CN101837146B - Improved biodegradable porous scaffold particle for injection and preparation method thereof - Google Patents
Improved biodegradable porous scaffold particle for injection and preparation method thereof Download PDFInfo
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Abstract
The invention discloses an improved biodegradable porous scaffold particle for injection and a preparation method thereof. The improved biodegradable porous scaffold particle mainly comprises biodegradable polymers. The preparation method comprises the following steps: dissolving the biodegradable polymers in organic solution; mixing with water and stirring to form softened solution; freezing, drying and foaming the softened solution at the specific temperature to form foaming substances; further crushing the foaming substances by a crusher; mixing the crushed foaming substances with softener solution; and freezing, drying and sterilizing. The invention has the following beneficial effects: the adopted raw material per se is not harmful to human body, while the endothelial cells and skin tissues of the human body can be easily attached to the raw material, thus providing the good growing environment for the cells and favoring for the growth of the cells; and the porous biodegradable scaffold particle can be naturally decomposed and absorbed in vivo within a certain period of time, thus avoiding the risks of in-vivo accumulation.
Description
Technical field
The present invention relates to a kind of biodegradable porous scaffold particle for injection and preparation method thereof, particularly design a kind of biodegradable porous scaffold particle for injection and manufacture method thereof of improvement.
Background technology
Biodegradable polymer be a kind of in human body multiple tissue such as epithelial tissue and cell etc. adhere to and growth aspect be easier to, and it is back by biodegradation in the cell or tissue growth, have the material that can be absorbed by the body or get rid of characteristic, be widely used in tissue engineering.
At first, make a general survey of the development history of medical macromolecular materials, the artificial implantation that the first generation is used such as ceramic, metal, composite and macromolecular material are used as the material of filling supporter.
The second filial generation uses the general industry material to be used for replacing the part of damage internal organs, and these materials are non-activities, to organism without any effect.The material of this respect such as polymethylacrylic acid skeleton, adhesive, dioctyl ester and be used in plasticization polrvinyl chloride of bags of blood aspect etc.
The third generation has utilized the material of biological activity state, and as the artificial femoral joint that water acidify apatite is made, collagen protein and alginic acid use at aspects such as artificial blood vessels.
What the 4th generation was used widely is the material that has utilized the histiocyte purposes of synthetic, generally uses as material with synthetic polymer, as mixed type artificial organ etc.
The problem that occurs at nearest manufacture of intraocular internal organs is: these materials are owing to lack for the organism adaptability with at the damage internal organs that substitute specific part or when organizing and lack Biofunctional, and its use has been subjected to very big restriction.In order to address this problem, decompose or the polymer of non-decomposability is fixed on the basis of the cell of internal organs and tissue or protein etc. in research, begun with this as basic cultured cell, and the research of the material with the same characteristic of organism of and functionalization more advanced the performance of the tissue of cultivating or internal organs.
Present research, as with bone, salivary gland, urinary tract, epithelial tissue, bladder, skin, cartilage, impaired neurocyte, the artificial organ that blood vessel and beautifying skin etc. is associated and the development and application of material are just extensively carried out.Be representative with artificial pancreas-langerhans cell wherein, these researchs are useful in thyroid, the hormonal system aspect of parathyroid gland etc.On the other hand, be representative with the artificial reactor of mixed type, be example with the artificial liver, the reactor form that manufacturing can provide hepatocyte to grow up makes the hepatocyte can representative Detoxication simultaneously, functions such as the purification of blood.
Representative as cellular system engineering scholar worker internal organs now also has following example: obtain artificial skin afri graph and the demagrapht of U.S. FDA selling license in May, 1998, just is being considered to be used in the treatment aspect of diabetes originality skin ulcer.In August, 1997, obtain the artificial cartilage that is used for knee surgery of the GENZAIM of the katicell venture business exploitation of U.S. FDA selling license, be characterized in the chondrocyte of taking from the patient after external a large amount of cultivations, being seeded in the prosthesis epimatrix, implant knee by surgical operation then.
But material at present commonly used is because the material self character brings out thrombotic disease easily in human body, and again because it does not have biological degradability, so stockpiling property problem in vivo.
For addressing the above problem, occurred and not stockpiled in vivo, after a while the technology of the biodegradable polymer that just can degrade.Use this basic fundamental as (D.J.Mooney, C.Breuer, K.Mcnamara, J.P.Vacanti, andR.Langer, Tissue Engineering, 1 (2), 107～118 (1995)), its method is described as follows:
At first, having porous laminated structure for the biodegradable polymer is manufactured, is size that the single crystals salt of 250um and the solution of Biodegradable polymer mix, behind the thickness that formation needs, salt is sloughed in dissolving in water, namely forms pore in the macromolecule laminated structure.After the porous laminated structure drying of Zhi Zaoing, being rolled into the cylindrical shape that needs bore like this, adheres with sticker in two ends, thereby is made into porous tubulose form.
Because the laminated structure of said method manufacturing can not be controlled the magnitude range of single crystals salt, so the pore magnitude range that forms is very uneven, with Water dissolve salt and dry process in, the problem that exists pore structure to separate; And through crushing process, cause the problem of biodegradable time shortening.
As the Biodegradable polymer of synthetic, the esters polymer of lactic acid and hydroxyacetic acid uses very wide now, and their biodegradation principle is based on its hydrolysis.
Polylactic acid PLA is used in the fixing head of knochenbruch now and makes on the biodegradable screw, and polyglycolic acid PGA uses as the water absorption stitching thread.Above polylactic acid and polyglycolic acid, the monomer-polymer biodegradation time separately, different according to molecular weight, but usually more than 1 year, their copolymer PLGA is according to the variation of mean molecule quantity, and degradation time is several weeks to tens of weeks in vivo.
The tissue regeneration that utilizes cellular system engineering to learn now with the characteristics that goods require to possess is: unexpected allergy and immunoreation and human body self tissue do not occur and have affinity when transplanting, can not produce the biodegradation cohesiveness surface of rejection.Therefore, solve the material wettability, rough surface, problems such as cellular structure and surface charge kind become the vital problem that we face.
The tissue regeneration material that present synthetic polymer and other polymer constitute has and is injecting the phenomenon that flows in the position when skin injects, and this also is the problem that must solve.
Summary of the invention
The objective of the invention is to overcome the deficiencies in the prior art, atypic porous injection biodegradation scaffold particle and manufacture method thereof with multiple size and form are provided.This porous injection biodegradation scaffold particle has characteristics such as wettability, rough surface, cellular structure, unexpected allergy and immunoreation do not appear when transplanting, has affinity with the human body self tissue, have the cohesiveness surface that is beneficial to the histiocyte apposition growth, and when injecting target site with syringe, can not separate.
