US3080287A - Analgesic compositions - Google Patents
Analgesic compositions Download PDFInfo
- Publication number
- US3080287A US3080287A US676392A US67639257A US3080287A US 3080287 A US3080287 A US 3080287A US 676392 A US676392 A US 676392A US 67639257 A US67639257 A US 67639257A US 3080287 A US3080287 A US 3080287A
- Authority
- US
- United States
- Prior art keywords
- parts
- hexobarbital
- barbituric acid
- compositions
- compounds
- 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
- 239000000203 mixture Substances 0.000 title claims description 19
- 230000000202 analgesic effect Effects 0.000 title claims description 11
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 claims description 17
- CPJSUEIXXCENMM-UHFFFAOYSA-N phenacetin Chemical compound CCOC1=CC=C(NC(C)=O)C=C1 CPJSUEIXXCENMM-UHFFFAOYSA-N 0.000 claims description 16
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 10
- 150000001875 compounds Chemical class 0.000 claims description 10
- UYXAWHWODHRRMR-UHFFFAOYSA-N hexobarbital Chemical compound O=C1N(C)C(=O)NC(=O)C1(C)C1=CCCCC1 UYXAWHWODHRRMR-UHFFFAOYSA-N 0.000 claims description 10
- 229960002456 hexobarbital Drugs 0.000 claims description 10
- 229960003893 phenacetin Drugs 0.000 claims description 10
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 9
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 claims description 8
- 229960001948 caffeine Drugs 0.000 claims description 8
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 claims description 8
- 150000007656 barbituric acids Chemical class 0.000 claims description 6
- IUJDSEJGGMCXSG-UHFFFAOYSA-N Thiopental Chemical compound CCCC(C)C1(CC)C(=O)NC(=S)NC1=O IUJDSEJGGMCXSG-UHFFFAOYSA-N 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 229960003279 thiopental Drugs 0.000 claims description 4
- 239000004615 ingredient Substances 0.000 description 10
- 230000000694 effects Effects 0.000 description 6
- 238000011287 therapeutic dose Methods 0.000 description 6
- 229940035676 analgesics Drugs 0.000 description 4
- 239000000730 antalgic agent Substances 0.000 description 4
- 229940125717 barbiturate Drugs 0.000 description 4
- -1 barbituric acid compound Chemical class 0.000 description 4
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 3
- 230000002195 synergetic effect Effects 0.000 description 2
- RMMXTBMQSGEXHJ-UHFFFAOYSA-N Aminophenazone Chemical compound O=C1C(N(C)C)=C(C)N(C)N1C1=CC=CC=C1 RMMXTBMQSGEXHJ-UHFFFAOYSA-N 0.000 description 1
- 206010019133 Hangover Diseases 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- LYZGJWXNOGIVQA-UHFFFAOYSA-M Thiamylal sodium Chemical compound [Na+].CCCC(C)C1(CC=C)C(=O)NC([S-])=NC1=O LYZGJWXNOGIVQA-UHFFFAOYSA-M 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229960000212 aminophenazone Drugs 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229960001525 thiamylal sodium Drugs 0.000 description 1
Classifications
-
- 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
- A61K31/60—Salicylic acid; Derivatives thereof
Definitions
- Combinations of analgesics with barbituric acid compounds have been suggested previously.
- the purpose of such combinations was not only to relieve pain, but also to simultaneously calm down nervous patients by the action of thereapeutic doses of the barbituric acid ingredient in the combinations.
- the use of such doses renders these compositions less suitable for daytime administration to patients who have to attend their work or other activities, since therapeutic doses of most barbiturates tend to induce sleep and make the patients drowsy.
- Another disadvantage of such compositions is the cumulative effect of repeated therapeutic doses of ba-rbituric acid compounds when the compositions have to be repeatedly administered during a protracted period of time.
- compositions in which the mild analgesics and the barbituric acid compounds described hereinafter are combined with each other under the conditions of the present invention are combined with each other under the conditions of the present invention.
- compositions embodying this invention drowsiness and hangover and other undesirable side-effects occurring in the use of known compositions, are usually not encountered.
