CA1069438A - Stable solutions and processes for their preparation - Google Patents
Stable solutions and processes for their preparationInfo
- Publication number
- CA1069438A CA1069438A CA253,612A CA253612A CA1069438A CA 1069438 A CA1069438 A CA 1069438A CA 253612 A CA253612 A CA 253612A CA 1069438 A CA1069438 A CA 1069438A
- Authority
- CA
- Canada
- Prior art keywords
- component
- composition according
- carbon atoms
- weight
- alcohol
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- General Chemical & Material Sciences (AREA)
- Dermatology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines Containing Plant Substances (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Saccharide Compounds (AREA)
Abstract
STABLE SOLUTIONS AND PROCESSES FOR THEIR PREPARATION
Abstract of the Disclosure Solutions of hydrogenated ergopeptide alkaloids in pharmacologically acceptable organic solvents have improved stability. Preferred solvents are alcohols, particularly mixtures of ethanol and propylene glyool.
Abstract of the Disclosure Solutions of hydrogenated ergopeptide alkaloids in pharmacologically acceptable organic solvents have improved stability. Preferred solvents are alcohols, particularly mixtures of ethanol and propylene glyool.
Description
This invention relates to solutions of ergot alkaloids and their synthetic derivatives including their hydrogenated derivatives and salt forms thereof.
Solutions of such compounds in predominantly aqueous media have the disadvantage that the concentration of the active species decreases on storage, for example because of oxidation reactions. For this reason it is normal practice to pass inert gas through the solution during filling o-f the vessels in which the solution is to be sold, and to protect the contents from air, light and high temperatures~
It has now been found that solutions of certain ergot alkaloids have improved stability when pharmaco-logically acceptable organic solvents are used in place of aqueous media.
The present invention provides a stable solution of hydx~genated ergopeptide alkaloids in which a pharma- -cologically acceptable organic solvent mixture is used as the solvent medium. Thus, the invention relates to a pharmaceutical composition in the form of a stable solu-tion consisting essentially of a) a hydrogenated ergopeptide alkaloid as herein de~ined, b) a pharmacologically acceptable monofunctional alcohol having up to 18 carbon atoms, c~ a polyfunctional alcohol having up to 6 carbon atoms and 6 hydroxy groups or a polymeric polyfunctional alcohol having a molecular weight of from 200 to 20,000 and d) up to 40% by weight of the solution water, the weight ratio of component b) to component c) being 1:0.1 to 1:100.
By the term 'hydrogenated ergopeptide alkaloids' is included hydrogenated natural or synthetic ergopeptide alkaloids, together with their salt forms.
~ . .
3~
Suitable pharmacologically acceptable mono-functional alcohols, include those having up to 18 carbon atoms, preferably up to 10 carbon atoms and most prefer ably up to 3 carbon atoms. An especially preferred solvent of t~is type is ethanol. Suitable pharmacologically acceptable polyfunctional-alcohols include those having up to 6, preferably 2 or 3 hydroxy groups, and up to 6, preferably 2 or 3 carbon atoms, e~pecially glycerol and propylene glycol. Polyfunctional alcohols may also be used in polymeric form, for example polyalkylene glycols, especially polyethylene glycol, polypropylene glyoo~ or their copolymers, having a molecular weight from 200 to 20,000, prefsrably ~rom 200 to 600. A particularly suitable polyalcohol is a polyethylene glycol with a molecular weight of approximately 400.
The monofunctional and the polyfunctional alcohol should be present in a ratio of from 1:0.1 to 1:100 by weight, preferably in a ratio of from 1:1 to 1:4, more preferably of 1:2 by weight. A mixture of ethanol and propylene glycol is particularly preferred. The solutions may of course contain a mixture of several mono- and/or polyfunctional aLcohols.
Furthermore, the compositions according to the invention may further containl as addikional solvents, pharmacologicaliy acceptable organic esters and ethers, particuIarly those formed from the above-mentioned mono-and polyfunctional-alcohols and fatty acids having from 12 - 18 carbon atoms, ~or example stearic acid, palmitic acid and oleic acid; or fatty a~cohols having from 12 to 18 carbon atoms, for example lauryl alcohol, cetyl alcohol and stearyl alcohol.
