US3071509A - N-alkyl-nornicotine:nicotine antagonist - Google Patents
N-alkyl-nornicotine:nicotine antagonist Download PDFInfo
- Publication number
- US3071509A US3071509A US94446A US9444661A US3071509A US 3071509 A US3071509 A US 3071509A US 94446 A US94446 A US 94446A US 9444661 A US9444661 A US 9444661A US 3071509 A US3071509 A US 3071509A
- Authority
- US
- United States
- Prior art keywords
- alkyl
- nicotine
- nornicotine
- mgm
- antagonist
- 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
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 title description 13
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 title description 13
- 229960002715 nicotine Drugs 0.000 title description 13
- 239000005557 antagonist Substances 0.000 title description 8
- 239000002552 dosage form Substances 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 6
- 230000037406 food intake Effects 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 231100000252 nontoxic Toxicity 0.000 claims description 4
- 230000003000 nontoxic effect Effects 0.000 claims description 4
- 150000007513 acids Chemical class 0.000 claims description 3
- MYKUKUCHPMASKF-VIFPVBQESA-N (S)-nornicotine Chemical class C1CCN[C@@H]1C1=CC=CN=C1 MYKUKUCHPMASKF-VIFPVBQESA-N 0.000 claims 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 241000208125 Nicotiana Species 0.000 description 4
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 239000000779 smoke Substances 0.000 description 4
- 238000013268 sustained release Methods 0.000 description 4
- 239000012730 sustained-release form Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000006461 physiological response Effects 0.000 description 3
- 230000000391 smoking effect Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 235000019504 cigarettes Nutrition 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- MYKUKUCHPMASKF-UHFFFAOYSA-N Nornicotine Natural products C1CCNC1C1=CC=CN=C1 MYKUKUCHPMASKF-UHFFFAOYSA-N 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000019506 cigar Nutrition 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 235000019788 craving Nutrition 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- -1 for example Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
Definitions
- the present invention provides a help to the solution of the above problems.
- the smoker orally ingests a unitary dosage form of a nicotine antagonist.
- the nicotine antagonists useful in the present invention are compounds which are chemically related to nicotine itself, but they differ from nicotine in that the methyl group present on the nitrogen atom in the 5- membered ring of nicotine has been replaced by a lower alkyl group containing from 2 to 8 carbon atoms.
- the compounds are, chemically, N-alkyl nornicotines.
- suitable alkyl groups there may be mentioned ethyl, propyl, isopropyl, hexyl, isobutyl, octyl, and, preferably, allyl, which is an unsaturated alkyl group.
- the antagonist may be used in the form of thefree base, but it is preferred to use it in the form of an acid addition salt.
- the salt may be of any non-toxic acid, for example, citric acid, m-alic acid, acetic acid, hydrochloric acid, sulfuric acid, phosphoric acid, and the like.
- the nicotine antagonists of the present invention diminish the physiological responses elicited in the smoker by nicotine and the related alkaloids absorbed from the smoke.
- the dosage of the antagonist should be of approximately the same order of magnitude as the amount of nicotine absorbed by the smoker.
- the daily dosage will be from about 5 mgm. to about 250 mgrn.
- the antagonist is preferably taken in split dosages, say three or four a day. Most desirably, the dosage is taken in the form of a sustained release capsule or tablet.
- the unitary dosage forms of the present invention may be formulated in accordance with conventional practices well-known in the art. Any compatible inert excipient may be used. Examples include starch, milk sugar, calcium phosphate and the like.
- the preparation of sustained release dosage forms is also a well developed art, and such forms of the antagonist may be prepared in accordance With Well-known methods.
- Example I Fifty mgm. of the citrate salt of N-alkyl nornicotine is mixed with 200 mgm. of starch, and the mixture is pressed into a tablet. One such tablet is taken at each of 3 meals daily by a smoker who averages forty cigarettes a day. The usual physiological responses due to smoking are diminished, and the craving for tobacco is decreased.
- a unitary dosage form suitable for oral ingestion comprising from about 5 to about 250 mgm. of a compound selected from the group consisting of N-alkyl nornico-tine compounds containing from 2 to 8 carbon atoms in the alkyl group, and addition salts thereof with non-toxic acids, together with a carrier.
- a sustained release unitary dosage form suitable for oral ingestion comprising from about 5 to about 250 mgm. of a compound selected from the group consisting of N-alkyl nornicotine compounds containing from 2. to 8 carbon atoms in the alkyl group, and addition salts thereof with non-toxic acids.
- a unitary dosage form suitable for oral ingestion comprising from about 5 to about 250 mgm. of the citrate of N-allyl nornicotine together with a carrier.
