CN102212158A - Conjugated polyunsaturated fatty acid polymer as well as preparation method and application thereof - Google Patents
Conjugated polyunsaturated fatty acid polymer as well as preparation method and application thereof Download PDFInfo
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- CN102212158A CN102212158A CN2010101633925A CN201010163392A CN102212158A CN 102212158 A CN102212158 A CN 102212158A CN 2010101633925 A CN2010101633925 A CN 2010101633925A CN 201010163392 A CN201010163392 A CN 201010163392A CN 102212158 A CN102212158 A CN 102212158A
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- polyunsaturated fatty
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Abstract
The invention relates to a conjugated polyunsaturated fatty acid polymer as well as a preparation method and application thereof. The conjugated polyunsaturated fatty acid polymer which has a granular structure and is insoluble in water and most of organic solvents is obtained by the steps of: firstly, preparing a thin film by means of solid reaction with one or more than one conjugated polyunsaturated fatty acid or derivative thereof as a monomer, and then polymerizing the thin film. The method has the advantages of mild conditions, simplicity in operation; and the prepared conjugated polyunsaturated fatty acid polymer has good biocompatibility and is suitable for the use as a tissue engineering alternative and other biomedical materials.
Description
Technical field
The present invention relates to a kind of conjugation polyunsaturated fatty acid polymkeric substance, Preparation Method And The Use.
Background technology
Tissue injury, the damaged dysfunction that causes are present common diseases.These diseases patient needs usually by surgical operation, promptly by autograft or xenotransplantation disease damage tissue or organ is repaired or is replaced.The organizational project surrogate plays an increasingly important role.These materials must compound some requirement.The most important thing is that wherein they must have biocompatibility.After biocompatible materials was implanted sick damage position, its mark sheet can not cause that now body produces untoward reaction, as: inflammatory reaction, blood aggegation etc.For avoiding or reduce these untoward reactions, people have proposed many schemes, comprise with drug treating material surfaces such as somatomedins such as bone morphogenetic protein or heparin etc.The most attractive thinking is by the coating at organizational project surrogate surface applied one deck good biocompatibility, then the normal cell in body source is transplanted to coatingsurface, forms a cellular layer.When this mixture being implanted sick damage position again,, make graft show good biocompatibility owing between material and body, have the cellular layer in body self source.Based on the conjugation polyunsaturated fatty acid, as conjugated linolic acid, conjugation docosahexenoic acid and conjugation timnodonic acid etc. all are essential fatty acids, has good biocompatibility, we develop novel conjugation polyunsaturated fatty acid polymkeric substance, and this polymkeric substance has excellent biological compatibility to normal cell.Therefore, this conjugation polyunsaturated fatty acid polymkeric substance has a good application prospect in field of tissue engineering technology as bio-medical material.
Summary of the invention
The problem to be solved in the present invention provides a kind of new conjugation polyunsaturated fatty acid polymkeric substance.
Another problem that the present invention will solve provides the synthetic method of above-mentioned conjugation polyunsaturated fatty acid polymkeric substance.
The problem that the present invention also will solve provides the purposes of above-mentioned conjugation polyunsaturated fatty acid polymkeric substance.
Conjugation polyunsaturated fatty acid polymkeric substance provided by the invention is to be the polymkeric substance that principal monomer forms with conjugation polyunsaturated fatty acid or derivatives thereof, comprises that with one or more conjugation polyunsaturated fatty acid or derivatives thereofs be the conjugation polyunsaturated fatty acid polymkeric substance that monomer forms.Mol ratio in the monomer component of conjugation polyunsaturated fatty acid polymkeric substance of the present invention between the different conjugation polyunsaturated fatty acid or derivatives thereofs is 1: 0～10.It is to have two or more pairs key, the wherein position conjugate of unsaturated double-bond in the carbochain that the monomeric constitutional features of described conjugation polyunsaturated fatty acid or derivatives thereof is recommended.Described conjugation polyunsaturated fatty acid is recommended conjugation docosahexenoic acid (CDHA), conjugation timnodonic acid (CEPA), conjugation therapic acid (CPnA), conjugation punicic acid, conjugation octadecadienoic acid; Described derivative is recommended methyl esters, ethyl ester, glyceryl ester, sucrose ester, the glycol ester of above-mentioned conjugation polyunsaturated fatty acid; Especially recommend conjugation therapic acid and derivative thereof.The film like product (Fig. 1) that conjugation polyunsaturated fatty acid polymkeric substance recommendation of the present invention is made up of grain pattern.Conjugation polyunsaturated fatty acid polymkeric substance of the present invention has excellent biological compatibility.
