CA2075060C - Novel vehicle gases and their use in medical preparations - Google Patents
Novel vehicle gases and their use in medical preparations Download PDFInfo
- Publication number
- CA2075060C CA2075060C CA002075060A CA2075060A CA2075060C CA 2075060 C CA2075060 C CA 2075060C CA 002075060 A CA002075060 A CA 002075060A CA 2075060 A CA2075060 A CA 2075060A CA 2075060 C CA2075060 C CA 2075060C
- Authority
- CA
- Canada
- Prior art keywords
- pharmaceutical preparation
- preparation according
- active substance
- specified
- group
- 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 - Lifetime
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
-
- 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
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/008—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/12—Aerosols; Foams
- A61K9/124—Aerosols; Foams characterised by the propellant
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K3/00—Materials not provided for elsewhere
- C09K3/30—Materials not provided for elsewhere for aerosols
Abstract
Besides 1,1,1,2,3,3,3-heptafluoropropane, novel advantageous vehicle gases may contain one or more further vehicle gas components and may be used in medical preparations.
Description
New pro ellent oases and their use in pharmaceutical preparations The invention relates to new propellent gases which contain as a typical ingredient 1,1,1,2,3,3,3-heptafluoro-propane (TG 227), the use of these propellent gases in pharmaceutical preparations suitable far producing aerosols, and these pharmaceutical preparations themselves.
Aerosols of powdered (micronised) drugs are used widely in therapy, e.g. in the treatment of obstructive diseases of the respiratory tract. If such aerosols are not produced by atomising the pharmaceutical powder or by spraying solutions, suspensions of the drugs in liquefied propellent gases are used. The latter consist primarily of mixtures of trichlorofluromethane (TG11), dichlorodifluoromethane (TG12) and 1,2-dichloro-1,1,2,2-tetrafluoroethane (TG114), optionally with the addition of lower alkanes such as butane or pentane, or with the addition of DME (dimethylether). Mixtures of this kind are known for example from German Patent 1178975.
Owing to their harmful effect on the earth's atmosphere (destruction of the ozone layer, Greenhouse effect) the use of chloroflurocarbons has become a problem, with the result that the search is on for other propellent gases or propellent gas mixtures which do not have the above-mentioned harmful effects or, at least, have them to a lesser degree.
However, this search has come up against major problems, since propellent gases for therapeutic use have to satisfy numerous criteria which cannot easily be reconciled, e.g. in terms of toxicity, stability, vapour pressure, density and solubility characteristics.
According to one broad aspect, the present invention provides a pharmaceutical preparation for inhalation containing a micronised pharmaceutically active substance in a liquified propellant gas, characterised in that 1,1,1,2,3,3,3-heptafluoro propane is used as propellant gas.
In a second broad aspect, the invention provides a pharmaceutical preparation, in which the propellant gas TG 227 (1,1,1,2,3,3,3-heptafluropropane, is in admixture with one of more propellent gases from the group comprising TG 11 (trichlorofluromethane), TG 12 (dichlorodifluoromethane), TG
114 (1,2-dichloro-1,1,2,2-tetrafluoroethane, propane, butane, pentane and DME
- la -,~0 750 80 (dimethylether). which is particularly suitable for use in therapeutic preparations.
The compounds to be used in addition to TG 227 are added if the properties of the propellent gas are to be modified, e.g. if the liquefied propellent gas is to have a different density, different pressure or different solubility characteristics. Pharmaceutical preparations based on the propellent gas contain an active substance in finely divided form, usually as a suspension, and generally also contain surface-active substances, e.g. a phospholipid (such as lecithin), an ester of a polyalcohol (such as sorbitol) with higher saturated or unsaturated fatty acids (e. g. stearic, palmitic or oleic acid), such as sorbitan trioleate, or a putyethoxysorbitan ester of a higher, preferably unsaturated fatty acid. The adjuvant may be present in the mixture in dissolved or undissolved form. In some cases, the suspensions produced with the new propellent gas have a tendency to separate out. However, it has been found that the separated suspensions can easily be uniformly distributed again in the suspension medium simply by shaking.
The ratios of quantities of the individual ingredients of the propellent gas mixture may be varied within wide limits. The proportion (in percent by weight) is 10~~to 100% in the case of TG 227. The mixture may also contain up to 50% propane and/or butane and/or pentane and/or DME and/or TG 11 and/or TG 12 and/or TG 114. Within the limits specified the ingredients are chosen to add up to 100%. Propellent gas mixtures which contain 30 to 100% TG 227 are preferred.
The proportion of suspended drug in the finished preparation is between 0.001 and 5%, preferably between 0.005 and 3%, more particularly between 0.01 and 2%.