Goal of the invention of the present invention is achieved through the following technical solutions: a kind of biodegradable porous scaffold particle for injection of improvement, it mainly is made up of Biodegradable polymer, wherein said Biodegradable polymer comprises one or both mixture in polylactic acid, polyglycolic acid, albumin, collagen protein, poly butyric ester, second diindyl butanoic acid, polycaprolactone and the poly-anhydride, and Biodegradable polymer weight average molecular weight scope is 10000～150000.
Biological degradability scaffold particle mean molecule quantity of the present invention is 90000～110000, and particle has the loose structure of the indefinite form of 10～200um size, and has the characteristic of wettability and rough surface.
A kind of preparation method of biodegradable porous scaffold particle for injection of improvement, it may further comprise the steps:
(1) Biodegradable polymer is dissolved in forms organic solution in the organic solvent, the percentage by weight of Biodegradable polymer and organic solvent is 1.67～45: 55-98.33, again organic solution is mixed with water, the percentage by weight of organic solution and water is 30～90: 10～70, above Biodegradable polymer in fact occupy machine solution and water gross weight 1.5%～20%;
(2) the mixture rotating speed with 2000～5000 rev/mins on blender with machine solution and water stirred 20～40 minutes, and the internal temperature of blender maintains 20～40 ℃, forms the solution of softening;
(3) softening solution is injected mould, ℃ freeze 7～9 hours in temperature-196～-80 after, freeze-dried and foamed 24～48 hours under-50～-40 ℃ temperature again;
(4) keep 20～25 ℃ of pulverizer external temperatures, under the condition that internal temperature is 15～20 ℃, pulverizing 5～10 seconds with 300～1000 rev/mins speed, pulverizing repeatedly 10 times, and as a circulation, carrying out this circulation 1～5 time repeatedly;
(5) softening agents is joined formation softening agents aqueous solution in the pure water, the percentage by weight of softening agents and pure water is 0.1～5: 95～99.9, then the ground product that obtains and softening agents aqueous solution, the percentage by weight of ground product and softening agents aqueous solution is 4.5～74.4: 25.6～95.5, in fact, the percentage by weight of softening agents is 97.92～98.22: 1.78～2.08 in ground product and the softening agents aqueous solution, and under-50～-40 ℃ temperature freeze-dried 24～48 hours, through 6～8 hours sterilization treatment, finish preparation process.
Wherein, described organic solvent comprises acetonitrile, dichloromethane, chloroform, oxolane He one or both mixture in the bioxin.Described softening agents comprises mannitol, water-soluble calcium, methylcellulose, sodium carboxymethyl cellulose, ethoxy, agar, hemicellulose, pentosan, galactan, pectin, natural gum, lignin, starch, amylose, amylopectin and by one or both mixture in the water-soluble chitosan.
After biological degradability scaffold particle of the present invention is implanted to various tissues such as the suitable endotheliocyte of human body or skin tissue cell, can play advantageous effect to the growth of tissue, after endotheliocyte and skin histology were finished growth, degradable polymer was by the mode natural degradation of absorption of human body or eliminating.
When using the biological degradability scaffold particle to come the cultured tissue cell, the growth of cell is carried out smoothly, at first used polymer surfaces cohesiveness must be got well, therefore, the growth of cell is determined by the space between the polymer surfaces character that constitutes the biological degradability scaffold particle and the biological degradability scaffold particle that polymer is formed.For this reason, the surface of biological degradability scaffold particle must possess the chemical characteristic of wettability (hydrophilic/hydrophobic), and the key elements such as roughening on the kind of surface charge and surface.At this moment, possess hydrophilic property character is when using syringe to inject raw material in the body, and evenly injection aspect of particle is hydrophobic better than having; And aspect surface charge, cation constitutes cell attachment in support and more favourable than anion to the cell growth of adhering to.
The present invention makes the growth of cell favourable, has given the characteristics that constitute the polymer surfaces roughening of biological degradability scaffold particle.Pulverization conditions has specificity, is not the variation by temperature being provided and pulverizing speed, but the number of times of the pulverizing by repeatedly increases to change and reaches above feature.Namely under this pulverization conditions, form the mutual roughening of biological degradability scaffold particle and change.Various kinds of cell such as epithelial cell, gonad cell, chondrocyte, vascular endothelial cell and organism stem cell etc. in that cultivate on biological degradability scaffold particle surface all can grow at tissue separately.
The present invention is Biodegradable polymer, after organic solvent and the processing of waterishlogging bubble, pulverize the sheet of foaming, produce shaggy biological degradability scaffold particle, can provide good growing environment for cell, and can produce the form of different biological degradability scaffold particles as required, make histiocytic growth and reparation become possibility, and in vivo can natural decomposition absorb and the danger that needn't worry in human body, to stockpile through certain hour.
When the present invention uses, add normal saline or autoserum and the histiocyte of oneself in clinical treatment, mixture is injected into the position that needs reparation.Because Biodegradable particle of the present invention has the indefinite form vesicular structure, so when using syringe, can not produce special bottleneck, be easy to inject human body and easily form support at organising content, simultaneously because the biological degradability scaffold particle has the indefinite form structure, so be easier to cell and tissue attachment and growth.
The invention has the beneficial effects as follows: because injection porous biological of the present invention degraded scaffold particle has the atypic loose structure of multiple size and form and has characteristics such as wettability, rough surface, mass transfer to blood, skin interstitial fluid, oxygen, carbon dioxide etc. has good result, and raw material self is harmless, above the endotheliocyte of human body and skin histology are attached to easily, for cell provides good growing environment, be favourable to the growth of cell.In vivo can natural decomposition absorb and the danger that can not worry in human body, to stockpile through this porous biological degraded scaffold particle behind the certain hour.
Description of drawings
Fig. 1 is the electromicroscopic photograph of the biodegradable porous scaffold particle for injection of improvement
Fig. 2 is the thermal analysis curue of the biodegradable porous scaffold particle for injection of improvement
Fig. 3 is the weight average molecular weight mensuration figure of PLGA in the biodegradable porous scaffold particle for injection of improveing
The specific embodiment
Further describe technical scheme of the present invention below in conjunction with embodiment, but the invention is not restricted to described embodiment.
[embodiment 1]
A kind of biodegradable porous scaffold particle for injection of improvement, it mainly is made up of Biodegradable polymer, and wherein said Biodegradable polymer is polylactic acid PLA, and its average molecular weight range is 150000.