The diffuse reflectance infrared spectroscopy of the polymkeric substance that the present invention recommends is: the characteristic absorbance (999cm of conjugation carbon-to-carbon double bond
-1, 881cm
-1, 721cm
-1) minimizing until disappearance; Superoxide absorption peak (3000-3600cm
-1) enhancing.Proton nmr spectra shows that the characterization displacement study of conjugation alkene hydrogen reduces at the 5-7ppm place until disappearance; The characterization displacement study of cycloaliphatic ring hydrogen strengthens gradually at the 1.5-2ppm place; The characterization displacement study of hydroperoxy-strengthens gradually at the 3-4ppm place.Carbon-13 nmr spectra shows that the characterization displacement study of conjugation olefinic carbon reduces at the 130-134ppm place until disappearance; The characterization displacement study of cycloaliphatic ring carbon strengthens gradually at the 23-28ppm place; The characterization displacement study of peroxide carbon strengthens gradually at the 45-55ppm place.The characterization displacement study of cycloaliphatic ring hydrogen, carbon strengthens gradually, illustrates by the reaction molecular motion to be restricted, and has generated polymkeric substance.
The conjugation polyunsaturated fatty acid polymkeric substance that the present invention recommends be yellowish-brown membranaceous, sem observation is to the grainy texture of diameter 500 nanometers-20 micron.
Conjugation polyunsaturated fatty acid polymkeric substance of the present invention, it prepares with the following method:
1. used conjugation polyunsaturated fatty acid or derivatives thereof is recommended to fill nitrogen before use, is stored in shading, below-20 ℃.
2. one or more conjugation polyunsaturated fatty acid or derivatives thereofs are dissolved in the organic solvent, are coated in bio-medical material surfaces such as organizational project surrogate, treat that organic solvent volatilization back forms one deck conjugation polyunsaturated fatty acid or derivatives thereof film.Film thickness can be adjusted by conventional film-forming method.The monomeric concentration of conjugation polyunsaturated fatty acid or derivatives thereof of recommending during dissolving is 0.01mg/ml～100mg/ml; Described organic solvent is the soluble organic solvent of conjugation polyunsaturated fatty acid or derivatives thereof, comprises aliphatic hydrocarbon, aromatic hydrocarbon, halogenated hydrocarbon organic solvent, as ether, benzene, trichloromethane, sherwood oil, hexanaphthene etc., especially recommends to be dissolved in the chloroform; Film-forming method recommends to use the method for spin casting.The conjugation polyunsaturated fatty acid or derivatives thereof of recommending as previously mentioned, the mol ratio between the different conjugation polyunsaturated fatty acid or derivatives thereofs of recommendation is 1: 0～10.
3. the material that will coat conjugation polyunsaturated fatty acid or derivatives thereof film places thermostat container (10-90 ℃), makes its polymerization (1 hour-1 month), and temperature of reaction is high more, and the reaction times is short more.The degree that reaction is carried out is recommended and can be come trace and mensuration by infrared spectra and NMR (Nuclear Magnetic Resonance) spectrum.
4. finish polymeric material surface repopulating cell, cell category is decided on application purpose.Implanting needs to repair or alternate tissue or organ sites.
The used conjugation polyunsaturated fatty acid or derivatives thereof of the present invention is that one or more conjugation polyunsaturated fatty acid or derivatives thereofs are the mixture of the conjugation polyunsaturated fatty acid or derivatives thereof of 1: 0～10 mixed with mol ratio.The constitutional features of described conjugation polyunsaturated fatty acid or derivatives thereof molecule is to have two or more pairs key, the wherein position conjugate of unsaturated double-bond in the carbochain.
