IL47666A - Tobacco compositions containing ascorbic or erythorbic acid or their salts their manufacture and their use in lowering nitrogen dioxide content of tobacco smoke - Google Patents

Abstract

1503364 Tobacco composition F HOFFMANN-LA ROCHE & CO AG 16 July 1975 [25 March 1975] 29860/75 Heading A2C Tobacco has dispersed therein salts of ascorbic or erythorbic acids either alone or in admixture with the corresponding acids. In the latter alternative the molar ratio of acid to salt should not exceed 3:1. Specification 1484663 is referred to. [GB1503364A]

Description

47666/2 utmipoK m.xa-ιπη m »Dan pats w msnyn paon fEj ipann nxiann-n ¾ maan nnin Tobacco compositions containing ascorbic or erythorbic acid or their salts, their manufacture and their use in lowering nitrogen dioxide content of tobaeco smoke SPARAHEDICA A.G..

C/ 45365 4226/65-1 The present invention is concerned with novel compositions comprising tobacco and, dispersed therein, one or more substances selected from the group consisting of pharmaceutically acceptable salts of ascorbic acid or eryth^ rbic acid or mixtures of said salts with their respective acids, wherein the molar ratio of acid to salt does not exceed about 3:1, with the acception of about equimolar mixtures of ascorbic acid or erythorbic acid with their respective pharmaceutically acceptable salts and mixtures thereof.

The invention further relates to the preparation of the above compositions, as well as to their use in the reduction of the nitrogen dioxide content in tobacco smoke.

The toxic effects of tobacco smoke, which had been suspect for many years, have now been firmly established by an overwhelming quantity of scientific evidence. Among the various harmful substances which have been shown to be present in tobacco smoke are the various oxides of nitrogen. Of these oxides of nitrogen normally present in tobacco smoke, nitrogen dioxide is the most toxic and most irritating. 'While the views of experts in the field are at a variance, it is estimated that as much as 50% of the nitrogen oxide content of tobacco smoke is nitrogen dioxide. The total nitrogen oxide content of tobacco smoke has been reported to range from about 145 ppm to about 1000 ppm.

In addition to the irritating and toxic properties of nitrogen dioxide per se in tobacco smoke, it has recently been shown that nitrogen dioxide and certain other oxides of nitrogen can form nitrosating intermediates, which in turn can react with susceptible organic amines in the unburned tobacco to from nitrosamines . It is reported in the literaturethat up to about 140 ng of N-dimethyl-nitrosamine can be present in the smoke of one cigarette. The nitrosamine content in the smoke from different types of tobacco can vary from practically none up to 140 ng/cigarette . The amount of nitrosamines present in the smoke of a given type of tobacco is influenced by a number of variables such as, for example, the amount of nitrogen-containing fertilizer used in growing the tobacco plants. N-dimethylnitrosamine is a highly toxic substance and is recognized as a potent carcinogen in animal experiments, even at low levels of administration. It is therefore readily apparent that means to effectively reduce the nitrogen dioxide content of tobacco smoke would be of considerable benefit to those individuals who smoke tobacco in some form, since reduction in the toxic, irritating nitrogen dioxide also results in a reduction in carcinogenic nitrosamines. Such a means is provided in accordance with the present invention.

The effect of smoking on the ascorbic acid content of the human body, as well as the benefit heavy smokers might possibly derive from ingestion of large amounts of ascorbic acid have been the subject of a number of reports in the literatur« Thus, for example the substantial depletion of vitamin C in the body, caused by smoking, is known and some experts rec nd the in estion of lar e amounts of ascorbic acid b termed "smoker's scurvy". This depletion of vitamin C in the body of heavy smokers has been substantiated by numerous others working in the field. These workers also have recommended that heavy smokers consume an abundance of vitamin C to prevent development of a deficiency thereof. These findings and recommendations are directed to the alleviation of one of the harmful effects of heavy smoking in the body, but do not effect the prevention of the formation of nitrosamines or oxides of nitrogen and their presence in the inhaled tobacco smoke .