- a sustained release unitary dosage form suitable for oral ingestion comprising from about 5 to about 250 mgm. of the citrate of N-allyl nornico-tine.
Description
United States Patent Ofifice Patented Jan. 1, 1963 3,071,509 N-Atkrt-Noarstcornsnuutcornsn ANrAooNisr No Drawing. Filed Mar. 9, 1961, Ser. No. 94,446 4 flaims. (Cl. 167-55) The present invention is concerned with certain novel pharmaceutical dosage forms. In particular, it is concerned with unitary dosage forms of certain compounds which I have found exert a physiological response antagonistic to that of nicotine.
The present application is a continuation in part of my copending application Serial Number 3,718, filed on January 21, 1960, noW Patent No. 2,981,641.
Many persons who smoke tobacco desire to break the smoking habit, or at least to diminish the amount of smoking. The reasons for such desire are many and varied, any may be based on advice from a physician or purely on economic considerations. in any case, it has been the experience of numerous smokers, and particularly of very heavy smokers, that it is very difficult to give up the tobacco habit. There are also many persons upon whom the nicotine absorbed from smoked tobacco exerts an undesired effect, for example, upon blood pressure or gastric secretion.
The present invention provides a help to the solution of the above problems. According to the present invention, the smoker orally ingests a unitary dosage form of a nicotine antagonist.
The nicotine antagonists useful in the present invention are compounds which are chemically related to nicotine itself, but they differ from nicotine in that the methyl group present on the nitrogen atom in the 5- membered ring of nicotine has been replaced by a lower alkyl group containing from 2 to 8 carbon atoms. The compounds are, chemically, N-alkyl nornicotines. As examples of suitable alkyl groups, there may be mentioned ethyl, propyl, isopropyl, hexyl, isobutyl, octyl, and, preferably, allyl, which is an unsaturated alkyl group.
The antagonist may be used in the form of thefree base, but it is preferred to use it in the form of an acid addition salt. The salt may be of any non-toxic acid, for example, citric acid, m-alic acid, acetic acid, hydrochloric acid, sulfuric acid, phosphoric acid, and the like.
When taken by the smoker, the nicotine antagonists of the present invention diminish the physiological responses elicited in the smoker by nicotine and the related alkaloids absorbed from the smoke.
On the average, about 3 to 4 mgm. of nicotine are absorbed from the puffed smoke of an average cigarette. The smoke of a 10 gram cigar may contain some to more than 40 mgm. of nicotine. (See Goodman and Gilman, The Pharmacological Basis of Therapeutics, 2nd Edition, 1956, p. 624.) The dosage of the antagonist should be of approximately the same order of magnitude as the amount of nicotine absorbed by the smoker. For the majority of smokers, the daily dosage will be from about 5 mgm. to about 250 mgrn. Particularly in the case of dosages toward the upper end of this range, the antagonist is preferably taken in split dosages, say three or four a day. Most desirably, the dosage is taken in the form of a sustained release capsule or tablet.
The unitary dosage forms of the present invention may be formulated in accordance with conventional practices well-known in the art. Any compatible inert excipient may be used. Examples include starch, milk sugar, calcium phosphate and the like. The preparation of sustained release dosage forms is also a well developed art, and such forms of the antagonist may be prepared in accordance With Well-known methods.
Example I Fifty mgm. of the citrate salt of N-alkyl nornicotine is mixed with 200 mgm. of starch, and the mixture is pressed into a tablet. One such tablet is taken at each of 3 meals daily by a smoker who averages forty cigarettes a day. The usual physiological responses due to smoking are diminished, and the craving for tobacco is decreased.
The foregoing example is given solely for the purposes of illustration and is not to be construed as limitation of the invention, many variations of which will occur to those skilled in the art Without departing from the spirit or scope thereof.
What is claimed is:
1. A unitary dosage form suitable for oral ingestion comprising from about 5 to about 250 mgm. of a compound selected from the group consisting of N-alkyl nornico-tine compounds containing from 2 to 8 carbon atoms in the alkyl group, and addition salts thereof with non-toxic acids, together with a carrier.
2. A sustained release unitary dosage form suitable for oral ingestion comprising from about 5 to about 250 mgm. of a compound selected from the group consisting of N-alkyl nornicotine compounds containing from 2. to 8 carbon atoms in the alkyl group, and addition salts thereof with non-toxic acids.
3. A unitary dosage form suitable for oral ingestion, comprising from about 5 to about 250 mgm. of the citrate of N-allyl nornicotine together with a carrier.
4. A sustained release unitary dosage form suitable for oral ingestion comprising from about 5 to about 250 mgm. of the citrate of N-allyl nornico-tine.
