CN1035763A - Make the method for cigarette - Google Patents

Abstract

This method can reduce risk of smoker's health.According to of the alcohols spraying of the dry again tobacco of also shredding of this law with one or more selections in advance, fashionable when the steam of alcohol by the smoker, can suppress or block at least a nitrosamine and/or their a kind of metabolite in the in-house selectivity of smoker location.After sparging alcoholic solution on the pipe tobacco,, make smoking article more according to a conventional method with its drying.Alcohol is heated effectively when cigarette is lighted and disengages and enter in the flue gas stream of cigarette, thereby causes desired BE in smoker's body.

Description

Make the method for cigarette

The present invention relates to tobacco smoking article and structure thereof, also relate to the method that a kind of smoker of reduction emits health risk, also relate to the method for making cigarette and the cigarette made from these methods.

As everyone knows, especially contain large quantities of potential carcinogenic substances and epicarcinogen in the smog of tobacco in the tobacco.Referring to: " Accounts of Chem.Res. ", S.Hecht etc., 12:92-98 page or leaf (1979); " Cancer Research ", D.Mc Coy etc., 41,2849-2854 page or leaf (1981) (chat in this manual and these papers and other each paper, patent, report and publication all are incorporated in this patent as a reference) with complete form.Some are that tobacco is distinctive in these potential carcinogens and epicarcinogen, that is to say, these carcinogenic substances just are related with the people by tobacco and enter human body.In fact, the nitrosamines in nearly all tobacco product all is carcinogenic.Publication (1978) referring to international cancer research institution: N-nitroso proline and N-nitroso hydroxy-proline " IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans ", the 17th volume, " some N-nitrosamines ", Lyon, the 303-311 page or leaf; The publication of U.S. Department of Health and Human Service (1982): " result that smoking causes health: cancer " be 82-50179 (DHHS(PHS)), Washington, D.C., U.S.Government Printing Office; Hecht, S.S., Castonguay, A., Riverson, A., Mu, B. ﹠amp; Hoffmann, D.(1983) " the distinctive nitrosamines of tobacco: carcinogenicity, metabolism and possible effect in human cancer ", J.Envivon.Sci, Health, C1,1-54 page or leaf.N '-nitrosonornicotine (NNN) be a kind of individually defined thing that is present in tobacco and tobacco smoke mutually in the main peculiar carcinogenic substance of tobacco, also be well-known.Referring to: the N-nitroso compound thing in the environment: " IARC Scientific Publication ", № 9, the 159-165 page or leaf, D.Hoffmann etc. (1975), also can be referring to the research of the reduction of nitroso-amines class in the tobacco, W.J.Chamberlain etc., Tabacco Science 81(1981)." the N-nitroso-derivative of known tobacco plant alkali is as N '-nitrosonornicotine (NNN) and 4-(N-methyl-N-nitroso amino)-1-(3-pyridine radicals-1-butanone (NNK) is powerful environmental carcinogen ".Referring to S.S.Hecht etc., " the distinctive nitrosamines of tobacco: form and in tobacco processing course, form and A is the carcinogenicity of mouse (Strain A Mice) by nicotine " external, J.Natl.Cancer Inst., the 60th volume № 4, in April, 1978, the 819-824 page or leaf.

Other relevant nitrosamines such as N-nitroso nafoxidine (NPYR) is present in the smog of ripe bacon and other finished meat and tobacco and tobacco.Referring to " IARC Science Publication ", D.Harvery etc., 17:313 page or leaf (1978).Therefore, the nitroso amine can be entered in the environment by good several sources.

The experiment of recently carrying out with NNN has confirmed far and away that this compound is a kind of to mammiferous strong carcinogenic substance or precarcinogen.Take NNN by drinking-water and bring out cancer of the esophagus on one's body the F-344 rat.Referring to: Carcinogenesis ", S.Hecht etc., 3:453-456 page or leaf (1982).In addition, take that NNN is also known to bring out canceration at rodentine olfactory organ epithelium, lung and salivary gland.Referring to: " Cancer Research ", W, Waddell etc., 40:3518-3523 page or leaf (1980) also has, and is verified by the radioactive label experiment, has the metabolin of NNN at the position that tumour forms.With ( ¹⁴C) NNN studies at the whole body radio-autograph picture that the male C57BL/6J mouse that grows up carries out on one's body, obtained NNN and metabolite thereof whole body the specific distribution situation in a organized way, disclosing the position that the tumour of position that radioactivity keeps and report in the past forms has wonderful correlation.Referring to " Cancer Research ", W.Waddell etc., 40:3518-3523 page or leaf (1980).

Find with interest that NNN has abnormal selectivity in the induced tumor forming process.More particularly, NNN is a formation at following five position induced tumors typically, i.e. nasal cavity, salivary gland, esophagus, bronchiolar epithelium and liver.Referring to " Cancer Resarch ", the same.Though NNN causes certain process of canceration not clear, evidence suggests, after the reaction of the 'alpha '-hydroxylation of NNN, formed the carcinogenic substance of base portion in vivo.Referring to " Cancer Research ", C.Chen etc., 38:3639-3645 page or leaf (1978); " Cancer Research ", W.Waddell etc., 40:3518-3523(1980).Experiment points out, for example, the esophagus of F-344 mouse, with other organize different, it preferentially in the catalyzing N NN molecule adjacent to the hydroxylating of the alpha-carbon atom of pyridine ring.Referring to: " Carcinogenesis ", S.Hecht. etc., 3:453-456(1982).Like this, NNN and metabolite thereof are detained in the selectivity that tumour preferentially forms the position, can explain the accumulation of molecule and the correlation between the carcinogenic activity satisfactorily.But, ignoring getting in touch strongly between this and tumour incidence that increases day by day, active nitrosamines such as NNN still continues common being present in the environment, particularly is present in the flue gas stream of tobacco.

The amount that some of the recommendations reduce the harmful substance in the flue gas stream that the smoker sucks has been proposed.These suggestions generally can be divided into three classes: the first kind is the method about the pungent that reduces itself, normally by special growth, processing or extraction, by partly or entirely replacing the method for tobacco with tobacco, change the composition of tobacco composition, perhaps by changing the ignition temperature of tobacco.Second class methods be about make smog enter in smoker's the mouth before dilution, for example by using the cigarette paper or the filter paper of high-penetrability, or with the cigarette paper perforation, so that air directly is inhaled in the flue gas stream.The suggestion of the 3rd class has been narrated filter and has been chewed the structure of itself, to reach the height filtering or optionally to remove particle matter.

Though many this class suggestions have realized commercialization respectively or synthetically, when reducing the content of the tar that produces in the cigarette and nicotine and excitor substance, the enjoyment that all is accompanied by the smoker correspondingly reduces at every turn.Even the so-called smokeless cigarette of introducing has also made many analysts and smoker's disappointment recently, because they have changed the happiness and the convention of common smoking.In addition, though many materials have been used as carcinogenic substance and have been isolated, but the tar that produces and a large amount of minimizings of nicotine and a large amount of minimizings of excitor substance fail optionally to reduce the carcinogenic substance of having isolated, these carcinogenic substances because these suggestions optionally or are not effectively isolated.Recent sales data shows, ignore various claiming to be, but the sales volume that has reduced the tobacco product of the tobacco product of tar and nicotine and stimulus content, particularly those commercial being categorized as " ultralow amount tar and nicotine " reduces but with unique content that had not only reduced tar and nicotine and stimulus, but also the tobacco product that kept the method for satisfied taste to produce.With top said consistent, claim that can optionally remove in a large number is the actual defects of whole a certain carcinogenic tobacco product of having isolated basically, is also confirmed by recent data.These data point out, the incidence of disease of cancer on long terms, and decreasing desired when adopting this class tobacco product unlike people is turned one's coat and increased.Though it is very important reducing the material relevant with health of smokers, but many suctions have reduced the smoker of the cigarette of tar and nicotine content to a certain extent have been gone back to and has inhaled the cigarette that higher tar and nicotine content are arranged, thus be good for one's health counter play invalid.Also have, the smoker that some inhale low tar and nicotine content cigarette by the smog of inhaling more cigarette or more in depth sucking these cigarettes, and has compensated the tar and the nicotine that should suck less originally.

In addition, the design of existing cigarette or cigarette filter tip also fails preferably to reduce or any compound of filtering especially any carcinogenic substance.Existing cigarette and cigarette filter tip can not spacer particles material or carcinogenic substances.

According to the known method of another kind, for reducing the generation of harmful smoke composition, tobacco after extracting or handling, homogenizing is laid equal stress on and newly is loaded in the suitable paper mold again, because fragrance is fully reappeared, so this conversion procedures causes the acceptable of these tobacco products significantly to reduce.

Therefore very clear, no matter be the content that reduces tar, nicotine and pungent, still reduce the effort of specific carcinogen content, the stimulus and the minimizing smoker that face for the minimizing smoker make the effect of the risk aspect that goes to bits be subjected to serious restriction because of facing the carcinogen that is found in the flue gas stream.Dissatisfied obtaining to super low loading tar and nicotine cigarette proves this point owing to can not accept very poor taste by the smoker.The conclusion that should further accept is, only by a large amount of constituents that reduce in the flue gas stream, be to be difficult to the carcinogen of having isolated in the flue gas stream is reduced to below the safe concentration, and aspect these carcinogenic substances of having isolated of elimination, then be a kind of defective course of action.

