CN1207324C - Biodegradable polyglycol-poly (lactamine-alkyl acetic acid) and its preparation method - Google Patents
Biodegradable polyglycol-poly (lactamine-alkyl acetic acid) and its preparation method Download PDFInfo
- Publication number
- CN1207324C CN1207324C CN 02138548 CN02138548A CN1207324C CN 1207324 C CN1207324 C CN 1207324C CN 02138548 CN02138548 CN 02138548 CN 02138548 A CN02138548 A CN 02138548A CN 1207324 C CN1207324 C CN 1207324C
- Authority
- CN
- China
- Prior art keywords
- polyethylene glycol
- polymers
- ala
- alkyl acetate
- diketone
- 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
Images
Landscapes
- Polyethers (AREA)
Abstract
The present invention discloses biologically decomposable type polyglycol-poly (lactamine-alkyl acetic acid). The preparation method of the biologically decomposable type polyglycol-poly (lactamine-alkyl acetic acid) comprises: adding 3-methyl-morpholine-2, 5-diketone and polyethylene glycol in the molar ratio of 10 to 500 to polyethylene glycol and 3-methyl-morpholine-2, 5-diketone which are processed by amido through end capping; processing the mixture through high temperature reaction under a vacuum condition or under the protection of inert gas, and then cooling the processed mixture until the temperature thereof is cooled to indoor temperature to obtain a yellowish coarse product; purifying the yellowish coarse product to obtain a purified white polymer. The present invention has the advantages that the polyethylene glycol processed by the amido through the end capping can be used for initiating the ring-opening polymerization of ring-shaped lactone to obtain a high polymer. Polymers with different intensity and degradation properties can be obtained through regulating polymerization proportion to meet application requirements, and the polymers have complete biocompatibility. Any initiator containing metal is not used in the process of polymerization so that the polymers do not have potential toxicity. Compared with single polyethylene glycol, the degradation speed of the polymers is obviously improved. The aqueous solubility of the polymers is greatly improved.
Description
One, technical field
The present invention relates to gather (L-Ala-alkyl acetate)-polyethylene glycol-(L-Ala-alkyl acetate) triblock copolymer and preparation method thereof.This material has good biocompatibility and degradation property, can be used as biodegradable medical material.
Two, background technology
That polyoxyethylene glycol (PEG) has is nontoxic, non-immunogenicity, good blood compatibility, fabulous wetting ability and be widely used in pharmacy and the bio-medical material.
The amino acid derivative of synthetic is owing to have some special nature, such as chirality, the polypeptide chain secondary structure: as α-Luo Xuanjiegou and βZhe Die sheet etc., and and cell, tissue and other biological composition show good consistency.Various functional groups can easier be incorporated on many naturally occurring amino acid.In addition, polyamino acid derivative also has biodegradability, and the hydrophilic and hydrophobic of control side-chain radical can change degradation speed.By block copolymerization with the be connected together segmented copolymer of formation of hydrophobic poly-(L-Ala-alkyl acetate) and hydrophilic polyglycol chain, not only have both advantages concurrently, and have close and distant water micro phase separation structure, so synthetic segmented copolymer of the present invention has a good application prospect as sustained-release and controlled release pharmaceutical carrier and degradable biological medical material.
General polyester uses metallic initiator to come initiated polymerization, might in product, leave over the material of biocompatible, this paper uses the active end group initiated polymerization of amino-terminated polyoxyethylene glycol, does not use metal initiator, and product has biocompatibility completely.
Three, summary of the invention
1, goal of the invention: the purpose of this invention is to provide triblock copolymer of a kind of biodegradation type polyamino acid-polyether-polyamino acid and preparation method thereof.
2, technical scheme: for achieving the above object, biodegradation type polyethylene glycol-of the present invention (L-Ala-alkyl acetate) is characterized in that the molecular formula of this biodegradation type polyethylene glycol-(L-Ala-alkyl acetate) is:
In the formula: two m and scope be 10-500, the scope of n is 10-250.
