CA1079641A - Pharmaceutical composition containing ergot alkaloids - Google Patents
Pharmaceutical composition containing ergot alkaloidsInfo
- Publication number
- CA1079641A CA1079641A CA263,423A CA263423A CA1079641A CA 1079641 A CA1079641 A CA 1079641A CA 263423 A CA263423 A CA 263423A CA 1079641 A CA1079641 A CA 1079641A
- Authority
- CA
- Canada
- Prior art keywords
- composition according
- polymer
- dispersion
- solid solution
- molecular weight
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired
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
- A61K31/33—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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/48—Ergoline derivatives, e.g. lysergic acid, ergotamine
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
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- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Neurosurgery (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
PHARMACEUTICAL COMPOSITION CONTAINING ERGOT ALKALOIDS
Abstract of the Disclosure Natural or hydrogenated ergot alkaloids are made up into a solid solution in a suitable polymer, for example polyvinylpyrrolidone. The solid solution may be formed by evaporating a methanolic solution of the alkaloid and the polymer. Pharmaceutical compositions containing such solid solutions give improved absorption of the alkaloid.
Abstract of the Disclosure Natural or hydrogenated ergot alkaloids are made up into a solid solution in a suitable polymer, for example polyvinylpyrrolidone. The solid solution may be formed by evaporating a methanolic solution of the alkaloid and the polymer. Pharmaceutical compositions containing such solid solutions give improved absorption of the alkaloid.
Description
iO~7'3641 PHARMACEUTICAL COMPOSITION CONTAINING ERGOT ALKALOIDS
This invention relates to new pharmaceutical com-positions of ergot allcaloids.
The invention provides pharmaceutical compositions comprising a solid solution or dispersion of one or more ergot alkaloids in pharmaceutically acceptable solid polymer which is soluble or swellable in gastric juices.
In the term "ergot alkaloids" is included naturally occurring ergot alkaloids for example ergotamine, ergo-cristine, ergocrypine and ergocornine; their synthetic derivatives, for example ergovaline; their hydrogenated forms, for example dihydroergotamine, and the salts of any of these. Suitable salts are those derived from pharmaceutically acceptable acids, for example organic acids such as methanesulphonic, tartaric and maleic acids or inorganic acids such as hydrochloric acid.
Preferably the polymer is a polyalkylene glycol, polyvinylpyrrolidone, a copolymer of vinylpyrrolidone and vinyl acetate or a mixture of these. If mixtures of polymers are used, the proportion of different polymers in the mixture is not critical; preferably, however, equal quantities of two or three different polymers may be present.
In the case of mixtures, one or more of the polymers may be a liquid, for example a low molecular weight polyalkylene glycol, provided that the resulting mixture of polymers is a solid.
Suitable polyalkylene glycols include polyethylene _l--:
., `, .
, q~
....
This invention relates to new pharmaceutical com-positions of ergot allcaloids.
The invention provides pharmaceutical compositions comprising a solid solution or dispersion of one or more ergot alkaloids in pharmaceutically acceptable solid polymer which is soluble or swellable in gastric juices.
In the term "ergot alkaloids" is included naturally occurring ergot alkaloids for example ergotamine, ergo-cristine, ergocrypine and ergocornine; their synthetic derivatives, for example ergovaline; their hydrogenated forms, for example dihydroergotamine, and the salts of any of these. Suitable salts are those derived from pharmaceutically acceptable acids, for example organic acids such as methanesulphonic, tartaric and maleic acids or inorganic acids such as hydrochloric acid.
Preferably the polymer is a polyalkylene glycol, polyvinylpyrrolidone, a copolymer of vinylpyrrolidone and vinyl acetate or a mixture of these. If mixtures of polymers are used, the proportion of different polymers in the mixture is not critical; preferably, however, equal quantities of two or three different polymers may be present.
In the case of mixtures, one or more of the polymers may be a liquid, for example a low molecular weight polyalkylene glycol, provided that the resulting mixture of polymers is a solid.
Suitable polyalkylene glycols include polyethylene _l--:
., `, .