French Patent No. 932,560 discloses a device such as cigarette paper, straw-like structure, holder, mouthpiece or similar article with which the smoke comes in contact as it is being inhaled. The device, which may or may not be burned with tobacco, is of a fibrous nature and is either impregnated or covered with a "metabolite" which is stated as being a substance which can interact with normal cell metabolism such as, for example, vitamins including ascorbic acid, enzymes, co-enzymes and the like. French Patent No. 932,561 discloses treatment of tobacco with such "metabolites". The stated object in having such substances impregnated in or coated on such a device or the tobacco, is that these metabolites are thereby mixed with the smoke in appreciable quantities thereby causing them to be inhaled with the smoke. The patents state that the presence of one or more of these metabolites in appreciable quantities in the smoke increases the tolerance of the user to "the toxic products (nicotine) " contained in the smoke. In operation, the metabolites contained in or 47666/2 mixed with and consumed with the smoke.

British Patent No. 1.204.018 describes the use of, inter alia , ascorbic acid in filters and other portions of smoking devices to increase the ascorbic acid conten to tobacco smoke and thus to increase the physiological availability of ascorbic acid into the lung.

The stated object of the'. methods disclosed and claimed these French patents is to increase the tolerance of the smoker to the toxic products (nicotine) in the smoke. The teachings of these French patents, therefore, parallel those concerning the systemic administration of ascorbic acid to offset the deleterious effects of smoking, in that all are concerned with attempting to minimize such effects after the smoke has been inhaled.

It has been found, in accordance with the present inven tion, that the amounts of at least one toxic substance, i.e. nitrogen dioxide, which is normally consumed with tobacco smoke can be sharply reduced before the smoke is inhaled.

The present invention is based on the discovery that the •nitrogen dioxide content of tobacco smoke is markedly reduced as it is being drawn · through uncombusted tobacco having dispersed therein an effective amount of one or more members of the group consisting of pharmaceutically acceptable salt of ascorbic acid or erythorbic acid, or mixtures of such salts with their respective acids.., wherein the molar ratio of acid to salt does hot exceed about 3:1, with the exception of about equimolar mixtures of ascorbic acid or erythorbic acid with their respective pharmaceutically acceptable salts and mixtures thereof. Further, where tobacco is treated with one or more substances in accordance with the invention, the redu-tion in nitrogen dioxide content of the smoke in turn causes a reduction in the formation of nitrosamines which can be inhaled with the smoke. The formation of nitrosamines has been shown to occur as a result of reaction of nitrogen dioxide in the smoke with susceptible organic amines in the uncombusted tobacco. Thus, the effects achieved according to the invention are most important, as nitrogen dioxide is recognized as being the most toxic and irritating of the nitrogen oxides normally present in tobacco smoke and at leaser one nitrosamine^ produced therefrom, i.e. N-dimethyl-nitrosamine, is a recognized carcinogen.

The compositions of the present invention can be prepared according to methods known per se, e.g. by dispersing throughout the tobacco an effective amount of a substance selected from the group consisting of pharmaceutically acceptable salts of ascorbic acid or erythorbic acid or mixtures of said salts with their respective acids, wherein the molar ratio of acid to salt does not exceed about 3:1, with the exception of about equimolar mixtures of ascorbic acid or erythorbic acid with their respective pharmaceutically acceptable salts and mixtures thereof.

The amount of such substances to be utilized in accordance with the invention will vary over a wide range depending on such criteria as the "tar" content of the tobacco and, more particularly, on the organic nitrogen content thereof.

Generally, treatment of tobacco or other smoking material with any amount of the substances named herein will cause some reduc-tion in the nitrogen dioxide content of the smoke. As a practical matter, it has been found that an effective amount of such substances, utilized to treat tobacco in the practice of the invention, constitutes from about 0.1% by weight to preferred embodiment, tobacco is treated with from about 1% by weight to about 4% by weight, on a dry basis, of one or more members of the group consisting of pharmaceutically acceptable salts of ascorbic acid or erythorbic acid or mixtures of such salts with their respective acids, wherein the molar ratio of acid to salt does not exceed about 3:1. As the average cigarette contains approximately one gram of tobacco, the above preferred percent range represents from about 10 mg to about 40 mg of the substances of the invention per cigarette.

It is recognized that the tar and impurity content of tobacco smoke is materially increased as the cigarette, cigar, etc. is consumed. Therefore, it is to be understood that treatment of tobacco in accordance with the present invention may not have an appreciable effect on the last two or three inhalations of smoke. Thus, in order to achieve the full effect of the method of the invention, smoking of a cigarette, cigar, etc. containing treated tobacco should be discontinued while a reasonable amount remains unburned. It has been demonstrated by taste tests on human volunteers that the amount of pharmaceutically acceptable salts of ascorbic acid or erythorbic acid or the herein specified mixtures of such salts and their respective acids, which is utilized to treat tobacco in accordance with the present invention, has no detectable adverse effect on the taste of the smoke.

