Topical skin composition and method for dispersion stabilization of heparin-like substance

Abstract

To provide a topical skin composition or the like which achieves improved dispersion stability of a heparin-like substance.SOLUTION: The present invention provides a topical skin composition comprising a heparin-like substance and a zinc oxide compound. Assuming that the content of the heparin-like substance in the topical skin composition is x (mass%) and the concentration of free zinc is y (ppm), the following relational expressions (1) and (2) are satisfied where 0.01≤x≤5. (1) y≤18.4x+1.92(0.01≤x<0.1), (2) y≤9x+2.86(0.1≤x≤5).SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a topical skin composition and a method for dispersing and stabilizing a heparin-like substance.

Background Art

[0002] Generally, as a component formulated in a topical skin composition, a heparin-like substance having effects such as excellent moisturizing action, anti-inflammatory action, and blood circulation promoting action is known. In addition, powders such as silicon dioxide and metal oxides are used as components for protecting the skin from ultraviolet rays, concealing wrinkles, pores, etc. to make them less noticeable, and improving the usability such as a smooth feeling.

[0003] Conventionally, topical skin compositions as disclosed in Patent Documents 1 and 2 are known. The topical skin composition of Patent Document 1 contains ceramide and a heparin-like substance. Such a topical skin composition improves the moisture retention effect of the skin, normalizes the skin barrier function, and effectively improves dry skin. Further, Patent Document 2 contains a powder such as a predetermined silicon dioxide and a heparin-like substance.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0005] However, in a liquid topical skin composition, when a heparin-like substance and a zinc oxide compound as a metal oxide coexist, the dispersion stability of the heparin-like substance decreases due to the electrostatic interaction between the zinc oxide compound itself and the heparin-like substance and the interaction between the free zinc released from the zinc oxide compound and the heparin-like substance.

Means for Solving the Problem

[0006] As a result of focusing on and researching, among the above problems, particularly on the "interaction between free zinc released from a zinc oxide compound and a heparin-like substance", the inventors of the present invention newly found that the dispersion stability of the heparin-like substance can be improved by defining the blending amount of the heparin-like substance and the concentration of free zinc so as to satisfy a predetermined relationship.

[0007] Each aspect for solving the above problems will be described. The skin external composition of Aspect 1 is a skin external composition containing a heparin-like substance and a zinc oxide compound. When the blending amount of the heparin-like substance in the skin external composition is x (mass%) and the concentration of free zinc is y (ppm), in the case of 0.01 ≦ x ≦ 5, it is characterized by satisfying the following relational expressions (1) and (2).

[0008] (1) y ≦ 18.4x + 1.92 (0.01 ≦ x < 0.1) (2) y ≦ 9x + 2.86 (0.1 ≦ x ≦ 5) Aspect 2 is the skin external composition according to Aspect 1, wherein the zinc oxide compound is a compound having a coating layer formed on the surface of zinc oxide particles.

[0009] Aspect 3 is the skin external composition according to Aspect 2, wherein the coating layer is composed of at least one selected from hydrous silica, silicone compounds, fluorine compounds, silane coupling agents, oily components, dextrin fatty acid esters, amino acids, lecithin, ceramides, and surfactants.

[0010] Aspect 4 is the skin external composition according to any one of Aspects 1 to 3, wherein the blending amount of the zinc oxide compound is 1.5 mass% or more as the amount of zinc oxide. Aspect 5 is the topical skin composition according to any one of Aspects 1 to 4, wherein when the ratio (B×100 / A) of the content (B) determined using a UV detector in the topical skin composition to the amount (A) of the heparin-like substance incorporated into the topical skin composition is taken as a quantitative value (%), the quantitative value is 90% or more.

[0011] Aspect 6 is the topical skin composition according to any one of Aspects 1 to 5, wherein the topical skin composition is an oil-in-water emulsion or a water-in-oil emulsion. Aspect 7 is the topical skin composition according to any one of Aspects 1 to 6, wherein the zinc oxide compound is fine particle zinc oxide.

