CA2324279A1 - Biodegradable polymers based on natural and renewable raw materials, especially isosorbite - Google Patents
Biodegradable polymers based on natural and renewable raw materials, especially isosorbite Download PDFInfo
- Publication number
- CA2324279A1 CA2324279A1 CA002324279A CA2324279A CA2324279A1 CA 2324279 A1 CA2324279 A1 CA 2324279A1 CA 002324279 A CA002324279 A CA 002324279A CA 2324279 A CA2324279 A CA 2324279A CA 2324279 A1 CA2324279 A1 CA 2324279A1
- Authority
- CA
- Canada
- Prior art keywords
- biodegradable
- acid
- polycondensates
- organic carboxylic
- polycondensate
- 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.)
- Abandoned
Links
- 229920002988 biodegradable polymer Polymers 0.000 title description 9
- 239000004621 biodegradable polymer Substances 0.000 title description 9
- 239000002994 raw material Substances 0.000 title description 4
- 230000006870 function Effects 0.000 claims abstract description 14
- 150000001735 carboxylic acids Chemical class 0.000 claims abstract description 10
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims abstract description 8
- 238000004519 manufacturing process Methods 0.000 claims abstract 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 11
- 150000001732 carboxylic acid derivatives Chemical group 0.000 claims description 9
- 230000008569 process Effects 0.000 claims description 8
- 239000013543 active substance Substances 0.000 claims description 7
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- 239000007858 starting material Substances 0.000 claims description 6
- KKEYFWRCBNTPAC-UHFFFAOYSA-N Terephthalic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-N 0.000 claims description 4
- 239000000155 melt Substances 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- ZHGGHNZZJCJQSL-UHFFFAOYSA-N 2-[2-(2-ethoxyethoxy)ethoxymethyl]propanedioic acid Chemical compound CCOCCOCCOCC(C(O)=O)C(O)=O ZHGGHNZZJCJQSL-UHFFFAOYSA-N 0.000 claims description 3
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 3
- DNXDYHALMANNEJ-UHFFFAOYSA-N furan-2,3-dicarboxylic acid Chemical compound OC(=O)C=1C=COC=1C(O)=O DNXDYHALMANNEJ-UHFFFAOYSA-N 0.000 claims description 2
- 239000011159 matrix material Substances 0.000 claims description 2
- 239000011975 tartaric acid Substances 0.000 claims description 2
- 235000002906 tartaric acid Nutrition 0.000 claims description 2
- 239000000463 material Substances 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 8
- 229920000642 polymer Polymers 0.000 description 20
- 150000001875 compounds Chemical class 0.000 description 11
- 238000012360 testing method Methods 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 8
- 230000015556 catabolic process Effects 0.000 description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 238000006731 degradation reaction Methods 0.000 description 6
- 125000000524 functional group Chemical group 0.000 description 6
- 238000005227 gel permeation chromatography Methods 0.000 description 6
- 238000010348 incorporation Methods 0.000 description 6
- KLDXJTOLSGUMSJ-KVTDHHQDSA-N (3r,3ar,6r,6ar)-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3,6-diol Chemical compound O[C@@H]1CO[C@@H]2[C@H](O)CO[C@@H]21 KLDXJTOLSGUMSJ-KVTDHHQDSA-N 0.000 description 5
- KLDXJTOLSGUMSJ-JGWLITMVSA-N Isosorbide Chemical compound O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 KLDXJTOLSGUMSJ-JGWLITMVSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 238000006065 biodegradation reaction Methods 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- KLDXJTOLSGUMSJ-UHFFFAOYSA-N 2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3,6-diol Chemical compound OC1COC2C(O)COC21 KLDXJTOLSGUMSJ-UHFFFAOYSA-N 0.000 description 4
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 229960002479 isosorbide Drugs 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 239000004793 Polystyrene Substances 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 229910002092 carbon dioxide Inorganic materials 0.000 description 3
- 238000006116 polymerization reaction Methods 0.000 description 3
- 229920002223 polystyrene Polymers 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
- NGSWKAQJJWESNS-UHFFFAOYSA-N 4-coumaric acid Chemical compound OC(=O)C=CC1=CC=C(O)C=C1 NGSWKAQJJWESNS-UHFFFAOYSA-N 0.000 description 2
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- AYJRCSIUFZENHW-UHFFFAOYSA-L barium carbonate Chemical compound [Ba+2].[O-]C([O-])=O AYJRCSIUFZENHW-UHFFFAOYSA-L 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 239000007857 degradation product Substances 0.000 description 2
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 239000001630 malic acid Substances 0.000 description 2
- 235000011090 malic acid Nutrition 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 230000005226 mechanical processes and functions Effects 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000006068 polycondensation reaction Methods 0.000 description 2
- 229920000728 polyester Polymers 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 229960002920 sorbitol Drugs 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
- KLDXJTOLSGUMSJ-UNTFVMJOSA-N (3s,3ar,6s,6ar)-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3,6-diol Chemical compound O[C@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 KLDXJTOLSGUMSJ-UNTFVMJOSA-N 0.000 description 1
- 239000001124 (E)-prop-1-ene-1,2,3-tricarboxylic acid Substances 0.000 description 1
- FQWNGSKQHPNIQG-UHFFFAOYSA-N 3-[[bis(2-chloroethyl)amino-(2-chloroethoxy)phosphoryl]amino]propan-1-ol Chemical compound OCCCNP(=O)(OCCCl)N(CCCl)CCCl FQWNGSKQHPNIQG-UHFFFAOYSA-N 0.000 description 1
- ALYNCZNDIQEVRV-PZFLKRBQSA-N 4-amino-3,5-ditritiobenzoic acid Chemical compound [3H]c1cc(cc([3H])c1N)C(O)=O ALYNCZNDIQEVRV-PZFLKRBQSA-N 0.000 description 1
- SJZRECIVHVDYJC-UHFFFAOYSA-N 4-hydroxybutyric acid Chemical compound OCCCC(O)=O SJZRECIVHVDYJC-UHFFFAOYSA-N 0.000 description 1
- KAUQJMHLAFIZDU-UHFFFAOYSA-N 6-Hydroxy-2-naphthoic acid Chemical compound C1=C(O)C=CC2=CC(C(=O)O)=CC=C21 KAUQJMHLAFIZDU-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- ODBLHEXUDAPZAU-ZAFYKAAXSA-N D-threo-isocitric acid Chemical compound OC(=O)[C@H](O)[C@@H](C(O)=O)CC(O)=O ODBLHEXUDAPZAU-ZAFYKAAXSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- ODBLHEXUDAPZAU-FONMRSAGSA-N Isocitric acid Natural products OC(=O)[C@@H](O)[C@H](C(O)=O)CC(O)=O ODBLHEXUDAPZAU-FONMRSAGSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 229940091181 aconitic acid Drugs 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- PWAXUOGZOSVGBO-UHFFFAOYSA-N adipoyl chloride Chemical compound ClC(=O)CCCCC(Cl)=O PWAXUOGZOSVGBO-UHFFFAOYSA-N 0.000 description 1
