CN101173040A

CN101173040A - High-performance biological degradation polyalcohol based on alpha-L-proline

Info

Publication number: CN101173040A
Application number: CNA2007100184452A
Authority: CN
Inventors: 张为鹏
Original assignee: Individual
Current assignee: Individual
Priority date: 2007-08-09
Filing date: 2007-08-09
Publication date: 2008-05-07
Anticipated expiration: 2027-08-09
Also published as: CN100582142C

Abstract

The invention relates to a biodegradation polymer with good allround properties on the basis of alpha-L-proline. The material uses the alpha-L-proline and one or a plurality of omega-amino acids, or the lactam of the omega-amino acid as raw materials, and does or does not contain other raw materials; wherein, the mole ratio of the alpha-L-proline in the raw materials is 8 to 60 percent. The material has better mechanical property, and the material, the raw materials and a degradation product have small toxicity and can have biodegradation. The material is not only expected to be used as a biology medical material, like the bracket material of a tissue project, the releasing material of medicine or gene, suture, artificial skin, etc., but also can be used as packing material of food and other things, moreover, can be used as biodegradation hot-melt adhesive.

Description

High-performance biological degradation polyalcohol based on alpha-L-proline

Invention field

The present invention relates to a class high-performance biological degradation macromolecular material.Such novel material has mechanical property (existing higher intensity has snappiness preferably again) preferably, and starting material, degraded product are for forming amino acid and the very little omega-amino acid of toxicity of organism.This material both had been expected to as bio-medical material, as tissue engineering bracket material, medicine or gene sustained-release and controlled release material, suture line, artificial skin etc., can be used for the wrapping material of food and other article again, and can be used as the use of biological degradation hot melt adhesive.

Background technology

Tissue engineering bracket material is one of gordian technique of organizational project.Timbering material provides the three-dimensional space of cell growth, differentiation and breeding.Yet present employed biodegradable polymer timbering material all has it to be difficult to overcome point really, poly(lactic acid), polyglycolic acid and copolymer degradation product thereof are acid preferably as synthetic class mechanical property, easily cause the non-bacterial infection of human body, while poly(lactic acid), polyglycolic acid and multipolymer thereof are hydrophobic, are unfavorable for cell attachment, differentiation.The collagen protein of natural tissues class, chitosan and derivative thereof be poor mechanical property then, and may produce antigen-reactive.Not only had excellent biological compatibility, but also biodegradable polymer timbering material with excellent mechanical property still global problem at present.

Material of the present invention has mechanical property (existing higher intensity has snappiness and plasticity preferably again) preferably, and this material, starting material and degraded product toxicity are very little simultaneously, and good hydrophilic property, are beneficial to cell attachment.Overcome above-mentioned two class materials point really to a certain extent.

At packaging field, eco-friendly biological degradation packaging material also is the urgent problems that solve of needs.With natural polymers such as starch is that the biological degradation cost of base is low, but mechanical property and manufacturability are poor; Synthetic macromolecule mechanical properties such as poly(lactic acid) are better, but degraded is very fast in aqueous environment or wet environment, are difficult for storing.

Enzymolysis mainly takes place in material of the present invention, and hydrolysis rate is very slow.Both can overcome the shortcoming of natural polymer poor mechanical property, can overcome the too fast shortcoming of degraded under moisture or wet environment again.

The biological degradation hot melt adhesive of environmental protection also is the urgent problems that solve of needs.The hot melt adhesive overwhelming majority in the market is non-degradation polymer, and environment is caused more and more serious pollution.The biological degradation hot melt adhesive of natural polymer subclass is intensity difference then.

Material of the present invention also can be used as the biological degradation hot melt adhesive and uses.Have the intensity height, adhesive power is strong, and biodegradable advantage.

Summary of the invention

α-L-amino acid is the fundamental unit of constitutive protein matter.Big quantity research proves that no matter be polyamino acid, still an amount of α-L-amino acid is introduced other hydrolyzable or non-degradation polymer, resulting multipolymer all is biodegradable, and enzymolysis plays a major role.Then can not enzymolysis by the amino acids formed polymkeric substance of α-D-.By the polymer that α-L-amino acid generates, degraded product is a basic amino acid of forming life entity, thereby has that toxicity is little, the advantage of good biocompatibility, in addition can by human body as nutritive ingredient absorb, metabolism.This class material both can be used for medical field, as tissue engineering bracket material, medicine and gene controlled release carrier material, also can be used as environment-friendly material and was used for packaging field.

Yet simple polyamino acid but has following shortcoming: 1, thermally labile.Decomposition temperature is lower than temperature of fusion, is difficult to carry out processing treatment; 2, starting material and product are insoluble to great majority organic solvent commonly used, generally need deleterious phosgene, two phosgene or triphosgene, generate the N-carbonylamino acid anhydrides to the moisture sensitivity, are considered to be difficult to large-scale production.3, the peptide chain of the generation of the different aminoacids more than three has immunogenicity.Therefore, except that water-soluble polyglutamic acid, poly aspartic acid, polylysine and derivative thereof, other polyamino acid as biomaterial research seldom.

With α-L-amino acid and other material copolymerization.Its various aspects of performance can greatly be improved.With alcohol acid or diacid and glycol or hydramine generation polyesteramide; With omega-amino acid or diacid and diamines generation copolyamide.Consider that from the angle of biocompatibility degraded product alcohol acid or diacid all show acidity, and the possibility that causes non-bacterial infection is arranged; And omega-amino acid structure and α-the L-amino acids seemingly, and usually demonstrate the physiological action useful to organism, for example, the 4-aminobutyric acid can be used for slow and oligophrenia of hemiplegia, dysmnesia, aphasis, children ' s intelligence development that hepatic coma and cerebrovascular disorder cause etc., also can resist spirit uneasy, hypertension is also had the improvement effect.6-aminocaprolc acid can be used as haemostatic medicament and orally uses.Therefore, α-L-amino acid and omega-amino acid generate copolyamide and should have more promising application prospect.