By this, primary and foremost purpose of the present invention provides a kind of new cigarette formation, and it does not have harmful effect, the enjoyment of the smoking that also can not detract, but can reduce some really selectively specifically about healthy worry and risk.

Another object of the present invention provides a kind of new tobacco product, and it does not need the smoker to change his common smoking habit, needn't change the normal procedure of manufacturing, distribution, storage and the sale of tobacco product yet.

Further object of the present invention provides a kind of tobacco product or smoking set, and it suppresses the optionally location of nitrosamines and metabolite thereof in smoker's respiratory tissue in nontoxic mode.

Another object of the present invention provides a kind of material and is added in the tobacco product, and it can reduce the health risks of smoker because of emitting in the flue gas that is exposed to tobacco, and the operation of any variation need not arranged when cigarette is inhaled.

A further object of the invention provides a kind of new cigarette structure, it can block the location that the people of NNN after those suck cigarette smoke cause on one's body, and can make by existing high-speed production method (it is about 1 that per minute is produced, 000-8,000).

The present invention has a purpose to provide a kind of new method again, and it can suppress to locate in the in-house selectivity of smoker (or those people around him) from the nitrosamines of tobacco smoke and metabolite thereof, especially NNN and metabolite thereof.

The present invention has a purpose to provide a kind of new cigarette to smoke smoking set again, it does not reduce any amount of substance that is present in the flue gas stream, do not need to reduce the wherein content of tar, nicotine and stimulus yet, but can reduce the risk that the smoker is emitted aspect healthy really.

The present invention has a purpose to provide a kind of cigarette again, and it contains a kind of additive in cigarette of uniqueness, and this additive is invisible to the naked eye, and does not also change size, shape and the sensation of cigarette, thereby has increased the possibility that this cigarette is sold and smoked.

The present invention has a purpose to provide a kind of method of making cigarette again, and it provides a kind of new cigarette of reducing the risk that they are emitted aspect healthy significantly to the smoker, the enjoyment that has fully kept the cigarette of today to provide to the smoker again.

The present invention has a purpose to provide a kind of improved cigarette formation again, and it can obtain the smoker and approve of fully, and consistent with the modern science viewpoint.

The present invention has purpose to provide a kind of new method of having improved again, can be with vitamin, particularly vitamin A be fed in the chewing of smoker and respiratory tract in.

The present invention has a purpose to provide a kind of method of making cigarette again, and it can reduce the risk that the smoker emits aspect healthy, and the enjoyment of shelf life, stability, outward appearance and smoking that can appreciable impact cigarette.

A further object of the invention provides a kind of cigarette of having improved and constitutes, and changes and can produce as long as the production line of existing cigarette manufacture producer is done very little (if any) especially.

A further object of the invention provides a kind of cigarette of having improved and constitutes, and has added harmless steam in its flue gas stream.

A further object of the invention provides a kind of cigarette of having improved and constitutes, and it has reduced the risk of healthy method, and do not change the taste of the desired common cigarette of smoker, and mouthfeel smokes and combustion characteristics.

The present invention has also proposed the new application of blocking agent, during it has and the effect of the peculiar nitrosamines of tobacco, and can the sort ofly not go the effort of isolating and specifically removing carcinogenic compound as what discussed the front, causes the unacceptable change of cigarette taste.The invention discloses a kind of method that can in the organ that the smoker determines, block this carcinogenic physiologically active on one's body.Therefore here advocate in flue gas stream and introduce blocking agent, rather than in flue gas stream, reduce any amount of substance.Obviously, this blocking agent it seems have only when being only when specific cell receptor contacts on the organ that it is determined in smoker's body or in the organ activated.Because do not need tar in the cigarette smoke of particular brand and nicotine content are done any minimizing, so the enjoyment of smoker on sense of taste is reduced.Blocking agent is incorporated in the cigarette goes though have many methods, they also have detailed discussion at this, preferable methods be in the process of cigarette manufacture operation, be sprayed to alcohols again dry and the tobacco that cuts into pieces on.

For the skilled person of specialty under the present invention, from top description also in conjunction with the accompanying drawings, other purpose of the present invention and advantage will obviously be found out.

Fig. 1 is an inhibition test result's of the present invention column figure presentation graphs;

Fig. 2 is the perspective view of first embodiment of the invention;

Fig. 3 is the perspective view of second embodiment of the invention;

Fig. 4 is the perspective view of third embodiment of the invention;

Fig. 5 is the side view of the 3rd embodiment of Fig. 4;

Fig. 6 is the perspective view of fourth embodiment of the invention;

Fig. 7 is the perspective view of fifth embodiment of the invention;

Fig. 8 is the perspective view that the sixth embodiment of the invention major part is explained usefulness separately;

Fig. 9 is the perspective view that the seventh embodiment of the invention major part is explained usefulness separately;

Figure 10 is the perspective view for the cigarette at the available position of other among the 6th and the 7th embodiment among key-drawing 8 and Fig. 9.

According to the present invention, disclose a kind of tobacco smoking article, can suppress some and notify nitrosamines such as NNN and the regioselective of metabolin at least mammiferous three kinds of tissues thereof that in mammalian tissues, accumulates by the additive in the smoke gas flow of tobacco. These three kinds of tissues are bronchiolar epithelium, salivary gland epithelium and liver. Coincidence is by no means, and nitrosamines such as NNN and metabolin thereof present carcinogenic effect in same these several tissues just.

NNN is one of maximum carcinogenic substance of the content found in the flue gas of cigarette. If NNN accumulates the formation that will cause malignant tumour in lung, although the actual biochemical process that wherein comprises is not also accurately determined, it seems that NNN alcohol blocking agent of the present invention be to work by one of following approach: a kind of may be position such as the lung that blocking agent molecular energy and NNN concentrate, the histiocytic superficial cell receptors bind of liver and salivary gland, thereby stoped the combination of NNN and carcinogenic metabolin and cell receptor, may to be the blocking agent molecule be combined with the cell receptor in the histocyte at these positions another kind, it is blocking-up, be to have changed the metabolic process of NNN in cell, thereby prevented the formation of the carcinogenic metabolite of NNN. In other words, the effect that the blocking agent molecule has obstruction lockhole (cell receptor), stops NNN key (molecule) to enter perhaps changes the NNN key and makes it no longer be applicable to the effect of lock. NNN can not enter or rest in the tissue like this, and from lung by and harmlessly be discharged from.

Aim of the present invention is to find out and suppresses nitrosamine and the selective location of metabolite in mammalian tissues thereof, rather than the treatment tumour. In other words, aim of the present invention does not lie in treatment tumour or cancer, but about nitrosamine and metabolite thereof, the scattering problem of some chemicals that just can in mammalian tissues, optionally locate. In fact tobacco product of the present invention or smoking set are especially effective when no tumour exists.

Surprisingly, have been found that some alcohol can suppress the selective location of nitrosamines such as NNN and metabolite thereof, according to the present invention, used alcohol comprises the alcohol that contains two or more carbon atoms, but the alcohol of preferentially selecting is the alkylol that those contain three or more carbon atoms at least. Alkyl partly can have the structure of straight or branched. In addition, alkyl can be ring-type or acyclic structure. The example of spendable alcohol has: ethanol, normal propyl alcohol, isopropyl alcohol, n-butanol, sec-butyl alcohol, isobutanol, the tert-butyl alcohol, 2-methyl-1-butene alcohol or photolytic activity amylalcohol, n-amyl alcohol, sec-amyl alcohol, tert-pentyl alcohol, n-hexyl alcohol and cyclohexanol. Found that also following compounds also can disperse the location of nitrosamines, they are: methyl-sulfoxide, imidazoles, pyrazoles, DDC and benzyl isothiocyanate. The alcohol of these and other and the compound among the present invention are listed in the following table I, and preferred alcohol is cyclohexanol in this table, because introduced some tastes when it enters in the smoke gas flow of tobacco, and the cigarette air-flow has pleasant fragrance. What should be specifically noted that is, menthol is unlike the compound that the present invention includes, and it can not suppress the location of nitrosamines.

