IL89276A - A preparation containing human relaxin - Google Patents

A preparation containing human relaxin

Info

Publication number: IL89276A
Authority: IL; Israel
Prior art keywords: relaxin; composition; buffer; formulation; gel
Prior art date: 1988-02-26

Application number

IL8927689A

Other languages

English (en)

Hebrew (he)

Other versions

IL89276A0 (en

Original Assignee

Genentech Inc

Priority date (The priority date 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 date listed.)

1988-02-26

Filing date

1989-02-14

Publication date

1994-06-24

1989-02-14 Application filed by Genentech Inc filed Critical Genentech Inc

1989-02-14 Priority to IL108658A priority Critical patent/IL108658A/en

1989-09-10 Publication of IL89276A0 publication Critical patent/IL89276A0/xx

1994-06-24 Publication of IL89276A publication Critical patent/IL89276A/en

Links

239000000203 mixture Substances 0.000 title claims abstract description 150
BJRCFZKVYNDCJE-WBSNEMHCSA-N 99489-95-9 Chemical compound C([C@@H]1NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@H](C(N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)NCC(=O)N2)[C@@H](C)CC)=O)CSSC[C@@H](C(NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CSSC[C@H](NC1=O)C(O)=O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O)[C@@H](C)CC)[C@@H](C)CC)C(C)C)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](N)CCCCN)C(C)C)[C@@H](C)CC)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCNC(N)=N)C(C)C)C1=CC=C(O)C=C1 BJRCFZKVYNDCJE-WBSNEMHCSA-N 0.000 title claims abstract description 54
238000009472 formulation Methods 0.000 title description 83
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 75
239000000872 buffer Substances 0.000 claims abstract description 39
239000011780 sodium chloride Substances 0.000 claims abstract description 38
239000007979 citrate buffer Substances 0.000 claims abstract description 24
239000003795 chemical substances by application Substances 0.000 claims abstract description 13
230000032696 parturition Effects 0.000 claims abstract description 7
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 49
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 43
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical group [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 34
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239000007788 liquid Substances 0.000 claims description 17
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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 claims description 10
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239000000594 mannitol Substances 0.000 claims description 10
235000010355 mannitol Nutrition 0.000 claims description 10
150000005846 sugar alcohols Chemical class 0.000 claims description 8
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 7
241000124008 Mammalia Species 0.000 claims description 5
239000008351 acetate buffer Substances 0.000 claims description 5
HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 4
150000007524 organic acids Chemical group 0.000 claims description 4
230000037195 reproductive physiology Effects 0.000 claims description 4
229910052783 alkali metal Inorganic materials 0.000 claims description 3
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 claims description 2
HEBKCHPVOIAQTA-QWWZWVQMSA-N D-arabinitol Chemical compound OC[C@@H](O)C(O)[C@H](O)CO HEBKCHPVOIAQTA-QWWZWVQMSA-N 0.000 claims description 2
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 claims description 2
239000004386 Erythritol Substances 0.000 claims description 2
UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 claims description 2
TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 2
229910052784 alkaline earth metal Inorganic materials 0.000 claims description 2
239000007853 buffer solution Substances 0.000 claims description 2
235000019414 erythritol Nutrition 0.000 claims description 2
UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 claims description 2
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239000000600 sorbitol Substances 0.000 claims description 2
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235000010447 xylitol Nutrition 0.000 claims description 2
HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 2
229960002675 xylitol Drugs 0.000 claims description 2
150000001340 alkali metals Chemical group 0.000 claims 2
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239000003937 drug carrier Substances 0.000 claims 1
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230000002378 acidificating effect Effects 0.000 abstract description 4
239000003381 stabilizer Substances 0.000 abstract description 2
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238000004007 reversed phase HPLC Methods 0.000 description 30
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WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 24
