MXPA00005413A - Oral antioxidant preparation comprising selenium and reduced glutathione - Google Patents

Abstract

A composition for reducing free radical damage induced by tobacco products and environmental pollutants. The composition includes reduced glutathione and a source of selenium. The composition can be administered orally in the form of a gel, lozenge, tablet or gum.

Description

ORAL PREPARATION, ANT IOXI DANTE, WHICH UNDERSTAND SELENIUM AND REDUCED GLUTATIONA TECHNICAL FIELD OF THE INVENTION The present invention relates to the combination of various antioxidants related to synergy, enzymatic cofactors and amino acids in appropriate delivery vehicles, used in solid carriers, such as tablets, pills and chewing gums, as a means for the prevention and alleviation of symptoms and complications of damage caused by a free radical species of the cavity of the pharynx-gold and mouth, which includes the oral mucosa gums and tongue, as well as the upper respiratory tract. Such free radical species are induced by tobacco smoke, non-smoked tobacco, harmful or malodorous substances, noxious, chewed or ingested; as well as other inhaled environmental pollutants and particulate matter, including tobacco to secondary smokers.

BACKGROUND OF THE INVENTION The harmful effects of tobacco abuse are well known, and the regulatory agencies as well as the public constantly react to these scientific and epidemiological evidences. Tobacco is a real threat to public health worldwide that has a significant morbidity and mortality. In spite of the places for smokers, an abundant oxidant attacks the oro-pharynx and the respiratory tract, in addition to the local atmospheric pollutants existing in such a specific environment, the evidence refers to the fact that the burnt oxidant is found in the body's entire organism. smoker, particularly in the development or increase of atherosclerosis, which causes cardiovascular damage, pulmonary diseases of chronic obstruction and various forms of cancer, including malignant tumors of the mouth, pharynx, esophagus and lung. Tobacco is a substance that consists of dried leaves and shoots of the Nicotiana Tabacum plant, which contains the drug nicotine, which is very addictive. The plant is native to North America but is now cultivated worldwide. Tobacco abuse has been identified as the single most avoidable cause of disease, morbidity and mortality. Tobacco smoke contains many toxic chemicals and free radical species. There are three main ways to consume tobacco: smoking, chewing, as well as submerging and aspirating. Some 50 million Americans smoke and countless more as secondary smokers are affected by tobacco smoke. Children of smokers breathe this secondhand smoke and have more respiratory problems than children of non-smokers. Smoking without smoking is used more or less by 12 million individuals and has a harmful effect on the oral cavity, in addition to the systematic effects on the oral absorption of nicotine and other chemicals. Chewing the loose leaves of tobacco and tobacco snuffed, ground, "submerged" in some moisture; they are the most common uses of tobacco without smoking. The "aspiration", that is, puffing dry tobacco powder into the nostrils is rarely used in this country. The risks to health from smoking without smoking is still very significant, and this is not a substitute for avoiding smoking. Studies have estimated that tobacco smoke has more than 3,000 different constituents, of which a number is toxic, some are carcinogenic and many others generate free radical species. Most of these compounds have been identified in the so-called main stream and the side stream of tobacco smoke. The trainer is the volume of smoke pulled through the mouthpiece of the tobacco product, this during the puff; while the sidestream is the smoke emitted from the cigarette with smoke without flame between the puffs. Although nicotine and tar are retained in the filter of cigarettes, this applies mainly to the smoke of the main stream, when the comparison between cigarettes with filter and cigarettes without it is presented. The emission of smoke in the mainstream is also markedly reduced in cigars with a low and ultra low tar production. Nevertheless, the emissions of toxic and carcinogenic components in the side streams of smoke, are not significantly reduced in filter cigarettes when compared to unfiltered cigarettes. Thus, sidestream smoke is the largest contributor to environmental smoke, which affects smokers and non-smokers, called secondary smokers. The low rates of consumption of cigarettes with high smoke production, have not reduced the internal pollutants of the carcinogenic substances, nor the free radicals which generate the potential of tobacco smoke, produced in the smoke of the side stream; despite their reduced levels in the main stream of smoke smoking filter cigarettes, and low production tobacco.

Cigarette smoke induces oxidative damage to lipids, DNA and proteins, particularly to SH protein groups because this smoke contains high levels of both; free radicals and aldehydes, including acetaldehyde (ethanol), propanol and acrolein, as well as other harmful molecules. In U.S. Patent No. 5,060,672 (October 29, 1991), which is incorporated herein for reference purposes, Irimi et al. Describe an efficient filter for tobacco smoke. Its mechanical component and absorption filtering also provide chemical absorption properties for the reduction of aldehydes in cigarette smoke.

Tobacco, whether it is smoked like cigarettes, cigars or pipe; or that is used in the modalities called smokeless, or those of chewing; causes common unfavorable effects in the oral cavity. Tobacco smoke has two opportunities to exert its harmful effects in the mouth; when it is inhaled by the smoker and when it comes out during the exhalation. The American Lung Association states that chewing tobacco, whether it is what is called sucking, chewing, compressing, or spitting it, or even smokeless tobacco, is still a form of tobacco. The content of nicotine is similar to the cigarette and this tobacco is eti or logically responsible for oral cancer, just where it is chewed or "stored" in the mouth, gums or cheeks.

Like cigarettes, the evidence shows that cigars are also toxic and addictive. Cigarette and cigarette smokers have a similar increased risk for oral and laryngeal cancers. While cigarette tobacco is usually cured with a slightly acidic resulting product, the slowest curing methods for pur or s. they produce this slight alkalinity. At this pH, nicotine is more easily absorbed. Unlike cigarettes, cigars are less homogeneous, and these vary in size and nicotine content. Cigar smokers can stay an hour smoking a single, "Havana", large; although some actively inhale very little of this smoke; However, in non-inhalers, nicotine levels can be elevated without toxic absorption, as in cigarette smokers. Cigar smokers also commonly keep a cigar in their mouth, which allows additional nicotine to have local absorption. Thus, the consumption of cigars can produce an equal or higher generation of smoke, exposure and free radicals generated locally in the oral cavity, which results in effects and risks of diseases in the pharyngeal oro-pharynx. For cigars, as for pipe tobacco as well as for non-smoking tobacco, there is less publicity and information available to their consumers, than for cigarette smokers, although the concomitant administration of anti-oxidant compositions, ine r g ti ti es, of the present application, can help oral cancers, and improve the complications of the pharynx by tobacco abuse; either d-e cigarettes, cigars, pipe or tobacco without smoking. Cigarette smoke is divided into 5 phases in 5 phases, tar and gas phase smoke. Tobacco tar contains high concentrations of free radicals. The most common oxidants include sequinone which is found in equilibrium with hydroquinones and quinones, particularly in the viscous matrix of tar. Many of the extracts of tar and oxidants, including the second; they are soluble water and reduce oxygen to superoxide radicals which can be changed to form H202. Importantly, glass filters, like fiberglass, retain almost all of the tar particles that are larger than 0.1 microns. Thus, the filter acts as a trap for the tar in the cigarette smoke. There is an excessively large number of free radicals, greater than 1015 in each puff in the gaseous phase of cigarette smoke.

While oxidants in tar are stable, those organic radicals in the gas phase smoke are reactive carbon and oxygen radicals centered with extremely short half-lives. Interestingly, the concentrations of free radicals remain at high levels of more than 10 minutes and tend to increase as tobacco grows older. In this way it is considered that these oxidants of the smoke in the gas phase are in a fixed state, this because both are continuously formed and destroyed. The last reactions are similar to those that are noticed present in smog, considering the extra harmful stimulus for primary and secondary smokers in polluted atmospheric environments. Although the best protection against oxidant damage in cigarette smoke is the cessation of smoking with personal and "environmental" abstinence, protection against oxidants is presented through oral solutions, spray and spray, as taught the present description, and by means of supplementary diets, as suggested by some clinical investigations. These inhalation and oral spray measures can improve and delay the oxidative damage of putative tobacco smoke in smokers and their close non-smoking neighbors, as well as those who use tobacco (chewing) without smoking.

