Oil-soluble reverse micelle composition with anti-wrinkle and firming effects as well as preparation method and application of oil-soluble reverse micelle composition

Abstract

The invention relates to the field of medical apparatuses and instruments, the field of medical or dressing preparations, the technical field of biological medicine manufacturing and the technical field of preparation manufacturing, in particular to an oil-soluble reverse micelle composition with anti-wrinkle and tightening effects and a preparation method and application of the oil-soluble reverse micelle composition. The composition comprises an active component, a yeast fermentation product, a stabilizer, grease and polyol, wherein the active ingredients comprise a centella asiatica extract, ginsenoside and aescin; the centella asiatica extract comprises asiaticoside, madecassic acid and asiatic acid; the yeast fermentation product comprises at least one of sophorolipid and rhamnolipid. The composition provided by the invention has good high-temperature stability and grease compatibility, is high in bioavailability and good in grease compatibility, and has obvious effects of resisting wrinkles, tightening, fading dark circles and improving vascular dark circles.

Description

Technical Field

[0001] This invention relates to the fields of medical devices, medical or cosmetic preparations, biopharmaceutical manufacturing technology, and formulation manufacturing technology, specifically to an oil-soluble reverse micelle composition with anti-wrinkle and firming effects, its preparation method, and its application. Background Technology

[0002] With the advancement of modern separation techniques and pharmacological research, the bioactive components of Centella asiatica extract and active substances have become increasingly clear. Their main active components are triterpenoids, including pentacyclic triterpenoid saponins such as asiaticoside, hydroxyasiaticoside, asiaticoside acid, and hydroxyasiaticoside, as well as free triterpenoid acids. Asiaticoside and hydroxyasiaticoside exhibit better water solubility due to their sugar chain structure, while asiaticoside and hydroxyasiaticoside exist as free acids and are more lipid-soluble. As triterpenoid saponins, asiaticoside and hydroxyasiaticoside, due to their sugar chain structure, have significantly better water solubility than triterpenoid acids. Hydroxyactoside, with one more hydroxyl substituent than asiaticoside, is even more water-soluble, being soluble in water (19.68 g / L, 90℃), while asiaticoside is only slightly soluble in water and readily soluble in ethanol and pyridine. Triterpenoid acids (asiatic acid, hydroxyasiatic acid) have poor water solubility due to the absence of sugar chains and low carboxyl ionization, but strong lipid solubility. They are soluble in DMSO, methanol, and ethanol, but insoluble in non-polar solvents such as petroleum ether and diethyl ether. The solubility issues of different active ingredients prevent Centella asiatica extracts and active ingredients from maximizing their efficacy, making improving their bioavailability a major research focus.

[0003] Ginsenosides are the main active ingredients of plants in the genus Panax (such as ginseng, American ginseng, and Panax notoginseng). They belong to the triterpenoid glycoside compounds. Most ginsenoside monomers have limited solubility in water and common solvents, exhibiting amphiphilic characteristics of "poor water solubility and poor lipid solubility", which greatly limits their application.

[0004] Therefore, there is still an urgent need for a composition containing active ingredients such as Centella asiatica extract that has high solubility, good stability, and high bioavailability. Summary of the Invention

[0005] To address the aforementioned technical problems, the present invention provides the following technical solutions.

[0006] In a first aspect, the present invention provides a composition.

[0007] A composition comprising: an active ingredient, a yeast fermentation product, a stabilizer, an oil, and a polyol; The active ingredients include: Centella asiatica extract, ginsenosides and aesculin; The Centella asiatica extract includes asiaticoside, hydroxyasiatic acid, and asiatic acid. The yeast fermentation product includes at least one of sophorolipid and rhamnolipin.

[0008] In some preferred embodiments, the yeast fermentation product is sophorolipid, which is more conducive to improving the solubility and stability of the active ingredients, more conducive to improving the compatibility and stability of the obtained composition with oils, and can improve the solubility problems of asiaticoside and hydroxyasiaticoside in oil in Centella asiatica extract, as well as the poor water solubility and fat solubility problems of ginsenosides.

[0009] In some embodiments, the oil comprises at least one selected from macadamia nut oil, sunflower seed oil, rapeseed oil, olive oil, and triglycerides. In some preferred embodiments, the oil comprises at least one selected from macadamia nut oil, sunflower seed oil, and rapeseed oil, which is beneficial for improving the solubility and stability of the active ingredients, improving the compatibility and stability of the resulting composition with the oil, and improving the solubility of asiaticoside and hydroxyasiaticoside in oil, as well as the poor water and fat solubility of ginsenosides in Centella asiatica extract. In some more preferred embodiments, the oil comprises at least two selected from macadamia nut oil, sunflower seed oil, or rapeseed oil, which is even more beneficial for improving the solubility and stability of the active ingredients, improving the compatibility and stability of the resulting composition with the oil, and improving the solubility of asiaticoside and hydroxyasiaticoside in oil, as well as the poor water and fat solubility of ginsenosides in Centella asiatica extract. In some embodiments, the oil is macadamia nut oil, or a combination of macadamia nut oil and sunflower seed oil, which is most beneficial for improving the solubility and stability of the active ingredients, the compatibility and stability of the resulting composition with the oil, and can improve the solubility of asiaticoside and hydroxyasiaticoside in the oil, as well as the poor water and fat solubility of ginsenosides.

[0010] In some embodiments, the ginsenosides include ginsenoside CK.