A kind of preparation method of biodegradable porous scaffold particle for injection of improvement, it may further comprise the steps:
(1) Biodegradable polymer is dissolved in the dichloromethane organic solvent, form organic solution, the Biodegradable polymer dissolving is 1.67: 98.33 with the percentage by weight of organic solvent, organic solution is mixed with water again, and the percentage by weight of organic solution and water is 30: 70;
(2) the mixture rotating speed with 2000 rev/mins on blender with machine solution and water stirred 40 minutes, and the internal temperature of blender maintains 20 ℃, forms the solution of softening;
(3) the softening solution of making is put in the mould of politef material, moment freezed 9 hours in-80 ℃ liquid nitrogen and ultra cold storage freezer, wherein, freezed in the liquid nitrogen 2 hours, freezed in the ultra cold storage freezer 7 hours, use the vacuum freezing drying machine-50 ℃ of following lyophilizations 24 hours then, make the sheet of foaming.
(4) keeping 20 ℃ of pulverizer external temperatures, under the condition that internal temperature is 15 ℃, pulverizing 5 seconds with 300 rev/mins speed, pulverize repeatedly 10 times, and as a circulation, carry out this circulation 1 time repeatedly, obtaining mean molecule quantity is 110000, and mean size is the particle of 20～200um;
(5) mannitol and sodium carboxymethyl cellulose are mixed with combined softening agents in 1: 1 ratio, and the adding pure water forms the softening agents aqueous solution in the softening agents for preparing, the percentage by weight of softening agents and pure water is 0.1: 99.9, then the ground product that obtains and softening agents aqueous solution, the percentage by weight of ground product and softening agents aqueous solution is 4.5: 95.5, and under-50 ℃ temperature vacuum freezing 24 hours, with ethylene oxide sterilization processes 7 hours, finish preparation process.
[embodiment 2]
A kind of biodegradable porous scaffold particle for injection of improvement, it mainly is made up of Biodegradable polymer, and wherein said Biodegradable polymer is polylactic acid PLA, and its average molecular weight range is 10000.
A kind of preparation method of biodegradable porous scaffold particle for injection of improvement, it may further comprise the steps:
(1) Biodegradable polymer is dissolved in the acetonitrile organic solvent, form organic solution, the Biodegradable polymer dissolving is 45: 55 with the percentage by weight of organic solvent, organic solution is mixed with water again, and the percentage by weight of organic solution and water is 90: 10;
(2) the mixture rotating speed with 5000 rev/mins on blender with machine solution and water stirred 20 minutes, and the internal temperature of blender maintains 40 ℃, forms the solution of softening;
(3) the softening solution of making is put in the mould of politef material, moment freezed 7 hours in-196 ℃ liquid nitrogen and ultra cold storage freezer, wherein, freezed in the liquid nitrogen 1 hour, freezed in the ultra cold storage freezer 6 hours, use the vacuum freezing drying machine-40 ℃ of following lyophilizations 48 hours then, make the sheet of foaming.
(4) keeping 25 ℃ of pulverizer external temperatures, under the condition that internal temperature is 20 ℃, pulverizing 8 seconds with 1000 rev/mins speed, pulverize repeatedly 10 times, and as a circulation, carry out this circulation 2 times repeatedly, obtaining mean molecule quantity is 90000, and mean size is the particle of 20～150um;
(5) in softening agents mannitol, add pure water and form the softening agents aqueous solution, the percentage by weight of softening agents and pure water is 5: 95, then the ground product that obtains and softening agents aqueous solution, the percentage by weight of ground product and softening agents aqueous solution is 74.4: 25.6, and under-40 ℃ temperature vacuum freezing 48 hours, with ethylene oxide sterilization processes 6 hours, finish preparation process.
[embodiment 3]
A kind of biodegradable porous scaffold particle for injection of improvement, it mainly is made up of Biodegradable polymer, and wherein said Biodegradable polymer is polylactic acid PLA, and its average molecular weight range is 120000.
A kind of preparation method of biodegradable porous scaffold particle for injection of improvement, it may further comprise the steps:
(1) Biodegradable polymer is dissolved in the dichloromethane organic solvent, form organic solution, the Biodegradable polymer dissolving is 15: 85 with the percentage by weight of organic solvent, organic solution is mixed with water again, and the percentage by weight of organic solution and water is 60: 40;
(2) the mixture rotating speed with 4000 rev/mins on blender with machine solution and water stirred 30 minutes, and the internal temperature of blender maintains 35 ℃, forms the solution of softening;
(3) the softening solution of making is put in the mould of politef material, moment freezed 8 hours in-85 ℃ liquid nitrogen and ultra cold storage freezer, wherein, freezed in the liquid nitrogen 1.5 hours, freezed in the ultra cold storage freezer 6.5 hours, use the vacuum freezing drying machine-45 ℃ of following lyophilizations 36 hours then, make the sheet of foaming.
(4) keeping 22 ℃ of pulverizer external temperatures, under the condition that internal temperature is 17 ℃, pulverizing 10 seconds with 1000 rev/mins speed, pulverize repeatedly 10 times, and as a circulation, carry out this circulation 3 times repeatedly, obtaining mean molecule quantity is 100000, and mean size is the particle of 10～100um;
(5) mannitol and sodium carboxymethyl cellulose are mixed with combined softening agents in 1: 1 ratio, and the adding pure water forms the softening agents aqueous solution in the softening agents for preparing, the percentage by weight of softening agents and pure water is 2: 98, then the ground product that obtains and softening agents aqueous solution, the percentage by weight of ground product and softening agents aqueous solution is 30: 70, and vacuum lyophilization 30 hours under-45 ℃ temperature, with ethylene oxide sterilization processes 7 hours, finish preparation process.
[embodiment 4]
A kind of biodegradable porous scaffold particle for injection of improvement, it mainly is made up of Biodegradable polymer, and wherein said Biodegradable polymer is polylactic acid PLA, and its average molecular weight range is 97400.
A kind of preparation method of biodegradable porous scaffold particle for injection of improvement, it may further comprise the steps:
(1) Biodegradable polymer is dissolved in the mixed organic solvents of being made up of dichloromethane and acetonitrile, form organic solution, the Biodegradable polymer dissolving is 30: 70 with the percentage by weight of organic solvent, dichloromethane and acetonitrile respectively account for 50% of mixed organic solvents, organic solution is mixed with water, the percentage by weight of organic solution and water is 50: 50 again;
(2) the mixture rotating speed with 4000 rev/mins on blender with machine solution and water stirred 30 minutes, and the internal temperature of blender maintains 35 ℃, forms the solution of softening;
(3) the softening solution of making is put in the mould of politef material, moment freezed 8 hours in-150 ℃ liquid nitrogen and ultra cold storage freezer, wherein, freezed in the liquid nitrogen 1.5 hours, freezed in the ultra cold storage freezer 6.5 hours, use the vacuum freezing drying machine-45 ℃ of following lyophilizations 36 hours then, make the sheet of foaming.