- 239000003570 air Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001371 alpha-amino acids Chemical class 0.000 description 1
- 235000008206 alpha-amino acids Nutrition 0.000 description 1
- 150000001408 amides Chemical group 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
- WXBLLCUINBKULX-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1 WXBLLCUINBKULX-UHFFFAOYSA-N 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- GTZCVFVGUGFEME-IWQZZHSRSA-N cis-aconitic acid Chemical compound OC(=O)C\C(C(O)=O)=C\C(O)=O GTZCVFVGUGFEME-IWQZZHSRSA-N 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- 230000000249 desinfective effect Effects 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000003337 fertilizer Substances 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- BMBDJILYIZBBMQ-UHFFFAOYSA-N furan-2,3-dicarbonyl chloride Chemical compound ClC(=O)C=1C=COC=1C(Cl)=O BMBDJILYIZBBMQ-UHFFFAOYSA-N 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000009477 glass transition Effects 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 239000012510 hollow fiber Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000000266 injurious effect Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- -1 isosorbitol Chemical class 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229920006280 packaging film Polymers 0.000 description 1
- 239000012785 packaging film Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920001432 poly(L-lactide) Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 239000010865 sewage Substances 0.000 description 1
- 239000010802 sludge Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- LXEJRKJRKIFVNY-UHFFFAOYSA-N terephthaloyl chloride Chemical compound ClC(=O)C1=CC=C(C(Cl)=O)C=C1 LXEJRKJRKIFVNY-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- ODBLHEXUDAPZAU-UHFFFAOYSA-N threo-D-isocitric acid Natural products OC(=O)C(O)C(C(O)=O)CC(O)=O ODBLHEXUDAPZAU-UHFFFAOYSA-N 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- GTZCVFVGUGFEME-UHFFFAOYSA-N trans-aconitic acid Natural products OC(=O)CC(C(O)=O)=CC(O)=O GTZCVFVGUGFEME-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- C—CHEMISTRY; METALLURGY
- C05—FERTILISERS; MANUFACTURE THEREOF
- C05G—MIXTURES OF FERTILISERS COVERED INDIVIDUALLY BY DIFFERENT SUBCLASSES OF CLASS C05; MIXTURES OF ONE OR MORE FERTILISERS WITH MATERIALS NOT HAVING A SPECIFIC FERTILISING ACTIVITY, e.g. PESTICIDES, SOIL-CONDITIONERS, WETTING AGENTS; FERTILISERS CHARACTERISED BY THEIR FORM
- C05G5/00—Fertilisers characterised by their form
- C05G5/40—Fertilisers incorporated into a matrix
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/02—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds
- C08G63/60—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds derived from the reaction of a mixture of hydroxy carboxylic acids, polycarboxylic acids and polyhydroxy compounds
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Abstract
The invention relates to biodegradable polycondensates, to the production of said polycondensates, and to their use for releasing specific substances. The polycondensates are derived from at least three components chosen from the following group: a) dianhydrohexites b) bivalent (polyvalent) organic carboxylic acids and c) polyvalent organic carboxylic acids which, in addition to two carboxylic acid functions, have at least one other, optionally capped, i.e. OH and/or COOH function.
Description
Biodegradable polymers based on naturaNy occurring and renewable raw materials, in particular isosorbitol The invention relates to biodegradable polycondensates based on dianhydrohexitols, to their preparation, and also to their use.
Biodegradable polycondensates degrade within a certain period of time in a biological medium, losing their original mechanical, physical and chemical properties as a result of breakdown into small fragments, also termed metabolites when the application is in the physiological sector - in particular in humans. An example which may be quoted is a biodegradable surgical suture which initially has the strength to hold together a sutured wound but then in the course of time is degraded by the body. Of course, there must be an appropriate relationship here between the rate of degradation and the healing of the wound.
For the purposes of the present invention, biological media in which biodegradable polymers may be used are media which occur in the natural environment, for example water, air or soil, and also human or animal bodies, and the interior of plants. Biodegradable polymers are frequently used in forms which serve only a single purpose, for example surgical sutures which have solely the function of securing the wound for a particular time, or waste sacks or packaging films, which undergo biodegradation after use, the degradation products themselves not having any particular function.
However, it is also possible to admix active substances with the biodegradable polymers, or as early as during the synthesis of the polymers to give these a chemical form which allows the polymers themselves to develop other active functions besides any mechanical function which they have. For example, it is possible to produce surgical sutures which, besides their mechanical function, have a disinfecting action, for example, or develop a certain medicinal action. Waste sacks may comprise, for example, substances whose odor repels dogs and cats.
Another important factor for biodegradable polymers is that the degradation products are substantially compatible with the medium in which they arise. For example, it is clear that biodegradable polymers can REPLACEMENT SHEET (RULE 26) only be used successfully in the medical sector if the fragments (known as metabolites) produced on biodegradation are nonhazardous.
Finally, there is also great interest in obtaining polycondensates substantially from starting materials which occur directly in the natural environment or are obtained from products which occur in the natural environment, that is to say from what are known as renewable raw materials. Particular compounds which are possible molecular building blocks here are those which occur in metabolism in the natural environment, either in humans, in animals or in plants. They also include compounds which can be obtained by hydrolysis, oxidation, redu~ion or elimination of water from products such as carbohydrates. These compounds also include what are known as dianhydrohexitols, which are obtained by dehydrating the corresponding hexahydric alcohols, specifically isosorbitol, a compound which is obtained by dehydrating sorbitol and is also called 1,4:3,6-dianhydro-D-sorbitol (DAS), 1,4:3,6-dianhydro-D-mannitol (DAM), a compound which is obtained by dehydrating mannitol, and 1,4:3,6-dianhydro-L-iditol (DAI).
