IL46461A - Process for the manufacture of tobacco compositions - Google Patents

Abstract

1484663 Tobacco composition F HOFFMANN-LAROCHE & CO AG 14 Feb 1975 [15 Feb 1974] 6275/75 Heading A2C To reduce the nitrogen dioxide content in tobacco smoke, tobacco is treated with either an equimolar mixture of ascorbic acid and a salt thereof, or an equimolar mixture of erythorbic (isoascorbic) acid and a salt thereof or a mixture of the two. Preferably the tobacco contains between 0.1 and 10% by weight of the acid/salt mixture. The preferred salt is the sodium salt. [GB1484663A]

Description

Process for the manufacture of a tobacco composition pao nai yn -nxv T^ nn SPARASfflELCfc A»G G. 44452 4226/65 The present invention is concerned ' with novel compositions comprising tobacco and, dispersed therein, a substance selected from the group consisting of an about equimolar mixture of ascorbic acid and a pharmaceutically acceptable salt thereof, an about equimolar mixture of erythorbic acid and a pharmaceutically acceptable salt thereof 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 those nitrogen oxides 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 through 1000 ppm.

In addition to the irritating and toxic properties of % 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 unturned tobacco to form nitrosamines . It is reported in the lite-rature that up to 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. 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 literature. Thus, for example, the substantial depletion of vitamin C in the body, caused by smoking, is known and some experts recommed the ingestion of large amounts of of what is 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 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 presen- ce 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 subBtance 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 or coated on the device or the tobacco, are stated as being progressively volatilized by the heat of combustion and are 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 content of tobacco smoke and thus to increase the physiological availability of ascorbic acid into the lung.

The stated object of the device disclosed and i claimed in these references is to increase the tolerance of the smoker to the toxic products (nicotine) in the smoke. The teachings of these references, 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 inve- 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 a substance selected from the group consisting of an about equimolar mixture of ascorbic acid and a pharmaceutically acceptable salt thereof, an about equimolar mixture of erythorbic acid and a pharmaceutically acceptable salt thereof and mixtures thereof. Further, where tobacco is treated with these substances in accordance with the invention, the reduction 46461/2 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 un-combusted tobacco. Thus the effects achieved according to the invention are most important, as nitrogen dioxide is the moat toxic and irritating of the nitrogen oxides normally preeent in the smoke and at least one nitrosamine, i.e.

N-dimethylnitrosamine, 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 effectiveamount of a substance selected from the group consisting of an about equimolar mixture of ascorbic acid and a pharmaceutically acceptable salt thereof, an about equimolar mixture of erythorbic acid and a pharmaceutically acceptable salt thereof and mixtures thereof .

The amount of such substances to be utilized in accor-dance 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 with any amount of the substances named herein will cause some reduction 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 about 10% by weight of the tobacco on a dry basis. In a more 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 of substances mentioned above. 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 threee 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 the substances to be dispersed in the tobacco 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-called "trapping" of the nitrogen dioxide, in addition to the lungs, acts to competitively inhibit the formation of carcinogenic nitrosamines by reaction of nitrogen dioxide with amines in the unburned tobacco. In one series of tests, it has been demonstrated that smoke from cigarettes prepared from com-positions in accordance with the present invention and comprising a mixture of about 12 mg of equal parts ascorbic acid and sodium ascorbate per cigarette, contains about one-third of the nitrogen dioxide content of untreated controls utilizing a slow puff test and about one-half the nitrogen dioxide con-tent of controls using a fast puff test. It has also been demonstrated, using cigarettes containing approximately 25 mg of an equimolar mixture of ascorbic acid and sodium ascorbate per cigarette, that essentially none of said substances is taken into the body with the smoke.

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 salts, as well as methods of preventing or retarding degradation thereof, are well known in the art of food and pharmaceutical formulating. It is - tion 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 po-L hydric alcohol or the like.

In accordance with the present invention, ascorbic acid, erythorbic acid and their pharmaceutical salts may be utilized in approximately equimolar proportions, but equimolar proportions are preferred. By pharmaceutically acceptable salts is meant those salts of ascorbic acid and erythorbic acid with pharmaceutically acceptable inorganic bases such as, for exam-pie, the sodium salt, the potassium salt, the calcium salt and the like.

