CN108619563A - A kind of poly (lactic acid) composition and preparation method thereof - Google Patents
A kind of poly (lactic acid) composition and preparation method thereof Download PDFInfo
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- CN108619563A CN108619563A CN201710155462.4A CN201710155462A CN108619563A CN 108619563 A CN108619563 A CN 108619563A CN 201710155462 A CN201710155462 A CN 201710155462A CN 108619563 A CN108619563 A CN 108619563A
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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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
- A61K31/765—Polymers containing oxygen
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/06—Flowable or injectable implant compositions
Abstract
A kind of poly (lactic acid) composition of present invention offer and preparation method thereof.The composition is made of polylactic acid, surfactant, suspending agent, excipient, and polylactic acid is 20~50 parts by weight percentage, and surfactant is 0.5~1 part, and suspending agent is 10~30 parts, and excipient is 20~50 parts.Feature is the microball preparation, is the polylactic acid microsphere that uniform particle diameter is prepared by quick membrane emulsification.The microspherulite diameter distribution width of the methods of traditional homogeneous or stirring preparation, size are larger and uncontrollable, strongly limit actual production and clinical application.Small size particle has larger specific surface area, and degradation is rapid, although and more large-sized particle degradation cycle is longer, when injection, need to use thicker syringe needle, increase patient pain.The present invention uses fast film emulsifying technology, can prepare the micron order polylactic acid microsphere of single-size, efficiently solve the above problem.And contain l-lactic acid and dextrorotation polylactic acid, it not only can be with quick acting, but also can achieve the effect that long-acting maintenance.
Description
Technical field
The present invention relates to a kind of poly (lactic acid) composition that uniform particle diameter is controllable and its preparation and preparation methods, specifically,
It is related to the aseptic composite and its preparation and preparation method of a kind of improved bispin polylactic acid microsphere implant, belongs to biological medicine
Technical field.
Background technology
In recent years, drug delivery system (Drug delivery system, DDS) was extending in biopharmaceutical macromolecular drug body
Half-life period, raising bioavilability and reduction toxic side effect etc. play important role.Various nano-micro level particles are made
For the most important a member of DDS, research and application are also got the attention.For polypeptide, protide these medicines for easily digesting
Object, can further improve targeting after being combined with particle, and then increases bioavilability, extend action time, improve drug and give
Prescription formula etc..Therefore, the development of nano-micro level particle has boundless application prospect and huge clinical treatment meaning.One
Aspect is the main reason for leading to patients stopping treatment clinically, therefore drop using the adverse reaction of generation because it is injection
Adverse reaction becomes the problem of urgently optimizing in the treatment of polylactic acid drug cosmetics after low injection.On the other hand, existing product is most
For l-lactic acid product, absorption of human body is slow, works slow, is still microball preparation project urgently to be resolved hurrily.
Currently, microflow control technique and film emulsifying technology are uniform controllable, the raising systems of two kinds of common realization microspherulite diameters
The method of standby repeatability.Microflow control technique prepares uniform lotion by the flow velocity of fluid in control channel, is obtained after solidification
One particle.The technology is easy regulation and control particle internal structure and grain shape, but low output and grain size are not suitable in micron range
Amplification production and practical application.And the rise of film emulsifying technology then solves the above problem, realizes more accurately particle size
The preparation of range and higher yield.
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, there are still roundings
The defect of difference is spent, it is specific insufficient as follows：1) it is high to block up needle possibility：26G syringe needle disposable syringes need to be used slow when injecting this product
Slow injection, stifled needle can lead to be subcutaneously injected uneven, the adverse reactions such as bulge after in turn resulting in hemotoncus, oedema or injecting.According to city
The product clinical data of selling shows that most clinical adverses are hemotoncus (28%)；2) it works slow：On the one hand because it contains only left-handed gather
Lactic 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 irregular, table
Face exposure end carboxyl differs, and palliating degradation degree differs, and cannot reach action steady in a long-term；3) it redissolves slow：When redissolving, each particle water
Dispersed degree 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 to can guarantee it
It is suspended completely uniform, and the longer suspension time will greatly improve preparation microbiological contamination possibility.
