CN113144288A - Composite multi-component collagen micro-emulsion filler and preparation method thereof - Google Patents
Composite multi-component collagen micro-emulsion filler and preparation method thereof Download PDFInfo
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/24—Collagen
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/06—Flowable or injectable implant compositions
Abstract
The invention discloses a composite multi-component collagen micro-emulsion filler and a preparation method thereof, the application is based on collagen, the multi-component composite micro-emulsion filler adopts a vacuum heating physical crosslinking means to physically crosslink collagen I, collagen III and hyaluronic acid, the mechanical property of the collagen is improved, the degradation time of the filler is prolonged, and the good biocompatibility of the collagen is fully exerted.
Description
Technical Field
The invention relates to a composite multi-component collagen micro-emulsion filler and a preparation method thereof, belonging to the field of medical cosmetology.
Background
The facial skin tissue of the human body maintains its structure by proteins such as collagen and elastin and an extracellular matrix containing mucopolysaccharides. When soft tissue loss occurs due to congenital or external impact or disease, a dermal filler containing a component similar to dermal tissue may be injected into a specific site by injection to restore or correct the morphology of the soft tissue.
At present, the commonly used dermal fillers mainly take microspheres such as artificially synthesized hydroxyapatite, polylactic acid microspheres, polymethyl methacrylate microspheres and the like as main components, and the dermal fillers have long service life and good stability.
The existing collagen filler products in domestic markets comprise two types, namely a crosslinking collagen filler and a non-crosslinking collagen filler, the degradation time of the non-crosslinking filler is short, although the degradation time of the crosslinking collagen filler is prolonged, the residual crosslinking agent can generate toxic and side effects on skin, and a series of adverse reactions are caused.
Disclosure of Invention
The invention overcomes the defects of the prior art and provides a composite multi-component collagen microemulsion filling agent and a preparation method thereof.
A preparation method of a composite multi-component collagen micro-emulsion filler comprises the following steps:
1) preparing phosphate matrix solution, and equally dividing the phosphate matrix solution into solution A, solution B and solution C;
2) adding vitamin E, sodium carboxymethylcellulose, soybean phospholipid and poloxamer into the solution A obtained in the step 1), heating to 60 ℃, stirring until the solution is dissolved, filtering and sterilizing to obtain a sterile oil phase;
3) adding ceramide, procyanidine, vitamin C, vancomycin, tetracaine hydrochloride and diclofenac into the solution B obtained in the step 1), stirring for dissolving, and filtering for sterilization to obtain a sterile water phase;
4) mixing the sterile oil phase obtained in the step 2) with the sterile water phase obtained in the step 3), and stirring at a high speed for emulsification to obtain a W/O emulsion;
5) taking the solution C to prepare a mixed solution containing type I collagen and type III collagen, adding hyaluronic acid, homogenizing under high pressure, drying in vacuum for 4-6h, cooling to room temperature, adding into the W/O emulsion prepared in the step 4), shearing, mixing, emulsifying, and filling in vacuum to obtain the composite multi-component collagen micro-emulsion filler.
Further, the preparation method of the phosphate base solution in the step 1) comprises the following steps:
adding injection-grade sodium chloride into the injection-grade phosphate buffer solution, wherein the final concentration of the sodium chloride is 0.9%, and filtering by using a 0.22 mu m filter to obtain a phosphate matrix solution.
Further, the vitamin E, the sodium carboxymethyl cellulose, the soybean lecithin and the poloxamer in the step 2) are mixed according to the mass ratio of (5-25): (1-3): (16-80): (3-100) in proportion.
Further, the ceramide, the procyanidine, the vitamin C, the vancomycin, the tetracaine hydrochloride and the diclofenac in the step 3) are in a mass ratio of (2-4): 6: (15-17): (2-4): 10: 1 in a ratio of 1.
Further, the mixed solution containing type I collagen and type III collagen in the step 4) has a final concentration of type I collagen of 20-80mg/mL and a final concentration of type III collagen of 5-20 mg/mL.
Further, the vacuum drying conditions in the step 5) are as follows: the drying temperature is 50-60 deg.C, and the vacuum degree is 8-10 Pa.
