CN100335527C - Water soluble polylactic-acid material, prepn. method and application thereof - Google Patents
Water soluble polylactic-acid material, prepn. method and application thereof Download PDFInfo
- Publication number
- CN100335527C CN100335527C CNB2005100366644A CN200510036664A CN100335527C CN 100335527 C CN100335527 C CN 100335527C CN B2005100366644 A CNB2005100366644 A CN B2005100366644A CN 200510036664 A CN200510036664 A CN 200510036664A CN 100335527 C CN100335527 C CN 100335527C
- Authority
- CN
- China
- Prior art keywords
- cyclodextrin
- polylactic acid
- preparation
- poly
- water
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- Materials For Medical Uses (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention discloses a water-solubility polylactic acid material and a preparation method thereof. The preparation method comprises the following steps: methyl pyrrolidone as a solvent is utilized to dissolve polylactic acid to prepare a polylactic acid solution; right amount of cyclodextrin is dissolved in the methyl pyrrolidone to prepare a cyclodextrin solution; the two kinds of solutions are mixed and stirred; the mixture is properly heated under the condition of continuous mixing and is treated under the condition with ultrasonic oscillations; the mixture is cooled and ultrafiltered or the water is dialyzed until the free cyclodextrin and the solvent are completely removed; after the dialyzed mixture is dried, the water-solubility polylactic acid product is obtained. The present invention also discloses the application of the water-solubility polylactic acid material in tissue engineering scaffolds and tissue filling materials, etc. The present invention has simple method, does not need complicated chemically reaction and can realize the scaled production. A poisonous and irritant solvent or other chemical reagents is or are not utilized in the modification course. The basic chemical property and the in vivo applied characteristics of the polylactic acid are not changed, and the biocompatibility of the polylactic acid can be improved.
Description
Technical field
The invention belongs to field of biomedical materials, particularly a kind of water soluble polylactic-acid material and preparation method thereof and application.
Background technology
Existing polylactic acid modified several aspects that mainly concentrate on: with poly(lactic acid) and other hydrophilic material mixes and blend, compound as materials such as poly(lactic acid) and chitin, collagen, hydroxyapatite, calcium phosphate; The graft modification of poly(lactic acid) is as the graft copolymerization of materials such as poly(lactic acid) and hydrophilic high molecular material polyoxyethylene glycol, polyvinyl alcohol, polyoxyethylene, propylene oxide; The top coat technology of poly-lactic acid material is as surface-coated albumin, collagen protein, fibronectin and ln etc.
In the document, be compounded to form the report of inclusion compound relevant for synthesized polymer materials such as cyclodextrin and polyvinyl alcohol, polymethyl siloxane, nylon, polyoxyethylene-propylene oxide-ethylene oxide copolymer and poly-epsilon-caprolactones abroad.The Preparation methods of cyclodextrin inclusion complexes of above-mentioned bibliographical information all is to adopt synthesized polymer material and cyclodextrin are dissolved in different solvents respectively, or even in the mutual exclusive solvent, make polymer and cyclodextrin molecular form inclusion compound by methods such as violent stirring.This method have a following shortcoming:
1. the inclusion compound formation efficiency is extremely low, even be far longer than under the high molecular situation still like this in cyclodextrin ratios;
2. cyclodextrin component content is extremely low in the inclusion compound, and the inclusion compound changes in material properties of preparation is minimum;
3. the required reaction times is very long;
4. the preparation of some inclusion compound need be used organic solvent, and these solvents are virose often, and volatility is high, is unfavorable for using in the organism;
5. do not relate to polylactic acid-based material.
Therefore, existing technology does not all have or can not fundamentally improve the aqueous solvent working ability of poly-lactic acid material, can only improve the wetting ability of poly-lactic acid material to a certain extent.Through document and related patent data library searching, do not find a kind of ideal poly(lactic acid) aqueous solution processing technology as yet.