The surface-active substances are added in amounts of from 0.01 to 10%, preferably 0.05 to 5%, more _ 3 _ particularly 0.1 to 3% (here, as in the case of the pharmaceutical substances, the percentage by weight of the finished preparation is given). The pharmaceutical substances used in the new preparations may be any of the substances suitable for use by inhalation or possibly for intranasal administration. They include, therefore, in particular betamimetics, anticholinergics, steroids, antiallergics, PAF-antagonists and combinations of these active substances.
The following are given as specific examples:
Examples of betamimetics:
Bambuterol Bitolterol Carb~terol Clenbuterol Fenoterol Hexoprenalin Ibuterol Pirbuterol Procaterol Reproterol Salbutamol Salmeterol Sulfonterol Terbutalin Tulobuterol 1-(2-fluoro-4-hydroxyphenyl)-2-[4-(1-benzimidazolyl)-2-methyl-2-butylamino]ethanol erythro-5'-hydroxy-8'-(1-hydroxy-2-isopropylaminobutyl)-2H-1,4-benzoxazin-3-(4H)-one 1-(4-amino-3-chloro-5-trifluoromethylphenyl)-2-tert.-butylamino)ethanol 1-(4-ethoxycarbonylamino-3-cyano-5-fluorophenyl)-2-(tert.-butylamino)ethanol.
Examples of anticholinergics:
Ipratropium bromide Oxitropium bromide Trospium chloride Benzilic acid-N-Q-fluoroethylnortropine ester methobromide Examples of steroids:
Budesonide Beclomethasone (or the 17, 21-dipropionate thereof) Dexamethason-21-isonicotinate Flunisolide Examples of antiallergics:
Disodium cromoglycate Nedocromil Examples of PAF-antagonists:
The active substances may also be combined, e.g.
betamimetics p~l.us anticholinergics or betamimetics plus antiallergics.
Examples of preparations according to the invention (amounts given in percent by weight):
1) 0.100 Oxitropium bromide 2) 0.3% Fenoterol 0.01% Soya lecithin 0.1% Soya lecithin 4.0% Pentane 10.00 Pentane 95.89% TG 227 70.0% TG 227 19.6% TG 134a _ X075080 3) 0.1% Ipratropium bromide 4) 0.3% Fenoterol 0.1% Soya lecithin 0.1% Soya lecithin 20.0% Pentane 30.0% TG 11 20.0% Hutane 69.6% TG 227 49.8% TG 11 10.0%
5) 1.5% Disodium 6) 0.3% Salbutamol cromoglicate 0.2% Span*85 0.1% Tween*20 20.0% Pentane 98.4% TG 227 60.0% TG 227 1.4% Butane 19.5% TG 12 7) 0.15% Fenoterol 8) 0.1% Ipratropium-0.06% Ipratropium- bromide . . . bromide 0.1% Soya lecithin 0.10% Soya lecithin 15.3% Propane 40.00% TG 11 30.5% TG 11 19.69% Propane 54.0% TG 227 40.00% TG 227 *Trade-mark
Aerosols of powdered (micronised) drugs are used widely in therapy, e.g. in the treatment of obstructive diseases of the respiratory tract. If such aerosols are not produced by atomising the pharmaceutical powder or by spraying solutions, suspensions of the drugs in liquefied propellent gases are used. The latter consist primarily of mixtures of trichlorofluromethane (TG11), dichlorodifluoromethane (TG12) and 1,2-dichloro-1,1,2,2-tetrafluoroethane (TG114), optionally with the addition of lower alkanes such as butane or pentane, or with the addition of DME (dimethylether). Mixtures of this kind are known for example from German Patent 1178975.
Owing to their harmful effect on the earth's atmosphere (destruction of the ozone layer, Greenhouse effect) the use of chloroflurocarbons has become a problem, with the result that the search is on for other propellent gases or propellent gas mixtures which do not have the above-mentioned harmful effects or, at least, have them to a lesser degree.
However, this search has come up against major problems, since propellent gases for therapeutic use have to satisfy numerous criteria which cannot easily be reconciled, e.g. in terms of toxicity, stability, vapour pressure, density and solubility characteristics.
According to one broad aspect, the present invention provides a pharmaceutical preparation for inhalation containing a micronised pharmaceutically active substance in a liquified propellant gas, characterised in that 1,1,1,2,3,3,3-heptafluoro propane is used as propellant gas.
In a second broad aspect, the invention provides a pharmaceutical preparation, in which the propellant gas TG 227 (1,1,1,2,3,3,3-heptafluropropane, is in admixture with one of more propellent gases from the group comprising TG 11 (trichlorofluromethane), TG 12 (dichlorodifluoromethane), TG
114 (1,2-dichloro-1,1,2,2-tetrafluoroethane, propane, butane, pentane and DME
- la -,~0 750 80 (dimethylether). which is particularly suitable for use in therapeutic preparations.
