KR960705554A - 산화질소 합성 효소 기질 및(또는) 공여체를 사용한 갱년기 질병의 치료 방법(Treatment of Climacteric Disorders with Nitric Oxide Synthase Substrates and/or Donors) - Google Patents
산화질소 합성 효소 기질 및(또는) 공여체를 사용한 갱년기 질병의 치료 방법(Treatment of Climacteric Disorders with Nitric Oxide Synthase Substrates and/or Donors)Info
- Publication number
- KR960705554A KR960705554A KR1019960702551A KR19960702551A KR960705554A KR 960705554 A KR960705554 A KR 960705554A KR 1019960702551 A KR1019960702551 A KR 1019960702551A KR 19960702551 A KR19960702551 A KR 19960702551A KR 960705554 A KR960705554 A KR 960705554A
- Authority
- KR
- South Korea
- Prior art keywords
- nitric oxide
- estrogen
- use according
- mammal
- progestin
- Prior art date
Links
- 239000000758 substrate Substances 0.000 title claims abstract 13
- 102000008299 Nitric Oxide Synthase Human genes 0.000 title claims 4
- 108010021487 Nitric Oxide Synthase Proteins 0.000 title claims 4
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical class C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 claims abstract description 18
- 239000000583 progesterone congener Substances 0.000 claims abstract description 13
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims abstract 15
- 229940011871 estrogen Drugs 0.000 claims abstract 15
- 239000000262 estrogen Substances 0.000 claims abstract 15
- 239000002840 nitric oxide donor Substances 0.000 claims abstract 9
- 206010027304 Menopausal symptoms Diseases 0.000 claims abstract 4
- 229930064664 L-arginine Natural products 0.000 claims description 6
- 235000014852 L-arginine Nutrition 0.000 claims description 6
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims 11
- 239000000203 mixture Substances 0.000 claims 9
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 claims 4
- 238000002657 hormone replacement therapy Methods 0.000 claims 4
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 claims 3
- 229960005309 estradiol Drugs 0.000 claims 3
- 229960003711 glyceryl trinitrate Drugs 0.000 claims 3
- -1 noestysterone Chemical compound 0.000 claims 3
- 239000000186 progesterone Substances 0.000 claims 3
- 229960003387 progesterone Drugs 0.000 claims 3
- WWYNJERNGUHSAO-XUDSTZEESA-N (+)-Norgestrel Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](CC)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 WWYNJERNGUHSAO-XUDSTZEESA-N 0.000 claims 2
- NCGICGYLBXGBGN-UHFFFAOYSA-N 3-morpholin-4-yl-1-oxa-3-azonia-2-azanidacyclopent-3-en-5-imine;hydrochloride Chemical compound Cl.[N-]1OC(=N)C=[N+]1N1CCOCC1 NCGICGYLBXGBGN-UHFFFAOYSA-N 0.000 claims 2
- RSEPBGGWRJCQGY-RBRWEJTLSA-N Estradiol valerate Chemical compound C1CC2=CC(O)=CC=C2[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CCCC)[C@@]1(C)CC2 RSEPBGGWRJCQGY-RBRWEJTLSA-N 0.000 claims 2
- 208000017657 Menopausal disease Diseases 0.000 claims 2
- 239000000006 Nitroglycerin Substances 0.000 claims 2
- 230000036765 blood level Effects 0.000 claims 2
- XEYBHCRIKKKOSS-UHFFFAOYSA-N disodium;azanylidyneoxidanium;iron(2+);pentacyanide Chemical group [Na+].[Na+].[Fe+2].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].[O+]#N XEYBHCRIKKKOSS-UHFFFAOYSA-N 0.000 claims 2
- 229930182833 estradiol Natural products 0.000 claims 2
- 229960004766 estradiol valerate Drugs 0.000 claims 2
- MOYKHGMNXAOIAT-JGWLITMVSA-N isosorbide dinitrate Chemical compound [O-][N+](=O)O[C@H]1CO[C@@H]2[C@H](O[N+](=O)[O-])CO[C@@H]21 MOYKHGMNXAOIAT-JGWLITMVSA-N 0.000 claims 2
- 229960000201 isosorbide dinitrate Drugs 0.000 claims 2
- YWXYYJSYQOXTPL-SLPGGIOYSA-N isosorbide mononitrate Chemical compound [O-][N+](=O)O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 YWXYYJSYQOXTPL-SLPGGIOYSA-N 0.000 claims 2
