CA2299393A1 - Copolymeres blocs en gels injectables et biodegradables servant a administrer un medicament - Google Patents
Copolymeres blocs en gels injectables et biodegradables servant a administrer un medicament Download PDFInfo
- Publication number
- CA2299393A1 CA2299393A1 CA002299393A CA2299393A CA2299393A1 CA 2299393 A1 CA2299393 A1 CA 2299393A1 CA 002299393 A CA002299393 A CA 002299393A CA 2299393 A CA2299393 A CA 2299393A CA 2299393 A1 CA2299393 A1 CA 2299393A1
- Authority
- CA
- Canada
- Prior art keywords
- poly
- block
- copolymer
- block copolymer
- polymer block
- 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
- 239000000499 gel Substances 0.000 title claims abstract description 42
- 238000012377 drug delivery Methods 0.000 title claims abstract description 16
- 229920001400 block copolymer Polymers 0.000 title claims description 67
- 229920000642 polymer Polymers 0.000 claims abstract description 54
- 229920001577 copolymer Polymers 0.000 claims abstract description 45
- 239000003814 drug Substances 0.000 claims abstract description 45
- 229940079593 drug Drugs 0.000 claims abstract description 44
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims abstract description 42
- -1 poly(ethylene oxide) Polymers 0.000 claims abstract description 36
- 230000002209 hydrophobic effect Effects 0.000 claims abstract description 33
- 230000007704 transition Effects 0.000 claims abstract description 32
- 230000036760 body temperature Effects 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims abstract description 14
- 238000001248 thermal gelation Methods 0.000 claims abstract description 13
- 239000000017 hydrogel Substances 0.000 claims abstract description 11
- 239000007788 liquid Substances 0.000 claims abstract description 10
- 241001465754 Metazoa Species 0.000 claims abstract description 9
- 239000011159 matrix material Substances 0.000 claims abstract description 9
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 6
- 238000013270 controlled release Methods 0.000 claims abstract description 3
- 229920000428 triblock copolymer Polymers 0.000 claims description 13
- 229920000359 diblock copolymer Polymers 0.000 claims description 11
- 239000004310 lactic acid Substances 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 9
- 229920001897 terpolymer Polymers 0.000 claims description 5
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 4
- SJZRECIVHVDYJC-UHFFFAOYSA-N 4-hydroxybutyric acid Chemical compound OCCCC(O)=O SJZRECIVHVDYJC-UHFFFAOYSA-N 0.000 claims description 4
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 4
- 239000001630 malic acid Substances 0.000 claims description 4
- 235000011090 malic acid Nutrition 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 2
- 239000008365 aqueous carrier Substances 0.000 claims 6
- 230000015556 catabolic process Effects 0.000 abstract description 4
- 238000006731 degradation reaction Methods 0.000 abstract description 4
- 231100000252 nontoxic Toxicity 0.000 abstract description 3
- 230000003000 nontoxic effect Effects 0.000 abstract description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 10
- JJTUDXZGHPGLLC-IMJSIDKUSA-N 4511-42-6 Chemical compound C[C@@H]1OC(=O)[C@H](C)OC1=O JJTUDXZGHPGLLC-IMJSIDKUSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- 229920001983 poloxamer Polymers 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 8
- 238000001879 gelation Methods 0.000 description 8
- 229920001223 polyethylene glycol Polymers 0.000 description 8
- 239000003960 organic solvent Substances 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 239000005057 Hexamethylene diisocyanate Substances 0.000 description 6
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 6
- 239000002202 Polyethylene glycol Substances 0.000 description 6
- RRAMGCGOFNQTLD-UHFFFAOYSA-N hexamethylene diisocyanate Chemical compound O=C=NCCCCCCN=C=O RRAMGCGOFNQTLD-UHFFFAOYSA-N 0.000 description 6