, q~
....
- 2 - 118-3347 glycol and polypropylene glycol and their copolymers having a ~olecular weight of 200 to 20,000, preferably 4000 to 15,000, more preferably 6000 to 13,000. By "polyvinyl-pyrrolidone" is meant uncrosslinked poly (N-vinyl)pyrrolidone, suitably of molecular weight between 10,000 and 100,000, preferably 11,500 to 40,000, more preferably 20,000 to 30,000. The copolymer of vinylpyrrolidone and vinyl acetate pr~ferably contains 60% by weight vinylpyrrolidone and 40%
by weight vinyl acetate and preferably has a molecular weight of 30,000 to 100,000, more preferab~y 40,000 to 90,000.
The solid solution or dispersion of ergot alkaloid and polymer may also contain certain additional pharma-ceutically acceptable ingredients, particularly surfactants such as sodium lauryl sulphate or polyethylene glycol fatty acid esters, preferably polyethylene glycol stearate; and stabilisers such as acids, preferably methanesulphonic acid, maleic acid and tartaxic acid, to adjust the pH of thé composition. The preferred pH range for the composition is pH 4-6, preferably pH 4-5.
In the solid solution or dispersion, the proportion by weight of ergot alkaloid to solid polymer together with additional ingredients, if present, may lie between 0.1:99.9 and 50:50, preferably between 5:95 and 15:85.
Wh~re additional ingredients are present, the proportion by weight of the additional ingredients to the ergot al~aloid is suitable from 1:45 to 10:1.
~079641
by weight vinyl acetate and preferably has a molecular weight of 30,000 to 100,000, more preferab~y 40,000 to 90,000.
The solid solution or dispersion of ergot alkaloid and polymer may also contain certain additional pharma-ceutically acceptable ingredients, particularly surfactants such as sodium lauryl sulphate or polyethylene glycol fatty acid esters, preferably polyethylene glycol stearate; and stabilisers such as acids, preferably methanesulphonic acid, maleic acid and tartaxic acid, to adjust the pH of thé composition. The preferred pH range for the composition is pH 4-6, preferably pH 4-5.
In the solid solution or dispersion, the proportion by weight of ergot alkaloid to solid polymer together with additional ingredients, if present, may lie between 0.1:99.9 and 50:50, preferably between 5:95 and 15:85.
Wh~re additional ingredients are present, the proportion by weight of the additional ingredients to the ergot al~aloid is suitable from 1:45 to 10:1.
~079641
- 3 - 118-3347 The solid solution or dispersion is preferably a tru~ solid solution of the ergot alkaloid in the polymer;
that is, it consists of only one solid phase. It may, how~ver, consist of a finely dispersed discontinuous phase of the ergot alkaloid in a continuous phase or matrix of the polymer.
The invention also provides a process for the-pre-par~tion of pharmaceutical compositions comprising the step o~ working up one or more ergot alkaloids into a solid solution or dispersion in a pharmaceu~ically acceptable solid polymer which is soluble or swellable in gastric juices, preferably consisting of a polyalkylene glycol, polyvinyl-pyrrolidone, a copolymer of vinylpyrrolidone and vinyl acetate, or ~ mixture of these. The solid solution or dispersion may be ~sed without further admixture, or may be compounded in kno~n manner with one or more conventional pharmaceutically acceptable excipients, and optionally with additional active ingredients.
Preferably, the solid solution or dispersion is obtained by dissolving the ergot alkaloid, the polymer and optionally any additional ingredients in a common solvent and evaporating to dryness the clear solution so obtained.
Suitable solvents include lower alcohols, having from 1 to 4 carbon atoms, for example ethanol and methanol. The solids are suitably dissolved by stirring with the solvent at a temperature of fro~ 30 to 70C, .
~, .
preferably 40-60C, and the solvent may be removed by evaporation under vacuum at the same temperatures. In the preparation of the solution it is also possible to add only a part of the polymer and the additional in-gredients, if any, and to add the remainder during the evaporation of the solvent. The resulting clear solution is left to solidify at room temperature (15-25C) and the solid solution or dispersion may then be ground to a fine powder and dried, suitably under vacuum at 30C, to remove all traces of the solvent.
