WO2022205645A1 - Charge dermique injectable et son procédé de préparation - Google Patents
Charge dermique injectable et son procédé de préparation Download PDFInfo
- Publication number
- WO2022205645A1 WO2022205645A1 PCT/CN2021/103197 CN2021103197W WO2022205645A1 WO 2022205645 A1 WO2022205645 A1 WO 2022205645A1 CN 2021103197 W CN2021103197 W CN 2021103197W WO 2022205645 A1 WO2022205645 A1 WO 2022205645A1
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- WIPO (PCT)
- Prior art keywords
- dermal filler
- sodium hyaluronate
- mixed solution
- suspension
- dispersant
- Prior art date
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Classifications
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- A—HUMAN NECESSITIES
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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- A—HUMAN NECESSITIES
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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
- A61L27/50—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
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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
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Definitions
- the present application relates to the technical field of medical cosmetology, in particular to an injectable dermal filler and a preparation method thereof.
- Soft tissue fillers on the market mainly include cross-linked sodium hyaluronate gel, collagen, polylactic acid and calcium hydroxyapatite.
- the action time of cross-linked sodium hyaluronate gel and collagen in the skin is 6 to 12 months, and the action time of polylactic acid and calcium hydroxyapatite in the skin is about more than 2 years.
- Polyester materials such as polylactic acid, polycaprolactone, etc.
- polylactic acid and polycaprolactone are used as the raw materials of dermal fillers, and many products containing polylactic acid and/or polycaprolactone have been used to fill skin wrinkles and depressions. Lactic acid microspheres and polycaprolactone microspheres, etc.
- the existing conventional emulsification method adopts a relatively toxic emulsifier when preparing the microparticles, so it needs to be removed after post-treatment, and then the microparticles are obtained by drying and separation, and finally the microparticles and other dispersants or suspending agents are mixed and dispersed to obtain Dermal fillers, the preparation process is complicated.
- the present application provides an injectable dermal filler and a preparation method thereof, which can simplify the preparation process of the dermal filler.
- the present application provides an injectable dermal filler
- the dermal filler includes the following raw materials by mass percentage: polyester material, sodium hyaluronate, and dispersant.
- the polyester material is 20% to 80%, the sodium hyaluronate is 10% to 40%, and the dispersant is 10% to 60%; the skin filler is made of sodium hyaluronate and dispersant wrapped in polyester particles formed on the surface of similar materials.
- the dermal filler also includes water; 5% to 20% of polyester microparticles, 1% to 5% of sodium hyaluronate, 2% to 10% of dispersant and 65% to 90% of water; the skin
- the filler is a suspension of polyester microparticles in sodium hyaluronate and a dispersant.
- microparticles here may be spherical, irregular, rod-like, or the like.
- the dispersing agent is amino acid or mannitol.
- the dispersing agent is mannitol and amino acid; further, the mass percentage of the amino acid in the dermal filler is 2% to 50%. The mass percentage of the mannitol in the dermal filler is 2% to 50%.
- the polyester-based material is selected from one or more of polycaprolactone, poly-L-lactic acid, poly-D-lactic acid, polyglycolic acid and polyhydroxyalkanoate; further, the polyester-based material
- the intrinsic viscosity of the polyester material is 0.2-5.0 dL/g; further, the particle size of the polyester-based material is 0.01-200 ⁇ m.
- amino acid is selected from one or more of glycine, alanine, valine, leucine, isoleucine, proline, serine, phenylalanine, tryptophan and histidine kind.
- the intrinsic viscosity of the sodium hyaluronate is 0.5 to 4.0 m 3 /kg.
- the present application provides, in a second aspect, a method for preparing a dermal filler as described in the first aspect, the preparation method comprising the following steps: Step 1: dissolving sodium hyaluronate and a dispersant in water, and preparing a first mixture Step 2: Dissolve the polyester material in an organic solvent to prepare a second mixed solution; Step 3: Quickly add the second mixed solution to the first mixed solution, and fully emulsify to obtain a water-in-water solution oil emulsion; step 4: desolventizing the oil-in-water emulsion to obtain a suspension; step 5: lyophilizing the suspension to obtain polyester microparticles.