In addition to the above, in other in vitro studies, cigarette smoke in the gas phase was evaluated in its complete state (without filtering) and filtered for oxidative effects in human plasma. Researchers have noted the frequency of lipid peroxidation in the plasma after exposure to smoke in the gas phase, but not in the smoke of the whole cigarette. The reaction of the lipid peroxidation does not occur until the endogenous ascorbic acid has been consumed, that is, vitamin C has been completely oxidized. It has been noted that exposure to cigarette smoke causes the oxidation of plasma protein thiols (amino acid cysteine and methionine bonds) and low density lipoproteins. It was concluded that the lipid peroxidation induced by the oxidants of the smoke in the gas phase ft leads to changes in the lipoproteins associated with the a t erogenous s i s. As already noted in this description, the synergy effect of reduced glutathione, the enome t-onine and the ascorbic acid, are beneficial to combat the oxidants of snuff in addition to improving and retarding the effects of tobacco smoke in the oro-pharynx and upper respiratory mucosa.

Cells subjected to oxidative stress severely affect cell function and cause damage to membrane lipids, proteins, cytoskeletal structures and DNA. The damage that causes the free radical to DNA has been measured as the formation of single strand breaks, double-strand breaks and chromosome aberrations. Cells exposed to ionizing radiation and cigarette smoke have also been shown to have increased intracellular DNA damage, a precursor of mutations, and a development of ma gins.

The macrophage cells and neutrophils have their phagocytic activity associated with the so-called "respiratory combustion" reaction, which is dependent on the NADPH oxidase activity of the plasma membrane. Then, the resulting oxygen radicals can be transformed to H202 by the dismutase superoxide. Researchers have shown that smokers have a higher "respiratory combustion" reaction of alveolar macrophages and peripheral neutrophils than nonsmokers, and the trainer also has a higher incidence of respiratory and oral signs and symptoms than non-smokers . It was determined that there is a decrease in the effect of this "respiratory combustion" reaction in smokers supplemented with oral megadoses of anotoxins. In the inhalation and intraoral preparations of the present invention, with antiretroviral drugs, they are thus beneficial for primary and secondary smokers.Due to the access of the pharynx to the environment, as well as the skin to oxygen and ultraviolet radiation, the structures of the oral cavity can be damaged by the inhalation, ingestion or chewing of harmful substances and gaseous as well as particulate materials, especially in both types of smokers, liabilities and assets, - as well as damages through the xenobiotic system and through endogenous processes, such as inflammatory reactions. Oxidation species by reaction, such as that induced by inhaled tobacco smoke, ozone and nitrous oxide, are important factors in the generation of free radicals as well as the induction of inflammatory reactions. As in other tissues, anti-oxidant enzymes exist in the oro-pharynx and include superoxide dismutase (SOD), which converts superoxide to hydrogen peroxide and catalase which reduces hydrogen peroxide in water. This reaction can also be catalyzed by selenium as a cofactor for the enzyme glutathione peroxidase using reduced glutathione (GSH) as a substrate. In addition, they can reduce the lipid peroxides to the corresponding alcohols also using GSH.

Glutathione, a sulfur containing tripeptide (L-gamma-glu t ami 1 - 1 - c i s t and ina-glycine), is the most abundant non-protein thiol in mammalian cells and is known as the main antigens. Glutathione, in its reduced form, known as GSH, acts as a substrate for the enzymes GSH-S-trans as well as the GSH-peroxidases (with the selenium cofactor) that catalyzes the reaction for the s in t ox i In the case of the xenobiotic compounds, and for the anti- oxidation of the reactive oxygen species and other free radicals, the GSH synthesis takes place in two steps: (1) an initial ratio limitation step catalyzed by range glutamyl cysteine synthetase to form glutamyl cysteine range. (2) glutathione synthetase catalyzes the reaction between glycine and glutamyl cysteine to form GSH. Intracellular stability is conferred to GSH by the resistance of gamma-glutamyl bond to intracellular peptidases. This link can be divided by means of the range glutamyl t r anspep t to which it is usually located on the outer surface of the membranes of the cell. This activity is high in the kidney, where the GSH is subjected to renal cleansing by tubular cells and by this tr anspep tion reaction, which results in the excretion of the urine or the retransport of the plasma as the amino acid constituent, glutamine, cysteine, and glycine. In this collection, together with the amino acids derived in a nutritional way from the digestion and small absorption of energy, these amino acids are available to the liver for the GSH synthesis. The liver and the lung also export GSH in its oxidized form denoted as GSSG, which is produced when the peroxides are detoxified by the GSH-peroxides a, the GSSG is recycled back to the reduced form, GSH, by the glutathione reductase in a reaction with NADPH.

The ubiquitous glutathione plays a vital role in the maintenance of the integrity of cellular components, sensitive, free radical species of reaction with oxygen. This is done through its direct role as an oxygenator, in its reduced form (GSH), as well as a cofactor like those previously mentioned. In cells, GSH concentrations for antioxidant activity are maintained in equilibrium by the enzyme glutathione reductase. Under the states of GSH reduction, which includes poor nutrition and severe oxidative stress, cells can then be injured from excess free radical damage and die.

Other nonenzymatic molecules that play an anti oxy oxy role include ascorbates (vitamin C) as free radical scavengers, in addition they react with oxidized glutathione (GSSG) and reduce it to GSH. Also, in the lipid membrane of the cells, the cells in the hydrophobic body (vitamin E) act inertly with vitamin C to inhibit lipid peroxidation, as this can be induced by the lipid peroxidation. smoke from a cigarette, by active depuration of lipid peroxides and other radicals.

Several studies have been correlated with the importance of oxidative stress for various organs resulting from tobacco smoke and other harmful environmental factors, and thus continue to play a role in the health of the public of all countries. Significant morbidity and mortality result from smoking tobacco from cigarettes, cigars, and pipes and the local oral pathology of chewing tobacco. Epidemiological studies have strongly related to smoking in the pathogenesis of atherosclerosis and several malignancies, including neoplasms of the respiratory tract and the oro-pharynx. Smoking cigarettes chronically is associated with the appearance of free radicals that induce oxidative damage. The measurement in the blood, urine and tissues of the various antioxidants or related products of the metabolic processes of free radicals, are supported by oxidative damage to tissue in the pathogenesis of several diseases associated with tobacco smoking and with environmental contaminants .

In the oro-pharynx, cigarette smoke accelerates the production of reactive oxygen species by recruiting local neutrophils, neutralizing and activating phagocytic cells in response to harmful agents. Attack by cigarette smoke, and free radicals on plasma proteins, can be measured by carbonyl assay and by loss of enzymatic activity and SH groups. Researchers have shown that gas smoke from the gas phase and complete, produces the formation of carbonyl in human plasma, which is particularly inhibited by GSH. In contrast, the exposure of human plasma to the gas phase but not to the complete smoke of the cigarette, produces oxidative damage to the lipids.

The leukoplakia, a white patch induced by tobacco to the buccal mucosa, as found in smokers, is a localized irritation due to the direct contact of smoked or non-smoked tobacco, and this is directly related to the frequency and years of use of tobacco. Although 1 to leucoplaqueia is a benign oral lesion, it has a potential for malignancy, which requires a biopsy of the lesion to remove the cancer. The leukoplakia can be removed or completely resolved when the use of tobacco products is discontinued. Appropriate oral examinations by primary physicians and dentists is very important to reduce the smoke induced in the mouth and the pathology of the teeth. In addition, tobacco contributes to other oral symptoms or pathologies of the mouth and teeth. Tobacco can cause halitosis, can hinder taste, and interfere with. the smell and taste of the food. This can stain teeth and contribute to tooth decay. Smokers have more dental calculus (calculus) than non-smokers. Tobacco is also associated with destructive periodontal disease (gums) and tooth loss. Acute necrotizing ulcerative gingivitis (cracked mouth) is a painful, destructive inflammatory condition that occurs mainly in smokers. Inflammation of the nose and sinus membranes have also been associated, significantly, in individuals who are "allergic" to tobacco smoke.