The composite multi-component collagen micro-emulsion filler prepared by the preparation method can be obtained.
Furthermore, the collagen micro-emulsion filler is applied to the removal of free radicals and the enhancement of the antioxidation of skin.
Furthermore, the collagen micro-emulsion filling agent is applied to preparing products for removing wrinkles and delaying skin aging.
Has the advantages that:
(1) according to the preparation method, part of components are subjected to primary emulsification to prepare the W/O emulsion, and then the crosslinked collagen and the W/O emulsion are subjected to secondary emulsification by using shearing emulsification equipment to obtain the microemulsion filler.
(2) The microemulsion filling agent for collagen prepared by the application realizes the effect of delaying skin aging for a long time by depending on the characteristics of stability and long-acting slow release of the microemulsion filling agent on the basis of ensuring the filling effect, and simultaneously can improve the supporting effect of the filling agent, delay the degradation of the filling agent and fully exert the good biocompatibility of the collagen.
Drawings
FIG. 1 is a state diagram of a W/O microemulsion filler solution of the present invention.
FIG. 2 is a view of a W/O microemulsion filler solution of the present invention observed under a microscope.
FIG. 3 is a state diagram of composite multicomponent collagen filler prepared by other micro-emulsification methods.
FIG. 4 is a state diagram of a composite multicomponent collagen filler prepared in a non-microemulsifying manner.
FIG. 5 is a state diagram of a collagen filler alone.
FIG. 6 is a pathological section of an animal degradation test.
Figure 7 comparison of the effect before and after injection.
Detailed Description
In order to make the technical solutions in the present application better understood, the present invention is further described below with reference to examples, which are only a part of examples of the present application, but not all examples, and the present invention is not limited by the following examples.
The reagent consumables adopted by the invention are all common products sold in the market and can be purchased in the market.
Wherein, the type I collagen and the type III collagen are obtained by extracting, separating and purifying fresh calf skin tissues and removing the sensitized telopeptide.
Example 1
1. Preparation of composite multicomponent collagen micro emulsion filler
(1) Preparing a matrix solution: adding injection-grade sodium chloride into injection-grade phosphate buffer solution, and performing filtration sterilization by using a 0.22 mu m filter to obtain phosphate matrix solution containing 0.9% of sodium chloride;
(2) taking half of the above matrix solution, adding vitamin E0.5 g, sodium carboxymethylcellulose 0.06g, soybean phospholipid 1.6g, and poloxamer 2.0g into the matrix solution, heating to 60 deg.C, stirring to dissolve completely, filtering with 0.22 μm filter to remove bacteria to obtain oil phase;
(3) adding ceramide 0.1g, procyanidin 1.8g, vitamin C0.5 g, vancomycin 0.1g, tetracaine hydrochloride 0.3g, and diclofenac 30mg into the rest matrix solution, and magnetically stirring to dissolve completely to obtain water phase;
(4) emulsifying the oil phase and the water phase uniformly by using a high-speed stirring emulsifier to prepare a W/O emulsion;
(5) preparing a collagen micro-emulsion filler:
taking the rest matrix solution, preparing collagen solutions with the collagen I content and the collagen III content (the mass ratio of the two is 4:1) of 40mg/mL and 10mg/mL respectively, adding 20mg of hyaluronic acid, uniformly mixing the collagen I solution and the collagen III solution by using a high-pressure homogenizer, placing the mixture in a vacuum drying oven, adjusting the temperature to 55 ℃ and the vacuum degree to 10Pa, taking out the mixture after 6 hours, cooling the mixture to room temperature, adding the mixture into the W/O emulsion prepared in the step (4), uniformly dispersing the components by using a shearing mixing emulsifier, filling and pre-encapsulating to obtain the collagen micro-emulsion filler.