The solid solution or dispersion may be used in the preparation of galenic forms such as tablets and capsules.
For this purpose it may be compounded with conventional excipients for example binding agents, lubricants, fillers and disintegrants as well as colouring agents, sweeteners and flavouring agents.
In the preparation of tablets, calcium carbonate, sodium carbonate, lactose, starch and talc may be used as fillers; starch and alginic acid as granulating and disintegrating agents; starch and gelatine as binding agents and magnesium stearate, stearic acid and talc as lubricants. Common pharmaceutical retarding agents such as waxes, fats, cellulose derivatives and other polymers may also be used. The tablets may be uncoated or coated in known manner.
, . .
.- :
-4_ ~ `
':
:, - , 107964~
In the preparation of soft gelatine capsules, the solid solution or dispersion is compounded in known manner for example with a mixture of glycerol, sorbitol and water together with preservative and optionally colouring matter. For filling hard gelatin capsules~ the solid solution or dispersion may be used alone or compounded in known manner with pharmaceutically acceptable diluents or carriers.
The pharmaceutical compositions according to the present invention have the advantageous property of giving increased absorption of the ergot alkaloids into the ;~
bloodstream of the recipient, thereby enhancing the known pharmacological properties of the ergot alkaolids.
The following Examples illustrate the invention:
:, . . .
, ,~.
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: . . :. . ....
`"~ 1079641 - ~ - 118-3347 EXAMPI,E 1:
34.6 g Dihydroergotamine methane6ulphonate, 195.4 g polyvinylpyrrolidone (av. mol.wt. ~5,000) and 500 ml methanol are charged into a 4 1 round-bottomed flask, which is then attached to a rotary evaporator. The flask is rotated at a bath temperature of 60C, until the flask contents reach 60~C, by which time a clear solution is obtained.
The bath temperature is maintained at 60C and the pressure is reduced to approx. 250 Torr. Methanol is removed by evaporation until the residue has a syrupy consistency. The residue is decanted into an evaporat~ng basin and left to solidify for two hours at room tem~
perature. The solid residue is dried in a vacuum oven at 30C, 1 Torr for 12 hours, ground to a fine powder and dried again.
EXAMPLE 2:
34.6 g Dihydroergotamine methanesulphonate, 193.2 g polyvinylpyrrolidone (av. mol.wt. 25,000) 2.26 g polyethylene .
glycol (1800~ stearate and 500 g methanol are charged into a 4 1 round-bottomed flask. The procedure of Example 1 is repeated, to obtain a dry powdered mixture.
EXAMPLE 3: Tablet Composition .
The following ingredients are compounded together in conventional manner and formed into tablets in a tablettin~ press:
.
10~7964~
Solid mixture of Example 1: 16.3 parts by weight `
lactose 104.0 " " "
corn starch 15 " " "
talc 12 " " "
cellulose powder32 l' ~' l' silicon dioxide0.7 l~
EXAMPLE 4: Composition for soft ~elatin capsules The following ingredients are compounded together in conventional manner and the mixture used to fill soft gelating capsules: :
Solid mixture of Example 1: 16.3 parts by weight ~`
Glycerol 9 " " " -Polyethylene glycol 400 74.7 " " "
EXAMPLE 5: Composition for hard g_latin capsules The follow$ng ingredients are compounded together .;
in conventional manner and the mixture used to fill hard gelating capsules: -Solid mixture of Example 1: 16.3 parts by weight Silicon dioxide 0.7 ~ corn starch 13 ., lactose 65 " " " `.
, EXANPLES ~-8 Examples 3-5 are repeated using the solid mixture of Example 2.
. ~ ~
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, ~ , '' `
that is, it consists of only one solid phase. It may, how~ver, consist of a finely dispersed discontinuous phase of the ergot alkaloid in a continuous phase or matrix of the polymer.
