CN116966341A - Preparation method and application of beauty filler - Google Patents
Preparation method and application of beauty filler Download PDFInfo
- Publication number
- CN116966341A CN116966341A CN202311084953.6A CN202311084953A CN116966341A CN 116966341 A CN116966341 A CN 116966341A CN 202311084953 A CN202311084953 A CN 202311084953A CN 116966341 A CN116966341 A CN 116966341A
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- Prior art keywords
- composite gel
- thousand
- molecular weight
- regenerated
- regenerated composite
- Prior art date
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- 239000000945 filler Substances 0.000 title claims abstract description 52
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 230000003796 beauty Effects 0.000 title abstract description 8
- 239000002131 composite material Substances 0.000 claims abstract description 97
- 239000007863 gel particle Substances 0.000 claims abstract description 65
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 41
- 239000002537 cosmetic Substances 0.000 claims abstract description 39
- 239000000243 solution Substances 0.000 claims abstract description 35
- 230000001954 sterilising effect Effects 0.000 claims abstract description 30
- 239000002245 particle Substances 0.000 claims abstract description 29
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 claims abstract description 26
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- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims abstract description 21
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Classifications
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- 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
- A61L27/225—Fibrin; Fibrinogen
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- 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
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/227—Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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- 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
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- 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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- 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
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
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Abstract
The invention discloses a preparation method and application of a cosmetic filler, and the specific preparation steps comprise: dissolving the substrate I protein and the substrate II polysaccharide substance into lithium bromide injection water solution respectively, adding the lithium bromide injection water solution into a multifunctional stirring kettle, adding a cross-linking agent and a regenerant, stirring, injecting into a model, compacting, placing into a constant-temperature oven for reaction to form regenerated composite gel with a network structure, taking out, cooling at room temperature, crushing into regenerated composite gel particles, dialyzing the particles by using water for injection, removing the rest cross-linking agent, sterilizing to obtain sterile regenerated composite gel particles A, dissolving an active ingredient, sodium carboxymethyl cellulose and glycerol in a solvent, filtering and sterilizing to obtain a sterile solution B, mixing the sterile regenerated composite gel particles A with the sterile solution B, and performing ultrasonic treatment to obtain the sterile regenerated cosmetic filler C. The product can support full skin in a short period, immediately achieve the effect of eliminating wrinkles, and maintain the long-term beauty effect.
Description
Technical Field
The invention belongs to the technical field of medical cosmetology, and particularly relates to a preparation method and application of a cosmetology filler.
Background
Research shows that with the age, the amount of collagen and elastic fiber in dermis is continuously reduced, and meanwhile, the fat gap under skin is continuously increased, so that the problems of wrinkles, skin laxity and the like are caused.
Human bones begin to shrink around age 45, bones are a supporting system of the face, and lack of effective support, and skin can loose, wrinkle and the like, so that cosmetic fillers for eliminating wrinkles are generated.
The conventional dermal fillers such as crosslinked hyaluronic acid in the market have only temporary filling effect, once the hyaluronic acid is absorbed by human body, the hyaluronic acid can be recovered, and can not stimulate the human body to generate collagen to support skin, so that the skin can maintain the effect. At present, some gel fillers mixed with microspheres exist, but the components of the gel are single, the cosmetic effect is limited, and the microspheres are unevenly distributed in the gel, so that the irritation degree of each part is easily different, and the overall effect is influenced. As mentioned in patent CN105126166B, the microspheres are simply mixed with a material such as crosslinked hyaluronic acid gel or collagen or chitosan, to obtain a mixed gel containing microspheres for injection.
The gel as a carrier for the regenerated dermal filler requires very good strength to have a remarkable supporting effect in a short period of time, so that the effect cannot be ensured by the usual physical crosslinking means, whereas the method mentioned in patent CN102836465B, firstly, sets a silk fibroin solution at 25 ℃ to gel and pulverizes it to silk fibroin particles, and then chemically crosslinks the particles with hyaluronate. Since silk fibroin itself forms a gel, it is exposed to the outside to react with hyaluronate at a few sites, resulting in a low degree of crosslinking between the two, and a complex gel having sufficient strength cannot be formed.
To sum up, the problems to be solved are:
1) Most of the regenerative fillers have no obvious effect of supporting the skin and eliminating wrinkles in a short period after injection;
2) The gel strength as a carrier of the regenerated skin filler is smaller, the supporting effect is poor in a short period, the components are single, and the long-term efficacy is not ideal;
3) The microspheres or the microparticles of the regenerant are unevenly distributed in the carrier gel, so that after entering the skin, the irritation degree of each part is different, the overall beauty effect is poor, and even granuloma is generated locally;
4) The regenerant microspheres or particles have no interaction with the carrier gel, the regenerant filler is easily involved by muscles after entering the skin, and the regenerant microspheres or particles move unidirectionally, so that the filling effect deviates from the expected design, and the overall beautifying effect is affected.
Disclosure of Invention
In view of the above, the present invention aims to provide a preparation method and application of a cosmetic filler.
