US3098793A - Sulfolane pharmaceutical compositions - Google Patents
Sulfolane pharmaceutical compositions Download PDFInfo
- Publication number
- US3098793A US3098793A US52348A US5234860A US3098793A US 3098793 A US3098793 A US 3098793A US 52348 A US52348 A US 52348A US 5234860 A US5234860 A US 5234860A US 3098793 A US3098793 A US 3098793A
- Authority
- US
- United States
- Prior art keywords
- sulfolane
- ingredients
- solution
- amounts
- give
- 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
- 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
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
Definitions
- This invention relates to new pharmaceutical compositions comprising solutions containing medicinal agents combined with sulfolane compounds as solvents for said medicinal agents for administration to animal organisms.
- these sulfolanes are useful as reaction solvents, for example they are solvents for the valuable penicillin intermediate, 6-aminopenicillanic acid.
- suliolane solvents described herein as essential ingredients of these novel compositions are nontoxic in doses greater than 2 g./kg. orally and at this dosage are, in fact, essentially inert and devoid of physiological activity.
- sulfolane solvents useful in the pharmaceutical composition of this invention may be represented by the following formulas:
- R represents lower alkylene having 2-4 carbon atoms
- R represents lower alkyl having 1-3 carbon atoms.
- the compounds of Formula II are particularly advantageous and potent pharmaceutical solvents.
- compositions according to this invention comprise a solvent of Formula I or Formula II and a medicinal agent substantially soluble in said solvent.
- the solvent is present in an amount sufiicient to dissolve completely the medicinal agent.
- the solutions usually contain about 140% by weight of the medicinal agent, depending of course upon the solubility, potency and desired dosage of the medicinal agent.
- the sulfolane solvents are water soluble.
- the pharmaceutical compositions of this invention may be diluted with water before administration.
- vent contains an amino group, as in Formula II in which either or both of X and X are amino, it may be desirable to butler the pharmaceutical composition with an acidsalt buffer combination such as boric acid-sodium borate or citric acid-sodium citrate.
- an acidsalt buffer combination such as boric acid-sodium borate or citric acid-sodium citrate.
- the pharmaceutical composition of this invention may be administered orally per se, orally aiter dilution with water to give an emulsion or suspension, or parenterally.
- the composition may be orally administered in gelatin capsules.
- the suliolane solvents are either known to the art or are prepared by reacting 3-sulfolene with the appropriate HX R X in the presence of an alkali metal hydroxide such as sodium or potassium hydroxide.
- the reactants are heated at about 40-60 C. for about 1-3 hours. Neutralization of the alkali and treatment of the solution with saturated salt solution, such as sodium chloride solution, separates the desired sulfolane compound.
- sulfolane compounds which are contained in the pharmaceutical compositions described herein are nontoxic, inert, water soluble solvents of high solvency power for a wide variety of medicinal agents and thus, surprisingly, have been found to meet a serious, existing need in the pharmaceutical industry.
- Example 1 Ingredients: Amounts, g. Sulfolane 100 Phenobarbital 10 Ten grams of phenobarbital is added to 100 g. of sulfolane with stirring to yield a solution. Solution is accelerated by warming to 70-80 C.
- Example 2 Thirty grams of methylaminoet'hanol, 23.6 g. of 3- sulfolene and 5 drops of 10% sodium hydroxide solution are mixed anud heated in a sealed bottle at 65 C. for three days. On concentration in vacuo an oil is obtained. Benzene and ether are added. The other layer is concentrated to give 3-(Z-methylaminoethoxy)sulfolane.
- Example 3 A mixture of 30.0 g. of 2-(N-methylamino)ethanol and 23.6 g. of 3-sulfolene is heated in a pressure bottle at 60 C. for 48 hours. Removal of the volatile materials in vacuo gives 3-[N-(2-hydroxyethyl)-N-methylamino]sulfolane.
- Example 4 3-sulfolene (20 g.) and dimethylaminoethylarnine (15.4 g.) are placed in a pressure bottle and heated at 60 C. for
- Example 5 Ingredients: Amounts, g. 3- [2-(N,N-dimethylamino) ethoxy1sulfolane 90 6-aminopenicillanic acid The 6-aminopenicillanic acid is added with stirring to the sulfolane derivative to give a solution.