- the organic solvent is one of ethyl acetate, chloroform, toluene and dichloromethane; further, the organic solvent is dichloromethane or chloroform.
- the volume ratio of the first mixed solution and the second mixed solution is 1-20:1; further, in the step 4, the temperature of the desolvation is 20 ⁇ 50°C.
- the mixed solution is emulsified by ordinary stirring or emulsifier to form an oil-in-water emulsion, and then The emulsion is vacuum dried to remove the organic solvent and part of the water in the emulsion to obtain a suspension; the suspension can be used as a dermal filler.
- the embodiments of the present application not only save the process of removing the emulsifier and drying the microparticles, but also save the process of redispersing the microparticles. Therefore, in the embodiments of the present application, the preparation of microparticles and the preparation of the dermal filler can be performed simultaneously, which simplifies the preparation process.
- the dermal fillers prepared in the examples of the present application are not only suitable for deep dermis and subcutaneous tissue injection to fill deep wrinkles and depressions, but also suitable for superficial dermal water light injection to fill shallow wrinkles.
- the dermal fillers of the embodiments of the present application can be used as long-acting water light needles.
- Fig. 1 is the scanning electron microscope picture of poly-L-lactic acid microparticles in the embodiment 1 of the present application;
- Fig. 2 is the scanning electron microscope image of poly-L-lactic acid microparticles in the embodiment 2 of the application;
- Fig. 3 is the scanning electron microscope picture of polycaprolactone microparticles in the embodiment 3 of the present application.
- Example 4 is a scanning electron microscope image of polylactic acid-polycaprolactone-polylactic acid particles in Example 4 of the present application;
- Example 5 is a scanning electron microscope image of poly-L-lactic acid-glycolic acid particles in Example 5 of the present application;
- Example 6 is a scanning electron microscope image of polycaprolactone microparticles in Example 6 of the present application.
- an injectable dermal filler comprising the following raw materials by mass percentage: polyester material, sodium hyaluronate, and a dispersant.
- sodium hyaluronate is used as the emulsifier and suspending agent for polyester microparticles. Since sodium hyaluronate is degradable and biocompatible, there is no need to remove sodium hyaluronate or add additional suspension.
- sodium hyaluronate can repair skin cells, Therefore, sodium hyaluronate can also be used as a functional raw material for dermal fillers, promoting the proliferation and differentiation of epidermal cells and scavenging oxygen free radicals, thereby preventing skin aging.
- polyester material 20% to 80% of polyester material, 10% to 40% of sodium hyaluronate, and 10% to 60% of dispersant; the dermal filler is wrapped by sodium hyaluronate and dispersant Microparticles formed on the surface of polyester materials.
- the dermal filler includes the following raw materials by mass percentage: 5% to 20% of polyester microparticles, 1% to 5% of sodium hyaluronate, 2% to 10% of dispersant and 65% of water. % to 90%; the skin filler is a suspension formed by polyester microparticles in sodium hyaluronate and a dispersant.
- the dermal fillers of the embodiments of the present application are used in the state of suspension during clinical use.
- the dermal filler of the freeze-dried powder is reconstituted to form a suspension for use.
- the suspension obtained after vacuum drying of the O/W emulsion in the preparation process is directly used for clinical use.
- sodium hyaluronate is used as the emulsifier and suspending agent for polyester microparticles. Since sodium hyaluronate is degradable and biocompatible, there is no need to remove sodium hyaluronate or add additional suspension.
- sodium hyaluronate can repair skin cells, Therefore, sodium hyaluronate can also be used as a functional raw material for dermal fillers, promoting the proliferation and differentiation of epidermal cells and scavenging oxygen free radicals, thereby preventing skin aging.