The specific technical scheme is as follows:
a method for preparing a cosmetic filler, comprising the steps of:
1) Respectively dissolving the substrate I protein and the substrate II polysaccharide substance into lithium bromide injection aqueous solution;
2) Adding the two aqueous solutions in the step 1) into a multifunctional stirring kettle, adding a crosslinking agent and a regenerant microsphere or microparticle, and stirring to form a uniform mixture;
3) Compacting the mixture obtained in the step 2) in a model, and putting the model into a constant-temperature oven at 30-60 ℃ for crosslinking reaction for 1-48h to form regenerated composite gel with a network structure and containing a regenerant;
4) After the reaction is finished, taking out the regenerated composite gel, cooling at room temperature, crushing into regenerated composite gel particles, dialyzing the particles with water for injection, and removing the rest crosslinking agent;
5) Sterilizing the regenerated composite gel particles in the step 4) to obtain sterile regenerated composite gel particles A;
6) Dissolving active ingredients, sodium carboxymethyl cellulose and glycerol in a solvent, and filtering and sterilizing to obtain a sterile solution B;
7) Under aseptic condition, aseptic regenerated composite gel particles A and aseptic solution B are mixed and ultrasonic treated for 3-30 min to obtain aseptic regenerated beautifying filler C, which is adsorbed in the network structure of gel.
Further, the substrate I protein in the step 1) is one or more of silk fibroin, I/II/III/IV/V/VII/XI type collagen, recombinant human type III collagen, elastin, fibronectin and fibronectin, and the volume concentration of the substrate I is 10-200 mg/ml; the molecular weight of the base material I is 1-200 ten thousand, the polysaccharide substance of the base material II is one or more of hyaluronic acid, sodium alginate and sodium carboxymethyl cellulose, the hyaluronic acid is one or more of sodium hyaluronate, calcium hyaluronate, potassium hyaluronate, magnesium hyaluronate and sodium hyaluronate acetyl, the volume concentration of the hyaluronic acid is 0-100 mg/ml, the molecular weight is 30-300 ten thousand, the volume concentration of the sodium alginate is 0-100 mg/ml, and the molecular weight is 2-20 ten thousand; the volume concentration of the sodium carboxymethyl cellulose is 0-100 mg/ml, the molecular weight is 9-70 ten thousand, and the mass ratio of the substrate I protein to the substrate II polysaccharide is 1:20-20:1.
Further, the cross-linking agent in the step 2) is one or more of 1, 4-butanediol diglycidyl ether, 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, N-hydroxysuccinimide, 4- (4, 6-dimethyltriazin-2-yl) -4-methylmorpholine hydrochloride, glutaraldehyde and genipin, the volume concentration of the cross-linking agent is 10-1000 ug/ml, the regenerant microsphere or microparticle is at least one of poly-L-lactic acid, poly-D-lactic acid, racemic poly-lactic acid, poly-caprolactone, poly-lactic acid-glycolic acid, polymethyl methacrylate, polyvinyl alcohol, hydroxyapatite and tricalcium phosphate, the average particle diameter of the regenerant microsphere or microparticle is 10-100um, the volume content of the regenerant microsphere or microparticle in the mixture is 1-50%, and the molecular weight of the poly-L-lactic acid, poly-D-lactic acid, racemic poly-lactic acid and poly-lactic acid-glycolic acid is 1-40 ten thousand; the molecular weight of the polycaprolactone is 0.5 to 20 ten thousand; polymethyl methacrylate has a molecular weight of 5-30 ten thousand; the molecular weight of the polyvinyl alcohol is 3 ten thousand to 20 ten thousand.
Further, the particle size of the regenerated composite gel particles in the step 4) is 100-400 meshes.
Further, the active ingredient in the step 6) is one or more of amino acid, vitamin, polypeptide, polydeoxyribonucleotide and polynucleotide, wherein the amino acid is at least one of glycine, alanine, proline, lysine and isoleucine, the volume concentration is 0-5.0 mg/ml, the vitamin is at least one of vitamin B2/B3/B5/B6/B7/B9 and vitamin C, the volume concentration is 0-10 ug/ml, the polypeptide comprises at least one of L-carnosine, glutathione, cupstrip, acetyl hexapeptide-3, palmitoyl pentapeptide-3 and acetyl tetrapeptide-5, the volume concentration is 0-2.0 mg/ml, the polydeoxyribonucleotide molecular weight is 5-50 ten thousand, the volume concentration is 0-20 mg/ml, the polynucleotide molecular weight is 70-150 ten thousand, the volume concentration is 0-20 mg/ml, the solvent is one of water for injection, physiological saline and phosphate buffer solution, the volume concentration of sodium carboxymethylcellulose is 0.1-30 mg/ml, and the volume concentration of glycerol is 0.1-100 mg/ml.
Further, the mass ratio of the sterile regenerated composite gel particles A to the sterile solution B in the step 7) is 1-100%, and the ultrasonic frequency in the step 7) is 20-30KHZ.