The method for making of described biodegradation type polyethylene glycol-(L-Ala-alkyl acetate); it is characterized in that its method for making is: in an encloses container; add amino-terminated polyoxyethylene glycol and 3-methyl-morpholine-2; the 5-diketone; both mol ratios are 10-500, under vacuum condition or protection of inert gas, carry out pyroreaction; cool to room temperature obtains little yellow crude product then.The molecular weight of wherein amino-terminated polyoxyethylene glycol is 400～5000; The temperature of pyroreaction is 100 ~ 200 ℃, and the time of reaction is 1-72 hour; Little yellow crude product can obtain purified white polymer by purifying.
The reaction formula of said process is:
Amino-terminated polyoxyethylene glycol (Jeffamine) 3-methylmorpholine-2, the 5-diketone
Poly-(L-Ala-alkyl acetate)-polyethylene glycol-(L-Ala-alkyl acetate)
Wherein: m represents to gather the number of (L-Ala-alkyl acetate) segment in the polymkeric substance the inside, and scope: 10-500 has two m in the formula, and these two m sizes are near equating, but neither be definitely the same, and scope noted here be both and.N is the number of the segment of polyoxyethylene glycol in the polymkeric substance the inside, and scope is: 10-250
The molecular-weight average of polymkeric substance draws according to the proton magnetic resonance (PMR) data computation,
Method of calculation are as follows:
Wherein: Hpeg is the proton sum on the methylene radical in the peg molecule.
B is the bimodal integral area in 1.34ppm place.
A is the unimodal integral area at 3.50ppm place.
The 129th, 3-methyl-morpholine-2, the molecular weight of a repeating unit of 5-diketone.
Mpeg is the molecular weight of polyoxyethylene glycol.
| Feed ratio (amino-terminated polyoxyethylene glycol (molecular weight 600)/3-methyl-morpholine-2,5-diketone) | Molecular-weight average |
| 1/90 | ?12000 |
| 1/120 | ?16100 |
| 1/150 | ?19300 |
| 1/200 | ?21200 |
| 1/400 | ?40000 |
3, beneficial effect: the present invention compared with prior art, its remarkable advantage is: (1) amino-terminated polyoxyethylene glycol can cause the ring-opening polymerization of annular lactone, obtains superpolymer.(2) by adjusting polymerization ratio, the polymkeric substance of varying strength and degradation property can be obtained, the application requiring of aspects such as timbering material can be satisfied such as organizational project.(3) polymkeric substance has biocompatibility completely.(3) do not use any containing metal initiator in the polymerization process, product does not have potential toxicity.(4) because of the introducing of amino acid segment, the degradation speed of polymkeric substance is obviously accelerated than simple polyoxyethylene glycol.(5) because the hydrophilic polyglycol segmental is introduced, the water-soluble of polymkeric substance is greatly improved.
Four, description of drawings
Fig. 1 is the typical infrared spectrogram of polymkeric substance.1754cm
-1The typical ester bond stretching vibration peak and the 1655cm at wave number place
-1, 1547cm
-1The acid amides characteristic peak at place has confirmed to contain in the multipolymer 3-methyl-morpholine-2,5-diketone structure unit.
Fig. 2 is the typical proton NMR spectrum figure of polymkeric substance, solvent DMSO, 8.44 the peak at～8.48ppm place, 4.48 the peak at～4.63ppm place, 4.37 the bimodal of the peak at～4.42ppm place and 1.34ppm place is respectively a in the molecular formula, b, c, the characteristic peak of d place proton, the unimodal of 3.50ppm place is the methylene radical characteristic peak of polyoxyethylene glycol.
Five, embodiment
Embodiment 1: with 3.0 gram 3-methyl-morpholine-2s, 5-diketone and the amino-terminated polyoxyethylene glycol (molecular weight 600) of 0.23 gram are put into Glass tubing, vacuumize half hour, tube sealing under vacuum state, 160 ℃ of reactions 1 hour, cool to room temperature obtains little yellow transparent solid, with dimethyl sulfoxide (DMSO) (DMSO) dissolving, join then in a large amount of methanol solutions, filter, obtain white polymer, molecular weight 12000.
