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CN111298196A - Polylactic acid porous microsphere, preparation method and application thereof - Google Patents

Polylactic acid porous microsphere, preparation method and application thereof Download PDF

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Publication number
CN111298196A
CN111298196A CN202010227693.3A CN202010227693A CN111298196A CN 111298196 A CN111298196 A CN 111298196A CN 202010227693 A CN202010227693 A CN 202010227693A CN 111298196 A CN111298196 A CN 111298196A
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polylactic acid
microspheres
microsphere
solution
porous
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张谦
管汉亮
耿文鑫
李立文
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Changzhou Institute Of Materia Medica Co ltd
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Changzhou Institute Of Materia Medica Co ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/18Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/20Polysaccharides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56Porous materials, e.g. foams or sponges
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58Materials at least partially resorbable by the body
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2400/00Materials characterised by their function or physical properties
    • A61L2400/06Flowable or injectable implant compositions

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Abstract

The invention relates to a preparation method of polylactic acid porous microspheres, which respectively prepares an oil phase solution and a water phase solution; pouring the oil phase solution into the water phase solution, and uniformly stirring to obtain O/W emulsion; stirring the O/W emulsion to obtain a polylactic acid microsphere suspension, screening microspheres with target particle sizes from the polylactic acid microsphere suspension, and collecting to obtain a polylactic acid microsphere semi-finished product; and (4) freeze-drying the polylactic acid microsphere semi-finished product to obtain a polylactic acid microsphere finished product. A polylactic acid porous microsphere is prepared by the method. An application of polylactic acid porous microspheres as a facial filler. On one hand, the collagen can be wrapped and fibrillated through chronic inflammatory tissue reaction to stimulate human collagen hyperplasia so as to achieve the effect of filling and beautifying, and on the other hand, the porous structural characteristics can effectively reduce the residue of organic reagents, thereby ensuring the safety of products.

Description

Polylactic acid porous microsphere, preparation method and application thereof
Technical Field
The invention relates to polylactic acid porous microspheres, a preparation method and application thereof.
Background
The polylactic acid material is a biomedical material approved by the Food and Drug Administration (FDA), has excellent biocompatibility and biodegradability, and is widely used for preparing medical instruments in various forms such as surgical sutures, microspheres, bone nails, 3D (three-dimensional) stents and the like in the field of biomedical high polymer materials. The polylactic acid microspheres have a round and round structure and unique physiological action, and are concerned in the medical and medical industries.
Polylactic acid microspheres are also called 'child-care needles' in the beauty industry, and are microspherical particle powder prepared from polylactic acid materials by an emulsification volatilization method, a spray drying method, a membrane emulsification method and the like, and when the polylactic acid microspheres are injected into a dermis layer through the skin, polylactic acid is slowly degraded in the body to form lactic acid. In the degradation process, through chronic inflammatory tissue reaction, encapsulation and fibrosis are generated, collagen hyperplasia is induced, the new collagen is enabled to set up an elastic support for supporting skin, and the new collagen replaces the original microspheres as the microspheres are gradually degraded and absorbed by a human body. Thereby achieving the effect of effectively stimulating the natural collagen hyperplasia of the human body and forming the long-time continuous repair. The injection 'child' needle has the functions of filling, tightening, pulling, youth and the like, has multiple effects, can improve the skin quality, tighten the skin and fill up the depression, and is highly advocated in the beauty treatment field.
Currently, there are mainly facial fillers on the market: hyaluronic acid, autologous fat, collagen, and the like, which are merely physically filled after injection, are gradually absorbed and disappear, and need to be repeatedly injected to maintain the therapeutic effect. After the polylactic acid microspheres are injected into a human body, the polylactic acid microspheres can stimulate the generation of collagen in the deep layer of the skin of the human body and stimulate the activity of cells. Therefore, the effect is slowly embodied, the appearance is more real, and the effect is more durable.
Conventional face fillers suffer from the following disadvantages:
firstly, the pure physical filling effect can be degraded and absorbed in the body, the action time is short, repeated injection is needed, and great pain and inconvenience are brought to consumers.
Secondly, the facial filler prepared from animal-derived materials has certain potential hypersensitivity risk and needs to be tested for hypersensitivity.
Thirdly, the facial filler prepared by artificially synthesizing the non-degradable material can cause long-term complications such as 'granuloma', and the like, and the long-term safety of the product needs to be highly concerned because the material is not degradable.
