TWI484958B - A composition for buccal absorption of nicotine for the purpose of smoking cessation - Google Patents

Description

Oral absorption of nicotine composition for smoking cessation

The present invention relates to a composition that provides oral absorption of nicotine, which allows the nicotine to enter the systemic circulation and distribute to the central nervous system, thereby providing a non-smoking nicotine replacement to assist in smoking cessation.

Extensive statistical studies conducted by smokers and non-smokers to demonstrate the effects of smoking on the human body. Smokers who smoked a pack of cigarettes a day consumed a systemic cycle of 20 to 30 mg of nicotine (Benowitz NL et al., Clin. Pharmacol. Ther. 44 (1988) 23-28). Nicotine is absorbed very rapidly and reaches the brain ten to twenty seconds after inhalation (Benowitz NL et al., Annu. Rev. Pharmacol. Toxicol. 36 (1996) 597-613). There is much evidence that nicotine affects dopamine receptors in the brain, leading to increased tolerance and addiction to nicotine in the brain (Hoffman D et al., Am. J. Health 73 (1983) 1050-1053). The way to quit smoking is to abandon nicotine addiction, a form of nicotine poisoning. The smoking cessation process is often a long-term war of resistance (Cummings KM, Hyland A, Ann. Rev. Pub. Health 26 (2005) 583-599).

Nicotine preparations of various routes of administration are utilized in the treatment of smoking cessation. For ease of use and to achieve adequate nicotine bioavailability, the most common mode of absorption is absorption through the oral mucosa. The concentration of nicotine in the blood that smokers want to achieve is 30 to 50 micrograms per liter (Lawson GM et al., J. Clin. Pharmacol. 38 (1998) 510-516). Since addiction is a pharmacological response to the immediate peak of high nicotine in the blood, slow release of nicotine is not helpful (Henningfield JE, Keenan RM, J. Consult. Clin. Psychol. 61 (1993) 743-750).

Chewing gum containing 2 mg or 4 mg of nicotine has a bioavailability (Shiffman S et al., Addiction 97 (2002) 505-516) of approximately 50% (Benowitz NL, Jacob P III, Savanapridi C, Clin. Pharmacol. Ther. 41 (1987) 467-473). In terms of stability, since the chewing gum slows the release of nicotine into the lumen, the concentration of nicotine in the blood changes with time in a manner different from that of smokers (Henningfield JE et al, Drug Alcohol Depend. 33 (1993) ) 23-29). The bioavailability of nicotine is mainly determined by the pH in the mouth. It is not recommended to drink a sour drink 15 minutes before and after chewing gum (Henningfield JE et al., JAMA 264 (1990) 1560-1564) because its ionized salt will decrease. Mucosal absorption. This type of use can also cause an unpleasant scalding in the mouth and throat (Henningfield JE et al., CA Cancer J. Clin. 55 (2005) 281-299). Nicotine release rates are difficult to control, and some manufacturers recommend avoiding excessive concentration of chewing to avoid excessive nicotine (US Patent 6,344,222).

Chewing gum and other lozenge products slow the dissolution of nicotine in the mouth (U.S. Patent No. 4,967,773), which is much slower than smoking (Russel MAH et al., Lancet 2 (1985) 1370). The prior patent has disclosed a composition for the faster dissolution of nicotine (U.S. Patent No. 6,280,761). In order to achieve a higher bioavailability, a pH of 7 to 9 is recommended, and the composition can be sufficiently stabilized by controlling the pH of the carbonate buffer (U.S. Patent No. 6,280,761). Increasing the pH to 7.4 to 8.5 increases the release rate of the non-ionized form from 30% to 80%, and the bioavailability can be increased by 3.8 times (U.S. Patent No. 6,110,495). Tablets have lower doses of nicotine and are less efficient. Therefore, the US approved doses range from 1 mg to 2 mg and 4 mg (Shiffman S et al., Arch. Intern. Med. 162 (2002) 1267-1276). Nicotine is released slowly and bioavailability is 25% higher than chewing gum (Choi JH et al., Nicotine Tob. Res. 5 (2003) 635-644). Another less common type is sublingual ingots. The medicinal body is small in size, soluble in water, and placed under the tongue when in use. The single-dose nicotine bioavailability is similar to that of chewing gum (Molander L, Lunell E, Eur. J. Clin. Pharmacol. 56 (2001) 813-819).