- Example 6 A mixture of diethylaminoethanethiol (13.0 g.), 3-sulfolene (14.8 g.) and 0.3 g. of powdered potas-siumhydroxide is heated in a pressure bottle for three days at 60 C. The resulting oil is dissolved in benzene. The solution is filtered and concentrated. The residue is converted to the picrate salt which is dissolved in acetonitrile and passed through an alumina column to decompose the picrate. Acetone is passed through the column. The resulting solution is treated with ethereal hydrogen bromide to separate 3-(Z-diethylaminoethylthio)sulfolane hydrobromide.
- Example 7 To 4.7 g. of potassium hydroxide dissolved in 68 ml. of methyl Cellosolve is added 100 g. of 3-sulfolene. The mixture is kept at 40 C. for 24 hours, then neutralized with hydrochloric acid. Washing with saturated sodium chloride, drying and distilling gives 3-(2-methoxyethoxy)- sulfolane.
- Example 8 A mixture of 11.6 g. of N-propylpropane-1,3-diamine and 11.8 g. of 3-sulfolene is heated in a pressure bottle at 55 C. for 48 hours to give 3-[3-(N-propylamino)propylaminoJsulfolane.
- Sulfisoxazole is added slowly with stirring to the sulfolane solvent containing sodium borate and boricacid to give a solution.
- Example 9 Potassium hydroxide (0.4 g.) is added to 14.4 g. of N,N,N'-triethylaminoethylamine. To this mixture is 4 added 11.8 g. of 3-sulfolene. After heating at 50 C. for two hours, an amount of hydrochloric acid sufiicient to neutralize the potassium hydroxide is added and the mixture is then treated with saturated sodium chloride solution. 3- [N-ethyl-N-(2-diethylaminoethyl) amino]sulfolane separates from the mixture.
- Example 10 Potassium hydroxide (0.4 g.) is added to 8.2 g. of 1,4- propanediol. To this mixture is added 11.8 g. of 3-sulfolene and the resulting solution is heated at 50 C. for two hours. Neutralizing with hydrochloric acid and washing with saturated sodium chloride solution separates 3-(4- hydroxybutoxy) sulfolane.
- Vitamin B12 The vitamin B is added slowly with stirring to 3-(4- hydroxybutoxy)sulfolane to give a solution.
- Example 11 A mixture of 11.7 g. of 1-methyl-2-propoxyethylamine and 11.8 g. of 3-sulfolene is heated in a pressure bottle at 55 C. for 72 hours to give 3-(l-methyl-Z-propoxyethylamino)sulfolane.
- the ingredients are mixed together and stirred until a solution is formed.
- Example 12 Ingredients: Amounts, g. 3-methylsulfolane 25 4-chloro-l9-nortestosterone acetate 5 The testosterone derivative is added to 3-methylsulfolane to form a pharmaceutical solution.
- Example 13 Allyalcohol (5.6 g.) and 3-sulfolene (11.8 g.) are mixed and heated in a pressure bottle at 50 C. for 48 hours. The resulting oil is taken up in benzene, treated with charcoal, filtered and concentrated in vacuoto give 3-al1yloxysulfolane.
- Example 14 Ingredients: Amounts, g. 3-[2-(N,N-dipropylamino)ethoxy1sulfolane Sulfathiazole 10 The ingredients are mixed together to form a solution.
- Example 15 Ingredients: Amounts, g. B-methoxysulfolane 9.8 Phenoxymethylpenicillin 0.2
- the ingredients are combined and stirred to form a solution.
- Example 16 Ingredients: Amounts, g. 3-hydroxysulfolane 9.5 Diphenylhydantoin 0.5
- the ingredients are mixed and warmed to 80 C. to 5 form a solution.
- Example 17 A mixture of 11.8 g. of 3-sulfolene, 3.2 g. of ethanol and 3 drops of sodium hydroxide is heated in a 10 sealed tube for 24 hours at 60% C. to give 3-ethoxysulfolane.
- the ingredients are mixed and warmed to 70 C. to give a pharmaceutical solution.
- Example 18 20 Ingredients: Amounts, g.