Patent application CN105664261A provides a kind of preparation method of novel injection implant.The invention uses solvent
Volatility process will cure and sieve in two steps and a step, though shortening preparation time, improve roundness, products obtained therefrom grain size point
Cloth is wide, it is necessary to just can reach final demand by screening, screening process reduces yield, improves cost.Patent application
CN102516565B provides a kind of method preparing polylactic acid nano/micro spheres using solvent evaporation method, and roundness is high, utilizes
A kind of dispersant with high efficiency overcomes using dosage too many drawback when other surfaces activating agent and above-mentioned patent roundness and cost
High problem, but the invention does not control the ratio between PLLA and PDLA in polylactic acid, and result can lead to journey of degrading between criticizing
It is big to spend difference, influences finished 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 sterile bispin poly (lactic acid) composition and its preparation of the uniform particle diameter of good reaction are suitable for injection implant face filling, are not necessarily to
Medicine is carried, and specific size distribution is uniform, 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, the bispin poly (lactic acid) composition of a kind of uniform particle diameter provided by the present invention, by poly- breast
Acid, surfactant, suspending agent, excipient composition, by weight percentage 20~50 parts of polylactic acid, surfactant 0.5~1
Part, 10~30 parts of suspending agent, 20~50 parts of excipient.
Heretofore described bispin poly (lactic acid) composition, it is characterised in that the polylactic acid relative molecular weight is 10~15W,
Its functional group is aldehyde radical, and inherent viscosity is 1.3~1.7dL/g.
Heretofore described bispin poly (lactic acid) composition, it is characterised in that the polylactic acid is poly- with dextrorotation containing l-lactic acid
The ratio between lactic acid is L：D=4:1~1:4.
Heretofore described bispin poly (lactic acid) composition, it is characterised in that the surfactant is polyvinyl alcohol or tween
It is one or more in 80.
Heretofore described bispin poly (lactic acid) composition, it is characterised in that the excipient is lactose, sucrose and mannitol
In it is one or more.
Heretofore described bispin poly (lactic acid) composition, it is characterised in that the suspending agent is sodium carboxymethylcellulose or sea
It is one or more in mosanom.
A kind of heretofore described bispin polylactic acid preparation is the microspheroidal body that average grain diameter is 35~60 microns, and
Smooth surface rounding contains above-mentioned bispin poly (lactic acid) composition.
The bispin polylactic acid preparation is preferably freeze-dried powder.
The bispin polylactic acid preparation, before use, being redissolved with water for injection, the redissolution time is 30~50s.
The preparation method of bispin polylactic acid preparation of the present invention includes the following steps：
1) 20~50 parts of polylactic acid are dissolved in organic solvent as oil phase O, the water containing surfactant and organic solvent
For solution as water phase W, the range of viscosities of water phase W is 15.3~20.7mPas (water), this two-phase is mixed with certain proportion, is used
Certain rotating speed homogeneous System forming O/W lotions；
2) O/W lotions obtained by step 1) are poured into the holding vessel of fast film emulsifier unit, adjusting nitrogen pressure 5~
Lotion is pressed through microporous barrier by 40kPa, repeats film 3 times.Magnetic agitation makes microballoon cure at room temperature, organic solvent volatilization, then will
Microballoon centrifugation, 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 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.
In the present invention, the preparation method, the long 10cm of microporous barrier, outer diameter used in fast film emulsifying technology in step 2)
1cm, membrane aperture are 30~60 microns.
Advantage of the present invention is as follows：
1) particle diameter distribution is narrow：The methods of traditional homogeneous or stirring prepare particle size distribution is wide, size is larger and difficult
With control, actual production and clinical application are strongly limited, and wider particle diameter distribution can influence cell phagocytosis efficiency and reduce
Particle targeting.If being sieved in the preparation later stage, workload can be increased and improve production cost.Small size particle has larger
Specific surface area, be easy to cause burst release, release it is fast phenomena such as, although and more large-sized particle sustained release the period it is long, injection when
Thicker syringe needle need to be used, patient pain can be increased.The present invention uses fast film emulsifying technology, can prepare the micro- of single-size
Meter level polylactic acid particle, efficiently solves the above problem.
