WO1997045114A1 - Traitement de maladies vasculaires avec des prostaglandines administrees par l'intermediaire d'un tampon dermique a liberation entretenue - Google Patents
Traitement de maladies vasculaires avec des prostaglandines administrees par l'intermediaire d'un tampon dermique a liberation entretenue Download PDFInfo
- Publication number
- WO1997045114A1 WO1997045114A1 PCT/US1997/009600 US9709600W WO9745114A1 WO 1997045114 A1 WO1997045114 A1 WO 1997045114A1 US 9709600 W US9709600 W US 9709600W WO 9745114 A1 WO9745114 A1 WO 9745114A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- day
- prostaglandin
- dosage
- misoprostol
- prostaglandins
- Prior art date
Links
- 150000003180 prostaglandins Chemical class 0.000 title claims abstract description 47
- 229940094443 oxytocics prostaglandins Drugs 0.000 title claims description 19
- 208000019553 vascular disease Diseases 0.000 title description 4
- 239000007933 dermal patch Substances 0.000 title description 3
- 238000013268 sustained release Methods 0.000 title description 2
- 239000012730 sustained-release form Substances 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 23
- 230000003480 fibrinolytic effect Effects 0.000 claims abstract description 14
- 230000003190 augmentative effect Effects 0.000 claims abstract description 13
- 230000020764 fibrinolysis Effects 0.000 claims abstract description 12
- 230000002093 peripheral effect Effects 0.000 claims abstract description 9
- 230000000304 vasodilatating effect Effects 0.000 claims abstract description 9
- 239000003527 fibrinolytic agent Substances 0.000 claims abstract description 8
- 206010003210 Arteriosclerosis Diseases 0.000 claims abstract description 5
- 208000011775 arteriosclerosis disease Diseases 0.000 claims abstract description 5
- OJLOPKGSLYJEMD-URPKTTJQSA-N methyl 7-[(1r,2r,3r)-3-hydroxy-2-[(1e)-4-hydroxy-4-methyloct-1-en-1-yl]-5-oxocyclopentyl]heptanoate Chemical compound CCCCC(C)(O)C\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(=O)OC OJLOPKGSLYJEMD-URPKTTJQSA-N 0.000 claims description 16
- 229960005249 misoprostol Drugs 0.000 claims description 15
- KAQKFAOMNZTLHT-OZUDYXHBSA-N prostaglandin I2 Chemical compound O1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-OZUDYXHBSA-N 0.000 claims description 13
- 239000008280 blood Substances 0.000 claims description 7
- 210000004369 blood Anatomy 0.000 claims description 7
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 5
- 230000000302 ischemic effect Effects 0.000 claims description 4
- PXGPLTODNUVGFL-BRIYLRKRSA-N (E,Z)-(1R,2R,3R,5S)-7-(3,5-Dihydroxy-2-((3S)-(3-hydroxy-1-octenyl))cyclopentyl)-5-heptenoic acid Chemical compound CCCCC[C@H](O)C=C[C@H]1[C@H](O)C[C@H](O)[C@@H]1CC=CCCCC(O)=O PXGPLTODNUVGFL-BRIYLRKRSA-N 0.000 claims description 3
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 claims description 3
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 claims description 3
- 230000007774 longterm Effects 0.000 claims description 3
- BHMBVRSPMRCCGG-OUTUXVNYSA-N prostaglandin D2 Chemical compound CCCCC[C@H](O)\C=C\[C@@H]1[C@@H](C\C=C/CCCC(O)=O)[C@@H](O)CC1=O BHMBVRSPMRCCGG-OUTUXVNYSA-N 0.000 claims description 3
- 229960002240 iloprost Drugs 0.000 claims description 2
- HIFJCPQKFCZDDL-ACWOEMLNSA-N iloprost Chemical compound C1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)C(C)CC#CC)[C@H](O)C[C@@H]21 HIFJCPQKFCZDDL-ACWOEMLNSA-N 0.000 claims description 2
- 229920002307 Dextran Polymers 0.000 claims 1
- GMVPRGQOIOIIMI-DWKJAMRDSA-N prostaglandin E1 Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(O)=O GMVPRGQOIOIIMI-DWKJAMRDSA-N 0.000 claims 1
- 230000000694 effects Effects 0.000 description 14
- 238000001802 infusion Methods 0.000 description 11
- 239000003814 drug Substances 0.000 description 8
- 229960001123 epoprostenol Drugs 0.000 description 8
- 229940079593 drug Drugs 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 6
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 230000002496 gastric effect Effects 0.000 description 5
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 4
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 230000024883 vasodilation Effects 0.000 description 4
- 208000002193 Pain Diseases 0.000 description 3
- 208000012322 Raynaud phenomenon Diseases 0.000 description 3
- 208000025865 Ulcer Diseases 0.000 description 3
- 230000002354 daily effect Effects 0.000 description 3