Disclosure of Invention
The invention provides a polylactic acid porous microsphere, a preparation method and application thereof, which aim to solve the problems.
In order to solve the technical problems, the invention provides a preparation method of polylactic acid porous microspheres, which comprises the following steps:
step S10, dissolving polylactic acid in dichloromethane to prepare a polylactic acid solution, and then adding polyethylene glycol as a pore-foaming agent and uniformly mixing to obtain an oil phase solution;
step S20, adding deionized water into polyvinyl alcohol and stirring until the polyvinyl alcohol is completely dissolved to obtain a polyvinyl alcohol solution, namely an aqueous phase solution;
step S30, pouring the oil phase solution into the water phase solution and stirring uniformly to obtain O/W emulsion;
step S40, stirring the O/W emulsion, volatilizing dichloromethane in the O/W emulsion to solidify and separate out polylactic acid into a microsphere material, and simultaneously forming a porous structure on the surface of the microsphere after polyethylene glycol is dissolved in water to obtain polylactic acid microsphere suspension;
s50, screening microspheres with target particle sizes from the polylactic acid microsphere suspension, and collecting to obtain a polylactic acid microsphere semi-finished product;
and step S60, freeze-drying the polylactic acid microsphere semi-finished product to obtain a polylactic acid microsphere finished product.
Further, in step S10, dissolving polylactic acid in dichloromethane by using a vortex mixer, wherein the concentration of the polylactic acid in dichloromethane is 10% -30%; the ratio of the dosage of the polyethylene glycol to the dosage of the polylactic acid is 0.1: 1-3: 1.
Further, in step S20, the polyvinyl alcohol raw material is poured into a beaker, deionized water is added, and the mixture is stirred at 97 ℃ by using a magnetic stirring water bath until the polyvinyl alcohol is completely dissolved, the solution is colorless and transparent, and is prepared into a polyvinyl alcohol solution with a concentration of 4.0% to 6.0%, and the polyvinyl alcohol solution is cooled to room temperature for later use.
Further, in step S30, an electric mixer is used as an emulsifying device, the rotation speed is set to be 200-600 rpm, the oil phase solution is poured into the polyvinyl alcohol solution, the volume ratio of the oil phase to the water phase is 1: 10-1: 50, the emulsifying time is 10-60 min, and the O/W emulsion is formed after stirring.
Further, in step S40, the O/W emulsion is transferred to a 35-40 ℃ water bath and stirred at a low speed of 50-200 rpm for 12-24 hours to volatilize the dichloromethane.
Further, in step S50, the microspheres smaller than 30 microns are removed, the microspheres larger than 80 microns are removed, and the particle size of the screened microspheres is 30-80 microns, so that the desired semi-finished polylactic acid microspheres are obtained.
Further, in step S60, 0.5% -2% sodium carboxymethylcellulose solution is added to the prepared polylactic acid microsphere semi-finished product, and after uniform mixing, the mixed solution is freeze-dried to obtain a polylactic acid microsphere finished product.
Further, in step S10, the polylactic acid has a molecular weight of 3W to 10W.
In addition, the polylactic acid porous microsphere prepared by the preparation method is provided.
In addition, the application of the polylactic acid porous microspheres as a facial filler is provided.
The invention has the beneficial effects that the polylactic acid porous microsphere provided by the invention, the preparation method and the application thereof have the following advantages:
1. in the process of emulsifying and stirring the water phase and the oil phase, the porous polylactic acid microspheres with uniform particle size are prepared by precisely and strictly adjusting various process parameters during emulsification and solidification, the recovery rate of the polylactic acid microspheres is improved, and the residue of the organic solvent is controlled below a safe level.
2. Polyethylene glycol is used as a pore-forming agent, a loose and porous structure is formed on the surface of the polylactic acid microsphere, volatilization of an organic solvent is facilitated, and the safety of the product is further ensured.
3. The sodium carboxymethylcellulose is used as an auxiliary raw material, so that the polylactic acid microspheres can be rapidly and uniformly dispersed in the solution, the rapid injection is convenient, the sodium carboxymethylcellulose also has a timely filling effect, and after the sodium carboxymethylcellulose is absorbed by a human body, the polylactic acid microspheres are released to stimulate the production of collagen of the human body, so that the effect of continuously filling and beautifying is achieved.
Additional features and advantages of the invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. The objectives and other advantages of the invention will be realized and attained by the structure particularly pointed out in the written description and claims hereof as well as the appended drawings.
