An injectable cosmetic filler composition, its preparation method and application

Abstract

This invention discloses an injectable cosmetic filler composition, its preparation method, and its application. The injectable cosmetic filler composition includes modified poly-L-lactic acid microspheres, cellulose ethers, and sodium hyaluronate; the modified poly-L-lactic acid microspheres are block copolymers of lactic acid and alcohol. The composition of this invention can be injected into the deep dermis to promote collagen regeneration, thereby correcting facial contour defects. It can effectively fill areas lacking facial support, is non-irritating, has good wrinkle-reducing effects, high biocompatibility, and good stability and safety.

Description

Technical Field

[0001] This invention belongs to the field of biotechnology and relates to an injectable cosmetic filler composition, its preparation method, and its application. Background Technology

[0002] Injectable cosmetic procedures are a type of non-surgical cosmetic surgery. They involve injecting biological or synthetic biocompatible materials into the dermis or subcutaneous layer to reduce skin wrinkles or achieve a more sculpted appearance through various mechanisms of action.

[0003] Sodium hyaluronate is a highly biocompatible polysaccharide biomaterial with a well-defined degradation and metabolism process in vivo, indicating its safety for human use. For example, CN113941027A discloses an injectable facial filler composition gel for cosmetic surgery and its preparation method, comprising 10-20 parts sodium hyaluronate, 90-100 parts an aqueous solution for injection, 2-5 parts collagen powder, 5-8 parts modified microparticles, 0.1-0.2 parts an extractant, and 0.4-0.7 parts a complex vitamin. However, current hyaluronic acid products have the following drawbacks: 1. High cost for consumers, with each injection costing thousands or even tens of thousands of yuan; 2. Hyaluronic acid gels are basically degraded and absorbed in the body within about 6 months, requiring repeated injections, increasing the burden and pain for consumers; 3. Potential for serious complications such as vascular embolism. Currently, cross-linked hyaluronic acid is widely used in minimally invasive cosmetic procedures, breast augmentation, and drug delivery. However, during use, it has been found that cross-linked hyaluronic acid has certain defects. When cross-linking hyaluronic acid is used alone, there may still be unreacted terminal groups exposed on the surface of the gel particles after cross-linking. This can cause redness and swelling in some users after surgery and does not have a skin repair effect. In addition, incomplete cross-linking can easily leave cross-linking agent residue, which may pose a safety hazard.

[0004] CN111249525A discloses an injectable facial filler composition gel for cosmetic surgery and its preparation method, comprising a combined gel matrix and poly-L-lactic acid. The combined gel matrix includes an injectable aqueous solution, sodium hyaluronate, and poly-L-lactide spheres. The poly-L-lactide spheres account for 0.5%-30% of the total weight of the injectable aqueous solution, and the sodium hyaluronate accounts for 0.1%-30% of the total weight of the injectable aqueous solution. This invention contains chemically cross-linked hyaluronic acid solutions containing PLA microspheres or crystals, which can be injected into the epidermis, middle or deep dermis to correct facial contour defects. Such compositions can also be injected into the loose connective tissue around the lip muscles or into the lips to improve the appearance of the lips, and can be applied to specific areas such as the face. However, the poly-L-lactide spheres and other substances only perform tissue filling and cannot effectively stimulate collagen regeneration in the dermis, resulting in poor biocompatibility.

[0005] In summary, current injectable cosmetic filler compositions suffer from poor cross-linking of hyaluronic acid, leading to redness and swelling in users, safety concerns, lack of skin repair effects, and potential for vascular embolism. Therefore, developing an injectable cosmetic filler composition that effectively fills areas of the face lacking support, is non-irritating, has good wrinkle-reducing effects, and high biocompatibility has become one of the urgent problems to be solved in the field of biotechnology. Summary of the Invention

[0006] To address the shortcomings of existing technologies and practical needs, this invention provides an injectable cosmetic filler composition, its preparation method, and its application. It solves the problems of poor cross-linking effect and safety hazards in existing cosmetic filler compositions. It can effectively fill areas of the face lacking support, is non-irritating, has a good wrinkle-reducing effect, can promote collagen regeneration in the dermis, and has high biocompatibility.

[0007] To achieve this objective, the present invention adopts the following technical solution:

[0008] In a first aspect, the present invention provides an injectable cosmetic filler composition comprising modified poly-L-lactic acid microspheres, cellulose ethers, and sodium hyaluronate; wherein the modified poly-L-lactic acid microspheres are block copolymers of lactic acid and alcohol.