Isolating stem cell is good at polymer surfaces growing state of the present invention from the SD rat marrow, is better than the Corning Tissue Culture Plate.Can be considered as organizational project surrogate coated material.The polymeric film of the present invention's preparation and Tissue Culture Plate biocompatibility comparative result are as shown in Figure 5.
The present invention is based on conjugation polyunsaturated fatty acid or derivatives thereof monomer, under mild conditions, make it that solid polymerization reaction take place, obtain polymerisate.This method mild condition, method is easy, and the polymkeric substance cell compatibility that makes is good, is suitable as bio-medical material, especially as the new bio medical material of organizational project surrogate coating.
Description of drawings
Fig. 1: the present invention is the electron scanning micrograph of the conjugation stearidonic acid polymer of being made up of grain pattern of monomer preparation with the conjugation therapic acid, and particle size is 500 nanometers.
Fig. 2: the proton nmr spectra of conjugation stearidonic acid polymer.
Fig. 3: the carbon-13 nmr spectra of conjugation stearidonic acid polymer.
Fig. 4: the present invention is the electron scanning micrograph of the conjugation stearidonic acid polymer of being made up of grain pattern of monomer preparation with conjugation therapic acid methyl esters, and particle size is 20 microns.
Fig. 5: (solid line) reaches the infrared spectra at solid-state polymerization 15 days (dotted line) before the reaction of conjugation therapic acid methyl esters.
Fig. 6: the conjugation stearidonic acid polymer (CPNAPM) of the present invention's preparation compares (the SD rat marrow stem cell population of cultivating after 2 days-NUMBER OF the MSCs cultured on different materials after 2 days) with the biocompatibility of Corning Tissue Culture Plate (PLASTIC) on differing materials.
Fig. 7: the present invention is the electron scanning micrograph of the conjugation stearidonic acid polymer of being made up of grain pattern of monomer preparation with conjugation therapic acid and conjugation therapic acid methyl esters (1: 1) mixture, and particle size is 8 microns.
Embodiment
To help to understand the present invention by following embodiment, but not limit content of the present invention.
Embodiment 1: pure conjugation polyunsaturated fatty acid
1. the conjugation therapic acid is dissolved in (0.01mg/ml) in the chloroform, gets in right amount with dropper, drops on the slide glass, makes film.
2. place 10 ℃ of thermostat container polymerizations 1 month.The electron scanning micrograph of polymkeric substance as shown in Figure 1, proton nmr spectra as shown in Figure 2, carbon-13 nmr spectra is as shown in Figure 3.
Embodiment 2: pure conjugation polyunsaturated fatty acid derivative
1. conjugation therapic acid methyl esters is dissolved in (20mg/ml) in the chloroform, gets in right amount with dropper, drops on the slide glass, makes film.
2. place 45 ℃ of thermostat container polymerizations 15 days.The electron scanning micrograph of polymkeric substance as shown in Figure 4, infrared spectra is (solid line: before the polymerization as shown in Figure 5; Dotted line: after the polymerization).
3. isolate stem cell from the SD rat marrow, place nutrient solution to cultivate 1-7 days, make cell proliferation, culture transferring is cultivated counting after 2 days, result such as Fig. 6 to conjugation therapic acid polymer surfaces then.
Embodiment 3: the mixture of conjugation polyunsaturated fatty acid or derivatives thereof
1. conjugation therapic acid and conjugation therapic acid methyl esters are dissolved in (final concentration is respectively 5mg/ml) in the chloroform with 1: 1 ratio, get in right amount with dropper, drop on the slide glass, make film.
2. place 90 ℃ of thermostat container polymerizations 1 hour.The electron scanning micrograph of polymkeric substance as shown in Figure 7.