- a pharmaceutical composition comprising a solvent selected from the group consisting of:
- R is a member selected from the group consisting of hydrogen, methyl, hydroxy, methoxy, ethoxy and allyloxy
- X is a member selected from the group consisting of -NH-, -NR S and 0
- X is a member selected from the group consisting of hydroxy, -OR
- R is lower alkylene having 24 carbon atoms and R is lower allay-1 having l-3 carbon atoms; and a diflicult ly soluble medicinal agent substantially soluble in said solvent.
- a pharmaceutical composition comprising 3-[N-(2- hydroxyethyl)-N-methylamino] sulfolane and a diflicultly solu ble medicinal agent substantially soluble therein.
- a pharmaceutical composition comprising 3-(2- methylami-noethoxy)sulfolane land a difiicult-ly soluble medicinal agent substantially soluble therein.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
United States Patent 3,098,793 SULFOLANE PHARMACEUTICAL CGMPGSKTIGNS Bernard L'oev, Broomall, Pa, assignor to Smith Kline &
French Laboratories, Philadelphia, Pa, a corporation of Pennsylvania No Drawing. Filed Aug. 29, 1966, der. No. 52,348
5 Claims. (Cl. 167-82) This invention relates to new pharmaceutical compositions comprising solutions containing medicinal agents combined with sulfolane compounds as solvents for said medicinal agents for administration to animal organisms.
Many valuable medicinal agents are extremely insoluble in the usual pharmaceutical solvents. In addition there are many potentially valuable drugs which are either inactive or produce erratic results because of poor solubility. Thus a need exists in the pharmaceutical industry for a nontoxic, inert, water soluble solvent of high solvency power.
The suliiolane solvents used in the pharmaceutical compositions of this invention are powerful solvents. for a wide variety of difficultly soluble medicinal agents, such as antibiotics for example chloramphenicol, staphyl-omycin, griseofiulvin and penicillin derivatives; steroid-s; barbiturates; hydantoins; vitamins; sulfa derivatives; pteridines, such as 2,4,7-triamino-6-phenylpteridine; pyrazoloindenone hydrazones such as 3-ethylpyrazolo[3,4-=a]-inden-4 (lH)-one hydrazone; and alkaloids such as reserpine and res-cinnamine. In addition these sulfolanes are useful as reaction solvents, for example they are solvents for the valuable penicillin intermediate, 6-aminopenicillanic acid.
The suliolane solvents described herein as essential ingredients of these novel compositions are nontoxic in doses greater than 2 g./kg. orally and at this dosage are, in fact, essentially inert and devoid of physiological activity.
The sulfolane solvents useful in the pharmaceutical composition of this invention may be represented by the following formulas:
Formula 1 Formula II methoxy,
R represents lower alkylene having 2-4 carbon atoms; and
R represents lower alkyl having 1-3 carbon atoms.
The compounds of Formula II are particularly advantageous and potent pharmaceutical solvents.
The pharmaceutical compositions according to this invention comprise a solvent of Formula I or Formula II and a medicinal agent substantially soluble in said solvent. The solvent is present in an amount sufiicient to dissolve completely the medicinal agent. The solutions usually contain about 140% by weight of the medicinal agent, depending of course upon the solubility, potency and desired dosage of the medicinal agent.
The sulfolane solvents are water soluble. Optionally the pharmaceutical compositions of this invention may be diluted with water before administration. When the sol- 3,098,793 Patented .luly 23, 196.3
"ice
vent contains an amino group, as in Formula II in which either or both of X and X are amino, it may be desirable to butler the pharmaceutical composition with an acidsalt buffer combination such as boric acid-sodium borate or citric acid-sodium citrate.
The pharmaceutical composition of this invention may be administered orally per se, orally aiter dilution with water to give an emulsion or suspension, or parenterally. The composition may be orally administered in gelatin capsules.
The suliolane solvents are either known to the art or are prepared by reacting 3-sulfolene with the appropriate HX R X in the presence of an alkali metal hydroxide such as sodium or potassium hydroxide. The reaction is conveniently carried out in the absence of alkali when the desired compound is a sulfolane of Formula II in which X =amino. The reactants are heated at about 40-60 C. for about 1-3 hours. Neutralization of the alkali and treatment of the solution with saturated salt solution, such as sodium chloride solution, separates the desired sulfolane compound.