There is already extensive literature, especially scientific publications, concerning the preparation of dianhydrohexitols and their use for preparing poiycondensates. In this connection it should be pointed out that, especially in German publications, different names are given to one and the same compound. For example, the terms isosorbide, isomannide and isoidide are found in addition to 1,4:3,6-dianhydro-D-sorbitol (DAS) etc.
E. Fl~che et al., for example in starch/st~rke 38(1 ), 26-30 (1986) describe the preparation and properties of isosorbitol. J. Thiem et al., in starch/st~rke 36 (5) 170-6 (1984) are concerned with the preparation and controlled polycondensation of anhydroalditol units from starch. Storbeck et al., in Makromol. Chem. 194, 53-46, 1993, describe the synthesis of polyesters from DAS, DAM (1,4:3,6-dianhydro-D-mannitol) and DAI
(1,4:3,6-dianhydro-L-iditol). Other literature references which may be mentioned are Polymer 34 (23) 5003-6 (1993); Journal of Polymer Science: Part A: Polymer Chemistry 3~, 2813-20 (1995); Journal of Applied Polymer Science 59, 1199-1202 (1996); Die Angewandte Makromolekulare Chemie 199 (No. 3530) 191-205 (1992) and 2~ (No. 3659) 173-196 (1993).
DE-C 1 263 981 describes modified polyesters in which the glycol component may be composed of up to 20% by weight of isosorbitol, and which may moreover have branching brought about by polyfunctional esters of tri- to pentabasic acids. However, these polycondensates are not biodegradable.
Polycondensates which have amide functions are described in Trends in Polymer Science 2(12)425-36 (1994) and Journal of Polymer Science Part A: Polymer Chemistry 30 2059-62 (1992), for example.
There are therefore numerous known biodegradable polycondensates, but these have a wide variety of disadvantages. For example, it is often difficult to establish a sufficiently high molecular weight, and other polycondensates release excessive amounts of injurious substances on biodegradation, and others again have limited availability due to high preparation costs. There is moreover a tack of polycondensates whose properties can be quite specifically adapted for particular applications.
Although there is already a wide variety of known biodegradable polycondensates, there is still a need for improved products, for improved preparation processes and for products which are versatile in use.
It is therefore an object of the invention to provide biodegradable polycondensates which have good degradation performance, are simple to produce and can be prepared partially or entirely from renewable raw materials, and which can be modified straightaway during their synthesis to make them suitable for a very wide variety of applications.
This object is achieved by means of biodegradable polycondensates as claimed in patent claim 1. Patent claims 2 to 7 give particularly advantageous embodiments of the novel polycondensates. These novel polycondensates may be prepared by processes as claimed in patent claims 8 to 11. Claims 12 and 13 give particularly advantageous ways of using the novel polycondensates.
Biodegradable polycondensates degrade within a certain period of time in a biological medium, losing their original mechanical, physical and chemical properties as a result of breakdown into small fragments, also termed metabolites when the application is in the physiological sector - in particular in humans. An example which may be quoted is a biodegradable surgical suture which initially has the strength to hold together a sutured wound but then in the course of time is degraded by the body. Of course, there must be an appropriate relationship here between the rate of degradation and the healing of the wound.
For the purposes of the present invention, biological media in which biodegradable polymers may be used are media which occur in the natural environment, for example water, air or soil, and also human or animal bodies, and the interior of plants. Biodegradable polymers are frequently used in forms which serve only a single purpose, for example surgical sutures which have solely the function of securing the wound for a particular time, or waste sacks or packaging films, which undergo biodegradation after use, the degradation products themselves not having any particular function.
However, it is also possible to admix active substances with the biodegradable polymers, or as early as during the synthesis of the polymers to give these a chemical form which allows the polymers themselves to develop other active functions besides any mechanical function which they have. For example, it is possible to produce surgical sutures which, besides their mechanical function, have a disinfecting action, for example, or develop a certain medicinal action. Waste sacks may comprise, for example, substances whose odor repels dogs and cats.
Another important factor for biodegradable polymers is that the degradation products are substantially compatible with the medium in which they arise. For example, it is clear that biodegradable polymers can REPLACEMENT SHEET (RULE 26) only be used successfully in the medical sector if the fragments (known as metabolites) produced on biodegradation are nonhazardous.
Finally, there is also great interest in obtaining polycondensates substantially from starting materials which occur directly in the natural environment or are obtained from products which occur in the natural environment, that is to say from what are known as renewable raw materials. Particular compounds which are possible molecular building blocks here are those which occur in metabolism in the natural environment, either in humans, in animals or in plants. They also include compounds which can be obtained by hydrolysis, oxidation, redu~ion or elimination of water from products such as carbohydrates. These compounds also include what are known as dianhydrohexitols, which are obtained by dehydrating the corresponding hexahydric alcohols, specifically isosorbitol, a compound which is obtained by dehydrating sorbitol and is also called 1,4:3,6-dianhydro-D-sorbitol (DAS), 1,4:3,6-dianhydro-D-mannitol (DAM), a compound which is obtained by dehydrating mannitol, and 1,4:3,6-dianhydro-L-iditol (DAI).
There is already extensive literature, especially scientific publications, concerning the preparation of dianhydrohexitols and their use for preparing poiycondensates. In this connection it should be pointed out that, especially in German publications, different names are given to one and the same compound. For example, the terms isosorbide, isomannide and isoidide are found in addition to 1,4:3,6-dianhydro-D-sorbitol (DAS) etc.
E. Fl~che et al., for example in starch/st~rke 38(1 ), 26-30 (1986) describe the preparation and properties of isosorbitol. J. Thiem et al., in starch/st~rke 36 (5) 170-6 (1984) are concerned with the preparation and controlled polycondensation of anhydroalditol units from starch. Storbeck et al., in Makromol. Chem. 194, 53-46, 1993, describe the synthesis of polyesters from DAS, DAM (1,4:3,6-dianhydro-D-mannitol) and DAI
(1,4:3,6-dianhydro-L-iditol). Other literature references which may be mentioned are Polymer 34 (23) 5003-6 (1993); Journal of Polymer Science: Part A: Polymer Chemistry 3~, 2813-20 (1995); Journal of Applied Polymer Science 59, 1199-1202 (1996); Die Angewandte Makromolekulare Chemie 199 (No. 3530) 191-205 (1992) and 2~ (No. 3659) 173-196 (1993).