(4) keeping 25 ℃ of pulverizer external temperatures, under the condition that internal temperature is 20 ℃, pulverizing 10 seconds with 1000 rev/mins speed, pulverize repeatedly 10 times, and as a circulation, carry out this circulation 5 times repeatedly, obtaining mean molecule quantity is 95000, and mean size is the particle of 10～60um;
(5) the softening agents sodium carboxymethyl cellulose is joined formation softening agents aqueous solution in the pure water, the percentage by weight of softening agents and pure water is 4: 96, then the ground product that obtains and softening agents aqueous solution, the percentage by weight of ground product and softening agents aqueous solution is 50: 50, and vacuum lyophilization 40 hours under-45 ℃ temperature, with ethylene oxide sterilization processes 8 hours, finish preparation process.
[embodiment 5]
A kind of biodegradable porous scaffold particle for injection of improvement, it mainly is made up of Biodegradable polymer, wherein said Biodegradable polymer is the copolymer p LGA that polylactic acid PLA and polyglycolic acid PGA constitute, wherein the percentage by weight between polylactic acid and the polyglycolic acid is 25: 75, and its average molecular weight range is 150000.
A kind of preparation method of biodegradable porous scaffold particle for injection of improvement, it may further comprise the steps:
(1) Biodegradable polymer is dissolved in the dichloromethane organic solvent, form organic solution, the Biodegradable polymer dissolving is 1.67: 98.33 with the percentage by weight of organic solvent, organic solution is mixed with water again, and the percentage by weight of organic solution and water is 30: 70;
(2) the mixture rotating speed with 2000 rev/mins on blender with machine solution and water stirred 40 minutes, and the internal temperature of blender maintains 20 ℃, forms the solution of softening;
(3) the softening solution of making is put in the mould of politef material, moment freezed 9 hours in-80 ℃ liquid nitrogen and ultra cold storage freezer, wherein, freezed in the liquid nitrogen 2 hours, freezed in the ultra cold storage freezer 7 hours, use the vacuum freezing drying machine-50 ℃ of following lyophilizations 24 hours then, make the sheet of foaming.
(4) keeping 20 ℃ of pulverizer external temperatures, under the condition that internal temperature is 15 ℃, pulverizing 5 seconds with 300 rev/mins speed, pulverize repeatedly 10 times, and as a circulation, carry out this circulation 1 time repeatedly, obtaining mean molecule quantity is 110000, and mean size is the particle of 20～200um;
(5) mannitol and sodium carboxymethyl cellulose are mixed with combined softening agents in 1: 1 ratio, and the adding pure water forms the softening agents aqueous solution in the softening agents for preparing, the percentage by weight of softening agents and pure water is 0.1: 99.9, then the ground product that obtains and softening agents aqueous solution, the percentage by weight of ground product and softening agents aqueous solution is 4.5: 95.5, and under-50 ℃ temperature vacuum freezing 24 hours, with ethylene oxide sterilization processes 7 hours, finish preparation process.
[embodiment 6]
A kind of biodegradable porous scaffold particle for injection of improvement, it mainly is made up of Biodegradable polymer, wherein said Biodegradable polymer is the copolymer p LGA that polylactic acid PLA and polyglycolic acid PGA constitute, wherein the percentage by weight between polylactic acid and the polyglycolic acid is 50: 50, and its average molecular weight range is 10000.
A kind of preparation method of biodegradable porous scaffold particle for injection of improvement, it may further comprise the steps:
(1) Biodegradable polymer is dissolved in the mixed organic solvents of being made up of dichloromethane and acetonitrile, form organic solution, the Biodegradable polymer dissolving is 45: 55 with the percentage by weight of organic solvent, dichloromethane and acetonitrile respectively account for 50% of mixed organic solvents, organic solution is mixed with water, the percentage by weight of organic solution and water is 90: 10 again;
(2) the mixture rotating speed with 5000 rev/mins on blender with machine solution and water stirred 20 minutes, and the internal temperature of blender maintains 40 ℃, forms the solution of softening;
(3) the softening solution of making is put in the mould of politef material, moment freezed 7 hours in-196 ℃ liquid nitrogen and ultra cold storage freezer, wherein, freezed in the liquid nitrogen 1 hour, freezed in the ultra cold storage freezer 6 hours, use the vacuum freezing drying machine-40 ℃ of following lyophilizations 48 hours then, make the sheet of foaming.。
(4) keeping 22 ℃ of pulverizer external temperatures, under the condition that internal temperature is 17 ℃, pulverizing 8 seconds with 1000 rev/mins speed, pulverize repeatedly 10 times, and as a circulation, carry out this circulation 2 times repeatedly, obtaining mean molecule quantity is 90000, and mean size is the particle of 20～150um;
(5) in softening agents mannitol, add pure water and form the softening agents aqueous solution, the percentage by weight of softening agents and pure water is 5: 95, then the ground product that obtains and softening agents aqueous solution, the percentage by weight of ground product and softening agents aqueous solution is 74.4: 25.6, and under-40 ℃ temperature vacuum freezing 48 hours, with ethylene oxide sterilization processes 6 hours, finish preparation process.
[embodiment 7]
A kind of biodegradable porous scaffold particle for injection of improvement, it mainly is made up of Biodegradable polymer, wherein said Biodegradable polymer is the copolymer p LGA that polylactic acid PLA and polyglycolic acid PGA constitute, wherein the percentage by weight between polylactic acid and the polyglycolic acid is 65: 35, and its average molecular weight range is 120000.
A kind of preparation method of biodegradable porous scaffold particle for injection of improvement, it may further comprise the steps:
(1) Biodegradable polymer is dissolved in the dichloromethane organic solvent, form organic solution, the Biodegradable polymer dissolving is 15: 85 with the percentage by weight of organic solvent, organic solution is mixed with water again, and the percentage by weight of organic solution and water is 60: 40;
(2) the mixture rotating speed with 4000 rev/mins on blender with machine solution and water stirred 30 minutes, and the internal temperature of blender maintains 35 ℃, forms the solution of softening;
(3) the softening solution of making is put in the mould of politef material, moment freezed 7 hours in-85 ℃ liquid nitrogen and ultra cold storage freezer, wherein, freezed in the liquid nitrogen 1.5 hours, freezed in the ultra cold storage freezer 6.5 hours, use the vacuum freezing drying machine-45 ℃ of following lyophilizations 36 hours then, make the sheet of foaming.
(4) keeping 22 ℃ of pulverizer external temperatures, under the condition that internal temperature is 17 ℃, pulverizing 10 seconds with 1000 rev/mins speed, pulverize repeatedly 10 times, and as a circulation, carry out this circulation 3 times repeatedly, obtaining mean molecule quantity is 100000, and mean size is the particle of 10～100um;
(5) mannitol and sodium carboxymethyl cellulose are mixed with combined softening agents in 1: 1 ratio, and the adding pure water forms the softening agents aqueous solution in the softening agents for preparing, the percentage by weight of softening agents and pure water is 4: 96, then the ground product that obtains and softening agents aqueous solution, the percentage by weight of ground product and softening agents aqueous solution is 30: 70, and vacuum lyophilization 30 hours under-45 ℃ temperature, with ethylene oxide sterilization processes 7 hours, finish preparation process.