Claims (8)
1. conjugation polyunsaturated fatty acid polymkeric substance, it is characterized in that with following method synthetic, conjugation polyunsaturated fatty acid or derivatives thereof be monomer component, conjugation polyunsaturated fatty acid polymkeric substance with excellent biological compatibility:
1) the monomeric mixture of one or more conjugation polyunsaturated fatty acid or derivatives thereofs of 0.01mg/ml～100mg/ml is dissolved in the organic solvent, is coated in the bio-medical material surface;
2) make it form film at material surface equably with conventional film-forming method, and allow organic solvent volatilize naturally;
3) material is placed 10-90 ℃ of thermostat container polymerization, polymerization time 1 hour to 1 month.
2. conjugation polyunsaturated fatty acid polymkeric substance as claimed in claim 1, it is characterized in that with one or more conjugation polyunsaturated fatty acid or derivatives thereofs be monomeric conjugation polyunsaturated fatty acid polymkeric substance, described conjugated polyunsaturated fatty acid is meant conjugation docosahexenoic acid, conjugation timnodonic acid, conjugation therapic acid, conjugation punicic acid, conjugation octadecadienoic acid; Described derivative comprises methyl esters, ethyl ester, glyceryl ester, sucrose ester, the glycol ester of above-mentioned conjugation polyunsaturated fatty acid.
3. as claim 1 and 2 described conjugation polyunsaturated fatty acid polymkeric substance, it is characterized in that the mol ratio between the used different conjugation polyunsaturated fatty acid or derivatives thereof monomers is 1: 0～10 in the preparation process.
4. as claim 1 and 2 described conjugation polyunsaturated fatty acid polymkeric substance, it is characterized in that having following spectral signature: compare the characteristic absorbance 999cm of conjugation carbon-carbon double bond in the infrared spectra with monomer
-1, 881cm
-1, 721cm
-1The place reduces until disappearance, superoxide absorption peak 3000-3600cm
-1The place strengthens; Conjugation alkene hydrogen reduces until disappearance at 5-7ppm place peak height in the proton nmr spectra, and cycloaliphatic ring hydrogen strengthens gradually at 1.5-2ppm place peak height, and the characterization displacement study of hydroperoxy-strengthens gradually at the 3-4ppm place; The characterization displacement study of conjugation olefinic carbon reduces until disappearance at the 130-134ppm place in the nucleus magnetic resonance, and the characterization displacement study of cycloaliphatic ring carbon strengthens gradually at the 23-28ppm place, and the characterization displacement study of peroxide carbon strengthens gradually at the 45-55ppm place.
5. as claim 1 and 2 described conjugation polyunsaturated fatty acid polymkeric substance, it is characterized in that for yellowish-brown membranaceous, sem observation is to the grainy texture of diameter 500 nanometers to 20 micron.
6. the preparation method of conjugation polyunsaturated fatty acid polymkeric substance as claimed in claim 1 is characterized in that following these steps to successively carry out:
A) one or more conjugation polyunsaturated fatty acid or derivatives thereof monomers with 0.01mg/ml to 100mg/ml are dissolved in the organic solvent, are coated in the bio-medical material surface;
B) make it form film at material surface equably with conventional film-forming method, and allow organic solvent volatilize naturally;
C) material is placed 10-90 ℃ of thermostat container polymerization, polymerization time 1 hour to 1 month.
7. the purposes of conjugation polyunsaturated fatty acid polymkeric substance as claimed in claim 1 is characterized in that as bio-medical material.
8. the purposes of conjugation polyunsaturated fatty acid polymkeric substance as claimed in claim 7 is characterized in that the coated material as the organizational project surrogate.
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| CN1925881A (en) * | 2004-02-28 | 2007-03-07 | 汉莫堤克科技公司 | Biocompatible coating, method, and use of medical surfaces |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1925881A (en) * | 2004-02-28 | 2007-03-07 | 汉莫堤克科技公司 | Biocompatible coating, method, and use of medical surfaces |
Non-Patent Citations (1)
| Title |
|---|
| 《廊坊师范学院学报》 20021231 周秋香等 《多不饱和脂肪酸(PUFAs)的生物合成与功能》 60-62 1-8 第18卷, 第4期 * |
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Application publication date: 20111012 |