- 210000003414 extremity Anatomy 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 229960002715 nicotine Drugs 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 229940100640 transdermal system Drugs 0.000 description 3
- 231100000397 ulcer Toxicity 0.000 description 3
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- 206010017711 Gangrene Diseases 0.000 description 2
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 2
- 238000002266 amputation Methods 0.000 description 2
- 230000003143 atherosclerotic effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 235000004626 essential fatty acids Nutrition 0.000 description 2
- PJMPHNIQZUBGLI-UHFFFAOYSA-N fentanyl Chemical compound C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 PJMPHNIQZUBGLI-UHFFFAOYSA-N 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 238000001361 intraarterial administration Methods 0.000 description 2
- 230000003387 muscular Effects 0.000 description 2
- WGJJROVFWIXTPA-OALUTQOASA-N prostanoic acid Chemical compound CCCCCCCC[C@H]1CCC[C@@H]1CCCCCCC(O)=O WGJJROVFWIXTPA-OALUTQOASA-N 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 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 description 1
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 241000766026 Coregonus nasus Species 0.000 description 1
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 1
- OJLOPKGSLYJEMD-LNQMSSPSSA-N Cyotec Chemical compound CCCCC(C)(O)CC=C[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(=O)OC OJLOPKGSLYJEMD-LNQMSSPSSA-N 0.000 description 1
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 1
- 239000000006 Nitroglycerin Substances 0.000 description 1
- SSLMELHDTWSXQT-KTVLMBSMSA-N OCCCCCCC[C@H]1C(CC[C@@H]1C=CCC(CCCC)(C)O)=O Chemical compound OCCCCCCC[C@H]1C(CC[C@@H]1C=CCC(CCCC)(C)O)=O SSLMELHDTWSXQT-KTVLMBSMSA-N 0.000 description 1
- 208000003782 Raynaud disease Diseases 0.000 description 1
- 108010023197 Streptokinase Proteins 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 229940063628 catapres Drugs 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 229960002896 clonidine Drugs 0.000 description 1
- 238000011443 conventional therapy Methods 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 229940099378 cytotec Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 229940099191 duragesic Drugs 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 229940074117 estraderm Drugs 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 210000003499 exocrine gland Anatomy 0.000 description 1
- 238000013265 extended release Methods 0.000 description 1
- 229960002428 fentanyl Drugs 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229960003711 glyceryl trinitrate Drugs 0.000 description 1
- 229940087496 habitrol Drugs 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 201000003152 motion sickness Diseases 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 229940072981 nitro-dur Drugs 0.000 description 1
- 230000036581 peripheral resistance Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 235000021085 polyunsaturated fats Nutrition 0.000 description 1
- 229940127293 prostanoid Drugs 0.000 description 1
- 150000003814 prostanoids Chemical class 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 229960002646 scopolamine Drugs 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 230000016160 smooth muscle contraction Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 229960005202 streptokinase Drugs 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 229940035321 transderm scop Drugs 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 230000002455 vasospastic effect Effects 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
- A61K31/5575—Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
Definitions
- Prostaglandins comprise a class of compounds denominated as
- mediators is a group of substances in the diet called essential fatty acids.
- the E 2 prostaglandin analogue CL1 1 5,347 (Cyanamid International)
- Vasodilation occurs only at a range of prostaglandin doses
- An aspect of this invention is to exploit a route of administration of
- Atherosclerotic disease has a distinct etiology from other
- the present invention addresses delivery by the patch of
- activity such as prostaglandins, and, more particularly, at non-reacted
- the resulting dose entering the blood stream tends to be very small.