[0011] In some embodiments, the polyol includes at least one selected from ethoxydiethylene glycol, 1,3-butanediol, dipropylene glycol, and isohexyl glycol. In some preferred embodiments, the polyol includes at least one selected from ethoxydiethylene glycol and dipropylene glycol, which is beneficial for improving the solubility and stability of the active ingredient, improving the compatibility and stability of the resulting composition with oils, and improving the solubility of asiaticoside and hydroxyasiaticoside in oils, as well as the poor water and fat solubility of ginsenosides in Centella asiatica extract. In some more preferred embodiments, the polyol includes dipropylene glycol or ethoxydiethylene glycol and dipropylene glycol, which is even more beneficial for improving the solubility and stability of the active ingredient, improving the compatibility and stability of the resulting composition with oils, and improving the solubility of asiaticoside and hydroxyasiaticoside in oils, as well as the poor water and fat solubility of ginsenosides in Centella asiatica extract.

[0012] In some embodiments, the stabilizer includes tocopherol.

[0013] This invention employs oil-soluble reverse micelle self-assembly technology to encapsulate Centella asiatica extract and ginsenosides. Simultaneously, aesculin is added to allow for self-assembly with ginsenosides and Centella asiatica extract through hydrogen bonding to form supramolecular structures. Extensive screening of fermentation products, solubilizers, polyols, and oils in the composition is conducted to select preferred specific yeast fermentation products, polyols, and oils. This improves the solubility and stability of the active ingredients, enhances the compatibility and stability of the resulting composition with oils, and addresses the solubility issues of asiaticoside and hydroxyasiaticoside in oils, as well as the poor water and lipid solubility of ginsenosides.

[0014] In some embodiments, the content of asiaticoside in the Centella asiatica extract is 20 wt% to 50 wt% based on the total mass of the Centella asiatica extract. In some embodiments, the content of asiaticoside in the Centella asiatica extract is 25 wt% to 35 wt% based on the total mass of the Centella asiatica extract. In some embodiments, the content of asiaticoside in the Centella asiatica extract is 30 wt% to 40 wt% based on the total mass of the Centella asiatica extract. In some embodiments, the content of asiaticoside in the Centella asiatica extract is 20 wt%, 25 wt%, 30 wt%, 35 wt%, 40 wt%, 45 wt%, 50 wt%, or any value within the range of any two of these values, based on the total mass of the Centella asiatica extract.

[0015] In some embodiments, the content of asiatic acid in the Centella asiatica extract is 20 wt% to 50 wt% based on the total mass of the Centella asiatica extract. In some embodiments, the content of asiatic acid in the Centella asiatica extract is 25 wt% to 35 wt% based on the total mass of the Centella asiatica extract. In some embodiments, the content of asiatic acid in the Centella asiatica extract is 30 wt% to 40 wt% based on the total mass of the Centella asiatica extract. In some embodiments, the content of asiatic acid in the Centella asiatica extract is 20 wt%, 25 wt%, 30 wt%, 35 wt%, 40 wt%, 45 wt%, 50 wt%, or any value within the range of any two of these values, based on the total mass of the Centella asiatica extract.

[0016] In some embodiments, the content of asiatic acid in the Centella asiatica extract is 10wt% to 50wt% based on the total mass of the extract. In some embodiments, the content of asiatic acid in the Centella asiatica extract is 10wt% to 30wt% based on the total mass of the extract. In some embodiments, the content of asiatic acid in the Centella asiatica extract is 15wt% to 20wt% based on the total mass of the extract. In some embodiments, the content of asiatic acid in the Centella asiatica extract is 10wt%, 15wt%, 20wt%, 25wt%, 30wt%, 35wt%, 40wt%, 45wt%, 50wt%, or any value within the range of any two of these values, based on the total mass of the extract.

[0017] In some embodiments, the total content of asiaticoside, hydroxyasiatic acid and asiatic acid in the Centella asiatica extract is 100 wt%, calculated based on the total mass of the Centella asiatica extract.

[0018] In some embodiments, the Centella asiatica extract further includes a Centella asiatica extract base, wherein the content of the Centella asiatica extract base in the Centella asiatica extract is greater than 0 wt% and less than or equal to 30 wt%, and the balance is asiaticoside, hydroxyasiatic acid and asiatic acid.

[0019] In some embodiments, the Centella asiatica extract further comprises a Centella asiatica extract base, wherein, based on the total mass of the Centella asiatica extract, the content of the Centella asiatica extract base in the Centella asiatica extract is greater than 0 wt% and less than or equal to 30 wt%, with the balance being asiaticoside, asiaticoside, and asiaticoside, wherein, based on the total mass of the Centella asiatica extract, the content of asiaticoside in the Centella asiatica extract is 20 wt% to 50 wt%, the content of asiaticoside in the Centella asiatica extract is 20 wt% to 50 wt%, and the content of asiaticoside in the Centella asiatica extract is 10 wt% to 50 wt%.

[0020] In some embodiments, the Centella asiatica extract further comprises a Centella asiatica extract base, wherein, based on the total mass of the Centella asiatica extract, the content of the Centella asiatica extract base in the Centella asiatica extract is greater than 0 wt% and less than or equal to 30 wt%, with the balance being asiaticoside, asiaticoside, and asiaticoside, wherein, based on the total mass of the Centella asiatica extract, the content of asiaticoside in the Centella asiatica extract is 25 wt% to 35 wt%, the content of asiaticoside in the Centella asiatica extract is 25 wt% to 35 wt%, and the content of asiaticoside in the Centella asiatica extract is 10 wt% to 30 wt%.

[0021] In some embodiments, the Centella asiatica extract further comprises a Centella asiatica extract base, wherein, based on the total mass of the Centella asiatica extract, the content of the Centella asiatica extract base in the Centella asiatica extract is greater than 0 wt% and less than or equal to 30 wt%, with the balance being asiaticoside, asiaticoside, and asiaticoside, wherein, based on the total mass of the Centella asiatica extract, the content of asiaticoside in the Centella asiatica extract is 30 wt% to 40 wt%, the content of asiaticoside in the Centella asiatica extract is 30 wt% to 40 wt%, and the content of asiaticoside in the Centella asiatica extract is 15 wt% to 20 wt%.