DE-C 1 263 981 describes modified polyesters in which the glycol component may be composed of up to 20% by weight of isosorbitol, and which may moreover have branching brought about by polyfunctional esters of tri- to pentabasic acids. However, these polycondensates are not biodegradable.
Polycondensates which have amide functions are described in Trends in Polymer Science 2(12)425-36 (1994) and Journal of Polymer Science Part A: Polymer Chemistry 30 2059-62 (1992), for example.
There are therefore numerous known biodegradable polycondensates, but these have a wide variety of disadvantages. For example, it is often difficult to establish a sufficiently high molecular weight, and other polycondensates release excessive amounts of injurious substances on biodegradation, and others again have limited availability due to high preparation costs. There is moreover a tack of polycondensates whose properties can be quite specifically adapted for particular applications.
Although there is already a wide variety of known biodegradable polycondensates, there is still a need for improved products, for improved preparation processes and for products which are versatile in use.
It is therefore an object of the invention to provide biodegradable polycondensates which have good degradation performance, are simple to produce and can be prepared partially or entirely from renewable raw materials, and which can be modified straightaway during their synthesis to make them suitable for a very wide variety of applications.
This object is achieved by means of biodegradable polycondensates as claimed in patent claim 1. Patent claims 2 to 7 give particularly advantageous embodiments of the novel polycondensates. These novel polycondensates may be prepared by processes as claimed in patent claims 8 to 11. Claims 12 and 13 give particularly advantageous ways of using the novel polycondensates.
a) The dianhydrohexitols used according to the invention, specifically isosorbitol, isomannitol and isoiditol, may be prepared by processes known per se, by dehydrating the corresponding hexitols, such as sorbitol, mannitol, etc. These compounds, e.g. isosorbitol, can be obtained in relatively large volumes from starch, and are available commercially.
b) The dibasic organic carboxylic acids used as second component may be aliphatic, cycloaliphatic or aromatic. Examples which may be mentioned here are terephthalic acid, adipic acid, furandicarboxylic acid, and also 3,6,9-trioxaundecanedicarboxylic acid, the use of which is preferred. The dicarboxylic acids may be used as such during the synthesis, but it is also possible to use appropriate derivatives, such as acid chlorides or esters o~
the carboxylic acids.
c) Examples which may be mentioned of the polyfunctional organic carboxylic acids which, besides two carboxylic acid functions, have at least one other uncapped or capped function, specifically OH and/or COOH, are tartaric acid, malic acid, hydroxysuccinic acid, citric acid, isocitric acid, aconitic acid and the like. In particular, use may also be made of cholic acid or deoxycholic acid, the biological functions of which make them particular suitable for incorporation in functional biopolymers.
An additional point which should be mentioned for group c) is that these carboxylic acids may be used as such, that is to say with the two or more functions uncapped, i.e. free and accessible for an immediate condensation reaction, or capped, e.g. etherified or esterified. It is fully possible here for all three functions of some trifunctional units to be involved in the polymerization reaction. Partial reactions are also conceivable in which the reaction of only one functional group leads to incorporation into the polymer. This is what is known as a polymer end group function, and the polymerization reaction does not involve the two other functional groups. The functional groups not taking part in the polymerization reaction may either remain capped (protected) or have their capping removed following the preparation of the polymer, in a polymer-WO 99/45054 PCT/EP99/Ot 112 analogous reaction. This corresponds chemically to the cleavage of what is known as a protecting group, initially introduced in order to cap the function.
Besides these three components a), b) and c), other components may be incorporated into the biodegradable polycondensates, in particular bifunctional components, such as alpha amino acids, e.g. serine, glutamine, lysine, giutamic acid, aspartic acid, and cystein, and it is also possible to make concomitant use of hydroxycarboxylic acids or of dihydroxy compounds. Incorporation of molecules of this type does not alter the stoichiometric ratio of the two different functional groups.
Incorporating, for example, 4-hydroxybenzoic acid increases the distances between monomers of the same type, as required by statistical laws, and thus has a controlled effect on the physical properties of the polymer in a manner known to the skilled worker, e.g. on glass transition temperature.
The polycondensation may be carried out by customary processes known per se, such as those known as one-pot reactions, in which all of the starting materials are mixed thoroughly at the very outset and are reacted with or without the use of a catalyst. This reaction may be carried out in the melt, or else in solution. However, continuous and semicontinuous processes are also possible.
Very suitable solvents besides dichloromethane, the use of which is preferred, include dimethylformamide, dimethyl sutfoxide and N
methylpyrrolidone.
It is appropriate for the reaction to be carried out by reacting equal molar amounts of OH and COOH groups. However, it is possible to deviate from the stoichiometric ratio, but the deviation from the stoichiometric ratio is preferably not more than 5 mol%.
Balancing of the stoichiometry of the different functional groups with respect to one another is generally advantageous. In the ideal case, diol components and dicarboxylic acid components, for example, are present in an equimolar ratio. For particular applications, e.g. if retarded or accelerated biodegradation is required, it may be appropriate to deviate WO 99/45054 PCTIEf'99/01112 from this ideal condition, and therefore it is also possible to pn3pare crosslinked polymers (gels) by methods known to the skilled worker.
The dianhydrohexitols, e.g. isosorbide, which are used according to the invention to build up the polycondensates react as glycols with the COOH
groups of the carboxylic acids used. The molar amounts of these compounds used are preferably such that at least 50 percent, preferably at least 70 percent, of the COOH groups of the acids can react with the OH
groups of the dianhydrohexitols.
The properties of the novel polycondensates may particularly advantageously be modified by incorporating other units, and it is therefore possible to prepare tailored polycondensates for specific applications. An example which may be mentioned here is the corxomitant use of amino acids and hydroxycarboxylic acids, e.g. hydroxybutyric acid, 4-hydroxybenzoic acid, 2-hydroxy-6-naphthoic acid, 4-aminobenzoic acid, glycolic acid, 4-hydroxybiphenyl-4-carboxylic acid, lithochdic acid, or 4-hydroxycinnamic acid.