[0012] The method for stabilizing the dispersion of a heparin-like substance according to Aspect 8 is a method for stabilizing the dispersion of a heparin-like substance in a topical skin composition containing a heparin-like substance and a zinc oxide compound. When the amount of the heparin-like substance incorporated into the topical skin composition is x (% by mass) and the concentration of free zinc is y (ppm), in the case of 0.01 ≦ x ≦ 5, the topical skin composition is prepared so as to satisfy the following relational expressions (1) and (2).

[0013] (1) y ≦ 18.4x + 1.92 (0.01 ≦ x < 0.1) (2) y ≦ 9x + 2.86 (0.1 ≦ x ≦ 5)

Advantages of the Invention

[0014] According to the present invention, in a topical skin composition containing a heparin-like substance and a zinc oxide compound, by paying attention to the concentration of free zinc from zinc oxide and regulating the concentration, the dispersion stability of the heparin-like substance can be improved.

Brief Description of the Drawings

[0015]

Figure 1

Figure 2

Mode for Carrying Out the Invention

[0016] <First Embodiment> A first embodiment in which the skin external composition according to the present invention is embodied will be described. The skin external composition of this embodiment contains a heparin-like substance and a zinc oxide compound.

[0017] (Heparin-like substance) The heparin-like substance used in this embodiment is a polysulfated ester of mucopolysaccharide obtained by sulfating a polysaccharide having a disaccharide composed of D-glucuronic acid and N-acetyl-D-galactosamine as a repeating unit. Specific examples of the heparin-like substance include, for example, cellulose sulfate, chitin sulfate, chitosan sulfate, pectin sulfate, chondroitin sulfate, inulin sulfate, alginic acid sulfate, glycogen sulfate, starch sulfate, polyvinyl alcohol sulfate, polyglucose sulfate, polylactose sulfate, laminarin sulfate, galactan sulfate, levan sulfate, and polysulfates thereof, and salts thereof. As the heparin-like substance, heparin-like substances listed in the Japanese Pharmaceutical Excipients Standards can be preferably used.

[0018] These heparin-like substances may be used alone or in combination of two or more. (Zinc oxide compound) The zinc oxide compound is blended as an ultraviolet scattering agent. As the zinc oxide compound, in addition to zinc oxide itself (ZnO), a compound in which zinc oxide particles are treated with a surface treatment agent and a coating layer is formed on the surface of the zinc oxide particles may be applied. By applying a compound in which a coating layer is formed on the surface of the zinc oxide particles, aggregation between metal oxides can be prevented, and it is expected to contribute to an improvement in makeup retention. In addition, the efficacy of the components constituting the coating layer can also be imparted to the zinc oxide compound. Examples of the components constituting the coating layer include hydrous silica, silicone compounds, fluorine compounds, silane coupling agents, oily components, dextrin fatty acid esters, amino acids, lecithin, ceramides, surfactants, and the like. Further, examples of the oily components include fatty acids, hydrocarbons, higher alcohols, esters, waxes, and rosin. Examples of the silane coupling agent include triethoxycaprylylsilane and the like.

[0019] As a method for forming a coating layer on the surface of the zinc oxide particles, a known method using a surface treatment agent can be applied. Examples of the surface treatment agent include alkoxysilane, amino acids or their derivatives, surfactants, metal soaps, fluorine compounds, higher fatty acids, higher alcohols, phospholipids, ceramides, and the like. Further, as the components constituting the coating layer, hydrous silica (hydrous silicic acid), hydrogen dimethicone, isostearic acid, and triethoxycaprylylsilane are particularly preferable.

[0020] These zinc oxide compounds may be used alone or in combination of two or more. The form of the zinc oxide compound is preferably particulate fine particle zinc oxide. In the blended form, it is preferably in powder form. The lower limit of the particle size of the zinc oxide compound is not particularly limited, but is preferably 1 nm or more, more preferably 5 nm or more, and even more preferably 20 nm or more. The upper limit of the particle size of the zinc oxide compound is not particularly limited, but is preferably 100 nm or less, more preferably 80 nm or less, still more preferably 50 nm or less, and particularly preferably 35 nm or less. It effectively exhibits a sunscreen effect on the skin surface by ultraviolet scattering action. The average particle size of the powder is the value (D50) measured by the laser diffraction / scattering method.

[0021] (Specification of Blending Amount) In the skin external composition, when the blending amount of the heparin-like substance is x (mass%) and the concentration of free zinc is y (ppm), it is defined so as to satisfy the following relational expressions (1) and (2) when 0.01 ≤ x ≤ 5.

