WO1995001177A1 - Medicaments containing vapiprost hydrochloride for the treatment of inflammatory diseases - Google Patents
Medicaments containing vapiprost hydrochloride for the treatment of inflammatory diseases Download PDFInfo
- Publication number
- WO1995001177A1 WO1995001177A1 PCT/EP1994/002105 EP9402105W WO9501177A1 WO 1995001177 A1 WO1995001177 A1 WO 1995001177A1 EP 9402105 W EP9402105 W EP 9402105W WO 9501177 A1 WO9501177 A1 WO 9501177A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- treatment
- vapiprost
- diseases
- inflammatory diseases
- inflammatory bowel
- Prior art date
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
Definitions
- Medicaments containi ng vapiprost hydrochloride for the treatment of inflammatory di seases.
- This invention relates to a new medical use for the hydrochloride salt of [IB-[1 ⁇ (Z), 2 ⁇ , 3 ⁇ , 5 ⁇ ]]-(+)-7-[5-[[(1 ,1 '-biphenyl)-4-yl]methoxy]-3-hydroxy-2-(1- piperidinyl)cyclopentyl]-4-heptenoic acid (hereinafter referred to as Vapiprost).
- Vapiprost the hydrochloride salt of [IB-[1 ⁇ (Z), 2 ⁇ , 3 ⁇ , 5 ⁇ ]]-(+)-7-[5-[[(1 ,1 '-biphenyl)-4-yl]methoxy]-3-hydroxy-2-(1- piperidinyl)cyclopentyl]-4-heptenoic acid
- Vapiprost relates to the use of Vapiprost in the treatment of certain inflammatory diseases, including inflammatory bowel diseases.
- Inflammatory bowel diseases such as Crohn's disease and ulcerative colitis are poorly treated, chronic progressive inflammatory conditions.
- Current management is based on the use of corticosteroids to reduce acute inflammation and sulfasalazine to maintain remission, or resection when chemotherapy fails.
- corticosteroids to reduce acute inflammation and sulfasalazine to maintain remission, or resection when chemotherapy fails.
- There is undoubtedly a need for improved therapy to replace or supplement existing management of these diseases which carry a high risk of progressing to serious conditions such as ileal stenosis, peritoneal adhesions, fistula formation, perforation and colon cancer.
- Vapiprost is a potent thromboxane receptor blocker which inhibits thromboxane A 2 and endoperoxide mediated aggregation of blood platelets and contraction of vascular smooth muscle and is of particular interest as an anti-thrombotic agent.
- Vapiprost is of use in the treatment of inflammatory bowel diseases such as Crohn's disease or ulcerative colitis and may be used to treat other chronic progressive intestinal inflammatory diseases of unknown aetiology.
- Vapiprost in the manufacture of a medicament for the treatment of chronic progressive intestinal inflammatory diseases of unknown aetiology (e.g. inflammatory bowel diseases) in a human or non-human animal subject.
- chronic progressive intestinal inflammatory diseases of unknown aetiology e.g. inflammatory bowel diseases
- Vapiprost in the manufacture of a medicament for the treatment of Crohn's disease or ulcerative colitis in a human or non-human animal subject.
- a method of treatment of a human or non-human animal subject suffering from or susceptible to chronic progressive intestinal inflammatory diseases of unknown aetiology e.g. inflammatory bowel diseases
- which method comprises administering to the said subject an effective amount of Vapiprost.
- a method of treatment of a human or non-human animal subject suffering from or susceptible to Crohn's disease or ulcerative colitis comprises administering to the said subject an effective amount of Vapiprost.
- references herein to treatment extend to prophylaxis as well as the treatment of established conditions.
- Vapiprost in the treatment of inflammatory bowel and related diseases may be demonstrated, for example, by its ability to inhibit dextran sulphate-induced colitis in mice using experiments analogous to those described by Shim et al. in Gastroenterology, 1991 ,100, A841.
- Figure 1 hereinafter provides the results of such an experiment.
- Figure 1 demonstrates that GR32191 B (i.e. Vapiprost) suppresses the DSS (i.e. dextran sulphate) effect on mouse colon when measured as a ratio of colon weight per unit length.
- GR32191 B i.e. Vapiprost
- DSS i.e. dextran sulphate
- Vapiprost in the form of a pharmaceutical composition.
- the present invention therefore also provides a pharmaceutical composition for use in the treatment of chronic progressive intestinal inflammatory diseases of unknown aetiology (e.g. inflammatory bowel disease) comprising Vapiprost, where desirable, together with one or more carriers or excipients.