2. Product characteristics
As shown in figure 1, the filler is placed under an umbrella shed lamp, the illumination is 1000lx, the filler rotates freely, and the filler is white, milky white or yellowish milky liquid observed from the horizontal direction and has no visible foreign matters; centrifuging at 2000rpm for 15min without layering; endotoxin detection was less than 0.5 EU/mL. Taking a small amount of liquid, uniformly coating on a glass slide, observing under an optical microscope to form complete spherical emulsion droplets, as shown in figure 2
Example 2
1. Preparation of composite multicomponent collagen micro emulsion filler
(1) Preparing a matrix solution: adding injection-grade sodium chloride into injection-grade phosphate buffer solution, and performing filtration sterilization by using a 0.22 mu m filter to obtain phosphate matrix solution containing 0.9% of sodium chloride;
(2) taking half of the above matrix solution, adding vitamin E0.5 g, sodium carboxymethylcellulose 0.06g, soybean phospholipid 1.6g, and poloxamer 2.0g into the matrix solution, heating to 60 deg.C, stirring to dissolve completely, filtering with 0.22 μm filter to remove bacteria to obtain oil phase;
(3) preparing a collagen micro-emulsion filler:
taking the rest matrix solution to prepare collagen solutions with the collagen I content and the collagen III content (the mass ratio of the collagen I content to the collagen III content is 4:1) of 40mg/mL and 10mg/mL respectively, adding 20mg of hyaluronic acid, uniformly mixing the collagen I content and the collagen III content by using a high-pressure homogenizer, placing the mixture in a vacuum drying oven, adjusting the temperature to 55 ℃ and the vacuum degree to 10Pa, taking out the mixture after 6 hours, cooling the mixture to room temperature, adding the mixture into the oil phase, and dispersing the components into uniform oily emulsion by using a shearing mixing emulsifier;
(4) adding ceramide 0.1g, procyanidin 1.8g, vitamin C0.5 g, vancomycin 0.1g, tetracaine hydrochloride 0.3g, and diclofenac 30mg into the rest matrix solution, and magnetically stirring to dissolve completely to obtain water phase;
(5) slowly and uniformly dripping the oily emulsion on the water phase, and uniformly emulsifying the oil phase and the water phase by using a high-speed stirring emulsifier to obtain the O/W emulsion.
2. Product characteristics
As shown in figure 1, the filler is placed under an umbrella shed lamp, the illumination is 1000lx, the filler rotates freely, and the filler is white, milky white or yellowish milky liquid observed from the horizontal direction and has no visible foreign matters; centrifuging at 2000rpm for 15min without layering; endotoxin detection was less than 0.5 EU/mL. A small amount of liquid is uniformly smeared on a glass slide, and is observed under an optical microscope to form complete spherical emulsion droplets, which is shown in figure 3.
Example 3
1. Preparation of composite multicomponent collagen common filler
(1) Preparing a matrix solution: adding injection-grade sodium chloride into commercially available injection-grade phosphate buffer solution, and performing filtration sterilization by using a 0.22 μm filter to obtain sterile phosphate matrix solution containing 0.9% of sodium chloride;
(2) homogenizing collagen: taking part of the matrix solution to prepare collagen solutions with the collagen I content and the collagen III content (the mass ratio of the collagen I to the collagen III is 4:1) of 40mg/mL and 10mg/mL respectively, adding the collagen solutions, and uniformly mixing the collagen solutions by using a high-pressure homogenizer;
(3) preparing a mixed filler: adding 0.5g of vitamin E, 0.06g of sodium carboxymethylcellulose, 1.6g of soybean phospholipid and 2.0g of poloxamer into the rest matrix solution, heating to 60 ℃ to dissolve, adding 0.1g of ceramide, 1.8g of procyanidine, 0.5g of vitamin C, 0.1g of vancomycin, 0.3g of tetracaine hydrochloride, 30mg of diclofenac, 30mg of hyaluronic acid and collagen homogenate, mixing and stirring until completely dissolving, and filtering and sterilizing by a 0.22-micrometer filter to obtain the sterile oil phase.
2. Product characteristics
As shown in fig. 3, the filling agent is placed under an umbrella shed lamp, the illumination is 1000lx, the filling agent can be rotated freely, and the filling agent is white, milk white or yellowish viscous liquid without visible foreign matters when observed from the horizontal direction; centrifuging at 2000rpm for 15min without layering; endotoxin detection was less than 0.5 EU/mL. See fig. 4.
