysaccharides (also called sulfated polysaccharides), such as hyaluronic acid, heparinoids, chondroitin sulfate, and dextran sulfate, have moisturizing, blood circulation-promoting, and anti-inflammatory properties, and 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 are limited to a maximum of 0.3% by mass in pharmaceuticals and 0.1% by mass in quasi-drugs, meaning that the amount cannot be increased even if the effects of the heparinoids are desired to be maximized.

[0004] Incidentally, 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 sulfated 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) a liquid oil, (C) a nonionic surfactant, and (D) one or more selected from (D1) phospholipids and (D2) sterols.

[0005] However, all of these techniques relate to new uses or new dosage forms of mucopolysaccharides, and are not techniques that can enhance the effects of mucopolysaccharides, particularly heparinoids, even within the range of their compounding amounts. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Japanese Patent Application Laid-Open No. 2000-169322 [Patent Document 2] Patent Publication No. 2021-116306 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 effects of heparinoids, which are expensive and have limited amounts that can be used. [Means for solving the problem]

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

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

[0010] The topical composition of the present invention is an excellent one in that the moisturizing effect and skin firming improving effect of the heparinoid are synergistically achieved by the combined use of the heparinoid and dextran sulfate sodium. [Brief explanation 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. [Figure 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. [Figure 3] FIG. 1 is a diagram showing the results of skin viscoelasticity measurement in a test to confirm the firmness improvement effect of Example 1. [Figure 4] FIG. 1 is a diagram showing the results of skin viscoelasticity measurement in a test to confirm the firmness improvement effect of Example 1. DETAILED DESCRIPTION OF THE INVENTION

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

[0013] The heparinoid used in the topical composition of the present invention is a general term for glycosaminoglycans consisting of alternating 1,4-linked uronic acid and glucosamine, which have the same effect as heparin, and are also called heparinoids. The heparinoid used in the topical composition of the present invention may be, for example, any of plant, animal, or 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 a molecular weight of 10,000 to 40,000 is preferred, with a molecular weight of 25,000 to 35,000 being more preferred. This molecular weight is measured by size exclusion chromatography using pullulan as a standard substance.

[0014] Preferred heparinoids used in the topical composition of the present invention include those conforming to the Japanese Pharmacopoeia Non-Drug Standards. Commercially available products of such heparinoids include Heparinoid (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, preferably 0.05 to 0.2% by mass.

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

[0017] Preferred examples of dextran sulfate sodium used in the topical composition of the present invention include those used in ordinary cosmetics, pharmaceuticals, and quasi-drugs. Commercially available examples of such dextran sulfate sodium include dextran sulfate sodium (product name: DST-H, Meito Sangyo Co., Ltd.).

[0018] The content of dextran sulfate sodium 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, more preferably 1:5-10.

[0020] In addition, the topical composition of the present invention preferably contains heparin-like substances and dextran sulfate sodium as mucopolysaccharides, and more preferably contains only heparin-like substances and dextran sulfate sodium as mucopolysaccharides, and does not contain any other mucopolysaccharides.

[0021] In addition to the essential components, the topical composition of the present invention preferably contains other components in accordance with the 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, and oils, 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, UV absorbers such as benzyl paramethoxycinnamate, moisturizers such as sugars, and plant extracts such as aloe extract. These other components may be added to the topical composition of the present invention in appropriate amounts in accordance with the 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, emulsion, cream, ointment, solid paste, paste, solid, powder, etc. Preferred dosage forms of the topical composition of the present invention include liquid, emulsion, cream, etc.

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

[0024] The topical composition of the present invention described above contains specific amounts of heparinoids and dextran sulfate sodium, and therefore has excellent moisturizing and skin firming 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 less sticky and 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 skin of a subject three times a day (morning, noon, and night) or twice a day (morning and night). [Example]

[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 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.) formulated alone and in combination. 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 contained neither heparinoid nor 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> At room temperature of 22°C and relative humidity of 50%, 50μL of each sample was applied to the inner forearm of each subject, and stratum corneum moisture content was measured every 15 minutes for 60 minutes after application using a stratum corneum moisture meter (Corneometer CM825: manufactured by Courage+Khazaka) according to the manual. The relative values, with the stratum corneum moisture content before application set at 100%, are plotted below (Figure 1). Sodium hyaluronate (HA) (manufactured by Speranexus Co., Ltd.) was also measured for stratum corneum moisture content when used alone (Formulation Example 5) and 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 heparinoid or dextran sulfate sodium was used together compared to when either was used alone, confirming that the combined use of heparinoid and dextran sulfate sodium exhibited a synergistic moisturizing effect.

[0032] In contrast, sodium hyaluronate, which is listed as a mucopolysaccharide along with heparinoids and dextran sulfate sodium 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] <Firmness improvement effect confirmation test> For the samples of formulations 1 to 4, skin viscoelasticity measurements were performed using a skin viscoelasticity measurement 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 subject's forearm. 15 minutes after application, the probe was placed in close contact with the skin and sucked for 2 seconds, then released (negative pressure was released). The skin displacement was plotted to evaluate viscoelasticity. R2 is the result of Ua (final return after release of negative pressure) / Uf (maximum suction height) (Figure 3), and R7 is the result of Ur (instantaneous return after release of negative pressure) / UF (maximum suction height) (Figure 4).

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

[0035] Furthermore, when heparinoids and dextran sulfate sodium were used in combination, stickiness and sliminess upon application were suppressed, providing an excellent feel when used.

[0036] Example 2 Preparation of external composition (milky): The following ingredients were mixed and emulsified according to a conventional method to prepare a composition for external use (in the form of a milky lotion). (component) (mass%) Heparinoid 0.2 Dextran sulfate sodium 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-type external composition can exert the same effects as in 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 sulfate sodium 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-like 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 and firming effects, and can be used for various skin care purposes.

Claims

1. A composition for external use, characterized by containing 0.01 to 0.3% by mass of a heparinoid and 0.1 to 2% by mass of dextran sulfate sodium.

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 to 15.

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

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

Images