阅读说明：本技术 一种含有透明质酸的氨甲环酸脂质体化妆品及其制备方法 (Tranexamic acid liposome cosmetic containing hyaluronic acid and preparation method thereof ) 是由 邹济高 王彬彬 代光玉 于 2021-09-28 设计创作，主要内容包括：本发明涉及一种含用透明质酸的氨甲环酸化妆品及其制备方法,本发明进一步涉及含用透明质酸的氨甲环酸的脂质体化妆品,透明质酸具有保湿作用,也具有的透皮吸收促进作用,本发明的化妆品同时具备袪斑与保湿作用。(The invention relates to a tranexamic acid cosmetic containing hyaluronic acid and a preparation method thereof, and further relates to a liposome cosmetic containing tranexamic acid of hyaluronic acid, wherein the hyaluronic acid has the moisturizing effect and also has the transdermal absorption promoting effect.)

1. A method for preparing a liposome cosmetic containing tranexamic acid, which comprises the following steps:

(1) preparing a phospholipid solution: weighing the following raw materials in percentage by mass: adding 4-20% of phospholipid, 1.2-6.0% of sterol and 74-95% of absolute ethyl alcohol into a closed container, fully mixing uniformly, dissolving, and keeping the temperature at 0-45 ℃;

(2) preparing a compound solution of tranexamic acid and hyaluronic acid:

adding water into a closed container, adding 0.5-6.0% of tranexamic acid and 0.1-1.0% of hyaluronic acid, stirring and dissolving, and keeping the temperature at 0-45 ℃;

(3) mixing the solution: adding a hot phospholipid solution into a complex solution of tranexamic acid and hyaluronic acid, wherein the weight ratio of phospholipid solution: the ratio of the tranexamic acid solution to the hyaluronic acid solution is 2-6: 1, and stirring is carried out to obtain a tranexamic acid and hyaluronic acid phospholipid mixed solution;

(4) spray drying or freeze drying: recovering the solvent from the mixed solution obtained in the step (3) by spray drying or freeze drying to obtain tranexamic acid and hyaluronic acid phospholipid mixed powder;

(5) hydration: taking a proper amount of tranexamic acid and hyaluronic acid hydrogenated phospholipid mixed powder, adding the mixed powder into purified water, stirring, and carrying out hydration conditions: hydration temperature: 0-65 ℃;

(6) homogenizing: homogenization conditions, homogenization temperature: 0-65 ℃; homogenizing pressure: more than 10000psi, the particle size range is controlled below 150 nm; and (3) metering the volume of the homogenized liquid to 1-10% by using sodium dihydrogen phosphate.

2. The production method according to claim 1, wherein the phospholipid is selected from the group consisting of: phosphatidyl choline, phosphatidyl serine, phosphatidic acid, phosphatidyl glycerol, dioleoylphosphatidylcholine, distearoylphosphatidyl choline, dipalmitoylphosphatidylcholine, palmitoyloleoylphosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, sphingomyelin, dicetyl phosphate, lysophosphatidylcholine, egg yolk lecithin, soybean lecithin or hydrogenated phospholipids.

3. The preparation method according to claim 1, wherein the sterol is selected from the group consisting of: cholesterol, dihydrocholesterol, cholesterol esters, phytosterols, sitosterol, stigmasterol, campesterol, cholestanol, or lanosterol.

4. The method according to claim 1, wherein the weight ratio of tranexamic acid to hyaluronic acid is: 5-8: 0.5-1.

5. The method according to claim 1, wherein the weight ratio of tranexamic acid to hyaluronic acid is: 5: 1. 5: 0.5, 8: 1.

6. the method of claim 1, wherein the weight ratio of phospholipid to sterol is: 24: 6-8.

7. The method of claim 1, wherein the weight ratio of phospholipid to sterol is: 24: 6. 24: 8.

8. the method of claim 1, wherein the phospholipid is selected from the group consisting of: hydrogenated soybean phospholipids, distearoyl phosphatidylcholine, distearoyl phosphatidylcholine, soybean phospholipids; wherein the sterol is selected from the group consisting of: cholesterol, dihydrocholesterol, cholesterol ester, sitosterol.