In order to make the aforementioned and other objects, features and advantages of the present invention comprehensible, preferred embodiments accompanied with figures are described in detail below.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and other drawings can be obtained by those skilled in the art without creative efforts.
FIG. 1 is a visual form of the polylactic acid microspheres under an optical microscope in the first embodiment;
FIG. 2 is a particle size distribution of one of the microspheres of the example;
FIG. 3 is the apparent morphology of the polylactic acid microspheres under an optical microscope in the second embodiment;
FIG. 4 is a particle size distribution of two microspheres of example;
FIG. 5 is the apparent morphology of the polylactic acid microspheres under an optical microscope in the third embodiment;
FIG. 6 is a particle size distribution of three microspheres of the example;
FIG. 7 is the apparent morphology of the polylactic acid microspheres under an optical microscope in the fourth embodiment;
FIG. 8 is the particle size distribution of the four microspheres of the example.
Detailed Description
To make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings, and it is apparent that the described embodiments are some, but not all embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
A preparation method of polylactic acid porous microspheres comprises the following steps:
step S10, dissolving polylactic acid in dichloromethane to prepare a polylactic acid solution, and then adding polyethylene glycol as a pore-foaming agent and uniformly mixing to obtain an oil phase solution;
specifically, in order to better dissolve the polylactic acid, the polylactic acid is dissolved in dichloromethane through a vortex mixer, and the concentration of the polylactic acid in the dichloromethane is 10-30%; the ratio of the dosage of the polyethylene glycol to the dosage of the polylactic acid is 0.1: 1-3: 1, and the molecular weight of the polylactic acid is 3W-10W.
Step S20, pouring the polyvinyl alcohol raw material into a beaker, adding deionized water, stirring at 97 ℃ by using a magnetic stirring water bath until the polyvinyl alcohol is completely dissolved, wherein the solution is colorless and transparent, and preparing the polyvinyl alcohol solution with the concentration of 4.0-6.0%, namely cooling the water phase solution to room temperature for later use.
Step S30, pouring the oil phase solution into the water phase solution and stirring uniformly to obtain O/W emulsion;
specifically, an electric stirrer is used as an emulsifying device, the rotating speed is set to be 200-600 rpm, an oil phase solution is poured into a polyvinyl alcohol solution, the volume ratio of an oil phase to a water phase is 1: 10-1: 50, the emulsifying time is 10-60 min, and an O/W emulsion is formed after stirring.
Step S40, transferring the O/W emulsion into a water bath kettle at 35-40 ℃, stirring at a low speed of 50-200 rpm for 12-24 hours to volatilize dichloromethane, solidifying and separating polylactic acid into a microsphere material, and simultaneously dissolving polyethylene glycol in water to form a porous structure on the surface of the microsphere to obtain a polylactic acid microsphere suspension;
s50, screening microspheres with target particle sizes from the polylactic acid microsphere suspension, and collecting to obtain a polylactic acid microsphere semi-finished product;
specifically, the mesh number of the screen mesh is 190 meshes and 500 meshes, microspheres smaller than 30 micrometers are removed by using the screen mesh of 500 meshes, microspheres larger than 80 micrometers are removed by using the screen mesh of 190 meshes, the particle size of the remaining microspheres is 30-80 micrometers, the needed semi-finished product polylactic acid microspheres are obtained, and then the auxiliary agents (polyethylene glycol and polyvinyl alcohol) are washed clean by using deionized water;
and step S60, adding 0.5-2% of sodium carboxymethylcellulose solution into the prepared polylactic acid microsphere semi-finished product, uniformly mixing, and freeze-drying the mixed solution to obtain a polylactic acid microsphere finished product, wherein the freeze-drying condition is pre-freezing at-40 ℃ for 2 hours, and after a sample is frozen, freeze-drying for 48 hours to obtain the polylactic acid microsphere finished product.
Specifically, the selected polylactic acid is medical grade polylactic acid, has the molecular weight of 3W-10W, is racemic polylactic acid (PDLLA), and belongs to an ester-based end-capped polymer.
The emulsifier used is polyvinyl alcohol, and the more preferred type is PVA-124.
The pore-forming agent is polyethylene glycol, and the more preferable model is PEG-400.
In particular to polylactic acid porous microspheres prepared by the preparation method.
In particular to an application of polylactic acid porous microspheres as a facial filler.