The following examples are given to further illustrate the invention.

Example 1 Tobacco removed from commercially prepared cigarettes was treated in the following manner. An aqueous solution containing 75 mg/ml of an equimolar mixture of ascorbic acid and sodium ascorbate was sprayed onto the tobacco. The amount of said solution applied was approximately 157° by weight based on the dry weight of the tobacco. The tobacco was then dried utilizing a stream of nitrogen gas until the weight gain of the treated tobacco was equal to the amount of the ascorbic acid/ sodium ascorbate mixture deposited, i.e. all the applied water had been removed. The tobacco thus-treated was then weighed to give the same proportionate fill as that previously recorded for the commercial cigarettes and formed into ' cigarettes .

Cigarettes prepared in this manner were approximately 7 cm in length and contained 0.83 grams of tobacco per cigarette.

A total of 15 grams of an equimolar mixture of ascorbic acid and sodium ascorbate was pulverized to a fine powder utilizing a mortar and pestle . A sufficient quantity of this mixture was added to the tobacco taken from commercially prepa-red cigarettes to represent 3·75 by weight thereof. The ascorbic acid mixture was added in small portions while rotating the mixing vessel thereby assuring homogeneous distribution. Cigarettes were prepared from this tobacco. removed from commercial cigarettes which had been sprayed with distilled water and dried utilizing nitrogen gas until the initial weight of the tobacco was achieved.

Example 2 Cigarettes were prepared in accordance with the method of example 1, utilizing a sufficient amount of an aqueous solution of an equimolar mixture of ascorbic acid and sodium as-corbate so that each cigarette contained a total of 25 mg. The cigarettes of the mixture were smoked in an apparatus similar to that described by Millar et al., Cancer Research, Vol. 28, pages 968-971 (1968). The collected tars from treated and untreated control cigarettes were individually analyzed for ascorbic acid content . The analytical procedure utilized was that outlined by Roe et al. "Methods of vitamin assay" third edition, pages 318 ff., Interscience (1966). The results of this analysis are given in the following table.

Table I ^ig. Ascorbic Acid in Sample tars from 20 cigarettes Untreated cigarettes 20 Untreated cigarettes + 100 >ug. added for analysis purposes 117 Treated cigarettes 27 The results of the foregoing analysis indicate that a- maximum of 1 part in 10,000 of the ascorbic acid content of the tobacco was carried over into the tar fraction of the smoke . The value of 27 micrograms per 20 cigarettes lies near the limit of detection for ascorbic acid under the analytical conditions utilized. It is therefore a reasonable assumption that more sensitive methods of testing may reveal that the value of ascorbic acid in the tar may be even lower than shown in the above table. The results given in the above Table can be inter- preted as indicating that essentially no ascorbic acid is transferred from the treated tobacco to the tar during the smoking process.

Example 3 Whatman No. 1 filter paper was cut into discs having a diameter of 13 mm. These discs were treated with an aqueous ' solution of equimolar concentrations of ascorbic acid and sodium ascorbate in accordance with the procedure of Example 1, so that the concentration thereof in each disc was 0.6 mg of the combination. Discs treated with distilled water served as controls. Such discs were individually mounted in an adapter 3 3 which was fitted onto a 5 cnr gas tight syringe. A 2 cm sample of a gaseous mixture containing 10 parts per million nitrogen dioxide was passed twice through each paper disc.

The nitrogen dioxide content of this Bample was analyzed by the method of Greiss-Saltzman, "Methods of Air Sampling and Analysis" American Public Health Assoc., page 333f (1972).

The results of this experiment show that the nitrogen dioxide content of the sample passed through the untreated controlled disc was approximately equal to that passed through the syringe with no disc at all and that the content of the sample passed through the treated disc was, on the average, approximately 10 of the original content of the sample .

