CN108619564A - A kind of composition and preparation method thereof for skin filling - Google Patents
A kind of composition and preparation method thereof for skin filling Download PDFInfo
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- CN108619564A CN108619564A CN201710162378.5A CN201710162378A CN108619564A CN 108619564 A CN108619564 A CN 108619564A CN 201710162378 A CN201710162378 A CN 201710162378A CN 108619564 A CN108619564 A CN 108619564A
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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
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
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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
- 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
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
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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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/62—Encapsulated active agents, e.g. emulsified droplets
Abstract
The present invention provides a kind of compositions and preparation method thereof for skin filling.The composition is made of polylactic acid, suspending agent, excipient, and polylactic acid is 20~50 parts by weight percentage, and suspending agent is 10~30 parts, and excipient is 20~50 parts.Said preparation is microball preparation, it is that the O/W lotions formed by polylactic acid and poly-vinyl alcohol solution homogeneous the freeze-drying that is suspended in the aqueous solution containing suspending agent and excipient is prepared, feature is that polylactic acid described in composition contains l-lactic acid and dextrorotation polylactic acid, because its degradation time differs, both quick actings can be reached by controlling its ratio, the effect of long-acting maintenance again, particle size range is 20~75 microns, and cleansing pin performance is good, is not susceptible to stifled needle phenomenon.
Description
Technical field
The present invention relates to a kind of compositions and preparation method thereof for skin filling, it particularly relates to a kind of improvement
Bispin polylactic acid microsphere implant aseptic composite and preparation method thereof, belong to biomedicine technical field.
Background technology
Polylactic acid (polylactide, PLA) and its copolymer are a kind of macromolecule polymeric materials, have good biology
Compatibility and biodegradability, all products are nontoxic, vitals will not be caused to assemble.By U.S.'s food and medicine
Management board (FDA) approves the beautifying use of PLA preparations, and for improving the wrinkles such as decree line (laugh line), majority is freeze-dried powder
Injection is redissolved into suspension with sterile water for injection when use.On the one hand, because it is injection, clinically not using generation
Good reaction is the main reason for leading to patients stopping treatment, therefore adverse reaction is controlled as polylactic acid drug cosmetics after reducing injection
The problem of urgently optimizing in treatment.On the other hand, existing product is mostly l-lactic acid product, and absorption of human body is slow, is worked slow, still
It is microball preparation project urgently to be resolved hurrily.
Commercially available productIt is a kind of l-lactic acid particle filling of Sai Nuofei (Sanofi) company production and sales
Preparation, be originally approved for treatment patient HIV facial fat missing, after by FDA approval be used for beauty industry.The kind is
The safety and effectiveness that polylactic acid fills preparation is demonstrated by 96 weekly datas of clinic, but because it is microparticle formulation (Fig. 2), there are still
The defect of roundness difference is specific insufficient as follows：1) it is high to block up needle possibility：It need to disposably be injected using 26G syringe needles when injecting this product
Device is slowly injected, and stifled needle can lead to be subcutaneously injected uneven, the adverse reactions such as bulge after in turn resulting in hemotoncus, oedema or injecting.
It is shown according to commercially available product clinical data, most clinical adverses are hemotoncus (28%)；2) it works slow：On the one hand because it contains only a left side
Revolve polylactic acid, absorb it is slow, therefore since the 8th week just obviously action；On the other hand because it is microparticle formulation, grain shape is not advised
Then, exposure end carboxyl in surface differs, and palliating degradation degree differs, and cannot reach action steady in a long-term；3) it redissolves slow：When redissolving, respectively
Pellet moisture dissipates property degree and differs, and is suspended in the same time uneven, has a large amount of particles to glue wall, the longer suspension time is needed just may be used
It is uniform to ensure that it is suspended completely, and the longer suspension time will greatly improve preparation microbiological contamination possibility.
