|Publication number||US2196322 A|
|Publication date||Apr 9, 1940|
|Filing date||Dec 4, 1937|
|Priority date||Dec 4, 1937|
|Publication number||US 2196322 A, US 2196322A, US-A-2196322, US2196322 A, US2196322A|
|Inventors||Christiansen Walter G, Nitardy Ferdinand W|
|Original Assignee||Squibb & Sons Inc|
|Export Citation||BiBTeX, EndNote, RefMan|
|Referenced by (5), Classifications (16)|
|External Links: USPTO, USPTO Assignment, Espacenet|
Patented Apr. 9, 1940 UNITED STATES PATENT OFFICE PHARMACEUTICAL No Drawing.
Application December 4, 1937,
Serial No. 178,132
,9 Claims. (Cl. 16758) This invention relates to inhalan s, i. e., preparations for nasal administration, as by dropping or spraying.
Heretofore, oil-soluble inhalant medicinal agents (e. g., ephedrine) have been incorporated in mineral-oil vehicles for the production of inhalants. Numerous cases of lipoid pneumonia have resulted from the use of such preparations, apparently because of the non-absorption of oil vehicle finding its way' into the alveoli of the lung.
It is the object of this invention to provide non-injurious inhalants; more particularly, to provide preparations of oil-soluble inhalant ll medicinal agents embodying a vehicle absorbable by the lungs.
It has been found that certain oily aliphatic esters are absorbable by the body and constitute effective vehicles for oil-soluble inhalant medlcg0 inal agents. In the event these absorbable oily aliphatic esters enter the lung, they do not remain there, either because of their tendency to pass into water solution or because of their susceptibility to enzyme hydrolysis. Moreover, the 535 slight water-solubility of some of these esters enhances the effectiveness of the .medicinal agents, since aqueous fluids are present in the nasal passages.
The following esters, inter alia, have been found to be absorbable eifective vehicles:
Aliphatic polyhydroxy compounds completely 5 esterified with higher fatty acids, such as ,glyceryl' trioleate, remain unabsorbed in the lung. The
absorbable vehicles specifically disclosed belong to the group: consisting of lower-alkyl esters of 'higher fatty acids and aliphatic polyhydroxy compounds partially esterified with higher fatty acids;
These absorbable vehicles are eflective for all inhalants embodying oil-soluble medicinal agents.
The following examples are illustrative of the application of this invention to plain and compound ephedrine inhalants and to non-ephedrine inhalants.
Example 1 A plain ephedrine inhalant is made by incorporating 1.5 g. ephedrine in 148.5 g. ethyl oleate.
Example 2 A compound ephedrine inhalant is made by incorporating the following in 144.0 g. ethyl l0 I Example 3- A non-ephedrine inhalant is made by incorporating the following in 144.0- g. ethyl oleate:
Grams Phenol 1.1
Menthol 1.1 25
Example 4 An inhalant is made by incorporating p-phenethyl amine, p-phenyl-isopropylamine, m (or p) hYdIOXY-a- (methylaminomethyl) -benzyl alcohol,
or the like in ethyl oleate.
Example 5 p-phenethyl amine or amed cinal derivative thereof is incorporated in the compound inhalant preparation of Example 2 in place of ephedrine.
In the compound inhalants, a variety of substances can be used instead of the phenol, camphor, menthol, oil of thyme, and oil of lilac. Menthol and camphor are employed torelieve congestion, and oil of thyme and oil of lilac to improve the odor of the product; and these may be replaced by other similarly efiective agents. The phenol is used because of its anesthetic and antiseptic properties; and may be, replaced by anesthetics such as 'benzyl alcohol, saligenin, chlorobutanol, or the alkyl esters of para-amino- 50 benzoic acid, and/or by antiseptics such as hydroxy-quinoline, chlor-hydroxy-quinoline, or
ethyl butyl resorcinol.
When the inhalant is unsatisfactory because of excessive viscosity of the vehicle, adjustment can u be made by replacing part of the viscous vehicle with ethyl oleate. Conversely, if the ethyl oleate preparations are too thin, this vehicle may be partly replaced with one having a higher viscosity. i
The invention may be variously otherwise embodied within the scope of the appended claims.
1. An inhalant essentially comprising an oilsoluble inhalant medicinal agent and a lungabsorbable vehicle of the group consisting of lower-alkyl esters of higher fatty acids and allphatic polyhydroxy compounds incompletely esterifled with higher fatty acids.
2. An inhalant essentially comprising an oil soluble inhalant medicinal agent and a lungabsorbable oily aliphatic mono-ester of a higher fatty acid. v
3. An inhalant essentially comprising an oil- 20 soluble inhalant medicinal agent and a lung'- absorbable oily aliphatic mono-ester of a higher unsaturated fatty acid.
4. An inhalant essentially comprising an oilsoluble inhalant medicinal agent and ethyl oleate.
5. An, inhalant essentially comprising an oilsoluble inhalant medicinal agent and an ethyl ester of the mixture of fatty acids derivable I from an oil of the group consisting of olive oil,
coconut oil, and linseed oil.
6. An inhalant essentially comprising an oilsoluble inhalant medicinal agent and glyceryl mono-oleate. i
7. An inhalant essentially comprising ephedrine and ethyl oleate.
8. An inhalant essentially comprising phenol, menthol, camphor, and ethyl oleate.
9.- A medicinal inhalant preparation essentially comprising p-phenethylamine and ethyl oleate.
FERDINAND W. NITARDY. WALTER G. CHRISTIANSEN.
|Citing Patent||Filing date||Publication date||Applicant||Title|
|US5143934 *||Oct 20, 1989||Sep 1, 1992||A/S Dumex (Dumex Ltd.)||Method and composition for controlled delivery of biologically active agents|
|US5175152 *||Sep 28, 1990||Dec 29, 1992||Singh Nikhilesh N||Composition containing ephedrine base and alkyl salicylate for the delivery of ephedrine base in vapor form|
|EP0160501A2 *||Apr 24, 1985||Nov 6, 1985||Eli Lilly And Company||Sustained release intranasal formulation and method of use thereof|
|EP0160501A3 *||Apr 24, 1985||Dec 30, 1986||Eli Lilly And Company||Sustained release intranasal formulation and method of use thereof|
|WO1992005781A1 *||Sep 26, 1991||Apr 16, 1992||The Procter & Gamble Company||Composition containing ephedrine base and alkyl salicylate for the delivery of ephedrine base in vapor form|
|U.S. Classification||514/653, 514/311, 424/727, 514/731, 514/654, 514/729, 424/768, 514/692, 424/769|
|International Classification||A61K36/55, A61K36/185, A61K9/00|
|Cooperative Classification||A61K9/0043, A61K9/007|
|European Classification||A61K9/00M20, A61K9/00M14|