.
~, . ' '.
.. . .. . .
The compositions may contain minor amounts of water, but the water content must not exceed 40% by weight of the composition, and preferably is not greater than 3% by weight of the composition.
Hydrogenated natural and synthetic ergopeptide alkaloids which may be stabilised in solution by the process of the invention include dihydroergotamine, dihydroergocristine, dihydroergocryptine, dihydroergo-cornine and mixtures thereof, particularly a mixture of dihydroergo~ristine, dihydroergocryptine,and dihydro~
ergocornine in 1:1:1 ratio. Suitable salt forms are salts of pharmacologically acceptable acids, for example the methane-sulphonate, maleate, tartrate, etc.
Although the concentration of the hydrogenated ergopeptide alkaloids in the solutions is not critlcal, it is preferred to use solutions with a concentration of active species of from 0.1 to 1~ by weight, preferably from 0.1 to 0.5% by weight. It is to be understood that the concentration to be used will depend upon the ap-plication for which the solution is intended.
The solutions may in addition contain furthersolubilising additives for example acids, particularly methanesulphonic acid, maleic acid, tartaric acid, etc.
me preparation of the compositions according to the invention is aarried out by dissolving the hydro-genated ergopeptide alkaloids in one of the described organic solvents or solvent mixtures by stirring, suitably undex an atmosphere of inert ga~, e.g. nitrogen, and suitably with exclusion of daylight and at room temperature ~15-25C).
The preparation of solvent mixtures is carried out - 3 _ ~ ~ . '.
. ~ . . . . .
~9~3~3 in conventional manner, and where one of the solvent components is solid at room temperature, mixing is suitably carried out at higher temperatures, e.g. at up to 80C.
Ethanol may advantageously be used as co-solvent.
Compositions according to the invention are useful as pharmaceuticals in the same way as corresponding aqueous solutions of the same active species. They may be administered orally, and may for this purpose be made up in vessels designed to dispense unit dosages, for example dropper bottles; or parenterally, in which case the solutions will normally be sterilized and may be sealed in ampoules of unit dosage.
EXAMPLE 1:
A mixture of 50.0 g propylene glycol and 41.9 g 94% ethanol was prepared and in this mixture was dis-solved, by stirring at room temperature under a nitrogen atmosphere, 0.1 g of a mixture of dihydroergocristine, dihydroergocryptine and dihydroergocornine (1:1:1). After filtration under pressure, the solution was used to fill dropper bottles.
EXAMPLE 2:
.
A mixture of 40.0 g propylene glycol, 34.0 g 94~ ethanol and 25.0 g anhydrous glycerol was prepared and in this mixture was dissolved, by stirring at room tem-perature under a nitrogen atmosphere, 0.1 g of a mixture dihydroergocristine, dihydroergocryptine and dihydro-ergocornine (1:1:1). After filtration under pressure, the solution was used to ill dropper bottles.
- EXAMPLE 3:
A mixture of 50 D 3 g propylene glycol and 41.9 g 94~ ethanol was prepared and in this mixture was dissolved, _ ~ _ .. . .. . . .. .... .. ... . . ..
9~38 by stirring at room temperature under a nitrogen atmos-phere, 0.1 g of dihydroergotamine methanesulphonate.
After filtration under pressure, the solution was used to fill dropper bottles.
''; ~
: ' . .
_ 5 _ - . : . . . : - . .
Solutions of such compounds in predominantly aqueous media have the disadvantage that the concentration of the active species decreases on storage, for example because of oxidation reactions. For this reason it is normal practice to pass inert gas through the solution during filling o-f the vessels in which the solution is to be sold, and to protect the contents from air, light and high temperatures~
It has now been found that solutions of certain ergot alkaloids have improved stability when pharmaco-logically acceptable organic solvents are used in place of aqueous media.