The table I

The present invention includes following all monobasics and polyalcohol and with the compound of resonance hydroxyl, they are made up of two to 40 carbon atoms, but the present invention has more than and is limited to the following compounds thing:

Monohydric alcohol: polyalcohol:

Ethanol ethylene glycol

Normal propyl alcohol 1.2-propane diols

Isopropyl alcohol 1.3-propane diols

Allyl alcohol 1.3-butanediol

Crotonyl alcohol 1.4-butanediol

N-butanol 2.3-butanediol

Isobutanol 1.5-pentanediol

Sec-butyl alcohol 1.6-hexylene glycol

Tert-butyl alcohol 1.10-decanediol

2-amylalcohol pinacol

3-amylalcohol glycerine

N-amyl alcohol 1.2.4-butantriol

Isoamyl alcohol 1.2.6-hexanetriol

Tert-pentyl alcohol has the compound of the hydroxyl that resonates

2-methyl-1-butene alcohol methyl-sulfoxide (DMSO)

3-methyl-2-butanols

Neopentyl alcohol

Cyclopentanol

N-hexyl alcohol

The 2-hexanol

The 3-hexanol

2-methyl-1-pentene alcohol

3-methyl-1-pentene alcohol

Cyclohexanol

N-octyl alcohol

Octanol

Decanol

Laruyl alcohol

Tetradecanol

Cetyl Alcohol

Octadecanol

Phenmethylol

Benzhydrol

Cinnamyl alcohol

Triphenylcarbinol

The consumption of alcohol can be arbitrarily, but must be more than for making the nitrosamine in affected mammalian tissues disperse required limit, and is less than the amount that produces any toxic side effects in mammalian body.According to the present invention, the oral dose of alcohol is about every gram weight of mammal 1 microlitre.After thinking over, the amount of the alcohol that is used to suck also should be than causing that the required amount of poisonous effect is little.See that also higher alcohol has lower toxicity; This poisonous effect is only limited to the sedation of central nervous system.The following table II has been summed up the toxin character of some typical alcohols.Show referring to Kirk-Othmer: Encyclopedia of Chemical Technology, the 1st volume 727 pages of (1978) and The Registry of Toxic Effects of Chemical Snbstances, U.S. sanitary, education and Department of Welfare publish, the 2nd volume (1977)

The table II

(annotating a)

Alcohol acute oral median lethal dose

(rat gram/kilogram)

Ethanol 14.

Normal propyl alcohol 5.4

Isopropyl alcohol 5.84

N-butanol 0.79

Isobutanol 2.46

The tert-butyl alcohol 3.5

N-amyl alcohol 3.03

Second amylalcohol 1.47

Amylalcohol 1.30

Tert-pentyl alcohol 1.0

Hexanol (annotating b) 3.7

Cyclohexanol 2.06

" activity " amylalcohol 4.9

(being 2-methyl-1-butene alcohol)

Retinol (vitamin A) 2.0

Menthol 3.18

4-methyl-2-amylalcohol 2.6

2-Ethylhexyl Alcohol 3.2-7.1

Isooctanol (annotating b) 1.5

Decyl alcohol (annotating b) 4.7-9.8

Lauryl alcohol, 98% 40

(derived from cocoa bean)

Hexadecanol 20

18 alcohol 20

(annotate a): cause the dosage of 50% experimental animal death, show with the gram numerical table of per kilogram of body weight compound used therefor.

(annotating b): isomer mixture

The acute oral toxicity value can be obeyed the median lethal dose LD of sodium chloride with rat ₅₀Be that 3.75 gram/kilograms compare median lethal dose LD ₅₀Be 15 gram/kilograms or higher material, be commonly considered as nontoxic.In contrast, the nicotine that is present in the tobacco is 1 milligram of a per kilogram of body weight (1mg/kg) for the acute deadly oral dose of an adult estimation.Show the 9th edition the 18th part (1975) of " endo-medicine principle " (Principles of Internal Medicine) referring to Harrison.Therefore, when use pure time-like of the present invention with the form of weak solution, these professional those skilled in the art should be able to easily realize the peptizaiton that the present invention proposes and avoid the toxicity of overdose to pay effect simultaneously.

Smoking also consumes some the B family vitamin in smoker's body except that introducing strong carcinogenic substance.Vitamin C and E also prove and can stop the formation of nitrosamines on epithelial membrane in addition; In addition, vitamin A and retinene class can suppress the development of tumour.Referring to N.S.Zedeck, M.Lipkin shows " inhibition of tumor promotion and development " (Inhibition of Tumor Induction and Development) book, Prenum Press, N.Y.1981.Therefore,, suppress the formation of nitrosamine or the development of inhibition tumour, all belong within the scope of the invention by pure and mild known because the various vitamins that smoking consumes and other reagent merge use.As for the consumption of some used vitamins or other reagent (as selenium), from the viewpoint of the disclosed theme of this patent, should be within these professional those skilled in the art's knowledge and limit of power.(, the same referring to " inhibition of tumor promotion and development ".

Should understand, example provided by the invention is for narrating problem clearlyer, rather than limits the scope of the invention with these examples.

Example 1

The male C 57 BL/6 J mouse of give growing up by every gram body weight intravenous injection 0.12 to 0.19 micromicrocurie 2 '- ¹⁴C NNN is equivalent to dosage (the New England Nuclear of 0.4 to 1.9 milligram of per kilogram of body weight; Spec.Act.18.4 or 51.7 millicuries/millimole).After one hour, with mouse with the slight anesthesia of ether and immerse in dry ice/hexane freezing.The whole sagittal slices of 20 micron thickness of freezing mouse is placed on the Scotch adhesive tape, carries out whole-body autoradiography (" destiny of medicine and metabolism: method and technology " (Drng Fate and Metabolism that edits at E.R.Garrett and J.L.Hirtz referring to people such as W.Waddell by known method then; Methods and Techniques) a book 1-25 page or leaf writes articles) (Marcel Dekker, New York, (1977).With ADG optical density instrument and have 3 millimeters curvature, optical density that the photoelectricity groove that is positioned at photography enlarger shelf top is measured the zone of the autoradiograph through developing, X-ray film is put into enlarger, and rising makes it to produce 35 times amplification effect on frame.

Accepting ¹⁴ C NNN 20 minutes in the past, with ethanol, the n-butanol and the tert-butyl alcohol are by the mouse administration of oral intubation to some tests, and ethanol is by 1 gram/kilogram and 5 gram/kilograms, the n-butanol and the tert-butyl alcohol make every every gram body weight of mouse accept 0.02 ml soln by 0.2 gram/kilogram and 1 gram/kilogram wiring solution-forming.(introducing alcohol in the mouse body by oral intubation, to do to reach tall and big haemoconcentration required average time be 20 minutes)

By using ethanol (a kind of chemical blocking agent of the present invention), disclose the portal vein week of salivary gland and bronchiolar epithelium and liver and the radioactivity location of central area has been reduced by radioautography; The degree that reduces during with n-butanol is bigger; If with heavy dose of tert-butyl alcohol, almost can eliminate fully ( ¹⁴C) NNN is in the location of bronchiolar epithelium portion.In addition, the minimizing of optical density is relevant with the dosage of alcohol.Fig. 1 points out the absorption in the zone of optical density instrumentation amount.For the ease of relatively, carried out control experiment.More particularly, Fig. 1 shows the mean value of the trap of optical density instrumentation amount.All observe the phenomenon that radioactivity location is suppressed in four zones, in every block diagram the figure of mark represent intravenous injection ( ¹⁴C) the gram number of the oral dose of the alcohol of giving by per kilogram of body weight in 20 minutes before the NNN.To inject ( ¹⁴C) mouse of NNN is freezing one hour, every mouse is taken at mean value (three radioautographies of 15 measurements that made in the arbitrary region of appointed part, 5 trap data of each measurement), each measurement all is to carry out after the trap zero setting of blood.Control value is the mean value of six mouse; The measurement mean value that carries out with 1 gram/kilogram n-butanol is from two mouse, and other mean value is from a mouse.The variation coefficient of each mean value is less than 10%.All measurements are to be carried out in same occasion for each all unwitting observer of processing of selected radioautography arbitrarily by same.

The further details and the explanation of example 1 are set forth in William I.Waddell, M.D. roll up the 51-53 page or leaf with Carolyn Marlowe at Science the 221st, that delivers among the July 1,1983 is entitled as in " location of the nitrosonornicotine of radioactivity is by the inhibition of alcohols " literary composition.One piece of recent article of the metabolism of relevant NNN in liver can be entitled as " the covalent bond characteristic of N-nitrosonornicotine in the mouse liver microsome " literary composition what Carcinogenesis the 7th volume (1986) was delivered referring to people such as M.F.Hughes.

Example 2

An adult C57BL/6J mouse is placed on the higher sieve plate in position in the beaker, puts into 2 milliliters of cyclohexanol below the beaker bottom sieve plate, the beaker top covers with sheet metal.When beaker bottom is kept 50 ℃ in water-bath, mouse was put into airtight beaker about 5 minutes.The reference standard tables of data, can to make the concentration of alcohol in the air in the beaker be 0.01% to the vapour pressure of cyclohexanol in the time of can calculating 50 ℃.Referring to " chemistry and physics handbook " (Handbook of Chemistry and Physics(1974)) D-203 to D-217.

Mouse put 5 minutes in beaker after, to it by every gram body weight intravenous injection 0.12 to 0.19 micromicrocurie (Z '- ¹⁴C) NNN(New England Wuclear; Spec.Act.18.4 or 51.7 millicuries/mM).After one hour, mouse with freezing in the slight anesthesia of ether and the immersion dry ice/hexane, is placed on the whole sagittal slices of 20 micron thickness of freezing mouse on the Scotch adhesive tape, as said in example 1, carries out whole-body autoradiography.The result does not detect radioactivity in the arbitrary part of bronchiolar epithelium.In order more also to have done control experiment, the result has arrived radioactivity in the respiratory epithelium location detection of control group.