Embodiment 2: with 4.5 gram 3-methyl-morpholine-2s, 5-diketone and the amino-terminated polyoxyethylene glycol (molecular weight 400) of 0.15 gram are put into Glass tubing, vacuumize half hour, tube sealing under vacuum state, 140 ℃ of reactions 5 hours, cool to room temperature obtains little yellow transparent solid, with dimethyl sulfoxide (DMSO) (DMSO) dissolving, join then in a large amount of methanol solutions, filter, obtain white precipitate, molecular weight 14000.
Embodiment 3: with 1.0 gram 3-methyl-morpholine-2s, 5-diketone and the amino-terminated polyoxyethylene glycol (molecular weight 2000) of 0.16 gram are put into Glass tubing, vacuumize half hour, tube sealing under vacuum state, 140～145 ℃ of reactions 20 hours, cool to room temperature obtains little yellow transparent solid, with dimethyl sulfoxide (DMSO) (DMSO) dissolving, join then in a large amount of methanol solutions, filter, obtain white polymer, molecular weight 18000.
Embodiment 4: with 1.0 gram 3-methyl-morpholine-2s, 5-diketone and the amino-terminated polyoxyethylene glycol (molecular weight 3000) of 0.15 gram are put into Glass tubing, vacuumize half hour, tube sealing under vacuum state, 155 ℃ of reactions 10 hours, cool to room temperature obtains little yellow transparent solid, with dimethyl sulfoxide (DMSO) (DMSO) dissolving, join then in a large amount of methanol solutions, filter, obtain white polymer, molecular weight 26200.
Embodiment 5: with 1.0 gram 3-methyl-morpholine-2s, 5-diketone and the amino-terminated polyoxyethylene glycol (molecular weight 5000) of 0.77 gram are put into Glass tubing, vacuumize half hour, tube sealing under vacuum state, 170 ℃ of reactions 5 hours, cool to room temperature obtains little yellow transparent solid, with dimethyl sulfoxide (DMSO) (DMSO) dissolving, join then in a large amount of methanol solutions, filter, obtain white polymer, molecular weight 14000.
Embodiment 6: with 6.0 gram 3-methyl-morpholine-2s, 5-diketone and the amino-terminated polyoxyethylene glycol (molecular weight 600) of 0.23 gram are put into Glass tubing, vacuumize half hour, fill argon gas or nitrogen and tube sealing, 160 ℃ of reactions 9 hours, cool to room temperature obtains little yellow transparent solid, with dimethyl sulfoxide (DMSO) (DMSO) dissolving, join then in a large amount of methanol solutions, filter, obtain white polymer, molecular weight 19300.
Claims (5)
1, a kind of biodegradation type polyethylene glycol-(L-Ala-alkyl acetate) is characterized in that the molecular formula of this biodegradation type polyethylene glycol-(L-Ala-alkyl acetate) is:
In the formula: the scope of two m sums is 10-500, and the scope of n is 10-250.
2, a kind of method of producing biodegradation type polyethylene glycol-as claimed in claim 1 (L-Ala-alkyl acetate); it is characterized in that its method for making is: in an encloses container; add amino-terminated polyoxyethylene glycol; with 3-methyl-morpholine-2,5-diketone, both mol ratios are 10-500; under vacuum condition or protection of inert gas; pyroreaction 1-72 hour, cool to room temperature obtained little yellow crude product then.
3, the method for making of biodegradation type polyethylene glycol-according to claim 2 (L-Ala-alkyl acetate) is characterized in that the molecular weight of described amino-terminated polyoxyethylene glycol is 400-5000.
4, the method for making of biodegradation type polyethylene glycol-according to claim 2 (L-Ala-alkyl acetate), the temperature that it is characterized in that described pyroreaction is 100-200 ℃, the time of reaction is 1-72 hour.