[0022] (1) y ≤ 18.4x + 1.92 (0.01 ≤ x < 0.1) (2) y ≤ 9x + 2.86 (0.1 ≤ x ≤ 5) By defining it within such a range, even when the heparin-like substance and the zinc oxide compound coexist, a decrease in the dispersion stability of the heparin-like substance can be suppressed. The suppression of the decrease in the dispersion stability of the heparin-like substance specifically refers to the range where the ratio (B × 100 / A) of the content (B: mass%) determined using a UV detector in the skin external composition to the blending amount (A: mass%) of the heparin-like substance in the skin external composition is 90% or more as a quantitative value (%). The content determined using a UV detector is the content determined by creating a calibration curve from the numerical value of the absorbance of the UV detector from a heparin-like substance-containing solution with a known concentration that does not contain a zinc oxide compound.

[0023] The lower limit of the blending amount (x) of the heparin-like substance in the skin external composition is 0.01 mass% or more, preferably 0.05 mass% or more. By defining it within such a range, the efficacy of the heparin-like substance can be further improved.

[0024] The upper limit of the compounding amount (x) of the heparin-like substance in the topical skin composition is 5% by mass or less, preferably 2% by mass or less, more preferably 0.3% by mass or less. By defining it within such a range, the efficacy of the heparin-like substance can be efficiently exerted. In addition, the dispersion stability of the heparin-like substance in the topical skin composition can be improved.

[0025] The concentration y (ppm: mg / L) of free zinc in the topical skin composition is defined to be not more than the value obtained from the above relational expressions (1) and (2). The concentration y of free zinc indicates the value measured by the following method. First, a zinc oxide compound to be compounded is added to the solvent constituting the topical skin composition, and after thoroughly mixing, it is allowed to stand to prepare a solution of the zinc oxide compound. It is diluted to an appropriate concentration with the same solvent, and after removing zinc oxide powder by filtration, centrifugation, etc., the free zinc concentration is measured with a zinc measuring instrument (absorbance measurement). Thereby, a calibration curve showing the relationship between the compounding amount of the zinc oxide compound in the solution and the free zinc concentration is created. From the compounding amount of the zinc oxide compound in the prepared topical skin composition and the calibration curve obtained previously, the free zinc concentration y (ppm) in the topical skin composition is determined.

[0026] The free zinc may be derived from the zinc oxide compound described above or may be otherwise. The free zinc concentration can be adjusted by the compounding amount of the zinc oxide compound, the type of the zinc oxide compound, the type of the coating layer, etc.

[0027] The lower limit of the compounding amount of the zinc oxide compound in the topical skin composition is not particularly limited, but as the amount of zinc oxide, it is preferably 0.3% by mass or more, more preferably 1.5% by mass or more, still more preferably 3% by mass or more. By defining it within such a range, the ultraviolet scattering effect can be improved.

[0028] The upper limit of the compounding amount of the zinc oxide compound in the topical skin composition is not particularly limited, but as the amount of zinc oxide, it is preferably 25% by mass or less, more preferably 20% by mass or less. By defining it within such a range, the ultraviolet scattering effect can be efficiently exerted.

[0029] (Other components) The skin-external composition of the present embodiment can contain known components that can be formulated in skin-external compositions other than the above. Examples of other components include water, solvents, water-soluble polymers, oily components, polyhydric alcohols, surfactants, pH adjusters, amino acids, preservatives, stabilizers, fragrances, antioxidants, ultraviolet scattering agents other than the above, ultraviolet absorbers, inorganic powders, humectants, and the like.

[0030] Examples of the solvent include lower alcohols such as ethanol and isopropanol, and aromatic alcohols. Examples of the oily component include fats and oils, waxes, hydrocarbons, ester oils, higher alcohols, higher fatty acids, alkyl glyceryl ethers, and silicones.

[0031] As the surfactant, an emulsifier or a component for solubilizing each component is emulsified or solubilized during use to adjust the viscosity or improve the viscosity stability. Examples of the surfactant include known anionic surfactants, cationic surfactants, amphoteric surfactants, and nonionic surfactants.