References Cited in the file of this patent UNITED STATES PATENTS 2,981,641 ONeill Apr. 25, 1961
Claims (1)
1. A UNITARY DOSAGE FORM SUITABLE FOR ORAL INGESTION COMPRISING FROM ABOUT 5 TO ABOUT 250 MGM. OF A COMPOUND SELECTED FROM THE GROUP CONSISTING OF N-ALKYL NORNICOTINE COMPOUNDS CONTAINING FROM 2 TO 8 CARBON ATOMS IN THE ALKYL GROUP, AND ADDITION SALTS THEREOF WITH NON-TOXIC ACIDS, TOGETHER WITH A CARRIER.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US94446A US3071509A (en) | 1961-03-09 | 1961-03-09 | N-alkyl-nornicotine:nicotine antagonist |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US94446A US3071509A (en) | 1961-03-09 | 1961-03-09 | N-alkyl-nornicotine:nicotine antagonist |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3071509A true US3071509A (en) | 1963-01-01 |
Family
ID=22245252
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US94446A Expired - Lifetime US3071509A (en) | 1961-03-09 | 1961-03-09 | N-alkyl-nornicotine:nicotine antagonist |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US3071509A (en) |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4574151A (en) * | 1982-08-20 | 1986-03-04 | Peter Robin Broughton Lawrence | Amine salts and products containing them |
| US4806356A (en) * | 1983-06-29 | 1989-02-21 | Shaw Alec S W | Tobacco product |
| US5122366A (en) * | 1989-01-21 | 1992-06-16 | The Arab Pharmaceutical Company | Antismoke mouth wash comprising silver nitrate and propylene glycol |
| US5316759A (en) * | 1986-03-17 | 1994-05-31 | Robert J. Schaap | Agonist-antagonist combination to reduce the use of nicotine and other drugs |
| US20080221085A1 (en) * | 2004-07-15 | 2008-09-11 | Universite Laval | Nicotinic Receptor Agonists for the Treatment of Inflammatory Diseases |
| US20080233197A1 (en) * | 2006-06-19 | 2008-09-25 | Francis Joseph Matthews | Pharmaceutical compositions |
| US20100152221A1 (en) * | 2007-12-17 | 2010-06-17 | Alpharma Pharmaceuticals, Llc | Pharmaceutical composition |
| US20100151014A1 (en) * | 2008-12-16 | 2010-06-17 | Alpharma Pharmaceuticals, Llc | Pharmaceutical composition |
| US20100266645A1 (en) * | 2007-12-17 | 2010-10-21 | Alfred Liang | Pharmaceutical compositions |
| US20110014280A1 (en) * | 2002-09-20 | 2011-01-20 | Garth Boehm | Sequestering subunit and related compositions and methods |
| US8557804B2 (en) | 2002-03-25 | 2013-10-15 | Universite Laval | Nicotinic receptor agonists for the treatment of inflammatory diseases |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2981641A (en) * | 1960-01-21 | 1961-04-25 | Stauffer Chemical Co | Tobacco products |
-
1961
- 1961-03-09 US US94446A patent/US3071509A/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2981641A (en) * | 1960-01-21 | 1961-04-25 | Stauffer Chemical Co | Tobacco products |
Cited By (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4574151A (en) * | 1982-08-20 | 1986-03-04 | Peter Robin Broughton Lawrence | Amine salts and products containing them |
| US4806356A (en) * | 1983-06-29 | 1989-02-21 | Shaw Alec S W | Tobacco product |
| US5316759A (en) * | 1986-03-17 | 1994-05-31 | Robert J. Schaap | Agonist-antagonist combination to reduce the use of nicotine and other drugs |
| US5574052A (en) * | 1986-03-17 | 1996-11-12 | Robert J. Schaap | Agonist-antagonist combination to reduce the use of nicotine and other drugs |
| US5935975A (en) * | 1986-03-17 | 1999-08-10 | Robert J. Schaap | Agonist-antagonist combination to reduce the use of nicotine and other drugs |
| US5122366A (en) * | 1989-01-21 | 1992-06-16 | The Arab Pharmaceutical Company | Antismoke mouth wash comprising silver nitrate and propylene glycol |
| US8557804B2 (en) | 2002-03-25 | 2013-10-15 | Universite Laval | Nicotinic receptor agonists for the treatment of inflammatory diseases |
| US8551983B2 (en) | 2002-03-25 | 2013-10-08 | Universite Laval | Nicotinic receptor agonists for the treatment of inflammatory diseases |
| US8685443B2 (en) | 2002-09-20 | 2014-04-01 | Alpharma Pharmaceuticals Llc | Sequestering subunit and related compositions and methods |