[0009] The composition of the present invention can be injected into the deep dermis to promote collagen regeneration, thereby correcting facial contour defects. It can effectively fill areas of insufficient facial support, is non-irritating, has good wrinkle-reducing effects, high biocompatibility, and good stability and safety.

[0010] Preferably, the ratio of lactic acid to alcohol in the modified poly-L-lactic acid microspheres is (5-30):(0.5-5).

[0011] The specific point values ​​in (5-30) above can be selected as 5, 6, 7, 8, 15, 16, 18, 20, 25, 27, 28, 29, 30, etc.

[0012] The specific point values ​​in (0.5-5) above can be 0.5, 0.6, 0.7, 0.8, 1, 2, 3, 4, 4.5, 4.7, 4.8, 4.9, 5, etc.

[0013] Preferably, the alcohol includes polyethylene glycol.

[0014] Preferably, the mass ratio of the modified poly(L-lactic acid) microspheres, cellulose ethers, and sodium hyaluronate is (10-40):(0.5-7):(0.1-5).

[0015] The specific point values ​​in (10-40) above can be selected as 10, 11, 13, 14, 25, 26, 37, 38, 39, 40, etc.

[0016] The specific point values ​​in (0.5-7) above can be 0.5, 0.6, 0.7, 1, 2, 3, 4, 5, 6, 7, etc.

[0017] The specific point values ​​in (0.5-1) above can be 0.5, 0.6, 0.7, 0.8, 0.9, 1, etc.

[0018] Preferably, the preparation method of the modified poly-L-lactic acid microspheres includes the following steps:

[0019] (1) After mixing L-lactide, ethyl acetate and ethanol, heat and filter. Cool the filtrate and stir. After all the crystals have precipitated, filter and dry to remove ethyl acetate and ethanol to obtain purified L-lactide.

[0020] (2) The purified L-lactide, polyethylene glycol and methoxy polyethylene glycol are mixed, heated to dissolve and reacted with the catalyst stannous octoate. The solid obtained after the reaction is kept at a certain temperature is mixed with dichloromethane and ethanol. The precipitated solid is collected and filtered and dried to remove dichloromethane and ethanol solvent, thus obtaining the modified poly-L-lactic acid polymer.

[0021] (3) The modified poly-L-lactic acid polymer, dichloromethane and polyvinyl alcohol were mixed, and the dichloromethane was removed by distillation with deionized water. The mixture was then allowed to stand. After standing, the solid precipitate was washed, centrifuged and dried to obtain the modified poly-L-lactic acid microspheres.

[0022] Preferably, the heating temperature in step (1) is 50-120°C.

[0023] The specific point values ​​in the range of 50-120 can be selected as 50, 60, 70, 80, 90, 100, 110, 115, 116, 120, etc.

[0024] Preferably, the cooling and stirring time in step (1) is 1-2 hours.

[0025] The specific point values ​​in 1-2 above can be selected as 1, 2, etc.

[0026] Preferably, the mass-volume ratio of L-lactide, ethyl acetate and ethanol in step (1) is (10-30g):(15-25mL):(5-15mL).

[0027] The specific point values ​​in the range 10-30 can be selected as 10, 11, 12, 13, 14, 15, 20, 25, 26, 30, etc.

[0028] The specific point values ​​in the range 15-25 above can be selected as 15, 16, 17, 18, 19, 20, 21, 22, 23, 25, etc.

[0029] The specific point values ​​in 5-15 above can be selected as 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, etc.

[0030] Preferably, the heating temperature in step (2) is 60-150°C.

[0031] The specific point values ​​in the range of 60-150 can be selected as 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, etc.

[0032] Preferably, the reaction time in step (2) is 1-6 hours.

[0033] The specific point values ​​in 1-6 above can be selected as 1, 2, 3, 4, 5, 6, etc.

[0034] Preferably, the mass-to-volume ratio of the purified L-lactide, polyethylene glycol, methoxy polyethylene glycol, dichloromethane and ethanol in step (2) is (10-25g):(0.5-1.5mL):(0.1-0.5mL):(30-70mL):(70-150mL).

[0035] The specific point values ​​in the range 10-25 can be selected as 10, 12, 14, 16, 28, 20, 22, 23, 24, 25, etc.