5, the method for making of biodegradation type polyethylene glycol-according to claim 2 (L-Ala-alkyl acetate) is characterized in that described little yellow crude product by purifying, obtains purified white polymer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02138548 CN1207324C (en) | 2002-11-07 | 2002-11-07 | Biodegradable polyglycol-poly (lactamine-alkyl acetic acid) and its preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02138548 CN1207324C (en) | 2002-11-07 | 2002-11-07 | Biodegradable polyglycol-poly (lactamine-alkyl acetic acid) and its preparation method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1405203A CN1405203A (en) | 2003-03-26 |
| CN1207324C true CN1207324C (en) | 2005-06-22 |
Family
ID=4749556
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 02138548 Expired - Fee Related CN1207324C (en) | 2002-11-07 | 2002-11-07 | Biodegradable polyglycol-poly (lactamine-alkyl acetic acid) and its preparation method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1207324C (en) |
-
2002
- 2002-11-07 CN CN 02138548 patent/CN1207324C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1405203A (en) | 2003-03-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0822217B1 (en) | Heterotelechelic block copolymers and process for producing the same | |
| KR960015447B1 (en) | Biodegradable polymer | |
| CA2419673C (en) | Polymeric networks | |
| KR0141431B1 (en) | Biodegradable hydrogel copolymer | |
| Aoi et al. | Glycopeptide Synthesis by an. alpha.-Amino Acid N-Carboxyanhydride (NCA) Method: Ring-Opening Polymerization of a Sugar-Substituted NCA | |
| CN105968367B (en) | A kind of amphipathic Polypeptide copolymer, self-assembly and preparation method and application | |
| Wu et al. | Comb-like poly (L-cysteine) derivatives with different side groups: synthesis via photochemistry and click chemistry, multi-responsive nanostructures, triggered drug release and cytotoxicity | |
| CN111019126A (en) | Polyester amide and preparation method thereof | |
| CN104558504A (en) | Preparation method of polylactic acid and polyethylene glycol copolymer | |
| CN1207324C (en) | Biodegradable polyglycol-poly (lactamine-alkyl acetic acid) and its preparation method | |
| CN1243042C (en) | Copolymer grafted by polyvinyl alcohol/poly paraoxide cyclohexanone and preparation method | |
| CN108530642B (en) | Biodegradable triblock hetero-arm star-shaped amphiphilic polymer material and preparation method thereof | |
| EP1641471A1 (en) | Biocompatible polymer networks | |
| CN101906210B (en) | Method for synthesizing polypeptide in presence of ammonia-base rare earth catalyst | |
| Ouhib et al. | Synthesis of new statistical and block co-polyesters by ROP of α, α, β-trisubstituted β-lactones and their characterizations | |
| CN111892703B (en) | Biodegradable thermoplastic polyester elastic material and preparation method thereof | |
| CN109880110B (en) | Poly (2-vinylpyridine) -containing polypeptide block copolymer and preparation method and application thereof | |
| CN1418901A (en) | Carboxy polylactic acid contained composition and preparation process thereof | |
| KR20140094932A (en) | Biomaterials containing contrast agent for tracing polymer in vivo and method for preparing the same | |
| Barakat et al. | Polymerization of glycolide promoted by ω‐Al‐alkoxide poly (ϵ‐caprolactone) macro‐initiators and formation of stable colloidal dispersions | |
| CN101899146B (en) | Hydroxyl telechelic polyester material based on piperazine block and preparation method thereof | |
| Li et al. | Lipase-catalyzed ring-opening copolymerization of macrocycles for diselenide-functionalized long-chain polycarbonate: Synthesis, kinetic process and ROS responsiveness | |
| CN1175601A (en) | Method for ring-opening polymerization of lactone by catalysis of rare-earth compound | |
| Studer et al. | Amino end-functionalized poly (ethylene oxide)-block-poly (methylidene malonate 2.1. 2) block copolymers: synthesis, characterization, and chemical modification for targeting purposes | |
| CN113980257B (en) | Crown ether lactone polymer and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20050622 Termination date: 20151107 |
|
| EXPY | Termination of patent right or utility model |