Example 4 Cigarettes treated with 12 mg/cigarette of equimolar mixtures of ascorbic acid/sodium ascorbate and erythorbic acid/ sodium erythorbate , in accordance with the aqueous solution method of Example l,were smoked in the following manner. A 50 ml syringe was utilized to draw smoke from a cigarette attached to an adaptor. The smoke was immediately deposited in a collection vessel containing Greiss-Saltzmann reagent. The smoke of treated and untreated (control) cigarettes was then analyzed for nitrogen dioxide content. A standardized fast draw and slow draw technique was utilized to smoke the cigarettes. The definitions of these techniques are set forth in Table I.

TABLE I Parameter Past Draw Slow Draw Puff volume 35 cur 35 cm5 Puff duration 2 sec 6 sec Puff frequency l/min l/min Average butt length 23 mm 23 mm The results of the tests are set forth in Table II, wherein the amount of nitrogen dioxide in the smoke is given as a percent of control.

TABIE II Slow Draw Fast Draw Ascorbic Acid & Sodium Ascorbate 38 58 Erythorbic Acid & Sodium Erythorbate 35 52 Example 5 Cigarettes prepared in accordance with Example 1 utilizing a sufficient amount of a powder mixture of equimolar amounts of ascorbic acid and sodium ascorbate so that each cigarette contained 35 mg of the mixture were smoked on an apparatus described by Millar et al. in Cancer Research, Vol. 28, pages 968-971, May, 1968. The tars from treated cigarettes and controls were analyzed for N-nitrosamine content according to the method of Rhoades et al. described in the Journal of the National Cancer Institute, "Vol. 48, pages 1841-1843 and 1845-1847 (1972). The results of this test show that the content of dimethyl-N-nitrosamine of the cigarette smoke in controls was reduced by approximately 70 in the treated cigarettes.

Claims (16)

Claims

1. Process for the manufacture of compositions based on tobacco, characterised in that a substance selected from the group consisting of an about equimolar mixture of ascorbic acid and a pharmaceuticall acceptable salt thereof, an about equimolar mixture of erythorbic acid and a pharmaceutically acceptable salt thereof and mixtures thereof is dispersed throughout the tobacco.

2. Process according to claim 1, characterized in that the ascorbic acid and a pharmaceutically acceptable salt thereof and the erythorbic acid and a pharmaceutically acceptable salt thereof, respectively, are used in equimolar proportions.

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

4. Process according to claim 1, 2 or 3> characterised in that the substance is used in an amount of from about 0,1 by weight to about 10$ by weight of the tobacco.

5. Process according to claim 4, characterised in that the substance is used in an amount of from about 1% by weight to about o by weight of the tobacco. 46461/2

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

7. Compositions comprising tobacco and, dispersed therein, a substance selected from the group consisting of an about equimolar mixture of ascorbic acid and a pharmaceutically acceptable Bait thereof, an about equMolar mixture of ery-thorbic acid and a pharmaceutically acceptable salt thereof and mixtures thereof.

8. Compositions according to claim 7, comprising the ascobirc acid and a pharmaceutically acceptable salt thereof and the erythorbic acid and a pharmaceutically acceptable salt thereof, respectively, in equimolar proportions.

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

10. Compositions according to claim 7, 8 or 9, wherein the substance is present in an amount of from about 0,1 by weight to about 10$ by weight of the tobacco.

11. Compositions acoording to claim 10, wherein the substance is present in an amount of from about 1% by weight to about 4$ by weight of the tobacco.

12. 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 a substance selected from the group consisting of an about equimolar mixture of ascorbic acid and a pharmaceutically acceptable salt thereof, an about equimolar mixture of erythorbic acid and a pharmaceutically acceptable salt thereof and mixtures thereof.

13. . A method according to claim 12, wherein the smoke is passes through tobacco having dispersed therein the ascorbic acid and a pharmaceutically acceptable salt thereof and the erythorbic acid and a pharmaceutically acceptable salt thereof, respectively, in equimolar proportions.

14. . A method according to claim 12 or 13, wherein the sodium salt is used as pharmaceutically acceptable salt of ascorbic and erythorbic acid.

15. · A method according to claim 12, 13 or 14, wherein the tobacco contains from about 0,l° by weight to about 10% by weight of the substance.

16. A method according to claim 15, wherein the tobacco contains from about 1% by weight to about 4% by weight of the substance .