- the dispersing agent is mannitol or amino acid; thus, by using mannitol or amino acid as the dispersing agent, not only can the polyester material in the second mixed solution be uniformly dispersed; but also It is degraded in the body, reducing the process of dispersing after dermal fillers.
- the mass percentage of the mannitol in the dermal filler is 2% to 50%, and the mass percentage of the amino acid in the dermal filler is 2% to 50%.
- mass percentage of the mannitol in the dermal filler is 2% to 50%.
- the polyester-based material is selected from one or more of poly-L-lactic acid, poly-D-lactic acid, polyglycolic acid, polyhydroxyalkanoate and polycaprolactone.
- the embodiment of the present application uses polyester material as the main component, which can not only prolong the degradation time of the dermal filler, but also effectively fill skin wrinkles and depressions.
- the intrinsic viscosity of the polyester-based material is 0.2-5.0 dL/g. Therefore, by selecting a polyester-based material with an appropriate intrinsic viscosity, the degradation rate of the dermal filler can be effectively controlled, thereby improving the cosmetic effect of the dermal filler.
- the particle size of the polyester material is 0.01-200 ⁇ m. Therefore, by selecting a polyester material with an appropriate particle size, not only can the depressions and wrinkles of the subcutaneous tissue be effectively filled, but also rapid pushing can be achieved during injection, avoiding difficulty in pushing.
- the amino acid is selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, proline, serine, phenylalanine, tryptophan and histidine one or more of.
- the intrinsic viscosity of the sodium hyaluronate is 0.5-4.0 m 3 /kg.
- the expected degradation time of the dermal filler can be controlled.
- the dermal fillers prepared in the examples of the present application can be used for filling and correcting wrinkles such as facial wrinkles, hand wrinkles, neck wrinkles, and stretch marks.
- the embodiments of the present application provide the preparation method of the dermal filler described in the first aspect of the embodiments of the present application.
- the method includes step 1: dissolving sodium hyaluronate and dispersant in water to prepare a first mixed solution; step 2: dissolving polyester materials in an organic solvent to prepare a second mixed solution; step 3: mixing The second mixed solution is quickly added to the first mixed solution, and fully emulsified to obtain an oil-in-water emulsion; step 4: desolventize the oil-in-water emulsion to obtain a suspension; step 5 : The suspension is lyophilized to obtain microparticles.
- a first mixed solution is obtained by dissolving sodium hyaluronate and a dispersant in water;
- a second mixed solution is obtained by dissolving the polyester material in an organic solvent; and then the second mixed solution is quickly added to the first mixed solution
- the emulsification treatment is carried out in the liquid, and the emulsified liquid after the emulsification treatment is desolvated to obtain a suspension.
- the process of removing the emulsifier and drying the microparticles is omitted, and the preparation of microparticles and the preparation of the dermal filler can be performed simultaneously, which simplifies the preparation process.
- the organic solvent is one of ethyl acetate, chloroform, toluene and dichloromethane; thus, the polyester material can be effectively dissolved.
- the organic solvent is chloroform or dichloromethane.
- the volume ratio of the first mixed solution and the second mixed solution is 1-20:1; in a further embodiment, the first mixed solution The volume ratio of the liquid to the second mixed liquid is 3 to 15:1; thus, a water-in-oil emulsion can be effectively obtained.
- the temperature of the desolvation is 20-50°C.
- any range recited in this application includes the endpoints and any values between the endpoints and any sub-ranges formed by the endpoints or any numbers between the endpoints.
- An injectable dermal filler comprising the following raw materials by mass percentage: poly-L-lactic acid 35.6%, sodium hyaluronate 23.7%, mannitol 40.7%; the dermal filler is wrapped in poly-L-lactic acid by sodium hyaluronate and mannitol. particles formed on the surface of lactic acid.