[0036] Preferably, the resting time in step (3) is 2-4 hours.

[0037] The specific point values ​​in 2-4 above can be 2, 3, 4, etc.

[0038] Preferably, the mass-to-volume ratio of the modified poly(L-lactic acid) polymer, dichloromethane, polyvinyl alcohol and deionized water in step (3) is (5-15g):(20-80mL):(15-50mL):(15-40mL).

[0039] The specific point values ​​in 5-15 above can be selected as 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, etc.

[0040] The specific point values ​​in the range of 20-80 can be selected as 20, 30, 40, 50, 60, 70, 80, etc.

[0041] The specific point values ​​in the range of 15-50 can be selected as 15, 16, 17, 18, 19, 20, 30, 40, 45, 50, etc.

[0042] The specific point values ​​in the range 15-40 can be selected as 15, 16, 17, 18, 19, 20, 30, 40, etc.

[0043] Preferably, the cellulose ethers include any one or a combination of at least two of methylcellulose, sodium carboxymethylcellulose, ethylcellulose, carboxyethylcellulose, hydroxypropylcellulose, or hydroxypropylmethylcellulose.

[0044] Preferably, the molecular weight of the sodium hyaluronate is 300,000-1,500,000 Daltons.

[0045] The specific point values ​​in the range of 300,000-1,500,000 can be selected from 300,000, 400,000, 500,000, 600,000, 700,000, 800,000, 1300,000, 1400,000, 1500,000, etc.

[0046] Preferably, the injectable cosmetic filler composition further includes glycerin, vitamin C, ginkgo biloba extract, anesthetic, and an aqueous solution for injection.

[0047] Preferably, the mass ratio of glycerin, vitamin, ginkgo leaf extract and anesthetic is (0.2-10):(0.1-2):(0.5-3):(0.05-1).

[0048] The specific point values ​​in the range 0.2-10 can be selected from 0.2, 0.3, 0.4, 0.5, 0.6, 1, 2, 4, 5, 6, 8, 9, 10, etc.

[0049] The specific point values ​​in 0.1-2 above can be selected as 0.1, 0.2, 0.3, 0.4, 0.5, 1, 1.5, 2, etc.

[0050] The specific point values ​​in the above 0.5-3 can be selected from 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.5, 2, 2.5, 3, etc.

[0051] The specific point values ​​in the above 0.05-1 can be 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, etc.

[0052] Preferably, the aqueous solution for injection comprises a sodium chloride solution or a phosphate buffer solution.

[0053] Preferably, the anesthetic agent includes any one or a combination of at least two of lidocaine, procaine, eticaine, promocaine, and quinicaine.

[0054] In a second aspect, the present invention provides a method for preparing the injectable cosmetic filler composition described in the first aspect, the method comprising:

[0055] The modified poly-L-lactic acid microspheres, cellulose ethers, and sodium hyaluronate are mixed, homogenized, and sterilized to obtain the injectable cosmetic filler composition.

[0056] Preferably, the sterilization temperature is 110-125℃ and the time is 15-30 minutes.

[0057] The specific point values ​​in the range 110-125 can be selected as 110, 111, 113, 114, 115, 120, 121, 122, 124, 125, etc.

[0058] The specific point values ​​in the range 15-30 can be selected as 15, 16, 17, 18, 19, 20, 21, 22, 24, 25, 28, 30, etc.

[0059] Thirdly, the present invention provides the application of the injectable cosmetic filler composition described in the first aspect in the preparation of injectable cosmetic fillers.

[0060] Compared with the prior art, the present invention has the following beneficial effects:

[0061] The composition of the present invention can be injected into the deep dermis to promote collagen regeneration, thereby correcting facial contour defects. It can effectively fill areas of insufficient facial support, is non-irritating, has good wrinkle-reducing effects, high biocompatibility, and good stability and safety. Attached Figure Description

[0062] Figure 1 Electron micrograph of the modified poly(L-lactic acid) microspheres prepared in Example 1. Detailed Implementation

[0063] To further illustrate the technical means and effects of this invention, the following description, in conjunction with embodiments and accompanying drawings, provides a further explanation of the invention. It is understood that the specific embodiments described herein are merely illustrative of the invention and not intended to limit it.

[0064] Where specific techniques or conditions are not specified in the examples, they shall be performed in accordance with the techniques or conditions described in the literature in this field, or in accordance with the product instructions. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased through legitimate channels.