9. A cosmetic composition prepared by the preparation method of claims 1 to 8.

10. The cosmetic composition according to claim 9, wherein hyaluronic acid and tranexamic acid are contained.

Technical Field

The invention relates to a tranexamic acid liposome cosmetic containing hyaluronic acid, which has the double functions of moisturizing and removing freckles.

Background

The skin includes epidermis, dermis, and subcutaneous tissue from the outside, and has the function of protecting the living body from external stimuli through its barrier function. The dermis and epidermis of the skin are composed of epidermal cells, fibroblasts, dermal cells, and the like. Proteoglycan forms a main polymer in the extracellular matrix of connective tissue together with collagen and the like. Young skin keeps moisture by keeping the interaction of these skin tissues constant, and maintains the state of looking tight and glossy by ensuring softness, elasticity, and the like.

The outermost layer of the epidermis further includes a horny layer, which is the last arriving part of 10 to 20 layers of corneocytes. Natural thermal insulation factors such as amino acids, urea, lactic acid, and the like exist in keratinocytes, and these substances combine with water to retain moisture and keep the skin soft. Dead cells without nuclei are visible on the outer side of the stratum corneum, but the barrier function of the stratum corneum, which functions to retain water and prevent dryness, is greatly related to the beauty of the skin.

However, the moisture content of the stratum corneum is decreased by external factors such as dryness and ultraviolet rays, and internal factors such as aging, visceral diseases and stress, and this causes a decrease in the barrier function of the skin, leading to rough skin, dry skin and various kinds of dermatitis. Therefore, in the cosmetic field and the dermatological field, the development of a moisturizing agent for maintaining the moisture content of the horny layer is essential.

On the other hand, in the field of cosmetics, as a means for delivering an active ingredient having a moisturizing function and a spot-removing function to the skin, the active ingredient is encapsulated in a liposome. Liposomes are lipid bilayers or multilayers, formed mainly of phospholipids, having a structure similar to a cell membrane. The water soluble active ingredient is entrapped in the aqueous phase of the liposome. It not only has high-efficiency encapsulation and good transdermal performance, but also can effectively carry drug molecules to penetrate through the stratum corneum and even reach deeper layers of the skin, and is a high-efficiency transparent carrier.

The hyaluronic acid is one of main matrixes of the epidermis layer and the dermis layer of a human body, has good biocompatibility, improves the nutrition metabolism of the skin, is an ideal moisturizing factor, and is a good transdermal absorption enhancer while moisturizing; can promote proliferation of fiber cells, promote repair of skin wound, reduce scar, and enhance immunity.

Tranexamic acid (tranexamic acid), also known as a tranexamic acid, is an artificially synthesized lysine derivative, belongs to a fibrinolytic agent, and exerts a hemostatic function by inhibiting the dissolution of fibrin. In 1979, in the process of treating chronic urticaria by using tranexamic acid, the two glossy privet fruits discover that the tranexamic acid can lighten chloasma of a patient for the first time, and researches show that the therapeutic effect and the onset speed of the tranexamic acid for treating chloasma are superior to those of vitamin C, so that the tranexamic acid is regarded as a new medicament for treating chloasma to attract attention of people. Tranexamic acid, which is a plasmin inhibitor, may act mainly by inhibiting the plasmin-plasminogen pathway, Arachidonic Acid (AA) and alpha-melanocyte stimulating hormone (alpha-MSH) increase with the increase of plasmin in keratinocytes, and prostatic acid (PG), which is a metabolite of arachidonic acid, can stimulate melanin synthesis and the production of melanocyte stimulating hormone, so that tranexamic acid can reduce the production of melanin by inhibiting the plasmin pathway, thereby achieving the effect of lightening spots. Tyrosinase is a key enzyme for melanin formation, and the chemical structure of the carbamate is partially similar to that of tyrosine, so that early research reports that the carbamate can compete with the tyrosine to treat chloasma, thereby interfering the catalytic action of the tyrosinase on the tyrosine and inhibiting the formation of ink pigments. Although the mechanism of tranexamic acid in treating chloasma is not completely elucidated at present. But the tranexamic acid is the first choice of the drugs for treating the chloasma at present due to the curative effect and the biological safety of the tranexamic acid for treating the chloasma.

