Preparation method of injection type facial filling hydrogel for cosmetic and plastic surgery

Abstract

The invention discloses a preparation method of injection type facial filling hydrogel for cosmetic and plastic surgery, and relates to the technical field of medical cosmetic and plastic surgery. The method comprises the following steps: S1, preparing bioactive glass microspheres; s2, preparing a bacterial cellulose coating bioactive glass microsphere crude product by utilizing the bioactive glass microsphere; s3, preparing the bacterial cellulose coating bioactive glass microspheres from the bacterial cellulose coating bioactive glass microsphere crude product; s4, preparing a face filling hydrogel pre-canning body by using the bacterial cellulose coating bioactive glass microspheres; and S5, carrying out negative pressure degassing on the face filling hydrogel pre-canning body, pressurizing and canning the face filling hydrogel pre-canning body in an injector, and sterilizing to obtain the face filling hydrogel for cosmetic and plastic surgery. The bioactive glass microspheres can stimulate collagen regeneration so as to delay facial aging, and the bioactive glass microspheres are convenient and controllable and can be continuously produced.

Description

Technical Field

[0001] The invention belongs to the technical field of medical cosmetic surgery, and in particular relates to a method for preparing an injectable facial filling hydrogel for cosmetic surgery. Background Art

[0002] As people age, collagen in human skin tissue gradually disappears, and coupled with the oxidation of oxygen free radicals in the body, the skin becomes loose and wrinkles appear, especially facial contour aging, which becomes increasingly severe, including visible skin wrinkles, deep nasolabial folds, frown lines, neck wrinkles, mouth wrinkles, and collapsed nose bridge. In addition, some mechanical injuries can also cause nasal bone collapse, and burns and scalds can leave scars on the face, causing inconvenience to people's daily lives. In addition, some people suffer from inferiority complex and cannot live a normal life due to congenital problems such as collapsed nose bridge and cleft lip and palate. Moreover, with the improvement of living standards and the development of cosmetic surgery technology, cosmetic surgery has gradually been accepted and trusted by people. All of these have promoted the development of cosmetic surgery technology and materials, especially injection cosmetic surgery technology and materials, because injection cosmetic surgery technology is non-surgical cosmetic surgery, with quick results, and the materials used have good biocompatibility. Among them, hyaluronic acid products are widely used by cosmetic surgery institutions for their good biocompatibility, few side effects after injection, and relatively long-lasting shaping effects.

[0003] Currently, the most widely used injectable cosmetic products are hyaluronic acid products, but hyaluronic acid products have the following defects: 1. The cost is relatively high, with one injection costing thousands to tens of thousands of yuan. 2. The maintenance time is short, and the degradation and absorption in the body is basically completed in about 6 months. Consumers need to re-inject, which increases the burden and pain of consumers. 3. It only has the effect of filling and tissue volume increase on the face, and cannot promote the synthesis of its own collagen, and cannot remove oxygen free radicals in the subcutaneous tissue of the face. 4. The situation of bleeding at the injection point of the skin of the injectable product is not considered, especially for hemophilia users, because the product itself has no hemostatic function. If bleeding problems occur, it will seriously endanger life. 5. The cross-linking agent in hyaluronic acid can cause inflammation, skin allergies and other phenomena.

[0004] In the published Chinese patent documents, technical information related to facial fillers for injection-type cosmetic surgery can be found. For example, CN113230452A recommends "a facial filler and its preparation method". In order to overcome the problem of rapid degradation of hyaluronic acid, hydroxyapatite and other ingredients are added to prolong the effect of hyaluronic acid, but the production time takes 5 days, the process is relatively complicated, and the residual cross-linking agent used will cause inflammation, allergies and other adverse reactions. Another example is CN108744054A, a facial filler composition gel for injection-type cosmetic surgery and its preparation method. Like CN113230452A, hydroxyapatite is used to prolong the effect of hyaluronic acid. The preparation process is simple and suitable for scale-up production, and no cross-linking agent is used, avoiding the risks brought by the cross-linking agent. However, compared with cross-linked hyaluronic acid, its degradation rate is faster, and only hydroxyapatite is left at the injection site, which will bring a granular feeling and cause discomfort to the user, and the product is not designed from the perspective of stimulating the tissue to produce collagen to delay aging.