- chronic progressive intestinal inflammatory diseases of unknown aetiology e.g. inflammatory bowel disease
- Vapiprost in combination therapy with another agent useful in the treatment of the same disease.
- Vapiprost may be co- administered with an immunosuppressive agent such as cyclosporin or FK-506.
- an immunosuppressive agent such as cyclosporin or FK-506.
- the present invention encompasses the co- administration of Vapiprost with another suitable agent, such as is described hereinabove, to treat chronic progressive intestinal inflammatory diseases of unknown aetiology, (e.g. inflammatory bowel diseases).
- the term 'co-administration' means either separate or simultaneous (e.g. as a single pharmaceutical composition) administration of the two active entities.
- the active ingredients must of course be stable and mutually compatible in the particular formulation employed.
- Vapiprost may be used according to the present invention in various formulations for oral, parenteral or rectal administration. Suitable formulations for oral or parenteral use according to the present invention are described in GB-B-2097397, GB-B-2127406 and GB-B-2211737. Specific examples of oral and parenteral formulations for use according to the present invention are given hereinafter. Suitable formulations for rectal use according to the present invention include, for example, enemas in suitable buffered aqueous vehicles and suppositories prepared, for example, with commercial suppository bases. Vapiprost is preferably administered by the oral route for use according to the present invention.
- Vapiprost to be administered will, of course, depend on a number of factors including, for example, the age, weight and condition of the patient, the route of administration and the specific disease to be treated.
- An effective oral dose is likely to be in the range from 0.05 to 20mg/kg body weight, preferably 0.05 to 5mg/kg body weight, per day, and administered in suitable dosage units.
- Vapiprost was dissolved in 35ml water suitable for injection and the ⁇ - cyclodextrin was added. This solution was titrated to pH7 with 0.02M sodium hydroxide solution and then adjusted to volume with water suitable for injection.
- the solution may then be sterilised by filtration and filled into vials or ampoules.
- Vapiprost was dissolved in approximately 25ml water suitable for injection.
- the ⁇ -cyclodextrin was dissolved therein and the resulting solution was titrated to pH6 with 0.02M sodium hydroxide solution and the phosphate buffer added.
- the sodium chloride was added to the solution and the pH adjusted to pH7 with sodium hydroxide.
- the solution was made up to volume with water suitable for injection. A sample of this solution was filled into a glass vial which was sealed with a rubber plug and metal overseal. This was then autoclaved.
- Vapiprost was dissolved in approximately 25ml water suitable for injection and the hydroxypropyl- ⁇ -cyclodextrin was added. The mannitol was then added and the solution titrated to pH 6 with 0.02M sodium hydroxide solution. The phosphate buffer solution was added and the solution adjusted to volume with water suitable for injection. The solution was then filtered and filled into glass vials which were sealed with rubber plugs and metal overseals. These were then autoclaved.
- Vapiprost was dissolved in approximately 25ml water suitable for injection.
- the ⁇ -cyclodextrin and mannitol were dissolved therein and the solution titrated to pH 6 with 0.02M sodium hydroxide solution.
- the sodium acid phosphate and anhydrous disodium phosphate were dissolved in water suitable for injection. This solution was added to the bulk solution which was made up to volume with water suitable for injection. The solution was filtered and filled into glass ampoules which were sealed and then autoclaved.
- Vapiprost was dissolved in approximately 25ml water suitable for injection and the cyclodextrin(s) was (were) added. The mannitol was then added and the solution titrated to pH 6 with 0.02M sodium hydroxide solution. The phosphate buffer solution was added and the solution was adjusted to volume with water suitable for injection. The solution was then filtered and filled into glass vials which were sealed with rubber plugs and metal overseals.
- Vapiprost (equivalent to 2.5mg base)
- These may be prepared by direct compression or wet granulation.
- the direct compression method is preferred but may not be suitable in all cases as it is dependent upon the dose level of the active ingredient.
- Vapiprost is sieved through a 250 n ⁇ 6 sieve, blended with the excipients and compressed using 10.0mm punches. Tablets of other strengths may be prepared by altering the compression weight and using punches to suit.
- Vapiprost is sieved through a 250 m "6 sieve and blended with the lactose, starch and pre-gelatinised starch.
- the mixed powders are moistened with purified water, granules are made, dried, screened and blended with the magnesium stearate.