The invention also provides a process for the-pre-par~tion of pharmaceutical compositions comprising the step o~ working up one or more ergot alkaloids into a solid solution or dispersion in a pharmaceu~ically acceptable solid polymer which is soluble or swellable in gastric juices, preferably consisting of a polyalkylene glycol, polyvinyl-pyrrolidone, a copolymer of vinylpyrrolidone and vinyl acetate, or ~ mixture of these. The solid solution or dispersion may be ~sed without further admixture, or may be compounded in kno~n manner with one or more conventional pharmaceutically acceptable excipients, and optionally with additional active ingredients.
Preferably, the solid solution or dispersion is obtained by dissolving the ergot alkaloid, the polymer and optionally any additional ingredients in a common solvent and evaporating to dryness the clear solution so obtained.
Suitable solvents include lower alcohols, having from 1 to 4 carbon atoms, for example ethanol and methanol. The solids are suitably dissolved by stirring with the solvent at a temperature of fro~ 30 to 70C, .
~, .
preferably 40-60C, and the solvent may be removed by evaporation under vacuum at the same temperatures. In the preparation of the solution it is also possible to add only a part of the polymer and the additional in-gredients, if any, and to add the remainder during the evaporation of the solvent. The resulting clear solution is left to solidify at room temperature (15-25C) and the solid solution or dispersion may then be ground to a fine powder and dried, suitably under vacuum at 30C, to remove all traces of the solvent.
The solid solution or dispersion may be used in the preparation of galenic forms such as tablets and capsules.
For this purpose it may be compounded with conventional excipients for example binding agents, lubricants, fillers and disintegrants as well as colouring agents, sweeteners and flavouring agents.
In the preparation of tablets, calcium carbonate, sodium carbonate, lactose, starch and talc may be used as fillers; starch and alginic acid as granulating and disintegrating agents; starch and gelatine as binding agents and magnesium stearate, stearic acid and talc as lubricants. Common pharmaceutical retarding agents such as waxes, fats, cellulose derivatives and other polymers may also be used. The tablets may be uncoated or coated in known manner.
, . .
.- :
-4_ ~ `
':
:, - , 107964~
In the preparation of soft gelatine capsules, the solid solution or dispersion is compounded in known manner for example with a mixture of glycerol, sorbitol and water together with preservative and optionally colouring matter. For filling hard gelatin capsules~ the solid solution or dispersion may be used alone or compounded in known manner with pharmaceutically acceptable diluents or carriers.
The pharmaceutical compositions according to the present invention have the advantageous property of giving increased absorption of the ergot alkaloids into the ;~
bloodstream of the recipient, thereby enhancing the known pharmacological properties of the ergot alkaolids.
The following Examples illustrate the invention:
:, . . .
, ,~.
~;:
::
:'~
: . . :. . ....
`"~ 1079641 - ~ - 118-3347 EXAMPI,E 1:
34.6 g Dihydroergotamine methane6ulphonate, 195.4 g polyvinylpyrrolidone (av. mol.wt. ~5,000) and 500 ml methanol are charged into a 4 1 round-bottomed flask, which is then attached to a rotary evaporator. The flask is rotated at a bath temperature of 60C, until the flask contents reach 60~C, by which time a clear solution is obtained.
The bath temperature is maintained at 60C and the pressure is reduced to approx. 250 Torr. Methanol is removed by evaporation until the residue has a syrupy consistency. The residue is decanted into an evaporat~ng basin and left to solidify for two hours at room tem~
perature. The solid residue is dried in a vacuum oven at 30C, 1 Torr for 12 hours, ground to a fine powder and dried again.
EXAMPLE 2:
34.6 g Dihydroergotamine methanesulphonate, 193.2 g polyvinylpyrrolidone (av. mol.wt. 25,000) 2.26 g polyethylene .
glycol (1800~ stearate and 500 g methanol are charged into a 4 1 round-bottomed flask. The procedure of Example 1 is repeated, to obtain a dry powdered mixture.
EXAMPLE 3: Tablet Composition .
The following ingredients are compounded together in conventional manner and formed into tablets in a tablettin~ press:
.