Alternatively heating the reactants in a closed bottle with a catalytic amount of an alkali metal hydroxide such as sodium or potassium hydroxide at about 60-75 C. for about 1072 hours yields the sulfolane compound.
The sulfolane compounds which are contained in the pharmaceutical compositions described herein are nontoxic, inert, water soluble solvents of high solvency power for a wide variety of medicinal agents and thus, surprisingly, have been found to meet a serious, existing need in the pharmaceutical industry.
The following examples are not limiting but are illustrative of the invention.
Example 1 Ingredients: Amounts, g. Sulfolane 100 Phenobarbital 10 Ten grams of phenobarbital is added to 100 g. of sulfolane with stirring to yield a solution. Solution is accelerated by warming to 70-80 C.
Example 2 Thirty grams of methylaminoet'hanol, 23.6 g. of 3- sulfolene and 5 drops of 10% sodium hydroxide solution are mixed anud heated in a sealed bottle at 65 C. for three days. On concentration in vacuo an oil is obtained. Benzene and ether are added. The other layer is concentrated to give 3-(Z-methylaminoethoxy)sulfolane.
Ingredients: Amounts, g. B-(Z-methylaminoethoxy)sulfolane 22S Chloramphenicol 25 The chloramphenicol is added with stirring to 3-(N- methylaminoethoxy)sulfolane to give a solution.
Example 3 A mixture of 30.0 g. of 2-(N-methylamino)ethanol and 23.6 g. of 3-sulfolene is heated in a pressure bottle at 60 C. for 48 hours. Removal of the volatile materials in vacuo gives 3-[N-(2-hydroxyethyl)-N-methylamino]sulfolane.
Ingredients: Amounts, g.
3- [N- Z-hydroxyethyl) -N-methylamino] sulfolane Sulfaethylthiadiazole 15 The ingredients are mixed to form a solution.
Example 4 3-sulfolene (20 g.) and dimethylaminoethylarnine (15.4 g.) are placed in a pressure bottle and heated at 60 C. for
48 hours. The resulting oil is taken up in benzene, charcoaled and concentrated togive 3-[2-(N,N-dimethylamino) ethylamino1sulfolane.
Ingredients: Amounts, g.
3- [2-(N,N-dimethylamino) ethylamino] sulfolane 45 Staphylomycin 5' The staphylomycin is added with stirring to the sulfolane solvent to form a solution.
Example 5 Ingredients: Amounts, g. 3- [2-(N,N-dimethylamino) ethoxy1sulfolane 90 6-aminopenicillanic acid The 6-aminopenicillanic acid is added with stirring to the sulfolane derivative to give a solution.
Example 6 A mixture of diethylaminoethanethiol (13.0 g.), 3-sulfolene (14.8 g.) and 0.3 g. of powdered potas-siumhydroxide is heated in a pressure bottle for three days at 60 C. The resulting oil is dissolved in benzene. The solution is filtered and concentrated. The residue is converted to the picrate salt which is dissolved in acetonitrile and passed through an alumina column to decompose the picrate. Acetone is passed through the column. The resulting solution is treated with ethereal hydrogen bromide to separate 3-(Z-diethylaminoethylthio)sulfolane hydrobromide.
An aqueous solution of the hydrobromide is neutralized with sodium hydroxide to give 3-[2-(N,N-diethy1amino)- ethylthio] sulfolane.
Ingredients: Amounts, g. 3- [2-(N,N-diethylamino)ethylthio]sulfolane 140 Reserpine 10 Reserpine (10 g.) is added with stirring to the sulfolane to give a solution.
Example 7 To 4.7 g. of potassium hydroxide dissolved in 68 ml. of methyl Cellosolve is added 100 g. of 3-sulfolene. The mixture is kept at 40 C. for 24 hours, then neutralized with hydrochloric acid. Washing with saturated sodium chloride, drying and distilling gives 3-(2-methoxyethoxy)- sulfolane.
Ingredients: Amounts, g. 3-(Z-methoxyethoxy)sulfolane 150 Griseofulvin 10 The ingredients are mixed to form a solution.