Further, the stirring paddle of the multifunctional stirring kettle is a ribbon stirring paddle, the bottom end of the stirring paddle is a discharge end, the discharge end is provided with a spiral groove, the bottom end of the spiral groove is a ball valve, and as the gap between the spiral groove and the discharge hole is very small, high-concentration viscous polymer solution is extruded through the rotation of the spiral groove, the molecular chains of the high-concentration viscous polymer solution are entangled with each other, and regenerant particles can be uniformly embedded in a high-molecular polymer structure.
Further, the sterilization mode in the step 5) is any one of irradiation sterilization, electron beam sterilization, damp-heat sterilization and EO sterilization.
A cosmetic filler prepared by the above preparation method is provided.
An application of cosmetic filler in preparing skin caring liquid is provided.
The invention has the beneficial effects that:
1. according to the invention, through chemical crosslinking of protein and polysaccharide substances, the network structure composite gel with better strength and toughness is formed, and the network structure composite gel has rich pores. Compared with gel formed by physical crosslinking, the gel has higher strength, supports the skin at the concave part, eliminates wrinkles, effectively prolongs the retention time of polysaccharide substances in a human body, maintains longer-term effect, and is beneficial to skin cells to climb and grow and proliferate on the gel. With the degradation of the protein component in the composite gel, amino acid is gradually released, skin tissue cells are nourished, and the long-term beautifying effect is maintained.
2. The active ingredients are uniformly distributed and adsorbed into the pores of the composite gel particles by the ultra-micro dispersion technology, and the active ingredients are slowly released along with the degradation of the composite gel particles, so that the skin-nourishing and repairing effects are achieved for a long time.
3. The invention embeds and fixes the regenerant microsphere or microparticle in the network structure of the composite gel through the interaction between the effective reactive group in the regenerant component and the polymer chain of the substrate I/II and the effective crosslinking reaction. Along with the injection of the regeneration filling agent into the dermis layer of the skin, the regeneration agent has an effect at a preset fixed point position, so that the situation that the actually filled position is inconsistent with the preset position and the overall beautifying filling effect is influenced due to the sliding of small-volume regeneration agent microspheres or particles caused by the movement of muscles in the skin is effectively avoided. And the uniformly distributed regenerant microspheres or particles enable all parts to be stimulated equally, so that granuloma caused by excessive stimulation is effectively avoided.
Drawings
FIG. 1 is a schematic structural view of a multifunctional stirred tank of the present invention;
FIG. 2 is a flow chart of the process for preparing the cosmetic filler of the present invention;
FIG. 3 is a comparison of the skin cell proliferation promotion of the cosmetic filler prepared in example 5 of the present invention with that of poly-L-lactic acid;
FIG. 4 is a graph showing the strength of the regenerated composite gel prepared in example 9 of the present invention compared to a conventional sodium hyaluronate gel;
FIG. 5 shows the distribution of the regenerant particles in a composite gel according to example 9 of the present invention.
In the figure: 1. a screw groove; 2. ball valve.
Detailed Description
The invention will be further described with reference to the drawings and examples of the specification, but the scope of the invention is not limited thereto.
As shown in fig. 1, the stirring paddle of the multifunctional stirring kettle used in the invention is a ribbon stirring paddle, the bottom end of the stirring paddle is a discharge end, the discharge end is provided with a screw groove 1, and the bottom end of the screw groove 1 is a ball valve 2.
As shown in fig. 2, a method for preparing a cosmetic filler comprises the steps of:
1) Preparation of sterile composite gel particles a: mixing the substrate I solution, the substrate II solution, the cross-linking agent and the regenerant microsphere or microparticle, pressing and reacting to obtain regenerated composite gel, crushing and sterilizing to obtain sterile composite gel particles A;
2) Preparation of a solution B containing the active ingredient: mixing the active ingredient, sodium carboxymethylcellulose and glycerol, filtering and sterilizing to obtain a sterile solution B;
3) Preparing a sterile regeneration cosmetic filler C: sterile composite gel particles A and the solution B containing active ingredients are mixed in a sterile mode, and ultrasound is carried out to obtain the sterile regenerated cosmetic filler C.
Example 1
1) Silk fibroin (molecular weight 50 ten thousand) and sodium hyaluronate (molecular weight 150 ten thousand) were dissolved in lithium bromide injection aqueous solution at 10mg/ml and 20mg/ml, respectively.
2) The above solution was added to a multifunctional stirred tank, 1, 4-butanediol diglycidyl ether was added at a concentration of 40ug/ml, poly-L-lactic acid microspheres (average particle size 40 um) were added at 20% wt, and stirred to a uniform mixture.
3) And (3) injecting the mixture into a model for compaction, and putting the model into a constant temperature oven at 60 ℃ for crosslinking reaction for 6 hours to form regenerated composite gel.
4) After the reaction, the regenerated composite gel was taken out and cooled at room temperature. After cooling, it was broken into 200 mesh regenerated composite gel particles.