Patent application CN103408784A and patent application CN105749359A provides a kind of preparation side of porous microsphere
Method is mainly used for sustained-release micro-spheres drug delivery technologies, and porous microsphere degradation is fast, is not suitable for long-acting injection filler；Patent application
CN104258470A describes a kind of injection polylactic acid microsphere and crosslinking hyaluronic acid mixed gel and preparation method thereof, this is specially
In sharp product, polylactic acid microsphere is stored in aqueous gel environment, because polylactic acid microsphere in water environment stability inferior poor, Ke Nengfa
The problems such as raw microballoon is adhered, the mixed gel there are stability it is poor, the term of validity is short the shortcomings of；Patent application CN102516565B is carried
A kind of method preparing polylactic acid nano/micro spheres using solvent evaporation method has been supplied, roundness is high, utilizes a kind of dispersant with high efficiency,
It overcomes using dosage too many drawback when other surfaces activating agent and above-mentioned patent roundness and problem of high cost, but the hair
Bright not control the ratio between PLLA and PDLA in polylactic acid, palliating degradation degree difference is big between result can cause batch, influences end
Product clinical effectiveness.
For defect existing for polylactic acid preparation in the prior art, it is necessary to design and develop one kind can overcome it is above-mentioned not
The bispin polylactic acid microsphere preparation of good reaction is suitable for injection implant face filling, and without carrying medicine, and specific size distribution is equal
It is even, there is better clinical effectiveness.
Invention content
The purpose of the present invention is to provide a kind of bispin poly (lactic acid) compositions for skin filling to be applicable in without carrying medicine
In injection implant formula face filling.
It is another object of the present invention to provide a kind of sterile bispin polylactic acid preparations for skin filling, without carrying
Medicine, it is spherical, it is suitable for injection implant formula face filling.
It is another object of the present invention to provide a kind of preparation methods preparing above-mentioned preparation.
To achieve the goals above, a kind of novel composition for skin filling according to the present invention, by poly- breast
Acid, suspending agent, excipient composition, by weight percentage 20~50 parts of polylactic acid, 10~30 parts of suspending agent, excipient 20~50
Part, wherein the ratio between l-lactic acid and dextrorotation polylactic acid are L in the polylactic acid：D=4:1~1:4.
Heretofore described poly (lactic acid) composition, it is characterised in that its functional group of the polylactic acid is aldehyde radical, and characteristic is viscous
Degree is 1.7~2.3dL/g.
Heretofore described poly (lactic acid) composition, it is characterised in that the excipient is in lactose, sucrose and mannitol
It is one or more
Heretofore described poly (lactic acid) composition, it is characterised in that the suspending agent is sodium carboxymethylcellulose or alginic acid
It is one or more in sodium.
It is 20~75 microns of microspheroidal body that a kind of heretofore described polylactic acid preparation, which is average grain diameter, and surface
Smooth rounding contains above-mentioned l-lactic acid composition.
The polylactic acid preparation is preferably freeze-dried powder.
The preparation method of polylactic acid preparation of the present invention includes the following steps：
1) polylactic acid that 20~50 parts of inherent viscosities are 1.7~2.3dL/g is dissolved in organic solvent as oil phase O, 2%
(w/v) aqueous solution of poly-vinyl alcohol solution and organic solvent is as water phase W, wherein the range of viscosities of water phase W be 15.3~
20.7mPas (water) mixes this two-phase with certain proportion, with certain rotating speed homogeneous System forming O/W lotions；
2) O/W lotions obtained by step 1) are removed into organic solvent by the way that volatilization is stirred at room temperature, then microballoon is centrifuged, washing；
3) microballoon obtained by step 2) is suspended in the water containing 20~50 parts of freeze-dried excipients and 10~30 parts of suspending agents
In solution, the range of viscosities of the aqueous solution is that 270~320mPas (water) obtains polylactic acid microsphere system by freeze-drying
Agent
In the present invention, the preparation method, homogenizing time is 100~300s, homogeneous rotating speed in step 1) homogenizing process
For 2000~4000rpm, water phase W and oil phase O ratios are W:O=3:1~10:1
In the present invention, the preparation method contains organic solvent, organic solvent in step 1) in water phase and oil phase
It is one or more in dichloromethane, ethyl acetate or tetrahydrofuran
Advantage of the present invention is as follows：
1) roundness is high：The present invention is microball preparation, and height rounding shows smooth densification, solved well because of rounding
The adverse reactions such as bulge after stifled needle caused by degree and injection.And 28G syringe needles are used when this product injection, it is used compared to commercially available product
26G syringe needles, and greatly reduce the sense of discomfort and adverse reaction probability of happening of injection.