[0022] In some embodiments, the Centella asiatica extract further comprises a Centella asiatica extract base, wherein the content of the Centella asiatica extract base in the Centella asiatica extract, calculated based on the total mass of the Centella asiatica extract, is greater than 0 wt% and less than or equal to 30 wt%, with the balance being asiaticoside, hydroxyasiatic acid, and asiatic acid. Specifically, the content of asiaticoside in the Centella asiatica extract, calculated based on the total mass of the Centella asiatica extract, is 20 wt%, 25 wt%, 30 wt%, 35 wt%, 40 wt%, 45 wt%, 50 wt%, etc. The content of asiatic acid in the Centella asiatica extract is 20wt%, 25wt%, 30wt%, 35wt%, 40wt%, 45wt%, 50wt%, or any value between any two of these values, and the content of asiatic acid in the Centella asiatica extract is 10wt%, 15wt%, 20wt%, 25wt%, 30wt%, 35wt%, 40wt%, 45wt%, 50wt%, or any value between any two of these values.

[0023] In some embodiments, the Centella asiatica extract further comprises a Centella asiatica extract base, wherein, based on the total mass of the Centella asiatica extract, the content of the Centella asiatica extract base in the Centella asiatica extract is greater than 0 wt% and less than or equal to 30 wt%, with the balance being asiaticoside, asiaticoside, and asiaticoside, wherein, based on the total mass of the Centella asiatica extract, the content of asiaticoside in the Centella asiatica extract is 30 wt%, the content of asiaticoside in the Centella asiatica extract is 30 wt%, and the content of asiaticoside in the Centella asiatica extract is 15 wt%.

[0024] In some embodiments, the content of the Centella asiatica extract is 1 wt% to 5 wt% based on the total weight of the composition. In some embodiments, the content of the Centella asiatica extract is 1 wt%, 2 wt%, 3 wt%, 4 wt%, 5 wt%, or any value within the range of any two of these values, based on the total weight of the composition.

[0025] In some embodiments, the content of ginsenosides, calculated based on the total weight of the composition, is 0.05 wt% to 0.5 wt%. In some embodiments, the content of ginsenosides, calculated based on the total weight of the composition, is 0.05 wt%, 0.1 wt%, 0.15 wt%, 0.2 wt%, 0.25 wt%, 0.3 wt%, 0.35 wt%, 0.4 wt%, 0.45 wt%, 0.5 wt%, or any value within the range of any two of these values.

[0026] In some embodiments, the content of aescin is 0.1 wt% to 1 wt% based on the total weight of the composition. In some embodiments, the content of aescin is 0.1 wt%, 0.5 wt%, 1 wt%, or any value within the range of any two of these values, based on the total weight of the composition.

[0027] In some embodiments, the content of the polyol, calculated based on the total weight of the composition, is 5 wt% to 20 wt%. In some embodiments, the content of the polyol, calculated based on the total weight of the composition, is 5 wt%, 10 wt%, 15 wt%, 20 wt%, or any value within the range of any two of these values.

[0028] In some embodiments, the content of the stabilizer is 0.1 wt% to 1 wt% based on the total weight of the composition. In some embodiments, the content of the stabilizer is 0.1 wt%, 0.5 wt%, 1 wt%, or any value within the range of any two of these values, based on the total weight of the composition.

[0029] In some embodiments, the content of the yeast fermentation product, calculated based on the total weight of the composition, is 1 wt% to 5 wt%. In some embodiments, the content of the yeast fermentation product, calculated based on the total weight of the composition, is 1 wt%, 2 wt%, 3 wt%, 4 wt%, 5 wt%, or any value within the range of any two of these values.

[0030] In some embodiments, the content of the oil is 68 wt% to 93 wt% based on the total weight of the composition. In some embodiments, the content of the oil is 68 wt%, 70 wt%, 75 wt%, 80 wt%, 85 wt%, 90 wt%, 93 wt% or any value within the range of any two of these values, based on the total weight of the composition.

[0031] In some embodiments, the total content of the active ingredient, the yeast fermentation product, the stabilizer, the oil and the polyol is 100 wt% based on the total weight of the composition.

[0032] In some embodiments, based on the total weight of the composition, the content of the Centella asiatica extract is 1wt%~5wt%, the content of the ginsenosides is 0.05wt%~0.5wt%, the content of the aesculinary aesculin is 0.1wt%~1wt%, the content of the polyols is 5wt%~20wt%, the content of the stabilizer is 0.1wt%~1.0wt%, the content of the yeast fermentation product is 1.0wt%~5.0wt%, and the balance is the oil.

[0033] In a second aspect, the present invention provides a method for preparing the composition described in the first aspect.

[0034] A method for preparing the composition according to the first aspect, characterized by comprising the following steps: (1) Preparation of solution 1: Mix the active ingredient and polyol, heat until dissolved, to obtain solution 1; (2) Preparation of solution 2: Mix yeast fermentation products, stabilizer and oil to obtain solution 2; (3) Preparation of solution 3: Add solution 1 to solution 2 while stirring to obtain solution 3; (4) The solution 3 obtained in step (3) is subjected to high-pressure homogenization or microfluidic technology to obtain the composition.

[0035] In some embodiments, the heating in step (1) is to heat to 65°C to 70°C (such as 65°C, 66°C, 67°C, 68°C, 69°C, 70°C or any value within the range of any two of these values) to dissolve the material.

[0036] In some embodiments, the mixing temperature in step (2) is 38°C to 45°C (e.g., 38°C, 39°C, 40°C, 41°C, 42°C, 43°C, 44°C, 45°C, or any value within a range of any two of these values).

[0037] In some embodiments, the mixing in step (3) includes: cooling the solution 1 obtained in step (1) to 45°C to 48°C (e.g., 45°C, 46°C, 47°C, 48°C or any value within the range of any two of these values), and then mixing it with the solution 2 obtained in step (2) at 38°C to 45°C (e.g., 38°C, 39°C, 40°C, 41°C, 42°C, 43°C, 44°C, 45°C or any value within the range of any two of these values).

