WO1992006684A1 - A new use of enprostil - Google Patents
A new use of enprostil Download PDFInfo
- Publication number
- WO1992006684A1 WO1992006684A1 PCT/US1990/005906 US9005906W WO9206684A1 WO 1992006684 A1 WO1992006684 A1 WO 1992006684A1 US 9005906 W US9005906 W US 9005906W WO 9206684 A1 WO9206684 A1 WO 9206684A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- enprostil
- nsaid
- erosions
- gastric ulcers
- effective amount
- Prior art date
Links
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
-
- 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
- A61K31/60—Salicylic acid; Derivatives thereof
Definitions
- the present invention is directed to the use of enprostil for the treatment of NSAID (non-steroidal anti-inflammatory drug) induced gastric disorders.
- NSAID non-steroidal anti-inflammatory drug
- Enprostil is a PGE-type prostaglandin compound having the chemical name of (dl)-9-keto-11 ⁇ ,15 ⁇ -dihydroxy-16-phenoxy- 17,18,19,20-tetranor ⁇ rosta-4,5,13-trans-trienoic acid methyl ester, and is disclosed in united States Patent No. 4,178,457 (issued December 11, 1979).
- the daily dose of enprostil given for the treatment may range from 1 mcg to 150 mcg, and enprostil may be administered concurrently with the NSAID(s).
- Suitable NSAIDs include aspirin, ibuprofen, naproxen, diclofenac, indomethacin and the like, and pharmaceutically acceptable salts thereof.
- osteoarthritis patients were entered, mean age of 63 years, who required continuous fixed dose NSAID therapy.
- the minimum entrance criterion was the presence of four gastric erosions or one gastric ulcer of less than 5 mm in diameter. Gastric erosion was a break in the mucosal epithelium with exudate;
- gastric ulcer was an erosion of at least 3 mm in diameter with appreciable depth. Endoscopy was performed at weeks -2 and 0 to establish a stable pre-treatment baseline, and at weeks 6 and 9 during treatment. Results
- E35-bid and E35-tid ulcer healing rates were 14%, 57% and 68% at 6 weeks and 19%, 68% and 74% at 9 weeks.
- 1 in 5 placebo patients as compared with 3 in 4 patients given 35 meg enprostil had complete healing of gastric ulcers at 9 weeks (E-bid vs PBO, p ⁇ , 0.006; E-tid vs PBO, p ⁇
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- 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)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Enprostil is effective in healing non-steroidal anti-inflammatory drug induced gastric erosions and ulcers.
Description
A NEW USE OF ENPROSTIL
The present invention is directed to the use of enprostil for the treatment of NSAID (non-steroidal anti-inflammatory drug) induced gastric disorders.
Conventional ulcer therapy is not effective in healing NSAID induced gastric ulcers or erosions if NSAIDs are
continued. Now it has been found that enprostil is an
effective treatment for such lesions during continued NSAID therapy, and it heals gastric ulcers and gastric erosions while protecting the mucosa against further NSAID-induced gastric injury.
Enprostil is a PGE-type prostaglandin compound having the chemical name of (dl)-9-keto-11α,15α-dihydroxy-16-phenoxy- 17,18,19,20-tetranorρrosta-4,5,13-trans-trienoic acid methyl ester, and is disclosed in united States Patent No. 4,178,457 (issued December 11, 1979).
The daily dose of enprostil given for the treatment may range from 1 mcg to 150 mcg, and enprostil may be administered concurrently with the NSAID(s).
Suitable NSAIDs include aspirin, ibuprofen, naproxen, diclofenac, indomethacin and the like, and pharmaceutically acceptable salts thereof.
Experimental
A 9-week double-blind trial was conducted comparing placebo (PBO) versus enprostil 35 meg twice a day (B35-bid) and enprostil 35 mcg three times a day (E35-tid). In this study use of antacids was not allowed. 144 rheumatoid and
osteoarthritis patients were entered, mean age of 63 years, who required continuous fixed dose NSAID therapy. The minimum entrance criterion was the presence of four gastric erosions or one gastric ulcer of less than 5 mm in diameter. Gastric erosion was a break in the mucosal epithelium with exudate;
gastric ulcer was an erosion of at least 3 mm in diameter with appreciable depth. Endoscopy was performed at weeks -2 and 0 to establish a stable pre-treatment baseline, and at weeks 6 and 9 during treatment.
Results
All groups were similar in regards to age, sex, weight and height. 92 of the 144 patients (64%) had gastric ulcers; 52 had only gastric erosions. The "healing rates" (complete healing of all ulcers) of the 92 patients with gastric ulcers are shown in Figure 1,
The placebo, E35-bid and E35-tid ulcer healing rates were 14%, 57% and 68% at 6 weeks and 19%, 68% and 74% at 9 weeks. Thus, 1 in 5 placebo patients as compared with 3 in 4 patients given 35 meg enprostil had complete healing of gastric ulcers at 9 weeks (E-bid vs PBO, p ≤, 0.006; E-tid vs PBO, p≤
0.001). Additional gastric erosions developed in 16% of patients given placebo but in none of the patients given enprostil.
Claims
1. The use of enprostil for the treatment of NSAID induced gastric ulcers and erosions.
2. The use of Claim 1 where the therapy with NSAID is continued.
3. The use of Claim 1 wherein enprostil is concurrently administered with NSAID(s).
4. The use of Claims 1-3 wherein enprostil is
administered at a daily dose of 1-150 meg.
5. A method for treating NSAID induced gastric ulcers and erosions which comprises administering an effective amount of enprostil to a patient in need of such treatment.