- Example 1 A mixture is prepared from the following ingredients:
- Example 2 Mixtures are prepared from the ingredients named in 3,080,287 Patented Mar. 5, 1963 the above Example 1, whereby the individual ingredients are used in the following ranges:
- Example 4 In any of the above Examples 1-3, an equal part by weight of thiamylal sodium or three times in weight doses of thiopental can be substituted for the hexobarbital. A mixture of these barbiturates can also be used. Furthermore, instead of the respective barbituric acid a therapeutically applicable salt thereof, e.g. the sodium salt, can be used and instead of caffeine an equivalent amount of a therapeutically applicable caffeine salt, can be used.
- a therapeutically applicable salt thereof e.g. the sodium salt
- caffeine an equivalent amount of a therapeutically applicable caffeine salt
- the above named in gredients i.e. aspirin, phenacetin, caffeine are used in the usual therapeutic doses, while a barbituric acid compound which is rapid on onset and short in duration, is used in sub-therapeutic doses.
- a substantially increased synergistic analgesic effect results, which cannot be obtained in the absence of ingredients and proportions called for by the present invention.
- composition according to the above Example 1 yields a considerably increased analgesic effect in comparison with a similar composition, in which the phenacetin is omitted or substituted by aspirin, or in which the aspirin is omitted or substituted by phenacetin, or in which the conditions called for by the present invention are not observed in other respects.
- Analgesic compositions containing as active ingredients (a) -390 parts of acetyl salicylic acid; (b) 65-260 parts of acetophenetidine; (0) 16-65 parts of a compound selected from the group consisting of caffeine and therapeutically applicable salts thereof; and at least one compound selected from the group consisting of hexobarbital, thioamylal, thiopental, analogous barbituric acid compounds rapid on onset and short in duration, and therapeutically applicable salts of these compounds, the hexobarbital being used in an amount of 20-60 parts and thioamylal, thiopental and said analogous barbituric acid 3 compounds, being used in amounts equivalent to 20-60 parts of hexobarbital.
- Analgesic compositions containing as active ingredients (a) aspirin, (b) acetophenetidine, (c) caffeine and (d) hexobarbital, in the proportions of (a) 3 /2 grains (1)) 2% grains (0) /2 grain and (d) 50 milligrams.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (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 3,080,287 ANALGESIC COMPOSITIONS Mozes Juda Lewenstein, 83-75 116th St, Kew Gardens, N.Y. No Drawing. Filed Aug. 5, 1957, Ser. No. 676,392 2 Claims. (Cl. 167-65) This invention relates to analgesic compositions and it has particular relation to compositions in which analgesic compounds of the type described hereinafter are used in combination with a barbituric acid compound of the type disclosed and under the conditions described hereinafter.
Combinations of analgesics with barbituric acid compounds have been suggested previously. The purpose of such combinations was not only to relieve pain, but also to simultaneously calm down nervous patients by the action of thereapeutic doses of the barbituric acid ingredient in the combinations. The use of such doses renders these compositions less suitable for daytime administration to patients who have to attend their work or other activities, since therapeutic doses of most barbiturates tend to induce sleep and make the patients drowsy. Another disadvantage of such compositions is the cumulative effect of repeated therapeutic doses of ba-rbituric acid compounds when the compositions have to be repeatedly administered during a protracted period of time.
The use of mild analgesics, such as aminopyrine or aspirin, in combination with barbiturates has also been suggested, but the results were not encouraging, because it has been found that little additional analgesia was conferred by barbiturates in combination with such mild analgesics, neither were other advantages obtained.
It has now unexpectedly been discovered that improved analgesic effects can be obtained by compositions in which the mild analgesics and the barbituric acid compounds described hereinafter are combined with each other under the conditions of the present invention.
According to the present invention it has been found that by using a therapeutic dose of (a) aspirin (acetyl salicylic acid) in combination with (b) phenacetin (acetophenetidine), (c) caffeine and (d) with a sub-therapeutic dose of a barbituric acid compound, which is rapid on onset and short in duration of its effect, composiitons are obtained in which the analgesic effect of the active ingredients is accelerated, increased and prolonged in comparison with the added effects of the individual ingredients, as well as in comparison with partial combinations, e.g. (a), (c) and (d) or (b), (c) and (d), and which are practically free from undesired side-effects. In other words, this increase and improvement of the effect requires the co-action of the ingredients (a), (b), (c) and (d) and represents a novel and unexpected synergistic effect of these ingredients.
In the use of compositions embodying this invention drowsiness and hangover and other undesirable side-effects occurring in the use of known compositions, are usually not encountered.