The compounds to be used in addition to TG 227 are added if the properties of the propellent gas are to be modified, e.g. if the liquefied propellent gas is to have a different density, different pressure or different solubility characteristics. Pharmaceutical preparations based on the propellent gas contain an active substance in finely divided form, usually as a suspension, and generally also contain surface-active substances, e.g. a phospholipid (such as lecithin), an ester of a polyalcohol (such as sorbitol) with higher saturated or unsaturated fatty acids (e. g. stearic, palmitic or oleic acid), such as sorbitan trioleate, or a putyethoxysorbitan ester of a higher, preferably unsaturated fatty acid. The adjuvant may be present in the mixture in dissolved or undissolved form. In some cases, the suspensions produced with the new propellent gas have a tendency to separate out. However, it has been found that the separated suspensions can easily be uniformly distributed again in the suspension medium simply by shaking.
The ratios of quantities of the individual ingredients of the propellent gas mixture may be varied within wide limits. The proportion (in percent by weight) is 10~~to 100% in the case of TG 227. The mixture may also contain up to 50% propane and/or butane and/or pentane and/or DME and/or TG 11 and/or TG 12 and/or TG 114. Within the limits specified the ingredients are chosen to add up to 100%. Propellent gas mixtures which contain 30 to 100% TG 227 are preferred.
The proportion of suspended drug in the finished preparation is between 0.001 and 5%, preferably between 0.005 and 3%, more particularly between 0.01 and 2%.
The surface-active substances are added in amounts of from 0.01 to 10%, preferably 0.05 to 5%, more _ 3 _ particularly 0.1 to 3% (here, as in the case of the pharmaceutical substances, the percentage by weight of the finished preparation is given). The pharmaceutical substances used in the new preparations may be any of the substances suitable for use by inhalation or possibly for intranasal administration. They include, therefore, in particular betamimetics, anticholinergics, steroids, antiallergics, PAF-antagonists and combinations of these active substances.
The following are given as specific examples:
Examples of betamimetics:
Bambuterol Bitolterol Carb~terol Clenbuterol Fenoterol Hexoprenalin Ibuterol Pirbuterol Procaterol Reproterol Salbutamol Salmeterol Sulfonterol Terbutalin Tulobuterol 1-(2-fluoro-4-hydroxyphenyl)-2-[4-(1-benzimidazolyl)-2-methyl-2-butylamino]ethanol erythro-5'-hydroxy-8'-(1-hydroxy-2-isopropylaminobutyl)-2H-1,4-benzoxazin-3-(4H)-one 1-(4-amino-3-chloro-5-trifluoromethylphenyl)-2-tert.-butylamino)ethanol 1-(4-ethoxycarbonylamino-3-cyano-5-fluorophenyl)-2-(tert.-butylamino)ethanol.
Examples of anticholinergics:
Ipratropium bromide Oxitropium bromide Trospium chloride Benzilic acid-N-Q-fluoroethylnortropine ester methobromide Examples of steroids:
Budesonide Beclomethasone (or the 17, 21-dipropionate thereof) Dexamethason-21-isonicotinate Flunisolide Examples of antiallergics:
Disodium cromoglycate Nedocromil Examples of PAF-antagonists:
The active substances may also be combined, e.g.
betamimetics p~l.us anticholinergics or betamimetics plus antiallergics.
Examples of preparations according to the invention (amounts given in percent by weight):
1) 0.100 Oxitropium bromide 2) 0.3% Fenoterol 0.01% Soya lecithin 0.1% Soya lecithin 4.0% Pentane 10.00 Pentane 95.89% TG 227 70.0% TG 227 19.6% TG 134a _ X075080 3) 0.1% Ipratropium bromide 4) 0.3% Fenoterol 0.1% Soya lecithin 0.1% Soya lecithin 20.0% Pentane 30.0% TG 11 20.0% Hutane 69.6% TG 227 49.8% TG 11 10.0%
5) 1.5% Disodium 6) 0.3% Salbutamol cromoglicate 0.2% Span*85 0.1% Tween*20 20.0% Pentane 98.4% TG 227 60.0% TG 227 1.4% Butane 19.5% TG 12 7) 0.15% Fenoterol 8) 0.1% Ipratropium-0.06% Ipratropium- bromide . . . bromide 0.1% Soya lecithin 0.10% Soya lecithin 15.3% Propane 40.00% TG 11 30.5% TG 11 19.69% Propane 54.0% TG 227 40.00% TG 227 *Trade-mark
Claims (19)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A pharmaceutical preparation for inhalation containing a micronised pharmaceutically active substance in a liquified propellant gas, characterised in that 1,1,1,2,3,3,3-heptafluoro propane is used as propellant gas.
2. A pharmaceutical preparation for inhalation according to claim 1, characterised in that the propellant gas is an admixture with one or more propellant gases from the group comprising trichlorofluromethane, dichlorodifluoromethane, 1,2-dichloro-1,1,2,2-tetrafluromethane, propane, butane, pentane and dimethyl ether.
3. A pharmaceutical preparation according to claim 1 or 2, characterised in that it additionally contains at least one surface-active substance.