Because simple poly-lactic acid material can only be dissolved in organic solvent, when using, be very limited as biomedical material, when especially particularly biological activity protein class medicine and genetically engineered field were as the dna vector material as pharmaceutical carrier, organic solvent was handled generations such as the activity of medicine and specific molecular configuration is had a strong impact on.In addition, organic solvent residue also will produce adverse consequences to using in the body of material, equally also limit the application of this material as tissue engineering bracket.
Summary of the invention
In order to solve above-mentioned the deficiencies in the prior art part, primary and foremost purpose of the present invention just provides the preparation method of simple, the practical water soluble polylactic-acid material of a kind of technology, this preparation method can make the poly lactic acid kind polyester macromolecular material possess in water dissolving or fully disperse, thereby realizes the poly lactic acid kind polyester macromolecular material is processed and improved its application performance.
Another object of the present invention just provides by the made water soluble polylactic-acid material of aforesaid method.
A further object of the present invention just provides the application of above-mentioned water soluble polylactic-acid material in tissue engineering bracket material, tissue filling material, soft tissue filling material or dental material etc.Poly-lactic acid material belongs to Biodegradable Polymers, has excellent biological compatibility, be widely used in biomedical material and goods, comprise degradable operating sutures, slow releasing carrier of medication, be used for various bone anchoring devices, artificial organs, cell and the tissue growth support etc. of operative treatment.
Primary and foremost purpose of the present invention is achieved through the following technical solutions: the preparation method of water soluble polylactic-acid material comprises the steps:
1) adopting methyl-2-pyrrolidone is the dissolution with solvents poly(lactic acid), and being made into concentration is the poly(lactic acid) solution of 0.1g/l～200g/l;
2) cyclodextrin with proper amt is dissolved in the methyl-2-pyrrolidone, is made into the cyclodextrin soln that concentration is 0.01g/l～1000g/l;
3) above-mentioned two solution are mixed, stir;
4) said mixture is handled 0.5～12h continuing suitably to be heated to 40～150 ℃ under the stirring under the ultra-sonic oscillation condition;
5) mixture is cooled to below 4 ℃, ultrafiltration or to water dialysis to removing free cyclodextrin and solvent fully;
6) be the water soluble polylactic-acid product after the mixture drying after the dialysis.
Described cyclodextrin comprises alpha-cylodextrin, beta-cyclodextrin, γ-Huan Hujing etc.Mixture drying means after the described dialysis adopts lyophilize, spraying drying or vacuum-drying.
Technical scheme of the present invention is the optimum solvent that poly(lactic acid) is dissolved in good biocompatibility---in the methyl-2-pyrrolidone, the cyclodextrin that in this solution, adds suitable proportion simultaneously, under the ultra-sonic oscillation condition, make wire poly(lactic acid) macromole enter cyclodextrin cavity, thereby form cyclodextrin---the Polymer Systems of poly(lactic acid) inclusion compound as object; Then, the inclusion compound crassitude ketone solvent that dialysis is removed in the system to water with preparation closes the cyclodextrin that has neither part nor lot in reaction; Be dried at last and can obtain water soluble polylactic-acid material.The molecular weight of compound cyclodextrin ratios and poly(lactic acid) is different in this material, can obtain being scattered in water and form stable colloidal solutions or have solid-state poly-lactic acid material than strongly hydrophilic.The present invention be by poly lactic acid kind polyester macromolecular material and cyclodextrin in having the cosolvent of good biocompatibility, form supramolecular system---inclusion compound by physical method, to obtain a kind of polylactic acid-based macromolecular material with property.
The present invention compared with prior art has following advantage and effect:
1. the inventive method is simple, does not need to carry out complicated chemical reaction, can accomplish scale production;
2. do not adopt poisonous, pungency in the modifying process of the present invention, may produce dysgenic solvent or other chemical reagent human body;
3. the present invention does not change and uses feature in the basic chemical property of poly(lactic acid) and the body and can improve its biocompatibility;
4. the present invention can obtain a class and has highly hydrophilic and can disperse to form the colloidal poly-lactic acid material in water; Simultaneously, the wetting ability of this material can be controlled;
5. the invention belongs to physically modified.