5) And (3) dialyzing the regenerated composite gel particles with water for injection for 48 hours, and collecting for later use after the dialysis is finished. 6) And (3) sterilizing the regenerated composite gel particles in the step (5) by using radiation, wherein the radiation dose is 20KGY, and obtaining the sterile regenerated composite gel particles A.
7) Glycine, proline, lysine, sodium carboxymethylcellulose and glycerol were prepared as mixed solutions at 2mg/ml, 1mg/ml, 0.5mg/ml and 5mg/ml, respectively, using water for injection, and sterilized by filtration to obtain a sterile solution B.
8) Under aseptic condition, mixing aseptic regenerated composite gel particles A and aseptic solution B in a mass ratio of 10%wt, and carrying out ultrasonic treatment for 5 minutes at an ultrasonic frequency of 20KHz to obtain aseptic regenerated cosmetic filler C.
Example 2
1) Recombinant human type III collagen (molecular weight: 2 ten thousand) and sodium alginate (molecular weight: 20 ten thousand) were dissolved in lithium bromide injection aqueous solution at 50mg/ml and 20mg/ml, respectively.
2) The above solution was added to a multifunctional stirred tank, genipin was added at a concentration of 60ug/ml, polycaprolactone microspheres (average particle size 60 um) were added at a content of 20% wt, and stirred to a uniform mixture.
3) And (3) injecting the mixture into a model for compaction, and putting the model into a constant temperature oven at 30 ℃ for crosslinking reaction for 48 hours to form the regenerated composite gel.
4) And after the reaction is finished, taking out the regenerated composite gel, cooling the regenerated composite gel at room temperature, and crushing the cooled regenerated composite gel into 200-mesh regenerated composite gel particles.
5) And (3) dialyzing the regenerated composite gel particles with water for injection for 48 hours, and collecting for later use after the dialysis is finished. 6) Sterilizing the regenerated composite gel particles in step 5) with EO to obtain sterile regenerated composite gel particles A.
7) L-carnosine, glutathione, vitamin B2, vitamin B3, sodium carboxymethylcellulose and glycerol are prepared into mixed solutions with water for injection of 1mg/ml, 0.5mg/ml, 3ug/ml, 5ug/ml, 10mg/ml and 20mg/ml respectively, and sterile solution B is obtained by filtration and sterilization.
8) Under aseptic condition, mixing aseptic regenerated composite gel particles A and aseptic solution B in a mass ratio of 50%wt, and carrying out ultrasonic treatment for 5 minutes at an ultrasonic frequency of 25KHz to obtain aseptic regenerated cosmetic filler C.
Example 3
1) Type IV collagen (molecular weight 50 ten thousand) and acetylated sodium hyaluronate (molecular weight 30 ten thousand) were dissolved in lithium bromide injection aqueous solution at 30mg/ml and 50mg/ml, respectively.
2) The above solution was added to a multifunctional stirred tank, 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride was added at a concentration of 100ug/ml, polymethyl methacrylate microspheres (average particle size 20 um) were added at a content of 30% by weight, and stirred into a uniform mixture.
3) And (3) injecting the mixture into a model for compaction, and putting the model into a constant temperature oven at 50 ℃ for crosslinking reaction for 24 hours to form the regenerated composite gel.
4) After the reaction, the regenerated composite gel was taken out and cooled at room temperature. After cooling, it was broken into 300 mesh regenerated composite gel particles.
5) The regenerated composite gel particles were dialyzed against water for injection for 48 hours. After the dialysis is finished, the blood is collected for standby. 6) And (3) sterilizing the regenerated composite gel particles in the step (5) by using radiation, wherein the radiation dose is 25KGY, and obtaining the sterile regenerated composite gel particles A.
7) Glycine, alanine, vitamin B5, vitamin B9, sodium carboxymethylcellulose and glycerol are prepared into mixed solutions at the concentration of 1.5mg/ml, 2mg/ml, 5ug/ml, 3ug/ml, 1mg/ml and 50mg/ml respectively by using water for injection, and sterile solution B is obtained by filtering and sterilizing.
8) Under aseptic condition, mixing aseptic regenerated composite gel particles A and aseptic solution B in a mass ratio of 30%wt, and carrying out ultrasonic treatment for 10 minutes at an ultrasonic frequency of 30KHz to obtain the aseptic regenerated cosmetic filler C.
Example 4
1) Elastin (molecular weight 10 ten thousand) and sodium carboxymethylcellulose (molecular weight 30 ten thousand) were dissolved in a lithium bromide injection aqueous solution at 60mg/ml and 20mg/ml, respectively.
2) The solution was added to a multifunctional stirred tank, 4- (4, 6-dimethyltriazin-2-yl) -4-methylmorpholine hydrochloride was added at a concentration of 200ug/ml, hydroxyapatite microspheres (average particle size 25 um) were added at a content of 35% by weight, and stirred to a uniform mixture.
3) And (3) injecting the mixture into a model for compaction, and putting the model into a constant temperature oven at 45 ℃ for crosslinking reaction for 12 hours to form the regenerated composite gel.
