US3108106A - Narcqtine camphosulfonate - Google Patents
Narcqtine camphosulfonate Download PDFInfo
- Publication number
- US3108106A US3108106A US3108106DA US3108106A US 3108106 A US3108106 A US 3108106A US 3108106D A US3108106D A US 3108106DA US 3108106 A US3108106 A US 3108106A
- Authority
- US
- United States
- Prior art keywords
- camphosulfonate
- narcotine
- narcqtine
- chronic
- patients
- 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
- XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- AKNNEGZIBPJZJG-MSOLQXFVSA-N Noscapine Chemical compound CN1CCC2=CC=3OCOC=3C(OC)=C2[C@@H]1[C@@H]1C2=CC=C(OC)C(OC)=C2C(=O)O1 AKNNEGZIBPJZJG-MSOLQXFVSA-N 0.000 description 18
- 229930014621 narcotine Natural products 0.000 description 16
- 230000001684 chronic Effects 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 206010011224 Cough Diseases 0.000 description 6
- 208000009856 Lung Disease Diseases 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 208000006673 Asthma Diseases 0.000 description 4
- 206010036790 Productive cough Diseases 0.000 description 4
- 108060007338 SDHAF4 Proteins 0.000 description 4
- 230000001154 acute Effects 0.000 description 4
- 239000007891 compressed tablet Substances 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 4
- 201000010001 silicosis Diseases 0.000 description 4
- 235000020357 syrup Nutrition 0.000 description 4
- 206010003598 Atelectasis Diseases 0.000 description 2
- 210000004369 Blood Anatomy 0.000 description 2
- 206010064913 Bronchial disease Diseases 0.000 description 2
- 210000001736 Capillaries Anatomy 0.000 description 2
- 229940102223 Injectable Solution Drugs 0.000 description 2
- 241001288024 Lagascea mollis Species 0.000 description 2
- 210000004072 Lung Anatomy 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 235000011158 Prunus mume Nutrition 0.000 description 2
- 240000002546 Prunus mume Species 0.000 description 2
- 208000007123 Pulmonary Atelectasis Diseases 0.000 description 2
- 230000003555 analeptic Effects 0.000 description 2
- 239000002269 analeptic agent Substances 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000003182 bronchodilatating Effects 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 230000000271 cardiovascular Effects 0.000 description 2
- 230000000875 corresponding Effects 0.000 description 2
- 230000001079 digestive Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000002349 favourable Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 230000003902 lesions Effects 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 230000000926 neurological Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000000241 respiratory Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 230000002048 spasmolytic Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 230000001225 therapeutic Effects 0.000 description 2
- 201000008827 tuberculosis Diseases 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
Definitions
- This invention is also concerned with a method of preparing a well-defined narcotine salt of which the solubility in water is such as to permit its use in therapeutics in the form of injectable solution as well as in pharmaceutic form for oral administration.
- Narcotine camphosulfonate is advantageous in that it combines the analeptic respiratory and cardiovascular properties of camphousulfonic acid with the spasmolytic and bronchodilating action of narcotine.
- PROPERTIES White needles completely soluble in water at soluble in methanol and ethanol. scarcely soluble in ethyl acetate but insoluble in purified ether.
- narcotine camphosulfonate according to this invention was administered in the form of compressed tablets 3,198,165 Patented Oct. 22, 1963 to patients suffering from various forms of acute or chronic pneumopathy with more or less pronounced coughing, this symptom being attended by mucous or muco-purulent expectoration.
- Acute Diseases (2) Chronic Diseases 6 chronic bronchites, some of which being secondary to a stabilized tuberculosis.
- TOLERANCE The product is always well tolerated and does not produce digestive, cutaneous, neurological or blood troubles.
- the product was administered in quantities ranging from 50 to 200 milligrams, that is, 1 to 4 tablets daily taken by fractions; actually, it can be administered in the form of compressed tablets containing 50 mg. of the product, with the usual excipients, or in the form of suppositories containing 50 mg. of the product, or in the form of sirup containing 100 mg. of the product in 250 cc. of flavored sugar sirup.
- the average dose adopted was 100 to mg. daily, and one patient was a definite success with only 50 mg.
- the four failures were all chronic patients of which the diseases had developed during several years; they were one bronchitic, one intricated asthma, one silicosis diagnosed 18 months before with a considerable nodular and emphysematous lesion and a lung cancer with abscessed atelectasis.
- the method of preparing narcotine camphosulfonate which comprises the steps of adding (l) narcotine base by small fractions to a solution of pure camphosulfonic acid in ethanol, completing the dissolution by heating to 40 to 50 C., filtering and evaporating to dryness in vacuo, dissolving the amorphous residue in ethyl acetate, allowing the camphosulfonate crystals to develop, washing these crystals and drying same in vacuo.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
United States Patent 3,108,106 NARCOTINE CAMPHOSULFONATE Jacques Maillard, Paris, France, assignor to Societe dilxploitation des Laboratoires Jacques Logeais, Issy-les- Moulineaux, France No Drawing. Filed July 29, 1960, Ser. No. 46,088 Claims priority, application Belgium July 30, 1959 1 Claim. ((11. 260-285) It is the object of the present invention to provide, by way of novel industrial product, a new salt of (l) narcotine, that is, (dl-) camphosulfonate, corresponding to the formula:
=0 & -CH3 I OCH:
This invention is also concerned with a method of preparing a well-defined narcotine salt of which the solubility in water is such as to permit its use in therapeutics in the form of injectable solution as well as in pharmaceutic form for oral administration.
Narcotine camphosulfonate is advantageous in that it combines the analeptic respiratory and cardiovascular properties of camphousulfonic acid with the spasmolytic and bronchodilating action of narcotine.