Embodiment
The present invention is described in further detail below in conjunction with embodiment, but embodiments of the present invention are not limited thereto.
Embodiment 1
1) taking by weighing viscosity-average molecular weight is that 500000 poly(lactic acid) 2g is dissolved in the 10ml methyl-2-pyrrolidone;
2) taking by weighing beta-cyclodextrin 0.5g is dissolved in the 10ml methyl-2-pyrrolidone;
3) beta-cyclodextrin solution is joined in the poly(lactic acid) solution, mix, stir;
4) mixing solutions is being continued to be heated to 80 ℃ under the stirring, under the ultrasonic power of 50W, oscillatory reaction 1h;
5) reaction product is cooled to 4 ℃, after the employing ultra-filtration technique concentrated, dialysis removed crassitude ketone solvent and unreacted beta-cyclodextrin to water;
6) product lyophilize (the lyophilize condition: product places the Freeze Drying Equipment freeze-drying being lower than 0 ℃ of following pre-freeze 1h) can obtain about 0.25g and be blocky beta-cyclodextrin and poly(lactic acid) inclusion compound;
7) dried product exhibited water mixing (the polydactyl acid concentration range is 0.5g/ml) again, the furnishing pasty state again through the lyophilize moulding, promptly can be used as tissue engineering bracket material.
Embodiment 2
1) taking by weighing viscosity-average molecular weight is 10000 poly(lactic acid) 1000g, is dissolved in the 10L methyl-2-pyrrolidone;
2) take by weighing alpha-cylodextrin 100g, be dissolved in the 1L methyl-2-pyrrolidone;
3) with after the above-mentioned two solution mixing, be heated to 60 ℃, under the ultrasonic power condition of 200W, oscillatory reaction 1h;
4) reaction product is cooled to room temperature, the dialysis tubing of packing into removes crassitude ketone solvent and unreacted alpha-cylodextrin to water dialysis (water yield is more than 10 times of sample size, and change water once per half an hour) 10h;
5) dialysis back solution spray drying can obtain being the inclusion compound material of pulverous 1100g alpha-cylodextrin and poly(lactic acid);
6) dried product exhibited adds entry furnishing pasty state, as the tissue filling material, is used for soft tissue filling material or dental material.
Embodiment 3
1) taking by weighing viscosity-average molecular weight is 100000 poly(lactic acid) 100g, is dissolved in the 1L methyl-2-pyrrolidone;
2) take by weighing γ-Huan Hujing 1g, be dissolved in the 10mL methyl-2-pyrrolidone;
3) with after the above-mentioned two solution mixing, be heated to 40 ℃, under the ultrasonic power condition of 100W, oscillatory reaction 4h;
4) reaction product is packed into dialysis tubing to water dialysis (water yield is more than 10 times of sample size, and change water once per half an hour) 10h, remove crassitude ketone solvent and unreacted γ-Huan Hujing;
5) dialysis back solution spray drying can obtain the inclusion compound material of pulverous γ-Huan Hujing of about 100g and poly(lactic acid).
Embodiment 4
1) taking by weighing viscosity-average molecular weight is that 500000 poly(lactic acid) 2g is dissolved in the 100ml methyl-2-pyrrolidone;
2) taking by weighing beta-cyclodextrin 0.5g is dissolved in the 10ml methyl-2-pyrrolidone;
3) beta-cyclodextrin solution is joined in the poly(lactic acid) solution, mix, stir;
4) mixing solutions is heated to 70 ℃, under the ultrasonic power of 150W, oscillatory reaction 2h;
5), adopt ultra-filtration equipment to remove crassitude ketone solvent and beta-cyclodextrin with reaction product cooling (being cooled to 0 ℃);
6) product lyophilize (the lyophilize condition: product places the Freeze Drying Equipment freeze-drying being lower than 0 ℃ of following pre-freeze 4h) can obtain about 0.25g and be blocky beta-cyclodextrin and poly(lactic acid) inclusion compound.
