IL89276A - תכשיר המכיל רלקסין של בני אדם - Google Patents

תכשיר המכיל רלקסין של בני אדם

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)

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/he

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
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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
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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
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210000000754 myometrium Anatomy 0.000 description 1
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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)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Epidemiology (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Engineering & Computer Science (AREA)
Oil, Petroleum & Natural Gas (AREA)
Organic Chemistry (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Reproductive Health (AREA)
Urology & Nephrology (AREA)
Endocrinology (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Dermatology (AREA)
Inorganic Chemistry (AREA)
Toxicology (AREA)
Zoology (AREA)
Gastroenterology & Hepatology (AREA)
Gynecology & Obstetrics (AREA)
Bioinformatics & Cheminformatics (AREA)
Genetics & Genomics (AREA)
Molecular Biology (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 תכשיר המכיל רלקסין של בני אדם IL89276A (he)

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 (he)	1994-06-24

Family

ID=26857232

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL8927689A IL89276A (he)	1988-02-26	1989-02-14	תכשיר המכיל רלקסין של בני אדם

Country Status (14)

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

Families Citing this family (38)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5166191A (en) *	1991-08-19	1992-11-24	Genentech, Inc.	Use of relaxin in cardiovascular therapy
US5478807A (en) *	1991-08-19	1995-12-26	Genentech, Inc.	Use of relaxin in the treatment of bradycardia
JPH07508341A (ja) *	1991-10-28	1995-09-14	ボード・オヴ・リージェンツ，ザ・ユニヴァーシティ・オヴ・テキサス・システム	生物サンプルおよび体液中の正常細胞と悪性腫瘍細胞とにおける分化マーカーの検出方法
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
WO1996011672A1 (en) *	1994-10-13	1996-04-25	Wakamoto Pharmaceutical Co., Ltd.	Lyophilized preparation providing reversibly thermogelling water-base medicinal composition
US5811395A (en) *	1995-06-07	1998-09-22	Medical University Of South Carolina	Relaxin analogs and derivatives methods and uses thereof
DE69624925T2 (de) *	1995-08-15	2003-09-04	Connetics Corp., Palo Alto	Verwendung von relaxin zur stimulierung der angiogenese
US5612051A (en) *	1995-11-17	1997-03-18	Yue; Samuel K.	Method of treating involuntary muscle dysfunction with relaxin hormone
EP0852951A1 (de)	1996-11-19	1998-07-15	Roche Diagnostics GmbH	Stabile lyophilisierte pharmazeutische Zubereitungen von mono- oder polyklonalen Antikörpern
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
NZ512644A (en) *	1998-12-18	2005-04-29	Palladin Healthcare Internatio	Composition for treatment of burns
DE60128540T2 (de) *	2000-02-09	2008-01-31	Bas Medical, Inc., San Mateo	Verwendung von relaxin zur behandlung von durch gefässverengung bedingten erkrankungen
US20050032683A1 (en) *	2000-10-04	2005-02-10	Amento Edward P.	Methods of modulating apoptosis by administration of relaxin agonists or antagonists
EP1391209A4 (en) *	2001-05-30	2009-12-16	Chugai Pharmaceutical Co Ltd	PROTEIN PREPARATION
US7660678B2 (en) *	2004-02-05	2010-02-09	Medpro Holdings, Llc	On-site method of providing analysis of potency and purity of pharmaceutical compounds
US20100134794A1 (en) *	2004-02-05	2010-06-03	Medpro Holdings, Llc	Analyzer for determining the concentration, 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
EP1753449A4 (en)	2004-04-30	2009-09-23	Corthera Inc	METHOD AND COMPOSITIONS FOR CONTROLLING FEDERAL GROWTH BY RELAXIN MODULATION
CA2576030A1 (en) *	2004-08-09	2006-02-23	Alios Biopharma Inc.	Synthetic hyperglycosylated, protease-resistant polypeptide variants, oral formulations and methods of using the same
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
AU2009246116B2 (en) *	2008-05-16	2013-02-14	Corthera, Inc.	Method of preventing premature delivery
WO2009140433A1 (en) *	2008-05-16	2009-11-19	Corthera, Inc.	Method of promoting wound healing
EP2405933A1 (en)	2009-03-13	2012-01-18	Medtronic, Inc	Method of treating heart failure
US20130053318A1 (en) *	2010-03-10	2013-02-28	Parry Laura	Modulating aquaporins with relaxin
SMT201900495T1 (it)	2010-08-17	2019-11-13	Ambrx Inc	Polipeptidi di relaxina modificati e loro usi
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
WO2016059593A1 (en) *	2014-10-16	2016-04-21	Piramal Enterprises Limited	Stable injectable composition of protein drugs and process for its preparation
CN107007822A (zh) *	2016-01-27	2017-08-04	江苏恒瑞医药股份有限公司	一种含有重组人松弛素‑2类似物的药物组合物及其制备方法
US10266578B2 (en)	2017-02-08	2019-04-23	Bristol-Myers Squibb Company	Modified relaxin polypeptides comprising a pharmacokinetic enhancer and uses thereof
MX2019011603A (es) *	2017-03-26	2021-08-16	Robyn Vivi Stafford	Metodo de tratamiento de las condiciones de la piel de los parpados.
WO2025056188A1 (en) *	2023-09-15	2025-03-20	Relaxera Pharmazeutische Gmbh & Co. Kg	Relaxin medication