- 239000000178 monomer Substances 0.000 description 6
- 239000012867 bioactive agent Substances 0.000 description 5
- 239000007822 coupling agent Substances 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 229960000448 lactic acid Drugs 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 229960000502 poloxamer Drugs 0.000 description 5
- 229920001432 poly(L-lactide) Polymers 0.000 description 5
- 238000007151 ring opening polymerisation reaction Methods 0.000 description 5
- KSBAEPSJVUENNK-UHFFFAOYSA-L tin(ii) 2-ethylhexanoate Chemical compound [Sn+2].CCCCC(CC)C([O-])=O.CCCCC(CC)C([O-])=O KSBAEPSJVUENNK-UHFFFAOYSA-L 0.000 description 5
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 description 4
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000008878 coupling Effects 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 125000005442 diisocyanate group Chemical group 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 239000004698 Polyethylene Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 238000010533 azeotropic distillation Methods 0.000 description 3
- 229920002988 biodegradable polymer Polymers 0.000 description 3
- 239000004621 biodegradable polymer Substances 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 229920013746 hydrophilic polyethylene oxide Polymers 0.000 description 3
- 239000007943 implant Substances 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 230000007794 irritation Effects 0.000 description 3
- 239000000693 micelle Substances 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 229920000573 polyethylene Polymers 0.000 description 3
- 238000006116 polymerization reaction Methods 0.000 description 3
- 229920001451 polypropylene glycol Polymers 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 229920001169 thermoplastic Polymers 0.000 description 3
- 229920001187 thermosetting polymer Polymers 0.000 description 3
- 239000004416 thermosoftening plastic Substances 0.000 description 3
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- 229920001244 Poly(D,L-lactide) Polymers 0.000 description 2
- 239000004721 Polyphenylene oxide Substances 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229920001519 homopolymer Polymers 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- QNILTEGFHQSKFF-UHFFFAOYSA-N n-propan-2-ylprop-2-enamide Chemical compound CC(C)NC(=O)C=C QNILTEGFHQSKFF-UHFFFAOYSA-N 0.000 description 2
- 229920001693 poly(ether-ester) Polymers 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 239000013557 residual solvent Substances 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 150000003573 thiols Chemical class 0.000 description 2
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 description 2
- NXLNNXIXOYSCMB-UHFFFAOYSA-N (4-nitrophenyl) carbonochloridate Chemical compound [O-][N+](=O)C1=CC=C(OC(Cl)=O)C=C1 NXLNNXIXOYSCMB-UHFFFAOYSA-N 0.000 description 1
- MTZUIIAIAKMWLI-UHFFFAOYSA-N 1,2-diisocyanatobenzene Chemical compound O=C=NC1=CC=CC=C1N=C=O MTZUIIAIAKMWLI-UHFFFAOYSA-N 0.000 description 1
- DTZHXCBUWSTOPO-UHFFFAOYSA-N 1-isocyanato-4-[(4-isocyanato-3-methylphenyl)methyl]-2-methylbenzene Chemical compound C1=C(N=C=O)C(C)=CC(CC=2C=C(C)C(N=C=O)=CC=2)=C1 DTZHXCBUWSTOPO-UHFFFAOYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- AGNTUZCMJBTHOG-UHFFFAOYSA-N 3-[3-(2,3-dihydroxypropoxy)-2-hydroxypropoxy]propane-1,2-diol Chemical compound OCC(O)COCC(O)COCC(O)CO AGNTUZCMJBTHOG-UHFFFAOYSA-N 0.000 description 1
- UPMLOUAZCHDJJD-UHFFFAOYSA-N 4,4'-Diphenylmethane Diisocyanate Chemical compound C1=CC(N=C=O)=CC=C1CC1=CC=C(N=C=O)C=C1 UPMLOUAZCHDJJD-UHFFFAOYSA-N 0.000 description 1
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- 101000730648 Homo sapiens Phospholipase A-2-activating protein Proteins 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