- 229960003827 isosorbide mononitrate Drugs 0.000 claims 2
- 229960004400 levonorgestrel Drugs 0.000 claims 2
- 229940083618 sodium nitroprusside Drugs 0.000 claims 2
- DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 claims 1
- PROQIPRRNZUXQM-UHFFFAOYSA-N (16alpha,17betaOH)-Estra-1,3,5(10)-triene-3,16,17-triol Natural products OC1=CC=C2C3CCC(C)(C(C(O)C4)O)C4C3CCC2=C1 PROQIPRRNZUXQM-UHFFFAOYSA-N 0.000 claims 1
- HAKRSIFCTAKBRD-TYFJVFSVSA-N (8s,9s,10r,13s,14s,17s)-17-acetyl-1-methoxy-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one Chemical compound C1C[C@@H]2[C@@]3(C)C(OC)CC(=O)C=C3CC[C@H]2[C@@H]2CC[C@H](C(C)=O)[C@]21C HAKRSIFCTAKBRD-TYFJVFSVSA-N 0.000 claims 1
- DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 claims 1
- 125000002059 L-arginyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C([H])([H])C([H])([H])N([H])C(=N[H])N([H])[H] 0.000 claims 1
- 229960004976 desogestrel Drugs 0.000 claims 1
- RPLCPCMSCLEKRS-BPIQYHPVSA-N desogestrel Chemical compound C1CC[C@@H]2[C@H]3C(=C)C[C@](CC)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 RPLCPCMSCLEKRS-BPIQYHPVSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- JGMOKGBVKVMRFX-HQZYFCCVSA-N dydrogesterone Chemical compound C1=CC2=CC(=O)CC[C@@]2(C)[C@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 JGMOKGBVKVMRFX-HQZYFCCVSA-N 0.000 claims 1
- 229960001348 estriol Drugs 0.000 claims 1
- PROQIPRRNZUXQM-ZXXIGWHRSA-N estriol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H]([C@H](O)C4)O)[C@@H]4[C@@H]3CCC2=C1 PROQIPRRNZUXQM-ZXXIGWHRSA-N 0.000 claims 1
- 229960003399 estrone Drugs 0.000 claims 1
- GCKFUYQCUCGESZ-BPIQYHPVSA-N etonogestrel Chemical compound O=C1CC[C@@H]2[C@H]3C(=C)C[C@](CC)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 GCKFUYQCUCGESZ-BPIQYHPVSA-N 0.000 claims 1
- SIGSPDASOTUPFS-XUDSTZEESA-N gestodene Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](CC)([C@](C=C4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 SIGSPDASOTUPFS-XUDSTZEESA-N 0.000 claims 1
- 229960005352 gestodene Drugs 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000011159 matrix material Substances 0.000 claims 1
- 230000003647 oxidation Effects 0.000 claims 1
- 238000007254 oxidation reaction Methods 0.000 claims 1
- 230000001590 oxidative effect Effects 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 description 4
- 241000700159 Rattus Species 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
-
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- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
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- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
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- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
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Abstract
본 발명은 산화질소 기질 및(또는) 산화질소 공여체 중 어느 하나 또는 두개 모두를 단독으로, 또는 임의로 프로게스틴과 혼합하여, 또는 임신하지 않은 여성의 경우에는 프로게스틴 또는 에스트로겐 중 어느 하나 또는 두개 모두와 혼합하여 투여함으로써 갱년기 증상을 회복시키는 방법을 제공한다.
Description
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제1도는 임신 중, 분만 중 및 분만 후의 여러 단계에서 쥐로부터 채취한 자연적으로 수축하는 자궁 스트립에 대한 L-아르기닌(0.1mM 내지 10mM)의 투여량 의존적 이완 효과를 나타낸다, 제2도는 난소가 절제된 임신하지 않은 어른 쥐로부터 채취한 자궁 스트립의 자발적 수축성에 대한 L-아르기닌(0.6mM 내지 10mM)의 투여반응 효과를 나타낸다, 제3도는 산화질소 억제제 L-NAME 50mg을 단독으로, 또는 L-아르기닌 및 프로게스틴 프로메게스톤, R5020 어느 하나 또는 둘 모두와 함께 혼합하여 투여한 후에 시험 동물(쥐)의 혈압에 대한 효과를 나타내는 막대 그래프이다, 제4도는 제3도와 동일한 실험에서 상기 화합물의 새끼 중량에 대한 효과를 보여주는 막대 그래프이다.
Claims (26)
- 임신하지 않은 포유동물 암컷 또는 수컷의 갱년기 장해 (갱년기 증상) 치료용 약제 제조시의 a) 산화질소 합성 효소 기질, b) 산화질소 공여체, 또는 둘 모두, 및 임의로, d)프로게스틴, 또는 포유동물이 암컷인 경우 c) 에스트로겐과 d) 프로게스틴 모두의 용도.