The present invention provides a stable solution of hydx~genated ergopeptide alkaloids in which a pharma- -cologically acceptable organic solvent mixture is used as the solvent medium. Thus, the invention relates to a pharmaceutical composition in the form of a stable solu-tion consisting essentially of a) a hydrogenated ergopeptide alkaloid as herein de~ined, b) a pharmacologically acceptable monofunctional alcohol having up to 18 carbon atoms, c~ a polyfunctional alcohol having up to 6 carbon atoms and 6 hydroxy groups or a polymeric polyfunctional alcohol having a molecular weight of from 200 to 20,000 and d) up to 40% by weight of the solution water, the weight ratio of component b) to component c) being 1:0.1 to 1:100.
By the term 'hydrogenated ergopeptide alkaloids' is included hydrogenated natural or synthetic ergopeptide alkaloids, together with their salt forms.
~ . .
3~
Suitable pharmacologically acceptable mono-functional alcohols, include those having up to 18 carbon atoms, preferably up to 10 carbon atoms and most prefer ably up to 3 carbon atoms. An especially preferred solvent of t~is type is ethanol. Suitable pharmacologically acceptable polyfunctional-alcohols include those having up to 6, preferably 2 or 3 hydroxy groups, and up to 6, preferably 2 or 3 carbon atoms, e~pecially glycerol and propylene glycol. Polyfunctional alcohols may also be used in polymeric form, for example polyalkylene glycols, especially polyethylene glycol, polypropylene glyoo~ or their copolymers, having a molecular weight from 200 to 20,000, prefsrably ~rom 200 to 600. A particularly suitable polyalcohol is a polyethylene glycol with a molecular weight of approximately 400.
The monofunctional and the polyfunctional alcohol should be present in a ratio of from 1:0.1 to 1:100 by weight, preferably in a ratio of from 1:1 to 1:4, more preferably of 1:2 by weight. A mixture of ethanol and propylene glycol is particularly preferred. The solutions may of course contain a mixture of several mono- and/or polyfunctional aLcohols.
Furthermore, the compositions according to the invention may further containl as addikional solvents, pharmacologicaliy acceptable organic esters and ethers, particuIarly those formed from the above-mentioned mono-and polyfunctional-alcohols and fatty acids having from 12 - 18 carbon atoms, ~or example stearic acid, palmitic acid and oleic acid; or fatty a~cohols having from 12 to 18 carbon atoms, for example lauryl alcohol, cetyl alcohol and stearyl alcohol.
.
~, . ' '.
.. . .. . .
The compositions may contain minor amounts of water, but the water content must not exceed 40% by weight of the composition, and preferably is not greater than 3% by weight of the composition.
Hydrogenated natural and synthetic ergopeptide alkaloids which may be stabilised in solution by the process of the invention include dihydroergotamine, dihydroergocristine, dihydroergocryptine, dihydroergo-cornine and mixtures thereof, particularly a mixture of dihydroergo~ristine, dihydroergocryptine,and dihydro~
ergocornine in 1:1:1 ratio. Suitable salt forms are salts of pharmacologically acceptable acids, for example the methane-sulphonate, maleate, tartrate, etc.
Although the concentration of the hydrogenated ergopeptide alkaloids in the solutions is not critlcal, it is preferred to use solutions with a concentration of active species of from 0.1 to 1~ by weight, preferably from 0.1 to 0.5% by weight. It is to be understood that the concentration to be used will depend upon the ap-plication for which the solution is intended.
The solutions may in addition contain furthersolubilising additives for example acids, particularly methanesulphonic acid, maleic acid, tartaric acid, etc.
me preparation of the compositions according to the invention is aarried out by dissolving the hydro-genated ergopeptide alkaloids in one of the described organic solvents or solvent mixtures by stirring, suitably undex an atmosphere of inert ga~, e.g. nitrogen, and suitably with exclusion of daylight and at room temperature ~15-25C).
The preparation of solvent mixtures is carried out - 3 _ ~ ~ . '.
. ~ . . . . .
~9~3~3 in conventional manner, and where one of the solvent components is solid at room temperature, mixing is suitably carried out at higher temperatures, e.g. at up to 80C.