[0038] In some embodiments, the temperature of solution 3 in step (4) before high-pressure homogenization or microfluidic treatment is 38°C-45°C (e.g., 38°C, 39°C, 40°C, 41°C, 42°C, 43°C, 44°C, 45°C or any value within any two of these ranges).

[0039] In some embodiments, the pressure of the high-pressure homogenization is 600 bar to 1000 bar (e.g., 600 bar, 650 bar, 700 bar, 750 bar, 800 bar, 850 bar, 900 bar, 950 bar, 1000 bar or any value within the range of any two of these values).

[0040] In some embodiments, the high-pressure homogenization is performed 4, 5, or 6 times.

[0041] In some embodiments, the microfluidic technology treatment includes homogenizing once, twice, three times, or four times under conditions of 100MPa to 200MPa (such as 100MPa, 110MPa, 120MPa, 130MPa, 140MPa, 150MPa, 160MPa, 170MPa, 180MPa, 190MPa, 200MPa, or any value within the range of any two of these values).

[0042] In some embodiments, the microfluidic technology treatment includes homogenization at 120 MPa for 1, 2, 3 or 4 times.

[0043] Thirdly, the present invention provides a formulation product.

[0044] A pharmaceutical product comprising the composition described in the first aspect or the composition prepared by the preparation method described in the second aspect.

[0045] In some embodiments, the formulation product includes a medical device or a cosmetic.

[0046] In some embodiments, the medical device includes medical dressings.

[0047] In some embodiments, the cosmetic is a functional cosmetic.

[0048] In some embodiments, the cosmetic product is formulated as an oil-based preparation, serum, lotion, emulsion, cream, mask, or spray.

[0049] In some embodiments, the oil-based formulation includes eye oil or care oil.

[0050] Thirdly, the present invention provides an application of the composition described in the first aspect or the composition prepared by the preparation method described in the second aspect.

[0051] The use of a composition described in the first aspect or a composition prepared by the preparation method described in the second aspect in the preparation of a formulation for firming, anti-wrinkle, anti-aging and / or dark circle removal.

[0052] In some embodiments, the dark circles include vascular dark circles.

[0053] In some embodiments, the formulation product includes a medical device or a cosmetic.

[0054] In some embodiments, the medical device includes medical dressings.

[0055] In some embodiments, the cosmetic is a functional cosmetic.

[0056] In some embodiments, the cosmetic product is formulated as an oil-based preparation, serum, lotion, emulsion, cream, mask, or spray.

[0057] In some embodiments, the oil-based formulation includes eye oil or care oil.

[0058] Beneficial effects Compared with the prior art, the technical solution provided by the present invention has at least one of the following beneficial technical effects: (1) The composition provided by the present invention has excellent elastase inhibition effect, excellent anti-wrinkle, skin elasticity enhancement, anti-skin aging, and dark circle lightening effects, and can relieve vasodilation to improve vascular dark circles.

[0059] (2) The composition provided by the present invention has excellent stability and excellent appearance and active ingredient content stability under high temperature, light and high and low temperature cycling conditions, and has unexpected technical effects.

[0060] (3) The composition provided by the present invention has excellent stability and compatibility in oil-based or oil-containing formulations. It can remain transparent, without precipitation, discoloration and stratification after being placed at a high temperature of 45°C or a low temperature of 5°C for 30 days, and has excellent compatibility and stability.

[0061] (4) Compared with other solubilizers or other fermentation products, the present invention preferably adds yeast fermentation products (especially sophorolipids), which is more conducive to the appearance and stability of active ingredient content of the obtained composition under high temperature, strong light and high and low temperature cycling conditions, and has unexpected technical effects.

[0062] (5) Compared with other polyols, the present invention prefers dipropylene glycol or dipropylene glycol and ethoxydiethylene glycol as the polyols in the composition of the present invention, which is more conducive to the appearance and stability of the active ingredient content of the obtained composition under high temperature, strong light and high and low temperature cycling conditions, and has unexpected technical effects.

[0063] (6) Compared with other oils, the present invention prefers macadamia nut oil and / or sunflower seed oil as the oils in the composition of the present invention, which is more conducive to the stability of the appearance and active ingredient content of the obtained composition under high temperature, strong light and high and low temperature cycling conditions, and has unexpected technical effects.

[0064] (7) In this invention, yeast fermentation products (especially sophorolipids) are preferably added, dipropylene glycol or dipropylene glycol and ethoxydiethylene glycol are preferably used as the polyols of this invention, and macadamia nut oil and / or sunflower seed oil are preferably used as the oils of this invention. These technical means are indispensable and work together to improve the appearance and stability of the active ingredient content of the obtained composition under high temperature, strong light and high and low temperature cycling conditions, and have unexpected technical effects.

[0065] (8) Compared with other fermentation products or other solubilizers, the composition of the present invention preferably uses yeast fermentation products (especially sophorolipids), which is more conducive to the compatibility of the obtained composition with most other oils (it can remain transparent, without precipitation, discoloration and stratification after being placed at a high temperature of 45°C or a low temperature of 5°C for 30 days, and has excellent compatibility and stability), which is conducive to improving the stability and compatibility of the obtained composition in oil-based or oil-containing preparations, and has unexpected technical effects.

[0066] (9) Compared with other polyols, the present invention prefers dipropylene glycol or dipropylene glycol and ethoxydiethylene glycol as the polyols in the composition of the present invention, which is more conducive to the compatibility of the obtained composition with most other oils (it can remain transparent, without precipitation, discoloration and stratification after being placed at a high temperature of 45°C or a low temperature of 5°C for 30 days, and has excellent compatibility and stability), which is conducive to improving the stability and compatibility of the obtained composition in oil-based preparations or oil-containing preparations, and has unexpected technical effects.