- the lubricated granules are compressed into tablets as described for the direct compression formula.
- the tablets may be film coated with suitable film forming materials, e.g. methyl cellulose or hydroxypropyl methyl cellulose using standard techniques. Alternatively the tablets may be sugar coated.
- suitable film forming materials e.g. methyl cellulose or hydroxypropyl methyl cellulose using standard techniques.
- the tablets may be sugar coated.
- Vapiprost is sieved through a 250 r ⁇ r 6 sieve and blended with the other materials.
- the mix is filled into No.2 hard gelatin capsules using a suitable filling machine.
- Other doses may be prepared by altering the fill weight and if necessary changing the capsule size to suit.
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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)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
This invention relates to the use of the hydrochloride salt of [IR^_-[1α(Z^_),2β,3β,5α]]-(+)-7-[5-[[(1,1'-biphenyl)-4-yl]methoxy]-3-hydroxy-2-(1-piperidinyl)cyclopentyl]-4-heptenoic acid (i.e. Vapiprost) in the treatment of certain inflammatory diseases, including inflammatory bowel diseases.
Description
Medicaments containi ng vapiprost hydrochloride for the treatment of inflammatory di seases.
This invention relates to a new medical use for the hydrochloride salt of [IB-[1 α (Z), 2β, 3β, 5α]]-(+)-7-[5-[[(1 ,1 '-biphenyl)-4-yl]methoxy]-3-hydroxy-2-(1- piperidinyl)cyclopentyl]-4-heptenoic acid (hereinafter referred to as Vapiprost). In particular, it relates to the use of Vapiprost in the treatment of certain inflammatory diseases, including inflammatory bowel diseases.
Inflammatory bowel diseases such as Crohn's disease and ulcerative colitis are poorly treated, chronic progressive inflammatory conditions. Current management is based on the use of corticosteroids to reduce acute inflammation and sulfasalazine to maintain remission, or resection when chemotherapy fails. There is undoubtedly a need for improved therapy to replace or supplement existing management of these diseases which carry a high risk of progressing to serious conditions such as ileal stenosis, peritoneal adhesions, fistula formation, perforation and colon cancer.
Vapiprost is a potent thromboxane receptor blocker which inhibits thromboxane A2 and endoperoxide mediated aggregation of blood platelets and contraction of vascular smooth muscle and is of particular interest as an anti-thrombotic agent.
We have now found that Vapiprost is of use in the treatment of inflammatory bowel diseases such as Crohn's disease or ulcerative colitis and may be used to treat other chronic progressive intestinal inflammatory diseases of unknown aetiology.
Thus, according to one aspect of the present invention, we provide the use of Vapiprost in the manufacture of a medicament for the treatment of chronic progressive intestinal inflammatory diseases of unknown aetiology (e.g. inflammatory bowel diseases) in a human or non-human animal subject.
In a particular embodiment we provide the use of Vapiprost in the manufacture of a medicament for the treatment of Crohn's disease or ulcerative colitis in a human or non-human animal subject.
In a further aspect of the invention, we provide a method of treatment of a human or non-human animal subject suffering from or susceptible to chronic
progressive intestinal inflammatory diseases of unknown aetiology (e.g. inflammatory bowel diseases) which method comprises administering to the said subject an effective amount of Vapiprost.
In a particular embodiment we provide a method of treatment of a human or non-human animal subject suffering from or susceptible to Crohn's disease or ulcerative colitis which method comprises administering to the said subject an effective amount of Vapiprost.
It will be appreciated that references herein to treatment extend to prophylaxis as well as the treatment of established conditions.
The potential for Vapiprost in the treatment of inflammatory bowel and related diseases may be demonstrated, for example, by its ability to inhibit dextran sulphate-induced colitis in mice using experiments analogous to those described by Shim et al. in Gastroenterology, 1991 ,100, A841.
Figure 1 hereinafter provides the results of such an experiment. Figure 1 demonstrates that GR32191 B (i.e. Vapiprost) suppresses the DSS (i.e. dextran sulphate) effect on mouse colon when measured as a ratio of colon weight per unit length.
Histological examination of the colon showed that in the DSS/GR32191 group the degree of inflammation and structual damage was markedly less than in the DSS alone group.
It is preferable for use according to the present invention to employ Vapiprost in the form of a pharmaceutical composition. The present invention therefore also provides a pharmaceutical composition for use in the treatment of chronic progressive intestinal inflammatory diseases of unknown aetiology (e.g. inflammatory bowel disease) comprising Vapiprost, where desirable, together with one or more carriers or excipients.