[0005] Currently, the most widely used injectable cosmetic products are hyaluronic acid products, but hyaluronic acid products still have certain defects, such as: high cost, short maintenance time, only filling and tissue volume expansion effects on the face, and cannot promote the synthesis of collagen itself. Among them, the short maintenance time is the basic problem, and the publicly available technical information related to facial filling for injectable cosmetic surgery all revolves around technical issues such as prolonging the degradation time of hyaluronic acid, controlling the displacement of injected gel, and promoting collagen synthesis itself. There is no injectable gel that combines antibacterial, anti-inflammatory, antioxidant, and hemostatic functions. Summary of the invention

[0006] The purpose of the present invention is to provide a method for preparing an injectable facial filling hydrogel for cosmetic surgery to solve the existing problems.

[0007] In order to solve the above technical problems, the present invention is achieved through the following technical solutions:

[0008] The present invention is a method for preparing an injectable facial filling hydrogel for cosmetic surgery, comprising the following steps:

[0009] S1. Preparation of bioactive glass microspheres;

[0010] S2, using the bioactive glass microspheres, small molecule sodium hyaluronate, agarose, protein polypeptide, yeast extract, malic acid, sodium hexametaphosphate, magnesium chloride and deionized water to prepare a culture medium, inoculating Acetobacter xylinum into the culture medium, and controlling the specific gravity of Acetobacter xylinum to the culture medium, culturing at 29-31° C. for 1-3 days, taking out the bioactive glass microspheres, washing them, and then soaking them in alkaline solution, and washing them again after soaking until the pH value of the bioactive glass microspheres is 6-8, and drying them with air to obtain crude bacterial cellulose coated bioactive glass microspheres;

[0011] S3, dispersing the crude bacterial cellulose coated bioactive glass microspheres in a 5-8% w / w polyethylene glycol aqueous solution for 8-24 hours, drying, and sterilizing to obtain bacterial cellulose coated bioactive glass microspheres;

[0012] S4, dissolving nano-scale sodium carboxymethyl cellulose in water for injection containing 0.9% w / w sodium chloride, adding nisin, mixing, adding the bacterial cellulose coated bioactive glass microspheres, cross-linking nisin with the nano-sodium hyaluronate in the bacterial cellulose coated bioactive glass microspheres, self-assembling, and obtaining a facial filling hydrogel pre-canned body;

[0013] S5, degassing the face-filling hydrogel pre-canned body under negative pressure, then pressurizing and canning it in a syringe, and sterilizing it to obtain the face-filling hydrogel for cosmetic surgery.

[0014] Furthermore, the preparation method of the bioactive glass microspheres is:

[0015] The modified nano bioactive glass is dispersed in a metal salt and an organic liquid containing 0.5-5% w / w of a solubilizer for hydrolysis, and after being evenly dispersed, it is concentrated to obtain a crude microsphere product A;

[0016] The crude microsphere product A is calcined at high temperature according to a calcination curve to obtain a crude microsphere product B;

[0017] The crude microsphere product B is sieved to collect microspheres with a particle size of 15 to 45 μm, namely the bioactive glass microspheres.

[0018] Furthermore, the preparation method of the modified nano bioactive glass is:

[0019] Weigh x1 parts of tetrahydrosilane and alkoxide and dissolve them in deionized water, adjust the pH value to 2-3, and stir until the solution is clear and transparent to obtain a first solution;

[0020] Weigh X2 parts of tri-n-butyl borate, dissolve it in the first solution, and stir until the solution is clear and transparent to obtain a second solution; add ammonia water to the second solution and stir for 60-180 minutes to obtain a third solution;

[0021] Add X3 parts of triethyl phosphate to the third solution and stir for 60-100 minutes to obtain a fourth solution;

[0022] Add X4 parts of calcium nitrate tetrahydrate to the fourth solution, stir for 60-100 minutes to obtain a fifth solution; transfer the fifth solution to a reaction kettle, react at 150-240° C. for 12-24 hours to obtain a sixth solution;

[0023] The sixth solution was filtered and washed with deionized water, and this process was repeated three times before freeze drying to obtain modified nano bioactive glass.