- the specific preparation method is as follows:
- Step 1 dissolving sodium hyaluronate with an intrinsic viscosity of 0.9 m 3 /kg in water to prepare a sodium hyaluronate aqueous solution, wherein the mass percentage of sodium hyaluronate and water in the sodium hyaluronate aqueous solution is 1%. 10.3 g of mannitol was added to the sodium hyaluronate aqueous solution, and the mixture was stirred and dissolved to obtain a first mixed solution; wherein the first mixed solution was an aqueous phase.
- Step 2 Weigh 9 g of poly-L-lactic acid with an intrinsic viscosity of 1.5 dL/g, dissolve it in 100 mL of dichloromethane, and prepare a second mixed solution; wherein the second mixed solution is an oil phase.
- Step 3 Quickly add the second mixed solution to the first mixed solution, and use an emulsifier to emulsify for 3 minutes at a rotational speed of 2000 r/min to obtain an O/W emulsion.
- Step 4 remove the solvent and part of the water from the emulsion at 30-50° C. to obtain a suspension; divide the suspension into multiple portions, place them in vials, and freeze-dry for 48 hours to obtain a dermal filler.
- Reconstitution test add 4 ml of water for injection to the prepared dermal filler, shake gently for 20 seconds to reconstitute to obtain a suspension; let the suspension stand for 10 minutes to remove air bubbles in the solution. From this, it can be seen that the reconstitution time of the dermal filler of the present embodiment is short.
- Pushing force test Use a 1 ml syringe to extract the suspension after standing, add a 30G needle, and use a microcomputer-controlled electronic universal testing machine to test the pushing force of the dermal filler. According to the test results, the average pushing force is 5N ⁇ 10N. It can be seen from this that the dermal filler of this embodiment can achieve smooth pushing.
- the particle size of the poly-L-lactic acid particles After the suspension after standing is washed and dried, the morphology of the particles is observed with a scanning electron microscope, and the particle size of the particles is tested. As shown in Figure 1, the poly-L-lactic acid particles The particle size is 2 to 34 ⁇ m. It can be seen that the morphology and particle size of the poly-L-lactic acid particles of the present application are uniform, and it is not only suitable for deep dermis and subcutaneous tissue injection to fill deep wrinkles and depressions, but also suitable for superficial dermal water light injection to fill shallow wrinkles.
- An injectable dermal filler comprising the following raw materials by mass percentage: poly-L-lactic acid 48.0%, sodium hyaluronate 20.0%, glycine 32.0%; the dermal filler is wrapped on the surface of poly-L-lactic acid by sodium hyaluronate and glycine particles formed.
- the specific preparation method is as follows:
- Step 1 dissolving sodium hyaluronate with an intrinsic viscosity of 2.1 m 3 /kg in water to prepare a sodium hyaluronate aqueous solution, wherein the mass percentage of sodium hyaluronate and water in the sodium hyaluronate aqueous solution is 0.5%.
- 4.0 g of glycine was added to the sodium hyaluronate aqueous solution, and the mixture was stirred and dissolved to obtain a first mixed solution; wherein the first mixed solution was an aqueous phase.
- Step 2 Weigh 6 g of poly-L-lactic acid with an intrinsic viscosity of 1.8 dL/g, dissolve it in 80 mL of chloroform, and prepare a second mixed solution; wherein the second mixed solution is an oil phase.
- Step 3 Quickly add the second mixed solution to the first mixed solution, and use an emulsifier to emulsify for 2 minutes at a rotational speed of 2500 r/min to obtain an O/W emulsion.
- Step 4 remove the solvent and part of the water from the emulsion at 20-50° C. to obtain a suspension; divide the suspension into multiple portions, place them in vials, and freeze-dry for 48 hours to obtain a dermal filler.
- Reconstitution test add 4 ml of water for injection to the prepared dermal filler, shake gently for 25 seconds to reconstitute to obtain a suspension; let the suspension stand for 10 minutes to remove air bubbles in the solution. From this, it can be seen that the reconstitution time of the dermal filler of the present embodiment is short.