[0065] Preparation Example 1

[0066] Prepared modified poly(L-lactic acid) microspheres.

[0067] (1) L-lactide was added to a mixed solvent of ethyl acetate and ethanol, dissolved completely at 120°C, and filtered while hot. The filtrate was stirred and cooled to room temperature and stirred for 2 hours. After all the crystals precipitated, the solution was filtered and dried to remove the solvent, and purified L-lactide was obtained. The purification was repeated 5 times. The mass ratio of L-lactide to ethyl acetate and ethanol was 30 g: 20 mL: 10 mL.

[0068] (2) The purified L-lactide was added to a mixture of polyethylene glycol and methoxy polyethylene glycol as a regulator. After complete dissolution at 150°C, stannous octoate catalyst was added and reacted for 6 hours. The mixture was then kept at this temperature to obtain a solid. The solid was dissolved in dichloromethane solvent, and the solution was poured into ethanol solvent. The precipitated solid was collected, filtered, and dried to remove the solvent, yielding a modified poly(L-lactic acid) polymer. The mass ratio of purified L-lactide to the volume ratio of polyethylene glycol, methoxy polyethylene glycol, dichloromethane, and ethanol was 25 g: 1 mL: 0.2 mL: 50 mL: 100 mL.

[0069] (3) The modified poly(L-lactic acid) polymer was dissolved in dichloromethane solvent to prepare a solution. The solution was then added to a polyvinyl alcohol solution and stirred for 8 hours. Deionized water was added to the mixed solution, and the dichloromethane solvent was removed by distillation. After solvent removal, the mixture was allowed to stand for 4 hours. The solid precipitate was washed with water for injection and then centrifuged and dried to obtain modified poly(L-lactic acid) microspheres. The mass ratio of the modified poly(L-lactic acid) polymer to the volume ratio of dichloromethane, polyvinyl alcohol solution, and deionized water was 15 g: 50 mL: 25 mL: 20 mL. The electron micrograph of the obtained modified poly(L-lactic acid) microspheres is shown below. Figure 1 As shown.

[0070] Preparation Example 2

[0071] Prepared modified poly(L-lactic acid) microspheres.

[0072] (1) L-lactide was added to a mixed solvent of ethyl acetate and ethanol, dissolved completely at 50°C, and filtered while hot. The filtrate was stirred and cooled to room temperature, and stirred continuously for 1 hour. After all the crystals precipitated, the filtrate was filtered and dried to remove the solvent, and purified L-lactide was obtained. The purification was repeated 4 times. The mass ratio of L-lactide to the volume ratio of ethyl acetate and ethanol was 10 g: 15 mL: 15 mL.

[0073] (2) The purified L-lactide was added to a mixture of polyethylene glycol and methoxy polyethylene glycol as a regulator. After complete dissolution at 150°C, stannous octoate catalyst was added and reacted for 6 hours. The mixture was then kept at this temperature to obtain a solid. The solid was dissolved in dichloromethane solvent, and the solution was poured into ethanol solvent. The precipitated solid was collected, filtered, and dried to remove the solvent, yielding a modified poly(L-lactic acid) polymer. The mass ratio of purified L-lactide to the volume ratio of polyethylene glycol, methoxy polyethylene glycol, dichloromethane, and ethanol was 25 g: 1 mL: 0.2 mL: 50 mL: 100 mL.

[0074] (3) The modified poly(L-lactic acid) polymer was added to dichloromethane solvent to prepare a solution. The solution was added to polyvinyl alcohol solution and stirred for 8 hours. Then, deionized water was added to the mixed solution and the dichloromethane solvent was removed by distillation. After the solvent was removed, the mixture was allowed to stand for 4 hours. The solid precipitate was washed with water for injection and then centrifuged and dried to obtain modified poly(L-lactic acid) microspheres. The mass ratio of the modified poly(L-lactic acid) polymer to the volume ratio of dichloromethane, polyvinyl alcohol solution and deionized water was 5 g: 20 mL: 15 mL: 40 mL. The modified poly(L-lactic acid) microspheres were obtained.

[0075] Preparation Example 3

[0076] Prepared modified poly(L-lactic acid) microspheres.