[0067] (10) Compared with other oils, the present invention prefers macadamia nut oil and / or sunflower seed oil as the oils in the composition of the present invention, which is more conducive to the compatibility of the obtained composition with most other oils (it can remain transparent, without precipitation, discoloration and stratification after being placed at a high temperature of 45°C or a low temperature of 5°C for 30 days, and has excellent compatibility and stability), which is conducive to improving the stability and compatibility of the obtained composition in oil-based preparations or oil-containing preparations, and has unexpected technical effects.

[0068] (11) In this invention, yeast fermentation products (especially sophorolipids) are preferably added, dipropylene glycol or dipropylene glycol and ethoxydiethylene glycol are preferably used as the polyols of this invention, and macadamia nut oil and / or sunflower seed oil are preferably used as the oils of this invention. These technical means are indispensable and work together to improve the compatibility of the obtained composition with most other oils (it can remain transparent, without precipitation, discoloration and stratification after being placed at a high temperature of 45°C or a low temperature of 5°C for 30 days, and has excellent compatibility and stability). This is beneficial to improving the stability and compatibility of the obtained composition in oil-based preparations or oil-containing preparations, and has unexpected technical effects.

[0069] Terminology Explanation In the foregoing description of this invention, all figures disclosed herein, whether or not the words “approximately” or “about” are used, are approximate values. Based on the disclosed figures, the value of each figure may vary by less than ±10% or by a difference that is considered reasonable by those skilled in the art, such as ±1%, ±2%, ±3%, ±4%, or ±5%.

[0070] The term “room temperature” refers to ambient temperature, which is between approximately 15°C and approximately 35°C, or approximately 20°C and approximately 30°C, or approximately 25°C.

[0071] The terms “optional,” “optional,” or “optionally” refer to events or situations that may, but are not necessarily, occur as described below.

[0072] The term “and / or” should be understood to mean any one of the options or any combination of two or more of the options.

[0073] The term "wt%" indicates a percentage by mass.

[0074] The term "balance" means that the indicated ingredient is added to the composition or mixture in a total amount of 100 wt%.

[0075] Centella asiatica extract: its CAS number is 16830-15-2.

[0076] Asiatic acid: its CAS number is 464-92-6.

[0077] Hydroxyasiatic acid: its CAS number is 18449-41-7.

[0078] "Centella Asiatica Extract Base" or "Centella Asiatica Extract Base" means: the remaining components of Centella Asiatica extract prepared from Centella Asiatica through extraction, separation and / or purification processes, after deducting asiaticoside, hydroxyasiatic acid and asiatic acid. These remaining components are derived solely from the Centella Asiatica raw material itself and do not contain exogenously added solvents, stabilizers, diluents or other process excipients. These remaining components contain other active ingredients and / or inactive ingredients.

[0079] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the present invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. Moreover, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described in this specification, as well as the features of different embodiments or examples. Detailed Implementation

[0080] To enable those skilled in the art to better understand the technical solutions of the present invention, some non-limiting embodiments are further disclosed below to provide a more detailed description of the present invention.

[0081] I. All reagents used in this invention can be purchased from the market or prepared by the method described in this invention.

[0082] Unless otherwise stated, the following information pertains to the components used in the embodiments and comparative examples of this invention: (1) Centella Asiatica extract: purchased from Guangxi Changzhou Natural Pharmaceutical Co., Ltd., product number F250303, product name: Centella Asiatica TECA 75%; wherein, the “Centella Asiatica TECA 75%” contains 30wt% asiaticoside, 15wt% asiatic acid, 30wt% hydroxyasiatic acid and 25wt% Centella Asiatica extract base.

[0083] (2) Ginsenosides: CAS No. 39262-14-1; purchased from Guangzhou Qingnang Biotechnology Co., Ltd., item number 25031201, product name: Ginsenoside CK.

[0084] (3) Aescin: CAS No. 6805-41-0; purchased from Guangzhou Aoxue Biotechnology Co., Ltd., item number 25031301, product name: ESCIN.

[0085] (4) Bacillus fermentation product: purchased from Beijing Yanwei Technology Co., Ltd., product number 240901, product name: Nano-Liquid Fusion.

[0086] II. Detection Methods If the sample to be tested shows phenomena such as stratification or precipitation, it should be shaken well before sampling and testing.

[0087] The content of asiaticoside was determined by high performance liquid chromatography (HPLC). The chromatographic conditions for HPLC were as follows: Column: Agilent Zorbax Extend C18 (4.6 mm × 250 mm, 5 μm); Mobile phase: Acetonitrile-2 mmol / L β-cyclodextrin aqueous solution (24:76, V / V); Detection wavelength: 205nm; Flow rate: 0.8~1.0 mL / min; Column temperature: 25~30℃.

[0088] Example 1: Preparation of the composition Formula: See Table 1.

[0089] Table 1: Formulation of the composition in Example 1 ; Preparation method: (1) Preparation of solution 1: Mix the active ingredient and polyol, heat to 65℃ (65℃~70℃) to dissolve, and obtain solution 1; (2) Preparation of solution 2: Mix yeast fermentation product, stabilizer and oil at 45℃ (or 38℃~45℃) to obtain solution 2; (3) Preparation of solution 3: Cool solution 1 to 46℃ (45℃-48℃), then add it to solution 2 at 45℃ (38℃~45℃) while stirring to obtain solution 3, and keep it at 46℃ (45℃~48℃). (4) The solution 3 obtained in step (3) is subjected to high pressure homogenization (800 bar (600 bar to 1000 bar), homogenization 4 times (4 to 6 times)) to obtain the composition.

[0090] Comparative Examples 1-2: Investigation of Yeast Fermentation Products Comparative Example 1: The only difference from Example 1 is that sophorolipid was replaced with polyglycerol-10 oleate, and the other conditions are the same as in Example 1.