Example 1 A mixture is prepared from the following ingredients:
(a) Aspirin grains 3 /2 (11) Phenacetin do 2% (c) Caffeine do (d) Hexobarbital milligrams 50 The above ingredients are incorporated in conventional manner in each table for oral administration.
Example 2 Mixtures are prepared from the ingredients named in 3,080,287 Patented Mar. 5, 1963 the above Example 1, whereby the individual ingredients are used in the following ranges:
Aspirin grains 2- 6 Phenacetin do 1- 4 Caffeine do A- 1 Hexobarbital milligrams 20-60 The resulting mixtures are formed to tablets in conventional manner.
Example 4 In any of the above Examples 1-3, an equal part by weight of thiamylal sodium or three times in weight doses of thiopental can be substituted for the hexobarbital. A mixture of these barbiturates can also be used. Furthermore, instead of the respective barbituric acid a therapeutically applicable salt thereof, e.g. the sodium salt, can be used and instead of caffeine an equivalent amount of a therapeutically applicable caffeine salt, can be used.
According to the present invention the above named in gredients, i.e. aspirin, phenacetin, caffeine are used in the usual therapeutic doses, while a barbituric acid compound which is rapid on onset and short in duration, is used in sub-therapeutic doses. In the above described proportions, due to co-action of these ingredients a substantially increased synergistic analgesic effect results, which cannot be obtained in the absence of ingredients and proportions called for by the present invention. Thus, for example the composition according to the above Example 1 yields a considerably increased analgesic effect in comparison with a similar composition, in which the phenacetin is omitted or substituted by aspirin, or in which the aspirin is omitted or substituted by phenacetin, or in which the conditions called for by the present invention are not observed in other respects.
The term rapid on onset and short in duration is used in the present application to denote barbituric acid compounds, the therapeutic action of which is analogous to that of the compounds described in the above Examples.
The parts mentioned above are parts by weight if not otherwise stated.
What is claimed is:
1. Analgesic compositions containing as active ingredients (a) -390 parts of acetyl salicylic acid; (b) 65-260 parts of acetophenetidine; (0) 16-65 parts of a compound selected from the group consisting of caffeine and therapeutically applicable salts thereof; and at least one compound selected from the group consisting of hexobarbital, thioamylal, thiopental, analogous barbituric acid compounds rapid on onset and short in duration, and therapeutically applicable salts of these compounds, the hexobarbital being used in an amount of 20-60 parts and thioamylal, thiopental and said analogous barbituric acid 3 compounds, being used in amounts equivalent to 20-60 parts of hexobarbital.
2. Analgesic compositions containing as active ingredients (a) aspirin, (b) acetophenetidine, (c) caffeine and (d) hexobarbital, in the proportions of (a) 3 /2 grains (1)) 2% grains (0) /2 grain and (d) 50 milligrams.
References Cited in the file of this patent Goodman et 211.: Pharmacological Basis of Therapeutics, 2nd ed., (1955), Macmillan Co., N.Y., pp 125, 127, 138 and 141.
Friedman et al.: J.A.M.A., vol. 163, No. 13, Mar. 30, 1957, pp. 11114117.
Orkin et al.: Survey of Anesthesiology, October 1957, pp. 460-464.
Batterman: I.A.M.A., vol. 155, No. 11, July 10, 1954, pp. 965-968.
Beecher: J.A.M.A., vol. 158, No. 5, June 4, 1955, pp. 399-401.
J.A.M.A., vol. 165, N0. 9, Nov. 2, 1957, pp. 1172- 1173.