[0032] (Dosage form) Examples of the dosage form of the skin-external composition of the present embodiment include liquid forms. Examples of the liquid form include aqueous solutions, dispersions, emulsions, etc., and forms such as gel-like, foam-like, and cream-like are also included in the liquid form. Examples of the emulsion further include water-in-oil emulsions and oil-in-water emulsions. Among these, water-in-oil emulsions and oil-in-water emulsions are preferred from the viewpoint of further improving the dispersion stability of the heparin-like substance.

[0033] (Form of use) As a specific formulation form of the skin-external composition of the present embodiment, it can be applied as cosmetics, skin-external agents, pharmaceuticals, quasi-drugs, etc. for the purpose of obtaining the above-described effects.

[0034] When applying the skin external composition of this embodiment to cosmetics, it can be produced by blending with a cosmetic base material. The cosmetic base material is generally commonly blended in cosmetics. For example, with oil, purified water, and alcohol as the main components, at least one selected from surfactants, humectants, antioxidants, thickeners, anti-seborrheic agents, blood circulation promoters, whitening agents, pH adjusters, pigment pigments, preservatives, and fragrances is appropriately blended.

[0035] The skin external composition of this embodiment preferably adopts the form of quasi-drugs. The dosage form is not particularly limited, and examples include gels, creams, or emulsions. Also, excipients, base materials, emulsifiers, solvents, stabilizers, etc. may be blended as additives.

[0036] (Effect of this embodiment) The effect of the skin external composition of this embodiment will be described. (1-1) In the skin external composition of this embodiment, the blending amount of the heparin-like substance and the concentration of free zinc are defined so as to be within the ranges of the above formulas (1) and (2). By focusing on and defining the free zinc concentration of zinc oxide, it is possible to suppress a decrease in the dispersion stability of the heparin-like substance.

[0037] In a liquid skin external composition, when a heparin-like substance and zinc oxide compound as a metal oxide coexist, during adjustment, adsorption occurs by ionic bonding between the heparin-like substance and the metal oxide itself, or between the heparin-like substance and the free zinc released from the metal oxide, resulting in a problem that the dispersion stability of the heparin-like substance decreases. Among them, for the latter problem, by only defining the concentration of free zinc and the blending amount of the heparin-like substance in the skin external composition, the heparin-like substance can be stably dispersed in the skin external composition containing the heparin-like substance and the zinc oxide compound.

[0038] (1-2) When a zinc oxide compound in which a coating layer is formed on the surface of zinc oxide particles with hydrous silica or the like is used, it is expected to prevent aggregation between metal oxides and contribute to an improvement in makeup retention. Further, by selecting the components constituting the coating layer, it is possible to reduce the concentration of free zinc released from zinc oxide.

[0039] (1-3) In the skin-external composition of the present embodiment, when the ratio (B×100 / A) of the content (B) determined using a UV detector in the skin-external composition to the blending amount (A) of the heparin-like substance in the skin-external composition is defined as a quantitative value (%), the quantitative value is 90% or more. Therefore, since a large amount of the heparin-like substance is stably present in the solution of the skin-external composition, the efficacy of the heparin-like substance can be effectively exhibited.

[0040] (1-4) In the skin-external composition of the present embodiment, when the dosage form is an oil-in-water emulsion or a water-in-oil emulsion, the dispersion stability of the heparin-like substance can be further improved. <Second Embodiment> Hereinafter, a second embodiment in which the method for stabilizing the dispersion of the heparin-like substance of the present invention (hereinafter referred to as the "dispersion stabilization method") is embodied will be described. Note that, for the second embodiment, the same configuration as that of the skin-external composition of the first embodiment is applied except for the following description.

[0041] The dispersion stabilization method of the present embodiment is a method for stabilizing the dispersion of a heparin-like substance in a skin-external composition containing the heparin-like substance and a zinc oxide compound. When the blending amount of the heparin-like substance in the skin-external composition is x (% by mass) and the concentration of free zinc is y (ppm), in the case of 0.01 ≦ x ≦ 5, the skin-external composition is prepared so as to satisfy the following relational expressions (1) and (2).