Embodiment 5
1) taking by weighing viscosity-average molecular weight is 100000 poly(lactic acid) 0.1g, is dissolved in the 1L methyl-2-pyrrolidone;
2) take by weighing γ-Huan Hujing 1g, be dissolved in the 100L methyl-2-pyrrolidone;
3) with after the above-mentioned two solution mixing, be heated to 150 ℃, under the ultrasonic power condition of 100W, oscillatory reaction 0.5h;
4) reaction product is packed into dialysis tubing to water dialysis (water yield is more than 10 times of sample size, and change water once per half an hour) 10h, remove crassitude ketone solvent and unreacted γ-Huan Hujing;
5) dialysis back solution for vacuum drying can obtain the inclusion compound material of pulverous γ-Huan Hujing of about 1.1g and poly(lactic acid).
Embodiment 6
1) taking by weighing viscosity-average molecular weight is 10000 poly(lactic acid) 800g, is dissolved in the 10L methyl-2-pyrrolidone;
2) take by weighing alpha-cylodextrin 1000g, be dissolved in the 1L methyl-2-pyrrolidone;
3) with after the above-mentioned two solution mixing, be heated to 120 ℃, under the ultrasonic power condition of 200W, oscillatory reaction 12h;
4) reaction product is cooled to room temperature, the dialysis tubing of packing into removes crassitude ketone solvent and unreacted alpha-cylodextrin to water dialysis (water yield is more than 10 times of sample size, and change water once per half an hour) 10h;
5) dialysis back solution spray drying can obtain being the inclusion compound material of pulverous 1800g alpha-cylodextrin and poly(lactic acid);
6) dried product exhibited adds entry furnishing pasty state (polydactyl acid concentration is 0.01g/ml), as the tissue filling material, is used for soft tissue filling material or dental material.
Embodiment 7
1) taking by weighing viscosity-average molecular weight is that 500000 poly(lactic acid) 50g is dissolved in the 1000ml methyl-2-pyrrolidone;
2) taking by weighing beta-cyclodextrin 5g is dissolved in the 1L methyl-2-pyrrolidone;
3) beta-cyclodextrin solution is joined in the poly(lactic acid) solution, mix;
4) mixing solutions is being continued to be heated to 100 ℃ under the stirring, under the ultrasonic power of 50W, oscillatory reaction 10h;
5) reaction product is cooled to 4 ℃, after the employing ultra-filtration technique concentrated, dialysis removed crassitude ketone solvent and unreacted beta-cyclodextrin to water;
6) product lyophilize (the lyophilize condition: product places the Freeze Drying Equipment freeze-drying being lower than 0 ℃ of following pre-freeze 2h) can obtain about 55g and be blocky beta-cyclodextrin and poly(lactic acid) inclusion compound;
7) dried product exhibited water mixing (polydactyl acid concentration is 1g/ml) again, the furnishing pasty state again through the lyophilize moulding, promptly can be used as tissue engineering bracket material.
Embodiment 8
1) taking by weighing viscosity-average molecular weight is 100000 poly(lactic acid) 0.5g, is dissolved in the 1L methyl-2-pyrrolidone;
2) take by weighing γ-Huan Hujing 1g, be dissolved in the 100L methyl-2-pyrrolidone;
3) with after the above-mentioned two solution mixing, be heated to 110 ℃, under the ultrasonic power condition of 100W, oscillatory reaction 6h;
4) reaction product is packed into dialysis tubing to water dialysis (water yield is more than 10 times of sample size, and change water once per half an hour) 10h, remove crassitude ketone solvent and unreacted γ-Huan Hujing;
5) dialysis back solution for vacuum drying can obtain the inclusion compound material of pulverous γ-Huan Hujing of about 1.5g and poly(lactic acid).