It will be appreciated that in the management of a particular intestinal inflammatory disease it may be appropriate to administer Vapiprost in combination therapy with another agent useful in the treatment of the same disease. Thus, for example, it may be appropriate to administer a corticosteroid
prior to treating the patient with Vapiprost, or alternatively, Vapiprost may be co- administered with an immunosuppressive agent such as cyclosporin or FK-506. It is to be understood that the present invention encompasses the co- administration of Vapiprost with another suitable agent, such as is described hereinabove, to treat chronic progressive intestinal inflammatory diseases of unknown aetiology, (e.g. inflammatory bowel diseases).
As used herein, the term 'co-administration' means either separate or simultaneous (e.g. as a single pharmaceutical composition) administration of the two active entities. In a combined formulation the active ingredients must of course be stable and mutually compatible in the particular formulation employed.
Vapiprost may be used according to the present invention in various formulations for oral, parenteral or rectal administration. Suitable formulations for oral or parenteral use according to the present invention are described in GB-B-2097397, GB-B-2127406 and GB-B-2211737. Specific examples of oral and parenteral formulations for use according to the present invention are given hereinafter. Suitable formulations for rectal use according to the present invention include, for example, enemas in suitable buffered aqueous vehicles and suppositories prepared, for example, with commercial suppository bases. Vapiprost is preferably administered by the oral route for use according to the present invention.
The precise dose of Vapiprost to be administered will, of course, depend on a number of factors including, for example, the age, weight and condition of the patient, the route of administration and the specific disease to be treated. An effective oral dose, however, is likely to be in the range from 0.05 to 20mg/kg body weight, preferably 0.05 to 5mg/kg body weight, per day, and administered in suitable dosage units.
The following, non-limiting examples, illustrate pharmaceutical compositions of Vapiprost for use according to the present invention.
Pharmaceutical examples of parenteral iniections/infusions
(i) Vapiprost
(equivalent to 50mg base)
β-Cyclodextrin hydrate 143mg 166mg 238mg
Sodium hydroxide solution to pH7 to pH7 to pH7
Water suitable for injection to 50ml to 50ml to 50ml
Vapiprost was dissolved in 35ml water suitable for injection and the β- cyclodextrin was added. This solution was titrated to pH7 with 0.02M sodium hydroxide solution and then adjusted to volume with water suitable for injection.
The solution may then be sterilised by filtration and filled into vials or ampoules.
(ii) Vapiprost (equivalent to 50mg base)
β-Cyclodextrin hydrate 166mg
Sodium chloride 450mg
pH7.0 phosphate buffer 2.5ml
Sodium hydroxide solution to pH7
Water suitable for injection to 50ml
Vapiprost was dissolved in approximately 25ml water suitable for injection. The β-cyclodextrin was dissolved therein and the resulting solution was titrated to pH6 with 0.02M sodium hydroxide solution and the phosphate buffer added.
The sodium chloride was added to the solution and the pH adjusted to pH7 with sodium hydroxide. The solution was made up to volume with water suitable for injection. A sample of this solution was filled into a glass vial which was sealed with a rubber plug and metal overseal. This was then autoclaved.
(iii) Vapiprost
(equivalent to 50mg base)
Hydroxypropyl-β-cyclodextrin 170mg
Mannitol 2.5g
pH 6.0 phosphate buffer 5.0ml
Sodium hydroxide solution to pH 6
Water suitable for injection to 50ml
Vapiprost was dissolved in approximately 25ml water suitable for injection and the hydroxypropyl-β-cyclodextrin was added. The mannitol was then added and the solution titrated to pH 6 with 0.02M sodium hydroxide solution. The phosphate buffer solution was added and the solution adjusted to volume with water suitable for injection. The solution was then filtered and filled into glass vials which were sealed with rubber plugs and metal overseals. These were then autoclaved.
(iv) Vapiprost
(equivalent to 50mg base)
β-Cyclodextrin hydrate 166mg
Mannitol 2.5g
Sodium acid phosphate 46mg
Disodium phosphate, anhydrous 5mg
Sodium hydroxide solution to pH 6
Water suitable for injection to 50ml
Vapiprost was dissolved in approximately 25ml water suitable for injection. The β-cyclodextrin and mannitol were dissolved therein and the solution titrated to pH 6 with 0.02M sodium hydroxide solution. The sodium acid phosphate and anhydrous disodium phosphate were dissolved in water suitable for injection. This solution was added to the bulk solution which was made up to volume with water suitable for injection. The solution was filtered and filled into glass ampoules which were sealed and then autoclaved.