[0077] (1) L-lactide was added to a mixed solvent of ethyl acetate and ethanol, dissolved completely at 120°C, and filtered while hot. The filtrate was stirred and cooled to room temperature, and stirred continuously for 1 hour. After all the crystals precipitated, the filtrate was filtered and dried to remove the solvent, and purified L-lactide was obtained. The purification was repeated 4 times. The mass ratio of L-lactide to the volume ratio of ethyl acetate and ethanol was 30 g: 25 mL: 5 mL.

[0078] (2) The purified L-lactide was added to a mixture of polyethylene glycol and methoxy polyethylene glycol as a regulator. After complete dissolution at 150°C, stannous octoate catalyst was added and reacted for 6 hours. The mixture was kept at this temperature to obtain a solid. The solid was dissolved in dichloromethane solvent, and then the solution was poured into ethanol solvent. The precipitated solid was collected, filtered, and dried to remove the solvent, yielding the modified poly(L-lactic acid) polymer. The mass ratio of purified L-lactide to the volume ratio of polyethylene glycol, methoxy polyethylene glycol, dichloromethane, and ethanol was 25 g: 0.5 mL: 0.1 mL: 50 mL: 70 mL.

[0079] (3) The modified poly(L-lactic acid) polymer was added to dichloromethane solvent to prepare a solution. The solution was added to polyvinyl alcohol solution and stirred for 8 hours. Then, deionized water was added to the mixed solution and the dichloromethane solvent was removed by distillation. After the solvent was removed, the mixture was allowed to stand for 4 hours. The solid precipitate was washed with water for injection and then centrifuged and dried to obtain modified poly(L-lactic acid) microspheres. The mass ratio of the modified poly(L-lactic acid) polymer to the volume ratio of dichloromethane, polyvinyl alcohol solution and deionized water was 15 g: 80 mL: 50 mL: 15 mL. The modified poly(L-lactic acid) microspheres were obtained.

[0080] Preparation Example 4

[0081] Prepared modified poly(L-lactic acid) microspheres.

[0082] The only difference between this preparation example and preparation example 1 is that in step (1), the mass ratio of L-lactide to the volume ratio of ethyl acetate and ethanol is changed to 5g:20mL:10mL.

[0083] Preparation Example 5

[0084] Prepared modified poly(L-lactic acid) microspheres.

[0085] The only difference between this preparation example and preparation example 1 is that in step (2), the mass ratio of purified L-lactide to the volume ratio of polyethylene glycol, methoxy polyethylene glycol, dichloromethane and ethanol is changed to 5g:1mL:0.2mL:50mL:100mL.

[0086] Example 1

[0087] This embodiment provides an injectable cosmetic filler composition. Preparation Example 1: 20g modified poly-L-lactic acid microspheres, 5g methylcellulose, 3g sodium hyaluronate, 5g glycerin, 1g vitamin C, 2g ginkgo biloba extract, 0.6g lidocaine (anesthetic), and 100mL sodium chloride solution.

[0088] Preparation method: Sodium hyaluronate was added to a portion of the sodium chloride solution under stirring. After swelling, it was allowed to stand at room temperature for 5 hours. Then, glycerol was added and stirred for 30 minutes. Vitamin C and ginkgo leaf extract were then added and stirred for 60 minutes. Modified poly-L-lactic acid microspheres were added to the remaining sodium chloride solution. Cellulose ether methylcellulose was slowly added under stirring. After stirring for 5 hours, the prepared product was added and homogenized for 60 minutes. Finally, it was sterilized and packaged. The sterilization method was moist heat sterilization at 125°C for 30 minutes.

[0089] Example 2

[0090] This embodiment provides an injectable cosmetic filler composition, prepared as follows: 20g of modified poly-L-lactic acid microspheres, 5g of sodium carboxymethyl cellulose, 3g of sodium hyaluronate, 5g of glycerin, 1g of vitamin C, 2g of ginkgo biloba extract, 0.6g of procaine (anesthetic), and 100mL of sodium chloride solution.

[0091] The preparation method is the same as in Example 1.

[0092] Example 3

[0093] This embodiment provides an injectable cosmetic filler composition. Preparation Example 1: 20g modified poly-L-lactic acid microspheres, 5g ethyl cellulose, 3g sodium hyaluronate, 5g glycerin, 1g vitamin C, 2g ginkgo biloba extract, 0.6g eticaine (anesthetic), and 100mL sodium chloride solution.

[0094] The preparation method is the same as in Example 1.