The novel polycondensates have very good biodegradability. Although there is no desire to lay down a theory here, it is bkely that the improvement in biodegradability over other biodegradable poaycondensates is brought about by the incorporation of the units with the at least three functions, i.e. by the polyfunctional carboxylic acid which have one or more additional OH or COOH functions, e.g. malic acid.
It is also possible to exert a further favorable effect on biodegradability by making concomitant use of condensable starting materials which have heteroatoms. 3,6,9-Trioxaundecanedicarboxylic acid espeaally shouki be mentioned here. It is also advantageous for there to be some concomitant incorporation of compounds which have amino functions.
For the purposes of the present invention, a biodegradable potycondensate is one which, when placed in an appropriate medium, is degraded over the course of time into relatively small cleavage products which are preferably nonhazardous to the environment, humans, animals and plants. For the purposes of the present invention, the concept of biodegradability includes _7_ concepts such as bioerodability, enzymatic cleavability, compostability, biodegradability, hydrolyzabil'rty, digestability, edibility etc.
The incorporation of compounds having more than two functional groups in the biodegradable polymers described here according to the invention makes these polymers especially suitable for use as functional biodegradable polymers.
The novel polymers may be processed in the melt, but may also be processed using appropriate solvents. They can be processed to give any conceivable type of molding, such as bags, films, tablets, capsules, fibers, hollow fibers, powders and the like.
They may be used in particular where controlled release of active substances is involved. The active substance here may have been incorporated into the polycondensate, and in this case is released during biodegradation in the medium itself and can then develop its action.
According to the invention it is also possible for the polycondensates to be used to produce articles, such as capsules, which encompass an active substance which is then either released after a certain time when the capsule has been dissolved or leached out from the capsule by the medium over the course of time.
However, it is also possible for the polycondensate to be used as a matrix, in this case the active ingredient is uniformly dispersed in the polymer, e.g.
in the melt or else in a solution, so that degradation of the polycondensate is accompanied by release of the active substance.
The polycondensates may be used in a very wide variety of sectors. For example, they may be used in agriculture for the controlled release of fertilizers or of herbicides, pesticides or the like. Another application sector is the pharmaceutical sector, where the polycondensates can be used as tablets, for example. In the medical sector, the polycondensates may also be used subcutaneously, e.g. in an appropriate form, for example in the form of microparticles or of extrudates.
The preparation process is very flexible and controllable, and it is therefore even possible to produce different molecular weights, or else polycondensates with a tailored property profile.
The invention is further described by the examples below:
Example 1 3.18 g (21.76 mmol) of L-isosorbitol, 2.472 g (10.88 mmol) of dichloro-2,3-o-isopropylidene L-tartrate, 2.209 g (10.88 mmol) of terephthalic dichloride, 50 ml of dried dichloromethane and 3.6 ml (44.60 mmol) of pyridine are mixed and refluxed for 3 days, with stirring. During this process a white precipitate forms. The polycondensate is then precipitated in cyclohexane, and after drying it is dissolved in tetrahydrofuran (TH~/acetone and precipitated in water, filtered off with suction and dried in vacuo.
White powder; yield 3.9 g corresponding to 64% of theory.
Elemental anal % C % H
sis:
calc. 56.3 4.9 found 56.8 5.3 Rotation determined in solution in dichloromethane a = +82.4°
D
Molecular weight 6,700 (MW) (after previous calibration of a gel permeation chromatography (GPC) system using polystyrene standard).
25 Example 2 3.046 g (20.8 mmol) of L-isosorbide, 1.15 g (6.28 mmol) of adipic dichloride, 3.31 g (14.57 mmol) of dichloro-2,3-o-isopropylidene L-tartrate, 70 ml of dried dichloromethane and 3.3 ml (41.72 mmol) of pyridine are mixed, and then the procedure continues as in example 1.
White powder, yield 3.8 g corresponding to 639'0 of theory.
_g Elemental sis:~ C ~ H
ana talc. 53.1 5.6 found 58.4 5.5 Rotation determined in solution in dichloromethane: a25 = + 78.6°
D
Molecular weight 6,400 Dalton (Mw), polydispersity (M",/M") = 2.9 (after previous calibration of a gel permeation chromatography (GPC) system using polystyrene standard).
Example 3 3.193 g (21.85 mmol) of L-isosorbide, 1.489 g (6.55 mmol) of dichloro-2,3-o-isopropylidene L-tartrate, 2.952 g (15.30 mmol) of furandicarboxylic dichloride, 70 ml of dried dichloromethane and 3.5 ml (44.5 mmol) of pyridine are mixed, and then the procedure continues as in example 1.
White powder, yield 4.9 g corresponding to 83% of theory.
Elemental anal % C % H
sis:
calc. 42.3 4.3 found 42.9 4.5 Rotation determined in solution in dichloromethane: a25 --35.3°
D
Molecular weight 8,200 Dalton (Mw) (after previous calibration of a gel permeation chromatography (GPC) system using polystyrene standard).
Example 4 The biodegradability of the polymers was studied using a modified Sturm test. The test was carried out to OECD Guideline 301 B (1992; Sturm test).
The test serves to determine the biodegradability of organic substances by aerobic microorganisms in an aqueous test medium. The organic test substance is the sole source of carbon in the experiment and is therefore the supplier of energy for the microorganisms. The degradation of the organic substances to be studied here is determined indirectly via measurement of the amount of carbon dioxide evolved. Each test lasts for 28 days. Sodium benzoate serves as an internal standard.
The detailed test conditions are: a supernatant used from activated sludge from the Frankfurt Niederrad sewage-treatment plant (10 ml per 1 I of test mixture); brown glass bottles of 5 I capacity; magnetic stirrer, room temperature, C02 determined via barium carbonate formation in aqueous Ba(OH)2 solution and back-titration of the excess of alkali.