Example 3

Keep 26 ℃ in the water-bath except beaker bottom is placed on, and mouse be placed in the airtight beaker beyond 5 minutes this point, all the other operations all with example 2 in said identical.It is 0.001% that the vapour pressure that the reference standard tables of data can calculate cyclohexanol in the time of 26 ℃ can make the content of alcohol in the air in the beaker.After injecting as example 2, mouse is handled by example 2 said methods, and compare with control group, the result does not detect radioactivity in bronchial epithelial any part.

Example 4

Give the dosage of an adult male C 57 BL/6 J mouse, carry out intraperitoneal injection by 0.02 milliliter of imidazoles aqueous solution of every gram body weight.The concentration of the imidazoles aqueous solution of being prepared will provide the imidazoles of 0.05 gram for per kilogram of body weight.Inject after 20 minutes, by every gram body weight 0.12 to 1.9 micromicrocurie (Z '- ¹⁴C) dosage of NNN is made intravenous injection (New Englad Nuclear; Spec, Act.18.4 or 51.7 millicuries/millimole).After one hour, mouse with the slight anesthesia of ether and immerse in dry ice/hexane freezing.The whole sagittal slices of 20 micron thickness of freezing mouse is placed on the Scotch adhesive tape, by known method whole-body autoradiography is carried out in section then, referring to example 1.Compare with control group mice, observing the nitrosamine of locating the mouse of having injected imidazoles solution on one's body has tangible dispersion.

Example 5

Repeat the operation of example 4, carry out intraperitoneal injection by the dosage of 0.02 milliliter of every gram body weight for an adult male mice, provide 0.25 imidazoles here but used imidazoles solution concentration can be per kilogram of body weight.After carrying out remaining experimental procedure by example 3 described programs, compare with mice in control group, the result has tangible dispersion at the nitrosamine that the mouse of having injected imidazoles solution observes the location on one's body.

As seen from Figure 1, when using the tert-butyl alcohol, can observe maximum inhibition at the bronchiolar epithelium position.When all three kinds of alcohol used by specified dosage, the effect that causes in two zones of liver was similar.At nose and esophagus epithelium position, the trap of control group and treated group does not have tangible difference.This result points out forcefully, alcohol used in the present invention is as a kind of chemical blocking agent, the location of nitrosamine in male C 57 BL/6 J mouse body entobronchus and salivary gland epithelium position and the liver can be suppressed at, but the location of the nitrosamine at nose and esophagus epithelium position can not be suppressed at.If by identical gram molecule dosed administration, then the tert-butyl alcohol ability that suppresses the nitrosamine location at bronchiolar epithelium seldom is 50 times of ethanol.

It may be in action a kind of in several mechanism that the selectivity that suppresses nitrosamine location at some positions is pointed out us.A kind of mechanism that may comprise is machine-processed with the competition inhibition of secondary alcohol dehydrogenase or cytochrome P-450 LM3a.Think that promptly alcohol of the present invention and this two kinds of systems can be successfully and α hydroxyl NNN substrate competition, thereby prevent contiguous carcinogenic formation.Though what might comprise is a kind of simple weaken effect, the selectivity at the position that inhibition is worked has the mechanism that these facts of visibly different effect support that consumingly metabolism suppresses with used different alcohols.

The explanation possible to another kind of the present invention is presented below.Covalency sex change that it is generally acknowledged chemical carcinogen or their metabolite and DNA is the committed step of the bringing out the canceration process (paper of reading out in the 8th annual meeting that Washington D.C holds at NACB1984 referring to S.S.Hecht: chemical carcinogenesis process: overview (Chemical Carcinogenisis:An Orerview), drug action mechanism, Clin.Physiol.Biochem.3:89-97,1985).The DNA base has the position of many nucleophilics easily to react (referring to Hecht with carcinogenic metabolin short of electricity or electrophilic; E.J.Lavoie, S.S.Hecht is at Hazard Assessment of Chemicals, the appraisal of the danger of Current Developments(chemicals, current development) article " chemical carcinogenesis process: external metabolism and activation " of a book the 1st volume 155-169 page or leaf, Academic Press, New York, 1981).In panoramic chemical carcinogen with different structure, be converted into can with the close electric metabolin of DNA reaction, it seems it is the character (Hecht) of their unanimities.

The NNN of TSNA and the metabolic pathway of NNK were once studied rat and hamster on one's body (referring to the u.s. department of health publication: " consequence that smoking causes health: the Medical Director's of health bureau portion report " (U.S.Department of Health, The Health consequences of Smoking, A Report of the Surgeon General, 1982), also studied on one's body (referring to A.Castonguay the marmoset monkey, H.Tjalave, N.Trushin, R d ' Argy and G.Sperber etc. are at Carcinogensis the 6th volume (№ 11) 1543-1550 page or leaf, 1985 papers of delivering that are entitled as " metabolism and the Tissue distribution of N-nitrosamines in marmoset monkey body that tobacco is proprietary ").NNN and NNK rat, hamster and monkey metabolism activation on one's body the spitting image of be from α-carbon hydroxylated one the step (u.s. department of health; A.Castonguay).Initial hydroxylating similarly be the intermediary by the chlE2 system carry out (referring to M.F.Hughes, W.J.Brock, L.J.Marion and M.vore are at Carcinogensis 7(1): 3-8 page or leaf (1986) is delivered is entitled as " covalency of N-nitrosonornicotine in rat liver microsome links characteristic " paper, Hecht), the close electric diazohydroxide intermediate of NNN and NNK has been identical (u.s. department of health) by evaluation.The intermediate of these parent's electricity or the carbonium ion of generation may be the final carcinogenic substance forms (u.s. department of health) of TSNA.These close electric intermediates or carbonium ion react the addition product that forms the TSNA-DNA combination with DNA then.

The research report of radioautography and biochemistry aspect has pointed out that the metabolite of NNN and NNK is to be connected on the big molecule of tracheal bronchus and schneiderian membrane, also is connected on the melanin of kidney, liver, sublingual gland and Sumaxillary gland, esophagus and eyes (u.s. department of health).The binding of this organ characteristic's of having property may take place by the intermediary of second kind of enzyme interacting, but to the understanding of this second kind of mechanism also seldom.Up to now, also there is not research work can identify that hepatomicrosome enzyme-TSNA links (Hughes) to the intermediary of nucleophile tissue.The enzyme and the research report of their TSNA that also do not have other organ characteristic's property to organizing nucleophile intermediary to link.

But believe that generally blocking compound of the present invention or alcohol can be blocked the common metabolic process of TSNA.In any case, there is no need by limiting the present invention based on any specific theory.

In order to suppress the selectivity location such as NNN and this class nitrosamine of metabolite thereof, alcohol of the present invention can come administration by some diverse ways.But the method that is adopted must be able to satisfy following four requirements, promptly (1) is only past or main toward desired site of action, for example airway epithelial portion provides the alcohol of high concentration, (2) only during the time interval that at utmost is exposed to smog, provide it, (3) only for or mainly be to provide it for the smoker, and (4) are exposed in this inhibiting substances other organ in smoker's body as far as possible less, the present invention is devoted to the structure that tobacco smokes product especially, these requirements above also satisfying during the flue gas that makes alcohol can be released into the smoker flows.More particularly, the present invention is devoted to the method that satisfies the cigarette of these requirements and make this cigarette.

Can reach the purpose that nitrosamine is disperseed when having multiple technologies can satisfy these requirements.For example, in the capsule that in general, that alcohol can be encapsulated in is rupturable, be filled with one or more alcohol of the present invention, and before smoking, mix, as in tobacco pipe, mixing with tobacco; Perhaps rupturable capsule can directly be put into the filter tip of tobacco or cigar or cigarette in manufacture process.In addition, rupturable capsule can be placed on the disposable filter of cigar or cigarette and chew, or is placed in the disposable smoke filter of tubular of plastics or papery, and it contains one or more alcohol of the present invention rupturable capsule.Narration here or propose in tobacco smoking set or goods (for example cigarette), the placement mechanism of any alcohol or the combination of fixed mechanism, also all within the scope of the present invention.

The tobacco smoking set that disengages these alcohols in flue gas stream is preferably constructed, and is alcohol is packed in the microcapsules, microcapsules is put in the smoking set again, should be noted that capsule isolates alcohol at first, controlledly discharges then, makes the environmental interaction of it and flue gas stream.The shell wall that microcapsules constitute should be able to fully coexistence of the alcohol that is comprised, till the heat that is maintained to cigarette causes when shell wall is opened.In other words, microcapsules should be stable in cigarette, only just break when being heated and controlledly discharge wherein alcohol.The microcapsules of melting are different with the microcapsules of volatilization, and it can be toward the steam of introduction in the flue gas stream itself, the by product that the latter forms when generally being the shell wall volatilization.Like this, alcohol just can automatically feel that with the smoker mode discharges easily, and the smoker needn't further operate tobacco product, and can guarantee that alcohol can disengage more consistently.