[0091] Comparative Example 2: The only difference from Example 1 is that sophorolipids are replaced with Bacillus fermentation products, and the other conditions are the same as in Example 1.

[0092] Comparative Examples 3-4: Investigation of Polyols Comparative Example 3: The only difference from Example 1 is that the dipropylene glycol in the polyol is replaced with glycerol, and the other conditions are the same as in Example 1.

[0093] Comparative Example 4: The only difference from Example 1 is that dipropylene glycol in the polyol is replaced with isohexyl glycol, and the other conditions are the same as in Example 1.

[0094] Comparative Examples 5-6: Examination of Oils Comparative Example 5: The only difference from Example 1 is that the macadamia nut oil in the oil is replaced with caprylic / capric triglyceride, and the other conditions are the same as in Example 1.

[0095] Comparative Example 6: The only difference from Example 1 is that the macadamia nut oil in the oil is replaced with isononyl isononanoate, and the other conditions are the same as in Example 1.

[0096] Examples 2-4: Preparation of the Composition Formula: See Table 2.

[0097] Table 2: Formulations of the compositions in Examples 2-4 ; Note: " / " indicates that this ingredient is not added.

[0098] Preparation methods of Examples 2, 4, and 5: The preparation methods of Example 1 were followed.

[0099] Preparation method of Example 3: The difference from the preparation method of Example 1 is that in the preparation method of Example 4, step (4) uses microfluidic technology (120MPa (can be 100MPa~200MPa), homogenizes twice (can be 1~4 times)) to treat the solution 3 obtained in step (3), and the rest of the operation is the same as in Example 1.

[0100] Experimental Example 1: Stability Study 24-hour room temperature test: The compositions obtained in the above examples and comparative examples were placed at room temperature (25°C) for 24 hours to test the product stability (appearance and asiaticoside content). The results are shown in Tables 3 and 4.

[0101] High-temperature stability study: The compositions obtained in the above examples and comparative examples were placed at 50°C to test the product stability (appearance and asiaticoside content) for 3 months. The results are shown in Tables 3 and 4.

[0102] Strong light irradiation test: The products obtained in each of the above embodiments or comparative examples were placed in transparent containers and placed in a light box with an illuminance of 4500 lx ± 500 lx for 10 days. Samples were taken on the 10th day for testing. The results are shown in Tables 3 and 4.

[0103] High and low temperature cycling: The sample to be tested was placed in a high and low temperature cycling chamber. The conditions were set as follows: placed at 45℃ for 24 hours, then restored to room temperature for 12 hours, then placed at 15℃ for 24 hours, and then restored to room temperature for 12 hours. This constitutes one high and low temperature cycle. Each sample to be tested needs to be tested for six cycles, and its stability is observed. The results are shown in Tables 3 and 4.

[0104] Table 3: Results of appearance characteristics during stability study ; Table 4: Results of stability study on asiaticoside content in each example ; Note: The percentage decrease in asiaticoside content compared to day 0 represents the value obtained by subtracting the asiaticoside content at the stability test time point from the asiaticoside content of the sample at day 0.

[0105] in conclusion: (1) Compared with other solubilizers or other fermentation products, the composition of the present invention preferably contains yeast fermentation products (especially sophorolipids), which is more conducive to the stability of the appearance and active ingredient content of the obtained composition under high temperature, strong light and high and low temperature cycling conditions, and has unexpected technical effects.

[0106] (2) Compared with other polyols, the present invention prefers dipropylene glycol or dipropylene glycol and ethoxydiethylene glycol as the polyols in the composition of the present invention, which is more conducive to the appearance and stability of the active ingredient content of the obtained composition under high temperature, strong light and high and low temperature cycling conditions, and has unexpected technical effects.

[0107] (3) Compared with other oils, the present invention prefers macadamia nut oil and / or sunflower seed oil as the oils in the composition of the present invention, which is more conducive to the stability of the appearance and active ingredient content of the obtained composition under high temperature, strong light and high and low temperature cycling conditions, and has unexpected technical effects.

[0108] (4) In this invention, yeast fermentation products (especially sophorolipids) are preferably added, dipropylene glycol or dipropylene glycol and ethoxydiethylene glycol are preferably used as the polyols of this invention, and macadamia nut oil and / or sunflower seed oil are preferably used as the oils of this invention. These technical means are indispensable and work together to improve the appearance and stability of the active ingredient content of the obtained composition under high temperature, strong light and high and low temperature cycling conditions, and have unexpected technical effects.

[0109] Experimental Example 2: Compatibility and Stability Study of the Composition with Oils The above-mentioned Example 4 was mixed with other oils (see Table 5), and then placed at a high temperature of 45°C and a low temperature of 5°C to examine its compatibility with different oils. The results are shown in Tables 5 and 6.

[0110] Table 5: Compatibility and stability study of the composition with some oils (high temperature 45℃) ; Table 6: Compatibility and stability study of the composition with some oils (low temperature 5℃) ; in conclusion: (1) Compared with other fermentation products or other solubilizers, the composition of the present invention preferably uses yeast fermentation products (especially sophorolipids), which is more conducive to the compatibility of the obtained composition with most other oils (it can remain transparent, without precipitation, discoloration and stratification after being placed at a high temperature of 45°C or a low temperature of 5°C for 30 days, and has excellent compatibility and stability), which is conducive to improving the stability and compatibility of the obtained composition in oil-based preparations or oil-containing preparations, and has unexpected technical effects.

[0111] (2) Compared with other polyols, the present invention prefers dipropylene glycol or dipropylene glycol and ethoxydiethylene glycol as the polyols of the composition of the present invention, which is more conducive to the compatibility of the obtained composition with most other oils (it can remain transparent, without precipitation, discoloration and stratification after being placed at high temperature of 45°C or low temperature of 5°C for 30 days, and has excellent compatibility and stability), which is conducive to improving the stability and compatibility of the obtained composition in oil-based preparations or oil-containing preparations, and has unexpected technical effects.