MODE or PREPARATION 8.26 grams (.02 M) of (l-) narcotine base are added by small fractions to a solution consisting of 4.64 grams (.02 M) of pure (dl-) camphosulfonic acid in 100 cc. of 96-degree ethanol. The dissolution is completed by heating a few minutes at 40 to 50 C.
The filtered solution is then evaporated to dryness in vacuo; the amorphous residue (13 grams) is redissolved in the cold in 100 cc. of ethyl acetate. The crystals are left overnight at 0 C. and subsequently washed firstly with ethyl acetate and then with purified ether, and finally dried in vacuo.
Weight: 11 grams; yield: 85%.
PROPERTIES White needles completely soluble in water at soluble in methanol and ethanol. scarcely soluble in ethyl acetate but insoluble in purified ether.
M.P. (capillary tube)=1*88 to 191 C.
At 33 C., a (rotatory power)=+32 7 (at a concentration c.=4.56% in water).
Loss of weight at 110=.16%.
Percent of camphosulfonic acid: 36.65
(theoret,=35.97%) (acidimetric proportion) C=59.38-59.37 (theoret.=59.51%). H=6.01-5.96 (theoret.=6.05%).
The narcotine camphosulfonate according to this invention was administered in the form of compressed tablets 3,198,165 Patented Oct. 22, 1963 to patients suffering from various forms of acute or chronic pneumopathy with more or less pronounced coughing, this symptom being attended by mucous or muco-purulent expectoration.
All the patients were males and aged from 25 to 67. Various types of pneumopathies observed:
(1) Acute Diseases (2) Chronic Diseases 6 chronic bronchites, some of which being secondary to a stabilized tuberculosis.
2 evolutive pleuro-pulmonar tuberculoses.
5 cancers of the lungs.
2 silicoses (pneumonokonioses).
l asthma.
It is worth noting the usual difliculty of treating functional troubles in these chronic patients who have been coughing for years.
TOLERANCE The product is always well tolerated and does not produce digestive, cutaneous, neurological or blood troubles.
In three cases the patients noted themselves, from the very second day of the treatment, a considerable increase in the expectoration (50 to cc. daily).
RESULTS The product was administered in quantities ranging from 50 to 200 milligrams, that is, 1 to 4 tablets daily taken by fractions; actually, it can be administered in the form of compressed tablets containing 50 mg. of the product, with the usual excipients, or in the form of suppositories containing 50 mg. of the product, or in the form of sirup containing 100 mg. of the product in 250 cc. of flavored sugar sirup.
The improvement was observed the most in all the favorable cases.
In 17 patients the cough was soothed; these were the five cases of acuate pneumopathies indicated hereinabove, and twelve cases of chronic bronchopathies.
The average dose adopted was 100 to mg. daily, and one patient was a definite success with only 50 mg.
The four failures were all chronic patients of which the diseases had developed during several years; they were one bronchitic, one intricated asthma, one silicosis diagnosed 18 months before with a considerable nodular and emphysematous lesion and a lung cancer with abscessed atelectasis.
The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:
The method of preparing narcotine camphosulfonate which comprises the steps of adding (l) narcotine base by small fractions to a solution of pure camphosulfonic acid in ethanol, completing the dissolution by heating to 40 to 50 C., filtering and evaporating to dryness in vacuo, dissolving the amorphous residue in ethyl acetate, allowing the camphosulfonate crystals to develop, washing these crystals and drying same in vacuo.
within 48 hours at (References on foliowing page) References Cited in the file of this patent (1911), citing Perkin et a1., Pros. Chem. 500., volume 26,
UNITED STATES PATENTS page; 131'. 1 Ab t t 1 37 6407 (1943) nemica s rac s, vo ume page 215451094 al 1951 citing Mercier et 211., J. Pharm. Chem. 9 1, 287-92 OTHER REFERENCES 5 1940 Chemical Abstracts (I), Decennial Index, volumes 1- Karrer Organic Chemistry 2nd edition, Pages 92402 10, pages 372526 (1907-1916), Subject Index.
Chcmical Abstracts II, volume 5, pages 864-865 MifZa 6181-, Nature, Volume 166, P g 271-2
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3108106A true US3108106A (en) | 1963-10-22 |
Family
ID=3452164
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US3108106D Expired - Lifetime US3108106A (en) | Narcqtine camphosulfonate |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US3108106A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4307099A (en) * | 1980-06-25 | 1981-12-22 | E. R. Squibb & Sons, Inc. | Reaction products of pyrazolo[1,5-c]quinazoline derivatives and proline derivatives and methods for reducing blood pressure while inhibiting allergic reactions with them |
| US6376516B1 (en) | 1997-08-19 | 2002-04-23 | Emory University | Noscapine and noscapine derivatives, useful as anticancer agents |
| US6673814B2 (en) | 1997-08-19 | 2004-01-06 | Emory University | Delivery systems and methods for noscapine and noscapine derivatives, useful as anticancer agents |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2545094A (en) * | 1950-01-21 | 1951-03-13 | Parke Davis & Co | Acylated amino diols |
-
0
- US US3108106D patent/US3108106A/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2545094A (en) * | 1950-01-21 | 1951-03-13 | Parke Davis & Co | Acylated amino diols |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4307099A (en) * | 1980-06-25 | 1981-12-22 | E. R. Squibb & Sons, Inc. | Reaction products of pyrazolo[1,5-c]quinazoline derivatives and proline derivatives and methods for reducing blood pressure while inhibiting allergic reactions with them |
| US6376516B1 (en) | 1997-08-19 | 2002-04-23 | Emory University | Noscapine and noscapine derivatives, useful as anticancer agents |
| US6673814B2 (en) | 1997-08-19 | 2004-01-06 | Emory University | Delivery systems and methods for noscapine and noscapine derivatives, useful as anticancer agents |
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