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150000001413 amino acids Chemical class 0.000 description 21
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CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 20
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238000002360 preparation method Methods 0.000 description 15
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QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 12
238000003860 storage Methods 0.000 description 12
238000002474 experimental method Methods 0.000 description 11
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
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QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 9
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230000008033 biological extinction Effects 0.000 description 9
210000004246 corpus luteum Anatomy 0.000 description 9
108090000765 processed proteins & peptides Proteins 0.000 description 9
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 8
230000006870 function Effects 0.000 description 8
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239000011777 magnesium Substances 0.000 description 8
IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 7
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IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 7
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KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
238000001990 intravenous administration Methods 0.000 description 6
238000007920 subcutaneous administration Methods 0.000 description 6
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 6
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WBZKQQHYRPRKNJ-UHFFFAOYSA-L disulfite Chemical compound [O-]S(=O)S([O-])(=O)=O WBZKQQHYRPRKNJ-UHFFFAOYSA-L 0.000 description 4
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KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
241001529936 Murinae Species 0.000 description 3
229910052782 aluminium Inorganic materials 0.000 description 3
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 3
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QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
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LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
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210000001365 lymphatic vessel Anatomy 0.000 description 1
239000008176 lyophilized powder Substances 0.000 description 1
125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
210000002540 macrophage Anatomy 0.000 description 1
OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 1
229910001623 magnesium bromide Inorganic materials 0.000 description 1
229940049920 malate Drugs 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
210000005075 mammary gland Anatomy 0.000 description 1
LUEWUZLMQUOBSB-GFVSVBBRSA-N mannan Chemical class O[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@H]3[C@H](O[C@@H](O)[C@@H](O)[C@H]3O)CO)[C@@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O LUEWUZLMQUOBSB-GFVSVBBRSA-N 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
229930182817 methionine Natural products 0.000 description 1
125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
238000010369 molecular cloning Methods 0.000 description 1
PJUIMOJAAPLTRJ-UHFFFAOYSA-N monothioglycerol Chemical compound OCC(O)CS PJUIMOJAAPLTRJ-UHFFFAOYSA-N 0.000 description 1
210000004877 mucosa Anatomy 0.000 description 1
230000003387 muscular Effects 0.000 description 1
210000000754 myometrium Anatomy 0.000 description 1
239000013642 negative control Substances 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
238000011587 new zealand white rabbit Methods 0.000 description 1
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239000011570 nicotinamide Substances 0.000 description 1
229960003512 nicotinic acid Drugs 0.000 description 1
PVNIIMVLHYAWGP-UHFFFAOYSA-N nicotinic acid Natural products OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
239000002736 nonionic surfactant Substances 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
239000002773 nucleotide Substances 0.000 description 1
125000003729 nucleotide group Chemical group 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
230000002611 ovarian Effects 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
230000037361 pathway Effects 0.000 description 1
229960001412 pentobarbital Drugs 0.000 description 1
239000000813 peptide hormone Substances 0.000 description 1
150000002978 peroxides Chemical class 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
239000004033 plastic Substances 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
230000008092 positive effect Effects 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000001103 potassium chloride Substances 0.000 description 1
235000011164 potassium chloride Nutrition 0.000 description 1
239000004224 potassium gluconate Substances 0.000 description 1