Embodiment 9
1) taking by weighing viscosity-average molecular weight is 10000 poly(lactic acid) 600g, is dissolved in the 10L methyl-2-pyrrolidone;
2) take by weighing alpha-cylodextrin 1000g, be dissolved in the 1L methyl-2-pyrrolidone;
3) with after the above-mentioned two solution mixing, be heated to 60 ℃, under the ultrasonic power condition of 200W, oscillatory reaction 8h;
4) reaction product is cooled to room temperature, the dialysis tubing of packing into removes crassitude ketone solvent and unreacted alpha-cylodextrin to water dialysis (water yield is more than 10 times of sample size, and change water once per half an hour) 10h;
5) dialysis back solution spray drying can obtain being the inclusion compound material of pulverous 1600g alpha-cylodextrin and poly(lactic acid);
6) dried product exhibited adds entry furnishing pasty state (polydactyl acid concentration is 0.1g/ml), as the tissue filling material, is used for soft tissue filling material or dental material.
As mentioned above, can realize the present invention preferably.
Claims (6)
1, a kind of preparation method of water soluble polylactic-acid material, its preparation method comprises the steps:
1) adopting methyl-2-pyrrolidone is the dissolution with solvents poly(lactic acid), and being made into concentration is the poly(lactic acid) solution of 0.1g/l～200g/l;
2) cyclodextrin is dissolved in the methyl-2-pyrrolidone, is made into the cyclodextrin soln that concentration is 0.01g/l～1000g/l;
3) above-mentioned two solution are mixed, stir;
4) said mixture is handled 0.5～12h continuing to be heated to 40～150 ℃ under the stirring under the ultra-sonic oscillation condition;
5) mixture is cooled to below 4 ℃, ultrafiltration or to water dialysis to removing free cyclodextrin and solvent fully;
6) be the water soluble polylactic-acid product after the mixture drying after the dialysis.
2, preparation method according to claim 1 is characterized in that, described cyclodextrin comprises alpha-cylodextrin, beta-cyclodextrin or γ-Huan Hujing.
3, preparation method according to claim 1 is characterized in that, the mixture drying means after the described dialysis adopts lyophilize, spraying drying or vacuum-drying.
4, the water soluble polylactic-acid material of preparation method's preparation according to claim 1.
5, the application of the described water soluble polylactic-acid material of claim 4 in tissue engineering bracket, tissue filling material.
6, the application of the described water soluble polylactic-acid material of claim 4 in soft tissue filling material or dental material.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100366644A CN100335527C (en) | 2005-08-22 | 2005-08-22 | Water soluble polylactic-acid material, prepn. method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100366644A CN100335527C (en) | 2005-08-22 | 2005-08-22 | Water soluble polylactic-acid material, prepn. method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1757660A CN1757660A (en) | 2006-04-12 |
| CN100335527C true CN100335527C (en) | 2007-09-05 |
Family
ID=36703244
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2005100366644A Expired - Fee Related CN100335527C (en) | 2005-08-22 | 2005-08-22 | Water soluble polylactic-acid material, prepn. method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100335527C (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101298504B (en) * | 2008-07-02 | 2011-01-05 | 武汉大学 | Supermolecule polymer micelle and preparation thereof |
| CN105213201A (en) * | 2015-09-30 | 2016-01-06 | 苏州蔻美新材料有限公司 | Teeth repairing material and preparation method thereof |
| CN105585743B (en) * | 2015-12-22 | 2018-04-03 | 新疆大学 | PLA cyclodextrin inclusion compound and preparation method thereof, product and application |
| CN113209370B (en) * | 2020-01-21 | 2023-11-28 | 渼颜空间(河北)生物科技有限公司 | Biodegradable injection filler, preparation method and application thereof |