[0095] Example 4

[0096] This embodiment provides an injectable cosmetic filler composition, which differs from Example 1 only in that the modified poly-L-lactic acid microspheres of Preparation Example 1 are replaced with the modified poly-L-lactic acid microspheres of Preparation Example 4.

[0097] The preparation method is the same as in Example 1.

[0098] Example 5

[0099] This embodiment provides an injectable cosmetic filler composition, which differs from Example 1 only in that the modified poly-L-lactic acid microspheres of Preparation Example 1 are replaced with the modified poly-L-lactic acid microspheres of Preparation Example 5.

[0100] The preparation method is the same as in Example 1.

[0101] Comparative Example 1

[0102] This comparative example provides an injectable cosmetic filler composition that differs from Example 1 only in that it does not contain modified poly-L-lactic acid microspheres, which are proportionally distributed in the mass of methylcellulose and sodium hyaluronate.

[0103] The preparation method is the same as in Example 1.

[0104] Comparative Example 2

[0105] This comparative example provides an injectable cosmetic filler composition that differs from Example 1 only in that it does not contain methylcellulose, which is proportionally distributed in the mass of modified poly-L-lactic acid microspheres and sodium hyaluronate.

[0106] The preparation method is the same as in Example 1.

[0107] Comparative Example 3

[0108] This comparative example provides an injectable cosmetic filler composition that differs from Example 1 only in that it does not contain sodium hyaluronate, which is proportionally distributed in the mass of modified poly-L-lactic acid microspheres and methylcellulose.

[0109] The preparation method is the same as in Example 1.

[0110] Comparative Example 4

[0111] This comparative example provides an injectable cosmetic filler composition that differs from Example 1 only in that it does not contain methylcellulose and sodium hyaluronate, but rather these are distributed in the mass of the modified poly-L-lactic acid microspheres.

[0112] The preparation method is the same as in Example 1.

[0113] Comparative Example 5

[0114] This comparative example provides an injectable cosmetic filler composition that differs from Example 1 only in that it does not contain modified poly-L-lactic acid microspheres and sodium hyaluronate, which are allocated to the mass of methylcellulose.

[0115] The preparation method is the same as in Example 1.

[0116] Comparative Example 6

[0117] This comparative example provides an injectable cosmetic filler composition that differs from Example 1 only in that it does not contain modified poly-L-lactic acid microspheres and methylcellulose, which are allocated to the mass of sodium hyaluronate.

[0118] The preparation method is the same as in Example 1.

[0119] Comparative Example 7

[0120] This comparative example provides an injectable cosmetic filler composition, which differs from Example 1 only in that the modified poly-L-lactic acid microspheres are replaced with unmodified poly-L-lactic acid microspheres.

[0121] The preparation method is the same as in Example 1.

[0122] Test Example 1

[0123] Skin irritation test.

[0124] Forty-eight healthy volunteers were selected as subjects for the study and were divided into 12 groups. A skin irritation test was conducted to examine the reactions of the injectable cosmetic filler compositions prepared in Examples 1-5 and Comparative Examples 1-7 under the test conditions. The injection method was multi-point microinjection, with each injection being 50 μL, for a total injection volume of 2 mL. The results were observed 96 hours and 1 week after injection, and are shown in Table 1.

[0125] Table 1

[0126]

[0127] Results: After 96 hours and 1 week of injection of the injectable cosmetic filler compositions of Examples 1-3, no erythema or edema occurred. Compared with Example 1, Examples 4 and 5 used different preparation methods for the modified poly-L-lactic acid microspheres, which were outside the proportions of this invention. The L-lactide mass to ethyl acetate and ethanol volume ratios were changed to 5g:20mL:10mL, and the purified L-lactide mass to polyethylene glycol, methoxy polyethylene glycol, dichloromethane, and ethanol volume ratios were changed to 15g:1mL:0.2mL:50mL:100mL. Erythema and edema occurred in these examples, and the erythema and edema persisted even after 1 week. This indicates that the precise control of the raw material ratios in the preparation of the modified poly-L-lactic acid microspheres in this invention can ensure that the injectable cosmetic filler compositions of this invention will not irritate the skin or cause adverse skin symptoms, demonstrating good safety.