2) roundness is high：The present invention is microball preparation, and roundness is high, can compensate for the deficiency of the said goods.The hair
It is bright solve well needle and injection are blocked up caused by roundness after the adverse reactions such as bulge.And use 28G needles when this product injection
Head, and greatly reduce the sense of discomfort and adverse reaction probability of happening of injection.
3) good effect：Existing polylactic acid formulation products are mostly l-lactic acid product, are worked slow.The present invention is the poly- breast of bispin
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.
4) 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 commercially available product scanning electron microscope (SEM) photograph；
Fig. 2 is that commercially available product is schemed with 4 made sample particle diameter profiles versus of embodiment；
Fig. 3 is the comparison electron microscope of polylactic acid microsphere prepared by embodiment, and crossing film pressure in embodiment is distributed as (a)
5kPa, (b) 20kPa, (c) stereoscan photograph and (d) grain size distribution of PLA microballoons prepared by 40kPa.
Embodiment and reference examples
Preparation method
1) polylactic acid is dissolved in organic solvent as oil phase O according to table 1, it is water-soluble containing surfactant and organic solvent
For liquid as water phase W, the range of viscosities of water phase W is 15.3~20.7mPas (water), this two-phase is mixed with certain proportion, with one
Determine rotating speed homogeneous System forming O/W lotions；
2) O/W lotions obtained by step 1) are poured into the holding vessel of fast film emulsifier unit, nitrogen pressure is adjusted, by lotion
Microporous barrier is pressed through, repeated film 3 times.Magnetic agitation makes microballoon cure at room temperature, organic solvent volatilization, then microballoon is centrifuged, is washed
It washs；
3) microballoon obtained by step 2) is suspended in the aqueous solution containing freeze-dried excipient and suspending agent, the aqueous solution
Range of viscosities be 270~320mPas (water), by freeze-drying, obtain polylactic acid microsphere preparation.
Prescription
1 each embodiment formulation and technology contrast table of table
Good effect is further illustrated the present invention below by way of experimental data：
1, yield is tested
With polylactic acid raw material m0On the basis of, microball preparation is prepared by the prescription and preparation method of above-described embodiment, measures system
Polylactic acid weight m in agent, is calculated according to the following formula yield W：
W=m ÷ m0X 100%.
It the results are shown in Table 2
2, cleansing pin performance test
Principle：More by the amount of same syringe needle suspension in same time, cleansing pin performance is better.
Method：Above-described embodiment and reference examples are taken, equal amount water for injection is added and is redissolved with same time and same procedure
At suspension, recorded out after injecting emitter in same time with same constant pressure with same syringe and same syringe needle
Liquid accumulates.The ratio for calculating embodiment volume and reference examples volume, its cleansing pin performance is weighed with this ratio, and ratio is bigger,
Cleansing pin performance is better.Test result is shown in Table 2
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.It is calculated 35 from test result
Ratio between~60 microns reflects its specified particle diameter yield with this ratio, and ratio is higher, and yield is higher.Span values are smaller, show
Particle diameter distribution is narrower, and size is more uniform.
Span=(D90-D10)/D50
Test result is shown in Table 2
The Comparative result of table 2 embodiment and reference examples
| Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | Commercially available product | |
| Yield (%) | 81.30 | 80.90 | 78.90 | 75.50 | - |
| Cleansing pin performance | 1.72 | 1.68 | 1.71 | 1.75 | 1.00 |
| Span values | 1.65 | 1.15 | 0.98 | 0.70 | 1.06 |
Conclusion：
According to shown in table 2 as a result, can obtain to draw a conclusion：
1) yield：As shown in Table 2, when each component ratio is in the scope of the present invention, yield can reach 75% or more,
If can balling-up etc. be impacted by changing technological parameter, and then influence yield；
2) cleansing pin performance：It is compared by 2 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 mobility and water dispersible side
All there is prodigious advantage in face than granular preparation, but because its particle size differs, also has difference, grain by the time of same syringe needle
Diameter is smaller, and cleansing pin performance is better；
3) particle diameter distribution：
A) with the continuous reduction for crossing film pressure, grain size is more uniform, and it is bigger to be distributed narrower and grain size.Pressure is too small, has
Lotion can be directly by fenestra without being crushed, and size is larger；Pressure is excessive, and lotion can directly be broken into more not of uniform size
Lotion, size is less than normal.With the increase for crossing film pressure, microspherulite diameter reduces, and single particle diameter distribution Span values but accordingly increase, because
Bigger for pressure, lotion is broken more violent when crossing film, easy tos produce more small particle microballoons, particle diameter distribution is caused to broaden.