As shown in Figure 2, these microcapsules 20 that are encapsulated with alcohol can place 22 places of the tobacco rod 26 of cigarette, the wrappage of embolism places 23 places, acetate filter tip to place 24 places, is sneaked into equably in the pipe tobacco 28 of chopping and/or in the filter tip 24 at these local microcapsules.Used dosage will be decided (work week by normal 8 times each workday and 40 hours calculates) by the time weighting mean value (TWA) of alcohol in human body, promptly to there be sufficient alcohols to be released, with the blocking-up cell receptor, and few of waste or excessive release.Dosage also can change according to different cigarette mixed compositions, for example will see it is the cigarette of low tar content, the cigarette of ultra-low tar content, is filled with the cigarette of spices, the cigarette that contains menthol still is cigarette of different trade marks etc.

The formation of shell wall can be used Insulation Technologies Corporation of Darby, the M-CAP method of Pennsylvania, pressing the general remark book of the relevant shell wall of M-CAP, is that fusing point is 64 to 650, little capsule to 3 microns.The speed that control discharges generally should be constant, but also can change.More particularly, contain the different capsule of fusing point in the Linear Leaf Speedwell cigarette, with guarantee when carbon burns down tobacco rod gradually and under fast burn higher temperature conditions extremely with filter tip wherein alcohols can both discharge consistently.Be designed to transformablely when disengaging speed, the size of the material of shell, thickness and/or capsule also should be able to change.M-CAP constitutes can provide uniform capsule and less than 50 microns capsule.

The capsule material of shell wall can be with the copolymer of ELVAX(ethylene/vinyl acetate) or similar man-made fibre material with desired character, it can produce programmable from 64 ° to 650 shell wall release temperature.ELVAX is a kind of resin of ethylene/vinyl acetate copolymerization, such as described in " material data of safety table-VAX001 ", and (Wilmingteon, the E.I.Dupont de Nemours ﹠amp of Delaware; Co.(Inc) .10/20/86 publishes).Second kind of possible shell wall material is EUDRAGIT E, and it is a kind of by the dimethylaminoethyl of methacrylic acid and the neutral synthetic cation copolymer of methacrylate, and can form the membranaceous coating of disintegratable.Other alternative shell wall material comprises BERMOCOLL, and it is a kind of ethylhydroxyethylcellulose of the Berol Kemi AB manufacturing of Sweden Stenungsund, and K﹠amp; K Gelatin, it is Kind ﹠amp; A kind of gelatin that Knox makes, Kind ﹠amp; Knox is Saddle Brook, the Knox Gelatine of N.J., Ino, a branch.

N-LOK has been a kind of material (55-129) of stable emulsion, also is another kind of capsule product.Can be to describing of it referring to the national starch of New Jersey Bridgewater and " product data: No. 447 communique " of chemical company

Another kind of formation of the present invention is the alcohol as blocking agent, such as cyclohexanol, in the capsule that the modified starch material of packing into from the bath of pulpous state is made, a kind of suitable example of this class material is the CAPSUL that describes in " product data: No. 409 communique " of the national starch of above-mentioned New Jersey Bridgewater and cereal product branch of chemical company, it is to be made by the corn of amylaceous sex change, be particularly suitable for the glue capsule, and present the easy dispersiveness of the liquid (particularly fragrant oils) sealed and good shelf stabilities.

For the stability that tolerance when manufacturing, packing and client smoke cigarette is broken, shell wall should account for 20% to 50% of capsule volume.In being placed on cigarette paper or the circumference of sneaking into capsule when going in the tobacco should be 3 to 10 microns, can avoid the collision of the cigarette paper that do not expect to have like this, and also see capsule in the pipe tobacco.If capsule is to be placed in the filter tip of cigarette, then big circumference to 50 microns also is an acceptable.Capsule can further make it hardening with plasticizer, in order to control their melt temperature.Also have, capsule can dye with food dye, make it with cigarette in the color of pipe tobacco be complementary.By capsule being reinstalled another capsule to guarantee its further stability, as using M-CAP method or condensing method etc., also within the scope of the invention.

According to a kind of formation of the present invention, attached to a kind of method on the cigarette paper, be disclosed method among No. 4,236,532, the United States Patent (USP) № with capsule.Pack into alcohols in the microcapsules, except can being attached on the cigarette paper, also can be attached to the covering of embolism or be included in the filter tip of cigarette, at this moment can be distributed in equably in the filter tip, also can constitute center of gravity, generally at as shown in Figure 3 30 places at the three air pocket filter tips of recapturing.A kind of like this three air pocket filter tips of recapturing constitute to also have the suppression system of a plasticizing, so that the alcohols that leaks from the capsule that breaks reduces to minimum.

In addition, capsule also can be attached on cigarette paper or the embolism covering via common gelatin or gelatinized corn starch coating.Capsule can be sneaked in the bonding agent, then paper is bathed and be coated with Fabric through slurry, similar in appearance to the method with the carbonless paper binding.Capsule preferably is placed on the filter tip part rather than in the tobacco rod part, can covers like this owing to discharging the undesirable pop-noise that alcohols causes.

It is two embolisms that filter that the another kind of mechanism that discharges alcohols of the present invention constitutes, as shown in Figure 4 and Figure 5.This pair of embolism of cigarette filters part 40 and sees position shown in 42 among the figure, generally is about 20 to 30 millimeters, and the most frequently used is 25 millimeters long.This pair of embolism filters partly 40, by one 10 millimeters long with filter 46 tails of the filter 44 of filter filling and one 15 millimeters long to tail be placed on and form in the cigarette.Each embolism wraps up respectively, more two embolisms is bundled together, and paper is chewed in the parcel filter again.10 millimeters filter 44 is near tobacco rod 48, and that of 15 millimeters partly is arranged in the back of 10 millimeters parts.Contain the alcohols that is contained in the microcapsules in 10 millimeters the part 44, these capsules distribute equably along the longitudinal axis.The circumference of capsule and shell thickness are as mentioned above.The preferably sequencing of the release temperature of shell wall as previously mentioned, is between 64 ° to 650 °F, highly can both discharge alcohols continuously when hot to guarantee that when beginning to aspirate cigarette lower temperature produces to the end.The fragrance promoting agent that adds can be added to 10 millimeters parts 44, as the some that is contained in the material in the capsule.When flue gas stream partly is sucked by 44, the shell wall fusing of capsule, being encapsulated in alcohols in the capsule and promptly being disengaged and taken to 46 places by flue gas stream, is to be made of common cellulose acetate here, did general the filtration and use before leaving the breathing desorption system that cigarette 42 enters the smoker.

The filtration part 44 that filter is filled contains the alcohols that is packaged in the capsule with sequencing shell wall, fragrance rebuild agent, vitamin A or other additive of the present invention.The example of sealing vitamin can be referring to United States Patent (USP) the 3rd, 339, No. 558.If desired, also can add other fragrance promoting agent and rebuild flue gas desired odor property after absorbing the blocking agent compound.United States Patent (USP) the 3rd, 144 has been set forth a kind of being used for by the constituting of the filter of the impregnated cigarette of flavouring ingredient for No. 024, and it can be used to design the effective device of a kind of the present invention of making.Preferably axially-aligned on all these this section of material filters, radial dispersion.

If the pure and mild ester that adds does not have capsule, or makes this alcohol with ester, all within the scope of the present invention yet.

Flood pipe tobacco, cigarette paper or the filter of chopping with alcohols of the present invention, thus when cigarette lighter, discharge alcohol steam and be inhaled into, also within the scope of the invention.Coated papers can soak with alcohol before outer packaging and In Aluminium Foil Packing cigarette packets.After stored for several weeks, alcohol will diffuse in the cigarette.This is similar in appearance to the method for menthol being put into cigarette, and it is a kind of very simple, more effective and inexpensive technology of the present invention.The instantiation of this dipping method may also will reduce and passive smoking associated health problem and the risk of being emitted.

Another mixes the method that it is discharged in the flue gas stream of tobacco effectively and can have a negative impact to the stability of cigarette and smoker's enjoyment with alcohol, is the inner face of its " seal " at cigarette paper.More particularly, the intaglio method can be used to the microcapsules that contain one or more alcohol of the present invention are imprinted on the inner face of cigarette paper.Create a kind of " ink " that contains pasty media for this method, wherein contained microcapsules.This ink is sent in the common printing machine, so printing machine just is imprinted on ink or be placed on the cigarette paper.

As shown in Figure 6, pack into alcohols in the microcapsules can be coated with Fabric or embed in the cigarette, it can be on the cigarette paper in the paper slip 54 52 or spread over disorderly and/or the filter tip coil paper 56 in paper slip 58 in or spread on the cylinder packing thing in coil paper and/or the paper slip disorderly or spread on the cigarette paper disorderly.In addition, or be used in combination with it, as shown in Figure 2, they can disorderly or be put into by the pattern of prior decision in the pipe tobacco of filter tip and/or chopping.Another kind method is with a kind of atomizer alcohol to be sprayed in the filter before smoking.