Claims (1)
1. ANALGESIC COMPOSITIONS CONTAINING AS ACTIVE INGREDIENTS (A) 130-390 PARTS OF ACETYL SALICYLIC ACID; (B) 65-260 PARTS OF ACETOPHENETIDINE; (C) 16-65 PARTS OF A COMPOUND SELECTED FROM THE GROUP CONSISTING OF CAFFEINE AND THERAPEUTICALLY APPLICABLE SALTS THEREOF; AND AT LEAST ONE COMPOUND SELECTED FROM THE GROUP CONSISTING OF HEXOBARBITAL, THIOMYLAL, THIPPENTAL, ANALOGOUS BARBITURIC ACID COMPOUNDS RAPID ON ONSET AND SHORT IN DURATION, AND THERAPEUTICALLY APPLICABLE SALTS OF THESE COMPOUNDS, THE HEXOBARBITAL BEING USED IN AN AMOUNT OF 20-60 PARTS AND THIOAMYLAL, THIOPENTAL AND SAID ANALOGOUS BARBITURIC ACID COMPOUNDS, BEING USED IN AMOUNTS EQUIVALENT TO 20-60 PARTS OF HEXOBARBITAL.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US676392A US3080287A (en) | 1957-08-05 | 1957-08-05 | Analgesic compositions |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US676392A US3080287A (en) | 1957-08-05 | 1957-08-05 | Analgesic compositions |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3080287A true US3080287A (en) | 1963-03-05 |
Family
ID=24714320
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US676392A Expired - Lifetime US3080287A (en) | 1957-08-05 | 1957-08-05 | Analgesic compositions |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US3080287A (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3218233A (en) * | 1963-01-24 | 1965-11-16 | Lewenstein Mozes Juda | Analgesic compositions |
| US3274203A (en) * | 1963-05-31 | 1966-09-20 | Du Pont | 1-carbamyl and thiocarbamyl-3-amino-4-nonsubstituted and substituted pyrazoles |
| US3320262A (en) * | 1964-09-22 | 1967-05-16 | Lewenstein | 14 hydroxy morphine and codeine carboxymethyloximes |
| US3331828A (en) * | 1964-09-30 | 1967-07-18 | Merck & Co Inc | Isolation of gamma-l-glutamyl dipeptides from glutamic acid fermentation broths by ion exchange |
| US4505862A (en) * | 1981-04-14 | 1985-03-19 | Bristol-Myers Company | Diphenydramine dihydrogencitrate |
| US4880791A (en) * | 1984-07-21 | 1989-11-14 | Hoechst Aktiengesellschaft | Combination product composed of xanthine derivatives and O-acetylsalicylic acid or its pharmacologically tolerated salts, and its use |
| US5055460A (en) * | 1990-04-26 | 1991-10-08 | Mitchell Friedlander | Method for weight loss |
| US5972916A (en) * | 1997-07-14 | 1999-10-26 | Bristol-Myers Squibb Company | Compositions containing the nonprescription combination of acetaminophen, aspirin and caffeine to alleviate the pain and symptoms of migraine |
| US6642243B1 (en) | 1999-07-22 | 2003-11-04 | Ashkan Imanzahrai | Migraine medicine and method for treating same |
-
1957
- 1957-08-05 US US676392A patent/US3080287A/en not_active Expired - Lifetime
Non-Patent Citations (1)
| Title |
|---|
| None * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3218233A (en) * | 1963-01-24 | 1965-11-16 | Lewenstein Mozes Juda | Analgesic compositions |
| US3274203A (en) * | 1963-05-31 | 1966-09-20 | Du Pont | 1-carbamyl and thiocarbamyl-3-amino-4-nonsubstituted and substituted pyrazoles |
| US3277100A (en) * | 1963-05-31 | 1966-10-04 | Du Pont | Novel substituted pyrazoles |
| US3320262A (en) * | 1964-09-22 | 1967-05-16 | Lewenstein | 14 hydroxy morphine and codeine carboxymethyloximes |
| US3331828A (en) * | 1964-09-30 | 1967-07-18 | Merck & Co Inc | Isolation of gamma-l-glutamyl dipeptides from glutamic acid fermentation broths by ion exchange |
| US4505862A (en) * | 1981-04-14 | 1985-03-19 | Bristol-Myers Company | Diphenydramine dihydrogencitrate |
| US4880791A (en) * | 1984-07-21 | 1989-11-14 | Hoechst Aktiengesellschaft | Combination product composed of xanthine derivatives and O-acetylsalicylic acid or its pharmacologically tolerated salts, and its use |
| US5055460A (en) * | 1990-04-26 | 1991-10-08 | Mitchell Friedlander | Method for weight loss |
| US5972916A (en) * | 1997-07-14 | 1999-10-26 | Bristol-Myers Squibb Company | Compositions containing the nonprescription combination of acetaminophen, aspirin and caffeine to alleviate the pain and symptoms of migraine |
| US6642243B1 (en) | 1999-07-22 | 2003-11-04 | Ashkan Imanzahrai | Migraine medicine and method for treating same |
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