Example 4
1. Filler for preparing pure collagen
(1) Preparing a matrix solution: adding injection-grade sodium chloride into commercially available injection-grade phosphate buffer solution, and performing filtration sterilization by using a 0.22 μm filter to obtain sterile phosphate matrix solution containing 0.9% of sodium chloride;
(2) homogenizing collagen: the content of type I collagen and type III collagen (the mass ratio of the type I collagen to the type III collagen is 4:1) are respectively prepared into collagen solutions of 40mg/mL and 10mg/mL, and the collagen solutions are uniformly mixed by a high-pressure homogenizer.
2. Product characteristics
As shown in figure 4, the filling agent is placed under an umbrella shed lamp, the illumination is 1000lx, the filling agent can be rotated freely, and the filling agent is white, milk white or yellowish viscous transparent liquid without visible foreign matters when observed from the horizontal direction; centrifuging at 2000rpm for 15min without layering; endotoxin detection was less than 0.5 EU/mL. See fig. 5.
Example 5 efficacy verification of animal experiments
1. Security verification
20 adult guinea pig males and females were selected, and 8 adult guinea pig males and females were selected for each group (male and female halves), and 4 groups, i.e., experimental group, and negative control group, and the numbers thereof were marked, and skin was exposed by shaving on the back, 0.5mL of the collagen microemulsion fillers prepared in examples 1, 2, 3, and 4 were implanted into the dermal layer of the back skin, respectively (example 1 was used for the experimental group, example 2 was used for the experimental group, example 3 was used for the experimental group, and example 4 was used for the experimental group), and 0.5mL of physiological saline was injected into the negative control group.
Guinea pigs were observed daily for skin conditions on the back for two weeks and scored daily for irritation intensity with reference to skin irritation response scoring criteria. (Note: one experimental group is the composite multicomponent collagen microemulsion filling agent prepared in example 1, two experimental groups are the composite multicomponent collagen filling agent prepared in another emulsification method prepared in example 2, three experimental groups are the composite multicomponent collagen filling agent prepared in a simple mixing method prepared in example 3, and four experimental groups are the pure collagen filling agents prepared in example 4.)
TABLE 1 skin irritation test Scoring
The results show that the experimental animals in two groups, three groups and four groups have relatively weak irritability, no erythema and local edema appear in the experimental animals in one group, and no significant difference from the average value of the negative control group. The product obtained by the invention has no skin irritation and good safety.
2. Degradation test verification
20 male and female adult guinea pigs are selected, one group is formed by 4 male and female adult guinea pigs, each group comprises 4 groups, namely an experimental group, an experimental group and a negative control group, the numbers are marked, the skin is exposed by shaving the back, 0.5mL of samples of different experimental groups are respectively implanted into the dermis layer of the back skin, and 0.5mL of physiological saline is injected into the negative control group.
About 0.5cm of dorsal skin of 1 guinea pig per group was taken 1 month after implantation2After fixing 10% neutral paraformaldehyde, pathological sections and sirius red staining are carried out, the degradation condition of collagen is observed, and the result shows that the content of the collagen is gradually reduced along with the prolonging of time, and the collagen is completely degraded after 1 month. (Note: one experimental group is the composite multicomponent collagen microemulsion filling agent prepared in example 1, two experimental groups are the composite multicomponent collagen filling agent prepared in another emulsification method prepared in example 2, three experimental groups are the composite multicomponent collagen filling agent prepared in a simple mixing method prepared in example 3, and four experimental groups are the pure collagen filling agents prepared in example 4.)
The result of E in FIG. 6, which is a negative control group, shows the skin condition of normal mice. FIG. 6A is a group of experiments, and the slicing results show that the skin of the mice is very dense and still has a large amount of undegraded collagen; b in FIG. 6 is two groups of experiments, and the slicing result shows that the skin of the mouse is relatively dense and part of the filling collagen which is not degraded is still remained; in fig. 6, C is three groups of experiments, and the slicing result shows that the compactness of the skin of the mouse is relatively weakened, and the filled collagen is basically degraded; the section result shows that the filling effect of the simple mixed filling agent only containing the collagen component or only combining the collagen with other components is not as good as that of the complex multi-component collagen micro-emulsion filling agent.