According to the invention, medical polylactic acid is taken as a basic raw material, polyethylene glycol-400 is taken as a pore-forming agent, and the porous polylactic acid microspheres with uniform particle size and size of 30-80 microns are prepared by an emulsification volatilization method, so that on one hand, the coating and fibrosis are generated through chronic inflammatory tissue reaction, the collagen hyperplasia of a human body can be effectively stimulated, the effect of filling and beautifying is achieved, on the other hand, the residue of an organic reagent can be effectively reduced due to the porous structural characteristics, and the safety of the product is ensured.
The following examples further illustrate embodiments of the present invention.
1. Yield test
Taking the input polylactic acid raw material M0 as a reference, and adopting an emulsification curing method to prepare the final polylactic acid microsphere with the weight of M1, wherein the recovery rate W of the microsphere is as follows:
W = M1/M0*100%
2. particle size and particle size distribution test
The particle size and particle size distribution test adopts wet method determination, taking polylactic acid microsphere powder, adding deionized water to prepare suspension, and using a Malvern MS2000 laser particle size tester to perform determination, wherein the proportion of target microspheres between 30 and 80 microns is calculated from the test result, and the higher the proportion value is, the higher the recovery rate of the target microspheres is. The particle size distribution of the microspheres is expressed by the Span value:
Span = (D90-D10)/D50
smaller Span values indicate narrower particle size distributions and more uniform sizes.
3. Observation of the surface morphology of the microspheres with a light mirror
Weighing 1 mg of polylactic acid microspheres, adding 5 mL of deionized water, performing ultrasound for 5 min to uniformly disperse the microspheres in the water, sucking 1mL of suspension, dripping the suspension on a glass slide, and observing the surface morphology of the microspheres by using an XSP-8C optical microscope.
Example one
Dissolving racemic polylactic acid (PDLLA) with the molecular weight of 5 ten thousand in dichloromethane to prepare a 15 wt% polylactic acid solution, adding polyethylene glycol (PEG-400) serving as a pore-forming agent into the solution according to the mass ratio of 2:1, mixing the polylactic acid solution with a prepared 4.8wt% polyvinyl alcohol aqueous solution (the volume ratio of the polylactic acid solution to the polyvinyl alcohol solution is 1: 25), and emulsifying and stirring the mixture at the temperature of 20 ℃, wherein the stirring speed is 500 r/min, and the stirring time is 40 min, so as to obtain the O/W emulsion. Then the emulsion is heated to 40 ℃ in water bath, after stirring for 12 h at low speed (60 rpm), the dichloromethane is basically completely volatilized, and the emulsion is solidified into a microsphere material to be separated out. After the microspheres are solidified, wet screening the polylactic acid microsphere suspension through a screen with a specific mesh number, screening out microspheres with the particle size of 30-80 microns, collecting to obtain a polylactic acid microsphere semi-finished product, and then washing with deionized water. And adding 1.0% sodium carboxymethylcellulose solution into the prepared polylactic acid microsphere semi-finished product, uniformly mixing, and freeze-drying the mixed solution to obtain a polylactic acid microsphere finished product. The test result shows that the obtained polylactic acid microspheres are round in shape, have porous structures on the surfaces (see figure 1), have the average particle size of 44.874 micrometers, have the Span value of 0.826 (see figure 2) and have the recovery rate of 74 percent by adopting an emulsion evaporation method under the process.
Example two
Dissolving racemic polylactic acid (PDLLA) with the molecular weight of 8 ten thousand in dichloromethane to prepare a polylactic acid solution with the concentration of 25 wt%, adding polyethylene glycol (PEG-400) serving as a pore-forming agent into the solution according to the mass ratio of 1:1, mixing the polylactic acid solution with a prepared 5.0wt% polyvinyl alcohol aqueous solution (the volume ratio of the polylactic acid solution to the polyvinyl alcohol solution is 1: 40), and carrying out emulsification and stirring at the temperature of 20 ℃, wherein the stirring speed is 400 r/min, and the stirring time is 30 min, so as to obtain the O/W emulsion. Then the emulsion is heated to 40 ℃ in water bath, after stirring for 16 h at low speed (60 rpm), the dichloromethane is basically completely volatilized, and the emulsion is solidified into a microsphere material to be separated out. After the microspheres are solidified, wet screening the polylactic acid microsphere suspension through a screen with a specific mesh number, screening out microspheres with the particle size of 30-80 microns, collecting to obtain a polylactic acid microsphere semi-finished product, and then washing with deionized water. And adding 1.5% sodium carboxymethylcellulose solution into the prepared polylactic acid microsphere semi-finished product, uniformly mixing, and freeze-drying the mixed solution to obtain a polylactic acid microsphere finished product. The test result shows that the obtained polylactic acid microspheres are round in shape, the surfaces of the polylactic acid microspheres have porous structures (shown in figure 3), the average particle size of the microspheres is 46.635 micrometers, the Span value is 0.895 (shown in figure 4), and the recovery rate of the microspheres is 71.2% by adopting an emulsion evaporation method.