10~7964~
Solid mixture of Example 1: 16.3 parts by weight `
lactose 104.0 " " "
corn starch 15 " " "
talc 12 " " "
cellulose powder32 l' ~' l' silicon dioxide0.7 l~
EXAMPLE 4: Composition for soft ~elatin capsules The following ingredients are compounded together in conventional manner and the mixture used to fill soft gelating capsules: :
Solid mixture of Example 1: 16.3 parts by weight ~`
Glycerol 9 " " " -Polyethylene glycol 400 74.7 " " "
EXAMPLE 5: Composition for hard g_latin capsules The follow$ng ingredients are compounded together .;
in conventional manner and the mixture used to fill hard gelating capsules: -Solid mixture of Example 1: 16.3 parts by weight Silicon dioxide 0.7 ~ corn starch 13 ., lactose 65 " " " `.
, EXANPLES ~-8 Examples 3-5 are repeated using the solid mixture of Example 2.
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, ~ , '' `
Claims (22)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A pharmaceutical composition comprising a solid solution or dispersion of one or more ergot alkaloids in a polymer selected from the group consisting of a polyalkylene glycol, uncrosslinked poly (N-vinyl)pyrrolidone, a copolymer of vinylpyrrolidone and vinyl acetate, or mixtures thereof, in which, in the solid solution or dispersion, the proportion by weight of ergot alkaloid to polymer, together with additional ingredients if present, is from 0.1:99.9 to 50:50.
2. A composition according to Claim 1 in which the polymer is polyethylene glycol, polypropylene glycol or a copolymer of these, having a molecular weight of 200 to 20,000.
3. A composition according to Claim 2, in which the polymer has a molecular weight of from 4000 to 15,000.
4. A composition according to Claim 3 in which the polymer has a molecular weight of from 6000 to 13,000.
5. A composition according to Claim 1 in which the polymer is uncrosslinked poly (N-vinyl) pyrrolidone of molecular weight from 11.500 to 40,000.
6. A composition according to Claim 5 in which the polymer has a molecular weight of from 20,000 to 30,000.
7. A Composition according to Claim 1 in which the polymer is a copolymer of vinylpyrrolidone and vinyl acetate, having a molecular weight of from 30,000 to 100,000.
8. A composition according to Claim 7 in which the polymer has a molecular weight of from 40,000 to 90,000.
9. A composition according to Claim 7 in which the polymer is a copolymer of 60% by weight vinylpyrrolidone and 40% by weight vinyl acetate.
10. A composition according to Claim 1 in which the solid solution or dispersion contains one or more ingredients in addition to the ergot alkaloid and the solid polymer.
11. A composition according to Claim 10 in which the proportion by weight of the additional ingredients to the ergot alkaloid is from 1:45 to 10:1.
12. A composition according to Claim 10 in which a surfactant is present as an additional ingredient.
13. A composition according to Claim 1 in which, in the solid solution or dispersion, the proportion by weight of ergot alkaloid to solid polymer together with additional ingredients if present, is from 5:95 to 15:85.
14. A composition according to Claim 1 comprising the solid solution or dispersion in association with one or more conventional pharmaceutically acceptable excipients.
15. A composition according to Claim 1 in the form of a tablet.
16. A composition according to Claim 1 in the form of a capsule.
17. A process for the production of a pharmaceutical composition according to Claim 1 comprising the steps of dissolving the ergot alkaloid and the polymer in a common solvent and then removing the solvent by evaporation.
18. A process according to Claim 17 in which the solvent is a lower alcohol having from 1-4 carbon atoms.
19. A process according to Claim 18 in which the solvent is methanol.
20. A process according to Claim 17 in which the solution and evaporation steps are carried out at a temperature between 40 and 60°C.
21. A process according to Claim 17 in which the residue from evaporation of the solvent is solidified, ground to a powder and dried.