4) After the reaction, the regenerated composite gel was taken out and cooled at room temperature. After cooling, it was broken into 150 mesh regenerated composite gel particles.
5) The regenerated composite gel particles were dialyzed against water for injection for 48 hours. After the dialysis is finished, the blood is collected for standby. 6) And (3) sterilizing the regenerated composite gel particles in the step (5) by using an electron beam, wherein the dosage is 20KGY, and obtaining the sterile regenerated composite gel particles A.
7) Proline, lysine, isoleucine, vitamin B2, vitamin B6, sodium carboxymethylcellulose and glycerol were formulated into mixed solutions at 2.5mg/ml, 1mg/ml, 3ug/ml, 5ug/ml, 10mg/ml and 5mg/ml, respectively, using water for injection, and sterilized by filtration to give a sterile solution B.
8) Under aseptic condition, mixing aseptic regenerated composite gel particles A and aseptic solution B in a mass ratio of 30%wt, and carrying out ultrasonic treatment for 10 minutes at an ultrasonic frequency of 20KHz to obtain aseptic regenerated cosmetic filler C.
Example 5
1) Silk fibroin (molecular weight 150 ten thousand) and sodium hyaluronate (molecular weight 200 ten thousand) were dissolved in a lithium bromide injection aqueous solution at 30mg/ml and 10mg/ml, respectively.
2) The above solution was added to a multifunctional stirred tank, 1, 4-butanediol diglycidyl ether was added at a concentration of 400ug/ml, poly-L-lactic acid microspheres (average particle size 35 um) were added at 30% wt, and stirred to a uniform mixture.
3) And (3) injecting the mixture into a model for compaction, and putting the model into a constant temperature oven at 55 ℃ for crosslinking reaction for 5 hours to form the regenerated composite gel.
4) After the reaction, the regenerated composite gel was taken out and cooled at room temperature. After cooling, it was broken into 200 mesh regenerated composite gel particles.
5) The regenerated composite gel particles were dialyzed against water for injection for 48 hours. After the dialysis is finished, the blood is collected for standby. 6) And (3) sterilizing the regenerated composite gel particles in the step (5) by using damp heat (121 ℃/15 min) to obtain sterile regenerated composite gel particles A.
7) Glycine, alanine, proline, PDRN (molecular weight 20 ten thousand), sodium carboxymethylcellulose and glycerol were prepared as mixed solutions at 2.5mg/ml, 1.5mg/ml, 2mg/ml, 10mg/ml and 15mg/ml, respectively, using water for injection, and sterilized by filtration to obtain sterile solution B.
8) Under aseptic condition, mixing aseptic regenerated composite gel particles A and aseptic solution B in a mass ratio of 35%wt, and carrying out ultrasonic treatment for 30 minutes at an ultrasonic frequency of 30KHz to obtain the aseptic regenerated cosmetic filler C.
Example 6
1) Type I collagen (molecular weight: 25 ten thousand) and type III collagen (molecular weight: 30 ten thousand) and sodium alginate (molecular weight: 10 ten thousand) were dissolved in a lithium bromide injection aqueous solution at 30mg/ml, 20mg/ml and 50mg/ml, respectively.
2) The above solution was added to a multifunctional stirred tank, genipin was added at a concentration of 500ug/ml, polylactic acid-glycolic acid microspheres (average particle size 40 um) were added at 45% wt, and stirred to a uniform mixture.
3) And (3) injecting the mixture into a model for compaction, and putting the model into a constant temperature oven at 35 ℃ for crosslinking reaction for 36 hours to form the regenerated composite gel.
4) After the reaction, the regenerated composite gel was taken out and cooled at room temperature. After cooling, it was broken into 200 mesh regenerated composite gel particles.
5) The regenerated composite gel particles were dialyzed against water for injection for 48 hours. After the dialysis is finished, the blood is collected for standby. 6) Sterilizing the regenerated composite gel particles in step 5) with EO to obtain sterile regenerated composite gel particles A.
7) Copper peptide, acetyl hexapeptide-3, PN (molecular weight 80 ten thousand), sodium carboxymethylcellulose and glycerin are prepared into mixed solutions respectively at 2.5mg/ml, 1.5mg/ml, 5mg/ml, 2mg/ml and 20mg/ml by using water for injection, and sterile solution B is obtained through filtration and sterilization.
8) Under aseptic condition, mixing aseptic regenerated composite gel particles A and aseptic solution B in a mass ratio of 60%wt, and carrying out ultrasonic treatment for 30 minutes at an ultrasonic frequency of 30KHz to obtain the aseptic regenerated cosmetic filler C.
Example 7
1) Silk fibroin (molecular weight 150 ten thousand), calcium hyaluronate (molecular weight 100 ten thousand) and sodium alginate (molecular weight 10 ten thousand) were dissolved in lithium bromide injection aqueous solutions at 20mg/ml, 35mg/ml and 20mg/ml, respectively. 2) The above solution was added to a multifunctional stirred tank, N-hydroxysuccinimide was added at a concentration of 200ug/ml, polyvinyl alcohol microspheres (average particle size 20 um) were added at a content of 20% by weight, and stirred to a uniform mixture.