Example 8 A mixture of 11.6 g. of N-propylpropane-1,3-diamine and 11.8 g. of 3-sulfolene is heated in a pressure bottle at 55 C. for 48 hours to give 3-[3-(N-propylamino)propylaminoJsulfolane.
Sulfisoxazole is added slowly with stirring to the sulfolane solvent containing sodium borate and boricacid to give a solution.
Example 9 Potassium hydroxide (0.4 g.) is added to 14.4 g. of N,N,N'-triethylaminoethylamine. To this mixture is 4 added 11.8 g. of 3-sulfolene. After heating at 50 C. for two hours, an amount of hydrochloric acid sufiicient to neutralize the potassium hydroxide is added and the mixture is then treated with saturated sodium chloride solution. 3- [N-ethyl-N-(2-diethylaminoethyl) amino]sulfolane separates from the mixture.
Ingredients: Amounts, g.
3-[N-ethyl-N-(Z-diethylaminoethyl)- aminolsulfolane 9O Testosterone propionate 10 The ingredients are mixed to give a solution.
Example 10 Potassium hydroxide (0.4 g.) is added to 8.2 g. of 1,4- propanediol. To this mixture is added 11.8 g. of 3-sulfolene and the resulting solution is heated at 50 C. for two hours. Neutralizing with hydrochloric acid and washing with saturated sodium chloride solution separates 3-(4- hydroxybutoxy) sulfolane.
Ingredients: Amounts, g. 3- (4-hydroxybutoxy)sulfolane 9.5 Vitamin B12 The vitamin B is added slowly with stirring to 3-(4- hydroxybutoxy)sulfolane to give a solution.
Example 11 A mixture of 11.7 g. of 1-methyl-2-propoxyethylamine and 11.8 g. of 3-sulfolene is heated in a pressure bottle at 55 C. for 72 hours to give 3-(l-methyl-Z-propoxyethylamino)sulfolane.
Ingredients: Amounts, g. 3-(1-methyl-2-propoxyethylamino)sulfolane 9.5 Cortisone 0.5
The ingredients are mixed together and stirred until a solution is formed.
Example 12 Ingredients: Amounts, g. 3-methylsulfolane 25 4-chloro-l9-nortestosterone acetate 5 The testosterone derivative is added to 3-methylsulfolane to form a pharmaceutical solution.
Example 13 Allyalcohol (5.6 g.) and 3-sulfolene (11.8 g.) are mixed and heated in a pressure bottle at 50 C. for 48 hours. The resulting oil is taken up in benzene, treated with charcoal, filtered and concentrated in vacuoto give 3-al1yloxysulfolane.
Ingredients: Amounts, g. 3-a1lyloxysulfolane 9.0 Rescinnamine 1.0
One gram of rescinnamine is added with stirring to nine grams of 3-allyloxysulfolane to give a solution.
Example 14 Ingredients: Amounts, g. 3-[2-(N,N-dipropylamino)ethoxy1sulfolane Sulfathiazole 10 The ingredients are mixed together to form a solution.
Example 15 Ingredients: Amounts, g. B-methoxysulfolane 9.8 Phenoxymethylpenicillin 0.2
The ingredients are combined and stirred to form a solution.
Example 16 Ingredients: Amounts, g. 3-hydroxysulfolane 9.5 Diphenylhydantoin 0.5
The ingredients are mixed and warmed to 80 C. to 5 form a solution.
Example 17 A mixture of 11.8 g. of 3-sulfolene, 3.2 g. of ethanol and 3 drops of sodium hydroxide is heated in a 10 sealed tube for 24 hours at 60% C. to give 3-ethoxysulfolane.
Ingredients: Amounts, g.
3-ethoxysulfolane 9.8 2,4,7-triamino-6-phenylpteridine 0.2
The ingredients are mixed and warmed to 70 C. to give a pharmaceutical solution.
Example 18 20 Ingredients: Amounts, g.