As the phospholipid that can be used, for example, phosphatidylcholine (lecithin), phosphatidylserine, phosphatidic acid, phosphatidylglycerol, dioleoylphosphatidylcholine, distearoylphosphatidylcholine, dipalmitoylphosphatidylcholine, palmitoyloleoylphosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, sphingomyelin, dicetyl phosphate, lysophosphatidylcholine (lysolecithin), egg yolk lecithin, soybean lecithin, or hydrogenated phospholipids thereof can be used without particular limitation. These phospholipids may be used singly or in combination.

In addition to the above-mentioned liposome-constituting components, other substances such as sterols having a stabilizing effect on the liposome membrane, for example, cholesterol, dihydrocholesterol, cholesterol ester, phytosterol, sitosterol, stigmasterol, campesterol, cholestanol, lanosterol, or the like may be added as necessary.

Disclosure of Invention

The invention aims to provide a liposome cosmetic.

The liposome cosmetic comprises tranexamic acid and hyaluronic acid, and has the effects of moisturizing and removing freckles.

The present invention further provides a method for preparing the liposome cosmetic of the present invention, which comprises encapsulating a part of hyaluronic acid having moisturizing effect and a part of tranexamic acid having anti-spotting effect in a liposome bilayer membrane, so that both components can well penetrate the epidermal layer and the dermal layer to exert the effects better when applied, and on the other hand, the remaining part of hyaluronic acid and tranexamic acid which are not encapsulated by the liposome can rapidly exert the effects.

To this end, the present invention provides a method for preparing a liposome cosmetic containing tranexamic acid, the method comprising the steps of:

(1) preparing a phospholipid solution: weighing the following raw materials in percentage by mass: adding 4-20% of phospholipid, 1.2-6.0% of sterol and 74-95% of absolute ethyl alcohol into a closed container, fully mixing uniformly, dissolving, and keeping the temperature at 0-45 ℃;

(2) preparing a compound solution of tranexamic acid and hyaluronic acid:

adding water into a closed container, adding 0.5-6.0% of tranexamic acid and 0.1-1.0% of hyaluronic acid, stirring and dissolving, and keeping the temperature at 0-45 ℃;

(3) mixing the solution: adding a hot phospholipid solution into a complex solution of tranexamic acid and hyaluronic acid, wherein the weight ratio of phospholipid solution: the ratio of the tranexamic acid solution to the hyaluronic acid solution is 2-6: 1, and stirring is carried out to obtain a tranexamic acid and hyaluronic acid phospholipid mixed solution;

(4) spray drying or freeze drying: recovering the solvent from the mixed solution obtained in the step (3) by spray drying or freeze drying to obtain tranexamic acid and hyaluronic acid phospholipid mixed powder;

(5) hydration: taking a proper amount of tranexamic acid and hyaluronic acid hydrogenated phospholipid mixed powder, adding the mixed powder into purified water, stirring, and carrying out hydration conditions: hydration temperature: 0-65 ℃;

(6) homogenizing: homogenization conditions, homogenization temperature: 0-65 ℃; homogenizing pressure: more than 10000psi, the particle size range is controlled below 150 nm; and (3) metering the volume of the homogenized liquid to 1-10% by using sodium dihydrogen phosphate.

The preparation method of the invention, wherein the phospholipid is selected from the group consisting of: phosphatidyl choline, phosphatidyl serine, phosphatidic acid, phosphatidyl glycerol, dioleoylphosphatidylcholine, distearoylphosphatidyl choline, dipalmitoylphosphatidylcholine, palmitoyloleoylphosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, sphingomyelin, dicetyl phosphate, lysophosphatidylcholine, egg yolk lecithin, soybean lecithin or hydrogenated phospholipids.

The preparation method of the invention, wherein the sterol is selected from the group consisting of: cholesterol, dihydrocholesterol, cholesterol esters, phytosterols, sitosterol, stigmasterol, campesterol, cholestanol, or lanosterol.

The preparation method comprises the following steps of: 5-8: 0.5-1.

The preparation method comprises the following steps of: 5: 1. 5: 0.5, 8: 1.

the preparation method comprises the following steps of: 24: 6-8.

The preparation method comprises the following steps of: 24: 6. 24: 8.

the preparation method of the invention is characterized in that the phospholipid is selected from the following: hydrogenated soybean phospholipids, distearoyl phosphatidylcholine, distearoyl phosphatidylcholine, soybean phospholipids; wherein the sterol is selected from the group consisting of: cholesterol, dihydrocholesterol, cholesterol ester, sitosterol.