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US2964448A (en) *	1959-01-27	1960-12-13	Anschel Joachim	Relaxin composition and process for preparing same
US3003117A (en) *	1959-09-29	1961-10-03	Gen Frecision Inc	Coincident frequency tracker
US3962416A (en) *	1971-01-25	1976-06-08	Sol Katzen	Preserved nutrients and products
EP0018609B1 (de) *	1979-04-30	1983-09-21	Hoechst Aktiengesellschaft	Gegen Denaturierung beständige, wässrige Protein-Lösungen, Verfahren zu ihrer Herstellung und ihre Verwendung
US4267101A (en) *	1980-02-01	1981-05-12	Serono Laboratories Inc.	Process for obtaining human relaxin from fetal membranes
DE3273597D1 (en) *	1981-11-28	1986-11-06	Sunstar Kk	Pharmaceutical composition containing interferon in stable state
IL69469A (en) *	1982-08-12	1991-06-10	Florey Howard Inst	Polypeptide having human h1-relaxin activity,double-stranded dna fragments coding therefor,vectors containing the dna fragments and methods for preparing the polypeptide,dna fragments and vectors
DE3236267A1 (de) *	1982-09-30	1984-04-05	Serono Pharmazeutische Präparate GmbH, 7800 Freiburg	Verfahren zur herstellung von relaxin und verfahren zur hochreinigung von relaxin
DE3236264A1 (de) *	1982-09-30	1984-04-05	Serono Pharmazeutische Präparate GmbH, 7800 Freiburg	Verfahren zur gewinnung von relaxin
IL70414A (en) *	1982-12-13	1991-06-10	Florey Howard Inst	Polypeptide having human h2-relaxin activity,double-stranded dna fragments coding therefor,vectors containing the dna fragments and methods for preparing the polypeptide,dna fragments and vectors
CH661662A5 (en) *	1984-04-16	1987-08-14	Georg L Prof Dr Floersheim	Product for the treatment of the skin and of the connective tissue
US4605555A (en) *	1984-09-20	1986-08-12	Sun Star Kabushiki Kaisha	Composition and method for treating keratosic disorder of skin and mucosa
US4806343A (en) *	1986-03-13	1989-02-21	University Of Southwestern Louisiana	Cryogenic protectant for proteins
AU612594B2 (en) *	1986-09-12	1991-07-18	Genentech Inc.	Human prorelaxin
US4717717A (en) *	1986-11-05	1988-01-05	Ethicon, Inc.	Stabilized compositions containing epidermal growth factor

1989
- 1989-02-08 JP JP1502501A patent/JP2815649B2/ja not_active Expired - Fee Related
- 1989-02-08 EP EP89902688A patent/EP0407401B1/en not_active Expired - Lifetime
- 1989-02-08 WO PCT/US1989/000502 patent/WO1989007945A1/en not_active Ceased
- 1989-02-08 DE DE89902688T patent/DE68906153T2/de not_active Expired - Fee Related
- 1989-02-08 AU AU31833/89A patent/AU626840B2/en not_active Ceased
- 1989-02-08 AT AT89902688T patent/ATE88352T1/de not_active IP Right Cessation
- 1989-02-13 IE IE45289A patent/IE63208B1/en not_active IP Right Cessation
- 1989-02-14 IL IL8927689A patent/IL89276A/he unknown
- 1989-02-16 NZ NZ228012A patent/NZ228012A/en unknown
- 1989-02-23 CA CA000591933A patent/CA1336403C/en not_active Expired - Lifetime
- 1989-02-24 PT PT89835A patent/PT89835B/pt not_active IP Right Cessation
- 1989-02-24 ES ES8900688A patent/ES2013394A6/es not_active Expired - Lifetime
- 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
CN1035619A (zh)	1989-09-20
AU3183389A (en)	1989-09-22
CN1052655C (zh)	2000-05-24
ES2013394A6 (es)	1990-05-01
DE68906153D1 (de)	1993-05-27
US5451572A (en)	1995-09-19
US5945402A (en)	1999-08-31
JP2815649B2 (ja)	1998-10-27
IL89276A0 (en)	1989-09-10
CA1336403C (en)	1995-07-25
WO1989007945A1 (en)	1989-09-08
EP0407401B1 (en)	1993-04-21
DE68906153T2 (de)	1993-10-28
PT89835A (pt)	1989-10-04
PT89835B (pt)	1994-01-31
IE890452L (en)	1989-08-26
JPH03502794A (ja)	1991-06-27
EP0407401A1 (en)	1991-01-16
NZ228012A (en)	1991-07-26
IE63208B1 (en)	1995-04-05
ATE88352T1 (de)	1993-05-15
AU626840B2 (en)	1992-08-13

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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