4. A pharmaceutical preparation according to claim 3, characterised in that the surface-active substance is a phospholipid, a sorbitan ester with a higher saturated or unsaturated fatty acid or a polyethoxysorbitan ester of a higher fatty acid.
5. A pharmaceutical preparation according to claim 4, characterized in that the ester is of a higher unsaturated fatty acid.
6. A pharmaceutical preparation according to claim 3, characterised in that the surface-active substance is a lecithin, a polyethoxyethylenesorbitan oleate or sorbitan trioleate.
7. A pharmaceutical preparation according to any one of claims 1 to 6, characterised in that it contains as active substance a betamimetic, an anticholinergic, a steroid, an antiallergic or a PAF-antagonist or a combination of such substances.
8. A pharmaceutical preparation according to claim 7, characterised in that the betamimetic used is selected from the group consisting of Bambuterol, Bitolterol, Carbuterol, Clenbuterol, Fenoterol, Hexoprenalin, Ibuterol, Pirbuterol, Procaterol, Reproterol, Salbutamol, Salmeterol, Sulfonterol, Terbutalin, Tulobuterol, 1-(2-fluoro-4-hydroxyphenyl)-2-[4-(1-benzimidazolyl)-2-methyl-2-butylamino]ethanol, erythro-5'-hydroxy-8'-(1-hydroxy-2-isopropylaminobutyl)-2H-1,4-benzoxazin-3-(4H)-one, 1-(4-amino-3-chloro-5-trifluoromethylphenyl)-2-tert.-butylamino)ethanol, and 1-(4-ethoxycarbonylamino-3-cyano-5-flurophenyl)-2-(tert.-butylamino)ethanol.
9. A pharmaceutical preparation according to claim 7 characterised in that the anticholinergic used is selected from the group consisting of Ipratropium bromide, Oxitropium bromide, Trospium chloride, and Benzilic acid-N-.beta.-fluoroethylnortropine ester methobromide.
10. A pharmaceutical preparation according to claim 7, characterised in that the steroid used is selected from the group consisting of Budesonide, Beclomethasone (or the 17, 21-dipropionate thereof), Dexamethason-21-isonicotinate, and Flunisolide.
11. A pharmaceutical preparation according to claim 7, characterised in that the antiallergic agent is Disodium cromoglycate or Nedocromil.
12. A pharmaceutical preparation according to claim 7, characterised in that the PAF-antagonist is WEB 2086, WEB
2170, or WEH 2347.
2170, or WEH 2347.
13. A pharmaceutical preparation according to claim 7, which comprises a combination of a betamimetic specified in claim 8 and an anticholinergic specified in claim 9.
14. A pharmaceutical preparation according to claim 7 which comprises a combination of a betamimetic specified in claim 8 and disodium chromoglycate.
15. A pharmaceutical preparation according to claim 7, which comprises a combination of a betamimetic specified in claim 8 and a PAF-antagonist specified in claim 12.
16. A pharmaceutical preparation according to claim 7, which comprises a combination of disodium chromoglycate and a PAF-antagonist specified in claim 12.
17. A process for preparing a pharmaceutical preparation, which process comprises suspending a micronised pharmaceutically active substance in liquefied 1,1,1,2,3,3,3-heptafluoropropane as propellant gas, the amount of pharmaceutically active substance in the finished preparation being between 0.001 and 5% by weight.
18. A process according to claim 17, wherein the micronised pharmaceutically active substance is suspended in an admixture composed of 1,1,1,2,3,3,3-heptafluoropropane and one or more propellant gases selected from the group consisting of trichlorofluromethane, dichlorodifluoromethane, 1,2,-dichloro-1,1,2,2-tetrafluoroethane, propane, butane, pentane and dimethyl ether.