| US8685444B2 (en) | 2002-09-20 | 2014-04-01 | Alpharma Pharmaceuticals Llc | Sequestering subunit and related compositions and methods |
| US20110014280A1 (en) * | 2002-09-20 | 2011-01-20 | Garth Boehm | Sequestering subunit and related compositions and methods |
| US20110027455A1 (en) * | 2002-09-20 | 2011-02-03 | Garth Boehm | Sequestering subunit and related compositions and methods |
| US20080221085A1 (en) * | 2004-07-15 | 2008-09-11 | Universite Laval | Nicotinic Receptor Agonists for the Treatment of Inflammatory Diseases |
| US8039459B2 (en) | 2004-07-15 | 2011-10-18 | Universite Laval | Nicotinic receptor agonists for the treatment of inflammatory diseases |
| US8158156B2 (en) | 2006-06-19 | 2012-04-17 | Alpharma Pharmaceuticals, Llc | Abuse-deterrent multi-layer pharmaceutical composition comprising an opioid antagonist and an opioid agonist |
| US20100143483A1 (en) * | 2006-06-19 | 2010-06-10 | Alpharma Pharmaceuticals, Llc. | Pharmaceutical compositions |
| US7682633B2 (en) | 2006-06-19 | 2010-03-23 | Alpharma Pharmaceuticals, Llc | Pharmaceutical composition |
| US7682634B2 (en) | 2006-06-19 | 2010-03-23 | Alpharma Pharmaceuticals, Llc | Pharmaceutical compositions |
| US20090162450A1 (en) * | 2006-06-19 | 2009-06-25 | Alpharma Pharmaceuticals, Llc. | Pharmaceutical composition |
| US20080233197A1 (en) * | 2006-06-19 | 2008-09-25 | Francis Joseph Matthews | Pharmaceutical compositions |
| US8846104B2 (en) | 2006-06-19 | 2014-09-30 | Alpharma Pharmaceuticals Llc | Pharmaceutical compositions for the deterrence and/or prevention of abuse |
| US8877247B2 (en) | 2006-06-19 | 2014-11-04 | Alpharma Pharmaceuticals Llc | Abuse-deterrent multi-layer pharmaceutical composition comprising an opioid antagonist and an opioid agonist |
| US20100266645A1 (en) * | 2007-12-17 | 2010-10-21 | Alfred Liang | Pharmaceutical compositions |
| US20100152221A1 (en) * | 2007-12-17 | 2010-06-17 | Alpharma Pharmaceuticals, Llc | Pharmaceutical composition |
| US8623418B2 (en) | 2007-12-17 | 2014-01-07 | Alpharma Pharmaceuticals Llc | Pharmaceutical composition |
| US20100151014A1 (en) * | 2008-12-16 | 2010-06-17 | Alpharma Pharmaceuticals, Llc | Pharmaceutical composition |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4971079A (en) | Pharmaceutical preparation possessing antinicotine effect and method of producing same in a gum carrier | |
| US3071509A (en) | N-alkyl-nornicotine:nicotine antagonist | |
| US2892753A (en) | Central nervous system stimulant | |
| JP3210945B2 (en) | Smoking alternatives | |
| JP2009240334A (en) | Tobacco product with vitamin e | |
| EA002711B1 (en) | Tobacco products with vitamin e | |
| JPS58134031A (en) | Dihydrocyclosporin d for treating multiple screlosis | |
| KR20010005642A (en) | Antitussive compositions | |
| McNair et al. | Effects of nicotine on weight change and food consumption in rats | |
| US2981641A (en) | Tobacco products | |
| JPS6058209B2 (en) | β,γ-dihydropolyprenyl alcohol and antihypertensive agents consisting of it | |
| EP0629400A1 (en) | Idebenone compositions for treating Alzheimer's disease | |
| Kennedy et al. | The bronchodilator action of khellin | |
| JP2872695B2 (en) | Nephritis treatment | |
| JP2014114253A (en) | Analgesic antiinflammatory composition containing crude drug | |
| US3622676A (en) | Smoking suppression | |
| JPH01197435A (en) | Plaster substituting smoking | |
| US4215117A (en) | Stable pharmaceutical formulations | |
| Sachs et al. | The nicotine withdrawal syndrome: Nicotine absence or caffeine excess? | |
| Sridharan et al. | Effect of various regimens of chronic and acute nicotine exposure on myocardial infarct size in the dog | |
| US3108041A (en) | Antitussive compositions | |
| Eisinger | Nicotine and addiction to cigarettes. | |
| JPS5953884B2 (en) | pharmaceutical composition | |
| KR100332840B1 (en) | The Antismoking Aid containing an Artemisia | |
| JPH01131114A (en) | Remedy for cardiac disease |