- Pushing force test Use a 1 ml syringe to extract the suspension after standing, add a 30G needle, and use a microcomputer-controlled electronic universal testing machine to test the pushing force of the dermal filler. According to the test results, the average pushing force is 5N ⁇ 10N. It can be seen from this that the dermal filler of this embodiment can achieve smooth pushing.
- the particle size of the poly-L-lactic acid particles After the suspension after standing is washed and dried, the morphology of the particles is observed with a scanning electron microscope, and the particle size of the particles is tested. As shown in Figure 2, the poly-L-lactic acid particles The particle size is 2 to 32 ⁇ m.
- An injectable skin filler comprising the following raw materials by mass percentage: polycaprolactone 5.3%, sodium hyaluronate 3.4%, alanine 3.2% and water 88.1%; the skin filler is made of polycaprolactone in Suspension formed in sodium hyaluronate and alanine.
- the specific preparation method is as follows:
- Step 1 dissolving sodium hyaluronate with an intrinsic viscosity of 2.6 m 3 /kg in water to prepare a sodium hyaluronate aqueous solution, wherein the mass percentage of sodium hyaluronate and water in the sodium hyaluronate aqueous solution is 0.8%.
- 5.4 g of alanine was added to the sodium hyaluronate aqueous solution, and the mixture was stirred and dissolved to obtain a first mixed solution; wherein the first mixed solution was an aqueous phase.
- Step 2 Weigh 9 g of polycaprolactone with an intrinsic viscosity of 1.6 dL/g, dissolve it in 90 mL of dichloromethane, and prepare a second mixed solution; wherein the second mixed solution is an oil phase.
- Step 3 quickly add the second mixed solution to the first mixed solution, and emulsify for 3 min with an emulsifying machine at a rotational speed of 2500 r/min to obtain an O/W emulsion.
- Step 4 remove the solvent and part of the water from the emulsion at 20-40°C to obtain a suspension; divide the suspension into multiple portions and fill them into prefilled syringes to obtain a dermal filler.
- Pushing force test add a 30G needle to the pre-filled syringe containing the suspension, and use a microcomputer-controlled electronic universal testing machine to test the pushing force of the dermal filler. According to the test results, the average pushing force is between 5N and 10N. . It can be seen from this that the dermal filler of this embodiment can achieve smooth pushing.
- the particle size of the polycaprolactone particles after the suspension after standing is washed and dried, the morphology of the particles is observed with a scanning electron microscope, and the particle size of the particles is tested, as shown in Figure 3.
- the particle diameter of the ester fine particles is 2 to 29 ⁇ m.
- An injectable skin filler comprising the following raw materials by mass percentage: polylactic acid-polycaprolactone-polylactic acid 45.2%, sodium hyaluronate 21.7%, serine 33.1%; the skin filler is composed of sodium hyaluronate and Microparticles formed by wrapping serine on the surface of polylactic acid-polycaprolactone-polylactic acid.
- the specific preparation method is as follows:
- Step 1 dissolving sodium hyaluronate with an intrinsic viscosity of 3.0 m 3 /kg in water to prepare a sodium hyaluronate aqueous solution, wherein the mass percentage of sodium hyaluronate and water in the sodium hyaluronate aqueous solution is 0.4%.
- 5.5 g of serine was added to the sodium hyaluronate aqueous solution, and the mixture was stirred and dissolved to obtain a first mixed solution; wherein the first mixed solution was an aqueous phase.
- Step 2 Weigh 7.5 g of polylactic acid-polycaprolactone-polylactic acid with an intrinsic viscosity of 1.3dL/g, dissolve it in 80 mL of dichloromethane, and prepare a second mixed solution; wherein the second mixed solution is an oil phase. .
- Step 3 Quickly add the second mixed solution to the first mixed solution, and use an emulsifying machine to emulsify for 2.5 minutes at a rotational speed of 2400 r/min to obtain an O/W emulsion.
- Step 4 remove the solvent and part of the water from the emulsion at 20-40° C. to obtain a suspension; divide the suspension into multiple portions, place them in vials, freeze-dry for 48 hours, and obtain a dermal filler.