Cyclodextrin Mixture β ±
(v) Vapiprost
(equivalent to 50mg base)
Cyclodextrin 143mg 190mg 119mg 136mg
Mannitol 2.5g 2.5g 2.5g
pH 6.0 Phosphate buffer 5.0ml 5.0ml 5.0ml
Sodium hydroxide solution to pH 6 to pH 6 to pH6
Water suitable for injection to 50ml to 50 ml to 50ml
Vapiprost was dissolved in approximately 25ml water suitable for injection and the cyclodextrin(s) was (were) added. The mannitol was then added and the solution titrated to pH 6 with 0.02M sodium hydroxide solution. The phosphate buffer solution was added and the solution was adjusted to volume with water suitable for injection. The solution was then filtered and filled into glass vials which were sealed with rubber plugs and metal overseals.
Pharmaceutical example of an oral svruπ comorisinα Vapiprost
Vapiprost (equivalent to 2.5mg base)
β-cyclodextrin hydrate 9mg
Citric acid to pH 4.5
Methyl hydroxybenzoate sodium 5mg
Propyl hydroxybenzoate sodium 2mg
Liquid orange flavour qs
Sucrose 3.25g
Purified water to 5.0ml
Dissolve the sucrose in a minimum quantity of water. Add Vapiprost and then the β-cyclodextrin with stirring; adjust the pH to 4.5 with citric acid. With continued stirring add a solution of the hydroxybenzoates and lastly the flavour. Adjust almost to volume with water and stir. Check the pH and adjust to 4.5 with citric acid if necessary. Make up to volume with water.
Pharmaceutical examples of tablets and capsules comprising Vapiprost
Tablets
These may be prepared by direct compression or wet granulation. The direct compression method is preferred but may not be suitable in all cases as it is dependent upon the dose level of the active ingredient.
A. Direct Compression mg/tablet
Vapiprost 100.00
Microcrystalline Cellulose BPC 298.00
Magnesium Stearate 2.00
Compression Weight 400.00 mg
Vapiprost is sieved through a 250 nτ6 sieve, blended with the excipients and compressed using 10.0mm punches. Tablets of other strengths may be prepared by altering the compression weight and using punches to suit.
B. Wet Granulation mg/tablet
Vapiprost 100.00
Lactose BP 238.00
Starch BP 40.00
Pregelatinised Maize Starch BP 20.00
Magnesium Stearate BP 2.00
Compression Weight 400.00 mg
Vapiprost is sieved through a 250 m"6 sieve and blended with the lactose, starch and pre-gelatinised starch. The mixed powders are moistened with purified water, granules are made, dried, screened and blended with the
magnesium stearate. The lubricated granules are compressed into tablets as described for the direct compression formula.
The tablets may be film coated with suitable film forming materials, e.g. methyl cellulose or hydroxypropyl methyl cellulose using standard techniques. Alternatively the tablets may be sugar coated.
Capsules mg/tablet
Vapiprost 100.00
*STA-RX 1500 99.00
Magnesium Stearate BP 1.00
Fill Weight 200.00 mg
* A form of directly compressible starch supplied by Colorcorn Ltd, Orpington, Kent.
Vapiprost is sieved through a 250 rτr6 sieve and blended with the other materials. The mix is filled into No.2 hard gelatin capsules using a suitable filling machine. Other doses may be prepared by altering the fill weight and if necessary changing the capsule size to suit.
Claims
1. Use of the hydrochloride salt of [IR-[1 α(Z), 2β, 3β, 5α]]-(+)-7-[5-[[(1 ,1 '- biphenyl)-4-yl]methoxy]-3-hydroxy-2-(1 -piperidinyl)cyclopentyl]-4-heptenoic acid
(i.e. Vapiprost) in the manufacture of a medicament for the treatment of chronic progressive intestinal inflammatory diseases of unknown aetiology in a human or non-human animal subject.
2. Use according to Claim 1 for the treatment of inflammatory bowel diseases.
3. Use according to Claim 2 for the treatment of Crohn's disease.
4. Use according to Claim 2 for the treatment of ulcerative colitis.
5. A pharmaceutical composition for use in the treatment of chronic progressive intestinal inflammatory diseases of unknown aetiology comprising Vapiprost, where desirable, together with one or more carriers or excipients.