In addition to the 1 eucop 1 aque-fe-ñ, another whitish form in the buccal mucosa represents the entity of oral submucosal fibrosis. This disease occurs mainly in India and is a premalignant, progressive, and chronic condition. The etiology is the chronic chewing of tobacco or the ureca or both. Fibrosis results in restriction of the opening of the mouth and involves the palate, the tonsilar fossa, the buccal mucosa and the nearby muscle. Associated with this condition are carcinomas of the oro-pharynx, also with a high frequency in India and associated in 70% of cases with the chewing of tobacco. The use of smokeless tobacco and areca is also common in Pakistan, Bangladesh and Java and in these Indian immigrants to the United States and the United Kingdom.

Annually, more than 30,000 new cases of cancer of the oral cavity have been diagnosed, representing two to four percent of all new cancers. Oral cancer kills 8,000 patients each year and only half of the cases diagnosed annually have five years of survival. The vast majority of these patients are users of tobacco products. Other risk factors include alcohol abuse, nutritional deficiencies and poor oral hygiene.

An e s t u d o r e c e n t eme n t has been related to benzopyrene, as in cigarette smoke, with mutations to the human P53 gene that leads to oral and respiratory malignancies. Notably, 3,4-benzopyrene is present in the polluted atmospheres of large cities such as Los Angeles, Mexico City, and London, which is produced as a product exhausted from the traffic of engines, especially diesel engines. Breathing air contaminated with high concentrations of this compound, particularly under hazy conditions such as in London, provides more than 100 times and another of this putative mutagen to cigarette smokers. Thus, the use of the present invention as taught should be beneficial to citizens, particularly if they are citizens of congested cities with a lot of traffic and smog and haze. This provides the individual with another protective measure for such mutagens generated in their bodies, not resisting measures to decontaminate atmospheric pollution and public and personal efforts for tobacco cessation.

Cigarette filters "trap" tar and nicotine but not the gas phase compounds. Epidemiological studies have been conducted in several countries to show the differential effects of tar content, quantity of smoked cigarette, type of smoked tobacco, and the use of filters in the risk of lung cancer and pharynx in smokers of cigarettes Cigarette smoke has effects not mentioned through free radicals and mechanisms of involvement of other organs, such as the skin. The doctor . Douglas Model of England in 1985 added to the term of medical lexicography the term "face of the smoker" of a study with photographs of 116 cases and appropriate controls for not smoking. Similar to a damaged photograph, smokers appear older and have more wrinkles. These also have a greater inclination to cancer of the lips and mouth.

Recently, cigarette sales have increased, partly due to popularity with women and the arrival of "cigarettes" that are friends of women. The evidence, however, occurs when the carcinogenic particles of the cigar exceed three cigarettes and the level of carbon monoxide is 30 times higher. The smoke of the cigars are of great consequence for secondary smokers. Epidemiological studies reveal higher frequencies of heart disease, emphysema, and cancers of the mouth and pharynx in cigarette smokers when compared to their non-smoking peers.

There are a number of preparations on the market such as toothpastes, gels, breath fresheners, mouth rinses and oral washes to protect the mouth and teeth from the effects of smoked or chewed tobacco. Cigarette tar can be deposited on the teeth, gums, water and other surfaces of the oral cavity of smokers. Tobacco tar, a viscous, oily, dark mixture of aliphatic and aromatic hydrocarbons po 1 i to cr i 1 i co s, is produced in the smoke of cigarettes, cigars, or pipe by means of the combustion of tobacco. The smoker inhales the tar and other products of tobacco combustion are pulled into the oral cavity and the respiratory passages. The smoke is then exhaled, passes for a second time through the mouth of the smoker, again depositing the tar. This causes the de struction of the teeth and other oral surfaces. Not only do they cause the smoker to "breathe badly", but it also rots the teeth and is harmful to the gums. Smoking without smoking is equally locally harmful. Food particles, oils and other substances can also be deposited on the surface of the mouth. Tars and smoke from the mainstream can produce free radicals and inflammatory responses in the mouth and other mucous surfaces. The antioxidants and the curing preparations of this invention can be prepared as oral and oral compositions as well as optional ingredients that are also breath fresheners, fluorides, an ti -mies, and solubilizers of tars and essential oils. . Most dental products used as "anti-smoking" are available in the form of toothpastes and gels.

Diamond patented a combination of anionic and nonionic surfactants with less an essential oil, such as dental and oral preparations for smokers, this to solubilize and separate the tars from tobacco as well as the essential oils of garlic and onion. The document US Patent No. ,514,366 (May 7, 1996), incorporated herein for reference purposes, teaches complementary uses of the preventive and restorative effects of the present invention. 25 GSH has been shown to have multiple functions in the des oxy oxy cation, and its reduction in tracelular fluids and cells is associated with an increased risk of chemical toxicity. Although there are large variations in the sulfur amino acid content, these variations are not related to GSH levels in the blood plasma collection. These levels of GSH, however, do not vary with the age, race and gender of the human subject and with the eating habits and intakes. Researchers have reported that extracellular GSH collections, including plasma, the respiratory tract that lines the fluid, and the small intestinal lumen are vital GSH protectors against chemically induced damage. These may include the chemicals included in tobacco smoke and other environmental contaminants as well as chemicals in the preparations of non-smoking tobacco and other chewable or orally ingested substances. The above-mentioned collections, through the GSH and the related synergistic aniiodides, as proposed in the present invention, detoxify ex-race chemicals, the delivery of GSH and its amino acid precursors to the cells and protect the damage to the extracellular surface of the plasma membrane. Alterations in GSH status could thus be a regulatory function by GSH and thereby minimize the threshold for cell death induced by apoptosis, making GSH a useful biomarker protector for the risks of a variety of harmful chemicals in mixtures or individual, such as in the various types of tobacco. Some rremifera cells are able to absorb the tripeptide glutathione intact. This can also be synthesized by some organs, particularly the liver. Some scientific stationers have directed a method to appropriately replace glutathione, particularly the increase in cellular levels in reduced-status glutathione. Certain diseases cause the reduction of glutathione from the inbred interaction with the metabolic intermediates, the various damages of free radical species. The glutathione labeled, at the intracellular level as the "physiologically appropriate antidote for neutralization and thus detoxification" by the formation of covalent bonds, of highly reactive toxic substances of exogenous or endogenous origin, "Pilotto and collaborators patented some dipeptide compounds with pharmaceutical properties I for filling the body levels of glutathione.US Patent No. 4,761,399 dated August 2, 1988, shows an increase in glutathione levels by several routes, including oral and inhalation parenteral methodology. US Patent No. 4,710,489 published December 1, 1987 teaches new molecules to increase glutathione levels The invention of the patent 98 relates to the use of pure alkyl monoesters of glutathione, wherein the ester is a glycine carboxylic acid These molecules can be administered orally or mediated In this way, it is an object of the present invention to provide various compositions and methods for employing such compositions for the prevention and diminution of the signs and symptoms and complications of the cavity of the pharynx and the mouth including the buccal mucosa, cheeks, teeth and tongue as well as the upper respiratory tract as a result of tobacco oxidants and other contaminants in particulate and gaseous material.

These and other objectives will be more readily appreciated when considered in the following description and appended claims.