| CN111840641A (en) * | 2020-08-31 | 2020-10-30 | 陈玉芝 | Poly-L-lactic acid filler and preparation method and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5743657A (en) * | 1980-08-27 | 1982-03-11 | Masakichi Kawahara | Preparation of lactic acid agent for coagulation of "tofu" |
| JPH01138202A (en) * | 1987-11-25 | 1989-05-31 | Ensuikou Seito Kk | Preparation of cyclodextrin having high solubility |
| JPH03275617A (en) * | 1990-03-22 | 1991-12-06 | Teikoku Seiyaku Co Ltd | Polylactic acid microsphere containing cyclodextrin-physiologically active substance clathrate compound |
-
2005
- 2005-08-22 CN CNB2005100366644A patent/CN100335527C/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5743657A (en) * | 1980-08-27 | 1982-03-11 | Masakichi Kawahara | Preparation of lactic acid agent for coagulation of "tofu" |
| JPH01138202A (en) * | 1987-11-25 | 1989-05-31 | Ensuikou Seito Kk | Preparation of cyclodextrin having high solubility |
| JPH03275617A (en) * | 1990-03-22 | 1991-12-06 | Teikoku Seiyaku Co Ltd | Polylactic acid microsphere containing cyclodextrin-physiologically active substance clathrate compound |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1757660A (en) | 2006-04-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Yan et al. | Injectable in situ forming poly (l-glutamic acid) hydrogels for cartilage tissue engineering | |
| CN1288197C (en) | Hyaluronic acid gel composition, process for producing the same, and medical material containing the same | |
| CN1232539C (en) | Match of organic medicine and beta-cyclodextrin derivative and its preparing process | |
| CN100335527C (en) | Water soluble polylactic-acid material, prepn. method and application thereof | |
| CN1083849C (en) | Polysaccharide gel composition | |
| CN103289107B (en) | Preparation method and application of injectable silk fibroin in-situ gel | |
| CN103524750A (en) | Polyethylene glycol chitosan self-assembled nanoparticles and preparation method thereof | |
| CN106188584B (en) | A kind of derivatives of hyaluronic acids hydrogel and preparation method thereof | |
| CN1021629C (en) | Medicine compound of non-suspending agent and stable sucralfate suspending liquid | |
| CN106362202A (en) | Hydrogel with microcurrent and medicine slow-release function and preparation method and application | |
| CN100344277C (en) | Nano-magnetic medicinal microglobule, its preparation method and application | |
| CN1265847C (en) | Mineralized fibrion/macromolecule composite porous material and preparation method | |
| CN1743008A (en) | Method for preparing nano liver-target biodegradating medicine carrier material | |
| CN103007342B (en) | Biodegradable and medical tricalcium phosphate/gamma-polyglutamic acid composite and preparation method thereof | |
| Abere et al. | Derivation of composites of chitosan-nanoparticles from crustaceans source for nanomedicine: A mini review | |
| CN102247602B (en) | Super-molecular hydrogel double-medicament carrier and preparation method as well as application thereof | |
| CN100351286C (en) | Method for preparing poly-aspartic-acid resin | |
| KR20220103756A (en) | Hydrogel of mercapto-modified high molecular compound and method and use thereof | |
| JPH0278629A (en) | Medical composition | |
| CN1724081A (en) | Material of porous composite calcium sulfate with polymer for support and preparation process thereof | |
| Nabipour et al. | Evaluation of Ibuprofen Release from Gelatin/Hydroxyapatite/Polylactic Acid Nanocomposites: Ibuprofen Release from Gelatin/Hydroxyapatite/Polylactic Acid Nanocomposites | |
| CN101485904A (en) | Injectable calcium sulphate-based sustained-release implantation component containing medicine-carrying particle and application | |
| WO2019192628A2 (en) | Thiolated chitosan derivative, chitosan hydrogel, and preparation methods therefor and applications thereof | |
| CN104710630A (en) | Bovine serum albumin nano microsphere preparation method | |
| CN106693067A (en) | Preparation of self-healing and template-free porous scaffold |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20070905 Termination date: 20110822 |