[embodiment 8]
A kind of biodegradable porous scaffold particle for injection of improvement, it mainly is made up of Biodegradable polymer, wherein said Biodegradable polymer is the copolymer p LGA that polylactic acid PLA and polyglycolic acid PGA constitute, wherein the percentage by weight between polylactic acid and the polyglycolic acid is 75: 25, and its average molecular weight range is 97400.
A kind of preparation method of biodegradable porous scaffold particle for injection of improvement, it may further comprise the steps:
(1) Biodegradable polymer is dissolved in the dichloromethane organic solvent, form organic solution, the Biodegradable polymer dissolving is 20: 80 with the percentage by weight of organic solvent, organic solution is mixed with water again, and the percentage by weight of organic solution and water is 60: 40;
(2) the mixture rotating speed with 4000 rev/mins on blender with machine solution and water stirred 30 minutes, and the internal temperature of blender maintains 35 ℃, forms the solution of softening;
(3) the softening solution of making is put in the mould of politef material, moment freezed 8 hours in-85 ℃ liquid nitrogen and ultra cold storage freezer, wherein, freezed in the liquid nitrogen 1.5 hours, freezed in the ultra cold storage freezer 6.5 hours, use the vacuum freezing drying machine-50 ℃ of following lyophilizations 36 hours then, make the sheet of foaming.
(4) keeping 25 ℃ of pulverizer external temperatures, under the condition that internal temperature is 20 ℃, the sheet of above-mentioned foaming was pulverized 10 seconds with 1000 rev/mins speed, pulverize repeatedly 10 times, and as a circulation, carry out this circulation 5 times repeatedly, obtaining mean molecule quantity is 95000, and mean size is the particle of 10～60um;
(5) preparing percentage by weight respectively is that 0.4% mannitol softening agents aqueous solution and weight ratio are 0.4% sodium carboxymethyl cellulose softening agents aqueous solution, above-mentioned ground product particle and by mannitol softening agents aqueous solution and sodium carboxymethyl cellulose softening agents aqueous solution, the percentage by weight between ground product, mannitol softening agents aqueous solution, the sodium carboxymethyl cellulose softening agents aqueous solution was respectively 15.85: 3.24: 80.91; Accordingly, the percentage by weight between ground product, mannitol, the sodium carboxymethyl cellulose was respectively 97.92: 0.08: 2, and vacuum lyophilization 36 hours under-45 ℃ temperature, with ethylene oxide sterilization processes 6 hours, finished preparation process.
[embodiment 9]
A kind of biodegradable porous scaffold particle for injection of improvement, it mainly is made up of Biodegradable polymer, wherein said Biodegradable polymer is the copolymer p LGA that polylactic acid PLA and polyglycolic acid PGA constitute, wherein the percentage by weight between polylactic acid and the polyglycolic acid is 75: 25, and its average molecular weight range is 97400.
A kind of preparation method of biodegradable porous scaffold particle for injection of improvement, it may further comprise the steps:
(1) Biodegradable polymer is dissolved in the dichloromethane organic solvent, form organic solution, the Biodegradable polymer dissolving is 20: 80 with the percentage by weight of organic solvent, organic solution is mixed with water again, and the percentage by weight of organic solution and water is 60: 40;
(2) the mixture rotating speed with 4000 rev/mins on blender with machine solution and water stirred 30 minutes, and the internal temperature of blender maintains 35 ℃, forms the solution of softening;
(3) the softening solution of making is put in the mould of politef material, moment freezed 8 hours in-85 ℃ liquid nitrogen and ultra cold storage freezer, wherein, freezed in the liquid nitrogen 1.5 hours, freezed in the ultra cold storage freezer 6.5 hours, use the vacuum freezing drying machine-50 ℃ of following lyophilizations 36 hours then, make the sheet of foaming.
(4) keeping 25 ℃ of pulverizer external temperatures, under the condition that internal temperature is 20 ℃, the sheet of above-mentioned foaming was pulverized 10 seconds with 1000 rev/mins speed, pulverize repeatedly 10 times, and as a circulation, carry out this circulation 5 times repeatedly, obtaining mean molecule quantity is 95000, and mean size is the particle of 10～60um;
(5) preparing percentage by weight respectively is that 0.4% mannitol softening agents aqueous solution and weight ratio are 0.4% sodium carboxymethyl cellulose softening agents aqueous solution, above-mentioned ground product particle and by mannitol softening agents aqueous solution and sodium carboxymethyl cellulose softening agents aqueous solution, the percentage by weight between ground product, mannitol softening agents aqueous solution, the sodium carboxymethyl cellulose softening agents aqueous solution was respectively 16.53: 3.37: 80.10; Accordingly, the percentage by weight between ground product, mannitol, the sodium carboxymethyl cellulose was respectively 98.02: 0.08: 1.9, and vacuum lyophilization 36 hours under-45 ℃ temperature, with ethylene oxide sterilization processes 6 hours, finished preparation process.
[embodiment 10]
A kind of biodegradable porous scaffold particle for injection of improvement, it mainly is made up of Biodegradable polymer, wherein said Biodegradable polymer is the copolymer p LGA that polylactic acid PLA and polyglycolic acid PGA constitute, wherein the percentage by weight between polylactic acid and the polyglycolic acid is 75: 25, and its average molecular weight range is 97400.
A kind of preparation method of biodegradable porous scaffold particle for injection of improvement, it may further comprise the steps:
(1) Biodegradable polymer is dissolved in the dichloromethane organic solvent, form organic solution, the Biodegradable polymer dissolving is 20: 80 with the percentage by weight of organic solvent, organic solution is mixed with water again, and the percentage by weight of organic solution and water is 60: 40;
(2) the mixture rotating speed with 4000 rev/mins on blender with machine solution and water stirred 30 minutes, and the internal temperature of blender maintains 35 ℃, forms the solution of softening;
(3) the softening solution of making is put in the mould of politef material, moment freezed 8 hours in-85 ℃ liquid nitrogen and ultra cold storage freezer, wherein, freezed in the liquid nitrogen 1.5 hours, freezed in the ultra cold storage freezer 6.5 hours, use the vacuum freezing drying machine-50 ℃ of following lyophilizations 36 hours then, make the sheet of foaming.