- Reconstitution test add water for injection to the prepared dermal filler, shake gently for 35 seconds to reconstitute to obtain a suspension; let the suspension stand for 10 minutes to remove air bubbles in the solution. From this, it can be seen that the reconstitution time of the dermal filler of the present embodiment is short.
- Pushing force test Use a 1 ml syringe to extract the suspension after standing, add a 30G needle, and use a microcomputer-controlled electronic universal testing machine to test the pushing force of the dermal filler. According to the test results, the average pushing force is 5N ⁇ 10N. It can be seen from this that the dermal filler of this embodiment can achieve smooth pushing.
- Particle size of polylactic acid-polycaprolactone-polylactic acid particles After the suspension after standing is washed and dried with water, the morphology of the particles is observed with a scanning electron microscope, and the particle size of the particles is tested, as shown in Figure 4 As shown, the particle size of the polylactic acid-polycaprolactone-polylactic acid microparticles is 2 to 34 ⁇ m.
- An injectable skin filler comprising the following raw materials by mass percentage: poly-L-lactic acid-glycolic acid 36.6%, sodium hyaluronate 16.3%, mannitol 47.1%; the skin filler is composed of sodium hyaluronate and mannitol Microparticles formed on the surface of poly-L-lactic-glycolic acid.
- the specific preparation method is as follows:
- Step 1 dissolving sodium hyaluronate with an intrinsic viscosity of 3.4 m 3 /kg in water to prepare a sodium hyaluronate aqueous solution, wherein the mass percentage of sodium hyaluronate and water in the sodium hyaluronate aqueous solution is 0.4%.
- 11.6 g of mannitol was added to the aqueous sodium hyaluronate solution, and stirred to dissolve to obtain a first mixed solution; wherein the first mixed solution was an aqueous phase.
- Step 2 Weigh 9 g of poly-L-lactic acid-glycolic acid with an intrinsic viscosity of 1.9 dL/g, dissolve it in 80 mL of chloroform, and prepare a second mixed solution; wherein the second mixed solution is an oil phase.
- Step 3 Quickly add the second mixed solution to the first mixed solution, and use an emulsifier to emulsify for 2 minutes at a rotational speed of 2800 r/min to obtain an O/W emulsion.
- Step 4 remove the solvent and part of the water from the emulsion at 20-40° C. to obtain a suspension; divide the suspension into multiple portions, place them in vials, freeze-dry for 48 hours, and obtain a dermal filler.
- Reconstitution test add water for injection to the prepared dermal filler, shake gently for 40 seconds to reconstitute to obtain a suspension; let the suspension stand for 10 minutes to remove air bubbles in the solution. From this, it can be seen that the reconstitution time of the dermal filler of the present embodiment is short.
- Pushing force test Use a 1 ml syringe to extract the suspension after standing, add a 30G needle, and use a microcomputer-controlled electronic universal testing machine to test the pushing force of the dermal filler. According to the test results, the average pushing force is 5N ⁇ 10N. It can be seen from this that the dermal filler of this embodiment can achieve smooth pushing.
- Particle size of poly-L-lactic acid-glycolic acid particles After the suspension after standing is washed and dried with water, the morphology of the particles is observed with a scanning electron microscope, and the particle size of the particles is tested, as shown in Figure 5, The particle size of the poly-L-lactic-glycolic acid fine particles is 2 to 34 ⁇ m.
- An injectable skin filler comprising the following raw materials by mass percentage: polycaprolactone 37.0%, sodium hyaluronate 11.5%, and mannitol 51.5%; the skin filler is wrapped in polycaprolactone by sodium hyaluronate and mannitol. Microparticles formed on the surface of lactones.
- the specific preparation method is as follows:
- Step 1 dissolving sodium hyaluronate with an intrinsic viscosity of 3.8 m 3 /kg in water to prepare a sodium hyaluronate aqueous solution, wherein the mass percentage of sodium hyaluronate and water in the sodium hyaluronate aqueous solution is 0.3%.