Ethanol may advantageously be used as co-solvent.
Compositions according to the invention are useful as pharmaceuticals in the same way as corresponding aqueous solutions of the same active species. They may be administered orally, and may for this purpose be made up in vessels designed to dispense unit dosages, for example dropper bottles; or parenterally, in which case the solutions will normally be sterilized and may be sealed in ampoules of unit dosage.
EXAMPLE 1:
A mixture of 50.0 g propylene glycol and 41.9 g 94% ethanol was prepared and in this mixture was dis-solved, by stirring at room temperature under a nitrogen atmosphere, 0.1 g of a mixture of dihydroergocristine, dihydroergocryptine and dihydroergocornine (1:1:1). After filtration under pressure, the solution was used to fill dropper bottles.
EXAMPLE 2:
.
A mixture of 40.0 g propylene glycol, 34.0 g 94~ ethanol and 25.0 g anhydrous glycerol was prepared and in this mixture was dissolved, by stirring at room tem-perature under a nitrogen atmosphere, 0.1 g of a mixture dihydroergocristine, dihydroergocryptine and dihydro-ergocornine (1:1:1). After filtration under pressure, the solution was used to ill dropper bottles.
- EXAMPLE 3:
A mixture of 50 D 3 g propylene glycol and 41.9 g 94~ ethanol was prepared and in this mixture was dissolved, _ ~ _ .. . .. . . .. .... .. ... . . ..
9~38 by stirring at room temperature under a nitrogen atmos-phere, 0.1 g of dihydroergotamine methanesulphonate.
After filtration under pressure, the solution was used to fill dropper bottles.
''; ~
: ' . .
_ 5 _ - . : . . . : - . .
Claims (13)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A pharmaceutical composition in the form of a stable solution consisting essentially of a) a hydrogenated ergopeptide alkaloid b) a pharmacologically acceptable monofunctional alcohol having up to 18 carbon atoms c) a polyfunctional alcohol having up to 6 carbon atoms and 6 hydroxy groups or a polymeric poly-functional alcohol having a molecular weight of from 200 to 20,000, and d) up to 40% by weight of the solution water, the weight ratio of component b) to component c) being 1:0.1 to 1:100.
2. A composition according to Claim 1 in which the concentration of component a) is from 0.1 to 1 per cent by weight.
3. A composition according to Claim 2 in which the concentration of component a) is from 0.1 to 0.5 per cent by weight.
4) A composition according to Claim 1 in which component b) has up to 10 carbon atoms and the ratio of component b) to component c) is 1:1 to 1:10.
5. A composition according to Claim 4 in which component b) has up to 3 carbon atoms and component c) is a polyhydroxy alcohol of 2 to 3 carbon atoms and 2 or 3 hydroxy groups or a polymeric polyhydroxy alcohol having a molecular weight of 200 to 600 and the ratio of component b) to component c) is 1:1 to 1:4.
6. A composition according to Claim 5 in which the ratio of component b) to component c) is 1:1 to 1:2.
7. A composition according to Claim 5 in which the ratio of component b) to component c) is 1:2.
8. A composition according to Claim 1 in which component a) is ethanol and component b) is propylene glycol or glycerol or a mixture thereof.
9. A composition according to Claim 1 in which the hydrogenated ergopeptide alkaloid is dihydroergotamine, dihydroergocristine, dihydroergocryptine, dihydroergo-cornine or pharmaceutically acceptable salts thereof or mixtures thereof.
10. A composition according to Claim 9 in which the hydrogenated ergopeptide alkaloid is a 1:1:1 mixture of dihydroergocristine, dihydroergocryptine and dihydro-ergocornine or pharmaceutically acceptable salts thereof.