(4) keeping 25 ℃ of pulverizer external temperatures, under the condition that internal temperature is 20 ℃, the sheet of above-mentioned foaming was pulverized 10 seconds with 1000 rev/mins speed, pulverize repeatedly 10 times, and as a circulation, carry out this circulation 5 times repeatedly, obtaining mean molecule quantity is 95000, and mean size is the particle of 10～60um;
(5) preparing percentage by weight respectively is that 0.4% mannitol softening agents aqueous solution and weight ratio are 0.4% sodium carboxymethyl cellulose softening agents aqueous solution, above-mentioned ground product particle and by mannitol softening agents aqueous solution and sodium carboxymethyl cellulose softening agents aqueous solution, the percentage by weight between ground product, mannitol softening agents aqueous solution, the sodium carboxymethyl cellulose softening agents aqueous solution was respectively 17.27: 3.52: 79.21; Accordingly, the percentage by weight between ground product, mannitol, the sodium carboxymethyl cellulose was respectively 98.12: 0.08: 1.8, and vacuum lyophilization 36 hours under-45 ℃ temperature, with ethylene oxide sterilization processes 6 hours, finished preparation process.
[embodiment 11]
A kind of biodegradable porous scaffold particle for injection of improvement, it mainly is made up of Biodegradable polymer, wherein said Biodegradable polymer is the copolymer p LGA that polylactic acid PLA and polyglycolic acid PGA constitute, wherein the percentage by weight between polylactic acid and the polyglycolic acid is 75: 25, and its average molecular weight range is 97400.
A kind of preparation method of biodegradable porous scaffold particle for injection of improvement, it may further comprise the steps:
(1) Biodegradable polymer is dissolved in the dichloromethane organic solvent, form organic solution, the Biodegradable polymer dissolving is 20: 80 with the percentage by weight of organic solvent, organic solution is mixed with water again, and the percentage by weight of organic solution and water is 60: 40;
(2) the mixture rotating speed with 4000 rev/mins on blender with machine solution and water stirred 30 minutes, and the internal temperature of blender maintains 35 ℃, forms the solution of softening;
(3) the softening solution of making is put in the mould of politef material, moment freezed 8 hours in-85 ℃ liquid nitrogen and ultra cold storage freezer, wherein, freezed in the liquid nitrogen 1.5 hours, freezed in the ultra cold storage freezer 6.5 hours, use the vacuum freezing drying machine-50 ℃ of following lyophilizations 36 hours then, make the sheet of foaming.
(4) keeping 25 ℃ of pulverizer external temperatures, under the condition that internal temperature is 20 ℃, the sheet of above-mentioned foaming was pulverized 10 seconds with 1000 rev/mins speed, pulverize repeatedly 10 times, and as a circulation, carry out this circulation 5 times repeatedly, obtaining mean molecule quantity is 95000, and mean size is the particle of 10～60um;
(5) preparing percentage by weight respectively is that 0.4% mannitol softening agents aqueous solution and weight ratio are 0.4% sodium carboxymethyl cellulose softening agents aqueous solution, above-mentioned ground product particle and by mannitol softening agents aqueous solution and sodium carboxymethyl cellulose softening agents aqueous solution, the percentage by weight between ground product, mannitol softening agents aqueous solution, the sodium carboxymethyl cellulose softening agents aqueous solution was respectively 18.08: 3.68: 78.24; Accordingly, the percentage by weight between ground product, mannitol, the sodium carboxymethyl cellulose was respectively 98.22: 0.08: 1.7, and vacuum lyophilization 36 hours under-45 ℃ temperature, with ethylene oxide sterilization processes 6 hours, finished preparation process.
[embodiment 12]
A kind of biodegradable porous scaffold particle for injection of improvement, it mainly is made up of Biodegradable polymer, and wherein said Biodegradable polymer is polylactic acid PLA, and its average molecular weight range is 97400.
A kind of preparation method of biodegradable porous scaffold particle for injection of improvement, it may further comprise the steps:
(1) Biodegradable polymer is dissolved in the dichloromethane organic solvent, form organic solution, the Biodegradable polymer dissolving is 20: 80 with the percentage by weight of organic solvent, organic solution is mixed with water again, and the percentage by weight of organic solution and water is 60: 40;
(2) the mixture rotating speed with 4000 rev/mins on blender with machine solution and water stirred 30 minutes, and the internal temperature of blender maintains 35 ℃, forms the solution of softening;
(3) the softening solution of making is put in the mould of politef material, moment freezed 8 hours in-85 ℃ liquid nitrogen and ultra cold storage freezer, wherein, freezed in the liquid nitrogen 1.5 hours, freezed in the ultra cold storage freezer 6.5 hours, use the vacuum freezing drying machine-50 ℃ of following lyophilizations 36 hours then, make the sheet of foaming.
(4) keeping 25 ℃ of pulverizer external temperatures, under the condition that internal temperature is 20 ℃, the sheet of above-mentioned foaming was pulverized 10 seconds with 1000 rev/mins speed, pulverize repeatedly 10 times, and as a circulation, carry out this circulation 5 times repeatedly, obtaining mean molecule quantity is 95000, and mean size is the particle of 10～60um;
(5) preparing percentage by weight respectively is that 0.4% mannitol softening agents aqueous solution and weight ratio are 0.4% sodium carboxymethyl cellulose softening agents aqueous solution, above-mentioned ground product particle and by mannitol softening agents aqueous solution and sodium carboxymethyl cellulose softening agents aqueous solution, the percentage by weight between ground product, mannitol softening agents aqueous solution, the sodium carboxymethyl cellulose softening agents aqueous solution was respectively 15.85: 3.24: 80.91; Accordingly, the percentage by weight between ground product, mannitol, the sodium carboxymethyl cellulose was respectively 97.92: 0.08: 2, and vacuum lyophilization 36 hours under-45 ℃ temperature, with ethylene oxide sterilization processes 6 hours, finished preparation process.
[embodiment 13]
A kind of biodegradable porous scaffold particle for injection of improvement, it mainly is made up of Biodegradable polymer, and wherein said Biodegradable polymer is polylactic acid PLA, and its average molecular weight range is 97400.
A kind of preparation method of biodegradable porous scaffold particle for injection of improvement, it may further comprise the steps:
(1) Biodegradable polymer is dissolved in the dichloromethane organic solvent, form organic solution, the Biodegradable polymer dissolving is 20: 80 with the percentage by weight of organic solvent, organic solution is mixed with water again, and the percentage by weight of organic solution and water is 60: 40;
(2) the mixture rotating speed with 4000 rev/mins on blender with machine solution and water stirred 30 minutes, and the internal temperature of blender maintains 35 ℃, forms the solution of softening;
(3) the softening solution of making is put in the mould of politef material, moment freezed 8 hours in-85 ℃ liquid nitrogen and ultra cold storage freezer, wherein, freezed in the liquid nitrogen 1.5 hours, freezed in the ultra cold storage freezer 6.5 hours, use the vacuum freezing drying machine-50 ℃ of following lyophilizations 36 hours then, make the sheet of foaming.