229960003189 potassium gluconate Drugs 0.000 description 1
LCPMNMXCIHBTEX-UHFFFAOYSA-M potassium;2-hydroxypropanoate;2-hydroxypropanoic acid Chemical compound [K+].CC(O)C(O)=O.CC(O)C([O-])=O LCPMNMXCIHBTEX-UHFFFAOYSA-M 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
239000010453 quartz Substances 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
230000008707 rearrangement Effects 0.000 description 1
238000005215 recombination Methods 0.000 description 1
230000006798 recombination Effects 0.000 description 1
239000012925 reference material Substances 0.000 description 1
239000013074 reference sample Substances 0.000 description 1
230000008929 regeneration Effects 0.000 description 1
238000011069 regeneration method Methods 0.000 description 1
238000000611 regression analysis Methods 0.000 description 1
238000007634 remodeling Methods 0.000 description 1
238000009877 rendering Methods 0.000 description 1
230000003252 repetitive effect Effects 0.000 description 1
230000004044 response Effects 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
238000005070 sampling Methods 0.000 description 1
125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
BHZOKUMUHVTPBX-UHFFFAOYSA-M sodium acetic acid acetate Chemical compound [Na+].CC(O)=O.CC([O-])=O BHZOKUMUHVTPBX-UHFFFAOYSA-M 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].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 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 description 1
HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
239000000176 sodium gluconate Substances 0.000 description 1
229940005574 sodium gluconate Drugs 0.000 description 1
OABYVIYXWMZFFJ-ZUHYDKSRSA-M sodium glycocholate Chemical compound [Na+].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)NCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 OABYVIYXWMZFFJ-ZUHYDKSRSA-M 0.000 description 1
229940001584 sodium metabisulfite Drugs 0.000 description 1
235000010262 sodium metabisulphite Nutrition 0.000 description 1
LLVQEXSQFBTIRD-UHFFFAOYSA-M sodium;2,3,4-trihydroxy-4-oxobutanoate;hydrate Chemical compound O.[Na+].OC(=O)C(O)C(O)C([O-])=O LLVQEXSQFBTIRD-UHFFFAOYSA-M 0.000 description 1
KMPHTYSTEHXSTL-UHFFFAOYSA-M sodium;2-hydroxypropanoate;2-hydroxypropanoic acid Chemical compound [Na+].CC(O)C(O)=O.CC(O)C([O-])=O KMPHTYSTEHXSTL-UHFFFAOYSA-M 0.000 description 1
VDZDAHYKYRVHJR-UHFFFAOYSA-M sodium;2-hydroxypropanoate;hydrate Chemical compound [OH-].[Na+].CC(O)C(O)=O VDZDAHYKYRVHJR-UHFFFAOYSA-M 0.000 description 1
OESFSXYRSCBAQJ-UHFFFAOYSA-M sodium;3-carboxy-3,5-dihydroxy-5-oxopentanoate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].OC(=O)CC(O)(C(O)=O)CC(O)=O.OC(=O)CC(O)(C(O)=O)CC([O-])=O OESFSXYRSCBAQJ-UHFFFAOYSA-M 0.000 description 1
DGPIGKCOQYBCJH-UHFFFAOYSA-M sodium;acetic acid;hydroxide Chemical compound O.[Na+].CC([O-])=O DGPIGKCOQYBCJH-UHFFFAOYSA-M 0.000 description 1
VBGUQBPWJMPQBI-UHFFFAOYSA-M sodium;butanedioic acid;4-hydroxy-4-oxobutanoate Chemical compound [Na+].OC(=O)CCC(O)=O.OC(=O)CCC([O-])=O VBGUQBPWJMPQBI-UHFFFAOYSA-M 0.000 description 1
JISIBLCXFLGVJX-UHFFFAOYSA-M sodium;butanedioic acid;hydroxide Chemical compound [OH-].[Na+].OC(=O)CCC(O)=O JISIBLCXFLGVJX-UHFFFAOYSA-M 0.000 description 1
239000007790 solid phase Substances 0.000 description 1
238000002798 spectrophotometry method Methods 0.000 description 1
230000006641 stabilisation Effects 0.000 description 1
238000013112 stability test Methods 0.000 description 1
238000012430 stability testing Methods 0.000 description 1
238000011105 stabilization Methods 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
230000002194 synthesizing effect Effects 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
210000004876 tela submucosa Anatomy 0.000 description 1
238000012360 testing method Methods 0.000 description 1
WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
229940035024 thioglycerol Drugs 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
239000012049 topical pharmaceutical composition Substances 0.000 description 1
238000013519 translation Methods 0.000 description 1
239000012588 trypsin Substances 0.000 description 1
125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
239000011123 type I (borosilicate glass) Substances 0.000 description 1
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
238000000108 ultra-filtration Methods 0.000 description 1
210000000689 upper leg Anatomy 0.000 description 1
210000004291 uterus Anatomy 0.000 description 1
210000001215 vagina Anatomy 0.000 description 1
210000003462 vein Anatomy 0.000 description 1
238000005303 weighing Methods 0.000 description 1
229920001285 xanthan gum Polymers 0.000 description 1
235000010493 xanthan gum Nutrition 0.000 description 1
239000000230 xanthan gum Substances 0.000 description 1
229940082509 xanthan gum Drugs 0.000 description 1
229920001221 xylan Polymers 0.000 description 1
150000004823 xylans Chemical class 0.000 description 1
UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1