The cosmetic composition prepared by the preparation method of the invention. The cosmetic composition contains hyaluronic acid and tranexamic acid.

The invention has the beneficial effects that: the tranexamic acid can remove the freckles, the hyaluronic acid can preserve moisture, the combination of the tranexamic acid and the hyaluronic acid can achieve the double effects of preserving moisture and removing the freckles, and meanwhile, the hyaluronic acid can improve the transdermal performance of the tranexamic acid, increase the stability of the tranexamic acid, improve the safety, take effect quickly and have lasting effect.

Detailed Description

The following examples are illustrative and should not be construed as limiting the invention.

Example 1

(1) Preparing a hydrogenated soybean phospholipid solution: weighing the following raw materials in percentage by mass: adding 24 g of hydrogenated soybean phospholipid, 8 g of cholesterol and 168 g of absolute ethyl alcohol into a closed container, fully mixing and dissolving. Keeping the temperature at 0-45 ℃.

(2) Preparing a tranexamic acid solution:

in a closed container, water is added, 5 g of tranexamic acid, 1 g of hyaluronic acid and 42 g of water are added. Stirring and dissolving, and keeping the temperature at 0-45 ℃.

(3) Mixing the solution: adding the hot hydrogenated soybean phospholipid solution into the composite solution of the tranexamic acid and the hyaluronic acid, and stirring to obtain a mixed solution of the tranexamic acid and the hyaluronic acid hydrogenated phospholipid.

(4) And (3) freeze drying: and (4) placing the mixed solution in the step (3) in a freeze dryer, and recovering the solvent through freeze drying.

(5) Hydration: taking a proper amount of tranexamic acid and hyaluronic acid hydrogenated phospholipid mixed freeze-dried substance, adding purified water to 100 g, stirring, and carrying out hydration conditions:

hydration temperature: 0 ℃ to 65 ℃.

(6) Homogenizing: conditions of homogenization

Homogenizing temperature: 0 ℃ to 65 ℃,

homogenizing pressure: greater than 10000psi of a silicone rubber composition,

the particle size range is controlled below 150 nm.

Adding sodium dihydrogen phosphate into the liposome obtained after homogenizing to prepare 4% tranexamic acid liposome aqueous solution.

Example 2

(1) Preparing a distearoyl phosphatidylcholine solution: weighing the following raw materials in percentage by mass: 24 g of distearoyl phosphatidylcholine, 8 g of dihydrocholesterol and 168 g of absolute ethyl alcohol are added into a closed container, and the mixture is fully mixed and dissolved. Keeping the temperature at 0-45 ℃.

(2) Preparing a tranexamic acid solution:

in a closed container, water is added, 5 g of tranexamic acid, 1 g of hyaluronic acid and 42 g of water are added. Stirring and dissolving, and keeping the temperature at 0-45 ℃.

(3) Mixing the solution: adding the hot hydrogenated soybean phospholipid solution into the composite solution of the tranexamic acid and the hyaluronic acid, and stirring to obtain a mixed solution of the tranexamic acid and the hyaluronic acid hydrogenated phospholipid.

(4) Spray drying: and (4) carrying out spray drying on the mixed solution in the step (3), and recovering the solvent through spray drying.

(5) Hydration: taking a proper amount of tranexamic acid and hyaluronic acid hydrogenated phospholipid mixed freeze-dried substance, adding purified water to 100 g, stirring, and carrying out hydration conditions:

hydration temperature: 0 ℃ to 65 ℃.

(6) Homogenizing: conditions of homogenization

Homogenizing temperature: 0 ℃ to 65 ℃,

homogenizing pressure: greater than 10000psi of a silicone rubber composition,

the particle size range is controlled below 150 nm.

Adding sodium dihydrogen phosphate into the homogenized liposome to prepare 5% tranexamic acid liposome aqueous solution.

Example 3

(1) Preparation of a phosphatidylcholine solution: weighing the following raw materials in percentage by mass: 24 g of phosphatidylcholine, 8 g of cholesterol and 168 g of absolute ethyl alcohol are added into a closed container, and the mixture is fully mixed and dissolved. Keeping the temperature at 0-45 ℃.