3. Anti-aging experimental verification
20 male and female adult Kunming mice are selected, each male and female mice are provided with one group of 4 mice and 5 groups of 5 mice, namely an experimental group, a negative control group and a model group, the numbers are marked, and when the aging model caused by the D-galactose is prepared, 500mg of D-galactose normal saline is injected into the abdominal cavity-1.d-1After being continuously administrated for 26 days, the galactose concentration in body cells is increased, and is reduced into galactitol under the catalysis of aldose reductase, the galactitol cannot be metabolized by cells and is accumulated in the cells, the normal osmotic pressure is influenced, the cells are swelled and dysfunctional, the cells are apoptotic, and finally, the aging is caused. (Note: one experimental group is the composite multicomponent collagen microemulsion filling agent prepared in example 1, two experimental groups are the composite multicomponent collagen filling agent prepared in another emulsification method prepared in example 2, three experimental groups are the composite multicomponent collagen filling agent prepared in a simple mixing method prepared in example 3, and four experimental groups are the pure collagen filling agents prepared in example 4.)
Samples of different experimental groups are respectively implanted into the dermis layer of the back skin by 0.5mL, and a negative control group is injected with 0.5mL of physiological saline. The mice were sacrificed on day 30, blood was collected and serum was separated, and SOD activity and MDA content in the serum were measured. Thymus and spleen were separated, weighed for future use, and organ coefficients were calculated. The organ coefficient is organ mass (g)/volume mass (g) × 100%.
TABLE 2 influence of collagen bulking agent on mouse serum SOD activity, MDA, and mouse organ coefficient content
Group of | n | SOD(NU/mL) | MDA(nmol/mL) | Coefficient of thymus | Spleen coefficient |
Experiment group | 8 | 67.38±2.16 | 14.43±0.38 | 4.11±0.75 | 22.65±5.64 |
Two groups of experiments | 8 | 65.15±3.37 | 15.86±0.69 | 3.27±0.89 | 21.43±4.15 |
Three groups of experiments | 8 | 65.26±4.25 | 16.23±0.66 | 2.56±0.55 | 21.45±3.53 |
Experiment four groups | 8 | 64.85±5.03 | 16.53±0.47 | 2.36±0.64 | 20.86±3.97 |
Negative control group | 8 | 65.23±3.53 | 16.12±0.41 | 2.24±0.31 | 20.33±4.06 |
Model set | 8 | 60.45±2.44 | 18.47±0.85 | 1.75±0.43 | 18.41±2.74 |
Note: model group and control group, # P <0.05, and experimental group and model group, # P < 0.05.
And (4) conclusion: the detection results of the SOD activity and the MDA content of the serum of the mouse show that the SOD activity of the serum of the model group is reduced, and compared with the negative control group, the SOD activity of the serum of the rat of the experimental group is obviously higher than that of the model group (P <0.05), and the SOD activity of the serum of the rat of the experimental group is not obviously different from that of the negative control group of the experimental group, the serum of the experimental group and the serum of the fourth group and the serum of the negative control group; the serum MDA content of the model group is obviously increased (P <0.05) compared with that of the negative control group, the serum MDA content of the rat in the experimental group is obviously lower than that of the model group (P <0.05), and the experimental group, the experimental group and the experimental group have no obvious difference with the negative control group; the thymus coefficient and the spleen coefficient of the rats in the model group are obviously reduced, and have significant difference (P <0.05) compared with the negative control group, the thymus coefficient and the spleen coefficient of the rats in the experimental group are obviously increased, and have significant difference (P <0.05) compared with the model group in the experimental group.
EXAMPLE 6 clinical treatment
8 cases were treated.
1. The preoperative examination of a curer shows that all indexes are normal, including: hematuria and stool routine, electrocardiogram, liver and kidney functions, HIV and HbsAg.