(4) keeping 25 ℃ of pulverizer external temperatures, under the condition that internal temperature is 20 ℃, the sheet of above-mentioned foaming was pulverized 10 seconds with 1000 rev/mins speed, pulverize repeatedly 10 times, and as a circulation, carry out this circulation 5 times repeatedly, obtaining mean molecule quantity is 95000, and mean size is the particle of 10～60um;
(5) preparing percentage by weight respectively is that 0.4% mannitol softening agents aqueous solution and weight ratio are 0.4% sodium carboxymethyl cellulose softening agents aqueous solution, above-mentioned ground product particle and by mannitol softening agents aqueous solution and sodium carboxymethyl cellulose softening agents aqueous solution, the percentage by weight between ground product, mannitol softening agents aqueous solution, the sodium carboxymethyl cellulose softening agents aqueous solution was respectively 16.53: 3.37: 80.10; Accordingly, the percentage by weight between ground product, mannitol, the sodium carboxymethyl cellulose was respectively 98.02: 0.08: 1.9, and vacuum lyophilization 36 hours under-45 ℃ temperature, with ethylene oxide sterilization processes 6 hours, finished preparation process.
[embodiment 14]
A kind of biodegradable porous scaffold particle for injection of improvement, it mainly is made up of Biodegradable polymer, and wherein said Biodegradable polymer is polylactic acid PLA, and its average molecular weight range is 97400.
A kind of preparation method of biodegradable porous scaffold particle for injection of improvement, it may further comprise the steps:
(1) Biodegradable polymer is dissolved in the dichloromethane organic solvent, form organic solution, the Biodegradable polymer dissolving is 20: 80 with the percentage by weight of organic solvent, organic solution is mixed with water again, and the percentage by weight of organic solution and water is 60: 40;
(2) the mixture rotating speed with 4000 rev/mins on blender with machine solution and water stirred 30 minutes, and the internal temperature of blender maintains 35 ℃, forms the solution of softening;
(3) the softening solution of making is put in the mould of politef material, moment freezed 8 hours in-85 ℃ liquid nitrogen and ultra cold storage freezer, wherein, freezed in the liquid nitrogen 1.5 hours, freezed in the ultra cold storage freezer 6.5 hours, use the vacuum freezing drying machine-50 ℃ of following lyophilizations 36 hours then, make the sheet of foaming.
(4) keeping 25 ℃ of pulverizer external temperatures, under the condition that internal temperature is 20 ℃, the sheet of above-mentioned foaming was pulverized 10 seconds with 1000 rev/mins speed, pulverize repeatedly 10 times, and as a circulation, carry out this circulation 5 times repeatedly, obtaining mean molecule quantity is 95000, and mean size is the particle of 10～60um;
(5) preparing percentage by weight respectively is that 0.4% mannitol softening agents aqueous solution and weight ratio are 0.4% sodium carboxymethyl cellulose softening agents aqueous solution, above-mentioned ground product particle and by mannitol softening agents aqueous solution and sodium carboxymethyl cellulose softening agents aqueous solution, the percentage by weight between ground product, mannitol softening agents aqueous solution, the sodium carboxymethyl cellulose softening agents aqueous solution was respectively 17.27: 3.52: 79.21; Accordingly, the percentage by weight between ground product, mannitol, the sodium carboxymethyl cellulose was respectively 98.12: 0.08: 1.8, and vacuum lyophilization 36 hours under-45 ℃ temperature, with ethylene oxide sterilization processes 6 hours, finished preparation process.
[embodiment 15]
A kind of biodegradable porous scaffold particle for injection of improvement, it mainly is made up of Biodegradable polymer, and wherein said Biodegradable polymer is polylactic acid PLA, and its average molecular weight range is 97400.
A kind of preparation method of biodegradable porous scaffold particle for injection of improvement, it may further comprise the steps:
(1) Biodegradable polymer is dissolved in the dichloromethane organic solvent, form organic solution, the Biodegradable polymer dissolving is 20: 80 with the percentage by weight of organic solvent, organic solution is mixed with water again, and the percentage by weight of organic solution and water is 60: 40;
(2) the mixture rotating speed with 4000 rev/mins on blender with machine solution and water stirred 30 minutes, and the internal temperature of blender maintains 35 ℃, forms the solution of softening;
(3) the softening solution of making is put in the mould of politef material, moment freezed 8 hours in-85 ℃ liquid nitrogen and ultra cold storage freezer, wherein, freezed in the liquid nitrogen 1.5 hours, freezed in the ultra cold storage freezer 6.5 hours, use the vacuum freezing drying machine-50 ℃ of following lyophilizations 36 hours then, make the sheet of foaming.
(4) keeping 25 ℃ of pulverizer external temperatures, under the condition that internal temperature is 20 ℃, the sheet of above-mentioned foaming was pulverized 10 seconds with 1000 rev/mins speed, pulverize repeatedly 10 times, and as a circulation, carry out this circulation 5 times repeatedly, obtaining mean molecule quantity is 95000, and mean size is the particle of 10～60um;
(5) preparing percentage by weight respectively is that 0.4% mannitol softening agents aqueous solution and weight ratio are 0.4% sodium carboxymethyl cellulose softening agents aqueous solution, above-mentioned ground product particle and by mannitol softening agents aqueous solution and sodium carboxymethyl cellulose softening agents aqueous solution, the percentage by weight between ground product, mannitol softening agents aqueous solution, the sodium carboxymethyl cellulose softening agents aqueous solution was respectively 18.08: 3.68: 78.24; Accordingly, the percentage by weight between ground product, mannitol, the sodium carboxymethyl cellulose was respectively 98.22: 0.08: 1.7, and vacuum lyophilization 36 hours under-45 ℃ temperature, with ethylene oxide sterilization processes 6 hours, finished preparation process.
Table 1 is to use injection biological degradability scaffold particle of the present invention to carry out 100 routine injectivity result of the tests:
Table 1
| Experimental project | Specification requirement | Testing result | Qualification rate | |
| Pyrogen | | Apyrogeneity | 100％ | |
| Hemolytic | Hemolysis rate answers＜5% | Hemolysis rate＜1% | 100％ | |
| Acute general toxicity | Should there be acute general toxic reaction | There is not acute general |
100％ |
| Cytotoxicity | Cell-cytotoxic reaction is answered the 1-0 level | 1 grade of |
100% |
| Sensitization | Should there be sensitivity response | No sensitivity response | 99% |
| Vivo degradation | Subcutaneous 12 weeks of implantation, support should all be degraded after 16 weeks | After subcutaneous 15 weeks of implantation, support is all degraded | 100% |
| Subcutaneous implantation | Implanted for 2 weeks, after 4 weeks and 12 weeks, the histologic reaction around the sample is good. | Implanted for 2 weeks, after 4 weeks and 12 weeks, the histologic reaction around the sample is good. | 99％ |
The result of table 1 shows, a period of time can natural degradation in vivo for support, has the favorable tissue compatibility and blood compatibility, does not have irritated reaction, no immunological rejection, and be beneficial to the apposition growth of cell and harmless.