2) curative effect：Existing polylactic acid formulation products are mostly l-lactic acid product, are worked slow.The present invention is bispin polylactic acid
Product, wherein dextrorotation polylactic acid absorb soon, and subcutaneous fibrotic cell can comparatively fast be stimulated to generate collagen, play true filling and make
With reaching quick acting, but because its degradation speed is fast, the longer l-lactic acid of degradation time need to be coordinated just to can reach together soon
The feature that speed works and drug effect is long.The present invention fine can be obtained by the ratio controlled between l-lactic acid and dextrorotation polylactic acid
Compatibility is rapid-action and continues long two big characteristics.
3) microbiological contamination risk is low：The present invention is microball preparation, and the smooth densification in surface, water dispersible is good, when redissolution only needs 30~
50s can be suspended uniformly, greatly reduce the microbiological contamination risk because caused by standing time is long.
The present invention is described further with reference to embodiment, but the present invention is not limited in embodiment, it is all according to this
This field equivalent replacement that disclosure of the invention content is done, all belongs to the scope of protection of the present invention.
Description of the drawings
Fig. 1 is the electron microscope of polylactic acid microsphere prepared by embodiment 4；
Fig. 2 is external commercially available productElectron microscope；
Fig. 3 is commercially available productWith the grain size comparison diagram of product of the embodiment of the present invention；
Embodiment and reference examples
Preparation method
Polylactic acid is dissolved in organic solvent as oil phase O by step 1) according to each recipe quantity of Tables 1 and 2 and technological parameter, and 2%
(w/v) aqueous solution of poly-vinyl alcohol solution and organic solvent is as water phase W, wherein water phase W range of viscosities be 15.3~
20.7mPas (water) mixes this two-phase with certain proportion, and O/W lotions are formed with certain rotating speed homogeneous certain time；
O/W lotions obtained by step 1) are removed organic solvent by step 2) by the way that volatilization is stirred at room temperature, then microballoon is centrifuged, is washed
It washs；
Microballoon obtained by step 2) is suspended in the aqueous solution containing freeze-dried excipient and suspending agent by step 3), water-soluble
Fluid viscosity ranging from 270~320mPas (water) obtains polylactic acid microsphere preparation after freeze-drying.
Prescription：
1 each embodiment formulation and technology contrast table of table
According to the prescription of embodiment 4 reference examples are prepared by following technique：
2 each reference examples formulation and technology contrast table of table
| Technological parameter | Reference examples 1 | Reference examples 2 | Reference examples 3 | Reference examples 4 | Reference examples 5 | Reference examples 6 |
| Water phase W：Oil phase O | 1:1 | 15:1 | 3:1 | 3:1 | 3:1 | 3:1 |
| Homogeneous rate/rpm | 4000 | 4000 | 4000 | 4000 | 1000 | 5000 |
| Homogenizing time/s | 200 | 200 | 50 | 400 | 200 | 200 |
Good effect is further illustrated the present invention below by way of experimental data：
1, yield is tested
Method：With polylactic acid raw material m0On the basis of, microball preparation is prepared by the prescription and preparation method of above-described embodiment, is surveyed
The polylactic acid weight m in preparation is obtained, yield W is calculated according to the following formula：
W=m ÷ m0X 100%.
Each embodiment the results are shown in Table 3~4 with reference examples
2, cleansing pin performance test
Principle：More by the amount of same syringe needle suspension in same time, cleansing pin performance is better.
Method：Take above-described embodiment and reference examples, be added equal amount water for injection through same time same procedure redissolve at
Suspension is injected emitter with same constant pressure in same time, is recorded out liquid afterwards with same syringe and same syringe needle
Volume.The ratio for calculating embodiment volume and reference examples volume, its cleansing pin performance is weighed with this ratio, and ratio is bigger, is led to
Needle performance is better.Test result is shown in Table 3~4
3, particle size range is tested
Method：Water for injection is added in above-described embodiment and reference examples and is prepared into suspension, is swashed using Malvern MS3000
Light particle size analyzer is measured under same test condition within the scope of same obscurity.Go out 35 from test result calculations~
Ratio between 60 microns reflects its specified particle diameter yield with this ratio, and ratio is higher, and yield is higher.Test result is shown in Table 3~4
4, time test is redissolved
Method：5ml waters for injection are drawn with disposable syringe, above-described embodiment is pushed into respectively with reference examples, is placed in
It on shaking table, is redissolved, is waited for without clearly visible particle with 100 revs/min of rate at room temperature, and after being uniformly dispersed, record the time,
This time is to redissolve the time.Test result is shown in Table 3~4.