EXAMPLE III
Dissolving racemic polylactic acid (PDLLA) with the molecular weight of 10 ten thousand in dichloromethane to prepare a 30 wt% polylactic acid solution, adding polyethylene glycol (PEG-400) serving as a pore-forming agent into the solution according to the mass ratio of 3:1, mixing the polylactic acid solution with a prepared 4.0wt% polyvinyl alcohol aqueous solution (the volume ratio of the polylactic acid solution to the polyvinyl alcohol solution is 1: 50), and emulsifying and stirring the mixture at the temperature of 20 ℃, wherein the stirring speed is 200 r/min, and the stirring time is 10 min, so as to obtain the O/W emulsion. Then the emulsion is heated to 40 ℃ in water bath, after stirring for 12 h at low speed (60 rpm), the dichloromethane is basically completely volatilized, and the emulsion is solidified into a microsphere material to be separated out. After the microspheres are solidified, wet screening the polylactic acid microsphere suspension through a screen with a specific mesh number, screening out microspheres with the particle size of 30-80 microns, collecting to obtain a polylactic acid microsphere semi-finished product, and then washing with deionized water. And adding 0.5% sodium carboxymethylcellulose solution into the prepared polylactic acid microsphere semi-finished product, uniformly mixing, and freeze-drying the mixed solution to obtain a polylactic acid microsphere finished product. The test result shows that the obtained polylactic acid microspheres are round in shape, have porous structures on the surfaces (see figure 5), have the average particle size of 54.423 micrometers, have the Span value of 0.826 (see figure 6) and have the recovery rate of 72.5 percent by adopting an emulsion evaporation method under the process.
Example four
Dissolving racemic polylactic acid (PDLLA) with the molecular weight of 3 ten thousand in dichloromethane to prepare a 10 wt% polylactic acid solution, adding polyethylene glycol (PEG-400) serving as a pore-forming agent into the solution according to the mass ratio of 0.1:1, mixing the polylactic acid solution with a prepared 6.0wt% polyvinyl alcohol aqueous solution (the volume ratio of the polylactic acid solution to the polyvinyl alcohol solution is 1: 10), emulsifying and stirring at the temperature of 20 ℃, wherein the stirring speed is 600 r/min, and the stirring time is 60min, so as to obtain the O/W emulsion. Then the emulsion is heated to 40 ℃ in water bath, after the stirring is continuously carried out for 14 h at a low speed (60 rpm), the dichloromethane is basically completely volatilized, and the emulsion is solidified into a microsphere material to be separated out. After the microspheres are solidified, wet screening the polylactic acid microsphere suspension through a screen with a specific mesh number, screening out microspheres with the particle size of 30-80 microns, collecting to obtain a polylactic acid microsphere semi-finished product, and then washing with deionized water. And adding 2% sodium carboxymethylcellulose solution into the prepared polylactic acid microsphere semi-finished product, uniformly mixing, and freeze-drying the mixed solution to obtain a polylactic acid microsphere finished product. The test result shows that the obtained polylactic acid microspheres are round in shape, have porous structures on the surfaces (see figure 7), have the average particle size of 43.461 micrometers, have the Span value of 0.705 (see figure 8) and have the recovery rate of 70.5 percent by adopting an emulsion evaporation method.
In summary, the invention provides a polylactic acid porous microsphere, a preparation method and an application thereof, and the polylactic acid porous microsphere has the following advantages:
1. in the process of emulsifying and stirring the water phase and the oil phase, the porous polylactic acid microspheres with uniform particle size are prepared by precisely and strictly adjusting various process parameters during emulsification and solidification, the recovery rate of the polylactic acid microspheres is improved, and the residue of the organic solvent is controlled below a safe level.
2. Polyethylene glycol is used as a pore-forming agent, a loose and porous structure is formed on the surface of the polylactic acid microsphere, volatilization of an organic solvent is facilitated, and the safety of the product is further ensured.