19. A process according to claim 17 or 18, wherein one or more surface-active substances are added to the suspension, the surface-active substance being selected from the group consisting of a phospholipid, a sorbitan ester with a higher saturated or unsaturated fatty acid, a polyethoxysorbitan ester of a higher saturated or unsaturated fatty acid, a lecithin, a polyethoxyethylenesorbitan oleate and sorbitan trioleate.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP4003270.1 | 1990-02-03 | ||
| DE4003270A DE4003270A1 (en) | 1990-02-03 | 1990-02-03 | NEW SPEED GASES AND THEIR USE IN MEDICINE PREPARATIONS |
| PCT/EP1991/000178 WO1991011496A1 (en) | 1990-02-03 | 1991-01-31 | Novel vehicle gases and their use in medical preparations |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2075060A1 CA2075060A1 (en) | 1991-08-04 |
| CA2075060C true CA2075060C (en) | 2001-01-02 |
Family
ID=6399399
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002075060A Expired - Lifetime CA2075060C (en) | 1990-02-03 | 1991-01-31 | Novel vehicle gases and their use in medical preparations |
Country Status (26)
| Country | Link |
|---|---|
| US (7) | US6419899B1 (en) |
| EP (1) | EP0513099B1 (en) |
| JP (1) | JP3497162B2 (en) |
| KR (1) | KR920703034A (en) |
| AT (1) | ATE185587T1 (en) |
| AU (1) | AU656129B2 (en) |
| CA (1) | CA2075060C (en) |
| CZ (1) | CZ285209B6 (en) |
| DE (2) | DE4003270A1 (en) |
| DK (1) | DK0513099T3 (en) |
| ES (1) | ES2139574T3 (en) |
| FI (1) | FI103348B1 (en) |
| GR (1) | GR3032176T3 (en) |
| HK (1) | HK1010737A1 (en) |
| HR (1) | HRP940737B1 (en) |
| HU (1) | HU218664B (en) |
| IL (1) | IL97024A0 (en) |
| NO (1) | NO302420B1 (en) |
| NZ (1) | NZ236974A (en) |
| PT (1) | PT96635B (en) |
| RU (1) | RU2118170C1 (en) |
| SI (1) | SI9110155B (en) |
| SK (1) | SK281440B6 (en) |
| WO (1) | WO1991011496A1 (en) |
| YU (1) | YU48509B (en) |
| ZA (1) | ZA91756B (en) |
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4003270A1 (en) * | 1990-02-03 | 1991-08-08 | Boehringer Ingelheim Kg | NEW SPEED GASES AND THEIR USE IN MEDICINE PREPARATIONS |
| MX9203481A (en) * | 1990-10-18 | 1992-07-01 | Minnesota Mining & Mfg | FORMULATIONS. |
| DE69105212T2 (en) * | 1990-10-18 | 1995-03-23 | Minnesota Mining & Mfg | AEROSOL PREPARATION CONTAINING BECLOMETASON 17.21 DIPROPIONATE. |
| DK0656207T4 (en) † | 1991-06-10 | 2009-11-30 | Schering Corp | Aerosol formulations without chlorofluorocarbon compounds |
| US5221492A (en) * | 1991-08-23 | 1993-06-22 | E. I. Du Pont De Nemours And Company | Azeotropic mixture of perfluoropropane and dimethyl ether |
| GB9118830D0 (en) * | 1991-09-03 | 1991-10-16 | Minnesota Mining & Mfg | Medical aerosol formulations |
| WO1993011744A1 (en) | 1991-12-12 | 1993-06-24 | Glaxo Group Limited | Medicaments |
| US5744123A (en) * | 1991-12-12 | 1998-04-28 | Glaxo Group Limited | Aerosol formulations containing P134a and particulate medicaments |
| US5653962A (en) * | 1991-12-12 | 1997-08-05 | Glaxo Group Limited | Aerosol formulations containing P134a and particulate medicaments |
| US5658549A (en) * | 1991-12-12 | 1997-08-19 | Glaxo Group Limited | Aerosol formulations containing propellant 134a and fluticasone propionate |
| US5916540A (en) * | 1994-10-24 | 1999-06-29 | Glaxo Group Limited | Aerosol formulations containing P134A and/or P227 and particulate medicament |
| US5736124A (en) * | 1991-12-12 | 1998-04-07 | Glaxo Group Limited | Aerosol formulations containing P134a and particulate medicament |
| IL104068A (en) * | 1991-12-12 | 1998-10-30 | Glaxo Group Ltd | Surfactant-free pharmaceutical aerosol formulation comprising 1,1,1,2-tetrafluoroethane or 1,1,1,2,3,3,3-heptafluoro-n- propane as propellant |
| AU663906B2 (en) * | 1991-12-12 | 1995-10-26 | Glaxo Group Limited | Medicaments |
| US5674471A (en) * | 1991-12-12 | 1997-10-07 | Glaxo Group Limited | Aerosol formulations containing P134a and salbutamol |
| US7105152B1 (en) | 1991-12-18 | 2006-09-12 | 3M Innovative Properties Company | Suspension aerosol formulations |
