Injection filling composition for plastic and aesthetic surgery and preparation method thereof

Abstract

The invention belongs to the technical field of medical cosmetic preparations, and particularly relates to an injection filling composition for plastic and aesthetic surgery and a preparation method thereof. The injection filling composition disclosed by the invention is prepared from the following components in parts by weight: 20 to 40 parts of polycaprolactone microspheres and 60 to 80 parts of suspending aid. The injection filling composition for plastic and aesthetic surgery shows a rapid filling effect after being injected, can stimulate fibroblasts to generate collagen and repair tissues, and has a lasting effect. The vitamin component and the tranexamic acid in the composition provide nutrition for skin tissues and also have the effects of resisting oxidation, reducing hyperpigmentation and whitening the skin, all the related components have good biocompatibility, and allergenicity cannot be caused after injection.

Description

Technical Field

[0001] The present invention belongs to the technical field of medical cosmetic preparations, and specifically relates to an injection filling composition for cosmetic surgery and a preparation method thereof. Background Art

[0002] Injection wrinkle removal is achieved by injecting fillers into the face to repair wrinkles, thereby achieving the effect of wrinkle removal. There are many kinds of materials for injection wrinkle removal, such as hyaluronic acid, collagen, autologous fat, botulinum toxin, polylactic acid, polycaprolactone, etc., all of which have immediate effects. This is also the reason why many people have chosen injection wrinkle removal in recent years.

[0003] There are many products for injectable wrinkle removal in the prior art, but their functions are relatively simple. Facial fillers such as hyaluronic acid, collagen, and autologous fat only play a physical filling role after injection and will be quickly absorbed by the human body. In order to maintain the filling effect, repeated injections are required.

[0004] Fillers containing polymer microspheres such as polylactic acid (PLA) and polycaprolactone (PCL) can stimulate the production of collagen in the deep layer of the skin after being implanted into the subcutaneous tissue of the human body, thus achieving a lasting repair effect. However, although such fillers containing polymer microspheres have an immediate filling and long-term repair effect, they do not have a whitening function.

[0005] In view of the above problems, it is necessary to develop a facial injectable filler that has both the effect of improving wrinkles for a long time and the effect of whitening. Summary of the invention

[0006] In view of the deficiencies of the above-mentioned prior art, the present invention provides an injectable filling composition for cosmetic surgery and a preparation method thereof, which not only has the function of filling depressions and improving wrinkles with a long-lasting effect, but also has a whitening effect.

[0007] The first object of the present invention is to provide an injectable filling composition for cosmetic surgery, which comprises 20 to 40 parts of polycaprolactone microspheres and 60 to 80 parts of a suspending liquid in parts by weight.

[0008] Furthermore, the preparation method of the polycaprolactone microspheres comprises the following steps:

[0009] S1: dissolving polycaprolactone in an organic solvent to obtain an oil phase solution;

[0010] S2: dissolving the emulsifier in water to obtain an aqueous phase solution;

[0011] S3: pouring the oil phase into the water phase, shearing and emulsifying to form a suspension emulsion; or adding the oil phase into the water phase through the membrane tube of a membrane emulsifier under pressure to obtain a suspension emulsion;

[0012] S4: removing the organic solvent from the suspension emulsion to form microspheres;

[0013] S5: Recover the polycaprolactone microspheres, wash, sieve and dry them to obtain polycaprolactone microspheres.

[0014] Furthermore, in step S1, the intrinsic viscosity of the polycaprolactone is 0.2 to 1.8 dL / g, preferably 0.2 to 1.2 dL / g.

[0015] Furthermore, the particle size of the polycaprolactone microspheres obtained in step S5 is 20 to 100 μm, preferably 20 to 80 μm, more preferably 20 to 60 μm, and the particle size span is ≤1.0.

[0016] Furthermore, in step S1, the organic solvent is one or more of dichloromethane, chloroform, acetone, methanol, etc.; in step S2, the emulsifier is one or more of methyl cellulose, Tween, polyvinyl alcohol.

[0017] Furthermore, the suspending liquid comprises sodium carboxymethylcellulose, tranexamic acid, complex vitamins, glycerol and phosphate buffer.

[0018] Furthermore, the suspending liquid includes, by weight, 3 to 5 parts of sodium carboxymethyl cellulose, 3 to 9 parts of tranexamic acid, 3 to 9 parts of multivitamins, 1.2 to 1.7 parts of glycerol and 75 to 90 parts of phosphate buffer.