- 제1항에 있어서, a)가 순환 L-아르기닌의 혈액 수준을 통상의 50~100nM 순환 수준보다 약 10~50mM 이상 더 높게 상승시키기에 유효환 양으로 사용되는 용도.
- 제1항 또는 제2항에 있어서, 포유동물이 갱년기 장해의 폐경기 증상으로 고통받는 임신하지 않은 여성인 용도.
- 제1항 또는 제2항에 있어서, 포유동물이 호르몬 대체 요법을 실시했거나 또는 실시한 예정의 임신하지 않은 여성인 용도.
- 제1항 또는 제2항에 있어서, 포유동물이 임신하지 않은 여성이고, a)가 산화질소 합성 효소 기질인 용도.
- 제5항에 있어서, 산화질소 기질이 L-아르긴닌인 용도.
- 제1항 또는 제2항에 있어서, 포유동물이 임신하지 않은 여성이고, a)가 산화질소 공여체인 용도.
- 제7항에 있어서, 산화질소 공여체가 소듐니트로프루사이드, 니트로글레세린, 글리세릴트리니트레이트, SIN-1, 이소소르비드모노니트레이트 또는 이소소르비드디니트레이트인 용도.
- 제7항에 있어서, 산화질소 공여체가 경구 투여용인 용도.
- 제1항 또는 제2항에 있어서, 포유동물이 임신하지 않은 여성이고, 산화질소기질 또는 공여체가 에스트로겐과 혼합된 경구 투여용인 용도.
- 제10항에 있어서, 에스트로겐이 에스트라디올 발레레이트, 말의 결합형 에스트로겐, 17β-에스트라디올, 에스트론 또는 에스트리올인 용도.
- 제1항 또는 제2항에 있어서, 포유동물이 임신하지 않은 여성이고, 산화질소기질 또는 공여체가 프로게스틴과 혼합된 경구 투여용인 용도.
- 제12항에 있어서, 프로게스틴이 프로게스테론, 디드로게스테론, 메드록시프로게스테론, 노르에티스테론, 레보노르게스트렐, 노르게스트렐, 게스토덴, 데소게스트렐 또는 3-케토-데소게스트렐인 용도.
- 제1항 또는 제2항에 있어서, 포유동물이 에스트로겐 또는 프로게스틴을 사용한 병존적이고 연속적인 호르몬 대체 요법을 받고 있는 임신하지 않은 여성인 용도.
- 제1항 또는 제2항에 있어서, 포유동물이 에스트로겐 및 프로게스틴을 사용한 병존적이고 순차적인 호르몬 대체 요법을 받고 있는 임신하지 않은 여성인 용도.
- 제1항 또는 제2항에 있어서, 포유동물이 에스트로겐 및 프로게스틴을 사용한 병존적이고 순차적인 호르몬 대체 요법을 받고 있는 남성인 용도.
- 제1항 또는 제2항에 있어서, 포유동물이 남성이고, 산화질고 기질 또는 공여체가 프로게스틴과 혼합된 투여용인 용도.
- (a) 산화질소 합성 기질, (b) 산화질소 공여체, 또는 둘 모두, 및 임의로, (c) 에스트로겐 또는 (d) 프로게스틴과 (c) 에스트로겐을 폐경기/폐경기 후의 포유동물 암컷에게 투여시 갱년기 증상을 회복시키는데 유효한 양으로 함유하는 혼합물로 이루어지는 것으로서, 에스트로겐은 1내지 2mg의 에스트라디올과 동등한 양의 유효량으로 및 프로게스틴은 50 내지 300mg의 주사된 프로게스테론과 생물학적으로 동등한 양으로 및 산화질소 합성 효소 기질, 산화기질 공여체 또는 두개 모두는 순환 L-아르기닌의 혈액 수준을 통상의 50 내지 100nM 순환 수준보다 약 10 내지 50nM 이상 더 높게 상승시키거나 또는 산화질소 공여체 수준을 약 1내지 1000nM까지 상승키기는데 유효한 양으로 함유되는 제약 조성물.
- 제18항에 있어서, (a)가 산화질소 합성 기질인 조성물.
- 제18항에 있어서, 산화질소 합성 기질 (a)가 L-아르기닌인 조성물.
- 제18항에 있어서, (b)가 산화질소 공여체인 조성물.
- 제21항에 있어서, 산화질소 공여체 (b)가 소듐니트로프루사이드, 니트로글리세린, 글리세릴트리니트라이드, SIN-1, 이소소르비드모노니트레이트 또는 이소소르비드디니트레이트인 조성물.
- 제18항에 있어서, 에스트로겐 (c)가 에스트라디올 발레레이트인 조성물.