[0024] Further, X1:X2:X3:X4=(42~48):(12~18):(5~7):(32~38), and X1+X2+X3+X4=100.

[0025] Furthermore, in the spray drying operation, the inlet temperature is controlled to be 260-360°C, the outlet temperature is 120-180°C, the feed rate is 22-48mL / min, the air intake volume is 580-980L / h, and the nozzle diameter is 0.6-1.0mm; the solubilizer is a non-ionic solubilizer; and the calcination curve is: heating from room temperature to 360°C at a heating rate of 3°C / min, and maintaining at 300°C for 90min, and then heating to 600°C at a heating rate of 4°C / min, and maintaining at 600°C for 150min.

[0026] Furthermore, the preparation method of the small molecule sodium hyaluronate is as follows: dissolve sodium hyaluronate in deionized water, stir evenly, homogenize under a pressure of 180-280 MPa, and freeze-dry the homogenized solution at a vacuum degree not exceeding 10 Pa and a temperature of -50°C to obtain small molecule sodium hyaluronate.

[0027] Furthermore, the mass ratio of the bioactive glass microspheres, small molecule sodium hyaluronate, agarose, protein polypeptide, yeast extract, malic acid, sodium hexametaphosphate and magnesium chloride is: (60-180): (1-8): (12-48): (6-8): (0.6-4.8): (0.2-3.8): (0.6-4.8): (8-18); the specific gravity of the Acetobacter xylinum to the culture medium is to control the volume weight ratio to (180-980) μL: 1000 g;

[0028] The sterilization conditions described in step S3 are: using a moist heat sterilizer and sterilizing at a temperature of 160° C. for 30-90 minutes.

[0029] Furthermore, the preparation method of the nano-scale sodium carboxymethyl cellulose is:

[0030] Sodium carboxymethyl cellulose is dissolved in deionized water, stirred evenly, homogenized at a pressure of 320-380 MPa, and the homogenized solution is freeze-dried at a vacuum degree not exceeding 10 Pa and a temperature of -58°C to obtain nano-grade sodium carboxymethyl cellulose.

[0031] Furthermore, the mass ratio of nisin to small molecule sodium hyaluronate is 1:1.

[0032] The present invention has the following beneficial effects:

[0033] The present invention can stimulate collagen regeneration through bioactive glass microspheres, thereby delaying facial aging; the bioactive glass microspheres contain boron oxide, which can regulate the alkaline microenvironment of tissues and cooperate with nisin to achieve an antibacterial effect; the nano-scale sodium carboxymethyl cellulose in the hydrogel can concentrate coagulation factors and promote rapid hemostasis at the bleeding site; the modified bioactive glass microspheres can be fixed through the sodium carboxymethyl cellulose gel to prevent the microspheres from being displaced after injection; the production process of the present invention is simpler and can meet the requirements of industrialized scale-up production.

[0034] Of course, any product implementing the present invention does not necessarily need to achieve all of the advantages described above at the same time. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings required for describing the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other accompanying drawings can be obtained based on these accompanying drawings without paying creative work.

[0036] Figure 1 The present invention is a schematic flow chart of a method for preparing an injectable facial filling hydrogel for cosmetic surgery. DETAILED DESCRIPTION

[0037] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0038] In the description of the present invention, it should be understood that the terms "upper", "middle", "outer", "inner" and the like indicating directions or positional relationships are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the components or elements referred to must have a specific direction, be constructed and operated in a specific direction, and therefore should not be understood as limiting the present invention.