- 12.1 g of mannitol was added to the sodium hyaluronate aqueous solution, and stirred and dissolved to obtain a first mixed solution; wherein the first mixed solution was an aqueous phase.
- Step 2 Weigh 8.7 g of polycaprolactone with an intrinsic viscosity of 1.2 dL/g, dissolve it in 90 mL of dichloromethane, and prepare a second mixed solution; wherein the second mixed solution is an oil phase.
- Step 3 Quickly add the second mixed solution to the first mixed solution, and emulsify for 3 min with an emulsifying machine at a rotational speed of 2300 r/min to obtain an O/W emulsion.
- Step 4 remove the solvent and part of the water from the emulsion at 20-40° C. to obtain a suspension; divide the suspension into multiple portions, place them in vials, freeze-dry for 48 hours, and obtain a dermal filler.
- Reconstitution test add water for injection to the prepared dermal filler, shake gently for 45 seconds to reconstitute to obtain a suspension; let the suspension stand for 10 minutes to remove air bubbles in the solution. From this, it can be seen that the reconstitution time of the dermal filler of the present embodiment is short.
- Pushing force test Use a 1 ml syringe to extract the suspension after standing, add a 30G needle, and use a microcomputer-controlled electronic universal testing machine to test the pushing force of the dermal filler. According to the test results, the average pushing force is 5N ⁇ 10N. It can be seen from this that the dermal filler of this embodiment can achieve smooth pushing.
- the particle size of the polycaprolactone particles After the suspension after standing is washed and dried with water, the morphology of the particles is observed with a scanning electron microscope, and the particle size of the particles is tested, as shown in Figure 6.
- the particle diameter of the ester fine particles is 2 to 36 ⁇ m.
- first and second are only used for descriptive purposes, and should not be construed as indicating or implying relative importance or implying the number of indicated technical features. Thus, a feature delimited with “first”, “second” may expressly or implicitly include at least one of that feature.
- plurality means two or more, unless otherwise expressly and specifically defined.
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Abstract
L'invention concerne une charge dermique injectable, comprenant les matières premières suivantes : un matériau polyester, du hyaluronate de sodium et un dispersant. Le matériau polyester est choisi parmi un ou plusieurs des éléments suivants : polycaprolactone, acide poly-L-lactique, acide poly-D-lactique, acide polyglycolique et polyhydroxyalcanoate ; le dispersant est représenté par du mannitol et un acide aminé ; et l'acide aminé est choisi parmi une ou plusieurs des éléments suivants : glycine, alanine, valine, leucine, isoleucine, proline, sérine, phénylalanine, tryptophane et histidine. L'invention concerne également un procédé de préparation de la charge dermique.
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CN113730652B (zh) * | 2021-09-01 | 2022-12-02 | 北京大清生物技术股份有限公司 | 一种注射用混合凝胶及其制备方法和应用 |
CN113616604B (zh) * | 2021-10-12 | 2021-12-21 | 北京蓝晶微生物科技有限公司 | 一种可注射聚羟基脂肪酸酯微球及其制备方法 |
CN114796619B (zh) * | 2022-04-14 | 2023-03-14 | 珠海麦得发生物科技股份有限公司 | 可注射透明质酸微球及其制备方法和用途 |
CN115282336A (zh) * | 2022-08-26 | 2022-11-04 | 浙江天妍生物科技有限公司 | 一种含脂肪族聚酯微球多糖混合凝胶及其制备方法和应用 |
CN115475284B (zh) * | 2022-09-14 | 2024-02-02 | 华东理工大学 | 一种具有三维多孔结构的微球及其制备方法 |
CN115584037A (zh) * | 2022-10-19 | 2023-01-10 | 上海威高医疗技术发展有限公司 | 一种含聚合物微球的交联凝胶材料、其制备方法和注射填充剂 |
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