Author of the present invention has synthesized the multipolymer of multiple α-L-amino acid, glycine and omega-amino acid, wherein the multipolymer excellent combination property of alpha-L-proline and omega-amino acid.Have following characteristics:

1. mechanical property is better.For example, when alpha-L-proline: when the 6-aminocaprolc acid mol ratio was 12%, tensile strength was about 40MPa (optimize polymerizing condition, intensity also has the leeway of improving), is better than the most biodegradated polymer materals in present bibliographical information; Elongation at break is 60%, and illustrative material has snappiness preferably.

2. material belongs to biodegradable material.According to document, the linear or cyclic oligomer that contains 8 or following 6-aminocaprolc acid can be by bacterium as the nutritive ingredient utilization.And molecular weight is low more, utilizes degree high more.Theoretically, when alpha-L-proline: the 6-aminocaprolc acid mol ratio is during greater than 1: 8, and material can be degraded in physical environment substantially fully.

3. starting material and degraded product are amino acid nontoxic or that toxicity is very little, and biocompatibility is better.Thereby be expected to as bio-medical material, as tissue engineering bracket material, medicine or gene sustained-release and controlled release material, suture line, artificial skin etc., can be used for the wrapping material of food and other article again, also can be used as the biological degradation hot melt adhesive and use.Cell toxicity test and animal experiment well afoot.

Macromolecular material of the present invention is with alpha-L-proline and one or more omega-amino acid, and perhaps the lactan of omega-amino acid is starting material, contains or do not contain other starting material; Wherein the mol ratio of alpha-L-proline in starting material is 8-60%, and preferential mol ratio is 12-50%; The lactan carbon atom number of omega-amino acid or omega-amino acid is 3-18, is preferably 6-12; Material is a random copolymers, or adopts suitable synthesis technique, makes alternating copolymer, segmented copolymer or graft copolymer; The synthetic energy that adopts is the various energy such as heat, microwave, light, electricity, ultrasonic wave, infrasound, nuclear.

Embodiment

Embodiment 1

Weighing 23 gram alpha-L-prolines, 235.8 gram 6-aminocaprolc acids mix (mol ratio 10: 90), under the nitrogen protection, place 500 ml flasks, in 250 ℃ of heating 1 hour, are to heat 3 hours under 13 handkerchiefs in 250 ℃ of vacuum tightnesss then.Stopped reaction, synthetic material melting point are 200 ℃, and tensile strength is 42.9MPa, and elongation at break is that 63%, 4 all enzymolysis rate of weight loss are 2.4%.

Embodiment 2

Weighing 46 gram alpha-L-prolines, 78.6 gram 6-aminocaprolc acids mixed (mol ratio 40: 60), place 250 ml flasks, in microwave oven 800W reaction 0.5 hour.Stopped reaction, synthetic material unformed shape, tensile strength is 7.8MPa, elongation at break is that 20%, 4 all enzymolysis rate of weight loss are 15.1%.

Embodiment 3

Weighing 69 gram alpha-L-prolines, 203 gram 6-aminocaprolc acids mix (mol ratio 30: 70), under the nitrogen protection, place 500 ml flasks, in 230 ℃ of heating 2 hours, are to heat 2 hours under 13 handkerchiefs in 250 ℃ of vacuum tightnesss then.Stopped reaction, synthetic material are unformed shape, and tensile strength is 13.0MPa, and elongation at break is that 48.5%, 4 all enzymolysis rate of weight loss are 10.2%.

Test method:

Fusing point uses the DSC method.

Mechanical property employing method is the test of GB/T1040-2006 plastic tensile performance, trial speed 50mm/min.

The enzymolysis test method: polymkeric substance is dissolved in formic acid, and cast is got each sample and is nearly weighed 0.05g into about the film of 0.1mm.After the drying, soak 72h in 50 ℃ of distilled water, remove solvable composition, vacuum-drying is to constant weight.

The 0.05M phosphate buffer solution of configuration PH6.0, the EDTA that adds 0.038M, 0.034M halfcystine activate, the sodium azide of adding 0.02% suppresses microorganism, papoid (Papain, 30000USP-U/mg for biochemistry EC3.4.22.2, Merck, German) concentration is 0.01%, is mixed with enzyme liquid.Sample is placed enzyme liquid, and temperature is 37 ℃, changes enzyme solution weekly one time, and vacuum-drying is to constant weight.Calculate rate of weight loss.Test-results is 5 sample means.

Claims

1. a family macromolecule material.This material is with alpha-L-proline and one or more omega-amino acid, and perhaps the lactan of omega-amino acid is starting material, contains or do not contain other starting material; Wherein the mol ratio of alpha-L-proline in starting material is 8-60%;

2. according to claim 1, described macromolecular material is a random copolymers; Or adopt suitable synthesis technique, make alternating copolymer, segmented copolymer or graft copolymer;

3. according to claim 1, the lactan carbon atom number of described omega-amino acid or omega-amino acid is 3-18;

4. according to claim 1, the synthetic energy that adopts of such material is the various energy such as heat, microwave, light, electricity, ultrasonic wave, infrasound, nuclear.