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- 102100032572 Phospholipase A-2-activating protein Human genes 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 239000000150 Sympathomimetic Substances 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M acrylate group Chemical group C(C=C)(=O)[O-] NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- SMZOGRDCAXLAAR-UHFFFAOYSA-N aluminium isopropoxide Chemical compound [Al+3].CC(C)[O-].CC(C)[O-].CC(C)[O-] SMZOGRDCAXLAAR-UHFFFAOYSA-N 0.000 description 1
- 229920006125 amorphous polymer Polymers 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 230000000578 anorexic effect Effects 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000003288 anthiarrhythmic effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 230000001142 anti-diarrhea Effects 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 229940035678 anti-parkinson drug Drugs 0.000 description 1
- 230000001139 anti-pruritic effect Effects 0.000 description 1
- 230000000561 anti-psychotic effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 230000002921 anti-spasmodic effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229960005475 antiinfective agent Drugs 0.000 description 1
- 229940005486 antimigraine preparations Drugs 0.000 description 1
- 229910000410 antimony oxide Inorganic materials 0.000 description 1
- 239000002579 antinauseant Substances 0.000 description 1
- 239000003908 antipruritic agent Substances 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 229940125716 antipyretic agent Drugs 0.000 description 1
- 229940124575 antispasmodic agent Drugs 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 239000000599 controlled substance Substances 0.000 description 1
- 238000007334 copolymerization reaction Methods 0.000 description 1
- 229940037530 cough and cold preparations Drugs 0.000 description 1
- 239000000850 decongestant Substances 0.000 description 1
- 229940124581 decongestants Drugs 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000005684 electric field Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229920001600 hydrophobic polymer Polymers 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 229940083747 low-ceiling diuretics xanthine derivative Drugs 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 231100000324 minimal toxicity Toxicity 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229940035363 muscle relaxants Drugs 0.000 description 1
- 239000003158 myorelaxant agent Substances 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- VTRUBDSFZJNXHI-UHFFFAOYSA-N oxoantimony Chemical compound [Sb]=O VTRUBDSFZJNXHI-UHFFFAOYSA-N 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 230000002445 parasympatholytic effect Effects 0.000 description 1
- 230000001499 parasympathomimetic effect Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 238000012643 polycondensation polymerization Methods 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- NREVZTYRXVBFAQ-UHFFFAOYSA-N propan-2-ol;yttrium Chemical compound [Y].CC(C)O.CC(C)O.CC(C)O NREVZTYRXVBFAQ-UHFFFAOYSA-N 0.000 description 1
- 239000003368 psychostimulant agent Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 229920006126 semicrystalline polymer Polymers 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 229940014800 succinic anhydride Drugs 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000001975 sympathomimetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- DVKJHBMWWAPEIU-UHFFFAOYSA-N toluene 2,4-diisocyanate Chemical compound CC1=CC=C(N=C=O)C=C1N=C=O DVKJHBMWWAPEIU-UHFFFAOYSA-N 0.000 description 1
- RUELTTOHQODFPA-UHFFFAOYSA-N toluene 2,6-diisocyanate Chemical compound CC1=C(N=C=O)C=CC=C1N=C=O RUELTTOHQODFPA-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 230000035899 viability Effects 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L71/00—Compositions of polyethers obtained by reactions forming an ether link in the main chain; Compositions of derivatives of such polymers