11. A composition according to Claim 1 con-tained in a sterilized, sealed ampoule.
12. A composition according to claim 1 con-tained in a dropper bottle.
13. A method of preparing a pharmaceutical composition in the form of a stable solution according to Claim 1 which comprises dissolving a hydrogenated ergopeptide alkaloid or a pharmaceutically acceptable acid addition salt thereof or mixture thereof in a solvent consisting essentially of; a) a pharmacologically acceptable monofunctional alcohol having up to 18 carbon atoms or mixture thereof; b) a polyfunctional alcohol having up to 6 carbon atoms and 6 hydroxy groups or a polymeric poly-functional alcohol having a molecular weight of from 200 to 20,000 or mixture thereof; and c) up to 40% by weight of the solution of water, the weight ratio of component b) to component c) being 1:0.1 to 1:100, under an atmosphere of inert gas with the exclusion of daylight and at a temperature of 15 to 25°C.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2524184 | 1975-05-31 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1069438A true CA1069438A (en) | 1980-01-08 |
Family
ID=5947910
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA253,612A Expired CA1069438A (en) | 1975-05-31 | 1976-05-28 | Stable solutions and processes for their preparation |
Country Status (26)
| Country | Link |
|---|---|
| JP (1) | JPS585167B2 (en) |
| AT (1) | AT355725B (en) |
| AU (1) | AU508625B2 (en) |
| BE (1) | BE842348A (en) |
| CA (1) | CA1069438A (en) |
| CS (1) | CS205023B2 (en) |
| DD (1) | DD125597A5 (en) |
| DK (1) | DK154606C (en) |
| ES (1) | ES448372A1 (en) |
| FI (1) | FI761461A (en) |
| FR (1) | FR2313059A1 (en) |
| GB (1) | GB1539083A (en) |
| GR (1) | GR60264B (en) |
| HK (1) | HK15383A (en) |
| HU (1) | HU171514B (en) |
| IE (1) | IE42999B1 (en) |
| IL (1) | IL49668A (en) |
| MY (1) | MY8300013A (en) |
| NL (1) | NL172616C (en) |
| NO (1) | NO145262C (en) |
| NZ (1) | NZ180984A (en) |
| PT (1) | PT65151B (en) |
| SE (1) | SE426782B (en) |
| SU (2) | SU952106A3 (en) |
| YU (1) | YU133076A (en) |
| ZA (1) | ZA763138B (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2935515A1 (en) * | 1979-09-03 | 1981-03-19 | Fa. Dr. Willmar Schwabe, 7500 Karlsruhe | MEDICINAL PRODUCT |
| FR2483235A1 (en) * | 1980-05-28 | 1981-12-04 | Fabre Sa Pierre | TOPICAL COMPOSITIONS CONTAINING RYE AND VINCA ROSEA ERGOT ALKALOIDS FOR THE TREATMENT OF HYPERSEBORRHOES |
| DE3227122A1 (en) * | 1982-07-20 | 1984-01-26 | Dr. Rentschler Arzneimittel Gmbh & Co, 7958 Laupheim | STABLE SOLUTIONS OF MOTHER CORNAL CALOIDS |
| HU192050B (en) * | 1983-04-22 | 1987-05-28 | Sandoz Ag | Process for production of medical preparative containing co-dergocrin and one piridin-dicarbonic acid diesthertype calcium-antagonist |
| IT1200609B (en) * | 1985-04-04 | 1989-01-27 | Poli Ind Chimica Spa | PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF CEREBROVASCULAR TURBES AND THE ELDERLY BRAIN |
| DE102007014947B4 (en) | 2007-03-23 | 2010-05-27 | Axxonis Pharma Ag | Stabilized aqueous solutions of ergoline compounds |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DD43402A (en) * | ||||
| US2033921A (en) * | 1931-08-28 | 1936-03-17 | Squibb & Sons Inc | Solution of ergot alkaloids |
| US1969382A (en) * | 1932-05-21 | 1934-08-07 | Squibb & Sons Inc | Preparation of a stable hydro-alcoholic extract of ergot |
-
1976
- 1976-05-24 NO NO761760A patent/NO145262C/en unknown
- 1976-05-24 FI FI761461A patent/FI761461A/fi not_active Application Discontinuation
- 1976-05-24 DK DK228676A patent/DK154606C/en not_active IP Right Cessation