[0042] (1) y ≦ 18.4x + 1.92 (0.01 ≦ x < 0.1) (2) y ≦ 9x + 2.86 (0.1 ≦ x ≦ 5) By defining it within such a range, even when a heparin analogue and a zinc oxide compound coexist, a decrease in the dispersion stability of the heparin analogue can be suppressed. As described in the first embodiment, suppressing a decrease in the dispersion stability of the heparin analogue specifically means that when the ratio (B×100 / A) of the content (B: mass%) determined using a UV detector in the skin external composition to the blending amount (A: mass%) of the heparin analogue in the skin external composition is taken as a quantitative value (%), it is in the range where the quantitative value is 90% or more. Note that the content determined using a UV detector is the content obtained by creating a calibration curve from the numerical value of the absorbance of the UV detector from a heparin analogue-containing solution with a known concentration that does not contain a zinc oxide compound.

[0043] As a method for blending the heparin analogue and the zinc oxide compound, known methods can be used and are not particularly limited. Also, the free zinc concentration can be adjusted according to the blending amount of the zinc oxide compound, the type of zinc oxide compound, the type of the coating layer, etc.

[0044] (Effect of this embodiment) According to the dispersion stabilization method of this embodiment, in addition to the effects of the first embodiment, the following effects can be obtained.

[0045] (2-1) In this embodiment, by defining the blending amount of the heparin analogue and the concentration of free zinc within a predetermined range, dispersion stabilization of the heparin analogue in the skin external composition is achieved. Therefore, in a skin external composition containing a heparin analogue and a zinc oxide compound, by focusing on and defining the free zinc concentration of zinc oxide, the heparin analogue can be easily and stably dispersed in the solution.

[0046] (Modification example) Note that the above embodiment may be modified as follows. The above embodiment and the following modification examples can be implemented in combination with each other within a technically non-contradictory range.

[0047] · In the above embodiment, the use of the cosmetic is not particularly limited, and examples thereof include makeup cosmetics such as sunscreen compositions, foundations, and lipstick compositions, and skincare cosmetics such as emulsions and moisturizing compositions.

Examples

[0048] Hereinafter, the configuration and effects of the present invention will be specifically described using examples and the like, but the present invention is not limited to these examples. <Test Example 1: Relationship between the blending amount of heparin-like substance and the concentration of free zinc> A composition for external use on the skin was prepared, and the relationship between the quantitative value of the heparin-like substance in the composition for external use on the skin and the concentration of free zinc was determined.

[0049] First, the concentration of free zinc in the composition for external use on the skin was determined as follows. A predetermined amount of zinc oxide was added as a zinc oxide compound to be blended to water, which is a solvent constituting the composition for external use on the skin, and after thoroughly mixing, the mixture was allowed to stand to prepare zinc oxide solutions of Sample Nos. 1 to 16. After diluting to an appropriate concentration with water and removing zinc oxide powder by a filter, the free zinc concentration was measured with a zinc measuring instrument (absorbance measurement). Thereby, a calibration curve showing the relationship between the blending amount (mass%) of zinc oxide and the free zinc concentration (ppm) in the aqueous solution was created. The obtained calibration curve is shown in FIG. 1.

[0050] Next, compositions for external use on the skin of each example consisting of a heparin-like substance, zinc oxide, and water shown in Table 2 were prepared. For the compositions for external use on the skin of Examples 2 to 9 and Comparative Examples 3 to 5, the free zinc concentration in the composition for external use on the skin was determined from the blending amount of zinc oxide in the zinc oxide aqueous solution of Table 1. For Example 1 and Comparative Examples 1 and 2, the free zinc concentration in the composition for external use on the skin was determined from the calibration curve of FIG. 1. The results are shown in Table 2.

[0051] The quantitative value of the heparin-like substance in the composition for external use on the skin of each example was determined by the following method. A calibration curve consisting of a relational expression between absorbance and concentration was created from the numerical value of the absorbance of a UV detector using a heparin analogue-containing solution with a known concentration that does not contain a zinc oxide compound. Next, after thoroughly mixing each composition, it was diluted to an appropriate concentration by the same operation with ultrapure water, the absorbance was measured using the same UV detector, and the content (B: mass %) of the heparin analogue in each composition was determined from the calibration curve obtained previously.