6. The method of Claim 5 where the therapy with NSAID is continued.
7. The method of Claim 5 wherein enprostil and NSAID(s) are concurrently administered to a patient.
8. The method of Claims 5-7 wherein the effective amount of enprostil is 1-150 meg per day.
9. The use of enprostil for the manufacture of a medicament suitable for treating NSAID induced gastric ulcers and erosions.
10. The use of Claim 9 for the manufacture of a
medicament suitable for administering to a patient requiring continued therapy with NSAID.
11. The use of Claim 9 for the manufacture of a
medicament suitable for administering concurrently with
NSAID(s).
12. The use of Claims 9-11 wherein the effective dose of enprostil is 1-150 meg per day.
13. An agent for treating NSAID induced gastric ulcers and erosions which comprises an effective amount of enprostil.
14. The agent of Claim 13 which is administered
concurrently with NSAID(s).
15. The agent of Claims 13 and 14 wherein the effective amount amounts to a daily dose of 1-150 meg.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US1990/005906 WO1992006684A1 (en) | 1990-10-18 | 1990-10-18 | A new use of enprostil |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US1990/005906 WO1992006684A1 (en) | 1990-10-18 | 1990-10-18 | A new use of enprostil |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1992006684A1 true WO1992006684A1 (en) | 1992-04-30 |
Family
ID=22221096
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1990/005906 WO1992006684A1 (en) | 1990-10-18 | 1990-10-18 | A new use of enprostil |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO1992006684A1 (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3781429A (en) * | 1972-09-29 | 1973-12-25 | American Cyanamid Co | Method of inhibiting ulcerogenesis induced by non-steroidal anti-inflammatory agents |
| US4083998A (en) * | 1976-02-17 | 1978-04-11 | The Upjohn Company | Treatment of inflammatory diseases of the mammalian large intestine with cytoprotective prostaglandins |
| GB2108960A (en) * | 1981-10-30 | 1983-05-25 | Upjohn Co | 6-oxo-pge analogues |
| DE3404209A1 (en) * | 1983-03-02 | 1984-09-06 | Farmitalia Carlo Erba S.p.A., Mailand / Milano | Human or veterinary pharmaceutical for the treatment of inflammatory states in humans or mammals |
| US4707495A (en) * | 1985-10-28 | 1987-11-17 | Ortho Pharmaceutical | Peptic ulcer treatment method |
-
1990
- 1990-10-18 WO PCT/US1990/005906 patent/WO1992006684A1/en active Application Filing
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3781429A (en) * | 1972-09-29 | 1973-12-25 | American Cyanamid Co | Method of inhibiting ulcerogenesis induced by non-steroidal anti-inflammatory agents |
| US4083998A (en) * | 1976-02-17 | 1978-04-11 | The Upjohn Company | Treatment of inflammatory diseases of the mammalian large intestine with cytoprotective prostaglandins |
| GB2108960A (en) * | 1981-10-30 | 1983-05-25 | Upjohn Co | 6-oxo-pge analogues |
| DE3404209A1 (en) * | 1983-03-02 | 1984-09-06 | Farmitalia Carlo Erba S.p.A., Mailand / Milano | Human or veterinary pharmaceutical for the treatment of inflammatory states in humans or mammals |
| US4707495A (en) * | 1985-10-28 | 1987-11-17 | Ortho Pharmaceutical | Peptic ulcer treatment method |
Non-Patent Citations (6)
| Title |
|---|
| CHEMICAL ABSTRACTS, Volume 101, No. 25, issued 17 December 1984, ROBERTO CESERANI et al., "Composition for treating inflammatory conditions in humans or mammals". See page 157, column 1, abstract No. 223545m; & DE,A,3 404 209 (Cl. A61K31 557), 06 September 1984. * |
| CHEMICAL ABSTRACTS, Volume 103, No. 9, issued 02 September 1985, N.D.W. REES et al., "Alkali secretion by isolated rabbit gastric mucosa: effects of non-steroidal anti-inflammatory drugs and prostaglandins". See page 4, column 2, abstract No. 64246n; & SCAND. J. GASTROENTEROL., Suppl. 1984, 19(92), 63-68 (eng). * |
| CHEMICAL ABSTRACTS, Volume 105, No. 21, issued 24 November 1986, CHRISTOPHER J. HAWKEY et al., "Reduction by enprostil of asprin-induced blood loss from human gastric mucosa". See page 152, column 2, abstract No. 184750K; & AM. J. MED. 1986, 81(2A), 50-53 (eng). * |
| CHEMICAL ABSTRACTS, Volume 105, No. 21, issued 24 November 1986, DANIEL STIEL et al., "Protective effect of enprostil against aspirin-induced gastroduodenal mucosal injury in man. Comparison with cimetidine and sucralfate". See page 152, column 2, abstract No. 184751m; & AM. J. MED. 1986, 81(2A), 54-58 (eng). * |
| CHEMICAL ABSTRACTS, Volume 109, No. 13, issued 26 September 1988, L.D. WATERBURY et al., "Stimulation of mucus production and prevention of aspirin induced ulcerogenesis by enprostil in the rat". See page 148, column 1, abstract No. 105434s; & PROC. WEST PHARMACOL. SOC. 1988, 31, 21-23 (eng). * |
| CHEMICAL ABSTRACTS, Volume III, No. 21, issued 20 November 1989, G. THIEFIN, "Protective effect of low dose of enprostil against gastric blood loss induced by aspirin in man ". See page 37, column 1, abstract No. 187119w; & SCAN. J. GASTROENTEROL 1989, 24(7), 827-832 (eng). * |
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