BRIEF DESCRIPTION OF THE INVENTION The present invention is directed to a composition of synergistic oxidants and to the use of this composition used in a supply system in chewing gums, tablets or pills, for the prevention and improvement of free radical damage induced by environmental pollutants and smoke of cigarette to the structures of the oro-pharynx and the upper respiratory tract. The active ingredients include reduced glutathione, selenium as an element or as an amino acid of selenium similar to the semisinone and optionally the sulfur-containing amino acids L-cysteine and N-acetyl-L cysteine and / or L-methionine. As an optional additional ingredient, the composition contemplates the use of the ascorbic acid and / or its derivatives, the a-f-o-o-f-o-er and / or its derivatives. Depending on the organ to be treated and the states of additional diseases or conditions found, other antigens or molecules can be included in these preparations. These include, but are not limited to, the bismuth superoxide enzyme of vitamin A, and / or be t here rot, fluorinated compounds and zinc.

DETAILED DESCRIPTION OF THE INVENTION Antioxidants have been found to inhibit all phases of carcinogens while other antioxidants are more specific and thus more effective against the initiation or promotion of tumor progression. It has been shown that glutathione and selenium play major roles in the protection of cancer and also in the prevention of other cancers, when selenium is taken orally, thereby recovering selenium from the body.

In the same way, glutathione inhibits carcinogenicity, and actually with concentrations is suppressed by chemicals in such a way that glutathione levels are significantly reduced, the chemical rate increases and the number of tumors increases. and the increase in the size of the tumor. By reducing the intracellular levels of GSH in cells, it increases their sensitivity to damage by oxidation. Studies have shown that the increase in intracellular GSH is beneficial. An L-cysteine delivery agent not only increases the concentration of the endogenous GSH cells, but also protects these cells from the endogenous damage of hydrogen peroxide. The preventive role of GSH is of significant biological value. Without being linked to any in particular, it is noted that the reduced glutathione is used in the protection of the oxidative stress cells themselves that are being oxidized. Thus, L-glutathione should act in combination with other enzyme systems to be reduced in such a way that they can be renewed in their role as a free radical scavenger. GSH also works in coordination with the enzyme glutathione peroxidase, which requires selenium as a cofactor to exert its biological antioxidant function. Selenium compounds have been shown to purify oxygen-focused radicals in vivo with reduced glutathione through glutathione peroxidase. It is believed that selenium-GSH-peroxidase catalyzes toxic acid peroxidase in the presence of reduced glutathione. This reaction reduces glutathione to oxidized glutathione GSSG. In turn, GSSG is again reduced to GSH reductase, thereby maintaining a GSH cell abundance to purify free radicals again.

In summary, the main functions of reduced glutathione (GSH) in protection against lipid peroxidation are related to three types of reactions, all interrelated and synergistic in combination with non-enzymatic and enzyme and anti-oxidant cleaners. dan tes provided by the diets. 1. GSH with the selenium cofactor of glutathione peroxidase eliminates toxic peroxides. 2. GSH reduces the oxidized forms of vitamin C, which, in turn, maintain vitamin E in its reduced form to promote its metabolic functions. Thus, the GSH supports the functions of free radicals and the functions that end in chain of radicals of two anti oxidants is nutrients, vitamins C and E. 3. GSH works through glutathione S-transferase to detoxify the reactive aldehydes created during the process of lipid peroxidation. As noted, some cells have sodium dependent systems for GSH, which allows cells to use GSH synthesized endogenously and GSH exogenously, which increases the ability of the cell for oxidative survival and Radical species of danger. In this modality, the extracellular GSH also protects the survival of the cells, Research studies have shown that the viability of cells is better related to the content of cells. In the absence of GSH, lipid peroxidation is uncontrollable and leads to cell damage and death. On the contrary, GSH protects the cells from the destruction of free radicals, working inertly with anti oxidant enzymes and vitamin-rich enzymes to the immune system.

For those in the gum or chewing gum industry, the base compositions for sugar-containing chewing gum, and for low-calorie chewing gums and bubble gum are well known. The present invention can be used with low calorie chewing gums, particularly with the xylitol and sorbitol polyols, but the invention is not limited to these sweeteners. These chewing gums generally contain 20-30% base chewing gum insoluble in water, and from 30 to 90% of a filler or texturizing agent (so-called bulky products). Flavors soluble in water are also added. The base of the chewing gum may also contain plasticizers or softeners to improve the consistency and texture of the chewing gum. Some of these chewing gums are chewing compositions that stimulate saliva with specific salivary stimulants. One such composition is described by Cherukuri et al., In U.S. Patent No. 4,980,177 dated December 25, 1990, which is incorporated herein for reference purposes.

Another method for the application of the active ingredients of this invention in chewing gums, balloon gums, lozenges and tablets is to incorporate the various antibodies, minerals and amino acids into the liposomes or other state of the art of encapsulating vehicles, similar to nanospheres, glycospheres and others as used in topical compositions. Liposomes are lecithin spheres that form an oily protective membrane around the putative active ingredients of these compositions. These carriers also supply the locally active ingredients for their therapeutic and preventive functions as well as systematically through the absorption of the buccal mucosa.

Unger et al. Have taught therapeutic drug delivery systems comprising gas-filled liposomes which are encapsulated with the active preparation in US Patent No. 5,580,575 dated December 3, 1996, which is incorporated herein for reference purposes. . Earlier, Chakrabarti et al., And U.S. Patent No. 5,5380,531 dated January 10, 1995, which is also incorporated herein for reference purposes; describes preparations comprising a lipid and a modified peptide for encapsulating amino acids within liposomes.

As noted above, xylitol to be used here as a sweetener, in order to dissimilate the taste of the present active ingredients. Xylitol chewing gums have been evaluated in various fields of study for their ability to influence the reasons for dental caries in children. Makinen and colleagues did a study of a blindfolded group of nine treatment groups, for 40 months, which included several doses of xylitol, on the relationship between the use of these chewable gums and the development of the cavities. The study was conducted between 1989-1993 in Belize in 1,277 children. These showed significant reductions in the proportions of dental caries in the groups treated with xylitol, in comparison with the groups that did not chew the gums and concluded that the systematic use of the gums based on the polyol, reduces the frequency of the cavities, with the Xylitol chewing gums are even more effective than sorbitol gums. Other studies have also revealed that confections with high xylitol content, including sweets and chewing gums are not only non-cariogenic but also inhibit caries.

As a preferred additional embodiment, the present application contemplates coating the chewing gums with at least one of the active ingredients to prevent tooth decay and dental plaque, as well as the aforementioned dunci fi cant and flavorings, in addition to the compounds that prevent halitosis, the linear salts of zinc, to act refreshing the breath and to combat the bad odors of the breath. The synergistic complex of anti-oxidants will be more important and include, as stated, at least 0.5 mg. of L-glutathione, 5 mcmg of selenium as the first 1 enome t i oni na and optionally 15 mg of vitamin C and 10 IU of vitamin E to neutralize and purify the free radicals in the oral cavity. Other optional ingredients include superoxide dismutase, vitamin A, beta-carotene, amino acids cysteine, methionine, taurine and / or arginine-as well as zinc salts, such as zinc acetate or gluconate. zinc. The substances incorporated in the gum are released in the amount to exert their beneficial effect during the chewing process. The active ingredients can act locally and can also be absorbed through the buccal mucosa for systemic use.

Hill in the Patent "530 summarizes the patents referred to ~ which are related to the chewing gums which provide flavors and which can supply active substances in the oral cavity.

US Patent No. 3,075,884 teaches the mixing of the active ingredients in corn syrup which are coated on a gum. U.S. Patent No. 3,011,919 teach a method for incorporating active by providing coatings with wet sugar. U.S. Patent No. 3,352,689 describes formulations of a gum to mash without sugar, which also releases active ingredients in the mouth.

The Hill "530 patent also discloses a number of references dealing with rubber compositions of chew that contains anti-plaque properties. In addition Hill m also teaches the use of xylitol and sorbitol in chewing gums.

Estall et al., in U.S. Patent No. 25 3,821,417 dated June 28, 1974, which is also incorporated herein for reference purposes; describe the use of dihydrochalcone as well as the use of various antioxydants in the chewing gums, mainly hydroxyani butylated, butylated hydroxytoluene and prop ilgalate.