TIME BLIND SODIUM SODIUM POLY-L-LACTIC ACID
(DAYS) MIXTURE BENZOATE BENZOATE DEGREE OF
C02 (mg) COZ (mg) DEGREE OF DEGRADATION (%) DEGRADATION COMPARATIVE
EXAMPLE
1 0.7 1.6 1 2 4 , 2.4 24.3 34 8 7 3.6 40.7 58 18 11 4.6 50.7 72 38 14 5.3 55.6 78 53 18 6.7 59.3 g 1 21 8.4 61.9 83 71 25 10.7 65.4 85 79 28 14.8 69.6 85 82 _11_ TIME SODIUM POLYMER POLYMER POLYMER
(DAYS) BENZOATE EXAMPLE 1 EXAMPLE 2 EXAMPLE 3 DEGREE OF DEGREE OF DEGREE OF DEGREE OF
DEGRADATIO DEGRADATlO DEGRADATIO DEGRADATIO
N % N % N % N
4 34 2 14 g 7 58 2~ 29 26 28 g5 89 8 85
b) The dibasic organic carboxylic acids used as second component may be aliphatic, cycloaliphatic or aromatic. Examples which may be mentioned here are terephthalic acid, adipic acid, furandicarboxylic acid, and also 3,6,9-trioxaundecanedicarboxylic acid, the use of which is preferred. The dicarboxylic acids may be used as such during the synthesis, but it is also possible to use appropriate derivatives, such as acid chlorides or esters o~
the carboxylic acids.
c) Examples which may be mentioned of the polyfunctional organic carboxylic acids which, besides two carboxylic acid functions, have at least one other uncapped or capped function, specifically OH and/or COOH, are tartaric acid, malic acid, hydroxysuccinic acid, citric acid, isocitric acid, aconitic acid and the like. In particular, use may also be made of cholic acid or deoxycholic acid, the biological functions of which make them particular suitable for incorporation in functional biopolymers.
An additional point which should be mentioned for group c) is that these carboxylic acids may be used as such, that is to say with the two or more functions uncapped, i.e. free and accessible for an immediate condensation reaction, or capped, e.g. etherified or esterified. It is fully possible here for all three functions of some trifunctional units to be involved in the polymerization reaction. Partial reactions are also conceivable in which the reaction of only one functional group leads to incorporation into the polymer. This is what is known as a polymer end group function, and the polymerization reaction does not involve the two other functional groups. The functional groups not taking part in the polymerization reaction may either remain capped (protected) or have their capping removed following the preparation of the polymer, in a polymer-WO 99/45054 PCT/EP99/Ot 112 analogous reaction. This corresponds chemically to the cleavage of what is known as a protecting group, initially introduced in order to cap the function.
Besides these three components a), b) and c), other components may be incorporated into the biodegradable polycondensates, in particular bifunctional components, such as alpha amino acids, e.g. serine, glutamine, lysine, giutamic acid, aspartic acid, and cystein, and it is also possible to make concomitant use of hydroxycarboxylic acids or of dihydroxy compounds. Incorporation of molecules of this type does not alter the stoichiometric ratio of the two different functional groups.
Incorporating, for example, 4-hydroxybenzoic acid increases the distances between monomers of the same type, as required by statistical laws, and thus has a controlled effect on the physical properties of the polymer in a manner known to the skilled worker, e.g. on glass transition temperature.
The polycondensation may be carried out by customary processes known per se, such as those known as one-pot reactions, in which all of the starting materials are mixed thoroughly at the very outset and are reacted with or without the use of a catalyst. This reaction may be carried out in the melt, or else in solution. However, continuous and semicontinuous processes are also possible.
Very suitable solvents besides dichloromethane, the use of which is preferred, include dimethylformamide, dimethyl sutfoxide and N
methylpyrrolidone.
It is appropriate for the reaction to be carried out by reacting equal molar amounts of OH and COOH groups. However, it is possible to deviate from the stoichiometric ratio, but the deviation from the stoichiometric ratio is preferably not more than 5 mol%.
Balancing of the stoichiometry of the different functional groups with respect to one another is generally advantageous. In the ideal case, diol components and dicarboxylic acid components, for example, are present in an equimolar ratio. For particular applications, e.g. if retarded or accelerated biodegradation is required, it may be appropriate to deviate WO 99/45054 PCTIEf'99/01112 from this ideal condition, and therefore it is also possible to pn3pare crosslinked polymers (gels) by methods known to the skilled worker.
The dianhydrohexitols, e.g. isosorbide, which are used according to the invention to build up the polycondensates react as glycols with the COOH
groups of the carboxylic acids used. The molar amounts of these compounds used are preferably such that at least 50 percent, preferably at least 70 percent, of the COOH groups of the acids can react with the OH
groups of the dianhydrohexitols.
The properties of the novel polycondensates may particularly advantageously be modified by incorporating other units, and it is therefore possible to prepare tailored polycondensates for specific applications. An example which may be mentioned here is the corxomitant use of amino acids and hydroxycarboxylic acids, e.g. hydroxybutyric acid, 4-hydroxybenzoic acid, 2-hydroxy-6-naphthoic acid, 4-aminobenzoic acid, glycolic acid, 4-hydroxybiphenyl-4-carboxylic acid, lithochdic acid, or 4-hydroxycinnamic acid.
The novel polycondensates have very good biodegradability. Although there is no desire to lay down a theory here, it is bkely that the improvement in biodegradability over other biodegradable poaycondensates is brought about by the incorporation of the units with the at least three functions, i.e. by the polyfunctional carboxylic acid which have one or more additional OH or COOH functions, e.g. malic acid.
It is also possible to exert a further favorable effect on biodegradability by making concomitant use of condensable starting materials which have heteroatoms. 3,6,9-Trioxaundecanedicarboxylic acid espeaally shouki be mentioned here. It is also advantageous for there to be some concomitant incorporation of compounds which have amino functions.
For the purposes of the present invention, a biodegradable potycondensate is one which, when placed in an appropriate medium, is degraded over the course of time into relatively small cleavage products which are preferably nonhazardous to the environment, humans, animals and plants. For the purposes of the present invention, the concept of biodegradability includes _7_ concepts such as bioerodability, enzymatic cleavability, compostability, biodegradability, hydrolyzabil'rty, digestability, edibility etc.
The incorporation of compounds having more than two functional groups in the biodegradable polymers described here according to the invention makes these polymers especially suitable for use as functional biodegradable polymers.
The novel polymers may be processed in the melt, but may also be processed using appropriate solvents. They can be processed to give any conceivable type of molding, such as bags, films, tablets, capsules, fibers, hollow fibers, powders and the like.
They may be used in particular where controlled release of active substances is involved. The active substance here may have been incorporated into the polycondensate, and in this case is released during biodegradation in the medium itself and can then develop its action.