[0019] Furthermore, the degree of substitution of the sodium carboxymethyl cellulose is 0.7 to 1.2, preferably 0.9.

[0020] Furthermore, the weight proportion of the tranexamic acid in the suspending liquid is preferably 4 to 8 parts, and the weight proportion of the multivitamin in the suspending liquid is preferably 4 to 8 parts.

[0021] Furthermore, the complex vitamin includes niacinamide, vitamin B6 and vitamin C, and the mass ratio of the niacinamide, vitamin B6 and vitamin C is 1:1:2.

[0022] Furthermore, the phosphate buffer is a phosphate solution with a pH of 7.4 prepared from potassium dihydrogen phosphate and sodium hydroxide.

[0023] The second object of the present invention is to provide a method for preparing the above-mentioned injection filling composition, comprising the following steps:

[0024] S1: placing tranexamic acid and multivitamins in a container, adding phosphate buffer, stirring and dissolving, to obtain solution 1;

[0025] S2: adding sodium carboxymethyl cellulose to the above solution 1, stirring to completely dissolve the sodium carboxymethyl cellulose, to obtain solution 2;

[0026] S3: adding glycerol to the above solution 2, stirring thoroughly and evenly, stirring under vacuum to remove bubbles, and obtaining a suspension;

[0027] S4: Add the prepared polycaprolactone microspheres into the above suspension, stir evenly under vacuum, and fill to obtain the product.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] The injection filling composition for cosmetic surgery provided by the present invention is a gel system including polycaprolactone microspheres and a suspension, which exhibits a rapid filling effect after injection, and can stimulate fibroblasts to produce collagen and repair tissues, and the effect is long-lasting. The vitamin components and tranexamic acid in the composition not only provide nutrition for skin tissue, but also have the effects of anti-oxidation, reducing pigmentation, and whitening. The components involved have good biocompatibility and will not cause allergies after injection. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 This is an image of polycaprolactone microspheres prepared in the preparation example of the present invention under a scanning electron microscope;

[0031] Figure 2 This is a particle size distribution test diagram of polycaprolactone microspheres prepared in the preparation example of the present invention;

[0032] Figure 3 This is an image of the injectable filling composition for cosmetic surgery prepared in Example 1 of the present invention under an optical microscope;

[0033] Figure 4 This is an image of the injectable filling composition for cosmetic surgery prepared in Comparative Example 1 of the present invention under an optical microscope. DETAILED DESCRIPTION

[0034] The following will describe the embodiments of the present invention in conjunction with the examples. It should be understood that the following examples are only for the purpose of explanation and should not be regarded as limiting the scope of the present invention. All other embodiments obtained by ordinary technicians in this field without creative work should belong to the scope of protection of the present invention.

[0035] Preparation Example

[0036] A method for preparing polycaprolactone microspheres comprises the following steps:

[0037] S1: Weigh 10.0 g of polycaprolactone with an intrinsic viscosity of 0.2 dL / g, add 90 ml of dichloromethane, stir and dissolve to obtain an oil phase solution;

[0038] S2: Weigh 2.0 g of methyl cellulose, add it into 200 ml of water under stirring, and stir until it is completely dissolved to obtain an aqueous phase solution;

[0039] S3: adding the oil phase solution to the water phase solution, shearing and dispersing, and obtaining a suspension emulsion;

[0040] S4: stirring the suspension emulsion at 300 rpm at 38° C. for 8 hours, removing the organic solvent, and obtaining microspheres;

[0041] S5: After collecting the above microspheres and washing them repeatedly with water, the microspheres between the 230-mesh sieve and the 500-mesh sieve are collected and dried to obtain polycaprolactone microspheres.

[0042] Example 1

[0043] A method for preparing an injectable filling composition for cosmetic surgery comprises the following steps:

[0044] S1: Weigh 1.0 g of tranexamic acid and 1.0 g of complex vitamins (including 0.25 g of niacinamide, 0.25 g of vitamin B6, and 0.5 g of vitamin C), add 11.24 g of a phosphate buffer solution of pH 7.4 prepared from potassium dihydrogen phosphate and sodium hydroxide, and stir to dissolve to obtain solution 1;

[0045] S2: Weigh 0.56 g of sodium carboxymethyl cellulose and add it to the above solution 1, stirring until the sodium carboxymethyl cellulose is completely dissolved to obtain solution 2;

[0046] S3: Weigh 0.2 g of glycerol, add it to the above solution 2, stir thoroughly, and stir under vacuum to remove bubbles to obtain a suspension;

[0047] S4: Weigh 6 g of the polycaprolactone microspheres prepared in the preparation example, add them to the above suspending liquid, stir evenly under vacuum conditions, and fill them into a prefilled syringe to obtain the microspheres.