Use respectively PLGA (25PLA: 75PGA), PLGA (50PLA: 50PGA), PLGA (65PLA: 35PGA), PLGA (75PLA: 25PGA) and five kinds of raw materials of 100%PLA make injection biological degradability scaffold particle according to the method for embodiment 1～15 and be expelled under the rabbit, carry out the vivo degradation experiment, experimental result such as table 2:
Table 2
| The monomer molar ratio | The scaffold degradation time (my god) |
| 25％PLA∶75 |
100 |
| 50％PLA∶50 |
80 |
| 65％PLA∶35％PGA | 90 |
| 75％PLA∶25％PGA | 120 |
| 100％PLA | 180 |
According to above-mentioned experiment, can see the monomer ratio that PLGA is different, its vivo degradation time is all variant.For the cell on the product can better be grown, and well and the patient identical from bulk phase, we select the PLGA of lactic acid and the combined polymerization in 75: 25 of hydroxyacetic acid mol ratio for use.
The physical property of biodegradable porous scaffold particle for injection of the present invention is as shown in table 3.
1) wettability: embody the contact angle of water, the contact angle on the PLGA sheet is 75～80 degree, so in aqueous solution, have higher free energy, therefore causes cell attachment and dysgonic influence.
2) surface charge: surface charge and water contact angle are similar, and all nanoparticles in the molecular configuration must have negative charge could be stablized, and available zeta potential difference machine is measured.
3) cells survival is whether in the aqueous solution: in aqueous solution (mannitol, sodium carboxymethyl cellulose, distilled water), and the affirmation that whether can survive of hypodermal cell.
4) hot strength: be that benchmark is measured with ASTM D 638:2003 method.
5) percentage elongation: be that benchmark is measured with ASTM D 638:2003 method.
6) modulus: be that benchmark is measured with KSM ISO 01827 method.
7) shore D-longitude: be that benchmark is measured with KSM ISO 2039-2:2003 method.
8) glass transition temperature: measure according to DSC, before principle takes place with reaction, baseline and reaction beginning, after the turning point of the connection endothermic reaction and the extrapolation contact of wiring and the turning point reaction, be expressed as baseline and extrapolation contact (as can not explain correct glass transition temperature, may because people's difference of explaining then have error a little).
9) solvent stability: get solution 100mL separately, stir 24h and measure, all whether particle determining of dissolving.
According to The above results, by the embodiment that provides of the present invention, can obtain average particle size is the interior biological degradability scaffold particle of 50～150um scope, can inject by the international standard syringe.
Fig. 1 is the electromicroscopic photograph of the biodegradable porous scaffold particle for injection of improvement.As can be seen from Figure 1, particle shape has indefinite formization, and average particle size is 50～150 microns.Simultaneously, by regulating pulverization conditions, in the big or small manufacturing process of the non-type of particle and particle, can regulate.
Fig. 2 is the thermal analysis curue of the injection biological degradability scaffold particle of manufacturing according to example 8～15 of the present invention.The employing differential scanning calorimetry is measured: sample is placed among the DSC (differential scanning calorimeter), makes ambient temperature rise to 100 ℃ in five minutes, then sample temperature is reduced to 25 ℃ with the speed of 20 ℃/min, and the speed with 10 ℃/min is reduced to-20 ℃ again.At last, again sample is elevated to 100 ℃ with the speed of 20 ℃/min, and its thermogram is analyzed vitrification point.This data show: the glass transition temperature of this support is 47～54 ℃.
Fig. 3 is that the weight average molecular weight (M/w) of PLGA in the injection biological degradability scaffold particle of making according to example 8～11 of the present invention is measured figure.What the weight average molecular weight of PLGA (M/w) was taked in the particle is that gel permeation chromatography (GPC) records.With sample dissolution in the chloroform that contains 0.025% toluene.In GPC system container storehouse, inject the 150ul sample solution, finish measurement with refractive index detector.The temperature maintenance of container storehouse and detector is about 40 ℃.Molecular weight analyte can calculate by comparing the polystyrene standard molecular weight, and the weight average molecular weight that obtains particle is 90000～110000.
Claims (1)
1. the biodegradable porous scaffold particle for injection of an improvement, it is characterized in that: it mainly is made up of Biodegradable polymer, wherein, described Biodegradable polymer is polylactic acid, the perhaps copolymer of polylactic acid and polyglycolic acid, described Biodegradable polymer weight average molecular weight scope is 10000～150000, the mean molecule quantity of the biodegradable porous scaffold particle for injection of described improvement is 90000～110000,10～200 microns of particle sizes, be loose structure, rough surface;
The preparation method of the biodegradable porous scaffold particle for injection of described a kind of improvement, it may further comprise the steps:
(1) Biodegradable polymer is dissolved in forms organic solution in the organic solvent, the percentage by weight of Biodegradable polymer and organic solvent is 1.67～45: 55-98.33, again organic solution is mixed with water, the percentage by weight of organic solution and water is 30～90: 10～70, described organic solvent is acetonitrile, dichloromethane, perhaps both mixture;
(2) the mixture rotating speed with 2000～5000 rev/mins on blender with organic solution and water stirred 20～40 minutes, and the internal temperature of blender maintains 20～40 ℃, forms the solution of softening;
(3) softening solution is injected mould, ℃ freeze 7～9 hours in temperature-196～-80 after, freeze-dried and foamed 24～48 hours under-50 ℃～-40 ℃ temperature again;
(4) keep 20～25 ℃ of pulverizer external temperatures, under the condition that internal temperature is 15～20 ℃, pulverizing 5～10 seconds with 300～1000 rev/mins speed, pulverizing repeatedly 10 times, and as a circulation, carrying out this circulation 1～5 time repeatedly;
(5) softening agents is joined formation softening agents aqueous solution in the pure water, the percentage by weight of softening agents and pure water is 0.1～5: 95～99.9, then the ground product that obtains and softening agents aqueous solution, the percentage by weight of ground product and softening agents aqueous solution is 4.5～74.4: 25.6～95.5, and under-50 ℃～-40 ℃ temperature freeze-dried 24～48 hours, through 6～8 hours sterilization treatment, finish preparation process; Described softening agents is mannitol, sodium carboxymethyl cellulose, perhaps both mixture.
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