- 제18항에 있어서, 에스트로겐 (c)가 에스트라디올인 조성물.
- 제18항에 있어서, 에스트로겐 (c)가 노르게스트렐인 조성물.
- 제18항에 있어서, 에스트로겐 (c)가 프로게스테론인 조성물.※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/153,345 US5595970A (en) | 1993-07-16 | 1993-11-16 | Treatment of climacteric disorders with nitric oxide synthase substrates and/or donors |
US08/153,345 | 1993-11-16 | ||
PCT/EP1994/003818 WO1995013800A1 (en) | 1993-11-16 | 1994-11-17 | Treatment of climacteric disorders with nitric oxide synthase substrates and/or donors |
Publications (1)
Publication Number | Publication Date |
---|---|
KR960705554A true KR960705554A (ko) | 1996-11-08 |
Family
ID=22546812
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1019960702551A KR960705554A (ko) | 1993-11-16 | 1994-11-17 | 산화질소 합성 효소 기질 및(또는) 공여체를 사용한 갱년기 질병의 치료 방법(Treatment of Climacteric Disorders with Nitric Oxide Synthase Substrates and/or Donors) |
Country Status (16)
Country | Link |
---|---|
US (2) | US5595970A (ko) |
EP (1) | EP0730445A1 (ko) |
JP (1) | JPH09505069A (ko) |
KR (1) | KR960705554A (ko) |
CN (1) | CN1135177A (ko) |
AU (1) | AU8144694A (ko) |
BR (1) | BR9408062A (ko) |
CA (1) | CA2176727A1 (ko) |
CZ (1) | CZ140096A3 (ko) |
FI (1) | FI962110A (ko) |
HU (1) | HUT74459A (ko) |
NO (1) | NO961994L (ko) |
NZ (1) | NZ276106A (ko) |
PL (1) | PL178130B1 (ko) |
SK (1) | SK63496A3 (ko) |
WO (1) | WO1995013800A1 (ko) |
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-
1993
- 1993-11-16 US US08/153,345 patent/US5595970A/en not_active Expired - Lifetime
-
1994
- 1994-11-17 BR BR9408062A patent/BR9408062A/pt not_active Application Discontinuation
- 1994-11-17 CZ CZ961400A patent/CZ140096A3/cs unknown
- 1994-11-17 AU AU81446/94A patent/AU8144694A/en not_active Abandoned
- 1994-11-17 CA CA002176727A patent/CA2176727A1/en not_active Abandoned
- 1994-11-17 WO PCT/EP1994/003818 patent/WO1995013800A1/en not_active Application Discontinuation
- 1994-11-17 EP EP95900760A patent/EP0730445A1/en not_active Withdrawn
- 1994-11-17 CN CN94194167A patent/CN1135177A/zh active Pending
- 1994-11-17 HU HU9601301A patent/HUT74459A/hu unknown
- 1994-11-17 PL PL94314466A patent/PL178130B1/pl unknown
- 1994-11-17 KR KR1019960702551A patent/KR960705554A/ko not_active Application Discontinuation
- 1994-11-17 SK SK634-96A patent/SK63496A3/sk unknown
- 1994-11-17 JP JP7514225A patent/JPH09505069A/ja active Pending
- 1994-11-17 NZ NZ276106A patent/NZ276106A/en unknown
-
1995
- 1995-06-06 US US08/466,538 patent/US5958878A/en not_active Expired - Fee Related
-
1996
- 1996-05-15 NO NO961994A patent/NO961994L/no not_active Application Discontinuation
- 1996-05-17 FI FI962110A patent/FI962110A/fi unknown
Also Published As
Publication number | Publication date |
---|---|
NZ276106A (en) | 1998-05-27 |
US5595970A (en) | 1997-01-21 |
NO961994L (no) | 1996-07-16 |
EP0730445A1 (en) | 1996-09-11 |
CA2176727A1 (en) | 1995-05-26 |
CZ140096A3 (en) | 1996-09-11 |
WO1995013800A1 (en) | 1995-05-26 |
BR9408062A (pt) | 1996-11-24 |
HU9601301D0 (en) | 1996-07-29 |
HUT74459A (en) | 1996-12-30 |
CN1135177A (zh) | 1996-11-06 |
PL314466A1 (en) | 1996-09-16 |
SK63496A3 (en) | 1997-03-05 |
FI962110A (fi) | 1996-07-15 |
AU8144694A (en) | 1995-06-06 |
PL178130B1 (pl) | 2000-03-31 |
US5958878A (en) | 1999-09-28 |
JPH09505069A (ja) | 1997-05-20 |
NO961994D0 (no) | 1996-05-15 |
FI962110A0 (fi) | 1996-05-17 |
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