|Publication number||US2222976 A|
|Publication date||Nov 26, 1940|
|Filing date||Nov 15, 1937|
|Priority date||Nov 15, 1937|
|Publication number||US 2222976 A, US 2222976A, US-A-2222976, US2222976 A, US2222976A|
|Inventors||Fox Sereck Hall|
|Original Assignee||Sharp & Dohme Inc|
|Export Citation||BiBTeX, EndNote, RefMan|
|Referenced by (5), Classifications (10)|
|External Links: USPTO, USPTO Assignment, Espacenet|
Patented-Nov. 26, 1940 NASAL DB-Ol'g Sereck Hall Fox, Birmingham, Mich, assignor to Sharp & Dohme,
Pa., a corporation of Maryland No Drawing.
Application November 15, 1937, Serial No. 174,721
.9 Claims; (01. 167-58) .two blending agents, the first of which is a good This invention relates to new compositions adapted for use as nasal sprays or nose drops inthe form of solutions of phenyl-l amino-2 propanol in an oil base; and more particularly to 5 solutions of phenyl-l'amino-2 propanol in a base consisting mainly of mineral oil, e g., light paraffin oil of about the viscosity usually used in oil base nose drops or nasal sprays.
Nose drops or nasal sprays are commonly made in the form of oil solutions of suitable vaso-constricting agents, particularly ephedrine, in which case the solutions may contain a blending agent, such as an oil-soluble aldehyde, oil-soluble ketone, alcohol, oxygenated terpene derivative, etc., to increase the solubility of the ephedrine in the mineral oil to permit the use of solutions of eilective therapeutic strength. V
PhenylJ amino-2 propanol has been found to have valuable properties as a vaso-constricting" agent for use in the treatment of head coldsand the like; but it has not heretofore been usable in mineral oil base compositions because of its very low solubility in such oils as light paraffin oil;' its solubility in such oilsbeing very limited even at temperatures well above room temperature and being almost zero at temperatures around 0 C. The solubility of phenyl-l amino-2 propanol in glyceride oils, such as vegetable and animal oils,
for example, cottonseed oil, is somewhat greater,- but is still so low as to make impractical the production of phenyl-l' amino-2 propanol solutions in such oils of therapeutic efiiciency. Nor can .the solubility of the phenyl-l amino-2 propanol in the mineral oils, which are the most valuable for-use as solvents for nasal sprays, nose drops and the like, be increased by the use of a single.
blending agent,.such as an aldehyde, ketone, or alcohol, to an extent suflicient to permit theproduction of commercially distributable solutions. In accordance with the present invention, solutions of phenyl-l amino-Zpropanol, which may contain as much as 5%of phenyl-l amino-2 propanol, in a solvent consisting for the most part of a light mineral oil, such as a paraffin oil, are" produced; the solution of the phenyll amino-2 propanol in the mineral oil being. effected by the use of at least two blending agents, one of which is a' good solvent for the phenyl-l' amino-.2 propanol andone of which serves as a blending agent between the mineral oil and the solution of the phenyl-l amino-2 propanol inthe first blendingage'ntfthis latter blending agent, while not necessarily a good solvent for the phenyl-l amino-'2 propanol, being readily soluble in thednineral oil and a good solvent for the first blending agent.
Thus in accordance withthe present invention,
mineral oil base compositions containing dis-' -'solved ph'enyl-l amino-2'propanol are produced by incorporated the phenyl-l amino-2 propanol m m the mineral oil base'with'tlie aid of at least solvent for the phenyl-l amino-2 propanol and H has some, though not necessarily high, solubility in mineral oil; while the second blending agent is quite soluble in the mineral oil, is agood sol-- ll vent for the first blendingv agent, and dissolves phenyl-l amino-2 propanol to some extent,
though the solubility of the" phenyl-l amino-2 properties of readily dissolving the phenyl-l in the second blending agent need not amino- 2 propanol and ready solubility in vegetable and animal oils, butnot necessarily in mineral oil, includes a wide class of organic com- 20 pounds of the general'nature of aldehydes, ke-
' tones, aliphatic and aralkyl alcohols, aromatics,
including "both the benzene and terpene aromatics, and other -mono-oxygen derivatives of relatively low molecular weight hydrocarbons, that is, hydrocarbons containing, in general, not more than about twelve carbon atoms, as well as fatty acids derived from animal or vegetable oils,
- such as stearic acid, oleic acid, palmitlc acid, etc.
chlorinated alcohols, sulfonated glyceride oils, and 30 the like. ,1 Included among compounds which have been found useful, and which are examples of this class of blending agents, are the following:
Benzyl alcohol n-Amyl alcohol 35 Isopropyl alcohol n-Hexyl alcohol Tertiary-butyl-alcohol n-Hept yl alcohol Methyl alcohol n-Octyl alcohol Ethyl alcohol n-Nonyl alcohol n-Propyl alcohol Iso-butyl alcohol 40 n-Butyl alcohol Iso-amyl alcohol Menthol Tertiary-amyl alcohol Gerani'ol Acetone I liienzaldehyde Acetophenone Thymol Ethyl. methyl ketone 45 Citronellol -Menthone Oil thyme. Phenyl ethyl alcohol Eucalyptol Phenyl propyl alcohol Camphor Ethyl propyl 'ketone Stearic acid 7 Sultonated fixed oils m Oleic acid Oil cassia Palmitic acid 011 cinnamon Oilpeppermint Oil rose Chlorbutanol 4 g v Said blending agents having the property of 1 referred to as an oxygen-containing blending w agent readily dissolving phenyl-1 amino-2 propanol and readily soluble in a glyceride oil.