The Comparative result of 3 Examples 1 to 4 of table
The Comparative result of 4 reference examples 1~6 of table
Conclusion：
According to shown in table 3~4 as a result, can obtain to draw a conclusion：
1) yield：By table 3~4 it is found that when each component ratio is in the scope of the present invention, yield can reach 85% with
On, if can balling-up etc. be impacted by changing technological parameter (reference examples 1~6), and then influence yield；
2) cleansing pin performance：It is compared by 3 Examples 1 to 4 of table and commercially available product it is found that the syringeability of embodiment is far superior to particle
Preparation (commercially available product) further proves the advantage of microball preparation, and microsphere features smooth surface is fine and close, in terms of mobility and water solubility,
All there is prodigious advantage than granular preparation.By table 3~4 it is found that reference examples are in the case of technological parameter, though to yield, grain size
Deng all having an impact, but it is still microball preparation, still better than granular preparation (commercially available product) in terms of syringeability, but because its grain size is big
It is small to differ, also there is difference by the time of same syringe needle, grain size is smaller, and cleansing pin performance is better；
3) time is redissolved：As shown in Table 3, commercially available product is microparticle formulation, in irregular shape, and water dispersible is inhomogenous, is redissolved
Time is long, and microball preparation water dispersible is good, redissolves the time faster.
4) particle diameter distribution：
A) with the difference of water phase and oil phase ratio, particle size has a little difference, after oil phase ratio increases, lotion
Viscosity is big, and after homogeneous, lotion is more difficult to be broken, and emulsion particle diameter is larger；When watr-proportion is excessive, surfactant increases, and needs
The droplet surface area of bigger is wanted to keep its absorption, microspherulite diameter smaller；
B) by table 3~4 it is found that constantly increasing with homogeneous rotating speed, the shearing force that lotion is subject to is bigger, easier formation
The smaller particle of grain size, homogenizing time is longer, and lotion is more easy to be fractured into smaller drop, and the microspherulite diameter of formation is also smaller；
C) by the way that experimental results demonstrate the ratio between 35~60 microns of specified particle diameter range reaches 30%~50%
When, this microball preparation has better clinical effectiveness, by table 3~4 it is found that grain size is by each component ratio and the common shadow of technological parameter
It rings, in the optimized scope that the present invention obtains, can reach the special ratios within the scope of specified particle diameter, there is clinical advantage.
5, external degradation test method
This test is tested according to the professional standard that number is YY/T 0474-2004.
1) preparation of buffer solution：Buffer solution used is phosphate buffer, the di(2-ethylhexyl)phosphate configured with sterile redistilled water
Hydrogen potassium and disodium hydrogen phosphate, the salt for being used to prepare the buffer solution should be analytically pure and dry to constant
A) 1/15mol/L potassium dihydrogen phosphates：9.078g potassium dihydrogen phosphates are dissolved in every liter of water；
B) 1/15mol/L disodium hydrogen phosphates：11.876g phosphate dihydrate disodium hydrogens are dissolved in every liter of water
The buffer solution is mixed by 18.2% solution a) and 81.8% solution b) (volume fraction).Difference should be measured weekly
PH value in container carries out pH adjustings when needing with the NaOH solution of 0.1mol/L, make the pH value of the buffer solution remain 7.4 ±
0.2；
2) sample preparation：It takes above-described embodiment 4 and commercially available product each 6 (500mg/ branch) to be respectively placed in beaker, pours into note
Penetrating ultrasound 5min after being redissolved with water makes it fully dissolve, centrifugal filtration, then is dried in vacuo to screening, weighs initial weight
m0, it is respectively placed in seal glass conical flask, sample, the wherein volume (ml) of buffer solution and examination is completely covered with 10ml buffer solutions
It tests the ratio between sample quality (g) and is more than 30:1, the real time degrade (each 3) maintain sample in (37 ± 1) DEG C with water bath with thermostatic control
Physiological temp, accelerated degradation (each 3) maintain sample in the physiological temp of (70 ± 1) DEG C with water bath with thermostatic control.