(2) Preparing a tranexamic acid solution:

in a closed container, water is added, and 5 g of tranexamic acid, 0.5 g of hyaluronic acid and 42 g of water are added. Stirring and dissolving, and keeping the temperature at 0-45 ℃.

(3) Mixing the solution: adding the hot hydrogenated soybean phospholipid solution into the composite solution of the tranexamic acid and the hyaluronic acid, and stirring to obtain a mixed solution of the tranexamic acid and the hyaluronic acid phospholipid.

(4) And (3) freeze drying: and (4) placing the mixed solution in the step (3) in a freeze dryer, and recovering the solvent through freeze drying.

(5) Hydration: taking a proper amount of tranexamic acid and hyaluronic acid phospholipid mixed powder, adding purified water to a proper amount, stirring, and carrying out hydration conditions:

hydration temperature: 0 ℃ to 65 ℃.

(6) Homogenizing: conditions of homogenization

Homogenizing temperature: 0 ℃ to 65 ℃,

homogenizing pressure: greater than 10000psi of a silicone rubber composition,

the particle size range is controlled below 150 nm.

Adding sodium dihydrogen phosphate into the homogenized liposome to prepare 5% tranexamic acid liposome aqueous solution.

Example 4

(1) Preparing a distearoyl phosphatidylcholine solution: weighing the following raw materials in percentage by mass: 24 g of distearoyl phosphatidylcholine, 8 g of cholesterol ester and 168 g of absolute ethyl alcohol are added into a closed container, and the mixture is fully mixed and dissolved. Keeping the temperature at 0-45 ℃.

(2) Preparing a tranexamic acid solution:

in a closed container, water is added, 5 g of tranexamic acid, 1 g of hyaluronic acid and 42 g of water are added. Stirring and dissolving, and keeping the temperature at 0-45 ℃.

(3) Mixing the solution: adding the hot distearoyl phosphatidylcholine solution into the compound solution of the tranexamic acid and the hyaluronic acid, and stirring to obtain the mixed solution of the tranexamic acid and the hydrogenated phospholipid of the hyaluronic acid.

(4) Spray drying: and (4) carrying out spray drying on the mixed solution in the step (3), and recovering the solvent through spray drying.

(5) Hydration: taking a proper amount of tranexamic acid and hyaluronic acid distearoyl phosphatidylcholine mixed freeze-dried substance, adding purified water to 100 g, stirring, and carrying out hydration conditions:

hydration temperature: 0 ℃ to 65 ℃.

(6) Homogenizing: conditions of homogenization

Homogenizing temperature: 0 ℃ to 65 ℃,

homogenizing pressure: greater than 10000psi of a silicone rubber composition,

the particle size range is controlled below 150 nm.

Adding sodium dihydrogen phosphate into the homogenized liposome to prepare 5% tranexamic acid liposome aqueous solution.

Example 5

(1) Preparing a soybean phospholipid solution: weighing the following raw materials in percentage by mass: adding 24 g of soybean phospholipid, 6 g of sitosterol and 170 g of absolute ethyl alcohol into a closed container, fully mixing uniformly and dissolving. Keeping the temperature at 0-45 ℃.

(2) Preparing a tranexamic acid solution:

in a closed container, water is added, and 8 g of tranexamic acid, 0.5 g of hyaluronic acid and 42 g of water are added. Stirring and dissolving, and keeping the temperature at 0-45 ℃.

(3) Mixing the solution: adding the hot soybean lecithin solution into the composite solution of the tranexamic acid and the hyaluronic acid, and stirring to obtain a mixed solution of the tranexamic acid and the hyaluronic acid soybean lecithin.

(4) Spray drying: and (4) placing the mixed solution in the step (3) into a spray dryer, and recovering the solvent through spray drying.

(5) Hydration: mixing appropriate amount of tranexamic acid and hyaluronic acid soybean lecithin into spray-dried powder, adding purified water to 100 g, stirring, and hydrating:

hydration temperature: 0 ℃ to 65 ℃.

(6) Homogenizing: conditions of homogenization

Homogenizing temperature: 0 ℃ to 65 ℃,

homogenizing pressure: greater than 10000psi of a silicone rubber composition,

the particle size range is controlled below 150 nm.

Adding sodium dihydrogen phosphate into the homogenized liposome to prepare 5% tranexamic acid liposome aqueous solution.