3) And (3) injecting the mixture into a model for compaction, and putting the model into a constant temperature oven at 45 ℃ for crosslinking reaction for 10 hours to form the regenerated composite gel.
4) After the reaction, the regenerated composite gel was taken out and cooled at room temperature. After cooling, it was broken into 200 mesh regenerated composite gel particles.
5) The regenerated composite gel particles were dialyzed against water for injection for 48 hours. After the dialysis is finished, the blood is collected for standby. 6) And (3) sterilizing the regenerated composite gel particles in the step (5) by using damp heat (121 ℃/15 min) to obtain sterile regenerated composite gel particles A.
7) Glutathione, acetyl hexapeptide-3, vitamin B5, vitamin C, PDRN (molecular weight 30 ten thousand), sodium carboxymethylcellulose and glycerol were formulated into mixed solutions at 2.5mg/ml, 1.5mg/ml, 5ug/ml, 3ug/ml, 10mg/ml, 5mg/ml and 15mg/ml, respectively, using water for injection, and sterilized by filtration to obtain a sterile solution B.
8) Under aseptic condition, mixing aseptic regenerated composite gel particles A and aseptic solution B in a mass ratio of 30%wt, and carrying out ultrasonic treatment for 25 minutes at an ultrasonic frequency of 25KHz to obtain aseptic regenerated cosmetic filler C.
Example 8
1) Type XI collagen (molecular weight 5 ten thousand), fibronectin (molecular weight 20 ten thousand) and sodium alginate (molecular weight 20 ten thousand) were dissolved in lithium bromide injection aqueous solutions at 10mg/ml, 20mg/ml and 25mg/ml, respectively. 2) The above solution was added to a multifunctional stirring tank, glutaraldehyde was added at a concentration of 500ug/ml, and mixed particles of poly-L-lactic acid microspheres (average particle size: 20 um) and hydroxyapatite microspheres (average particle size: 30 um) were added at a content of 25% by weight, and stirred into a uniform mixture.
3) And (3) injecting the mixture into a model for compaction, and putting the model into a constant temperature oven at 35 ℃ for crosslinking reaction for 48 hours to form the regenerated composite gel.
4) After the reaction, the regenerated composite gel was taken out and cooled at room temperature. After cooling, it was broken into 150 mesh regenerated composite gel particles.
5) The regenerated composite gel particles were dialyzed against water for injection for 48 hours. After the dialysis is finished, the blood is collected for standby.
6) And (3) sterilizing the regenerated composite gel particles in the step (5) by using an electron beam, wherein the dosage is 20KGY, and obtaining the sterile regenerated composite gel particles A.
7) Glycine, alanine, vitamin B3, vitamin B5, vitamin C, PN (molecular weight 100 ten thousand), sodium carboxymethylcellulose and glycerol were formulated into mixed solutions at 1mg/ml, 1.5mg/ml, 2ug/ml, 5ug/ml, 2mg/ml, 5mg/ml and 10mg/ml, respectively, using water for injection, and sterilized by filtration to obtain sterile solution B.
8) Under aseptic condition, mixing aseptic regenerated composite gel particles A and aseptic solution B in a mass ratio of 20%wt, and carrying out ultrasonic treatment for 20 minutes at an ultrasonic frequency of 30KHz to obtain aseptic regenerated cosmetic filler C.
Example 9
1) Silk fibroin (molecular weight 150 ten thousand) and sodium hyaluronate (molecular weight 100 ten thousand) were dissolved in a lithium bromide injection aqueous solution at 30mg/ml and 10mg/ml, respectively.
2) The above solution was added to a multifunctional stirring tank, 1, 4-butanediol diglycidyl ether was added at a concentration of 600ug/ml, and mixed particles of poly-L-lactic acid fine particles (average particle size: 35 um) and tricalcium phosphate fine particles (average particle size: 30 um) were added at a content of 35% by weight, and stirred into a uniform mixture.
3) And (3) injecting the mixture into a model for compaction, and putting the model into a constant temperature oven at 40 ℃ for crosslinking reaction for 12 hours to form the regenerated composite gel.
4) After the reaction, the regenerated composite gel was taken out and cooled at room temperature. After cooling, it was broken into 150 mesh regenerated composite gel particles.
5) The regenerated composite gel particles were dialyzed against water for injection for 48 hours. After the dialysis is finished, the blood is collected for standby.
6) And (3) sterilizing the regenerated composite gel particles in the step (5) by using an electron beam, wherein the dosage is 20KGY, and obtaining the sterile regenerated composite gel particles A.
7) Glycine, alanine, vitamin B6, vitamin B7, vitamin C, PDRN (molecular weight 30 ten thousand), sodium carboxymethylcellulose and glycerol were formulated into mixed solutions at 1mg/ml, 1.5mg/ml, 2ug/ml, 5ug/ml, 10mg/ml, 5mg/ml and 10mg/ml, respectively, using water for injection, and sterilized by filtration to obtain sterile solution B.