[0039] In the description of the present invention, it should be noted that, unless otherwise clearly specified and limited, the terms "installed", "provided with", "connected", etc. should be understood in a broad sense. For example, "connected" can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection, or it can be indirectly connected through an intermediate medium, or it can be the internal communication of two components. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0040] See also Figure 1 As shown, the preparation method of the injectable facial filling hydrogel for cosmetic surgery of this embodiment comprises the following steps:

[0041] S1. Preparation of bioactive glass microspheres;

[0042] S2. Prepare a culture medium using bioactive glass microspheres, small molecule sodium hyaluronate, agarose, protein polypeptide, yeast extract, malic acid, sodium hexametaphosphate, magnesium chloride and deionized water, inoculate Acetobacter xylinum into the culture medium, and control the specific gravity of Acetobacter xylinum to the culture medium. After culturing at 29-31° C. for 1-3 days, take out the bioactive glass microspheres, wash them, and then soak them in alkaline solution. After soaking, wash them again until the pH value of the bioactive glass microspheres is 6-8. After air drying, obtain a crude product of bacterial cellulose coated bioactive glass microspheres.

[0043] S3, dispersing the crude bacterial cellulose coated bioactive glass microspheres in a 5-8% w / w polyethylene glycol aqueous solution for 8-24 hours, drying, and sterilizing to obtain bacterial cellulose coated bioactive glass microspheres;

[0044] S4, dissolving nano-scale sodium carboxymethyl cellulose in water for injection containing 0.9% w / w sodium chloride, adding nisin, mixing, adding bacterial cellulose coated bioactive glass microspheres, cross-linking nisin with nano-sodium hyaluronate in the bacterial cellulose coated bioactive glass microspheres, self-assembling, and obtaining a facial filling hydrogel pre-canned body;

[0045] S5. Degas the pre-filled hydrogel for facial filling under negative pressure, then can it into a syringe under pressure and sterilize it to obtain the hydrogel for facial filling for cosmetic surgery.

[0046] The preparation method of bioactive glass microspheres is:

[0047] The modified nano bioactive glass is dispersed in a metal salt and an organic liquid containing 0.5-5% w / w of a solubilizer for hydrolysis, and after being evenly dispersed, it is concentrated to obtain a crude microsphere product A;

[0048] The crude microsphere A is calcined at high temperature according to the calcination curve to obtain the crude microsphere B;

[0049] The crude microsphere product B is sieved to collect microspheres with a particle size of 15 to 45 μm, namely, bioactive glass microspheres.

[0050] The preparation method of modified nano bioactive glass is as follows:

[0051] Weigh x1 parts of tetrahydrosilane and alkoxide and dissolve them in deionized water, adjust the pH value to 2-3, and stir until the solution is clear and transparent to obtain a first solution;

[0052] Weigh X2 parts of tri-n-butyl borate, dissolve it in the first solution, and stir until the solution is clear and transparent to obtain a second solution; add ammonia water to the second solution and stir for 60-180 minutes to obtain a third solution;

[0053] Add X3 parts of triethyl phosphate to the third solution and stir for 60-100 minutes to obtain a fourth solution;

[0054] Add X4 parts of calcium nitrate tetrahydrate to the fourth solution, stir for 60-100 minutes to obtain a fifth solution; transfer the fifth solution to a reaction kettle, react at 150-240° C. for 12-24 hours to obtain a sixth solution;

[0055] The sixth solution was filtered and washed with deionized water, and this process was repeated three times before freeze drying to obtain modified nano bioactive glass.

[0056] Further, X1:X2:X3:X4=(42~48):(12~18):(5~7):(32~38), and X1+X2+X3+X4=100.

[0057] During the spray drying operation, the inlet temperature is controlled at 260-360°C, the outlet temperature is controlled at 120-180°C, the feed rate is controlled at 22-48mL / min, the air volume is controlled at 580-980L / h, and the nozzle diameter is controlled at 0.6-1.0mm; the solubilizer is a non-ionic solubilizer; the calcination curve is: heating from room temperature to 360°C at a heating rate of 3°C / min, and maintaining at 300°C for 90 minutes, then heating to 600°C at a heating rate of 4°C / min, and maintaining at 600°C for 150 minutes.