3) microballoon and solution are detached：Vacuum filtration makes polylactic acid microsphere be detached with degraded solutions, and analysis water washing three is used in combination
It is secondary, it collects filter residue and is used for inherent viscosity, mass loss and droplet measurement, collect filtrate and detect use for lactic acid content.
4) catabolite measures：Using ion chromatograph detecting step 3) content of lactic acid anion (surveys three bottles in filtrate
Filtrate), chromatographic column be Dai An companies of U.S. AG22 columns, leacheate be NaHCO3 solution (6.0mmol/L), flow velocity 1ml/min,
Sampling volume be 10 μ L, 30 DEG C of column temperature, 35 DEG C of Chi Wen, electric conductivity detector detection, measure initial lactic acid anion-content a0, then
Lactic acid anion-content a is measured in the set time, degradation percentage W is calculated according to following equation：
W=(a/a0- 1) x100%
5) characteristic viscosity determining：Filter residue isolated in step 3) is placed in 40 DEG C and is dried under vacuum to constant weight, after be dissolved in
Chloroform is configured to a concentration of 0.1% test sample, and by GB/T1632 (ISO1628-1), with micro determination of ubbelohde viscometer, it is special
Property viscosity (survey three bottles of filter residues).
Test result is shown in Table 5~8.
5 external real time of table degradation percent data contrast table
6 external accelerated degradation percent data contrast table of table
The front and back physicochemical property contrast table of 7 real time of table degradation
Physicochemical property contrast table before and after 8 accelerated degradation of table
Because the degradation of polylactic acid is a complicated process, high polymer is first decomposed into single-stranded, then is decomposed into lactic acid monomer, therefore
The present invention reflects the degradation rate of polylactic acid with the quantity of lactic acid anion to a certain degree.
It can be seen that by table 5~6, either accelerated degradation or real time degradation, commercially available product particle later stage degradation rate
Be significantly faster than that microballoon of the present invention, because the present invention is added to dextrorotation polylactic acid, degradation is very fast, so degradation early period can be faster than it is commercially available
Product, but the later stage slow down gradually again, can reach quick acting again can maintain the effect of permanent drug effect；It can be seen that by table 7~8, at any time
The continuous degradation of polylactic acid, dry mass reduce, and molecular weight reduces, and inherent viscosity and grain size reduce therewith.Because of the drop of polylactic acid
Solution can be divided mainly into the water suction of high polymer, the hydrolytic cleavage of ester bond, soluble oligomer three processes of diffusion dissolution, absorbing water
In the process, since the hydrolysis of the diffusion ratio ester bond of water wants much faster, the hydrolysis of ester bond in the incipient stage be it is uniform, with
The continuation of degradation, the autocatalysis of end carboxyl is more apparent, can further increase degradation rate.
Though this data is in-vitro measurements, can side reflect its material result, and then prove solid fine and close microballoon compared to
Superiority of the grain in efficacy time length above.
Claims (10)
1. a kind of bispin poly (lactic acid) composition for skin filling is made of polylactic acid, suspending agent, excipient, it is characterized in that：
20~50 parts of polylactic acid by weight percentage, 10~30 parts of suspending agent, 20~50 parts of excipient, wherein left-handed in the polylactic acid
The ratio between polylactic acid and dextrorotation polylactic acid are L：D=4:1~1:4.
2. bispin poly (lactic acid) composition according to claim 1, it is characterised in that the polylactic acid inherent viscosity be 1.7~
2.3dL/g, functional group are aldehyde radical.
3. bispin poly (lactic acid) composition according to claim 1, it is characterised in that the excipient is lactose, sucrose and sweet
Reveal one or more in alcohol.
4. bispin poly (lactic acid) composition according to claim 1, it is characterised in that the suspending agent is carboxymethyl cellulose
It is one or more in sodium and sodium alginate.
5. a kind of bispin polylactic acid preparation, it is characterised in that：It is combined containing polylactic acid any one of Claims 1-4
Object forms, smooth surface rounding, the microspheroidal body that average grain diameter is 20~75 microns.
6. bispin polylactic acid preparation according to claim 5, which is characterized in that finished product is a kind of freeze-dried jelly
Dry powder injection formulation.