- C08L71/02—Polyalkylene oxides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Inorganic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Dispersion Chemistry (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Dermatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Polyesters Or Polycarbonates (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US5517497P | 1997-08-08 | 1997-08-08 | |
| US60/055,174 | 1997-08-08 | ||
| US13096798A | 1998-08-07 | 1998-08-07 | |
| US09/130,967 | 1998-08-07 | ||
| PCT/US1998/016418 WO1999007343A1 (fr) | 1997-08-08 | 1998-08-08 | Copolymeres blocs en gels injectables et biodegradables servant a administrer un medicament |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2299393A1 true CA2299393A1 (fr) | 1999-02-18 |
Family
ID=26733929
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002299393A Abandoned CA2299393A1 (fr) | 1997-08-08 | 1998-08-08 | Copolymeres blocs en gels injectables et biodegradables servant a administrer un medicament |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP1024790A4 (fr) |
| JP (1) | JP2001517603A (fr) |
| KR (1) | KR20010022708A (fr) |
| CA (1) | CA2299393A1 (fr) |
| WO (1) | WO1999007343A1 (fr) |
Families Citing this family (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2291622C (fr) | 1997-06-06 | 2007-09-04 | Anna Gutowska | Copolymere a gelification reversible, et son procede d'obtention |
| DE69829204T2 (de) * | 1997-10-03 | 2005-12-15 | Macromed Inc., Salt Lake City | Biologisch abbaubare triblock-poly(lactide-co-glycolide)-polyethylenglycol-copolymere mit umgekehrter thermischer gelierung |
| US6201072B1 (en) * | 1997-10-03 | 2001-03-13 | Macromed, Inc. | Biodegradable low molecular weight triblock poly(lactide-co- glycolide) polyethylene glycol copolymers having reverse thermal gelation properties |
| US6841617B2 (en) | 2000-09-28 | 2005-01-11 | Battelle Memorial Institute | Thermogelling biodegradable aqueous polymer solution |
| US7087244B2 (en) | 2000-09-28 | 2006-08-08 | Battelle Memorial Institute | Thermogelling oligopeptide polymers |
| EP1413296A1 (fr) * | 1998-05-07 | 2004-04-28 | ALZA Corporation | Procédé de fabrication d'une forme galénique à bandes contenant des agents actifs à libération prolongée |
| US6451346B1 (en) * | 1998-12-23 | 2002-09-17 | Amgen Inc | Biodegradable pH/thermosensitive hydrogels for sustained delivery of biologically active agents |
| US6245740B1 (en) * | 1998-12-23 | 2001-06-12 | Amgen Inc. | Polyol:oil suspensions for the sustained release of proteins |
| AU1792601A (en) * | 1999-12-07 | 2001-06-18 | Amgen, Inc. | Thermosensitive biodegradable hydrogels based on low molecular weight pluronics |
| KR100358027B1 (ko) * | 2000-02-14 | 2002-10-25 | 한국과학기술연구원 | 의료용 생분해성 삼중블록 공중합체 및 그의 제조 방법 |
| US7160931B2 (en) | 2000-03-15 | 2007-01-09 | Yu-Ling Cheng | Thermally reversible implant and filler |
| US7193007B2 (en) | 2000-03-15 | 2007-03-20 | Yu-Ling Cheng | Environment responsive gelling copolymer |
| AU2001242144A1 (en) * | 2000-03-15 | 2001-09-24 | Yu-Ling Cheng | Environment responsive gelling copolymer |
| KR100418916B1 (ko) * | 2000-11-28 | 2004-02-14 | 한국과학기술원 | 생분해성 고분자와 항암제의 접합체를 이용한 서방형미셀제제의 제조방법 |
| US7659314B2 (en) | 2002-05-19 | 2010-02-09 | University Of Utah Research Foundation | PH-sensitive polymeric micelles for drug delivery |
| US7229973B2 (en) * | 2002-05-19 | 2007-06-12 | You Han Bae | pH-sensitive polymeric micelles for drug delivery |
| US8263664B2 (en) | 2002-05-19 | 2012-09-11 | University Of Utah Research Foundation | pH-sensitive polymeric micelles for drug delivery |
| JP4440888B2 (ja) | 2003-11-04 | 2010-03-24 | スプラポリックス・ビー．ブイ． | 重合体幹内に４重水素結合単位を含む超分子重合体の製造 |
| EP1773903B1 (fr) | 2004-07-12 | 2017-08-09 | SupraPolix B.V. | Ionomeres supramoleculaires |
| US8357391B2 (en) | 2004-07-30 | 2013-01-22 | Advanced Cardiovascular Systems, Inc. | Coatings for implantable devices comprising poly (hydroxy-alkanoates) and diacid linkages |