[0058] The preparation method of the small molecule sodium hyaluronate is as follows: dissolve sodium hyaluronate in deionized water, stir evenly, homogenize under a pressure of 180-280 MPa, and freeze-dry the homogenized solution at a vacuum degree not exceeding 10 Pa and a temperature of -50°C to obtain small molecule sodium hyaluronate.

[0059] The mass ratio of bioactive glass microspheres, small molecule sodium hyaluronate, agarose, protein polypeptide, yeast extract, malic acid, sodium hexametaphosphate and magnesium chloride is: (60-180): (1-8): (12-48): (6-8): (0.6-4.8): (0.2-3.8): (0.6-4.8): (8-18); the specific gravity of Acetobacter xylinum to culture medium is to control the volume weight ratio to (180-980) μL: 1000 g;

[0060] The sterilization conditions in step S3 are: using a moist heat sterilizer, sterilizing at a temperature of 160° C. for 30-90 minutes.

[0061] The preparation method of nano-scale sodium carboxymethyl cellulose is:

[0062] Sodium carboxymethyl cellulose is dissolved in deionized water, stirred evenly, homogenized at a pressure of 320-380 MPa, and the homogenized solution is freeze-dried at a vacuum degree not exceeding 10 Pa and a temperature of -58°C to obtain nano-grade sodium carboxymethyl cellulose.

[0063] The mass ratio of nisin to small molecule sodium hyaluronate is 1:1.

[0064] In the description of this specification, the description with reference to the terms "one embodiment", "example", "specific example", etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner.

[0065] The preferred embodiments of the present invention disclosed above are only used to help explain the present invention. The preferred embodiments do not describe all the details in detail, nor do they limit the invention to the specific implementation methods described. Obviously, many modifications and changes can be made according to the content of this specification. This specification selects and specifically describes these embodiments in order to better explain the principles and practical applications of the present invention, so that those skilled in the art can understand and use the present invention well. The present invention is limited only by the claims and their full scope and equivalents.

Claims

1. A method for preparing an injectable facial filling hydrogel for cosmetic surgery, characterized in that: The following steps are involved: S1. Preparation of bioactive glass microspheres; S2, using the bioactive glass microspheres, small molecule sodium hyaluronate, agarose, protein polypeptide, yeast extract, malic acid, sodium hexametaphosphate, magnesium chloride and deionized water to prepare a culture medium, inoculating Acetobacter xylinum into the culture medium, and controlling the specific gravity of Acetobacter xylinum to the culture medium, culturing at 29-31° C. for 1-3 days, taking out the bioactive glass microspheres, washing them, and then soaking them in alkaline solution, and washing them again after soaking until the pH value of the bioactive glass microspheres is 6-8, and drying them with air to obtain crude bacterial cellulose coated bioactive glass microspheres; S3, dispersing the crude bacterial cellulose coated bioactive glass microspheres in a 5-8% w / w polyethylene glycol aqueous solution for 8-24 hours, drying, and sterilizing to obtain bacterial cellulose coated bioactive glass microspheres; S4, dissolving nano-scale sodium carboxymethyl cellulose in water for injection containing 0.9% w / w sodium chloride, adding nisin, mixing, adding the bacterial cellulose coated bioactive glass microspheres, cross-linking nisin with the nano-sodium hyaluronate in the bacterial cellulose coated bioactive glass microspheres, self-assembling, and obtaining a facial filling hydrogel pre-canned body; S5, degassing the face-filling hydrogel pre-canned body under negative pressure, then pressurizing and canning it in a syringe, and sterilizing it to obtain the face-filling hydrogel for cosmetic surgery.