[0128] Comparative Examples 1-3, each lacking one of the components of modified poly-L-lactic acid microspheres, methylcellulose, and sodium hyaluronate, all showed edema and erythema after 96 hours. Erythema and persistent edema persisted after one week. Comparative Examples 4-6, also lacking one of the components of modified poly-L-lactic acid microspheres, methylcellulose, and sodium hyaluronate, all showed edema and erythema. Erythema and persistent edema persisted after one week. This indicates that the modified poly-L-lactic acid microspheres, cellulose ethers, and sodium hyaluronate in the injectable cosmetic filler composition of the present invention have a synergistic effect in improving the safety of the filler composition. Compared with Example 1, Comparative Example 7 used unmodified poly-L-lactic acid microspheres, resulting in erythema and edema. Erythema and persistent edema persisted after one week. This indicates that the injectable cosmetic filler composition of the present invention does not irritate the skin, does not cause skin discomfort, and has good safety.

[0129] Test Example 2

[0130] Wrinkle improvement trial.

[0131] Using 12 healthy volunteers as subjects, the effects of the injectable cosmetic filler compositions prepared in Examples 1-5 on skin wrinkles under experimental conditions were investigated. 2 mL of each of the injectable cosmetic filler compositions prepared in Examples 1-5 and Comparative Examples 1-7 was injected into the skin on the back of the hands of the subjects, and the wrinkles at the injection sites were observed visually before injection and 24 hours after injection. Wrinkle scores were assigned from 1 to 9, with 9 being the highest wrinkle level and 1 being the lowest (no wrinkles). The results are shown in Table 2.

[0132] Table 2

[0133]

[0134]

[0135] Results: Three months after injection of the injectable cosmetic filler compositions of Examples 1-3, wrinkles at the injection sites were significantly reduced, indicating that the injectable cosmetic filler compositions prepared in this invention can reduce wrinkles, soften the skin, revitalize the skin, and maintain a youthful appearance. Examples 4 and 5 differed from Example 1 in the preparation method of the modified poly-L-lactic acid microspheres, and were outside the formulation range of this invention. Specifically, the mass ratio of L-lactide to ethyl acetate and ethanol was changed to 5g:20mL:10mL, and the mass ratio of purified L-lactide to polyethylene glycol, methoxy polyethylene glycol, dichloromethane, and ethanol was changed to 15g:1mL:0.2mL:50mL:100mL. Three months after injection, the wrinkle-reducing effect score of these compositions was only 5, indicating that the injectable cosmetic filler compositions of this invention can effectively reduce wrinkles, soften the skin, revitalize the skin, and maintain a youthful appearance.

[0136] Comparative Examples 1-3, each lacking one of the components of modified poly-L-lactic acid microspheres, methylcellulose, and sodium hyaluronate, showed a wrinkle-reducing effect of only 5 after 3 months. Comparative Examples 4-6, each lacking one of the components of modified poly-L-lactic acid microspheres, methylcellulose, and sodium hyaluronate, showed wrinkle-reducing effect scores of 5 or 6 after 3 months. This indicates that the modified poly-L-lactic acid microspheres, cellulose ethers, and sodium hyaluronate in the injectable cosmetic filler composition of the present invention have a synergistic effect in enhancing the skin's softening and reducing wrinkles. Compared with Example 1, Comparative Example 7 used unmodified poly-L-lactic acid microspheres, and the wrinkle-reducing effect score was 6 after 3 months. This shows that the injectable cosmetic filler composition prepared by the present invention can reduce wrinkles, soften the skin, revitalize the skin, and maintain a youthful appearance.

[0137] In summary, the composition of the present invention can be injected into the deep dermis to correct facial contour defects, effectively fill areas lacking facial support, is non-irritating, has good wrinkle-reducing effects, high biocompatibility, and good stability and safety.

[0138] The applicant declares that the detailed method of the present invention is illustrated by the above embodiments, but the present invention is not limited to the above detailed method, that is, it does not mean that the present invention must rely on the above detailed method to be implemented. Those skilled in the art should understand that any improvements to the present invention, equivalent substitutions of the raw materials of the product of the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