| WO2006047279A2 (fr) * | 2004-10-21 | 2006-05-04 | University Of Iowa Research Foundation | Systeme d'administration in situ de medicaments a liberation controlee |
| ES2376888T3 (es) | 2005-05-04 | 2012-03-20 | Suprapolix B.V. | Materiales supramoleculares activos biológicamente, modulares biorreabsorbibles o biomédicos |
| US8246990B2 (en) | 2005-05-04 | 2012-08-21 | Suprapolix B.V. | Hydrogen bonded hydrogels |
| ATE527305T1 (de) | 2006-11-20 | 2011-10-15 | Suprapolix Bv | Supramolekulare polymere aus niedrigschmelzenden, leicht verarbeitbaren bausteinen |
| US8628789B2 (en) | 2007-03-23 | 2014-01-14 | Suprapolix, B.V. | Strong reversible hydrogels |
| ATE515538T1 (de) | 2007-03-23 | 2011-07-15 | Suprapolix Bv | Starke umkehrbare hydrogels |
| KR100838809B1 (ko) | 2007-05-03 | 2008-06-17 | 성균관대학교산학협력단 | 겔강도가 우수한 온도 및 피에치 민감성 블록 공중합체 및이의 제조방법과 이를 이용한 약물전달체 |
| JP5171146B2 (ja) * | 2007-07-27 | 2013-03-27 | 学校法人 関西大学 | 温度応答性を有する生分解性ポリマー及びその製造方法 |
| KR100951554B1 (ko) | 2008-06-04 | 2010-04-09 | 아주대학교산학협력단 | 마이셀 형성 및 약물 방출 제어가 가능한 6-팔ｐｌｌａ-ｐｅｇ 블록 공중합체 |
| WO2010002262A1 (fr) | 2008-07-04 | 2010-01-07 | Suprapolix B.V. | Composés supramoléculaires à grande fluidité |
| EP2450394B1 (fr) | 2010-11-05 | 2017-06-07 | SupraPolix B.V. | Procédé de préparation d'un polymère supra-moléculaire |
| CN104758256B (zh) * | 2014-02-14 | 2016-05-04 | 苏州海特比奥生物技术有限公司 | 一种多西他赛纳米聚合物胶束冻干制剂及其制备方法 |
| US10358521B2 (en) | 2014-07-28 | 2019-07-23 | Suprapolix B.V. | Durable hydrogen bonded hydrogels |
| US10835637B2 (en) | 2015-08-24 | 2020-11-17 | 3-D Matrix, Ltd. (Tokyo, Japan) | Biodegradable injectable gel |
| KR102552356B1 (ko) * | 2016-08-26 | 2023-07-07 | 에스케이 조인트 벤처스 | 보툴리눔 독소의 효능 증대를 위한 생분해성 폴리머 제제 |
| AR113096A1 (es) | 2017-07-17 | 2020-01-29 | Medincell | Mezclas de composiciones biodegradables que modulan la cinética de liberación de al menos un ingrediente activo en la administración de fármacos |
| CN110156971A (zh) | 2018-02-13 | 2019-08-23 | 上海时莱生物技术有限公司 | 一种两亲性嵌段共聚物及其制备方法和纳米胶束载药系统 |
| FI129022B (en) * | 2019-09-10 | 2021-05-14 | Aabo Akademi Univ | Polymer and composition made from a renewable source |
| CN114727946A (zh) * | 2019-09-13 | 2022-07-08 | 美蒂森股份公司 | 药物递送制剂 |
| EP4014963A1 (fr) * | 2020-12-16 | 2022-06-22 | Medincell | Composition pharmaceutique |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0092918B1 (fr) * | 1982-04-22 | 1988-10-19 | Imperial Chemical Industries Plc | Formulations à libération continue |
| US4438253A (en) * | 1982-11-12 | 1984-03-20 | American Cyanamid Company | Poly(glycolic acid)/poly(alkylene glycol) block copolymers and method of manufacturing the same |
| GB8416234D0 (en) * | 1984-06-26 | 1984-08-01 | Ici Plc | Biodegradable amphipathic copolymers |
| US5306501A (en) * | 1990-05-01 | 1994-04-26 | Mediventures, Inc. | Drug delivery by injection with thermoreversible gels containing polyoxyalkylene copolymers |
| KR960015447B1 (ko) * | 1993-03-16 | 1996-11-14 | 주식회사 삼양사 | 의료용 생분해성 고분자 |
| EP0717999A1 (fr) * | 1994-12-19 | 1996-06-26 | The University Of Miami | Composition pour délivrer un médicament |
| KR0180334B1 (ko) * | 1995-09-21 | 1999-03-20 | 김윤 | 블럭 공중합체 미셀을 이용한 약물전달체 및 이에 약물을 봉입하는 방법 |
-
1998
- 1998-08-08 KR KR1020007001304A patent/KR20010022708A/ko not_active Application Discontinuation
- 1998-08-08 CA CA002299393A patent/CA2299393A1/fr not_active Abandoned
- 1998-08-08 WO PCT/US1998/016418 patent/WO1999007343A1/fr not_active Application Discontinuation
- 1998-08-08 EP EP98940801A patent/EP1024790A4/fr not_active Withdrawn
- 1998-08-08 JP JP2000506937A patent/JP2001517603A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP1024790A4 (fr) | 2000-10-25 |
| JP2001517603A (ja) | 2001-10-09 |
| EP1024790A1 (fr) | 2000-08-09 |
| KR20010022708A (ko) | 2001-03-26 |
| WO1999007343A1 (fr) | 1999-02-18 |
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