Classifications

- 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
- A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
- 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
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/64—Relaxins
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
Epidemiology (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Oil, Petroleum & Natural Gas (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Urology & Nephrology (AREA)
Reproductive Health (AREA)
Endocrinology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Molecular Biology (AREA)
Bioinformatics & Cheminformatics (AREA)
Toxicology (AREA)
Zoology (AREA)
Gastroenterology & Hepatology (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Genetics & Genomics (AREA)
Inorganic Chemistry (AREA)
Gynecology & Obstetrics (AREA)
Dermatology (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Medicinal Preparation (AREA)
Steroid Compounds (AREA)
Electrotherapy Devices (AREA)
Materials For Medical Uses (AREA)
Control Of Motors That Do Not Use Commutators (AREA)
Peptides Or Proteins (AREA)

IL8927689A 1988-02-26 1989-02-14 A preparation containing human relaxin IL89276A (en)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
IL108658A IL108658A (en)	1988-02-26	1989-02-14	Human relaxin pharmaceutical gel compositions

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US16079788A	1988-02-26	1988-02-26
US30377989A	1989-01-27	1989-01-27

Publications (2)

Publication Number	Publication Date
IL89276A0 IL89276A0 (en)	1989-09-10
IL89276A true IL89276A (en)	1994-06-24

Family

ID=26857232

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL8927689A IL89276A (en)	1988-02-26	1989-02-14	A preparation containing human relaxin

Country Status (14)

Country	Link
US (2)	US5451572A (fr)
EP (1)	EP0407401B1 (fr)
JP (1)	JP2815649B2 (fr)
CN (1)	CN1052655C (fr)
AT (1)	ATE88352T1 (fr)
AU (1)	AU626840B2 (fr)
CA (1)	CA1336403C (fr)
DE (1)	DE68906153T2 (fr)
ES (1)	ES2013394A6 (fr)
IE (1)	IE63208B1 (fr)
IL (1)	IL89276A (fr)
NZ (1)	NZ228012A (fr)
PT (1)	PT89835B (fr)
WO (1)	WO1989007945A1 (fr)

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US5166191A (en) *	1991-08-19	1992-11-24	Genentech, Inc.	Use of relaxin in cardiovascular therapy
AU3123393A (en) *	1991-10-28	1993-06-07	Board Of Regents, The University Of Texas System	A method for detecting a differentiation marker in normal and carcinoma cells and in biological samples and body fluid
US5192743A (en) *	1992-01-16	1993-03-09	Genentech, Inc.	Reconstitutable lyophilized protein formulation
US5830848A (en) *	1992-10-09	1998-11-03	The Regents Of The University Of California	Method and agents for inducement of endogenous nitric oxide synthase for control and management of labor during pregnancy
US5756552A (en) *	1994-10-13	1998-05-26	Wakamoto Pharmaceutical Co., Ltd.	Lyophilized pharmaceutical preparations capable of providing aqueous drug composition having property of reversible thermosetting gelation
US5811395A (en) *	1995-06-07	1998-09-22	Medical University Of South Carolina	Relaxin analogs and derivatives methods and uses thereof
CA2229479C (fr)	1995-08-15	2010-03-30	Connective Therapeutics, Inc.	Procede de stimulation de l'angiogenese
US5612051A (en) *	1995-11-17	1997-03-18	Yue; Samuel K.	Method of treating involuntary muscle dysfunction with relaxin hormone
EP0852951A1 (fr)	1996-11-19	1998-07-15	Roche Diagnostics GmbH	Compositions pharmaceutiques stables, lyophilisées d'anticorps monoclonaux ou polyclonaux
US5994148A (en)	1997-06-23	1999-11-30	The Regents Of University Of California	Method of predicting and enhancing success of IVF/ET pregnancy
US6251863B1 (en)	1998-09-08	2001-06-26	Samuel K. Yue	Method of preventing and treating symptoms of aging and neurodegenerative dysfunctions with relaxin
PT1140001E (pt) *	1998-12-18	2005-09-30	Palladin Healthcare Internat L	Composicao para tratamento de queimaduras
EP1253929B1 (fr) *	2000-02-09	2007-05-23	BAS Medical, Inc.	Utilisation de relaxine dans le traitement de maladies liees a la vasoconstriction
US20050032683A1 (en)	2000-10-04	2005-02-10	Amento Edward P.	Methods of modulating apoptosis by administration of relaxin agonists or antagonists