6. A composition according to Claim 5 for use in the treatment of inflammatory bowel diseases.
7. A combination of Vapiprost and a corticosteriod or immunosuppressive agent for the treatment of chronic progressive intestinal inflammatory diseases of unknown aetiology.
8. A combination according to Claim 7 for use in the treatment of inflammatory bowel diseases.
9. A method of treatment of a human or non-human animal subject suffering from or susceptible to chronic progressive intestinal inflammatory diseases of unknown aetiology which method comprises administering to the said subject an effective amount of Vapiprost.
10. A method according to Claim 9 for the treatment of inflammatory bowel diseases.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU73839/94A AU7383994A (en) | 1993-07-01 | 1994-06-29 | Medicaments containing vapiprost hydrochloride for the treatment of inflammatory diseases |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB939313649A GB9313649D0 (en) | 1993-07-01 | 1993-07-01 | Medicaments |
| GB9313649.7 | 1993-07-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1995001177A1 true WO1995001177A1 (en) | 1995-01-12 |
Family
ID=10738145
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP1994/002105 WO1995001177A1 (en) | 1993-07-01 | 1994-06-29 | Medicaments containing vapiprost hydrochloride for the treatment of inflammatory diseases |
Country Status (5)
| Country | Link |
|---|---|
| AU (1) | AU7383994A (en) |
| GB (1) | GB9313649D0 (en) |
| IL (1) | IL110169A0 (en) |
| WO (1) | WO1995001177A1 (en) |
| ZA (1) | ZA944671B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011057262A3 (en) * | 2009-11-09 | 2011-08-11 | Evolva Inc. | Treatment of infections with tp receptor antagonists |
| US8486994B2 (en) | 2007-01-18 | 2013-07-16 | Evolva Sa | Prodrugs of substituted 1,3-dioxanes and their uses |
| US8536196B2 (en) | 2007-01-18 | 2013-09-17 | Evolva Sa | Substituted 1,3-dioxanes useful as PPAR modulators |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0448274A2 (en) * | 1990-03-19 | 1991-09-25 | E.R. Squibb & Sons, Inc. | Use of a thromboxane A2 receptor antagonist for the manufacture of a medicament for the treatment of ulcerative gastrointestinal conditions |
-
1993
- 1993-07-01 GB GB939313649A patent/GB9313649D0/en active Pending
-
1994
- 1994-06-29 ZA ZA944671A patent/ZA944671B/en unknown
- 1994-06-29 AU AU73839/94A patent/AU7383994A/en not_active Abandoned
- 1994-06-29 WO PCT/EP1994/002105 patent/WO1995001177A1/en active Application Filing
- 1994-06-30 IL IL11016994A patent/IL110169A0/en unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0448274A2 (en) * | 1990-03-19 | 1991-09-25 | E.R. Squibb & Sons, Inc. | Use of a thromboxane A2 receptor antagonist for the manufacture of a medicament for the treatment of ulcerative gastrointestinal conditions |
Non-Patent Citations (2)
| Title |
|---|
| "Vapiprost Hydrochloride GR-32191", DRUGS FUTURE, vol. 16, no. 11, 1991, pages 1075 - 5 * |
| BR.J.CLIN.PHARMAC., vol. 29, 1990, pages 431 - 36 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8486994B2 (en) | 2007-01-18 | 2013-07-16 | Evolva Sa | Prodrugs of substituted 1,3-dioxanes and their uses |
| US8536196B2 (en) | 2007-01-18 | 2013-09-17 | Evolva Sa | Substituted 1,3-dioxanes useful as PPAR modulators |
| US8952053B2 (en) | 2007-01-18 | 2015-02-10 | Evolva Sa | Prodrugs of substituted 1,3-dioxanes and their uses |
| US9260406B2 (en) | 2007-01-18 | 2016-02-16 | Evolva Sa | Substituted 1,3-dioxanes useful as PPAR modulators |
| WO2011057262A3 (en) * | 2009-11-09 | 2011-08-11 | Evolva Inc. | Treatment of infections with tp receptor antagonists |
Also Published As
| Publication number | Publication date |
|---|---|
| GB9313649D0 (en) | 1993-08-18 |
| ZA944671B (en) | 1995-01-16 |
| IL110169A0 (en) | 1994-10-07 |
| AU7383994A (en) | 1995-01-24 |
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