- 1976-05-24 SE SE7605841A patent/SE426782B/en not_active IP Right Cessation
- 1976-05-25 FR FR7615744A patent/FR2313059A1/en active Granted
- 1976-05-26 GB GB21809/76A patent/GB1539083A/en not_active Expired
- 1976-05-26 ZA ZA00763138A patent/ZA763138B/en unknown
- 1976-05-27 IL IL49668A patent/IL49668A/en unknown
- 1976-05-28 JP JP51062848A patent/JPS585167B2/en not_active Expired
- 1976-05-28 PT PT65151A patent/PT65151B/en unknown
- 1976-05-28 DD DD193077A patent/DD125597A5/xx unknown
- 1976-05-28 NL NLAANVRAGE7605745,A patent/NL172616C/en not_active IP Right Cessation
- 1976-05-28 AT AT390476A patent/AT355725B/en not_active IP Right Cessation
- 1976-05-28 AU AU14422/76A patent/AU508625B2/en not_active Expired
- 1976-05-28 NZ NZ180984A patent/NZ180984A/en unknown
- 1976-05-28 IE IE1138/76A patent/IE42999B1/en unknown
- 1976-05-28 CA CA253,612A patent/CA1069438A/en not_active Expired
- 1976-05-28 BE BE167442A patent/BE842348A/en not_active IP Right Cessation
- 1976-05-29 GR GR50841A patent/GR60264B/en unknown
- 1976-05-29 ES ES448372A patent/ES448372A1/en not_active Expired
- 1976-05-31 CS CS763620A patent/CS205023B2/en unknown
- 1976-05-31 HU HU76SA00002923A patent/HU171514B/en not_active IP Right Cessation
- 1976-05-31 SU SU762362650D patent/SU952106A3/en active
- 1976-05-31 SU SU762362650A patent/SU677664A3/en active
- 1976-05-31 YU YU01330/76A patent/YU133076A/en unknown
-
1983
- 1983-05-12 HK HK153/83A patent/HK15383A/en unknown
- 1983-12-30 MY MY13/83A patent/MY8300013A/en unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU681579B2 (en) | Rapamycin formulation for IV injection | |
| US4138565A (en) | Stable solutions and processes for their preparation | |
| JP4073503B2 (en) | Liquid formulation containing cyclosporine and method for its preparation | |
| US5880133A (en) | Pharmaceutical formulations of highly lipophilic camptothecin derivatives | |
| CA1177399A (en) | Injectable composition of rapamycin | |
| JP3617055B2 (en) | Stable pharmaceutical composition containing 4,5-epoxymorphinan derivative | |
| AU689488B2 (en) | Rapamycin formulation for IV injection | |
| JP2002540136A (en) | Dihydroergotamine compositions with high potency | |
| PL184750B1 (en) | Pharmaceutic compositions | |
| CA2133179A1 (en) | Rapamycin formulation for iv injection | |
| EP0193287A2 (en) | Etoposide preparations | |
| JP2006312651A (en) | Suspension comprising oxcarbazepine | |
| CZ293747B6 (en) | Aqueous pharmaceutical solution suitable for injection into a host and use thereof | |
| US4366145A (en) | Soft gelatin capsule with a liquid ergot alkaloid center fill solution and method of preparation | |
| CA1069438A (en) | Stable solutions and processes for their preparation | |
| EP0812587A1 (en) | Transdermal compositions containing Nimesulide | |
| CA1111348A (en) | Solution containing a hydrogenated ergopeptide alkaloid | |
| DE202016008852U1 (en) | Ready-to-use Bortezomibester solution | |
| RU2084226C1 (en) | Composition exhibiting antitumor action | |
| ZA200604757B (en) | Pharmaceutical formulations of camptothecins and process for making same | |
| US6306843B1 (en) | Method for producing stable acetylsalicylic acid solutions | |
| JPH0339489B2 (en) | ||
| CN115666579A (en) | Stable, ready-to-dilute formulations of carfilzomib | |
| US4078065A (en) | Organic compounds | |
| HU200923B (en) | Process for producing pharmaceutical compositions ensuring percutaneous resorption and comprising nicorandyl |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |