WO2006037848A1 - Method and preparation for binding aldehydes in saliva - Google Patents
Method and preparation for binding aldehydes in saliva Download PDFInfo
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- WO2006037848A1 WO2006037848A1 PCT/FI2005/000429 FI2005000429W WO2006037848A1 WO 2006037848 A1 WO2006037848 A1 WO 2006037848A1 FI 2005000429 W FI2005000429 W FI 2005000429W WO 2006037848 A1 WO2006037848 A1 WO 2006037848A1
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- composition
- tobacco product
- aldehyde
- holder
- filter
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Classifications
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- A—HUMAN NECESSITIES
- A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
- A24D—CIGARS; CIGARETTES; TOBACCO SMOKE FILTERS; MOUTHPIECES FOR CIGARS OR CIGARETTES; MANUFACTURE OF TOBACCO SMOKE FILTERS OR MOUTHPIECES
- A24D3/00—Tobacco smoke filters, e.g. filter-tips, filtering inserts; Filters specially adapted for simulated smoking devices; Mouthpieces for cigars or cigarettes
- A24D3/06—Use of materials for tobacco smoke filters
- A24D3/14—Use of materials for tobacco smoke filters of organic materials as additive
-
- A—HUMAN NECESSITIES
- A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
- A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
- A24B15/00—Chemical features or treatment of tobacco; Tobacco substitutes, e.g. in liquid form
- A24B15/18—Treatment of tobacco products or tobacco substitutes
- A24B15/28—Treatment of tobacco products or tobacco substitutes by chemical substances
- A24B15/30—Treatment of tobacco products or tobacco substitutes by chemical substances by organic substances
-
- A—HUMAN NECESSITIES
- A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
- A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
- A24B15/00—Chemical features or treatment of tobacco; Tobacco substitutes, e.g. in liquid form
- A24B15/18—Treatment of tobacco products or tobacco substitutes
- A24B15/28—Treatment of tobacco products or tobacco substitutes by chemical substances
- A24B15/30—Treatment of tobacco products or tobacco substitutes by chemical substances by organic substances
- A24B15/32—Treatment of tobacco products or tobacco substitutes by chemical substances by organic substances by acyclic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
- A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- This invention relates to compositions for locally binding aldehydes in saliva during smoking.
- This invention relates also to a method, a kit and a tobacco product for decreasing the risk of developing cancer of the mouth and pharynx, larynx, oesophagus and stomach.
- Acetaldehyde has been shown to be highly toxic and mutagenic under various experimental conditions. Epidemiological and biochemical studies on Asian heavy drinkers with aldehyde dehydrogenase-2 (ALDH2)-deficiency strongly suggest that acetaldehyde is a local and topical carcinogen in man. This deficiency results in the accumulation of acetaldehyde in saliva and also in markedly increased risk for upper GI-tract cancers.
- ADH2 aldehyde dehydrogenase-2
- WO 02/36098 suggests the use of compounds comprising free sulphhydryl and/or amino group for locally binding acetaldehyde in the long term in saliva, the stomach or the large intestine.
- the compounds were mixed to a substance capable of releasing the acetaldehyde binding substances for at least 30 minutes in the conditions of the mouth, stomach or large intestine.
- the aim was to bind the increased acetaldehyde that occurs in connection with consuming alcoholic drinks or smoking.
- compositions for reducing the blood level of acetaldehyde in order to prevent and treat hangover symptoms and prevent and treat liver damages associated with acetaldehyde.
- US 5,202,354 describes a composition comprising acetaldehyde binding substance, such as L-cysteine, ascorbic acid or salt thereof, a disulfide type thiamine derivative, or a salt thereof, and a cholagogue.
- US 4,528,295 describes a composition comprising methionine, vitamin B6 and potassium citrate.
- 5,829,449 suggests a composition for inclusion within a cigarette, cigar or pipe.
- the patent publication suggests that the composition can be included within the tobacco itself, a filter for filtering tobacco smoke once burned or within the paper or wrapper surrounding the tobacco product.
- the composition was said to be capable of reducing free radical damage to the oro-pharyngeal cavity, respiratory tract and lungs resulting from tobacco smoke.
- the composition included L-glutathione, and a source of selenium, such as L- selenomethionine or L-selenocysteine.
- the composition may comprise also L-cysteine and N-acetyl-1-cysteine.
- U.S. Patent No. 4,532,947 suggests a filter for use in association with tobacco cigarette, which comprises non-toxic salts of 2-mercapto-alkalene sulphonates and/or cysteine and acetylcysteine. These compositions were to be added to cigarette filters or cigarette holders comprising a filter for the purposes of reducing toxic tobacco substances in situ, while smoking cigarettes.
- the object of the invention is to provide a method and a composition for removing or decreasing the aldehyde content of the saliva during smoking.
- the composition and the method according to the invention are very useful in locally binding the increased amount of aldehyde that occurs in connection with smoking.
- the invention is based on the surprising observation that the harmful amount of aldehydes locally occurring in saliva during smoking can be bound locally and quickly into a chemically safe form by using the preparations according to the present invention.
- the substances that bind aldehydes are released in contents high enough to saliva throughout the period of effect of the aldehydes, the local concentration of aldehydes in saliva remains low. In this way, the local risk of contracting cancer caused by aldehydes decreases.
- Aldehydes in particular acetaldehyde present in tobacco smoke dissolves very quickly into saliva. It is of advantage, if the content of aldehydes dissolved in saliva can be lowered or the aldehydes entirely removed from saliva, before the aldehyde has caused damage to the mucosal cells in mouth or in upper respiratory tract or in stomach.
- the preparations of the present invention are able to bind aldehydes very effectively in saliva keeping the aldehyde content much lower or at the level of non-smoking situation.
- the prior art does not suggest preparations or methods, which would keep the aldehyde concentration in saliva essentially lower or prevent the increase of aldehyde concentration during smoking.
- compounds that comprise one or more free sulphhydryl and/or amino groups are used to prepare a composition, which is used to locally bind the aldehydes in saliva.
- the composition comprises one or more substances that bind aldehydes optionally admixed with a carrier suitable for human consumption (sucking and/or chewing and/or keeping) in mouth.
- the substances contained by the composition are selected so that the substances are capable of binding aldehydes and are released within a short period of time.
- This invention provides also a method according to claim 10 for decreasing the effect of aldehydes, which causes cancer, in human mouth, pharynx, larynx, oesophagus and stomach.
- the aldehydes contained in saliva are locally bound into a safe form by using a composition that releases one or more aldehyde-binding substances.
- this invention provides a composition according to claim 19, a kit according to claim 28 and a tobacco product according to claim 30.
- US 5,829,449 and US 4,532,947 disclose tobacco products and filters comprising compounds capable of binding harmful substances from tobacco smoke. However, it has turned out, that such filters are not capable of binding acetaldehyde, since the filter is too dry to let the reaction happen. The presence of acetaldehyde binding substances in tobacco product filters does not solve the problem of decreasing or removing the acetaldehyde or other aldehydes in saliva during smoking.
- the filters and other tobacco products disclosed in US 5,829,449 and US 4,532,947 are aimed for binding harmful substances from tobacco smoke, not from saliva.
- the preparations are also suggested to be used as a daily dosage, for example in the morning and in the evening, not specifically connected to smoking.
- Preparations affecting/increasing intracellular protection mechanisms, for example by low- dose cysteine, against acetaldehyde toxicity are insufficient to protect (or to bind acetaldehyde directly) upper gastrointestinal tract mucosa from the high acetaldehyde exposure during active smoking.
- compositions comprising substances capable of binding aldehyde(s) can be used to decrease the risk of developing cancer of the mouth.
- the compositions according to the invention can be used for heavy smokers.
- the average amount of saliva excreted by a human is 1.5 litres a day.
- the areas of influence of the aldehyde(s) contained in the saliva include the mouth, the pharynx, the oesophagus, and the stomach.
- the compositions of the present invention are capable of decreasing the risk of developing cancer of all these areas.
- aldehyde-binding substances for example cysteine is, that the binding of harmful aldehydes is not limited only to aldehydes, but they are able to bind also other harmful and toxic compounds of tobacco smoke dissolved into saliva.
- the present invention is examined more closely with the aid of a detailed description and examples.
- Figure 1 shows in vivo salivary acetaldehyde after ethanol ingestion in smokers (without concomitant smoking) and in non-smokers.
- Figure 2 shows in vivo salivary acetaldehyde after ethanol ingestion in smokers (with concomitant smoking) and in non-smokers. Differences between acetaldehyde concentrations are significant at all time points from 40 to 160 min (p ⁇ 0.05).
- Figure 3 shows salivary acetaldehyde in smokers after smoking one cigarette (without concomitant alcohol drinking).
- Figure 4 shows the salivary acetaldehyde after 5 min smoking with placebo, and with 1.25 mg, 2,5 mg, 5 mg or 10 mg cysteine tablets.
- Figure 5, 6 and 7 show various ways of attaching the preparation to a cigarette or cigar.
- Figure 8 shows a holder which keeps the preparation in contact with saliva during smoking and through which tobacco smoke is inhaled.
- Figure 9 and 10 show the impregnation of a holder or the surface of a holder with aldehyde binding substances.
- Figure 11 shows the impregnation of a filter or the surface of a filter of a cigarette with aldehyde binding substances.
- the aldehyde-binding substance refers to a compound comprising one or more free sulphhydryl groups and/or one or more amino groups. According to the disclosure preferred compounds have one or more free sulphhydryl groups and one or more amino groups. By amino groups are meant -NH 2 s -N, -NH- and NH 3 + groups.
- aldehydes comprise Ci - C 4 aldehydes potentially containing a double bond in the hydrocarbon chain.
- aldehydes include formaldehyde, acetaldehyde, crotonaldehyde and acrolein, acetaldehyde being particularly important.
- the aldehyde-binding substance refers also to compounds that are converted in mouth to an aldehyde binding substance. Such compounds are for example methionine and cystine.
- the binding of acetaldehyde refers to a chemical reaction between the acetaldehyde and the compound that has a free sulphhydryl and amino group, wherein the acetaldehyde jointly with the "acetaldehyde-binding substance" forms a larger molecule, and water can be formed in the reaction.
- the acetaldehyde when reacting with cysteine, the acetaldehyde binds itself both to the sulphhydryl and the amino group and forms 2-methyl-L- thiazolidine-4-carboxylic acid and water.
- the acetaldehyde can bind itself to the amino group of almost any protein, whereby Schiff s base or a 2-methyl-imidazole ring is formed.
- Preferred compounds according to the disclosure are cysteine, its derivatives, compounds that are converted to cysteine and other compounds that function in a similar manner.
- Suitable substances for the use according to the disclosure are in particular cysteines and N-acetyl-cysteines, preferably L- and D-cysteines.
- Preferred aldehyde-binding substances are naturally those that are not harmful for humans or which do not form harmful substances from aldehyde by chemical binding. It is also of advantage, if the compounds do not have unpleasant taste or smell.
- Suitable compounds for binding aldehydes, in particular acetaldehyde in saliva also include the compounds according to the formula:
- R 1 is hydrogen or an acyl group with 1-4 carbon atoms
- R 2 is a sulphhydryl or sulphonic group
- n is an integer of 1 or 2.
- a Shiff s base is formed.
- the acetaldehyde binding molecule should contain one or more free amino groups and one or more free -SH groups.
- the -SH group is at a suitable place of the molecule, it facilitates the forming of a Shiff s base and stabilizes the formed adduct.
- Amino acids or other compounds that suitably bind aldehyde comprise one or more free sulphhydryl (SH) group and amino (-NH 2 , -N, -NH- or NH 3 + ) group and comprise:
- the effect of some of the acetaldehyde-binding or other aldehyde-binding substances may be improved by vitamins, such as L-ascorbic acid.
- aldehyde-binding compounds according to the present invention should be non-toxic. Compounds suitable for the preparations according to the present invention should cause no health hazard in the amounts used in the invention.
- the compounds do not have unpleasant or very strong taste or smell. It is possible to mask the unpleasant taste of the effective compound by using suitable sweeteners and flavourings, but by using compounds having mild and/or pleasant taste it is possible to keep the composition simple, and its production is easier. Another way of decreasing the significance of the taste of the compounds is to use them in as small amounts as possible.
- Tobacco can be used by smoking, chewing and dipping and snuffing. According to our studies, especially smoking seems to cause the formation of acetaldehyde in the mouth.
- Smoking in connection with the present invention means typically the use of cigarettes or cigars or alternatively pipe smoking.
- the short-term binding of acetaldehyde means that acetaldehyde formed during smoking is bound immediately and that the binding effect lasts as long as one cigar or cigarette is smoked or a few minutes longer.
- the binding effect lasts preferably at least 5 minutes, more preferably at least 10 minutes, most preferably at least 15 minutes.
- Cigar smoking may last longer than cigarette smoking and therefore a preparation capable of binding acetaldehyde longer than 15 minutes is of advantage. However, the time is preferably shorter than 30 minutes.
- a person smoking a cigar may use more than one preparation during smoking of one cigar.
- the preparation according to the present disclosure should be able for the release of the acetaldehyde (or other aldehydes) binding substance to saliva at the conditions prevailing in the mouth within less than 30 minutes and preferably within less than 15 minutes from the point of time when the preparation is contacted with the saliva.
- Acetaldehyde binding substances should thus be released within 0 - 5 minutes, more preferably within 0 - 10 minutes, most preferably within 0 - 15 minutes from the point of time when the preparation is contacted with the saliva.
- the release of acetaldehyde binding substances lasts preferably essentially the time of smoking of one cigar or cigarette i.e. the time of actual smoking and a couple of minutes longer.
- a harmful/carcinogenic content of acetaldehyde in the human mouth, oesophagus, stomach, and large intestine is about 20-800 ⁇ mol/1 of saliva, although it is difficult to define an amount of acetaldehyde, which would not be harmful.
- Such a harmful or carcinogenic content of acetaldehyde in the human mouth can be obtained in connection with for example smoking and/or alcohol drinking.
- acetaldehyde (or other aldehydes) content essentially lower than without the use of the preparation of the present invention means keeping the acetaldehyde content of saliva at a level that is at least 20%, preferably at least 40%, more preferably at least 60 %, and most preferably at least 80% lower than when not using the composition.
- “In connection with smoking” herein refers to the period of time that begins from starting to smoke and ends, when smoking is stopped and 1 or 2 minutes before and after the actual smoking.
- a local preparation that is placed in the mouth refers to all preparations that are sucked or chewed in the mouth or that may be placed between the cheek, the lip or the tongue and the gum (gingiva), and in which the release of the substance is intended to have a local effect in the mouth.
- the preparation has effect also in the pharynx, the oesophagus or the stomach.
- composition means here the composition comprising the effective substance(s) optionally admixed with a suitable carrier.
- suitable carrier may be in the form of a local preparation suitable for use in mouth.
- a local preparation according to the invention may be selected from the group of chewable or sucking tablets, buccal tablets, sublingual tablets, candies, pastilles, chewing gums, bubble gums, gels and lozenges.
- the compounds that are used in the preparation that binds aldehydes can be compounds comprising one or more free sulphhydryl and amino groups.
- the preparation comprises preferably at least one carrier substance that does not hinder or facilitates the release of the effective substance. It is preferred that the preparation has a form that facilitates keeping it in the mouth when smoking.
- the preparation may be circular or oval, convex, ring-formed and small enough and have a form that does not harm or change the smoking action.
- the preparation may be put to the mouth during smoking or it may be attached by a suitable way to the tobacco product.
- the preparation may be kept attached to the tobacco product during smoking or it may be detached from the tobacco product and put to the mouth when starting to smoke.
- the amount of the effective substance can be kept as low as possible, since there is then no or minor need to mask the taste of the compound, if the taste of the substance is unpleasant.
- the person using the composition need not consume too high concentrations of the compound.
- the preparation will also be less expensive.
- the preparation of the present invention comprises preferably 1 to 300 mg aldehyde- binding, in particular acetaldehyde-binding substances, more preferably the amount is 1 to 250 mg, still more preferably 1 to 200 mg, even more preferably 1 to 150 mg, most preferably 1 to 100 mg. Higher amounts are specifically preferred when the aim is to bind various aldehydes in addition to acetaldehyde. The amount may be lower, if the aim is, in particular, to bind acetaldehyde.
- the preparation of the present invention comprises 1 — 50 mg, more preferably 5 - 30 mg, more and more preferably 5 — 10 mg, or even 1 - 5 mg, typically 10 -20 mg, or 1 - 20 mg, in some embodiments 15 - 20 mg aldehyde-binding, in particular acetaldehyde-binding substance or substances.
- the amount of the substances may preferably be higher, if the preparation is kept attached to the tobacco product during smoking as compared to, when the preparation is put to the mouth when starting to smoke.
- a composition comprising the effective substance(s) may be concentrated and/or dried and/or impregnated to a tobacco product, to a filter or to a holder.
- the composition is preferably attached to that part of a tobacco product, filter or holder, which is put to the mouth when smoking. This may be about 1 to 10 mm from the tip of the tobacco product.
- the composition is attached to the surface of the tobacco product, filter or holder. This means that the concentration of the aldehyde-binding substance(s) is preferably higher on the surface of a tobacco product compared to the concentration inside of the tobacco product, filter or holder.
- the composition may, for example, be concentrated and/or dried and/or impregnated on the surface of the paper of a tobacco product, or filter or on the surface of a holder.
- the paper of a tobacco product may be protected by nonporous material not to let the aldehyde-binding substances to become absorbed into the paper and through the paper to the tobacco product or filter or holder.
- the composition may be impregnated to the surface area of a tobacco product, to a filter or to a holder. The area may extend 1 or 2 mm from the surface towards the inside of the tobacco product, filter or holder.
- the impregnated filter may also be separate from the tobacco product and may, for example, be attached to the tobacco product or located into a holder of a tobacco product.
- the amount of aldehyde-binding substances may in these applications preferably be higher than in a preparation kept in the mouth.
- the amount of aldehyde-binding substances may be more than 5 mg, preferably more than 10 mg, more preferably more than 20 mg, most preferably more than 30 mg, even more preferably more than 50 mg per one tobacco product or filter or holder. Smaller amounts are preferred, if the composition is concentrated and/or dried and/or impregnated only to the surface of a filter, a tobacco product or a holder.
- composition may comprise:
- compositions comprising pharmaceutically acceptable diluents (fillers, bulking agents), 2. sweetening agents such as sugars and sugar alcohols, 3. flavouring agents and 4. lubricants/glidants.
- Sugars may comprise for example sucrose, fructose or glucose or a combination of these.
- Sugar alcohols may comprise mannitol, sorbitol, maltitol, lactitol, isomalt or xylitol or a combination of these.
- none of the additives reacts with other ingredients in the preparation.
- a preferable sweetening agent is mannitol, because it is not very sweet and its amount in the preparation can be quite high and thus its acts at the same time as a diluent.
- Flavouring agents may comprise for example spearmint, peppermint, menthol, citrusfruit, eucalyptus or aniseed or a combination of these.
- the preparation may comprise also other components, such as agents masking oral malodor, agents acting as breath freshener and/or agents preventing dental caries, or the preparation may comprise vitamins.
- the preparation may comprise also agents enhancing the excretion of saliva.
- these additional components should not prevent the quick release of the aldehyde binding substance to the saliva. As described here earlier, the preparation should release aldehyde binding substance so effectively that an essential amount of aldehyde is bound in saliva, before aldehyde affects the mucous membrane cells in mouth.
- the preparation (for example one tablet) may comprise or consist essentially of: Aldehyde binding substance(s) 1 - 50 mg
- the preparation may be a sucking tablet comprising:
- the composition is prepared by mixing the powder mass and compressing it into sucking tablets by well known methods.
- the amount of aldehyde-binding substances is increased, the amount of diluent(s)/sweetening agent(s) and flavouring agents may be increased also, since the taste of aldehyde-binding substances may be needed to be masked.
- Aldehyde-binding substances 1 - 50 mg Gum base comprising sweetening or other agents 500 - 1500 mg Flavouring agent q.s.
- the gum base may comprise medical chewing gums (Morjaria, Y. et al., Drug Delivery Systems & Sciences, vol. 4, no 1, 2004.), which comprise natural or synthetic elastomers, plasticizers, waxes and lipids.
- Natural gum bases including chicle and smoked natural rubber are permitted by FDA.
- modern gum bases are mostly synthetic and include styrenebutadiene rubber, polyethylene and polyvinylacetate.
- the gum base makes up to 15 to 40 % of the chewing gum. The remainder consists of drug, sugar, sweeteners, softeners, flavouring and colouring agents.
- the majority of chewing gum based drug delivery systems are manufactured using conventional processes. However, directly compressible powdered gums are modern alternatives for medical chewing gums.
- Pharmagum is a compactable new gum system. It is a mixture of polyol(s) and/or sugars with gum base. Formulation containing Pharmagums can be compacted into a gum tablet using conventional tablet presses. The manufacturing process is rapid and cheap.
- the amount of the gum base comprising sweetening agents may be in a preparation 50 - 500 mg, preferably 500 - 1500 mg.
- Pharmagum S contains gum base and sorbitol
- Pharmagum M contains gum base, mannitol and isomalt.
- the preparation may be a chewing gum comprising:
- the composition is prepared by mixing the powder mass and compressing it into chewing tablets.
- the preparation may be a buccal tablet, which comprises:
- Non-ionised macromolecules include, for example, methylcellulose (MC), hydroxypropylcellulose (HPC), and hydroxypropyl-methylcellulose (HPMC), and polyethylene glycol (PEG).
- Ionising polymers include, for example, sodium carboxy- methyl cellulose (NaCMC), alginic acid, sodium alginate, chitosan, polycarbophil (NoveonTM), and carbomer (CarbopolTM).
- the preparation may also be a sublingual tablet, which comprises or consists essentially of:
- Diluents include, for example lactose, calcium phosphates, starch, carboxymethylcellulose, hydroxymethylcellulose.
- Sweetening agent can be for example mannitol or xylitol.
- the preparation is capable of binding aldehyde in saliva during smoking of 1, 2 or 3 cigarettes or cigars.
- the kit may comprise a tobacco pack or box for cigars or cigarettes connected with another box or pack for the preparations.
- the cigars or cigarettes and the preparations may be in the same or separate pack or box.
- the two packs or boxes may be separate or connected.
- the kit comprises essentially the same or higher number of preparations as cigars or cigarettes.
- the preparation may be attached to a tobacco product, such as a cigar, cigarette, holder or pipe.
- the preparation may be in any suitable form, such as chewing or sucking tablet, buccal tablet, sublingual tablet, candy, pastille, lozenge, chewing gum or gel.
- the preparation may be of any suitable shape, such as circular, oval, convex, nail-like, cylinder-like, ring- like or rectangular.
- the preparation may be attached to a cigar, cigarette, holder or pipe in a detachable way.
- a person starting smoking may detach the preparation from the tobacco product by hands, by teeth or by some other way and chew, suck or keep the preparation in mouth, for example under the tongue or between the cheek and the gum thereby keeping the preparation in contact with saliva.
- the preparation is preferably attached to that part of a cigar or cigarette (with or without a filter), holder or pipe, which is put to the mouth during smoking. This is because the preparation should come into contact with saliva during smoking.
- the preparation is preferably attached to the surface and near the tip or at the tip of a cigar, cigarette, pipe or holder.
- the preparation should also release the aldehyde-binding substances easily to saliva.
- the diameter of the preparation may be about the same as the diameter of a cigar or cigarette, about 3 to 10 mm, preferably about 3 to 8 mm.
- the preparation may be attached to the tip or near the tip of a cigar, cigarette, holder or pipe by a non-toxic adhesive-like material or by using a tape-like system.
- Adhesive-like materials suitable for foodstuff use are known to a person skilled in the art. Such materials are for example starch-based, sugar-based or protein-based adhesive-like materials.
- the preparation may be attached to the tobacco product mechanically, for example by pressing it to the surface of the tobacco product.
- the preparation may comprise a projection with which the preparation is kept attached to the tobacco product, in particular to a cigar or cigarette.
- the shape and size of the preparation may be suitable in order to keep it attached to the tobacco product, for example ring-formed or half-ring-formed.
- the preparation may be kept attached to the cigar, cigarette, holder or pipe by using an arrangement for keeping the preparation in contact with the tobacco product, filter or holder.
- the arrangement may be a vehicle holding or carrying the preparation.
- the arrangement may, for example, be a cylinder-formed part, which lengthens the tobacco product by about 1 to 5 mm. It may carry the preparation in such a way that the preparation becomes in contact with saliva when the tobacco product is put into mouth during smoking allowing at the same time the smoke go through the arrangement.
- the arrangement may be some inert material, such as plastic.
- the preparation and the arrangement may be attached to the tobacco products by the manufacturer of the tobacco products or by the smoker.
- a composition comprising aldehyde binding subtance(s) may be impregnated to that part of a cigar or cigarette (with or without filter), which is put to mouth when smoking.
- the composition may be impregnated also to a holder for cigarette or cigar.
- the composition may be impregnated also to a separate filter, which may be put in front of the tobacco product optionally with a holder.
- the composition is impregnated and/or concentrated and/or dried to the surface of a cigar, cigarette, filter or to the surface of a holder, which is used when smoking.
- the composition may, for example, be impregnated directly to the surface of a cigar, cigarette or holder or into a suitable material, such as cellulose, which is attached to the surface.
- a composition comprising aldehyde-binding subtance(s) and concentrated and/or dried and/or impregnated to a tobacco product, to a filter or to a holder, in particular to the surface of a cigar, cigarette, filter or to the surface of a holder, may be used as a solution or in solid form, for example as a powder optionally with or without a carrier.
- the composition may comprise the same components as the local preparation. It may comprise also a diluent, which may be any suitable, volatile diluent, preferably water, which is evaporated during the preparation procedure.
- the content of aldehyde formed in saliva as a consequence of smoking can be decreased so that in connection with smoking, a preparation, preferably one or two preparations at a time, is/are placed in the mouth, under the tongue or in the cheek, or between the cheek and gum for example, which at a suitable and preferably at a constant rate release(s) cysteine (or an aldehyde-binding agent having essentially the same effect as cysteine) continuously and preferably until one tobacco product is used.
- a new aldehyde-binding preparation is placed in the mouth.
- the aldehyde content of saliva decreases by over 20%, preferably by over 40%, more preferably over 60%, typically by 60-80% compared to placebo.
- the preparation is able to decrease aldehyde content of saliva during the smoking of one cigar, cigarette or pipe to a level aldehyde was before smoking.
- aldehyde- binding preparation is repeated as many times as a new tobacco product is started. It is of advantage, if the preparation is placed in the mouth already before starting a new cigar, cigarette or pipe.
- the amount of aldehyde-binding substance(s) in one preparation should be essentially sufficient to bind aldehyde in saliva to a level aldehyde was before smoking.
- the aldehyde-binding composition is attached to a tobacco product, filter or holder, by an adhesive-type material, by an arrangement or by any other way or by concentrating, drying or impregnating the composition to the tobacco product, filter or holder, the amount of the effective substance should essentially be sufficient to bind aldehyde in saliva during the smoking of one tobacco product, preferably the amount should be at least 2, preferably at least 5, more preferably at least 10 times higher.
- a sucking tablet was prepared comprising:
- Mannitol or equivalent sugar or sugar alcohol
- the composition was prepared by mixing the powder mass and compressing it into sucking tablets.
- Sucking tablets were prepared as in Example 1, but comprising 1.25 mg, 2.5 mg, 5mg and 10 mg cysteine.
- a chewing gum was prepared comprising:
- composition was prepared by mixing the powder mass and compressing it into chewing gums.
- Another composition was prepared comprising 500 mg Pharmagum S or M and 20 mg magnesium stearate.
- a buccal tablet was prepared comprising:
- composition was prepared by mixing the powder mass and compressing it into buccal tablets.
- Example 5 A sublingual tablet was prepared comprising:
- the composition was prepared by mixing the powder mass and compressing it into sublingual tablets.
- Example 1 The preparation prepared in Example 1 was tested by two test persons.
- the acetaldehyde content of saliva of the test persons was measured before smoking and then after each 5 min during smoking, i.e. 0 min, 5 min, 10 tnin and 15 min after the test persons had started smoking.
- Both of the test persons smoked one cigarette at the same time collecting saliva to their mouth and sucking a placebo tablet. The smoking lasted 5 min.
- the test persons repeated the study by sucking a tablet comprising 20 mg cysteine.
- Sucking tablets, chewing gum, buccal tablet and sublingual tablets are prepared comprising 5 mg L-cysteine.
- a cigarette (1) is prepared according to conventional methods.
- the cigarette may comprise a filter (2) or it may be without a filter.
- a cysteine comprising preparation (3) is prepared as disclosed here earlier.
- the shape of the preparation may be any suitable shape, such as circular, oval, convex, nail-formed, ring-formed, cylinder or rectangular.
- the preparation (3) is attached to the cigarette (1) by an adhesive-like material suitable for human use.
- the cysteine composition is in the shape of a ball attached to that part of the cigarette, which is put to the mouth when smoking
- Figure 5 B is shown the cigarette with the preparation as a cross-section.
- the preparation (3) is at the tip of the cigarette (1) at that part of the cigarette, which is put into mouth when smoking.
- Figure 6B is a cross-section of the same.
- the preparation (3) is rectangular and it is bent around the tip of the cigarette at that part of the cigarette (1), which is put to the mouth when smoking
- Figure 7B is cross-section of the same.
- a cylinder (5) is attached to the tip of the filter (2) of a cigarette (1).
- a preparation (3) comprising cysteine is located inside the cylinder.
- a holder (4) or the surface of a holder is impregnated by cysteine (3).
- a holder (4) or the surface of a holder is impregnated by cysteine comprising composition (3) and the shape of the holder is suitable for holding in particular a cigar.
- the filter (2) or the surface of a filter of the cigarette (1) is impregnated by cysteine (3).
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Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2007535189A JP5654726B2 (en) | 2004-10-08 | 2005-10-10 | Methods and formulations for binding aldehydes in saliva |
FI20070261A FI20070261A (en) | 2004-10-08 | 2007-04-03 | Method and preparation for binding aldehydes from saliva |
US11/783,333 US20080000489A1 (en) | 2000-10-30 | 2007-04-09 | Method and preparation for binding aldehydes in saliva |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US61729904P | 2004-10-08 | 2004-10-08 | |
US60/617,299 | 2004-10-08 | ||
US66072305P | 2005-03-11 | 2005-03-11 | |
US60/660,723 | 2005-03-11 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/783,333 Continuation US20080000489A1 (en) | 2000-10-30 | 2007-04-09 | Method and preparation for binding aldehydes in saliva |
Publications (1)
Publication Number | Publication Date |
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WO2006037848A1 true WO2006037848A1 (en) | 2006-04-13 |
Family
ID=36142320
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/FI2005/000429 WO2006037848A1 (en) | 2000-10-30 | 2005-10-10 | Method and preparation for binding aldehydes in saliva |
Country Status (2)
Country | Link |
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JP (1) | JP5654726B2 (en) |
WO (1) | WO2006037848A1 (en) |
Cited By (11)
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WO2008136000A2 (en) * | 2007-05-07 | 2008-11-13 | Technion Research & Development Foundation Ltd. | Compositions, articles and methods for preventing or reducing tobacco-associated damage |
WO2008139042A1 (en) * | 2007-05-16 | 2008-11-20 | Biohit Oyj | Filter for a tobacco product |
WO2009034232A1 (en) | 2007-09-14 | 2009-03-19 | Biohit Oyj | Preparation and a component intended to be added to a tobacco product |
JP2009537613A (en) * | 2006-05-22 | 2009-10-29 | ビオヒット・ユルキネン・オサケユキテュア | Food composition for binding acetaldehyde |
US20120012123A1 (en) * | 2007-05-07 | 2012-01-19 | Technion Research & Development Foundation Ltd. | Compositions, articles and methods for preventing or reducing tobacco-associated damage |
WO2013178880A1 (en) | 2012-05-28 | 2013-12-05 | Biohit Oyj | Composition for preventing headaches |
WO2014118438A1 (en) * | 2013-02-01 | 2014-08-07 | Biohit Oyj | Composition for binding aldehydes in the mouth |
WO2014140411A1 (en) | 2013-03-12 | 2014-09-18 | Biohit Oyj | Encapsulated composition for binding aldehydes in the stomach |
WO2014140410A1 (en) | 2013-03-12 | 2014-09-18 | Biohit Oyj | Composition for oral administration for binding aldehydes in the gastrointestinal tract |
WO2015132472A1 (en) | 2014-03-06 | 2015-09-11 | Biohit Oyj | Composition for binding aldehydes and free radicals in the gastrointestinal tract |
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WO2011158689A1 (en) * | 2010-06-19 | 2011-12-22 | 天野エンザイム株式会社 | Agent for reducing acetaldehyde in oral cavity |
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US20120012123A1 (en) * | 2007-05-07 | 2012-01-19 | Technion Research & Development Foundation Ltd. | Compositions, articles and methods for preventing or reducing tobacco-associated damage |
JP2010526550A (en) * | 2007-05-16 | 2010-08-05 | ビオヒット・ユルキネン・オサケユキテュア | Filter for tobacco products |
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EP2197436A1 (en) | 2007-09-14 | 2010-06-23 | Biohit Oyj | Preparation and a component intended to be added to a tobacco product |
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EA030968B1 (en) * | 2007-09-14 | 2018-10-31 | Биохит Оий | Preparation and a component intended to be added to a tobacco product |
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