8) Under aseptic condition, mixing aseptic regenerated composite gel particles A and aseptic solution B in 45 wt% and ultrasonic for 15min at 30KHz to obtain aseptic regenerated cosmetic filler C.
Example 10
Taking the beauty filler and the poly-L-lactic acid beauty filler prepared by the method in the example 5, adding the beauty filler and the poly-L-lactic acid beauty filler into 5ml penicillin bottles, adding 10mg of sample and 100ul of cell culture solution with known cell concentration into each penicillin bottle, placing the penicillin bottles into a constant temperature incubator at 37 ℃ for culturing for a certain period of time, taking out the samples after 3 days, 5 days, 7 days and 14 days respectively, placing the samples into a 2ml plastic centrifuge tube, repeatedly freezing and thawing the samples, adding 300ul of 10mg/ml papain-EDTA aqueous solution, digesting the samples for 24 hours in a 65 ℃ water bath, taking out the samples, centrifuging the samples at 1000rpm for 2 minutes as a solution to be tested for standby, diluting the Tris buffer solution for 5 times, diluting the samples for 10000 times by using the Tris buffer solution, taking 100ul of solution to be tested and 2ml of test solution for standby, and measuring the absorption intensity on a fluorescence spectrometer after mixing the 100ul of solution to be tested evenly, wherein the excitation wavelength is 360nm and the emission wavelength is 460nm; from the results shown in fig. 3, it can be seen that the cosmetic filler of example 4 has a very high proliferation rate of skin cells after 3 days of culture, and the poly-L-lactic acid cosmetic filler is relatively slow, which means that the cosmetic filler of the present invention promotes cell growth in the initial stage, and forms a new metabolism of skin aging cells, thereby exhibiting the effects of instantly reducing fine lines and glowing skin. The poly-L-lactic acid cosmetic filler contains poly-L-lactic acid microsphere, sodium carboxymethylcellulose and mannitol. The cosmetic filler prepared in example 5 contains proteins, polysaccharides and active ingredients, which help promote the growth, metabolism and renewal of skin cells when the product enters the dermis layer of the skin, compared with the poly-L-lactic acid cosmetic filler.
Example 11
The compound gel prepared in example 9 of the present invention and the ordinary sodium hyaluronate gel were taken separately and tested with an Advanced Rheology Expansion System (ARES) using a parallel plate mode (25 mm diameter, 1.8mm spacing), 37℃at a frequency range of 0.1-100rad/s and a strain range of 0.1-100%. The compound gel of the invention has obviously improved dynamic storage modulus along with the increase of frequency, and the common sodium hyaluronate gel strength is not greatly improved, which proves that the regenerated compound gel of the invention has larger gel strength, is favorable for playing a good role in supporting and filling when products enter skin wrinkles, and reducing the depth of the wrinkles, and can be seen in fig. 5 that the regenerant particles are fixed in the pores of the compound gel, are distributed uniformly in the visual field range and do not gather on a large scale.
Claims (10)
1. A method for preparing a cosmetic filler, comprising the steps of:
1) Respectively dissolving the substrate I protein and the substrate II polysaccharide substance into lithium bromide injection aqueous solution;
2) Adding the two aqueous solutions in the step 1) into a multifunctional stirring kettle, adding a crosslinking agent and a regenerant microsphere or microparticle, and stirring to form a uniform mixture;
3) Compacting the mixture obtained in the step 2) in a model, and putting the model into a constant-temperature oven at 30-60 ℃ for crosslinking reaction for 1-48h to form regenerated composite gel with a network structure and containing a regenerant;
4) After the reaction is finished, taking out the regenerated composite gel, cooling at room temperature, crushing into regenerated composite gel particles, dialyzing the particles with water for injection, and removing the rest crosslinking agent;
5) Sterilizing the regenerated composite gel particles in the step 4) to obtain sterile regenerated composite gel particles A;
6) Dissolving active ingredients, sodium carboxymethyl cellulose and glycerol in a solvent, and filtering and sterilizing to obtain a sterile solution B;
7) Under aseptic condition, mixing aseptic regenerated composite gel particles A with aseptic solution B, and ultrasound for 3-30 min to obtain aseptic regenerated cosmetic filler C.
2. The method for preparing a cosmetic filler according to claim 1, wherein the substrate I protein in step 1) is one or more of silk fibroin, type I/II/III/IV/V/VII/XI collagen, recombinant human type III collagen, elastin, fibronectin, and the volume concentration of substrate I is 10 to 200mg/ml; the molecular weight of the base material I is 1-200 ten thousand, the polysaccharide substance of the base material II is one or more of hyaluronic acid, sodium alginate and sodium carboxymethyl cellulose, the hyaluronic acid is one or more of sodium hyaluronate, calcium hyaluronate, potassium hyaluronate, magnesium hyaluronate and sodium hyaluronate acetyl, the volume concentration of the hyaluronic acid is 0-100 mg/ml, the molecular weight is 30-300 ten thousand, the volume concentration of the sodium alginate is 0-100 mg/ml, and the molecular weight is 2-20 ten thousand; the volume concentration of the sodium carboxymethyl cellulose is 0-100 mg/ml, the molecular weight is 9-70 ten thousand, and the mass ratio of the substrate I protein to the substrate II polysaccharide is 1:20-20:1.