| ES2216800T3 (en) * | 1991-12-18 | 2004-11-01 | Minnesota Mining And Manufacturing Company | AEROSOL FORMULATIONS IN SUSPENSION. |
| US7101534B1 (en) | 1991-12-18 | 2006-09-05 | 3M Innovative Properties Company | Suspension aerosol formulations |
| US20030103907A1 (en) * | 1991-12-18 | 2003-06-05 | Schultz Robert K. | Suspension aerosol formulations |
| WO1993019117A1 (en) * | 1992-03-26 | 1993-09-30 | Great Lakes Chemical Corporation | Azeotrope-like compositions of 1,1,1,2,3,3,3-heptafluoropropane and 1,1-difluoroethane |
| RO117414B1 (en) * | 1992-12-09 | 2002-03-29 | Jager Paul D Waterbury | Pharmaceutical composition of gas dispersoid in solution |
| CA2178473C (en) * | 1993-12-20 | 2004-08-24 | Tsi-Zong Tzou | Flunisolide aerosol formulations |
| PL320856A1 (en) | 1994-12-22 | 1997-11-10 | Astra Ab | Aerosol drug preparations |
| US6135628A (en) * | 1995-10-13 | 2000-10-24 | Boehringer Ingelheim Pharmceuticals, Inc. | Method and apparatus for homogenizing aerosol formulations |
| US6054488A (en) * | 1996-06-11 | 2000-04-25 | 3M Innovative Properties Company | Medicinal aerosol formulations of formoterol |
| US6039932A (en) * | 1996-09-27 | 2000-03-21 | 3M Innovative Properties Company | Medicinal inhalation aerosol formulations containing budesonide |
| DE19652790A1 (en) * | 1996-12-18 | 1998-06-25 | Hermes Fabrik Pharm Praeparate | Pharmaceutical preparations |
| US6235265B1 (en) * | 1998-10-28 | 2001-05-22 | Alliedsignal Inc. | Evaporative coolant for topical anesthesia comprising hydrofluorocarbons and/or hydrochlorofluorocarbons |
| DE19921693A1 (en) * | 1999-05-12 | 2000-11-16 | Boehringer Ingelheim Pharma | Pharmaceutical composition for treating respiratory disorders, e.g. asthma, comprises combination of anticholinergic and beta-mimetic agents having synergistic bronchospasmolytic activity and reduced side-effects |
| US6706726B2 (en) | 2000-10-14 | 2004-03-16 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Anticholinergics which may be used as medicaments as well as processes for preparing them |
| DE10050994A1 (en) * | 2000-10-14 | 2002-04-18 | Boehringer Ingelheim Pharma | New diphenylalkanoic acid azabicyclooctane ester quaternary salts useful as anticholinergic agents, especially in treatment of asthma and chronic obstructive pulmonary disease |
| DE10062712A1 (en) * | 2000-12-15 | 2002-06-20 | Boehringer Ingelheim Pharma | New drug compositions based on anticholinergics and corticosteroids |
| DE10130371A1 (en) * | 2001-06-23 | 2003-01-02 | Boehringer Ingelheim Pharma | New drug compositions based on anticholinergics, corticosteroids and betamimetics |
| GB0208742D0 (en) | 2002-04-17 | 2002-05-29 | Bradford Particle Design Ltd | Particulate materials |
| US7754242B2 (en) * | 2002-03-20 | 2010-07-13 | Alkermes, Inc. | Inhalable sustained therapeutic formulations |
| US7582284B2 (en) * | 2002-04-17 | 2009-09-01 | Nektar Therapeutics | Particulate materials |
| US7273603B2 (en) | 2003-07-11 | 2007-09-25 | Boehringer Ingelheim International Gmbh | HFC solution formulations containing an anticholinergic |
| US20050136009A1 (en) * | 2003-10-20 | 2005-06-23 | Schering Corporation | Pharmaceutical compositions |
| CA2571519C (en) * | 2004-07-02 | 2013-05-14 | Boehringer Ingelheim International Gmbh | Aerosol suspension formulations containing tg 227 ea or tg 134 a as a propellant |
| WO2006114379A1 (en) * | 2005-04-23 | 2006-11-02 | Boehringer Ingelheim International Gmbh | Combination of medicaments to be inhaled, containing a betamimetic agent and a steroid in addition to an anticholinergic agent |
| DE102006017320A1 (en) * | 2006-04-11 | 2007-10-18 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Aerosol suspension formulations with TG 227 ea or TG 134 a as propellant |
| CN104188907A (en) | 2007-02-11 | 2014-12-10 | Map药物公司 | Method of therapeutic administration of DHE to enable rapid relief of migraine while minimizing side effect profile |
| EP2282418A3 (en) | 2009-06-23 | 2011-03-09 | Alcatel Lucent | A station comprising at least two transmit antennas, and a method of transmitting therefrom |