01 these compounds, the aralkyl alcohols, such as benzyl alcohol, phenyl ethyl alcohol, phenyl propyl alcohol, etc., have important advanta es.
- The invention will be illustrated by the following specific example, although it is not limited from cloudiness at low temperatures. If desired,
to such solutionsniay be added one or more of the aromatics, such as menthol, camphor; or the like, and chlorbutanol or other analgesic and local anaesthetic; these substances not only serving to "make the composition pleasant in use, but also serving as additional blending agents to increase the solubility of the phenyl-1 amino-2 propanol in the final composition.
In such compositions, the phenyl-1 amino-2 propanol is readily soluble in the benzyl alcohol; and the cottonseed oil serves as a blending agent between the mineral oil and the benzyl alcohol solution of the phenyl-1 amino-2 propanol, The
cottonseed" oil is required because the benzyl a1- cohol has but limited solubility in the mineral oil, and cleansolutions cannot be obtained without its use, or the use of some-similar oil, if sufficient phenyl-1" amino-.2 propanol for therapeutic efiectiveness'be used. Y
In general, the amount of the blending agents used may be varied over more or less wide ranges. Ifhe amount of the agent in which the phenyl-1 amino-2 propanol is readily soluble may range up to 4 or 4 molecular equivalents of the amifrunt of phenyl-1 amino-2 propanol, while the other blending agent, such as an animal or vegetable oil, may be used in amounts ranging up to 10 to 20%, advantageously just suflicient of this material being-used to insure the production'of clear solutions with the amount of phenyl-1 amino-2 propanol used at all ordinary temperatures. The animal or vegetable oil used may be regarded as an intermediate solvent between the solution of Y phenyl-1 amino-2 propanol in the oxygenated hydrocarbon or sulfonated glyceride oil and the mineral oil, and, in general, should not be used in amounts greatly exceeding that required for the I production of the desired clear solutions.
1. A composition containinga mineral oil, a glyceride oil, an alcohol and phenyl-1 amino-2 propanol, said composition being in the form of a clear solution free from cloudiness at normal 5 temperatures. 1
2. A composition containing a mineral oil, a. glyceride oil, an aralkyl alcohol and phenyl-1 amino-2 propanol, said (composition being in the form of a clear solution free from cloudiness at normal temperatures.
, 3. A composition containing a major proportion of mineral oil, a minor proportion; of a glyceride .oil, benzyl alcohol and phenyl-1 amino-2 propanol. v I C 4. A composition containinga major proportion of mineral oil, a minor proportion of cottonseed oil, benzyl alcohol and phenyl-1 amino-2 propanol. v
5. A composition containing a major proportion of a mineral oil, a minor proportion of a glyceride oil, a small'amount of phenyl-l amino-2 propanol and an oxygen-containing organic blending agent readily soluble in said glyceride oil and which blending agent readily dissolves phenyl-1 amino-2 propanol. I
6. A composition containing a major proportion' of mineral oil, a minor proportion of a glyceride oil, phenyl-1 amino-2 propanol and a member selected from the group consistingof menthol, thymol and eucalyptol. g
'1. A composition containing a major proportion of mineral oil, a minor proportionpf a. glyceride oil, phenyl-1 amino-2 propanol, a monooxy derivative of a'hydrocarbon having not more than 12 carbon atoms, said mono-oxv derivative of such hydrocarbon dissolving readily in said glyceride oil and alsojreadilydissolving saidphenyl-l amino-2 propanol.
-8. A composition containing a major propor- 40" tion of mineral oil, aminor proportion ofa glyceride oil, phenyl-1 amino-2 propanol, a mono-oxy:
a derivative of a. hydrocarbon having not more than V 12 carbon atoms, said monoaxy derivative ofcsuch hydrocarbon dissolving readily in saidglyceride oil and also readily dissolving said phenyl-l amino-2 propanol, said composition also containing at least one member selected from the group consisting of thymol, menthol and-.eucalyptol.
9. A composition containing a major propor tion of mineral oil, a minor proportion of cottonseed oil, a small amount of phenyl-1 amino-2 propanol and benzyl alcohol, and at least one member selected. from the group consisting of menthol, thymol and eucalyptol.
- SERECK HALL FOX.
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|US2868691 *||Mar 21, 1956||Jan 13, 1959||Riker Laboratories Inc||Self-propelling compositions for inhalation therapy containing a salt of isoproterenol or epinephrine|
|US3144485 *||Jan 17, 1961||Aug 11, 1964||Boots Pure Drug Co Ltd||Alpha-(nu-aryl, aralkyl) acetamidoxiones|
|US4797422 *||Jul 23, 1986||Jan 10, 1989||Michele Testa||Pharmaceutical compounds effective against several disorders of the eye in particular the cataract and composition containing them|
|EP0160501A2 *||Apr 24, 1985||Nov 6, 1985||Eli Lilly And Company||Sustained release intranasal formulation and method of use thereof|
|EP0213091A1 *||Jul 31, 1986||Mar 4, 1987||Michele Testa||Use of compounds for the manufacture of a medicament for the treatment of cataract|
|U.S. Classification||514/653, 564/364, 514/783, 514/786|
|International Classification||A61K9/00, A61K35/06|
|Cooperative Classification||A61K9/0043, A61K35/06|
|European Classification||A61K35/06, A61K9/00M14|