JP7599762B1 - External Composition - Google Patents

Abstract

The present invention provides a composition for external use that enhances the effects of heparinoids, which are expensive and have limitations on the amount that can be used. The composition for external use contains 0.01 to 0.3% by mass of a heparinoid and 0.1 to 2% by mass of dextran sulfate sodium. [Selected Figure] Figure 1

Description

The present invention relates to a topical composition containing a heparinoid and dextran sulfate sodium.

Mucopolysaccharides (also called sulfate 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 pharmaceutical topical preparations, and in recent years have also become widely used as active ingredients in quasi-drugs.

Heparinoids are particularly expensive among mucopolysaccharides, and their amount is limited to 0.3% by mass or less in pharmaceuticals and 0.1% by mass or less in quasi-drugs. Therefore, even if one wishes to maximize the effects of heparinoids, it is not possible to increase the amount.

There are many known techniques for using mucopolysaccharides in quasi-drugs. 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.

However, all of these technologies were related to new uses or new dosage forms of mucopolysaccharides, and were not technologies that could enhance the effects of mucopolysaccharides, especially heparinoids, even within the range of their formulation amounts.

JP 2000-169322 A JP 2021-116306 A

The objective 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.

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

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 sodium sulfate.
(2) The topical composition described in (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 described in (1) or (2) for improving skin firmness.

The topical composition of the present invention is an excellent product 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.

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. 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. FIG. 2 is a diagram showing the results of skin viscoelasticity measurement in a firmness improvement effect confirmation test in Example 1. FIG. 2 is a diagram showing the results of skin viscoelasticity measurement in a firmness improvement effect confirmation test in Example 1.

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.

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 effect 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, 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 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. This molecular weight is a value measured by size exclusion chromatography using pullulan as a standard substance.

Preferred heparinoids for use in the topical composition of the present invention include those that comply with the Japanese Pharmacopoeia's non-prescription drug standards. Commercially available products of such heparinoids include, for example, Heparinoid (API Co., Ltd.).

The content of the heparinoid in the topical composition of the present invention is 0.01 to 0.3% by mass, preferably 0.05 to 0.2% by mass.

The dextran sulfate sodium used in the topical composition of the present invention is the sodium salt of the sulfate ester of dextran. Examples of the dextran sulfate sodium used in the topical composition of the present invention include fermentation semi-synthetic products in which dextran obtained from dextran-producing bacteria is sulfated and sodium salted. The physical properties of the dextran sulfate sodium are not particularly limited, but it is preferable that the molecular weight is, for example, 1,000 to 3,000. Note that this molecular weight is a value measured by size exclusion chromatography.

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. Examples of commercially available dextran sulfate sodium include dextran sulfate sodium (product name: DST-H, Meito Sangyo Co., Ltd.).

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.

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.

In addition, the topical composition of the present invention preferably contains a heparinoid and dextran sodium sulfate as mucopolysaccharides, and more preferably contains only a heparinoid and dextran sodium sulfate as mucopolysaccharides, and does not contain any other mucopolysaccharides.

In addition to the above 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, ultraviolet absorbers such as benzyl paramethoxycinnamate, moisturizers such as sugars, and plant extracts such as aloe extract. These other components may be contained in the topical composition of the present invention in appropriate amounts in accordance with the various dosage forms.

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

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

The topical composition of the present invention described above contains specific amounts of heparinoids and dextran sulfate sodium, and has excellent moisturizing and skin firming properties, so it can be used for a variety of skin care applications, but is particularly preferably used for moisturizing and improving skin firmness.

In addition, the topical composition of the present invention reduces stickiness and sliminess when applied, providing an excellent feel when used.

When using such a topical composition of the present invention for various skin care applications, for example, an appropriate amount may be applied to the subject's skin three times a day, morning, noon, and night, or twice a day, morning and night.

The present invention will be described in detail below with reference to examples of the present invention, but the present invention is not limited to these examples.

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 contained neither heparinoid nor dextran sodium sulfate, served as the control. The compositions of formulations 1 to 6 are shown in Table 1.

<Moisturizing effect confirmation test>
Under the 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). Similarly, the moisture content of the keratin was measured for sodium hyaluronate (HA) (manufactured by SperaNexus Co., Ltd.) when used alone (Formulation Example 5) and when used in combination with a heparinoid (Formulation Example 6) (Figure 2).

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 in combination compared to when either was used alone, confirming that the combined use of heparinoid and dextran sulfate sodium provided a synergistic moisturizing effect.

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

<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 placed in close contact with the skin and sucked for 2 seconds, then released (negative pressure was released), and the deformation of the skin was plotted to evaluate viscoelasticity. R2 is the result of Ua (final return after negative pressure is released)/Uf (maximum suction height) (Figure 3), and R7 is the result of Ur (instantaneous return after negative pressure is released)/UF (maximum suction height) (Figure 4).

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.

In addition, when heparinoids and sodium dextran sulfate were used in combination, the stickiness and sliminess upon application were suppressed, providing an excellent feel when used.

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).
(Components) (% by 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 Residual

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

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).
(Components) (% by 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 Residual

This cream-like composition for external use can exert the same effect as that of Example 1.

The topical composition of the present invention has excellent moisturizing and firming effects, and can be used for various skin care purposes.

Claims (4)

A composition for external use, comprising 0.01 to 0.3% by mass of a heparinoid having a molecular weight of 10,000 to 40,000 and 0.1 to 2% by mass of dextran sodium sulfate having a molecular weight of 1,000 to 3,000 . 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. The composition for external use according to claim 1 or 2, which is for moisturizing purposes. The topical composition according to claim 1 or 2, which is used to improve skin firmness.