Way during other flue gas that makes alcohol be discharged into cigarette 60 flows provides the dual air pocket shown in 62 in a kind of preferably image pattern 7.The center cavity 64 of filter tip 66 comprises microcapsules and/or the crystalloid alcohols that alcohols is housed and/or is immersed in alcohols on the charcoal 68 as we can see from the figure, and the steam of alcohol is released when cigarette 60 is lighted.

Be encapsulated in alcohols in the microcapsules also can image pattern 8 in generally shown in 72 like that, in a kind of device of suspention, be positioned in the cigarette 70.Suspension apparatus 72 comprises the plastics spoke 76 that is installed on the rigidity plastics hub cap 78, and the outside circumference of plastics hub cap and cigarette cylinder is tightly fitted.Be encapsulated in alcohol 82 in the microcapsules be suspended on the spoke 76 and hub cap 78 in, after cigarette is lighted, promptly be released in the flue gas stream 84.As further explanation, typical cigarette 90 of explanation in Figure 10 comprises tobacco rod part 92, the filter tip 94 of connection and the top bag paper 96 that overlaps.The device 74 of suspention can be placed in and be indicated as being among the figure on any one position of 98,100 or 102.

A kind of dual air pocket 15 of aspirating release that draw separately in 110 places in Fig. 9 also can be inserted into and be marked as among Figure 10 on arbitrary position of 98,100 or 102.Dual air pocket 110 comprises first air pocket 112, second air pocket 114 and the film 116 of separating their gluing.First air pocket 112 comprises and is contained in alcohols in the microcapsules and/or crystalloid, and seal with film 116 on its top.When suction film 116 break and the alcohols of packaging be released in second air pocket 114.Second air pocket comprises a plastic channel, and it contains the alcohols that remains to be disengaged, and the surface that be exposed to flue gas stream 118 of alcohols with maximum is provided.It can prevent that also alcohols from leaking from cigarette.

The composition that contains alcohols, put any position in the filter tip into, comprise with large capsule placing filter, with the method beyond the heating, for example pierce through, push, pulverize etc., manually or automatically the large capsule fragmentation that is placed in the filter tip, also within the scope of the invention, referring to United States Patent (USP) the 3rd, 547,130 and 3,339, No. 558.

In the cigarette that alcohols also can be comprised in the cigarette of enfleuraging is chewed.The formation (not shown) that a kind of cigarette is chewed is made of plastics, length generally be standard 84 millimeters long with 3/4ths of cigarette with filter tip.The butt of cigarette makes it to be suitable for opening one end that cigarette chews and peace jail at this openend by squeezing or pressing.The other end that cigarette is chewed is tapered so that be placed in the chewing of smoker.Be attached at cigarette with general any cigarette of buying and chew, promptly chew in the flue gas stream that controllably discharges and enter the cigarette of being lighted by cigarette as the alcohol (class) of blocking agent.Here can be referring to United States Patent (USP) the 3rd, 713, No. 451, a kind of airtight container that contains a little tobacco pipe fragrance pipe tobacco has wherein been described, the latter remains on a cigarette that is placed in back, the contiguous place of filter tip and chews.When cigarette lighter, the flue gas of heat discharges the volatile flavor in the airtight container and enter in the flue gas stream.

Alcohols of the present invention also can place tobacco pipe to constitute (not shown) or special tobacco pipe pipe tobacco prescription, and these skilled persons to specialty under the present invention will be clearly.

The present invention also is in international patent application PCT/US87/01978 number of C.A.Blockers company of Kentucky State Louisville, is entitled as a kind of popularization of the disclosed technology of patent of " tobacco product ".A kind of warp is preferred, one or more alcohols of the present invention or compounds as blocking agent, be discharged into the method for going in the flue gas stream of tobacco product such as cigarette, picture is set forth in the patent documentation of that part international application, be in the manufacture process of tobacco product (cigarette), be sprayed to again alcohol (class) dry and the tobacco leaf that cuts into pieces on, make pipe tobacco part or bar portion in the cigarette of making contain this alcohol.It is stable that this alcohol preferably can keep in cigarette, and up to cigarette lighter, at this moment alcohol is heated and is released in the flue gas stream that is sucked by the smoker.For avoiding excessive evaporation, after dry again this step operation of cigarette manufacture program, alcohol is sprayed on the pipe tobacco of chopping, after this alcohol is in the impregnated pipe tobacco that enters chopping.Also have, for reaching best effect, be sprayed at the amount of the alcohol on the pipe tobacco, must guarantee fully that enough pure molecules are sucked in the smog gas by the smoker, make it to equal to be present in number with the nitrosamines molecule in the volume smog number of NNN or NNK molecule (or equal at least).

On the other hand, the amount of the alcohol that is sucked by the smoker and shift must be on level of security, and be less than any one existing government regulation, such as at " U.S.'s employment security and health control (OSHA) the time weighting mean value (TWA) " of the U.S. to the highest volumetric concentration that each alcohol allowed.Other helpful publication (generally acknowledged safety date sheet GRAS that instructs data that " spice extract manufacturing " association is arranged.The publication of (Generally Regards As Safe list) and Great Britain Hunter committee (Hunter Committee from Great Britain).If a kind of material is also without existing literature review mistake, it is fixed that the toxicity of this material (alcohol) just should be assessed before using.Compound of the present invention or alcohols be by one by one analysis, and the toxicity of that the most malicious a kind of compound is considered to the toxicity of the mixture be made up of several compounds in these compounds.Generally be desirably in the cigarette that comprises 400-1200 milligram pipe tobacco (about more specifically 800 milligrams), the alcohol (class) as blocking agent of 1-1000 microgram (800 micrograms more specifically) need be arranged on its pipe tobacco of chopping.The another kind of method that limits the amount of alcohol is its aerial concentration, generally should approximately be 0.1% to 0.001%(to see above-mentioned example 3).

Although additive and material in the relevant cigarette are adjusted in cigarette manufacture industry mostly voluntarily, manufacturing firm still does everything possible and decides initiate additive for mankind's safety whether.There are some data to can be used for instructing these manufacturing firms.For example, OSHA has tested the limit (TWA) that the maximum of many ordinary matters allows since 1972, be poisonous to the mankind when determining to be exposed to a kind of material to what degree, what degree then to be non-toxicity in.These tables of data have been expanded in the publication of the above-mentioned GRAS and the Hunter committee and other national research work.Like this, consider what blocking-up additive should put into go in the cigarette in, can reexamine the toxicity data of compound to be selected.To the compound of having delivered, concrete TWA value is arranged, it is human to be used for contact immediately, as long as the degree of this contact or exposure has just reached or has been lower than said limit.Therefore because comprise many alcohols that do not have known limits among the present invention, only after the further toxicological study work that they are carried out is done, these alcohol just can be used to mix in the commercial commercially available cigarette.

Also have, alcohols selected and that be sprayed on the pipe tobacco must have suitable physical property, makes cigarette carry out mechanization production with the speed of modern production cigarette, and alcohol will still keep stable in cigarette, when lighting till.For example, enough low vapour pressure should be arranged, to avoid excessively volatilization during the shelf life of cigarette through preferred alcohol as blocking agent; When be loaded with enough amounts on pipe tobacco, in the time of transferring to lung and play blocking effect, it should not produce spot or make pipe tobacco become wet on pipe tobacco; And chemical change should not take place in the pyrolytic process of pipe tobacco.

Importantly, Chun TLV value must fully reach the effect of desired blocking effect.Fortunately, now the carcinogenic metabolic pathway of this class is had many understandings, and the guidance of the potential effect of considering a compound also clearly is provided in the document.For example, known compound at first metabolism become intermediate with the DNA bonding.This metabolic process can be by intermediary of enzyme effect institute.Though the enzyme of arbitrary number is arranged, has only the TSNA molecule of some to can be used for metabolism.Therefore, it is in waiting mole theory, and a kind of compounds effective should be measured by 1: 1 molecule number ratio in the flue gas stream that sucks.But the discussion that waits mole theory here should not limit the scope of the invention because might (but also not knowing now) as long as a part of blocking agent gets final product complete blocking nitrosamine formation class.

Sample calculates

It seems that cyclohexanol meet these requirements.OSHA thinks that the cyclohexanol that contains 200 milligrams in continuous 8 hours every cubic metres of air is safe.In the Linear Leaf Speedwell cigarette, approximately its scope of 10%(is 5% to 20%) be stated from first in alcohol on the pipe tobacco is transferred to the flue gas that the smoker sucked in smoking process the volume.

Be surprisingly, by waiting mole matching theory, the minimum of the blocking agent that the contents level of this cyclohexanol is more required than the molecular concentration of the nitrosamines that is used to mate all suctions, want high times, as follows: the concentration of a distinctive nitrosamines of lighting fully of tobacco that filter-tip disengaged, in 140 nanograms in 830 nanogram scopes, the scope that concrete nitrosamine disengages sees Table III and (takes from Hoffman, D., Lavoie, E.I., and Hecht, S.S, at " Cancer Letters ", the 26(1985) report delivered of 67-75)

The table III

By the nitrosamines that disengages in the smog with cigarette with filter tip:

Mean molecule quantity concentration range (every nanogram number in cigarette)

NNN 177 50-310

NNK 207 30-150

NATB+

NABS＊ 190 60-370

The NNN-N-nitrosonornicotine

NNK-4-(methyl nitrosamino-)-the 1-(3-pyridine radicals)-the 1-butanone

NATB-N-nitroso anatabine

The NABS-N-nitroso anabasine

The maximum concentration of the nitrosamines that provides in the III for table is used to mate the amount of the required blocking agent of the molecular concentration of these upper limits, has calculated to be listed in the following table IV.