Although the chewing gums and balloon gums of this invention will preferably be low calorie compositions, the present invention may optionally include compositions that are well known in the art and may include a gum base (about 40% to 60% by weight). weight of the composition), which comprises an elastomer, a polyvinyl acetate polymer, an acetylated monoglyceride, a wax with a melting point of less than 60 ° C, an elastomeric solvent, a plasticizer and a filler. The gum is subsequently provided with the present synergistic antioxidant complex, such that each of the pieces of chewing gum has approximately at least 0.1 mg of L-glutathione, 2.0 mcgm of selenium such as selenomethionine, 10 mg of ascorbic acid. -jt¿ .-- 2.5 IU of vitamin E and 1.0 mg of L-cysteine or 1.5 mg of N-acetylcysteine. It is noted that the reduced calorie gum may contain xiiitoi or lactitol as the thickener while the standard calorie gum will have sucrose, lactose or mono- or di-acid, more flavoring. The chewable gums may also contain saliva stimulating compounds, such as those described by Cherukuri et al., In their patent 177.

As optional modalities, other ingredients may be added, such as breath and freshening agents. breath cleansers (anti-alitosis). Plevy in Pate Estadou ide No. 4,740,368 filed on April 26, 1908, which is here incorporated by reference, shows compositions with amylase as breath-cleansing preparations. Alpha amylase is synthesized by the salivary glands as an exocrine pancreas and is capable of digesting carbohydrates. Plevy preparations use 1-8-skb alpha to i-lase units of fungal origin to degrade the starch. Along with sweeteners and artificial flavors, this enzyme is the ingre &This is the main basis of edible preparations, such as gums and pills. In a separate manner, Pear in U.S. Pat. No. 4,775,525 issued on October 4, 1988, which is also incorporated herein by reference, shows a dental formulation containing sodium alginate. It is used as a calcium chelating agent which weakens the bonds between the plaque and the tooth. The referenced patent supports the concomitant use of benzalkonium chloride and zinc.

In addition, the proportion of these synergistic antioxidants in standard chewable gums for chewing gum is contemplated. Co-mestic cosmetic gums are not digestible or biodegradable and cause an unpleasant appearance in their release. The substituyent.es of b d gum which are edible, have been the object of several teachings. For example, U.S. Patent No. 5,366,740 to J.J Shaw filed on November 22, 1994, which is incorporated herein by reference, uses a wheat gluten preparation as an edible "chewable gum". Its manufacture includes calcium carbonate, glutinous rice flour and ascorbic acid as wheat gluten softeners, as well as other ingredients commonly used as conditioners of wheat arina pulp. If used herein, such a chewable gum may also provide for the application of current oral antioxidants to the oral mucosa to combat tobacco smoke, chewable tobacco or other inhaled or ingested contaminants in the diet, all of which They induce free radicals. Edible gum may also have lime fresheners. All compounds of chewable gum, other than the commercially available "chewable tablets" can then be ingested while their carbohydrate and protein base are digested. All vitamins, minerals and amino acids not absorbed by the oral mucosa during the chewing process, will be ingested and then systematically made available in the body after intestinal absorption. This may be similar to the constituents mentioned above in conventional masticatory gums, which are ingested dissolved or dispersed in the saliva. When the present invention is in the form of gels, lozenges, gums, candies, chewable tablets or chewable gums, the flavoring can be added. The flavor can be based on oils of green pepper and pepper. Other flavoring materials can I nd, ol ol, cl o, n l, g ul eri, citrus fruits, eucalyptus, anise seed and others which are commercially available. The flavor may vary in concentrations that depend on the product from about 0.1 to about six percent by weight of the total composition.

When the products are in a gel form, the bicarbonates may be present in the composition with agents thickeners, in a concentration from O.b to 5.0% by weight. The thickeners of the state of the art with a bicarbonate and zinc salts, include but are not limited to, chewing gum, xanthan, gum arabic, karaya or tragacanth Alginates, carrageenans or mosses and cellulose derivatives such as the carboxymethyl sodium, methyl, hydroxyethyl compound can also be included, also as surfactants and surfactants. To decrease tooth decay and add flavor, if to use metabolizable sugars, sweeteners such as saccharin and sodium cyclamate, sorbitol, aspartame and others, can be used in concentrations from 0.005 to 5.0 per weight percent of the total composition, although as stated, xylitol is the preferred sweetener.

Researchers in Finland, showed that masti.cable gum containing the natural sweetener xylitol, reduces chronic ear infections in children. Xylitol, a five-carbon sugar alcohol found in maple and birch trees and corn cob, has also been used to combat the deterioration of the tooth, since the local bacterium of the mouth can not digest this sweetener. It seems that xylitol prevents the bacteria from attacking the cells in the posterior area of the mouth from when they enter the ear passage and cause an infection. Xylitol is of value pac ^ --- 1 oral hygiene, since it is not metabolized by the bacteria of the mouth, so that no organic acids are produced which attack xylitol tooth reduces tooth decay. reduces the amount of plaque-forming bacteria (streptococcus mutants (in the mouth). Several clinical studies in other countries have confirmed the unique dental benefits of Xylitol, that is, of particular use in pediatric mellitus. Therefore, xylitol will preferably be used as a sweetener in these compositions, particularly in the chewable gums and lozenges of the present invention for its known healthy, non-caloric dental and oral effects. Lactitol can also be used as a substitute for sucrose in the sugar-free compositions of the present invention. Lactitol is a disaccharide sugar alcohol derived from lactose, highly soluble in water and hydroscopic, making a non-caloric sweetener suitable for use in tablets and other forms of solid dosages.

A number of compounds are. { They could add to the chewable tablets, pills, sweets and gums present, to increase their aromas or flavors. These substances can also impart fragrances to those mentioned above. The aroma and flavor of grapefruit and citrus have been included in the articles of tobacco to be smoked both before smoking and when smoking, both in the main stream and in the sidestream smoke stream. Pentanol methylphenyl derivatives have been used to increase and increase the aomas, such as in perfumes and colognes. Sc reck patented these derivatives for use in tobacco and tobacco articles, in U.S. Patent No. 4,458,699 filed July 10, 1994, which is incorporated herein by reference. The aroma and nuances of floral, erdes, herbal, fruit, mint, citrus, oriental and pepper-like flavors are well known to experts in the flavors and fragrances technique, which can be used in present oral compositions, including chewable gums, bubble gum or balloons, chewable tablets, pills and candies. The flavored hard tablets and tablets prepared in accordance with the present invention are made with the recommendation that the user dissolve them in such a way that the ingredients are released into the oral cavity and the remaining molecules, not absorbed by the buccal mucosa, will be mixed with saliva and swallowed normally. The sweet in the form of tablet with. Various flavors and the sweetening xylitol are made using the state of the art in the art as it is known in the preparation industry. These tablets are proposed to carry out the synergistic antioxidant complex described above. For example, a tablet can have the following ingredients in amounts as indicated: 4 (four) tablets equal the following dosage per day: L-glutathione 40 mg Selenomethionine 25 mcgm Ascorbic acid (Vitamin C) 30 mg Alpha tocopherol (Vitamin E) 15 IU Retinyl acetate (Vitamin C) 2500-L-cysteine 10 mg The tablets can be "flavored" with standard therapeutic agents such as menthol, eucalyptus, and ingredients known in the "cooling products" industry. The components of the present synergistic antioxidant complex can be incorporated into chewable flavored tablets. Such chewable tablets can be increased with sugars similar to sucrose, fructose and / or lactose. Alternatively, artificial sweeteners, such as xylitol, lactitol, sorbitol and the like, can be used here. Natural flavorings such as citrus, fruit, cherry, strawberry, grape, and various mint flavors, to name a few, can be incorporated into the chewable tablets of the present invention. The inactive ingredients as vehicles for these flavorings include dextrins, starch, silica, gelatin, hydrogels, magnesium stearate and phosphate, glycerides of stearic and palmitic acids, and customary fillers and thickeners commonly used in chewable tablets and vitamins, such as those that are commercially available. 5 The sizes of potions of these chewable tablets may vary, such that a consumer may ingest from one to four chewable tablets per day. The active ingredients contained within the The tablet may vary, so that in consumption, in the recommended number of tablets, usual one to four, the user will ingest the minimum daily requirement or co-pending of the active ingredient, as prescribed by the guidelines. dietary supplements. For example, a chewable tablet designated as dosages of two in a day (in the morning and e noc e), may have the following active ingredients: L-glutathione 20 mg Selenomethionine 25 mcgm Ascorbic acid (Vitamin C) 30 mg Alpha tocopherol (Vitamin E) 15 IU Retinyl acetate (Vitamin C) 2500-g J L-cysteine 10 mg To this tablet, one may also include xylitol and lactitol as the sweetener with flavors according to taste. In a more preferred aspect of the present invention, the aforementioned inhaled or oral pharmaceuticals, the active amino acids and antioxidants containing the composition have a formulation for total daily consumption including the recommended daily servings of reduced L-ascorbic acid, tocopherols , and other vitamins. In addition to L-glutathione, the preferred seienium dosage is approximately 10 mcgm of elemental selenium per day, more preferably 25 mcgm per day. This can also be used as slenomethionine, which is commercially available in 0.5% trituration with dibasic calcium phosphate. This fine powder contains from 5,000 to 5,300 mcgm of selenium per gram of the selenomethionine preparation. The compositions may also have about 30 IU of D, L-alpha tocopherol, and about 1000 mcgm of vitamin A, as the retinol equivalent or 5,000 units as vitamin A with a range of 20-40% of beta carotene. These are recommended daily rations and these active ingredients can be administered in oral liposomes, either encapsulated alone or in combinations. Knight and coworkers in U.S. Pat. No. 5,049,388 (September 17, 1991), incorporated herein by reference, describe liposomes in small particle aerosols. These particles have diameters of less than 5 microns. The medicaments are combined with the liposomes in such a way that the drug or the active ingredient interacts with the liposome membrane.

The compositions mentioned above can be particularly employed in the prevention and treatment of exposure to tobacco or other gases or particulate materials. They represent a delicate balance of ingredients, which serve not only to reduce the number of free radicals but also to inhibit metabolic oxidation. The most preferred formulations according to the present invention also increase the yield of the composition by the recirculation of certain antioxidant ingredients in the formulation after they are absorbed and by offering the formulation admissible for use by the manufacturer. prolonged term. The compositions, when provided in sufficient dosages over a period of time, can be used in the treatment and prevention of damage to the pharynx and upper respiratory tract, by exposure to smoke, to smokeless tobacco. and other ambient contaminants.

The glutathione and the selenium act s i nergí s t i camen t e in vivo, existing in both constituents of the same enzymatic system. The GSH serves as a specific donor substrate, while selenium, provided from food sources or locally topically administered selenium preparations, selenoamino acids or selenium yeast extract, provide the prosthetic group of the GSH peroxidase. The antioxidant functions of glutathione and selenium are intrinsically related, since in a peroxidase in action, GSH and seleium contribute to the elimination of the product of dismutation of oxygen free radicals., ll m do, hydrogen peroxide. In a broad sense, GSH and selenium modulate free radical chains initiated or sustained by hydroperoxides. Selenium is used in the present invention for its role as an antioxidant, as well as for its anti-carcinogenic and cationic properties. Thus, the selenium-glutathione complex may decrease • the level of potentially harmful peroxide radicals that are generated from various carcinogenic promoter chemicals, including inhaled derivatives or by-products of tobacco smoke in the gas phase. and the tar phase, particularly sidestream smoke streams.

The peroxidase glutathione, a group of water soluble enzymes, also catalyze the destruction of both hydroperoxides attached to the membrane and aqueous. In the deficiency diet of selenium, these levels of enzymes, decrease markedly, resulting in the damage of several free adicas to the tissues involved. The other related antioxidant systems can not be adjusted for the lowered local activity of selenium and the selenium-dependent enzymes.

Thus, the importance of providing selenium in these antioxidant preparations in ra-orale s, as well as the verification of adequate nutritional supplements. Selenium can be provided as an acid selenoamino, such as selemethionine, such as tl, it is pro- tected in oral lipo somes.

L-ascorbic acid (vitamin C) or its derivatives can be used in these compositions mainly for their antioxidant activities. Stabilized vitamin C is used in such a way that it does not lose its physiological reduction activity due to its high susceptibility to oxidation. The minimum daily requirement for adults has been established. It seems, however, that cigar smokers need supplemental vitamin C-a. Vitamin C, as an antioxidant, has been used in vitamins, beverages, foods, pharmaceuticals and cosmetic preparations. Vitamin C has also been used for the prevention of viral diseases and a preventive for its antioxidant properties of the development of cutaneous pre-malignant lesions and malignant tumors. Sakai, et al in U.S. Patent No. 5,508,390 (April 16, 1996) has summarized uses of an L-ascorbic acid. Such stabilized vitamin C is used as an additive in various preparations. The emphasis of this ascorbic acid preparation is on a function of reduction and reduction. Todd, Jr., in U.S. Patent No. 5,084,293 (January 28, 1992) discloses a method of using "activated" ascorbic acid preparations with antioxidant compositions. These include anhydrous compositions for incorporating propylene glycol or surface activating agents or nonionic surfactants to provide vitamin C with increased antioxidant activity in its fats, acetyl-carotenoids.

Ascorbic acid, vitamin C, plays a major or important role in human metabolism. As an antioxidant, it protects the skin from damage by free radicals, induced by radiation, smoke or tobacco and other environmental pollutants that are inhaled or triaged. L vit min C promotes the intima of collagen, tissue repair and wound healing. Vitamin C also provides important protection against the harmful chemicals associated with cigarette smoke, which includes icotine, carbon monoxide, nitrogen oxides, nitric acid gas and others. Although ascorbic acid can be reduced in the purifying film, the scorb root can then be removed by the NaDPH enzyme systems as reducing sources of molecules. Thus, vitamin C can be recycled to reduce or reduce the process of lipid peroxidation due to its synergistic function with others. Markham in U.S. Patent No. 4,022,891, refers to oral administration of vitamin C to demonstrate its Ti-radical attributes. Others have shown that chronic tobacco smokers have higher urinary levels of 8-EPI-prostaglandin F2A than non-smokers. Oral supplementation with vitamin C suppresses the urinary levels of this metabolite, suggesting a reduction of oxidative stress in these subjects.

Cigarette smokers often have 0 lower plasma levels of ascorbic acid that match the controls of non-smokers. Clinical and research evidence suggests that smokers may have a requirement for higher ascorbic acid and that supplementation of the vitamin C in the diet, can be protective of the smoker. In vitro studies have shown that antioxidants and reducing substances can prevent the removal of the capacity of the elastase inhibitor induced by cigar umo.

Other components are also investigated for being employed in the practice of this invention, for example, sulfur containing amino acid cysteine is one of the three constituent amino acids of tripeptide antioxidant glutathione. Studies have shown that cysteine and the cysteine derivatives as mentioned in U.S. Patent No. 4,910,222 by Furicelli, have liquefying and xpector properties. E ta co cts can be administered orally as a solid (capsules), or as a liquid (remul s ions) and by aerosol sprays.

Vitamin A is an essential nutrient. The 'relative deficiency of vitamin A, can adversely affect the skin and mucous membranes, including the mucous membrane of the oral cavity. These alterations are reversible in satiety with vitamin A or one of its derivatives.