| US9394314B2 (en) | 2012-12-21 | 2016-07-19 | Map Pharmaceuticals, Inc. | 8′-hydroxy-dihydroergotamine compounds and compositions |
Family Cites Families (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2490764A (en) * | 1945-07-04 | 1949-12-13 | Kinetic Chemicals Inc | Fluorinated organic compounds |
| BE555319A (en) * | 1956-03-21 | 1900-01-01 | ||
| BE556587A (en) | 1957-01-31 | 1957-04-11 | ||
| GB902590A (en) | 1960-03-22 | 1962-08-01 | Allied Chem | Production of heptafluoropropane |
| US3095355A (en) * | 1961-10-12 | 1963-06-25 | Revlon | Aerosol composition |
| NL289785A (en) * | 1962-11-29 | |||
| DE1542076A1 (en) * | 1966-04-21 | 1970-03-26 | Colgate Palmolive Co | Aerosol propellant |
| US3369913A (en) * | 1967-03-20 | 1968-02-20 | Union Carbide Corp | Self-propelling food mixture |
| DE1719443B2 (en) | 1967-10-07 | 1973-04-05 | SUSPENSION AEROSOLS AND THE PROCESS FOR THEIR PRODUCTION | |
| US4044126A (en) * | 1972-04-20 | 1977-08-23 | Allen & Hanburys Limited | Steroidal aerosol compositions and process for the preparation thereof |
| IL51314A (en) | 1976-01-30 | 1980-03-31 | Fisons Ltd | Disodium cromoglycate of low moisture content and pharmaceutical compositions containing it |
| NL7708731A (en) * | 1976-08-13 | 1978-02-15 | Montedison Spa | PROCESS FOR THE PREPARATION OF NEW DRIVER COMPOSITIONS FOR AEROSOLS. |
| US4174795A (en) * | 1977-02-14 | 1979-11-20 | Bohm Leslie E | Pannier mounting arrangement for cycles |
| GB2001334B (en) | 1977-07-19 | 1982-03-03 | Fisons Ltd | Pressurised aerosol formulation |
| CA1136547A (en) | 1979-03-08 | 1982-11-30 | Song-Ling Lin | Aerosol anesthetic compositions |
| JPS55131096A (en) | 1979-03-30 | 1980-10-11 | Daikin Ind Ltd | Working fluid for rankine cycle |
| US4352789A (en) | 1980-03-17 | 1982-10-05 | Minnesota Mining And Manufacturing Company | Aerosol compositions containing finely divided solid materials |
| AU7288081A (en) * | 1980-07-16 | 1982-01-21 | Glaxo Group Limited | 11alpha-amino-androstanes |
| GB8432063D0 (en) * | 1984-12-19 | 1985-01-30 | Riker Laboratories Inc | Physically modified steroids |
| GB8501015D0 (en) * | 1985-01-16 | 1985-02-20 | Riker Laboratories Inc | Drug |
| US4778674A (en) * | 1986-05-28 | 1988-10-18 | Richardson-Vicks Inc. | Dry aerosol foam |
| DE3735467A1 (en) | 1987-10-20 | 1989-05-03 | Bayer Ag | METHOD FOR PRODUCING FLUORINATED C (DOWN ARROW) 4 (DOWN ARROW) - TO C (DOWN ARROW) 6 (DOWN ARROW) HYDROCARBONS AND NEW CYCLIC FLUORED HYDROGENED FUEL SOURCES (4) - UP TO C (DOWN ARROW) 6 (DOWN ARROW) HYDROCARBONS AS A FLUID GAS AND WORKING LIQUID FOR HEAT PUMP SYSTEMS |
| US5225183A (en) * | 1988-12-06 | 1993-07-06 | Riker Laboratories, Inc. | Medicinal aerosol formulations |
| DE3903336A1 (en) | 1989-02-04 | 1990-08-09 | Bayer Ag | USING C (ARROW DOWN) 3 (DOWN ARROW) - UP TO C (DOWN ARROW) 5 (DOWN ARROW) -POLYFLUOROUS CANS AS PRESSURE GASES |
| DE3905726A1 (en) * | 1989-02-24 | 1990-08-30 | Hoechst Ag | COMPRESSED GAS PACKING AND DRIVING AGENT FOR AEROSOLS |
| JP2642738B2 (en) | 1989-04-13 | 1997-08-20 | ライオン株式会社 | Aerosol products for human body application |
| DE4003270A1 (en) | 1990-02-03 | 1991-08-08 | Boehringer Ingelheim Kg | NEW SPEED GASES AND THEIR USE IN MEDICINE PREPARATIONS |
| IL97065A (en) | 1990-02-02 | 1994-01-25 | Fisons Plc | Aerosol propellant compositions |
| DE4003272A1 (en) * | 1990-02-03 | 1991-08-08 | Boehringer Ingelheim Kg | NEW GAS MIXTURES AND THEIR USE IN MEDICINE PREPARATIONS |
| US5118494A (en) * | 1990-03-23 | 1992-06-02 | Minnesota Mining And Manufacturing Company | Use of soluble fluorosurfactants for the preparation of metered-dose aerosol formulations |
| US5182097A (en) * | 1991-02-14 | 1993-01-26 | Virginia Commonwealth University | Formulations for delivery of drugs by metered dose inhalers with reduced or no chlorofluorocarbon content |
| EP0504112A3 (en) | 1991-03-14 | 1993-04-21 | Ciba-Geigy Ag | Pharmaceutical aerosol formulations |