3. The sodium carboxymethylcellulose is used as an auxiliary raw material, so that the polylactic acid microspheres can be rapidly and uniformly dispersed in the solution, the rapid injection is convenient, the sodium carboxymethylcellulose also has a timely filling effect, and after the sodium carboxymethylcellulose is absorbed by a human body, the polylactic acid microspheres are released to stimulate the production of collagen of the human body, so that the effect of continuously filling and beautifying is achieved.
In light of the foregoing description of the preferred embodiment of the present invention, many modifications and variations will be apparent to those skilled in the art without departing from the spirit and scope of the invention. The technical scope of the present invention is not limited to the content of the specification, and must be determined according to the scope of the claims.

Claims (10)

1. A preparation method of polylactic acid porous microspheres is characterized by comprising the following steps: the method comprises the following steps:
step S10, dissolving polylactic acid in dichloromethane to prepare a polylactic acid solution, and then adding polyethylene glycol as a pore-foaming agent and uniformly mixing to obtain an oil phase solution;
step S20, adding deionized water into polyvinyl alcohol and stirring until the polyvinyl alcohol is completely dissolved to obtain a polyvinyl alcohol solution, namely an aqueous phase solution;
step S30, pouring the oil phase solution into the water phase solution and stirring uniformly to obtain O/W emulsion;
step S40, stirring the O/W emulsion, volatilizing dichloromethane in the O/W emulsion to solidify and separate out polylactic acid into a microsphere material, and simultaneously forming a porous structure on the surface of the microsphere after polyethylene glycol is dissolved in water to obtain polylactic acid microsphere suspension;
s50, screening microspheres with target particle sizes from the polylactic acid microsphere suspension, and collecting to obtain a polylactic acid microsphere semi-finished product;
and step S60, freeze-drying the polylactic acid microsphere semi-finished product to obtain a polylactic acid microsphere finished product.
2. The method for preparing porous polylactic acid microspheres according to claim 1, wherein:
in step S10, dissolving polylactic acid in dichloromethane through a vortex mixer, wherein the concentration of the polylactic acid in the dichloromethane is 10-30%; the ratio of the dosage of the polyethylene glycol to the dosage of the polylactic acid is 0.1: 1-3: 1.
3. The method for preparing porous polylactic acid microspheres according to claim 1, wherein:
in step S20, the polyvinyl alcohol raw material is poured into a beaker, deionized water is added, and the mixture is stirred at 97 ℃ in a magnetic stirring water bath until the polyvinyl alcohol is completely dissolved, the solution is colorless and transparent, and is prepared into a polyvinyl alcohol solution with a concentration of 4.0% -6.0%, and the polyvinyl alcohol solution is cooled to room temperature for later use.
4. The method for preparing porous polylactic acid microspheres according to claim 1, wherein:
in step S30, an electric stirrer is used as an emulsifying device, the rotation speed is set to be 200-600 rpm, the oil phase solution is poured into the polyvinyl alcohol solution, the volume ratio of the oil phase to the water phase is 1: 10-1: 50, the emulsifying time is 10-60 min, and an O/W emulsion is formed after stirring.
5. The method for preparing porous polylactic acid microspheres according to claim 1, wherein:
in step S40, the O/W emulsion is transferred to a 35-40 ℃ water bath and stirred at a low speed of 50-200 rpm for 12-24 hours to volatilize the dichloromethane.
6. The method for preparing porous polylactic acid microspheres according to claim 1, wherein:
in step S50, the microspheres smaller than 30 microns are removed, the microspheres larger than 80 microns are removed, and the particle size of the screened microspheres is 30-80 microns, thus obtaining the desired semi-finished polylactic acid microspheres.
7. The method for preparing porous polylactic acid microspheres according to claim 1, wherein:
in step S60, 0.5% -2% sodium carboxymethylcellulose solution is added to the prepared polylactic acid microsphere semi-finished product, and after uniform mixing, the mixed solution is freeze-dried to obtain a polylactic acid microsphere finished product.
8. The method for preparing porous polylactic acid microspheres according to claim 1, wherein:
in step S10, the polylactic acid has a molecular weight of 3W to 10W.
9. The polylactic acid porous microspheres prepared by the preparation method of any one of claims 1 to 8.
10. Use of the porous microspheres of polylactic acid according to claim 9 as a facial filler.
CN202010227693.3A 2020-03-27 2020-03-27 Polylactic acid porous microsphere, preparation method and application thereof Pending CN111298196A (en)

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