JP5052736B2 (ja) *	2001-05-30	2012-10-17	中外製薬株式会社	タンパク質製剤
US20100134794A1 (en) *	2004-02-05	2010-06-03	Medpro Holdings, Llc	Analyzer for determining the concentration, potency and purity of pharmaceutical compounds
US7660678B2 (en) *	2004-02-05	2010-02-09	Medpro Holdings, Llc	On-site method of providing analysis of potency and purity of pharmaceutical compounds
US7878978B2 (en)	2004-03-18	2011-02-01	University Of Pittsburgh- Of The Commonwealth System Of Higher Education	Use of relaxin to increase arterial compliance
JP4836942B2 (ja) *	2004-04-30	2011-12-14	コーセラ，インコーポレイテッド	リラキシンの調節による胎仔の発育の制御のための方法および組成物
WO2006020580A2 (fr) *	2004-08-09	2006-02-23	Alios Biopharma Inc.	Variants de polypeptides synthetiques hyperglycosyles resistants a la protease, formulations orales et leurs procedes d'utilisation
US7597884B2 (en)	2004-08-09	2009-10-06	Alios Biopharma, Inc.	Hyperglycosylated polypeptide variants and methods of use
US20060052304A1 (en) *	2004-09-02	2006-03-09	Bas Medical, Inc.	Method for remodeling bone and related sutures
US20080241260A1 (en) *	2005-09-28	2008-10-02	Padma Venkitachalam Devarajan	Compositions for Enhanced Absorption of Biologically Active Agents
MX2010012454A (es) *	2008-05-16	2011-03-29	Corthera Inc Star	Metodo para promover la curacion de heridas.
RU2501573C2 (ru) *	2008-05-16	2013-12-20	Кортера, Инк.	Способ предупреждения преждевременных родов
WO2010105081A1 (fr)	2009-03-13	2010-09-16	Medtronic, Inc.	Procédé de traitement d'insuffisance cardiaque
EP2544706B1 (fr)	2010-03-10	2015-06-17	The University Of Melbourne	Modulation d'aquaporines par le biais de la relaxine
EA030886B1 (ru)	2010-08-17	2018-10-31	Амбркс, Инк.	Модифицированные полипептиды релаксина, содержащие некодируемую в природе аминокислоту, связанную с полимером, и их применение
CN102133200B (zh) *	2011-03-16	2012-07-25	济南环肽医药科技有限公司	一种人类松弛素-2 Relaxin的注射用冻干粉制剂
US9393288B2 (en)	2012-05-29	2016-07-19	The University Of Vermont And State Agricultural College	Methods of treating diseases associated with PPARγ
CN103768584A (zh) *	2014-02-10	2014-05-07	济南环肽医药科技有限公司	一种松弛肽注射液
CN104922661B (zh) *	2014-03-20	2018-08-24	深圳翰宇药业股份有限公司	一种含有serelaxin的药物组合物及其制备方法
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1989
- 1989-02-08 AU AU31833/89A patent/AU626840B2/en not_active Ceased
- 1989-02-08 WO PCT/US1989/000502 patent/WO1989007945A1/fr not_active Ceased
- 1989-02-08 EP EP89902688A patent/EP0407401B1/fr not_active Expired - Lifetime
- 1989-02-08 DE DE89902688T patent/DE68906153T2/de not_active Expired - Fee Related
- 1989-02-08 AT AT89902688T patent/ATE88352T1/de not_active IP Right Cessation
- 1989-02-08 JP JP1502501A patent/JP2815649B2/ja not_active Expired - Fee Related
- 1989-02-13 IE IE45289A patent/IE63208B1/en not_active IP Right Cessation
- 1989-02-14 IL IL8927689A patent/IL89276A/en unknown
- 1989-02-16 NZ NZ228012A patent/NZ228012A/en unknown
- 1989-02-23 CA CA000591933A patent/CA1336403C/fr not_active Expired - Lifetime
- 1989-02-24 ES ES8900688A patent/ES2013394A6/es not_active Expired - Lifetime
- 1989-02-24 PT PT89835A patent/PT89835B/pt not_active IP Right Cessation
- 1989-02-25 CN CN89100947A patent/CN1052655C/zh not_active Expired - Fee Related
1993
- 1993-04-20 US US08/050,745 patent/US5451572A/en not_active Expired - Lifetime
1995
- 1995-06-06 US US08/471,920 patent/US5945402A/en not_active Expired - Lifetime

Also Published As

Publication number	Publication date
PT89835B (pt)	1994-01-31
EP0407401B1 (fr)	1993-04-21
AU3183389A (en)	1989-09-22
IE890452L (en)	1989-08-26
IL89276A0 (en)	1989-09-10
WO1989007945A1 (fr)	1989-09-08
US5945402A (en)	1999-08-31
NZ228012A (en)	1991-07-26
ES2013394A6 (es)	1990-05-01
CN1052655C (zh)	2000-05-24
CN1035619A (zh)	1989-09-20
US5451572A (en)	1995-09-19
ATE88352T1 (de)	1993-05-15
AU626840B2 (en)	1992-08-13
JPH03502794A (ja)	1991-06-27
CA1336403C (fr)	1995-07-25
PT89835A (pt)	1989-10-04
DE68906153D1 (de)	1993-05-27
IE63208B1 (en)	1995-04-05
DE68906153T2 (de)	1993-10-28
JP2815649B2 (ja)	1998-10-27
EP0407401A1 (fr)	1991-01-16

Legal Events

Date	Code	Title
1999-07-14	KB	Patent renewed
2003-04-10	KB	Patent renewed
2007-05-21	KB	Patent renewed

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