Claims

1. An injectable cosmetic filler composition, characterized in that, The injectable cosmetic filler composition includes modified poly-L-lactic acid microspheres, cellulose ethers, and sodium hyaluronate; The modified poly(L-lactic acid) microspheres are block copolymers of lactic acid and alcohol; The preparation method of the modified poly-L-lactic acid microspheres includes the following steps: (1) After mixing L-lactide, ethyl acetate and ethanol, heat and filter. Cool the filtrate and stir. After all the crystals have precipitated, filter and dry to remove ethyl acetate and ethanol to obtain purified L-lactide. The mass-volume ratio of L-lactide, ethyl acetate and ethanol is (10-30g):(15-25mL):(5-15mL). (2) The purified L-lactide, polyethylene glycol and methoxy polyethylene glycol are mixed, heated to dissolve, and then reacted with the catalyst stannous octoate. The solid obtained after the reaction is kept at a certain temperature is mixed with dichloromethane and ethanol. The precipitated solid is collected and filtered and dried to remove the dichloromethane and ethanol solvents to obtain the modified poly-L-lactic acid polymer. The mass-volume ratio of the purified L-lactide, polyethylene glycol, methoxy polyethylene glycol, dichloromethane and ethanol is (10-25g):(0.5-1.5mL):(0.1-0.5mL):(30-70mL):(70-150mL). (3) The modified poly-L-lactic acid polymer, dichloromethane and polyvinyl alcohol were mixed, and the dichloromethane was removed by distillation with deionized water. The mixture was then allowed to stand. After standing, the solid precipitate was washed, centrifuged and dried to obtain the modified poly-L-lactic acid microspheres.

2. The injectable cosmetic filler composition according to claim 1, characterized in that, The mass ratio of lactic acid to alcohol in the modified poly-L-lactic acid microspheres is (5-30):(0.5-5).

3. The injectable cosmetic filler composition according to claim 1, characterized in that, The alcohols include polyethylene glycol.

4. The injectable cosmetic filler composition according to claim 1, characterized in that, The mass ratio of the modified poly(L-lactic acid) microspheres, cellulose ethers, and sodium hyaluronate is (10-40):(0.5-7):(0.1-5).

5. The injectable cosmetic filler composition according to claim 1, characterized in that, The heating temperature in step (1) is 50-120℃.

6. The injectable cosmetic filler composition according to claim 1, characterized in that, The cooling and stirring time in step (1) is 1-2 hours.

7. The injectable cosmetic filler composition according to claim 1, characterized in that, The heating temperature in step (2) is 60-150℃.

8. The injectable cosmetic filler composition according to claim 1, characterized in that, The reaction time described in step (2) is 1-6 hours.

9. The injectable cosmetic filler composition according to claim 1, characterized in that, The resting time mentioned in step (3) is 2-4 hours.

10. The injectable cosmetic filler composition according to claim 1, characterized in that, The mass-volume ratio of the modified poly(L-lactic acid) polymer, dichloromethane, polyvinyl alcohol and deionized water in step (3) is (5-15g):(20-80mL):(15-50mL):(15-40mL).

11. The injectable cosmetic filler composition according to claim 1, characterized in that, The cellulose ethers include any one or a combination of at least two of methylcellulose, sodium carboxymethylcellulose, ethylcellulose, carboxyethylcellulose, hydroxypropylcellulose, or hydroxypropylmethylcellulose.

12. The injectable cosmetic filler composition according to claim 1, characterized in that, The molecular weight of the sodium hyaluronate is 300,000-1,500,000 Daltons.

13. The injectable cosmetic filler composition according to claim 1, characterized in that, The injectable cosmetic filler composition also includes glycerin, vitamin C, ginkgo biloba extract, anesthetic, and an aqueous solution for injection.

14. The injectable cosmetic filler composition according to claim 13, characterized in that, The mass ratio of glycerol, vitamin C, ginkgo leaf extract and anesthetic is (0.2-10):(0.1-2):(0.5-3):(0.05-1).

15. The injectable cosmetic filler composition according to claim 13, characterized in that, The aqueous solution for injection includes sodium chloride solution or phosphate buffer solution.

16. The injectable cosmetic filler composition according to claim 13, characterized in that, The anesthetic agent includes any one or a combination of at least two of lidocaine, procaine, eticaine, promocaine, and quinicaine.

17. A method for preparing an injectable cosmetic filler composition according to any one of claims 1-12, characterized in that, The method includes: The modified poly-L-lactic acid microspheres, cellulose ethers, and sodium hyaluronate are mixed, homogenized, and sterilized to obtain the injectable cosmetic filler composition.

18. The method for preparing an injectable cosmetic filler composition according to claim 17, characterized in that, The sterilization temperature is 110-125℃, and the time is 15-30 minutes.

19. The use of the injectable cosmetic filler composition according to any one of claims 1-16 in the preparation of injectable cosmetic fillers.

Images