According to the invention it is also possible for the polycondensates to be used to produce articles, such as capsules, which encompass an active substance which is then either released after a certain time when the capsule has been dissolved or leached out from the capsule by the medium over the course of time.
However, it is also possible for the polycondensate to be used as a matrix, in this case the active ingredient is uniformly dispersed in the polymer, e.g.
in the melt or else in a solution, so that degradation of the polycondensate is accompanied by release of the active substance.
The polycondensates may be used in a very wide variety of sectors. For example, they may be used in agriculture for the controlled release of fertilizers or of herbicides, pesticides or the like. Another application sector is the pharmaceutical sector, where the polycondensates can be used as tablets, for example. In the medical sector, the polycondensates may also be used subcutaneously, e.g. in an appropriate form, for example in the form of microparticles or of extrudates.
The preparation process is very flexible and controllable, and it is therefore even possible to produce different molecular weights, or else polycondensates with a tailored property profile.
The invention is further described by the examples below:
Example 1 3.18 g (21.76 mmol) of L-isosorbitol, 2.472 g (10.88 mmol) of dichloro-2,3-o-isopropylidene L-tartrate, 2.209 g (10.88 mmol) of terephthalic dichloride, 50 ml of dried dichloromethane and 3.6 ml (44.60 mmol) of pyridine are mixed and refluxed for 3 days, with stirring. During this process a white precipitate forms. The polycondensate is then precipitated in cyclohexane, and after drying it is dissolved in tetrahydrofuran (TH~/acetone and precipitated in water, filtered off with suction and dried in vacuo.
White powder; yield 3.9 g corresponding to 64% of theory.
Elemental anal % C % H
sis:
calc. 56.3 4.9 found 56.8 5.3 Rotation determined in solution in dichloromethane a = +82.4°
D
Molecular weight 6,700 (MW) (after previous calibration of a gel permeation chromatography (GPC) system using polystyrene standard).
25 Example 2 3.046 g (20.8 mmol) of L-isosorbide, 1.15 g (6.28 mmol) of adipic dichloride, 3.31 g (14.57 mmol) of dichloro-2,3-o-isopropylidene L-tartrate, 70 ml of dried dichloromethane and 3.3 ml (41.72 mmol) of pyridine are mixed, and then the procedure continues as in example 1.
White powder, yield 3.8 g corresponding to 639'0 of theory.
_g Elemental sis:~ C ~ H
ana talc. 53.1 5.6 found 58.4 5.5 Rotation determined in solution in dichloromethane: a25 = + 78.6°
D
Molecular weight 6,400 Dalton (Mw), polydispersity (M",/M") = 2.9 (after previous calibration of a gel permeation chromatography (GPC) system using polystyrene standard).
Example 3 3.193 g (21.85 mmol) of L-isosorbide, 1.489 g (6.55 mmol) of dichloro-2,3-o-isopropylidene L-tartrate, 2.952 g (15.30 mmol) of furandicarboxylic dichloride, 70 ml of dried dichloromethane and 3.5 ml (44.5 mmol) of pyridine are mixed, and then the procedure continues as in example 1.
White powder, yield 4.9 g corresponding to 83% of theory.
Elemental anal % C % H
sis:
calc. 42.3 4.3 found 42.9 4.5 Rotation determined in solution in dichloromethane: a25 --35.3°
D
Molecular weight 8,200 Dalton (Mw) (after previous calibration of a gel permeation chromatography (GPC) system using polystyrene standard).
Example 4 The biodegradability of the polymers was studied using a modified Sturm test. The test was carried out to OECD Guideline 301 B (1992; Sturm test).
The test serves to determine the biodegradability of organic substances by aerobic microorganisms in an aqueous test medium. The organic test substance is the sole source of carbon in the experiment and is therefore the supplier of energy for the microorganisms. The degradation of the organic substances to be studied here is determined indirectly via measurement of the amount of carbon dioxide evolved. Each test lasts for 28 days. Sodium benzoate serves as an internal standard.
The detailed test conditions are: a supernatant used from activated sludge from the Frankfurt Niederrad sewage-treatment plant (10 ml per 1 I of test mixture); brown glass bottles of 5 I capacity; magnetic stirrer, room temperature, C02 determined via barium carbonate formation in aqueous Ba(OH)2 solution and back-titration of the excess of alkali.
TIME BLIND SODIUM SODIUM POLY-L-LACTIC ACID
(DAYS) MIXTURE BENZOATE BENZOATE DEGREE OF
C02 (mg) COZ (mg) DEGREE OF DEGRADATION (%) DEGRADATION COMPARATIVE
EXAMPLE
1 0.7 1.6 1 2 4 , 2.4 24.3 34 8 7 3.6 40.7 58 18 11 4.6 50.7 72 38 14 5.3 55.6 78 53 18 6.7 59.3 g 1 21 8.4 61.9 83 71 25 10.7 65.4 85 79 28 14.8 69.6 85 82 _11_ TIME SODIUM POLYMER POLYMER POLYMER
(DAYS) BENZOATE EXAMPLE 1 EXAMPLE 2 EXAMPLE 3 DEGREE OF DEGREE OF DEGREE OF DEGREE OF
DEGRADATIO DEGRADATlO DEGRADATIO DEGRADATIO
N % N % N % N
4 34 2 14 g 7 58 2~ 29 26 28 g5 89 8 85
Claims (13)
1. A biodegradable polycondensate which derives from at least three components, selected from the group consisting of a) dianhydrohexitols b) dibasic organic carboxylic acids, and c) polyfunctional organic carboxylic acids which, besides two carboxylic acid functions, have at least one other uncapped or capped function, specifically OH and/or COOH.
2. A biodegradable polycondensate as claimed in claim 1, wherein the dibasic organic carboxylic acid is terephthalic acid.
3. A biodegradable polycondensate as claimed in claim 1, wherein the dibasic organic carboxylic acid is 3,6,9-trioxaundecanedicarboxylic acid.
4. A biodegradable polycondensate as claimed in claim 1, wherein the dibasic organic carboxylic acid is furan dicarboxylic acid.
5. A biodegradable polycondensate as claimed in at least one of claims 1 to 4, wherein the polyfunctional organic carboxylic acid of c) is tartaric acid.