3. The method for preparing a cosmetic filler according to claim 1, wherein the crosslinking agent in the step 2) is one or more of 1, 4-butanediol diglycidyl ether, 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, N-hydroxysuccinimide, 4- (4, 6-dimethyltriazin-2-yl) -4-methylmorpholine hydrochloride, glutaraldehyde, genipin, the volume concentration of the crosslinking agent is 10 to 1000ug/ml, the regenerant microsphere or microparticle is at least one of poly-l-lactic acid, poly-d-lactic acid, racemic poly-lactic acid, polycaprolactone, poly-lactic acid-glycolic acid, polymethyl methacrylate, polyvinyl alcohol, hydroxyapatite and tricalcium phosphate, the average particle diameter of the regenerant microsphere or microparticle is 10 to 100um, the volume content of the regenerant microsphere or microparticle in the mixture is 1 to 50%, and the molecular weight of poly-l-lactic acid, poly-d-lactic acid, racemic poly-lactic acid and poly-glycolic acid is 1 to 40 tens of thousands; the molecular weight of the polycaprolactone is 0.5 to 20 ten thousand; polymethyl methacrylate has a molecular weight of 5-30 ten thousand; the molecular weight of the polyvinyl alcohol is 3 ten thousand to 20 ten thousand.
4. The method for producing a cosmetic filler according to claim 1, wherein the regenerated composite gel particles in step 4) have a particle size of 100 to 400 mesh.
5. The method according to claim 1, wherein the active ingredient in the step 6) is at least one of amino acid, vitamin, polypeptide, polydeoxyribonucleotide and polynucleotide, wherein the amino acid is at least one of glycine, alanine, proline, lysine and isoleucine, the volume concentration is 0-5.0 mg/ml, the vitamin is at least one of vitamin B2/B3/B5/B6/B7/B9 and vitamin C, the volume concentration is 0-10 ug/ml, the polypeptide comprises at least one of L-carnosine, glutathione, copper peptide, acetyl hexapeptide-3, palmitoyl pentapeptide-3 and acetyltetrapeptide-5, the volume concentration is 0-2.0 mg/ml, the polydeoxyribonucleotide molecular weight is 5-50 ten thousand, the volume concentration is 0-20 mg/ml, the polynucleotide molecular weight is 70-150 ten thousand, the volume concentration is 0-20 mg/ml, the solvent is water for injection, the volume concentration of sodium carboxymethyl cellulose in physiological saline and phosphate buffer is 0-1.1 mg/ml, and the volume concentration of sodium in the buffer is 0-100.1 mg/ml.
6. The method for preparing a cosmetic filler according to claim 1, wherein the mass ratio of the sterile regenerated composite gel particles a to the sterile solution B in step 7) is 1% to 100%, and the ultrasonic frequency in step 7) is 20 to 30KHZ.
7. The method for preparing the cosmetic filler according to claim 1, wherein the stirring paddle of the multifunctional stirring kettle is a ribbon stirring paddle, the bottom end of the stirring paddle is a discharge end, the discharge end is provided with a spiral groove (1), and the bottom end of the spiral groove (1) is a ball valve (2).
8. The method for producing a cosmetic filler according to claim 1, wherein the sterilization means in step 5) is any one of radiation sterilization, electron beam sterilization, damp-heat sterilization and EO sterilization.
9. A cosmetic filler prepared by the preparation method according to claim 1.
10. Use of the cosmetic filler according to claim 9 for the preparation of a dermatological cosmetic liquid.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN117205366A (en) * | 2023-11-07 | 2023-12-12 | 南京东万生物技术有限公司 | Collagen-hyaluronic acid composite hydrogel for facial filling and preparation method thereof |
| CN117599247A (en) * | 2023-12-14 | 2024-02-27 | 浙江来益美生物医药有限公司 | Silk fibroin microcarrier skin filling preparation, and preparation method and application thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117205366A (en) * | 2023-11-07 | 2023-12-12 | 南京东万生物技术有限公司 | Collagen-hyaluronic acid composite hydrogel for facial filling and preparation method thereof |
| CN117205366B (en) * | 2023-11-07 | 2024-01-02 | 南京东万生物技术有限公司 | Collagen-hyaluronic acid composite hydrogel for facial filling and preparation method thereof |
| CN117599247A (en) * | 2023-12-14 | 2024-02-27 | 浙江来益美生物医药有限公司 | Silk fibroin microcarrier skin filling preparation, and preparation method and application thereof |
| CN117599247B (en) * | 2023-12-14 | 2024-05-31 | 浙江来益美生物医药有限公司 | Silk fibroin microcarrier skin filling preparation, and preparation method and application thereof |
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