22. A process according to Claim 17 in which the solid solution or dispersion is compounded in know manner with one or more pharmaceutically acceptable excipients and formed into tablets or capsules.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2546577A DE2546577B2 (en) | 1975-10-17 | 1975-10-17 | Solid substances made from polyvinylpyrrolidone and ergot alkaloids |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1079641A true CA1079641A (en) | 1980-06-17 |
Family
ID=5959411
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA263,423A Expired CA1079641A (en) | 1975-10-17 | 1976-10-14 | Pharmaceutical composition containing ergot alkaloids |
Country Status (28)
| Country | Link |
|---|---|
| JP (1) | JPS5854122B2 (en) |
| AT (1) | AT362510B (en) |
| AU (1) | AU508628B2 (en) |
| BE (1) | BE847368A (en) |
| CA (1) | CA1079641A (en) |
| CH (1) | CH643737A5 (en) |
| CS (1) | CS199647B2 (en) |
| DE (1) | DE2546577B2 (en) |
| DK (1) | DK146194C (en) |
| ES (1) | ES452420A1 (en) |
| FI (1) | FI762875A (en) |
| FR (1) | FR2327764A1 (en) |
| GB (1) | GB1560406A (en) |
| GR (1) | GR61268B (en) |
| HK (1) | HK3183A (en) |
| HU (1) | HU172533B (en) |
| IE (1) | IE43778B1 (en) |
| IL (1) | IL50686A (en) |
| MY (1) | MY8400063A (en) |
| NL (1) | NL184558C (en) |
| NO (1) | NO144468C (en) |
| NZ (1) | NZ182341A (en) |
| PH (1) | PH14513A (en) |
| PT (1) | PT65719B (en) |
| SE (1) | SE430379B (en) |
| SG (1) | SG63082G (en) |
| SU (1) | SU1165223A3 (en) |
| ZA (1) | ZA766166B (en) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1572226A (en) * | 1977-11-03 | 1980-07-30 | Hoechst Uk Ltd | Pharmaceutical preparations in solid unit dosage form |
| US4411882A (en) | 1978-12-21 | 1983-10-25 | Sandoz Ltd. | Galenical compositions |
| DK154607C (en) * | 1978-12-21 | 1989-06-05 | Sandoz Ag | PROCEDURE FOR PREPARING A PHARMACEUTICAL FORM FOR ORAL ADMINISTRATION OF ERGOTAL KALOIDS |
| FR2454804B1 (en) * | 1979-04-26 | 1986-11-21 | Sanofi Sa | DIHYDROERGOTOXIN-BASED MEDICINAL PRODUCT AND PROCESS FOR PREPARING THE SAME |
| US4366145A (en) * | 1981-06-24 | 1982-12-28 | Sandoz, Inc. | Soft gelatin capsule with a liquid ergot alkaloid center fill solution and method of preparation |
| US4898729A (en) * | 1983-12-09 | 1990-02-06 | Euroceltique, S.A. | Treatment of hypertension, compounds and compositions for antihypertension and diuresis |
| HU198844B (en) * | 1984-06-14 | 1989-12-28 | Sandoz Ag | Process for producing new galenic pharmaceutical composition ensuring retarded release of active ingredient |
| ATE72111T1 (en) * | 1987-01-14 | 1992-02-15 | Ciba Geigy Ag | THERAPEUTIC SYSTEM FOR POORLY SOLUBLE ACTIVE INGREDIENTS. |
| FR2610827B1 (en) * | 1987-02-18 | 1991-09-13 | Pf Medicament | DIHYDROERGOTAMINE (D.H.E.) TABLET OF THE HYDROPHILIC MATRIX TYPE AND MANUFACTURING METHOD THEREOF |
| US5064656A (en) * | 1989-11-14 | 1991-11-12 | Dr. Gergely & Co. | Uncoated pharmaceutical reaction tablet |
| DE4401646A1 (en) * | 1994-01-21 | 1995-07-27 | Krewel Werke Gmbh | Optimally releasing kava extracts |
| US6524832B1 (en) | 1994-02-04 | 2003-02-25 | Arch Development Corporation | DNA damaging agents in combination with tyrosine kinase inhibitors |