3- [N- (Z-hydroxyethyl) -N-methylamino] sulfolane 7.5 3-ethylpyrazolo [3,4-a1-inden-4( 1H) -one hydrazone 2.5 The ingredients are stirred to form a solution. What is claimed is: 1. A pharmaceutical composition comprising a solvent selected from the group consisting of:
B1 X1R2X2 and i s s in which R is a member selected from the group consisting of hydrogen, methyl, hydroxy, methoxy, ethoxy and allyloxy; X is a member selected from the group consisting of -NH-, -NR S and 0; X is a member selected from the group consisting of hydroxy, -OR
R is lower alkylene having 24 carbon atoms and R is lower allay-1 having l-3 carbon atoms; and a diflicult ly soluble medicinal agent substantially soluble in said solvent.
2. A pharmaceutical composition in accordance with claim 1 in which said solvent is present in an amount suflicient to dissolve completely said medicinal agent.
3. A pharmaceutical composition in accordance with claim 1 in which said medicinal agent is selected from the group consisting of antibiotics, steroids, barbiturates, hydantoins, vitamins, sulfa derivatives, pteridines, pyrazoloindenone hydrazones and alkaloids.
4. A pharmaceutical composition comprising 3-[N-(2- hydroxyethyl)-N-methylamino] sulfolane and a diflicultly solu ble medicinal agent substantially soluble therein.
5. A pharmaceutical composition comprising 3-(2- methylami-noethoxy)sulfolane land a difiicult-ly soluble medicinal agent substantially soluble therein.
References Cited in the file of this patent UNITED STATES PATENTS 2,357,344 Morris et \al. Sept. 5, 1944 2,578,565 Mahan et a1 Dec. 11, 1951 FOREIGN PATENTS 539,555 Canada Apr. 16, 1957
Claims (1)
1. A PHARMACEUTICAL COMPOSITION COMPRISING A SOLVENT SELECTED FROM THE GROUP CONSISTING OF:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US52348A US3098793A (en) | 1960-08-29 | 1960-08-29 | Sulfolane pharmaceutical compositions |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US52348A US3098793A (en) | 1960-08-29 | 1960-08-29 | Sulfolane pharmaceutical compositions |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3098793A true US3098793A (en) | 1963-07-23 |
Family
ID=21977028
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US52348A Expired - Lifetime US3098793A (en) | 1960-08-29 | 1960-08-29 | Sulfolane pharmaceutical compositions |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US3098793A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3322790A (en) * | 1962-11-01 | 1967-05-30 | Union Carbide Corp | Nonionic surfactants |
| US3357996A (en) * | 1964-06-18 | 1967-12-12 | Phillips Petroleum Co | Sulfolane compounds |
| US3376207A (en) * | 1965-05-17 | 1968-04-02 | Patent Serm Ag | Electrodeposition of nickel and electrolytes therefor |
| US3510561A (en) * | 1965-05-20 | 1970-05-05 | Canada Packers Ltd | Sulfone-enhanced heparin absorption through mucous membranes |
| US3950532A (en) * | 1971-05-14 | 1976-04-13 | L'oreal | Topical application of cis of trans 3,4-thiolanediol to reduce the greasy appearance of hair and skin |
| US4080465A (en) * | 1971-05-14 | 1978-03-21 | Societe Anonyme Dite: L'oreal | Topical application of cis or trans 3,4-thiolannediol to reduce or substantially eliminate the greasy appearance of the skin |
| US4108868A (en) * | 1974-01-18 | 1978-08-22 | Uniroyal, Inc. | 3-(Hydroxyhydrocarbylsecondaryamino)thiophene 1,1-dioxides and polyurethanes chain extended therewith |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2357344A (en) * | 1943-06-15 | 1944-09-05 | Shell Dev | Solvent extraction process |
| US2578565A (en) * | 1948-12-28 | 1951-12-11 | Phillips Petroleum Co | Hydrogenating sulfolenes to sulfolanes |