[0048] The degree of substitution of sodium carboxymethyl cellulose is 0.9.

[0049] Example 2

[0050] A method for preparing an injectable filling composition for cosmetic surgery comprises the following steps:

[0051] S1: Weigh 1.2 g of tranexamic acid and 1.2 g of complex vitamins (including 0.3 g of niacinamide, 0.3 g of vitamin B6, and 0.6 g of vitamin C), add 10.9 g of a phosphate buffer solution of pH 7.4 prepared from potassium dihydrogen phosphate and sodium hydroxide, and stir to dissolve to obtain solution 1;

[0052] S2: Weigh 0.5 g of sodium carboxymethyl cellulose and add it to the above solution 1, stirring until the sodium carboxymethyl cellulose is completely dissolved to obtain solution 2;

[0053] S3: Weigh 0.2 g of glycerol, add it to the above solution 2, stir thoroughly, and stir under vacuum to remove bubbles to obtain a suspension;

[0054] S4: Weigh 6 g of the polycaprolactone microspheres prepared in the preparation example, add them to the above suspending liquid, stir evenly under vacuum conditions, and fill them into a prefilled syringe to obtain the microspheres.

[0055] The degree of substitution of sodium carboxymethyl cellulose is 0.7.

[0056] Example 3

[0057] A method for preparing an injectable filling composition for cosmetic surgery comprises the following steps:

[0058] S1: Weigh 1.2 g of tranexamic acid and 0.8 g of complex vitamins (including 0.2 g of niacinamide, 0.2 g of vitamin B6, and 0.4 g of vitamin C), add 11.3 g of a phosphate buffer solution of pH 7.4 prepared from potassium dihydrogen phosphate and sodium hydroxide, and stir to dissolve to obtain solution 1;

[0059] S2: Weigh 0.5 g of sodium carboxymethyl cellulose and add it to the above solution 1, stirring until the sodium carboxymethyl cellulose is completely dissolved to obtain solution 2;

[0060] S3: Weigh 0.2 g of glycerol, add it to the above solution 2, stir thoroughly, and stir under vacuum to remove bubbles to obtain a suspension;

[0061] S4: Weigh 6 g of the polycaprolactone microspheres prepared in the preparation example, add them to the above suspending liquid, stir evenly under vacuum conditions, and fill them into a prefilled syringe to obtain the microspheres.

[0062] The degree of substitution of sodium carboxymethyl cellulose is 0.9.

[0063] Example 4

[0064] A method for preparing an injectable filling composition for cosmetic surgery comprises the following steps:

[0065] S1: Weigh 1.2 g of tranexamic acid and 0.8 g of complex vitamins (including 0.2 g of niacinamide, 0.2 g of vitamin B6, and 0.4 g of vitamin C), add 11.3 g of a phosphate buffer solution of pH 7.4 prepared from potassium dihydrogen phosphate and sodium hydroxide, and stir to dissolve to obtain solution 1;

[0066] S2: Weigh 0.5 g of sodium carboxymethyl cellulose and add it to the above solution 1, stirring until the sodium carboxymethyl cellulose is completely dissolved to obtain solution 2;

[0067] S3: Weigh 0.2 g of glycerol, add it to the above solution 2, stir thoroughly, and stir under vacuum to remove bubbles to obtain a suspension;

[0068] S4: Weigh 6 g of the polycaprolactone microspheres prepared in the preparation example, add them to the above suspending liquid, stir evenly under vacuum conditions, and fill them into a prefilled syringe to obtain the microspheres.

[0069] Among them, the degree of substitution of sodium carboxymethyl cellulose is 1.2.