It is hypothesized that the substances utilized to treat tobacco in accordance with the present invention, react with nitrogen dioxide to form nitric oxide and water. This so- removing a substantial amount thereof from the smoke taken into the lungs, acts to competitively inhibit the formation of carcinogenic nitrosamines by reaction of nitrogen dioxide with amines in the unburned tobacco.

The method of incorporating the substances of the present invention into the tobacco is not critical to the invention. Any method commonly recognized in the tobacco arts for incorporating additives into tobacco, which results in a substantially uniform dispersion of the additive may be utilized, so long as the conditions are not such as would adversely affect the active compounds used in the practice of this invention, i.e., excessive heat and prolonged exposure to moisture. The stability characteristics of ascorbic and erythorbic acid and their pharmaceutically acceptable salts, as well as methods of preventing or retarding degradation thereof are well known in the arts of food and pharmaceutical formulating. It is preferred to add the active compounds of the present invention to tobacco by blending therewith in the dry state or by applying them as a solution or suspension in a suitable solvent such as water, ethanol, a polyhydric alcohol or the like.

In accordance with the present invention, pharmaceutically acceptable salts of ascorbic acid and/or eryt &horbic acid may be utilized individually or in combination with their respective acids, wherein the molar ratio of acid to salt does not exceed about 3:1, with the exception of about equimolar mixtures of ascorbic or erythorbic acid with their respective pharmaceutically acceptable salts and mixtures the Tables in the examples which follow, pharmaceutically acceptable salts of ascorbic acid or erythorbic acid or the combinations thereof with their respective acids defined herein are highly efficacious and are considered to be unexpectedly efficacious in comparison with pure acid utilized in tobacco in the manner of the invention.

Combinations of ascorbic acid or erythorbic acid with their respective pharmaceutically acceptable salts in a molar ratio of about 3:1 acid to salt have, as a 0.1 N aqueous solution, a pH of about 4. Since increasing the ratio of salt in such combinations will raise the pH, a pH of about 4 or above for a 0.1 N aqueous solution of a given combination of ascorbic acid or erythorbic acid and their respective pharmaceutically acceptable salts, is considered to be an indication of the efficacy thereof in the practice of the invention, notwithstanding the fact that tobacco treated in accordance with the invention is in a dry state.

The following example is given to further illustrate the invention.

Example The following experiment was conducted to determine the relative effectiveness of sodium ascorbate and three molar ratios thereof with ascorbic acid, i.e. 1:3, 1:1 and 3:1 in comparison with ascorbic acid alone and distilled water (control) .

Sealed 25 cm^ vials containing distilled water (controls) and solutions containing 50 mg of sodium ascorbate, ascorbic acid and combinations of 1:3, 1:1 and 3:1 molar ratios thereof respectively, were exposed to nitrogen dioxide gas, which was injected via a gas tight syringe. The solutions were exposed to fixed quantities of nitrogen dioxide gas, i.e. 15, 39 or 90 μg for 5 seconds. Five seconds was selected for the residence time of nitrogen dioxide in the vial since it represents average normal puff duration in smoking (2-6 seconds) . The quantities of nitrogen dioxide utilized were selected to represent an approximation of the range of O2 formed in the smoking of one cigarette (a good average value being approximately 75 Mg per cigarette) .

After a five second exposure, the nitrogen dioxide was removed from the vial and injected into a second vial for analysis by the method of Greiss-Saltzman, "Methods of Air Sampling and Analysis" American Public Health Association, page 333, (1972) . The results of this experiment are reported in Table I. In each instance, the distilled water controls absorbed some nitrogen dioxide. The values given for the various concentrations of ascorbic acid (AA) , sodium ascor corrected by substracting therefrom the value for control.