| CA539555A (en) * | 1957-04-16 | Beesley Stanley | Sulpholane derivatives |
-
1960
- 1960-08-29 US US52348A patent/US3098793A/en not_active Expired - Lifetime
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA539555A (en) * | 1957-04-16 | Beesley Stanley | Sulpholane derivatives | |
| US2357344A (en) * | 1943-06-15 | 1944-09-05 | Shell Dev | Solvent extraction process |
| US2578565A (en) * | 1948-12-28 | 1951-12-11 | Phillips Petroleum Co | Hydrogenating sulfolenes to sulfolanes |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3322790A (en) * | 1962-11-01 | 1967-05-30 | Union Carbide Corp | Nonionic surfactants |
| US3357996A (en) * | 1964-06-18 | 1967-12-12 | Phillips Petroleum Co | Sulfolane compounds |
| US3376207A (en) * | 1965-05-17 | 1968-04-02 | Patent Serm Ag | Electrodeposition of nickel and electrolytes therefor |
| US3510561A (en) * | 1965-05-20 | 1970-05-05 | Canada Packers Ltd | Sulfone-enhanced heparin absorption through mucous membranes |
| US3950532A (en) * | 1971-05-14 | 1976-04-13 | L'oreal | Topical application of cis of trans 3,4-thiolanediol to reduce the greasy appearance of hair and skin |
| US4080465A (en) * | 1971-05-14 | 1978-03-21 | Societe Anonyme Dite: L'oreal | Topical application of cis or trans 3,4-thiolannediol to reduce or substantially eliminate the greasy appearance of the skin |
| US4108868A (en) * | 1974-01-18 | 1978-08-22 | Uniroyal, Inc. | 3-(Hydroxyhydrocarbylsecondaryamino)thiophene 1,1-dioxides and polyurethanes chain extended therewith |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US3388129A (en) | 1-methyl ergot alkaloids | |
| US3098793A (en) | Sulfolane pharmaceutical compositions | |
| Hassner et al. | Synthesis and Ring Opening of Fused Steroidal Aziridines*, 1 | |
| DE1545575C2 (en) | N, N'-Bis- square bracket to 3 "(3 ', 4', 5'-trimethoxybenzoyloxy) -propyl square bracket to -homopiperazine | |
| CS203036B2 (en) | Process for preparing 1,3-dibenzoyloxy-17alpha-ethinyl-7alpha-methyl-1,3,5/10/-estatrien-17beta-ole | |
| US2403483A (en) | Tertiary amino derivatives of dihydro-anthracene | |
| DK151806B (en) | METHOD OF ANALOGUE FOR THE PREPARATION OF VINCAMINE SUCCHARINATE | |
| US20100279994A1 (en) | Ansamycin Formulations and Methods of Use Thereof | |
| JPS6232170B2 (en) | ||
| US3880862A (en) | 6{62 -Azido-17-cycloalkylmethyl-4,5{60 -epoxymorphinan-3-ols | |
| US2397903A (en) | Methylene-bis-2 hydroxy-3 naphthoates | |
| DK149750B (en) | METHOD OF ANALOGUE FOR THE PREPARATION OF N-ALKENYL MORANOLINE DERIVATIVES OR PHARMACEUTICAL ACCEPTABLE ACID ADDITION SALTS. | |
| US4046811A (en) | Antiviral 1,2,3,4-tetrahydro-1,4-alkanonaphthalenamine derivatives | |
| US3567713A (en) | Derivatives of 2alpha,3alpha-epithioandrostane and process for preparing them | |
| US3413285A (en) | Amino-acetylamino-cholestanes | |
| US2458430A (en) | Medicinal solutions | |
| SE434835B (en) | N- (1-METHYL-2-PYRROLIDINYLMETHYL) -2,3-DIMETOXY-5-METHYLSULPHAMOYL-BENZAMIDE, ITS PREPARATION AND PHARMACOLOGICAL COMPOSITION CONTAINING THIS NEW BENZAMIDE | |
| DE1147589B (en) | Process for the preparation of bactericidally active derivatives of 1- (5-nitrofurfurylidene-amino) -hydantoin substituted in the 3-position | |
| US3175945A (en) | Antihypertensive quaternary ammonium salts of 1:2:3:4-tetrahydroisoquinoline | |
| US3124592A (en) | Water-insoluble salts of basic anti- | |
| US3098858A (en) | 7-halogenated adrenochrome derivatives | |
| US3140233A (en) | Tasteless pharmaceutical composition and process | |
| US3278529A (en) | Nitro-furfurylidene acid hydrazides | |
| NO743174L (en) | ||
| US4004017A (en) | Method of inducing infertility in male animals and inhibiting the growth of the prostate |