[0070] Comparative Example 1

[0071] A method for preparing an injectable filling composition for cosmetic surgery comprises the following steps:

[0072] S1: Weigh 0.2 g of tranexamic acid and 0.2 g of complex vitamins (including 0.05 g of niacinamide, 0.05 g of vitamin B6, and 0.1 g of vitamin C), add 9.8 g of a phosphate buffer solution of pH 7.4 prepared from potassium dihydrogen phosphate and sodium hydroxide, and stir to dissolve to obtain solution 1;

[0073] S2: weigh 0.8 g of sodium carboxymethyl cellulose and add it to the above solution 1, stir and dissolve to obtain solution 2;

[0074] S3: Weigh 0.2 g of glycerol, add it to the above solution 2, stir evenly, and obtain solution 3;

[0075] S4: Weigh 8.8 g of polycaprolactone microspheres, add them to the above solution 3, stir evenly under vacuum conditions, and put them into a prefilled syringe to obtain.

[0076] The degree of substitution of sodium carboxymethyl cellulose is 0.9.

[0077] Comparative Example 2

[0078] A method for preparing an injectable filling composition for cosmetic surgery comprises the following steps:

[0079] S1: Weigh 0.6 g of sodium carboxymethyl cellulose and add it to 12.6 g of phosphate buffer (pH 7.4) prepared by potassium dihydrogen phosphate and sodium hydroxide, and stir until completely dissolved to obtain solution 1;

[0080] S2: Weigh 0.2 g of glycerol, add it to the above solution 1, stir evenly, and obtain solution 2;

[0081] S3: Weigh 6.6 g of polycaprolactone microspheres, add them to the above solution 2, stir evenly, and put them into a prefilled syringe to obtain.

[0082] The degree of substitution of sodium carboxymethyl cellulose is 0.9.

[0083] Testing and Experimentation:

[0084] (1) The morphology and size of the polycaprolactone microspheres prepared in Preparation Example were observed under a scanning electron microscope. Figure 1 shown.

[0085] Depend on Figure 1 It can be seen that the polycaprolactone microspheres prepared in the present invention are round in shape and uniform in size.

[0086] (2) The particle size of the polycaprolactone microspheres prepared in the preparation example was measured using a Malvern Mastersizer 3000 laser particle size analyzer. The results are as follows: Figure 2 shown.

[0087] Depend on Figure 2 It can be seen that the polycaprolactone microspheres prepared in the present invention have a D10 of 25.4 μm, a D50 of 38.3 μm, a D90 of 56.5 μm, and a particle size span of 0.812.

[0088] It should be noted that the particle size span (Span) = (D90-D10) / D50, D10 refers to the particle size corresponding to when the cumulative particle size distribution number of the degradable microspheres reaches 10%, D50 refers to the particle size corresponding to when the cumulative particle size distribution percentage of the degradable microspheres reaches 50%, and D90 refers to the particle size corresponding to when the cumulative particle size distribution number of the degradable microspheres reaches 90%.

[0089] (3) The images of the injectable filling compositions for cosmetic surgery prepared in Example 1 and Comparative Example 1 under an optical microscope are as follows: Figure 3 and Figure 4 shown.

[0090] Depend on Figure 3 It can be seen that in the composition prepared in Example 1, the polycaprolactone microspheres are uniformly dispersed in the suspending liquid without agglomeration, which can avoid needle blocking during use; Figure 4 It can be seen that in the composition prepared in Comparative Example 1, the polycaprolactone microspheres agglomerated, and needle blocking was easily caused during use.

[0091] (4) The injection force of the injectable filling compositions for cosmetic surgery prepared in Examples 1 to 4 and Comparative Examples 1 and 2 was tested using a TA.XT plus texture analyzer. The results are shown in Table 1.

[0092] Table 1

[0093] project Injection needle model Push speed Injection force (N) Example 1 27G 20mm / min 29 Example 2 27G 20mm / min 28 Example 3 27G 20mm / min 27 Example 4 27G 20mm / min 31 Comparative Example 1 27G 20mm / min 53 Comparative Example 2 27G 20mm / min 32

[0094] From the results in Table 1, it can be seen that the injection force of the injection filling composition for cosmetic surgery prepared in Examples 1 to 4 of the present invention and Comparative Example 2 is appropriate and can be smoothly pushed out during use; however, the injection filling composition prepared in Comparative Example 1 requires a larger pushing force to be smoothly pushed out due to the excessively high content of polycaprolactone microspheres and sodium carboxymethyl cellulose and the high viscosity of the system, which is inconvenient for clinical use.