Xylitol, the sweetest of all sugar substitutes in volume, tastes like sugar, does not leave a residual taste, and has 40% fewer calories than sugar. A caloric value of 2.4 kcal / gram is accepted by the nutritional markers. This sugar alcohol of five carbons, has a negative heat of solution, which causes a cooling effect when it dissolves - eD, - 1 to mouth, particularly using concomitantly a mint flavor. When the sugars are ingested, the micro-anism in the mouth ferments the sugars with a consequent drop in the Pw even a low pH of When the contents in the mouth are acid, there is a demineralization of tooth enamel. The stimulated flow of alkaline saliva is then necessary to return the pH of the mouth to normal levels. Thus, the use of xiiitol reduces the susceptibility to dental caries by helping to neutralize the affected tooth and to reduce the sminerization of the tooth. Studies also show that adults who chew xylitol gum and / or sorbitol gums or mouth rinses significantly develop less dental plaque than chewed sucrose gums as controls. Dental plaque also shows an improvement in the ability to remove any drop in pH. In the xylitol groups, studies have shown that xylitol inhibits the growth of several oral cariogenic bacteria, particularly those of the mutants of S t rept ococcus.

Although susceptibility to dental caries is influenced by several factors including dietary patterns and diets, the proportions of tooth surface and saliva are also important. The resistance of enamel and dentin can be increased by regular exposure of the teeth to systemically fluorides. This is covered via the intake of water and fluoride tablets or tonic via toothpaste, gels and mouth rinses. Several studies have shown that the consumption of even small amounts of xylitol increases the beneficial effects of the existing fluoridation program, resulting in the reduction in nu v c ri. Tests have been observed where xylitol is applied topically such as a mouthwash.

When the present preparations are in the form of gums, tablets or dragees, flavors can be added to these compositions, as per the state of the art in these respective industries. The flavors can be based on the oils of spearmint and mint. Other flavoring materials include menthol, clove, cinnamon, wintergreen, citrus fruits, eucalyptus, ft seed of anise and others commercially available for these flavoring purposes.

The flavors may vary in concentrations that depend on the product from about 0.1 to about 6.0% by weight of the total composition.

When the products are in the gel form, the bicarbonates may be present in the composition with thickening agents, in a concentration from O.b to b.0% by weight. The state of the art of the thickeners with Bicarbonate and zinc salts include, but are not limited to, cyclic, gom rabies, karaya or tragacanth. Alginates, carrageenans, mosses and cellulose derivatives such as carboxymethyl sodium compounds, Methyl or hydroxyethyl as appropriate for the proposed preparations, surface activators and abrasives may also be included. Alcohols will be otherwise, avoided by their known risk factor for oral cancers. To diminish tooth decay and add flavor, without using to abolish them, sweetening agents such as saccharin, sodium cyclamate, sorbitol, aspartame and others can be used in concentrations from 0.005% to 5.0% by weight of the co-position. total, it is preferred if the xylitol, vide upr.

Lactitol can also be used as a substitute for sucrose in our sugar-free compositions. Lactitol is a disaccharide sugar alcohol derived from lactose, high water soluble and low hydroscopic, making it a non-caloric sweetener suitable for use in solid dosage forms.

A number of compounds can be added to the various liquid compositions of this invention, to increase the flavors or aromas of these preparations. These substances can also impart fragrances to those mentioned above. The aroma and boron grapefruit and citrus, have been included in the articles of snuff to smoke both before smoking and when smoking, both in the mainstream and in the stream of side smoke. The derivatives of peret, anil methylphenyl, have been used to increase and increase the aromas, such as in perfumes and colognes. Schreck took these derivatives for use in tobacco and tobacco articles, and U.S. Patent No. 4,458,699 (July 10, 1994), which is incorporated herein by reference. The aroma and nuances of flavors - floral, green, with herbs, a fruits, mint, citrus fruits, orientals and green pepper comp, are well known to those skilled in the art of flavors and fragrances for such compositions as in oral ato izadores, mouth rinses, i - =, mouthpieces, gels -, dentifrices, and other medicinal, nutritional or breath-freshening products.

Wahl and co-t raba j adores at the National Institutes of Health show methods for treat chronic inflammatory conditions in U.S. Patent No. 5,499,688 (September 12, 1995), which is incorporated herein by reference. They administer effective amounts of nitric oxide pu rification to reduce the amount of putative nitric oxide present at the site: < !§;-- the inflammation. These compounds belong to complexes with L-arginine, L-canavanine, citrulline and aminoguanidine. They note, similar to this flavor argument, the use of antioxidants to neutralize free radicals. E p t nt 688 predicts m all p r treat gingivitis and per ior t i t i s. Kleinberg in U.S. Patent No. RE31181 (March 15, 1983), which is also incorporated herein by reference, also teaches arginine and arginine peptides for preparations for oral care.

For centuries, Chinese herbalists have identified individual herbs that have either beneficial effects on the body or even therapeutic properties. The Institute of Healt has recently established an agency to search for these so-called alternative therapies.

It is preferred that the antioxidants of the present invention be provided in a form which is as pure as possible. They should be present without harmful lubricants (sands, soaps, talcum), fillers, colors, binders, dispersants, or as adjuvants sometimes used as release excipients in the aerosol pharmaceutical industry.

Several products can be administered to reduce the viscosity of mucin in saliva. Productive coughing is a common symptom. The mucosa in the respiratory tract, especially in chronic tobacco smokers, as well as in other conditions that include cystic fibrosis, can be treated with cough syrups for expectorants. Ceramin and Tabachik describe in U.S. Patent No. 4,424,216 (January, 1984), which is incorporated herein by reference, the use of reduced sulfhydryl compounds to decrease the "viscosity of saline in patients with ne mon, chronic bronchitis. and cystic fibrosis It is proposed as the preferred sulfhydryl agent WR 2721, to be given orally in gelatin capsules, so that in vi, it can then liberate free sulfhydryl groups.

Tumor suppressors, bronchodilators, also agents such as cysteine, arginine, methionine, taurine, vitamin A and others, to reduce the viscosity of mucin, can be added to these compositions. The latter will elaborate saliva 5 ás liquid and easier to expectorate, for these patients and for chronic abusers of t b co. L Pat E t dounid No. 4,927,859, here incorporated by reference, describes methionine in oral preparations or parenteraies for the reduction of inflammatory symptoms of respiratory diseases. As an optional modality, the components here cri with an oxidants Synergistic agents to fight free radicals in the oropharynx can also contain zinc or zinc compounds. In the state of the art of oral care and hygiene the value of zinc has been widely recognized for neutralize oral malodor and the value of zinc ions for their anti-plaque and an i-calculus properties. The buc l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l l oral and dental preventive care.

Several patents have different zinc compounds and other complexes in the oral compositions. Domke and Bergman ft show in U.S. Patent No. • 5 5,587.17 (December 24, 1996), which is incorporated herein by reference, a complex of zi nc-pol i amide aqueous as a solution for the control of halitosis, dental care and to decrease the astringency and metallic taste of the zinc in the mouth. This patent describes previous documents related to zinc salts, such as zinc chloride, zinc sulphonate, zinc citrate and other zinc complexes, some of which also significantly pres n c ivi a anti icrobian s or l. The concentrations of zinc ions in these compositions will be at least 0.1 to 3.0 weight percent and these will preferably be at an alkaline pH to avoid demineralization of the tooth at acid levels. In any event, these aqueous compositions will not have a pH below 6, and preferably about 7.