As can be seen when the maximum concentration level of all nitrosamines is blocked by cyclohexanol, the TWA value that the concentration of blocking agent adopts by OSHA is calculated and is carried out the consumption that molecule mates than the required nitrosamine molecule that is used to make cyclohexanol and all existence and also will have more 142 times.

Table 4

The blocking-up of nitrosamines (every cigarette in the smoke from cigarette

The nanogram number of middle cyclohexanol)

^*Cyclohexanol concentration in the smoke from cigarette of the TWA limit that OSHA adopts

^*Suppose to wait under the condition of mole coupling

Though menthol has blocking effect to nitrosamine unlike alcohol of the present invention, existing menthol add the method for going in the tobacco but have appropriate because menthol stability of fixed transfer efficiency and shell in cigarette is all fine.Like this, the fusing point of menthol, boiling point, vapour pressure and molecular weight just become the relevant reference standard of selecting used preferred alcohol.For example, do not have toxicity or hypotoxic preferred alcohol directly to be added on the pipe tobacco, after this when pipe tobacco is lighted, be heated and discharge; Aspect the characteristic of molecule, i.e. stability in tobacco rod and transfer to and be comparable to menthol aspect the efficient in the smog; Aspect molecular weight, then can compare,, preferably also pleasant taste and fragrance will be arranged, the blocking effect of expectation will be arranged certainly so that required be added to that amount that pipe tobacco gets on is unlikely to make too wet to pipe tobacco with NNN.

Though chat in this specification and any one alcohol all can be directly used in the method for this direct spraying, it seems that preferred alcohol be: monohydric alcohol: n-octyl alcohol and octanol; Polyalcohol: 1,3-butanediol, pinacol and 1,2,4-butantriol; The compound that has the hydroxyl that resonates: Decanol, laruyl alcohol, Cetyl Alcohol, octadecanol and cinnamyl alcohol; Also has other alcohol: 2-ethyl butanol, ethyl hexanol, n-nonyl alcohol and methyl cyclohexanol.Though Cetyl Alcohol and octadecanol molecular proportion are bigger, owing to do not have toxicity, so be also included within here.These pure character and special little being illustrated in the following table V

Table 5

Table 5(is continuous)

^*TWA OSHA: except as otherwise noted, be meant normal eight-hour day and 40 hours work, the time weighting in week average (what OSHA adopted)

Table 5(is continuous)

^*Symbolic significance: i=is insoluble to q=and is dissolved in a little

S=dissolves in v=and is soluble in very much

#=can be dissolved in by all proportions

Today, the manufacturing of cigarette generally comprised following 18 operations: (1) purchase tobacco leaf; (2) remove the preceding check of offal; (3) remove stalk; (4) dry again; (5) estimate; (6) aging; (7) arrangement; (8) mix; (9) arrangement; (10) build up bulk; (11) cutting; (12) drying; (13) cooling; (14) surface treatment; (15) make bulk; (16) make; (17) packing; (18) store the goods of making.A kind of known variation is that (14) step and (15) step are turned around, promptly makes bulk before surface treatment earlier.In addition, also have manyly, in " research and manufacturing in U.S.'s cigarette industry " (1980) one books (Research and Manufacturing in the U.S.Cigarette Industry) that Max Samfield is shown, very detailed discussion is arranged about making cigarette and cigarette formations, the formation of smog and the contents such as composition of smog.In (16) step (" manufacturing "), the pipe tobacco that cuts into pieces is made cigarette by machine.In the cigarette factory in modern age, the conveyor system of fast turn-around is used to continuously the pipe tobacco of well cutting is sent to highly-mechanized production line.After being verified, going stalk, evaluation, mixing, baking, surface treatment tobacco and making bulk, the producer promptly makes cigarette to it, adds filter tip and the product of making is sent to the packing machine place.

Blocking-up alcohol of the present invention or compound preferably are added on the pipe tobacco of well cutting after last drying of (12) step, promptly add when going on foot refrigerating work procedure when carrying out (13).The general cooler of using is revolving, and an actionless shower nozzle is arranged in its Cylinder, calls surperficial blending or surface treatment on (13) step refrigerating work procedure carries out in the process compound being added to the pipe tobacco of chopping.Used blending material and arrangement, their method and effect etc. can referring to Max Samfield 5/1984 October of Tobacco Journal Iuternational number deliver be entitled as " arrangement of cigarette and blending " literary composition.Compound is to be sprayed on the pipe tobacco when rolling in the cylinder of pipe tobacco at cooler of chopping.Spices as alcohols or other compound of relevant this subject, adds after last drying one step operation or is sprayed on the pipe tobacco, so that their loss reduces to minimum.And the machine that preferably just will enter the tobacco curing volume adds before.Pipe tobacco is preferably dry again before carrying out surface treatment, because surface treatment is badly aging, vapors away easily.Like this, this is the standard industry practice of a cigarette manufacture, and method of the present invention, promptly blocking compound is added to the pipe tobacco that cuts and gets on, can utilize the modern production machine, only need it is carried out very little change, speed that promptly can 3,200 to 8,000 cigarettes of per minute is produced.The alcohol of blocking-up usefulness can be sprayed by the same nozzle of spray perfume, also can be sprayed on the pipe tobacco that cuts with other treatment process or after other operation.

May need to make carrier solution, be downloaded on the tobacco fully alcohol is all even guaranteeing for the alcohol of blocking-up usefulness.In other words, be stated from the selected alcohol on the tobacco of specified rate such as the consumption of cyclohexanol, may not provide sufficient solution to come wetting equably tobacco, thereby need make alcohol the solution of carrier.The alcohol of the major part blocking-up usefulness that the present invention is used dissolves in ethanol, and it also is a kind of preferred solvent of cyclohexanol (and methyl cyclohexanol), because it vapors away on dissolving cyclohexanol easily and being easy to by pipe tobacco after finishing the load task in one step.Ethanol is the solvent of the specially appointed alcohols of the present invention, also is the solvent that is widely used as in surperficial blending or the surface treatment procedure simultaneously.Cyclohexanol minimum concentration in ethanol is the required concentration of solubilising cyclohexanol, and Cmax is to make cyclohexanol be distributed in concentration required in the rotating cylinder of cooler equably.This upper limit will change with the size of cooling unit and/or the amount of rotating speed and the pipe tobacco in cooler.Water is another kind of solvent, but its application is restricted, because it increases the water content of pipe tobacco, requires to be lower than 1 ten two five of its weight and the water content of cigarette is general.In addition, the solubility of alcohols in water in most of the cases also is limited.

As discussed earlier, one or more vitamins such as vitamin A, B, C and E, also can join in the alcoholic solution.Particularly vitamin A is considered to suppress cancer.Using further specifying of vitamin A in cigarette can be referring to United States Patent (USP) 3,339, and 558 and Japan Patent 55-79,319(Sharmam, June 14,1980).

Example 6

Cyclohexanol is mixed in the cigarette, and specific practice is to inject the bar of a cigarette that makes equably with the syringe holder alcohol that machinery is controlled.For detecting initial conversion, 8750 microgram cyclohexanol are loaded on the Linear Leaf Speedwell cigarette, 60 such cigarettes are placed on the smoking machine of standard and light.Collect specific particle phase with Cambridge filter pad, be loaded with major part material to be collected on it.Determined 10% conversion ratio with this test cigarette.Make like this and contain 2778 milligrams of cyclohexanol in every cubic metre of smoke from cigarette, or 1389TLV%.Carry out GC then and proofread and correct, the production of cigarette of holding or participate in a prayer service at a temple of going forward side by side.Every cigarette 620 microgram cyclohexanol of loading, conversion ratio 10%.Determining alcohol in the smoke from cigarette is 99% of cyclohexanol TLV, therefore is considered to safe.The cigarette of this new Mechanical Method manufacturing can be disengaged the cyclohexanol of safe concentration, and surpasses 132 times of the TSNA total concentration be present in the cigarette.

In addition, the present invention can successfully produce with the speed of 3,200 cigarettes of per minute, and the alcohol (cyclohexanol) of blocking-up usefulness is sprayed on the pipe tobacco, and does not need to change the equipment of any manufacturing cigarette, also can not produce the cigarette loss of any routine.

This cigarette has the shelf life the same with common cigarette, and does not have the trend that increases spot or distortion.The most important thing is when this cigarette can optionally be reduced the smoker and is exposed to a large amount of carcinogenic substance that exists in the smoke from cigarette illeffects to smoker lung, lung is the key organ with the smoking diseases associated.