[0095] (5) Twelve healthy adult tricolor guinea pigs were selected and randomly divided into four groups, with three in each group. The brown skin area was taken, the hair was removed, and UVB ultraviolet rays were irradiated once a day for 1 hour each time for 7 days. The skin melanin value was regularly detected using a skin melanin tester. On the 8th day, the first group was subcutaneously injected with the injection filling composition for cosmetic surgery prepared in Example 1 at the ultraviolet irradiation site; the second group was subcutaneously injected with the injection filling composition for cosmetic surgery prepared in Comparative Example 1 at the ultraviolet irradiation site; the third group was subcutaneously injected with the injection filling composition for cosmetic surgery prepared in Comparative Example 2 at the ultraviolet irradiation site; and the fourth group was used as a blank group and was not treated. The test was carried out for 3 consecutive weeks, and the skin melanin change rate was calculated. Melanin change rate (%) = (melanin content value measured after injection of the composition / melanin content value measured before injection of the composition) × 100%. The results are shown in Table 2.

[0096] Table 2

[0097]

[0098] From the test results in Table 2, it can be seen that after using the injection filling composition for cosmetic surgery of the present invention, the melanin content of the guinea pigs in Example 1 group was significantly reduced, and the melanin content of the guinea pigs in Comparative Example 1 group, Comparative Example 2 group and the blank group was reduced, but the effect was significantly different from that in Example 1. Therefore, the present invention can effectively reduce the content of melanin in the skin and has a whitening effect.

[0099] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A cosmetic plastic surgery injection filling composition, characterized in that: In parts by weight, the invention comprises 20 to 40 parts of polycaprolactone microspheres and 60 to 80 parts of suspending liquid.

2. The injection filling composition according to claim 1, characterized in that The preparation method of the polycaprolactone microspheres comprises the following steps: S1: dissolving polycaprolactone in an organic solvent to obtain an oil phase solution; S2: dissolving the emulsifier in water to obtain an aqueous phase solution; S3: pouring the oil phase into the water phase, shearing and emulsifying to form a suspension emulsion; or adding the oil phase into the water phase through the membrane tube of a membrane emulsifier under pressure to obtain a suspension emulsion; S4: removing the organic solvent from the suspension emulsion to form microspheres; S5: Recover the polycaprolactone microspheres, wash, sieve and dry them to obtain polycaprolactone microspheres.

3. The injection filling composition according to claim 2, characterized in that In step S1, the intrinsic viscosity of the polycaprolactone is 0.2-1.8 dL / g.

4. The injection filling composition according to claim 2, characterized in that The particle size of the polycaprolactone microspheres obtained in step S5 is 20-100 μm, and the particle size span is ≤1.

0.

5. The injection filling composition according to claim 2, characterized in that In step S1, the organic solvent is one or more of dichloromethane, chloroform, acetone, methanol, etc.; in step S2, the emulsifier is one or more of methyl cellulose, Tween, polyvinyl alcohol.

6. The injection filling composition according to claim 1, characterized in that The suspending liquid comprises sodium carboxymethylcellulose, tranexamic acid, complex vitamins, glycerol and phosphate buffer.

7. The injection filling composition according to claim 6, characterized in that In parts by weight, the suspending liquid comprises 3-5 parts of sodium carboxymethyl cellulose, 3-9 parts of tranexamic acid, 3-9 parts of complex vitamins, 1.2-1.7 parts of glycerol and 75-90 parts of phosphate buffer.

8. The injection filling composition according to claim 7, characterized in that The degree of substitution of the sodium carboxymethyl cellulose is 0.7 to 1.

2.

9. The injection filling composition according to claim 7, characterized in that The complex vitamin comprises niacinamide, vitamin B6 and vitamin C, and the mass ratio of the niacinamide, vitamin B6 and vitamin C is 1:1:

2.

10. A method for preparing the injection filling composition according to any one of claims 1 to 9, characterized in that: The steps include: S1: placing tranexamic acid and multivitamins in a container, adding phosphate buffer, stirring and dissolving, to obtain solution 1; S2: adding sodium carboxymethyl cellulose to the above solution 1, stirring to completely dissolve the sodium carboxymethyl cellulose, to obtain solution 2; S3: adding glycerol to the above solution 2, stirring thoroughly and evenly, stirring under vacuum to remove bubbles, and obtaining a suspension; S4: Add the prepared polycaprolactone microspheres into the above suspension, stir evenly under vacuum, and fill to obtain the product.

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