Another method of application of the active ingredients in the gum products, tablets or lozenges of the present invention, is to incorporate the various anti-oxidants, inorganic and amino acids into liposomes or other encapsulating vehicles of the state of the tea. cnic, alphanospheres, glycospheres and others also used in topical compositions. Liposomes are spheres of lecithin that form an oil protective membrane around the putative active ingredients of the composition. These carriers also release the locally active ingredients for their preventive and therapeutic functions as well as systemically through the mucosal absorption of the mouth. Unger and co-t raba j adore s, in U.S. Pat. No. 5,580,575 (December 3, 1996), which is incorporated herein by reference, shows to have therapeutic drug delivery systems, comprising liposomes filled with gas, which encapsulate the active preparation. Earlier, Chakrabati et al., In U.S. Patent No. 5,380,531 (January 10, 1995), which is also incorporated herein by reference, disclose preparations comprising a lipid and a modified peptide for similar uses of amino acids and peptides in the liposomes Knight et al. (US Patent 388) shows having compositions of lipo om and lipo om in aero or small particles approximately for medical release uses. 10 It is noted that in relation to this date, the best method known by the applicant to carry out the aforementioned invention is that which is clear from the present description of the invention.

Having described the foregoing, the property contained in the following is claimed as property:

Claims (33)

CLAIMS .íg ^ -

1. A composition for reducing the damage of free radicals induced by tobacco products and environmental contaminants characterized in that it comprises, as active ingredients, reduced glutathione and a selenium ring selected from the group consisting of the same element, lenom ionin and These ingredients are combined with suitable carriers and flavorings for intra-oral administration such as gels, lozenges, tablets and gums in concentrations to reduce free radical damage induced by b co products and another with intes mbi the oral cavity, pharynx and upper respiratory tract, of a user and secondary smoker.

2. The composition of claim 1, characterized in that each of said gels, lozenges, tablets and gums contains at least about 0.5 mg of said reduced glutathione.

3. The composition of the rei vindi caj ^ -i ón 1, characterized in that said gels, tablets, tablets and gums contain at least about b mcgm of said selenium source.

4. The composition of the claim 1, characterized in that said gels, pills, tablets and gums also contain at least about Ib mg of vitamin C as ascorbic acid as an ascorbic acid derivative

5. The composition of the claim 1, characterized in that said gels, pills, tablets and gums also contain at least about 10 IU of vitamin E as alpha tocopherol.

6. The composition of the claim 1, characterized in that said gels, tablets, tablets and gums also contain dismutase superoxide.

7. The composition of the claim 1, characterized in that said gels, pills, tablets and gums also contain vitamin A.

8. The composition of the claim 1, characterized in that said gels, pills, tablets and gums also contain beta carotene.

9. The composition of claim 1, characterized in that said gels, lozenges, tablets and gums also contain at least one amino acid selected from the group consisting of cysteine, methionine, taurine and arginine.

10. The composition of claim 1, characterized in that said gels, lozenges, tablets and gums also contain a zinc salt.

11. The composition of claim 10, characterized in that said zinc salt comprises zinc glutonate.

12. A gum to reduce free radical damage induced, by tobacco products and environmental pollutants characterized in that it comprises, as active ingredients, reduced glutathione and a source of selenium selected from the group consisting of elemental selenium, selenomethionine and was read na, combined in a suitable carrier containing flavorings to produce a chewable gum in concentrations to reduce the damage of free radicals induced by tobacco products and other environmental pollutants to the oral cavity, pharynx and upper respiratory tract - dyg.r_ a user and secondary smoker. you

13. The gum of claim 12, characterized in that said gum further includes a gum base comprising about 40 to 60% by weight of the gum composition.

14. The rubber of claim 13, characterized in that said gum base comprises an elastomer, a polyvinyl acetate polymer, an acetylated monogiiceride, a 15 wax with a melting point below about 60 ° C, an elastomeric solvent, a plasticizer and a filter.

15. The gum of claim 12, characterized in that it comprises at least about 0.1 mg of reduced glutathione, 20 mcgm of said selenium source and further comprises at least about 10 mg of C5 ascorbic acid, 25 IU of vitamin E and 1.0 mg of a cysteine selected from the group-x¿_-consisting of L-cysteine and N-acet i 1 cis steine.

16. The gum of claim 12, characterized in that it further comprises a sweetener selected from the group consisting of xiiitol, lactitol, sucrose, lactose and a saccharide.

17. A tablet for reducing free radical damage induced by tobacco products and environmental contaminants characterized in that it comprises, as active ingredients, reduced glutathione and a source of selenium selected from the group consisting of elemental selenium, selenomethionine and selenium. na, combined in a suitable carrier to allow the tablet to slowly dissolve in the user's mouth, the release of said active ingredients in concentrations to reduce the damage of free radicals induced by environmentally friendly products contour the cavity oral, pharynx and respiratory tract-fcp-xi or higher of a user and secondary smoker.

18. The tablet of claim 1, characterized in that said tablet is of a specified size such that a user may administer said active ingredients from one to four tablets to supply a recommended daily serving of said active ingredients.

19. The tablet of claim 18, characterized in that said tablet is of a specified size to be provided to a user, with approximately 40 mg of reduced glutathione, 25 mcgm of selenomethionine, 30 mg of ascorbic acid, 15 IIJ of alpha tocopherol, 2500 II ! of retinyl acetate, and 10 mg of L-cysteine, daily.

20. A chewable tablet to reduce free radical damage induced by tobacco products and environmental contaminants characterized in that it comprises, as active ingredients, reduced glutathione and a source of selenium selected from the group consisting of elemental selenium, selenomethionine and selenium, combined with a suitable carrier to allow the chewable tablet to be chewed by the user's teeth by releasing said active ingredients in concentrations to reduce the damage of free radicals induced by tobacco products and other environmental contaminants to the oral cavity. , pharynx and upper respiratory tract, of a user and secondary smoker

21. The chewable tablet of claim 20, characterized in that said chewable tablet is of a specified size, such that a user can administer said active ingredients from one to four tablets to supply a recommended daily ration of d ± Xh or s active ingredients.

22. The chewable tablet of claim 21, characterized in that said chewable tablet is of a specified size, such that one to four chewable tablets are of specified size to be provided to a user with approximately at least 40 mg of reduced glutathione, 25 iricgm of selenomethionine, 30 mg of ascorbic acid, 15 IU of alpha tocopherol, 2500 IU of retinyl acetate, and 10 mg of L-cysteine, daily.

23. A method for reducing free radical damage induced by tobacco products and environmental pollutants characterized in that it comprises administering in a suitable carrier, in concentrations to effectively reduce said free radical damage to the oral cavity, pharynx, and upper respiratory tract of a user, - i - a combination of reduced glutathione and a source of selenium as an element selected from the group consisting of elemental selenium, selenomethionine and selenocysteine in the form of a gel, gum, lozenge or mast tablet cable .

24. The method of claim 23, characterized in that each of said gels, lozenges, tablets and gums contain at least about 0.5 mg of said reduced glutathione.

25. The method of claim 23, characterized in that each of said gels, lozenges, tablets and gums contain at least about 5 mcgm of said selenium source.

26. The method of claim 37, characterized in that said gels, lozenges, tablets and gums also contain at least about 15 mg of vitamin C as ascorbic acid or as a derivative of ascorbic acid.

27. The method of claim 23, characterized in that said gels, lozenges, tablets and gums also contain at least about 10 IU of vitamin E as alpha tocopherol.

28. The method of claim 23, characterized in that said gels, lozenges, tablets and gums also contain dismutase superoxide.

29. The method of claim 23, characterized in that said gels, lozenges, tablets and gums also contain vitamin A.

30. The method of the vindi caci? -H¿ ~ 23, characterized in that said gels, pills, tablets and gums also contain beta carotenes.

31. The method of claim 23, characterized in that said gels, lozenges, tablets and gums also contain at least one amino acid selected from the group consisting of cysteine, methionine, taurine and arginine. .

32. The method of claim 23, characterized in that said gels, lozenges, tablets and gums also contain a zinc salt.

33. The method of claim 32, characterized in that said zinc salt comprises zinc glutonate. A composition to reduce free radical damage induced by tobacco products and environmental contaminants. The composition includes reduced glutathione and a source of selenium. The composition can be administered orally in the form of a gel, lozenges, tablets or chewing gums.