[0112] (3) Compared with other oils, the present invention prefers macadamia nut oil and / or sunflower seed oil as the oils in the composition of the present invention, which is more conducive to the compatibility of the obtained composition with most other oils (it can remain transparent, without precipitation, discoloration and stratification after being placed at a high temperature of 45°C or a low temperature of 5°C for 30 days, and has excellent compatibility and stability), which is conducive to improving the stability and compatibility of the obtained composition in oil-based preparations or oil-containing preparations, and has unexpected technical effects.

[0113] (4) In this invention, yeast fermentation products (especially sophorolipids) are preferably added, dipropylene glycol or dipropylene glycol and ethoxydiethylene glycol are preferably used as the polyols of this invention, and macadamia nut oil and / or sunflower seed oil are preferably used as the oils of this invention. These technical means are indispensable and work together to improve the compatibility of the obtained composition with most other oils (it can remain transparent, without precipitation, discoloration and stratification after being placed at a high temperature of 45°C or a low temperature of 5°C for 30 days, and has excellent compatibility and stability). This is beneficial to improving the stability and compatibility of the obtained composition in oil-based preparations or oil-containing preparations, and has unexpected technical effects.

[0114] Experimental Example 3: Efficacy Assessment 1. Elastase inhibition rate experiment: (1) Solution preparation: • Enzyme solution: Porcine pancreatic elastase (Sigma E1250) was prepared to 0.5 U / mL using 0.1 mol / L Tris-HCl buffer (pH 8.0); • Substrate solution: N-succinyl-L-alanyl-L-alanyl-L-alanine (Sigma S4760) was prepared with buffer to a concentration of 1 mmol / L; • Test solution: Dissolve the compositions obtained in each example in buffer solution to prepare a 0.1 wt% solution (calculated based on the total weight of the composition to be tested).

[0115] (2) Experimental Groups: • Sample group: 50 μL enzyme solution + 50 μL test solution + 100 μL substrate solution; • Sample background group: 50 μL buffer solution + 50 μL test solution + 100 μL substrate solution; • Solvent group: 50 μL enzyme solution + 50 μL buffer solution + 100 μL substrate solution; • Solvent background group: 50 μL buffer + 50 μL buffer + 100 μL substrate solution; Positive control group: 0.1% EGCG (epigallocatechin gallate glucoside) aqueous solution (as a substitute for the test substance solution).

[0116] (3) Experimental procedure: (3.1) After mixing the solutions, incubate at 37°C for 15 minutes; (3.2) The absorbance (A) was measured at a wavelength of 410 nm using an ELISA reader, and the inhibition rate was calculated according to the formula: Inhibition rate (%) = [1 - (Sample A - Sample A background) / (Solvent A - Solvent A background)] × 100%; in, Sample A represents the absorbance of the sample group solution at 410 nm; Sample background A represents the absorbance of the sample background group at 410 nm; A solvent background represents the absorbance of the solvent background group at 410 nm.

[0117] The inhibition rate of the positive control group was calculated using a similar method, with the absorbance of the positive control group at 410 nm used as sample A, and the absorbance of water at 410 nm used as the background of sample A.

[0118] Each group had 3 parallel holes, and the experiment was repeated 3 times. The average value was taken, and the results are shown in Table 7.

[0119] Table 7: Results of elastase inhibition rate (n=3) ; (4) Conclusion As shown in Table 7, the composition provided by the present invention has excellent elastase inhibition effect and excellent anti-wrinkle, skin elasticity enhancement and anti-skin aging effects.

[0120] 2. Human efficacy test for reducing dark circles: Thirty-two eligible volunteers, half male and half female, aged 23-47 years, were selected. Test areas were marked on the left and right sides of each volunteer's face (the left cheek was the test sample (obtained by mixing the composition of Example 1 with sunflower seed oil, where the composition of Example 1 accounted for 5 wt%), and the right cheek was a blank sample without any treatment). The test oil was applied twice daily, at 9:00 AM and 8:00 PM. During the experiment, volunteers were not allowed to apply any other cosmetics to the test areas. The test oil was used continuously for one month. On day 0 (before use), day 14, and day 28, volunteers washed the applied areas with water. The melanin index (MI) was measured using a Mexameter MX18 (MI values ​​range from 0-999, with higher values ​​indicating higher melanin content), and the ITA value was measured using a Colorimeter CL400 (higher ITA values ​​indicate lighter skin tone). Simultaneously, the L and a values ​​of the skin color at the application sites were measured using a spectrophotometer. The test results show the numerical changes in Tables 8 and 9.

[0121] Table 8: Results of Melanin Index (MI) and ITA Value Detection ; in conclusion: Test results showed that, compared with the baseline value (day 0 (before use)), the melanin in the skin around the eyes was significantly reduced on the experimental side at the follow-up visits on days 14 and 28, and the ITA value of the skin color around the eyes was significantly increased compared with day 0, proving that the composition provided by the present invention has a good effect on lightening dark circles.

[0122] Table 9: Results of Colorimetric L and a Value Tests ; Application of L value: Vascular dark circles are caused by poor skin translucency due to vasodilation, resulting in a low L value. After improvement, the L value increases, indicating improved skin brightness.

[0123] Application of the a value: The bluish-purple color of vascular dark circles belongs to the "red-purple" tone (high a value). After improvement, the a value is significantly reduced, indicating that the bluish-purple tone is weakened and the vasodilation is relieved.

[0124] in conclusion: Test results showed that, compared with the baseline value (day 0 (before use)), the L value of the eye skin was significantly improved and the a value of the eye skin was significantly reduced when the test side was revisited on day 14 and day 28. This indicates that the composition provided by the present invention has the effect of improving dark circles and can relieve vasodilation, thereby improving vascular dark circles.