B) membrane aperture is bigger, and the influence that emulsion size and particle diameter distribution have received film pressure is bigger.
4, 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 3~6.
3 external real time of table degradation percent data contrast table
4 external accelerated degradation percent data contrast table of table
The front and back physicochemical property contrast table of 5 real time of table degradation
Physicochemical property contrast table before and after 6 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 3~4, 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 5~6, 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 poly (lactic acid) composition is made of polylactic acid, surfactant, suspending agent, excipient, it is characterized in that：By weight
20~50 parts of percentage polylactic acid, 0.5~1 part of surfactant, 10~30 parts of suspending agent, 20~50 parts of excipient.
2. poly (lactic acid) composition according to claim 1, it is characterised in that the polylactic acid relative molecular weight be 10~
15W, functional group are aldehyde radical, and inherent viscosity is 1.3~1.7dL/g.
3. poly (lactic acid) composition according to claim 2, which is characterized in that contained l-lactic acid and dextrorotation polylactic acid it
Than for L：D=4:1~1:4.
4. poly (lactic acid) composition according to claim 1, it is characterised in that the surfactant is polyvinyl alcohol or spits
One kind in temperature 80.
5. poly (lactic acid) composition according to claim 1, wherein the excipient is one in lactose, mannitol and sucrose
Kind is a variety of.
6. poly (lactic acid) composition according to claim 1, it is characterised in that the suspending agent be sodium carboxymethylcellulose and
It is one or more in sodium alginate.
7. a kind of polylactic acid preparation, it is characterised in that：Containing poly (lactic acid) composition according to any one of claims 1 to 6
At, smooth surface rounding, the microspheroidal body that average grain diameter is 35~60 microns.
8. according to the polylactic acid preparation described in claim 7, which is characterized in that said preparation is freeze-dried powder, before use
It is redissolved with water for injection, the redissolution time is 30~50s.
9. a kind of preparation method of the polylactic acid preparation described in claim 6~8 comprising following steps：
1) 20~50 parts of polylactic acid are dissolved in organic solvent as oil phase O, 2% (w/v) polyvinyl alcohol and organic solvent it is water-soluble
For liquid as water phase W, the range of viscosities of water phase W is 15.3~20.7mPas (water), this two-phase is mixed with certain proportion, with one
Determine rotating speed homogeneous System forming O/W lotions；
2) O/W lotions obtained by step 1) are poured into the holding vessel of fast film emulsifier unit, adjusting nitrogen pressure ranging from 5~
Lotion is pressed through microporous barrier by 40kPa, repeats film 3 times.Magnetic agitation makes microballoon cure at room temperature, organic solvent volatilization, then will
Microballoon centrifugation, 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.
10. preparation method according to claim 9, which is characterized in that microporous barrier used is long in fast film emulsifying technology
10cm, outer diameter 1cm, membrane aperture are 30~60 microns.
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| CN109998997A (en) * | 2019-04-04 | 2019-07-12 | 山东谷雨春生物科技有限公司 | A method of polyesters organic high polymer microsphere is prepared using membrane emulsification |
| 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 |
| CN110721339A (en) * | 2019-10-29 | 2020-01-24 | 普丽妍（南京）医疗科技有限公司 | Rapid preparation method of injectable L-polylactic acid particles |
| 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 |
| CN111558083A (en) * | 2020-01-14 | 2020-08-21 | 北京四环制药有限公司 | Biodegradable injection filler, preparation method and application thereof |
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| CN111558083A (en) * | 2020-01-14 | 2020-08-21 | 北京四环制药有限公司 | Biodegradable injection filler, preparation method and application thereof |
| CN111617315B (en) * | 2020-01-14 | 2021-07-06 | 北京四环制药有限公司 | Biodegradable injection filler, preparation method and application thereof |
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| 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 |
| 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 |
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| CN112755245A (en) * | 2020-11-26 | 2021-05-07 | 北京尚盛楚逸医药科技有限公司 | Polylactic acid filling agent for injection and preparation method thereof |
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