2. The method for preparing the facial filling hydrogel for cosmetic surgery according to claim 1, characterized in that: The preparation method of the bioactive glass microspheres is as follows: The modified nano bioactive glass is dispersed in a metal salt and an organic liquid containing 0.5-5% w / w of a solubilizer for hydrolysis, and after being evenly dispersed, it is concentrated to obtain a crude microsphere product A; The crude microsphere product A is calcined at high temperature according to a calcination curve to obtain a crude microsphere product B; The crude microsphere product B is sieved to collect microspheres with a particle size of 15 to 45 μm, namely the bioactive glass microspheres.

3. The method for preparing the facial filling hydrogel for cosmetic surgery according to claim 2, characterized in that: The preparation method of the modified nano bioactive glass is: Weigh x1 parts of tetrahydrosilane and alkoxide and dissolve them in deionized water, adjust the pH value to 2-3, and stir until the solution is clear and transparent to obtain a first solution; Weigh X2 parts of tri-n-butyl borate, dissolve it in the first solution, and stir until the solution is clear and transparent to obtain a second solution; add ammonia water to the second solution and stir for 60-180 minutes to obtain a third solution; Add X3 parts of triethyl phosphate to the third solution and stir for 60-100 minutes to obtain a fourth solution; Add X4 parts of calcium nitrate tetrahydrate to the fourth solution and stir for 60-100 minutes to obtain a fifth solution; The fifth solution was transferred to a reaction kettle, and reacted at 150-240° C. for 12-24 hours to obtain a sixth solution; The sixth solution was filtered and washed with deionized water, and this process was repeated three times before freeze drying to obtain modified nano bioactive glass.

4. The method for preparing the facial filling hydrogel for cosmetic surgery according to claim 3, characterized in that: X1:X2:X3:X4=(42~48):(12~18):(5~7):(32~38), and X1+X2+X3+X4=100.

5. The method for preparing the facial filling hydrogel for cosmetic surgery according to claim 2, characterized in that: In the spray drying operation, the inlet temperature is controlled to be 260-360°C, the outlet temperature is 120-180°C, the feed rate is 22-48mL / min, the air volume is 580-980L / h, and the nozzle diameter is 0.6-1.0mm; the solubilizer is a non-ionic solubilizer; and the calcination curve is: The temperature was increased from room temperature to 360°C at a heating rate of 3°C / min and maintained at 300°C for 90 min, then increased to 600°C at a heating rate of 4°C / min and maintained at 600°C for 150 min.

6. The method for preparing an injectable facial filling hydrogel for cosmetic surgery according to claim 1, characterized in that: The preparation method of the small molecule sodium hyaluronate is as follows: dissolving sodium hyaluronate in deionized water, stirring evenly, homogenizing under a pressure of 180-280 MPa, and freeze-drying the homogenized solution at a vacuum degree not exceeding 10 Pa and a temperature of -50°C to obtain the small molecule sodium hyaluronate.

7. The method for preparing the facial filling hydrogel for cosmetic surgery according to claim 1, characterized in that: The mass ratio of the bioactive glass microspheres, small molecule sodium hyaluronate, agarose, protein polypeptide, yeast extract, malic acid, sodium hexametaphosphate and magnesium chloride is: (60-180): (1-8): (12-48): (6-8): (0.6-4.8): (0.2-3.8): (0.6-4.8): (8-18); the specific gravity of the Acetobacter xylinum to the culture medium is controlled to have a volume weight ratio of (180-980) μL: 1000 g; The sterilization conditions described in step S3 are: using a moist heat sterilizer and sterilizing at a temperature of 160° C. for 30-90 minutes.

8. The method for preparing the facial filling hydrogel for cosmetic surgery according to claim 1, characterized in that: The preparation method of the nano-scale sodium carboxymethyl cellulose is: Sodium carboxymethyl cellulose is dissolved in deionized water, stirred evenly, homogenized at a pressure of 320-380 MPa, and the homogenized solution is freeze-dried at a vacuum degree not exceeding 10 Pa and a temperature of -58°C to obtain nano-grade sodium carboxymethyl cellulose.

9. The method for preparing the facial filling hydrogel for cosmetic surgery according to claim 1, characterized in that: The mass ratio of nisin to small molecule sodium hyaluronate is 1:1.

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