[0052] The ratio (B × 100 / A) of the content (B: mass %) of the heparin analogue to the blending amount (A: mass %) of the heparin analogue in the topical composition for skin was determined as a quantitative value (%). The results are shown in Table 2.

[0053] (Relational expression) The point of the free zinc concentration of 2.84 ppm at a quantitative value of 90% when the blending amount of the heparin analogue is 0.05 mass % and the point of the free zinc concentration of 3.76 ppm at a quantitative value of 90% when the blending amount of the heparin analogue is 0.1 mass % were connected by a straight line to obtain a relational expression. As a result, it was confirmed that (1) y = 18.4x + 1.92.

[0054] Also, the point of the free zinc concentration of 3.76 ppm at a quantitative value of 90% when the blending amount of the heparin analogue is 0.1 mass % and the point of the free zinc concentration of 5.56 ppm at a quantitative value of 90% when the blending amount of the heparin analogue is 0.3 mass % were connected by a straight line to obtain a relational expression. As a result, it was confirmed that (2) y = 9x + 2.86.

[0055] Relational expressions (1) and (2) of the blending amount x (mass %) of the heparin analogue and the free zinc concentration y (ppm) are shown in Figure 2.

[0056]

Table 1

[0057]

Table 2

[0058] <Formulation Example> The formulation examples shown in Table 3 were prepared. The numerical values in the table indicate mass %. The zinc oxide that has been surface-treated A is surface-treated with hydrous silica and hydrogen dimethicone. The zinc oxide that has been surface-treated B is surface-treated with hydrogen dimethicone. For Formulation Example 1, the free zinc concentration was first determined from the calibration curve prepared from the compounding amount and the free zinc concentration in the aqueous solution using an aqueous solution containing zinc oxide that has been surface-treated A in the same manner as in Test Example 1. Thereby, the free zinc concentration in Formulation Example 1 containing 10 mass % of zinc oxide that has been surface-treated A was determined. The free zinc concentration of Comparative Formulation Example 1 was also determined in the same manner. Also, the quantitative value (%) of the heparin-like substance was determined in the same manner as in Test Example 1. The results are shown in Table 3.

[0059]

Table 3

Claims

1. A topical skin composition containing a heparin analogue and a zinc oxide compound, wherein when the content of the heparin analogue in the topical skin composition is x (mass %) and the concentration of free zinc is y (ppm), in the range of 0.01 ≦ x ≦ 5, the following relational expressions (1) and (2) are satisfied. (1) y ≦ 18.4x + 1.92 (0.01 ≦ x < 0.1) (2) y ≦ 9x + 2.86 (0.1 ≦ x ≦ 5)

2. The topical skin composition according to claim 1, wherein the zinc oxide compound is a compound having a coating layer formed on the surface of zinc oxide particles.

3. The topical skin composition according to claim 2, wherein the coating layer is composed of at least one selected from hydrous silica, silicone compounds, fluorine compounds, silane coupling agents, oily components, dextrin fatty acid esters, amino acids, lecithin, ceramides, and surfactants.

4. The topical skin composition according to any one of claims 1 to 3, wherein the content of the zinc oxide compound is 1.5 mass % or more in terms of the amount of zinc oxide.

5. When the ratio (B × 100 / A) of the content (B) determined using a UV detector in the topical skin composition to the content (A) of the heparin analogue in the topical skin composition is defined as a quantitative value (%), the topical skin composition according to any one of claims 1 to 3, wherein the quantitative value is 90% or more.

6. The topical skin composition according to any one of claims 1 to 3, wherein the topical skin composition is an oil-in-water emulsion or a water-in-oil emulsion.

7. The topical skin composition according to any one of claims 1 to 3, wherein the zinc oxide compound is fine particle zinc oxide.

8. A method for stabilizing the dispersion of a heparin analogue in a topical skin composition containing a heparin analogue and a zinc oxide compound, wherein when the content of the heparin analogue in the topical skin composition is x (mass %) and the concentration of free zinc is y (ppm), in the range of 0.01 ≦ x ≦ 5, the topical skin composition is prepared so as to satisfy the following relational expressions (1) and (2). (1) y ≦ 18.4x + 1.92 (0.01 ≦ x < 0.1) (2) y ≦ 9x + 2.86 (0.1 ≦ x ≦ 5)

Images