| EP0653205B1 (en) | 1991-06-10 | 2002-10-16 | Schering Corporation | Non-chloroflurocarbon aerosol formulations |
| DK0656207T4 (en) | 1991-06-10 | 2009-11-30 | Schering Corp | Aerosol formulations without chlorofluorocarbon compounds |
| US5653962A (en) * | 1991-12-12 | 1997-08-05 | Glaxo Group Limited | Aerosol formulations containing P134a and particulate medicaments |
| US5674471A (en) * | 1991-12-12 | 1997-10-07 | Glaxo Group Limited | Aerosol formulations containing P134a and salbutamol |
| EP0550031B1 (en) | 1991-12-31 | 1996-05-08 | Hoechst Aktiengesellschaft | Aerosol compositions |
| GB9425160D0 (en) * | 1994-12-10 | 1995-02-08 | Glaxo Group Ltd | Medicaments |
| PL320856A1 (en) | 1994-12-22 | 1997-11-10 | Astra Ab | Aerosol drug preparations |
| CA2218179A1 (en) * | 1995-04-14 | 1996-10-17 | Glaxo Wellcome Inc. | Metered dose inhaler for beclomethasone dipropionate |
| CA2280099C (en) | 1997-02-05 | 2005-12-27 | Jago Pharma Ag | Medical aerosol formulations |
| US5891420A (en) * | 1997-04-21 | 1999-04-06 | Aeropharm Technology Limited | Environmentally safe triancinolone acetonide aerosol formulations for oral inhalation |
-
1990
- 1990-02-03 DE DE4003270A patent/DE4003270A1/en not_active Withdrawn
-
1991
- 1991-01-24 IL IL97024A patent/IL97024A0/en not_active IP Right Cessation
- 1991-01-30 YU YU15591A patent/YU48509B/en unknown
- 1991-01-30 SI SI9110155A patent/SI9110155B/en unknown
- 1991-01-31 CA CA002075060A patent/CA2075060C/en not_active Expired - Lifetime
- 1991-01-31 JP JP50368791A patent/JP3497162B2/en not_active Expired - Lifetime
- 1991-01-31 EP EP91903267A patent/EP0513099B1/en not_active Revoked
- 1991-01-31 NZ NZ236974A patent/NZ236974A/en unknown
- 1991-01-31 ES ES91903267T patent/ES2139574T3/en not_active Expired - Lifetime
- 1991-01-31 RU SU5052884A patent/RU2118170C1/en active
- 1991-01-31 HU HU9202508A patent/HU218664B/en unknown
- 1991-01-31 DE DE59109161T patent/DE59109161D1/en not_active Revoked
- 1991-01-31 KR KR1019920701826A patent/KR920703034A/en not_active Application Discontinuation
- 1991-01-31 WO PCT/EP1991/000178 patent/WO1991011496A1/en not_active Application Discontinuation
- 1991-01-31 AU AU72116/91A patent/AU656129B2/en not_active Expired
- 1991-01-31 AT AT91903267T patent/ATE185587T1/en not_active IP Right Cessation
- 1991-01-31 DK DK91903267T patent/DK0513099T3/en active
- 1991-02-01 ZA ZA91756A patent/ZA91756B/en unknown
- 1991-02-01 PT PT96635A patent/PT96635B/en not_active IP Right Cessation
- 1991-02-04 CZ CS91265A patent/CZ285209B6/en not_active IP Right Cessation
- 1991-02-04 SK SK265-91A patent/SK281440B6/en not_active IP Right Cessation
-
1992
- 1992-07-31 NO NO923040A patent/NO302420B1/en not_active IP Right Cessation
- 1992-08-03 FI FI923491A patent/FI103348B1/en active
-
1994
- 1994-10-24 HR HR940737A patent/HRP940737B1/en not_active IP Right Cessation
-
1998
- 1998-10-21 HK HK98111443A patent/HK1010737A1/en not_active IP Right Cessation
-
1999
- 1999-12-17 GR GR990403262T patent/GR3032176T3/en unknown
-
2000
- 2000-03-14 US US09/525,431 patent/US6419899B1/en not_active Expired - Fee Related
-
2002
- 2002-02-06 US US10/072,400 patent/US20020071812A1/en not_active Abandoned
-
2003
- 2003-08-12 US US10/638,987 patent/US20040028618A1/en not_active Abandoned
-
2004
- 2004-09-03 US US10/934,611 patent/US7160538B2/en not_active Expired - Lifetime
-
2006
- 2006-10-27 US US11/553,508 patent/US20070065370A1/en not_active Abandoned
-
2008
- 2008-07-25 US US12/179,785 patent/US20090104127A1/en not_active Abandoned
-
2010
- 2010-09-27 US US12/891,076 patent/US20110014134A1/en not_active Abandoned
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2075060C (en) | Novel vehicle gases and their use in medical preparations | |
| US6413497B1 (en) | Pharmaceutical composition using a mixture of propellant gases for a metered dose inhaler | |
| CA2129855C (en) | Pressurized gas packagings using polyoxyethylene glyceryl-oleates | |
| JPH02200627A (en) | Medical aerosol preparation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKEX | Expiry |