[0125] The method of this invention has been described through preferred embodiments. Those skilled in the art will readily be able to modify or appropriately alter and combine the methods and applications described herein within the scope, spirit, and context of this invention to implement and apply the technology of this invention. Those skilled in the art can refer to the content herein to appropriately improve process parameters. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art and are considered to be included within the scope of this invention.

Claims

1. A composition, characterized in that, Comprise: active ingredients, yeast fermentation product, stabilizer, oil and polyol; wherein the active ingredients comprise: Centella asiatica extract, ginsenoside and aescine; the Centella asiatica extract comprises asiaticoside, madecassic acid and madecassic acid; the yeast fermentation product comprises at least one of sophorolipid and rhamnolipid.

2. The composition according to claim 1, wherein the oil comprises at least one of macadamia nut oil, sunflower seed oil, rapeseed oil, olive oil, triglyceride, preferably at least one of macadamia nut oil, sunflower seed oil and rapeseed oil, more preferably at least two of macadamia nut oil, sunflower seed oil and rapeseed oil, most preferably at least one of macadamia nut oil, sunflower seed oil and rapeseed oil; and / or the ginsenoside comprises ginsenoside CK.

3. The composition according to any one of claims 1-2, wherein the polyol comprises at least one of ethoxydiglycol, 1,3-butanediol, dipropylene glycol and isohexide; preferably at least one of ethoxydiglycol and dipropylene glycol; more preferably dipropylene glycol or ethoxydiglycol and dipropylene glycol; and / or the stabilizer comprises tocopherol; and / or the asiaticoside is present in the Centella asiatica extract in an amount of 20wt%-50wt% based on the total mass of the Centella asiatica extract; and / or the madecassic acid is present in the Centella asiatica extract in an amount of 20wt%-50wt% based on the total mass of the Centella asiatica extract; and / or the madecassic acid is present in the Centella asiatica extract in an amount of 10wt%-50wt% based on the total mass of the Centella asiatica extract; and / or the total amount of the asiaticoside, madecassic acid and madecassic acid in the Centella asiatica extract is 100wt% based on the total mass of the Centella asiatica extract; and / or the Centella asiatica extract further comprises a Centella asiatica extract base, and the amount of the Centella asiatica extract base in the Centella asiatica extract is greater than 0wt% and less than or equal to 30wt% based on the total mass of the Centella asiatica extract, and the rest is the asiaticoside, madecassic acid and madecassic acid.

4. The composition according to any one of claims 1-3, wherein the amount of the Centella asiatica extract is 1wt%-5wt% based on the total weight of the composition; and / or the amount of the ginsenoside is 0.05wt%-0.5wt% based on the total weight of the composition; and / or the amount of the aescine is 0.1wt%-1wt% based on the total weight of the composition; and / or the amount of the polyol is 5wt%-20wt% based on the total weight of the composition; and / or the amount of the stabilizer is 0.1wt%-1wt% based on the total weight of the composition; and / or the amount of the yeast fermentation product is 1wt%-5wt% based on the total weight of the composition; and / or the amount of the oil is 68wt%-93wt% based on the total weight of the composition. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ 5. The composition of any one of claims 1-3, wherein the content of the extract of Centella asiatica is 1 wt% to 5 wt%, the content of the ginsenoside is 0.05 wt% to 0.5 wt%, the content of the aescin is 0.1 wt% to 1 wt%, the content of the polyol is 5 wt% to 20 wt%, the content of the stabilizer is 0.1 wt% to 1.0 wt%, the content of the yeast fermentation product is 1.0 wt% to 5.0 wt%, and the balance is the oil.

6. A process for the preparation of a composition according to any one of claims 1 to 5, characterized in that, comprising the following steps: (1) Preparation of solution 1: mixing the active ingredients and the polyol, heating to dissolve, to obtain solution 1; (2) Preparation of solution 2: mixing the yeast fermentation product, the stabilizer and the oil to obtain solution 2; (3) Preparation of solution 3: adding solution 1 to solution 2, stirring while adding, to obtain solution 3; (4) Homogenizing or microfluidizing the solution 3 obtained in step (3) to obtain the composition.

7. The preparation method of claim 6, wherein the heating in step (1) is heating to 65°C to 70°C for dissolving; and / or the mixing in step (2) is at a temperature of 38°C to 45°C; and / or The mixing of step (3) comprises: solution 1 obtained in step (1) is cooled to 45°C to 48°C, and then mixed with solution 2 obtained in step (2) at 38°C to 45°C; and / or the temperature of solution 3 before being homogenized or microfluidized in step (4) is 38°C to 45°C; and / or the pressure of the high-pressure homogenization is 600 bar to 1000 bar; and / or the number of times of high-pressure homogenization is 4 times, 5 times or 6 times; and / or the microfluidization includes homogenizing 1 time, 2 times, 3 times or 4 times at 100 MPa to 200 MPa or 120 MPa.

8. A formulation product, characterized by, the composition of any one of claims 1-5 or the composition prepared by the preparation method of claim 7; optionally, the formulation product comprises a medical device or a cosmetic product; optionally, the medical device comprises a medical patch; optionally, the cosmetic product is a functional cosmetic product; optionally, the formulation form of the cosmetic product is an oil-based formulation, a serum, a toner, a lotion, a cream, a mask or a spray; optionally, the oil-based formulation comprises an eye oil or a care oil.

9. Use of the composition of any one of claims 1-5 or the composition prepared by the preparation method of claim 7 in the preparation of a formulation product for firming, anti-wrinkling, anti-aging and / or dark circle removal.

10. The use of claim 9, wherein the dark circle comprises a blood vessel type dark circle; optionally, the formulation product comprises a medical device or a cosmetic product; optionally, the medical device comprises a medical patch; optionally, the cosmetic product is a functional cosmetic product; optionally, the formulation form of the cosmetic product is an oil-based formulation, a serum, a toner, a lotion, a cream, a mask or a spray; optionally, the oil-based formulation comprises an eye oil or a care oil.