- stage' was defined as a clinical condition of existing or impending
- PGE prostaglandins
- prostaglandin E (Cytotec ® , G. D. Searle).
- Other suitable prostaglandins (Cytotec ® , G. D. Searle).
- Transdermal drug administration is known in the pharmaceutical art.
- transdermal drug administration examples include clonidine
- Transdermal System Marion Merrell Dow
- scopolamine administration for 7 motion sickness Transderm Scop Transdermal Therapeutic System, Ciba
- This invention comprises a method of treating arteriosclerosis by
- chronically augmenting peripheral fibrinolytic function comprising:
- treatment may be extended until healing of the ulcers.
- the prostaglandin is selected from the group consisting of misoprostol, prostacyclin, E, and E 2 series 8 prostaglandins, as well as PGF 2 ⁇ and PGD 2 ⁇ Particular note is made of
- misoprostol is administered from about 2 ⁇ g
- misoprostol from about 0.5 ⁇ g/kg/day
- misoprostol dosage is at least about 0.006 ⁇ g/hr as well as at
- the method includes a dosage of
- prostaglandin from about 2 ⁇ g to about 25 ⁇ g/day, and particularly from
- misoprostol at a rate of about 1 to about 6ng/hr
- buccal or sublingual administration or by nasal administration (such as by
- Peripheral as to augmented fibrinolysis, shall mean limbs, including
- Non-vasodilating shall mean not greater that 20% increase in blood
- Transdermal is used to encompass patch-type delivery. While
- Subjects is used expansively to include animals, mammals and,
- prostaglandins or their analogs for the therapy of arteriosclerosis including
- a non-vasodilating dose can be used to treat a wide range of diseases and conditions.
- a non-vasodilating dose can be used to treat a wide range of diseases and conditions.
- Articles of interest include:
- Prostaglandin E infusion in unstable angina: effects on anginal frequency
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
L'invention décrit un procédé permettant de traiter l'arthériosclérose par augmentation chronique de la fonction fibrinolytique périphérique, et consistant à administrer par voie transdermique à un sujet ayant besoin d'un tel traitement une dose d'une prostaglandine non vaso-dilatatrice augmentant la fibrinolyse.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US1882896P | 1996-05-30 | 1996-05-30 | |
| US60/018,828 | 1996-05-30 | ||
| US85916197A | 1997-05-20 | 1997-05-20 | |
| US08/859,161 | 1997-05-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1997045114A1 true WO1997045114A1 (fr) | 1997-12-04 |
Family
ID=26691566
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1997/009600 WO1997045114A1 (fr) | 1996-05-30 | 1997-05-30 | Traitement de maladies vasculaires avec des prostaglandines administrees par l'intermediaire d'un tampon dermique a liberation entretenue |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO1997045114A1 (fr) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7718701B2 (en) | 2002-08-09 | 2010-05-18 | Taisho Pharmaceutical Co., Ltd. | Antipruritic agent |
| US7737182B2 (en) | 2002-08-09 | 2010-06-15 | Taisho Pharmaceutical Co., Ltd. | Pharmaceuticals for xerosis |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3965143A (en) * | 1974-03-26 | 1976-06-22 | G. D. Searle & Co. | 16-Oxygenated prostanoic acid derivatives |
| US4132738A (en) * | 1978-02-23 | 1979-01-02 | Miles Laboratories, Inc. | Preparation of 15-deoxy-16-hydroxyprostaglandins |
-
1997
- 1997-05-30 WO PCT/US1997/009600 patent/WO1997045114A1/fr active Application Filing
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3965143A (en) * | 1974-03-26 | 1976-06-22 | G. D. Searle & Co. | 16-Oxygenated prostanoic acid derivatives |
| US4132738A (en) * | 1978-02-23 | 1979-01-02 | Miles Laboratories, Inc. | Preparation of 15-deoxy-16-hydroxyprostaglandins |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7718701B2 (en) | 2002-08-09 | 2010-05-18 | Taisho Pharmaceutical Co., Ltd. | Antipruritic agent |
| US7737182B2 (en) | 2002-08-09 | 2010-06-15 | Taisho Pharmaceutical Co., Ltd. | Pharmaceuticals for xerosis |
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