Table I Composition Amount of NO2 Introduced/ in Solution Percent Destroyed 15 iq 39 g 90 .g 0.25 ml 8 18 14 AA 13 20 0 AA+SA (3:1 molar ratio) 31 55 19 AA+SA (1:1 molar ratio) 34 38 44 AA+SA (1:3 molar ratio) 43 48 41 SA 48 57 42 0.5 ml 8 16 16 AA 13 10 3 AA+SA (3:1 molar ratio) 26 39 32 AA+SA (1:1 molar ratio) 70 53 54 AA+SA (1:3 molar ratio) 60 42 47 SA 40 18 51 1.0 ml 6 17 14 AA 16 11 5 AA+SA (3:1 molar ratio) 22 31 37 AA+SA (1:1 molar ratio) 39 44 58 AA+SA (1:3 molar ratio) 56 64 25 SA 55 49 54 2.0 ml 8 15 18 AA 22 15 11 AA+SA (3:1 molar ratio) 44 24 41 AA+SA (1:1 molar ratio) 71 37 63 AA+SA (1:3 molar ratio) 86 36 37 SA 58 45 55 A similar experiment conducted with 39 g of nitrogen dioxide and 1.0 ml of solution with sodium ery^horbate (SE) and erythorbic acid (EA) gave the following results.

Composition of Solution Percent NO, Removed EA 0 EA+SE (3:1 molar ratio) 44 EA+SE (1:1 molar ratio) 58 EA+SE (1:3 molar ratio) 37 SE 54

Claims (14)

Claims

1. Process for the manufacture of compositions based on tobacco, characterized in that one or more substances selected from the group consisting of pharmaceutically acceptable salts of ascorbic acid or ^rythorbic acid or mixtures of said salts with their respective acids, wherein the molar ratio of acid to salt does not exceed about 3:1, with the exception of about equimolar mixtures of ascorbic acid or erythorbic acid with their respective pharmaceutically acceptable salts and mixtures thereof, are dispersed throughout the tobacco.

2. Process according to claim 1, characterized in that the sodium salt is used as pharmaceutically acceptable salt of ascorbic and erythorbic acid.

3. Process according to claim 1 or 2, characterized in that, the substances are used in an amount of from about 0.1% by weight to about 10% by weight of the tobacco.

4. Process according to claim 1, 2 or 3, characterized in that the substances are used in an amount of from about 1% by weight to about 4% by weight of the tobacco.

5. Process for the manufacture of compositions as hereinbefore particularly described, especially with reference to the foregoing example.

6. Compositions comprising tobacco and, dispersed therein, one or more substances selected from the group consisting of pharmaceutically acceptable salts of ascorbic acid or erythorbic acid or mixtures of said salts with their respective acids, wherein the molar ratio of acid to salt does not exceed about 3:1, with the exception of about equimolar mixtures of ascorbic acid or erythorbic acid with their respective pharmaceutically acceptable salts and mixtures thereof, whenever prepared by the process as claimed in any one of claims 1 to 5, or by an obvious equivalent thereof.

7. Compositions comprising tobacco and, dispersed therein, one or more substances selected from the group consisting of pharmaceutically acceptable salts of ascorbic acid or erythorbic acid or mixtures of said salts with their respective acids, wherein the molar ratio of acid to salt does not exceed about 3:1, with the exception of about equimolar mixtures of ascorbic acid or erythorbic acid with their respective pharmaceutically acceptable salts and mixtures thereof.

8. Compositions according to claim 7, wherein the sodium salt is present as pharmaceutically acceptable salt of ascorbic acid and erythorbic acid.

9. Compositions according to claim 7 or 8, wherein the substances are present in an amount of from about 0.1% by weight to about 10% by weight of the tobacco.

10. Compositions according to claim 7, 8 or 9, wherein the substances are present in an amount of from about 1% by weight to about 4% by weight of the tobacco.

11. A method for the reduction of nitrogen dioxide content in tobacco smoke, which comprises passing said smoke through uncombusted tobacco having dispersed therein an effective amount of one or more substances selected from the group consisting of pharmaceutically acceptable salts of ascorbic acid or erythorbic acid or mixtures of said salts with their respective acids, wherein the molar ratio of acid to salt does not exceed about 3:1, with the exception of about equimolar mixtures of ascorbic acid or erythorbic acid with their respective pharmaceutically acceptable salts and mixtures thereof.

12. A method according to claim 11, wherein the sodium salt is used as pharmaceutically acceptable salt of ascorbic and erythorbic acid.

13. A method according to claim 11 or 12, wherein the tobacco contains from about 0.1% by weight to about 10% by weight of the substances.

14. A method according to claim 11, 12 or 13, wherein the tobacco contains from about 1% by weight to about 4% by weight of the substances.