2. The injection site was sterilized with iodophor.
3. The patient should be in the lying position or semi-lying position, the needle insertion direction should be along the direction of the wrinkle furrow, the shallower position is inserted into the superficial cortex of the skin at an angle of 10-25 degrees, and the deeper position is inserted into the dermis of the skin at an angle of 45 degrees. The injection amount is 1.0-2.0 times of the corrected defect depth, the product is injected according to the depth of the depression, 3-5 needles are implanted along the defect part, the needle is slowly withdrawn while the injection is carried out, and the more uniform the injection is, the better the injection is. If the skin color is not whitened, the needle should be withdrawn and the needle should be inserted again with a multi-point bevel.
The course of treatment is as follows: the injection site was injected 1 time in total.
The wrinkles basically disappear or obviously become shallow after injection, and the effect is good. A comparison of the effect before and after injection is shown in FIG. 7.
Claims (9)
1. A preparation method of a composite multi-component collagen micro-emulsion filler is characterized by comprising the following steps:
1) preparing phosphate matrix solution, and equally dividing the phosphate matrix solution into solution A, solution B and solution C;
2) adding vitamin E, sodium carboxymethylcellulose, soybean phospholipid and poloxamer into the solution A obtained in the step 1), heating to 50-60 ℃, stirring until the solution is dissolved, filtering and sterilizing to obtain a sterile oil phase;
3) adding ceramide, procyanidine, vitamin C, vancomycin, tetracaine hydrochloride and diclofenac into the solution B obtained in the step 1), stirring for dissolving, and filtering for sterilization to obtain a sterile water phase;
4) mixing the sterile oil phase obtained in the step 2) with the sterile water phase obtained in the step 3), and stirring at a high speed for emulsification to obtain a W/O emulsion;
5) taking the solution C to prepare a mixed solution containing type I collagen and type III collagen, adding hyaluronic acid, homogenizing under high pressure, drying in vacuum for 4-6h, cooling to room temperature, adding into the W/O emulsion prepared in the step 4), shearing, mixing, emulsifying, and filling in vacuum to obtain the composite multi-component collagen micro-emulsion filler.
2. A further method of preparation according to claim 1, wherein the phosphate base solution formulation method described in step 1) comprises the steps of:
adding injection-grade sodium chloride into the injection-grade phosphate buffer solution, wherein the final concentration of the sodium chloride is 0.9%, and filtering by using a 0.22 mu m filter to obtain a phosphate matrix solution.
3. The further preparation method according to claim 1, wherein the vitamin E, the sodium carboxymethylcellulose, the soybean phospholipids and the poloxamer in step 2) are mixed according to the mass ratio of (5-25): (1-3): (16-80): (3-100) in proportion.
4. The further preparation method according to claim 1, wherein the ceramide, the procyanidin, the vitamin C, the vancomycin, the tetracaine hydrochloride and the diclofenac in the step 3) are in a mass ratio of (2-4): 6: (15-17): (2-4): 10: 1 in a ratio of 1.
5. The method according to claim 1, wherein the final concentration of type I collagen and the final concentration of type III collagen in the mixed solution containing type I collagen and type III collagen in step 4) are 20 to 80mg/mL and 5 to 20mg/mL, respectively.
6. The further preparation process according to claim 1, wherein the vacuum drying conditions in step 5) are: the drying temperature is 50-60 deg.C, and the vacuum degree is 8-10 Pa.
7. The complex multicomponent collagen microemulsion filling agent prepared by the preparation method as set forth in any one of claims 1 to 6.
8. The use of a collagen microemulsion filler as defined in claim 7 for scavenging free radicals and enhancing antioxidant effect.
9. Use of a collagen microemulsion filling agent as defined in claim 7 for the preparation of a product for the removal of wrinkles and the retardation of skin aging.
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CN115350328A (en) * | 2022-08-19 | 2022-11-18 | 江苏西宏生物医药有限公司 | Long-acting particle III type collagen implant |
CN115350329A (en) * | 2022-08-19 | 2022-11-18 | 江苏西宏生物医药有限公司 | Long-acting particle type I and type III collagen composite implant |
CN115671390A (en) * | 2022-12-27 | 2023-02-03 | 北京思尔根生物科技有限公司 | Compound collagen composition and preparation method thereof |
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