| DE69821984T2 (en) * | 1997-12-22 | 2004-12-30 | Schering Corp. | PREPARATION CONTAINS A MOLECULAR DISPERSION WITH INCREASED BIOAVAILABILITY |
| US6632455B2 (en) | 1997-12-22 | 2003-10-14 | Schering Corporation | Molecular dispersion composition with enhanced bioavailability |
| US6316462B1 (en) | 1999-04-09 | 2001-11-13 | Schering Corporation | Methods of inducing cancer cell death and tumor regression |
| US7771746B2 (en) | 1999-12-03 | 2010-08-10 | Polichem Sa | Methods for making sustained-release pharmaceutical compositions of ergot alkaloids having improved bioavailability and compositions thereof |
| KR100504618B1 (en) * | 1999-12-03 | 2005-08-04 | 폴리켐 에스.아. | Methods for making sustained-release pharmaceutical compositions of ergot alkaloids having improved bioavailability and compositions thereof |
| US7135436B2 (en) | 2003-05-05 | 2006-11-14 | J.F. Daley International, Ltd. | Solid algicide, preparation and usage in recirculating water |
| DE60309356T2 (en) * | 2003-06-27 | 2007-08-30 | Bioprogress S.P.A. | COMPOSITION, BY COMPRESSING COMPOUND OF AN ACTIVE AGENT WITH AN N-VINYL-2-PYRROLIDONE / VINYL ACETATE COPOLYMERS AVAILABLE |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1175430A (en) * | 1966-04-07 | 1969-12-23 | Sandoz Ltd | Pharmaceutical Compositions containing Ergot Alkaloids |
-
1975
- 1975-10-17 DE DE2546577A patent/DE2546577B2/en not_active Withdrawn
-
1976
- 1976-10-01 CH CH1244876A patent/CH643737A5/en not_active IP Right Cessation
- 1976-10-08 FI FI762875A patent/FI762875A/fi not_active Application Discontinuation
- 1976-10-08 SE SE7611189A patent/SE430379B/en not_active IP Right Cessation
- 1976-10-08 NO NO763446A patent/NO144468C/en unknown
- 1976-10-08 DK DK454176A patent/DK146194C/en not_active IP Right Cessation
- 1976-10-13 NL NLAANVRAGE7611295,A patent/NL184558C/en not_active IP Right Cessation
- 1976-10-14 CA CA263,423A patent/CA1079641A/en not_active Expired
- 1976-10-14 FR FR7630866A patent/FR2327764A1/en active Granted
- 1976-10-14 PH PH19008A patent/PH14513A/en unknown
- 1976-10-15 ES ES452420A patent/ES452420A1/en not_active Expired
- 1976-10-15 ZA ZA00766166A patent/ZA766166B/en unknown
- 1976-10-15 NZ NZ182341A patent/NZ182341A/en unknown
- 1976-10-15 HU HU76SA00002985A patent/HU172533B/en not_active IP Right Cessation
- 1976-10-15 AT AT767976A patent/AT362510B/en not_active IP Right Cessation
- 1976-10-15 IL IL50686A patent/IL50686A/en unknown
- 1976-10-15 CS CS766685A patent/CS199647B2/en unknown
- 1976-10-15 AU AU18754/76A patent/AU508628B2/en not_active Expired
- 1976-10-15 GB GB42907/76A patent/GB1560406A/en not_active Expired
- 1976-10-15 BE BE171578A patent/BE847368A/en not_active IP Right Cessation
- 1976-10-15 PT PT65719A patent/PT65719B/en unknown
- 1976-10-15 SU SU762412401A patent/SU1165223A3/en active
- 1976-10-15 IE IE2282/76A patent/IE43778B1/en not_active IP Right Cessation
- 1976-10-16 JP JP51123463A patent/JPS5854122B2/en not_active Expired
- 1976-10-16 GR GR51952A patent/GR61268B/en unknown
-
1982
- 1982-12-23 SG SG630/82A patent/SG63082G/en unknown
-
1983
- 1983-01-20 HK HK31/83A patent/HK3183A/en unknown
-
1984
- 1984-12-30 MY MY63/84A patent/MY8400063A/en unknown
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