7. bispin polylactic acid preparation according to claim 6, which is characterized in that before use, being redissolved with water for injection, redissolve
Time is 30~50s.
8. the bispin poly (lactic acid) composition preparation method described in a kind of any one of claim 5~7 comprising following step
Suddenly：
1) polylactic acid that 20~50 parts of inherent viscosities are 1.7~2.3dL/g is dissolved in organic solvent as oil phase O, 2% (w/v)
For the aqueous solution of poly-vinyl alcohol solution and organic solvent as water phase W, the range of viscosities of water phase W is 15.3~20.7mPas
(water) mixes this two-phase with certain proportion, with certain rotating speed homogeneous System forming O/W lotions；
2) O/W lotions obtained by step 1) are removed into organic solvent by the way that volatilization is stirred at room temperature, then microballoon is centrifuged, washing；
3) microballoon obtained by step 2) is suspended in the aqueous solution containing 20~50 parts of freeze-dried excipients and 10~30 parts of suspending agents
In, the range of viscosities of the aqueous solution is that 270~320mPas (water) obtains polylactic acid microsphere preparation by freeze-drying.
9. preparation method according to claim 8, which is characterized in that in step 1) homogenizing process homogenizing time be 100~
300s, homogeneous rotating speed are 2000~4000rpm, and water phase W and oil phase O ratios are W:O=3:1~10:1.
10. preparation method according to claim 8, it is characterised in that contain organic solvent in water phase and oil phase, have
Solvent is one or more in dichloromethane, ethyl acetate or tetrahydrofuran.
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Cited By (11)
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|---|---|---|---|---|
| CN110051882A (en) * | 2019-06-11 | 2019-07-26 | 中国科学院长春应用化学研究所 | A kind of polylactic acid microsphere, preparation method and application |
| CN110066500A (en) * | 2019-04-11 | 2019-07-30 | 成都迪康中科生物医学材料有限公司 | Degradable injection class polylactic acid filler of one kind and preparation method thereof |
| CN110327488A (en) * | 2019-07-18 | 2019-10-15 | 王月玲 | A kind of injection fillers microball preparation and preparation method thereof |
| CN110339397A (en) * | 2019-07-11 | 2019-10-18 | 山东省药学科学院 | A kind of injectable dermal filler and its preparation method and application without suspending agent |
| CN110559489A (en) * | 2019-09-25 | 2019-12-13 | 广州益诚生物科技有限公司 | Injection filler |
| CN110787319A (en) * | 2019-11-19 | 2020-02-14 | 上海摩漾生物科技有限公司 | Implant for facial cosmetic lifting and application thereof |
| CN110964215A (en) * | 2019-12-26 | 2020-04-07 | 华熙生物科技股份有限公司 | Preparation method of L-polylactic acid and cross-linked hyaluronic acid composite gel for injection and obtained product |
| CN111298196A (en) * | 2020-03-27 | 2020-06-19 | 常州药物研究所有限公司 | Polylactic acid porous microsphere, preparation method and application thereof |
| CN113244449A (en) * | 2021-05-17 | 2021-08-13 | 常州药物研究所有限公司 | Preparation method of instant polylactic acid microspheres |
| CN113546539A (en) * | 2020-04-24 | 2021-10-26 | 透策生技股份有限公司 | Treatment method for accelerating dispersion of injection filler by using pressurization means |
| CN114404370A (en) * | 2021-12-13 | 2022-04-29 | 苏州市立医院 | Nano-fat functionalized injectable super-lubricating microsphere and preparation method and application thereof |
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| CN110559489A (en) * | 2019-09-25 | 2019-12-13 | 广州益诚生物科技有限公司 | Injection filler |
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| CN113546539A (en) * | 2020-04-24 | 2021-10-26 | 透策生技股份有限公司 | Treatment method for accelerating dispersion of injection filler by using pressurization means |
| CN113244449A (en) * | 2021-05-17 | 2021-08-13 | 常州药物研究所有限公司 | Preparation method of instant polylactic acid microspheres |
| CN114404370A (en) * | 2021-12-13 | 2022-04-29 | 苏州市立医院 | Nano-fat functionalized injectable super-lubricating microsphere and preparation method and application thereof |
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