6. A biodegradable polycondensate as claimed in at least one of claims 1 to 4, wherein the polyfunctional organic carboxylic acid of c) is uvic acid.
7. A biodegradable polycondensate as claimed in at least one of claims 1 to 4, wherein the polyfunctional organic carboxylic acid of c) is citric acid.
8. A process for preparing biodegradable polycondensates as claimed in any of claims 1 to 7, which comprises reacting the starting materials in the melt.
9. The process for preparing biodegradable polycondensates as claimed in any of claims 1 to 7, wherein the starting materials are reacted in a solvent.
10. The process as claimed in claim 9, wherein dichloromethane is used as solvent.
11. The process for preparing biodegradable polycondensates as claimed in any of claims 8 to 10, wherein the ratio in which the starting materials are reacted, based on the OH and COOH
functions, is equimolar ~ 5 mol%.
functions, is equimolar ~ 5 mol%.
12. The use of the biodegradable polycondensates as claimed in any of claims 1 to 7, or else prepared by a process as claimed in any of claims 8 to 11, as an encapsulating material for active substances.
13. The use of the biodegradable polycondensates as claimed in any of claims 1 to 7, or prepared by a process as claimed in any of claims 8 to 11, as a matrix material for receiving active substances.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19809913A DE19809913A1 (en) | 1998-03-07 | 1998-03-07 | Biodegradable polymers based on natural and renewable raw materials, especially isosorbitol |
DE19809913.4 | 1998-03-07 | ||
PCT/EP1999/001112 WO1999045054A1 (en) | 1998-03-07 | 1999-02-20 | Biodegradable polymers based on natural and renewable raw materials, especially isosorbite |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2324279A1 true CA2324279A1 (en) | 1999-09-10 |
Family
ID=7860126
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002324279A Abandoned CA2324279A1 (en) | 1998-03-07 | 1999-02-20 | Biodegradable polymers based on natural and renewable raw materials, especially isosorbite |
Country Status (6)
Country | Link |
---|---|
EP (1) | EP1062259B1 (en) |
JP (1) | JP2002505359A (en) |
CA (1) | CA2324279A1 (en) |
DE (2) | DE19809913A1 (en) |
HU (1) | HUP0101019A3 (en) |
WO (1) | WO1999045054A1 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9605108B2 (en) | 2014-04-24 | 2017-03-28 | New Jersey Institute Of Technology | Isosorbide-derived epoxy resins and methods of making same |
EP2276789B2 (en) † | 2008-05-08 | 2018-07-18 | Novamont S.p.A. | Aliphatic-aromatic biodegradable polyester |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6485819B2 (en) | 2000-12-19 | 2002-11-26 | E. I. Du Pont De Nemours And Company | Aliphatic-aromatic copolyesters |
US6368710B1 (en) | 2000-12-19 | 2002-04-09 | E. I. Du Pont De Nemours And Company | Sulfonated aliphatic-aromatic copolyesters |
JP4881127B2 (en) * | 2005-11-07 | 2012-02-22 | キヤノン株式会社 | Polymer compound and synthesis method thereof |
CN100432118C (en) * | 2006-03-22 | 2008-11-12 | 南昌大学 | Synthesis of degradable aromatic/fatty copolymer ester by in-situ ester |
US20080108759A1 (en) * | 2006-11-08 | 2008-05-08 | Sodergard Nils D A | Lactic Acid Polymers |
JP5120944B2 (en) * | 2008-04-25 | 2013-01-16 | 独立行政法人産業技術総合研究所 | Biodegradable high molecular weight aliphatic polyester and method for producing the same |
JP5950391B2 (en) * | 2012-05-01 | 2016-07-13 | 花王株式会社 | Binder resin for toner |
WO2023111923A1 (en) * | 2021-12-16 | 2023-06-22 | Reliance Industries Limited | A biodegradable polymer and a process for its preparation |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4034334A1 (en) * | 1990-10-29 | 1992-04-30 | Basf Ag | USE OF WINE ACID CONCENTRATED POLYESTERS AS A DETERGENT ADDITIVE, METHOD OF PREPARING POLYESTER AND POLYESTER FROM WINE ACIDS AND TETRACARBONE ACIDS |
EP0514790A2 (en) * | 1991-05-24 | 1992-11-25 | Hoechst Aktiengesellschaft | Polycondensates containing tartaric acid derivatives, process for preparation thereof and their use |
-
1998
- 1998-03-07 DE DE19809913A patent/DE19809913A1/en not_active Withdrawn
-
1999
- 1999-02-20 HU HU0101019A patent/HUP0101019A3/en unknown
- 1999-02-20 JP JP2000534594A patent/JP2002505359A/en active Pending
- 1999-02-20 CA CA002324279A patent/CA2324279A1/en not_active Abandoned
- 1999-02-20 WO PCT/EP1999/001112 patent/WO1999045054A1/en active IP Right Grant
- 1999-02-20 DE DE59907372T patent/DE59907372D1/en not_active Expired - Lifetime
- 1999-02-20 EP EP99908935A patent/EP1062259B1/en not_active Expired - Lifetime
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2276789B2 (en) † | 2008-05-08 | 2018-07-18 | Novamont S.p.A. | Aliphatic-aromatic biodegradable polyester |
US10316139B2 (en) | 2008-05-08 | 2019-06-11 | Novamont S.P.A. | Aliphatic-aromatic biodegradable polyester |
US10526442B2 (en) | 2008-05-08 | 2020-01-07 | Novamont S.P.A. | Aliphatic-aromatic biodegradable polyester |
US11345779B2 (en) | 2008-05-08 | 2022-05-31 | Novamont S.P.A. | Aliphatic-aromatic biodegradable polyester |
US9605108B2 (en) | 2014-04-24 | 2017-03-28 | New Jersey Institute Of Technology | Isosorbide-derived epoxy resins and methods of making same |
Also Published As
Publication number | Publication date |
---|---|
JP2002505359A (en) | 2002-02-19 |
EP1062259B1 (en) | 2003-10-15 |
HUP0101019A3 (en) | 2001-11-28 |
HUP0101019A2 (en) | 2001-07-30 |
WO1999045054A1 (en) | 1999-09-10 |
DE59907372D1 (en) | 2003-11-20 |
EP1062259A1 (en) | 2000-12-27 |
DE19809913A1 (en) | 1999-09-09 |
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