Cigarette of the present invention formation can be effectively be discharged into the respiratory system that enters the smoker in the flue gas gas colloidal sol of tobacco then to the alcohol of blocking-up.When entering in the flue gas stream of cigarette tobacco, the alcohol as blocking agent that adds to strengthen smoker lung to a series of known carcinogenic tolerances when making cigarette, and can not influence taste, mixing, mouthfeel, suction or the burning of cigarette, can increase some aromatic odors to cigarette pack on the contrary.And it seems and also do not interact with the hybrid cigarette of any particular type as the alcohol of blocking agent.

When in addition, there is no need to be limited in room temperature liquid alcohol of the present invention.In room temperature is that solid-state alcohol also belongs in the scope of the present invention, and used alcohol is solid-state or liquid unimportant, and importantly the alcohols of Shi Yonging can satisfy those four requirements above-mentioned.

Another specific embodiment of the present invention is that alcohols is put into face shield.By wearing the steam that face shield can suck the alcohols that discharges.This face shield can exist in polluted industrial environment or air in the environment of nitrosamines and uses.

A kind of sprayer unit that is used for chewing is arranged, in contact environment, before any nitrosamines, particularly contact before the flue gas stream of those tobaccos, can be used to optionally suck the steam of alcohols.Therefore, another specific embodiments is a kind of device (not shown) that is used for chewing spraying or produces mist, and the tubular shape main body that it has plastics or metal wherein contains one or more alcohols of the present invention.Available compressed air or nitrogen are as nontoxic carrier gas or driving gas.So just formed the aerosol of the tobacco smoke air-flow that contains alcohols.When the mode administration of alcohols of the present invention by sucking, the aerial concentration of alcohols approximately is 0.001% just to be enough to reach the purpose of disperseing nitrosamines at the respiratory epithelium position.Can be referring to United States Patent (USP) 4,016, No. 279,4,232, No. 002 and 4,243, No. 543.

From top detailed description, can obviously find out, in these professional those of skill in the art's limits of functions and powers, can also do some changes, variation or modification to the present invention.But all these changes that do not depart from spirit of the present invention all should be considered to belong within the scope of the present invention, limit as claim of the present invention.

Claims (50)

1, a kind of method of making cigarette comprises the following steps:

With at least a alcohol that contains two or more carbon atoms, spraying is through the tobacco of dry and chopping again, and when its steam is sucked by the smoker, energy suppresses at least a nitrosamine or its metabolite optionally is positioned in smoker's the tissue, the consumption of alcohol should be able to fully suppress the selectivity location of nitrosamine, but can not produce any poisonous effect to the smoker, and

To spray tobacco alcohol, dry chopping again with machine and make cigarette.

2, method according to claim 1 comprises that also said spray process is the solution of the said alcohol of spraying.

3, method according to claim 2 comprises that also said solution comprises ethanol.

4, method according to claim 3 comprises that also said at least a alcohol comprises cyclohexanol.

5, method according to claim 2 comprises that also said solution comprises water.

6, method according to claim 1 comprises that also said at least a alcohol has enough low vapour pressure, to avoid evaporation excessive during the shelf life of cigarette.

7, method according to claim 1 comprises that also said at least a alcohol is the solution of dipropylene glycol monomethyl ether in a kind of ether.

8, method according to claim 1 comprises that also said at least a alcohol has suitable molecular weight, thereby unlikely causing produces wet spot or moistening on the pipe tobacco.

9, method according to claim 1 comprises that also said at least a alcohol does not produce chemical change in the pyrolytic process of the tobacco of chopping.

10, method according to claim 1 comprises that also said at least a alcohol comprises at least a monohydric alcohol.

11, method according to claim 10 comprises that also said monohydric alcohol is n-octyl alcohol or octanol.

12, method according to claim 1 comprises that also said at least a alcohol comprises at least a polyalcohol.

13, method according to claim 12 comprises that also said polyalcohol is 1.3-butanediol, pinacol or 1,2, the 4-butantriol.

14, method according to claim 1 comprises that also said at least a alcohol comprises at least a compound that has the hydroxyl that resonates.

15, method according to claim 14 comprises that also said at least a compound is to be selected from a positive decyl alcohol, laruyl alcohol, Cetyl Alcohol, octadecanol and cinnamyl alcohol.

16, method according to claim 1 comprises that also said at least a alcohol is to be selected from 2-ethyl butanol, ethyl hexanol, n-nonyl alcohol and methyl cyclohexanol.

17, method according to claim 1 comprises that also the used amount of said at least a alcohol is enough to guarantee to make the molecule number of pure molecular transfer in the smog that is sucked by the smoker, equals the number of the nitroso-amines molecule that exists in the smog with volume.

18, method according to claim 1, comprise that also the used amount of said at least a alcohol is enough to guarantee to make the molecule number of pure molecular transfer in the smog that is sucked by the smoker, generally will be at least as the number of the nitroso-amines molecule that exists in the smog with volume as many.

19, method according to claim 1 also comprises the used amount of said at least a alcohol, is enough to guarantee to make the molecule number of pure molecular transfer in the smog that is sucked by the smoker, at least as with the number of the NNN molecule that exists in the volume smog as many.

20, method according to claim 1 comprises that also said spray process is that the solution of said at least a alcohol is sprayed, said solution make the water content of cigarette be lower than it weight 1 ten two five.

21, method according to claim 1 comprises that also said spray process is when tobacco rolls said at least a alcohol to be sprayed on the tobacco in container.

22, method according to claim 21 comprises that also said rolling is tobacco rolling in the cylinder of a cooling of rotating.

23, method according to claim 1 also comprises toward adding flavoring in the tobacco dry, chopping again.

24, method according to claim 23 comprises that also one step of said adding spices carries out in said spraying a one-step process.

25, method according to claim 23 comprises that also one step of said adding spices carried out before said spray process.

26, method according to claim 23 comprises that also one step of said adding spices carries out after said spray process.

27, method according to claim 1 comprises also that said use machine comprises on tobacco rod to add filter tip.

28, method according to claim 1 also is included in said use machine and allows before beginning the alcohol that is sprayed on the pipe tobacco dry.

29, method according to claim 1, comprise that also said alcohol is to be selected from n-octyl alcohol, octanol, 1,3-butanediol, pinacol, 1,2,4-butantriol, Decanol, laruyl alcohol, Cetyl Alcohol, octadecanol, cinnamyl alcohol, 2-ethyl butanol, ethyl hexanol, n-nonyl alcohol, the pure and mild cyclohexanol of methyl cyclohexane.

30, method according to claim 1 comprises that also said alcohol is in the solution that contains a kind of vitamin at least, and this vitamin is to be selected from vitamin A, B, C and E.

31, method according to claim 1 comprises that also said alcohol contains three carbon atoms at least.

32, method according to claim 1 comprises that also said alcohol contains four carbon atom at least.

33, method according to claim 1 comprises that also the carbon atom that said alcohol contains is less than 33.

34, method according to claim 1 comprises that also the carbon atom that said alcohol contains is less than 41.

35, method according to claim 1 also comprises when cigarette lighter, and said alcohol is heated and disengages and enter in the flue gas stream of tobacco.

36, method according to claim 1 comprises that also said tissue is bronchiolar epithelium, saliva pipe or hepatic tissue.

37, method according to claim 1 comprises that also said at least a nitrosamine is NNN, NPYB or NNK or their metabolite.

38, method according to claim 1 comprises that also said alcohol is no more than 200 milligrams cyclohexanol.

39, method according to claim 1 comprises that also the tobacco of said chopping comprises 750 to 1100 milligrams tobacco, and,

Said alcohol comprises 1 to 1000 milligram alcohol.

40,, comprise that also said alcohol comprises 800 milligrams alcohol according to the described method of claim 39.

41,, comprise that also the tobacco of said chopping comprises about 800 milligrams of tobaccos according to the described method of claim 39.

42,, comprise that also said alcohol comprises about 800 milligrams alcohol according to the described method of claim 41.

43, method according to claim 1 comprises that also said alcohol is methyl cyclohexanol.

44, method according to claim 1 also comprises when the consumption of said alcohol when spraying should be able to make nitrosamine molecule of the every suction of smoker at least also sucking a pure molecule.

45, method according to claim 1 comprises that also said alcohol has 0.1% to 0.001% concentration in air.

46, a kind of cigarette made from the method for claim 1.

47, a kind of method of making cigarette comprises the following steps:

Produce a kind of ink that contains a kind of microcapsules pasty media of alcohol, this alcohol contains two or more carbon atoms, when overflowing in by microcapsules, its steam is sucked by the smoker, thereby can suppress at least a nitrosamine or its metabolite in the in-house selectivity of smoker location, the amount of said alcohol should be able to fully suppress above-mentioned selectivity location, but can not produce any poisonous effect to the smoker, and above-mentioned ink is imprinted on the cigarette paper.

48,, comprise that also said alcohol is cyclohexanol according to the described method of claim 47.

49,, also comprise a certain amount of tobacco is involved in the above-mentioned cigarette paper according to the described method of claim 47.

50, a kind of cigarette made from the method for claim 47.

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