Nasal sprays are another form of nicotine preparation. Such formulations are restricted to use by medical prescribes in the United States (Henningfield JE et al., CA Cancer J. Clin. 55 (2005) 281-299). At the time of use, 50 microliters of solvent containing 0.5 mg of nicotine was administered to each side of the nasal cavity. Nicotine is absorbed very rapidly, and the advantage of the spray is that the nicotine dose can be set according to the degree of addiction of the patient (Schneider NG et al., Clin. Pharmacokinet. 31 (1996) 65-80). This preparation often causes nasal mucosal allergy in the initial stage of use.

The oral spray of WO/1997/038662 and EP 0 904 055 is composed of an effective substance of alcohol, water or a polyethylene glycol solution and a flavor additive, and the nicotine and its salts, pyridoxamine and steroid hormones are applied via a pump. ejection. Other patented techniques also include the application of nicotine formulations to the oral cavity using a pump sprayer (U.S. Patent No. 5,186,925); oral sprays containing nicotine microspheres are also protected by prior patents (U.S. Patent No. 5,939,100).

The so-called electronic cigarette system is the most novel and popular nicotine preparation product type (European Patent Application No. 1618803). Nicotine is absorbed by the mouth and lungs after ingestion. The World Health Organization expressed its doubts about the safety and efficacy of this product in a formal statement and claimed that it was not recommended as an aid to smoking cessation (Anon., Marketers of electronic cigatettes should halt unproved therapy claims. World Health Organization, 2008-09 -19).

Exhaled nicotine smoke concentrations in the closed space of vehicles are a worrying issue for non-smokers. In particular, children's ability to detoxify nicotine is far less than that of adults, and is therefore more affected.

Nicotine is a highly efficient natural substance belonging to alkaloids. The effect is very rapid, affecting a variety of organs, especially the heart, blood vessels and brain. The lethal dose (LD 50) is 30 to 60 mg (Gosselin RE, Clinical toxicology of commercial products, VI. Ed., Williams & Wilkins, Baltimore 1988, pp 311-313), but 4 to 8 mg can make non-smoking The person produces a serious toxic reaction, and the dangerous dose threshold is lower for children. No effective antidote has been found for this substance.

All alkaloids, including nicotine, are more likely to pass through the biological barrier when applied in a non-ionized form of solution, i.e., the more the pH exceeds the pKa value, the better. The pKa value is a parameter used to express the pH value when a substance is equal in ionization and non-ionization type. Physiological conditions must also be considered when administering biologically active substances. The trade-off between the physiologically optimal pH (ectopic acid solution) and the pH of the most penetrating barrier is the so-called euacid solution. This appropriate acidic pH ensures sufficient bioavailability at both pH values suitable for both the biological environment and the substance to be administered. The bioavailability is a parameter that expresses the ratio of the total amount of applied material entering the systemic circulation or the target tissue or structure.

In many materials, this appropriate acidic pH is achieved by mixing the acid or base form of a substance with its salt in an appropriate ratio. In the present invention, the nicotine salt formed by using nicotine (nicotine base) in combination with the addition of an appropriate amount of acid is a source of nicotine.

In order to improve the bioavailability of substances, in addition to increasing the proportion of non-ionized forms, another method particularly suitable for oral administration of substances is to reduce the barrier function of mucin. Mucin is a high molecular weight glycoprotein characterized by high aqueous solution viscosity. The phlegm remover reduces its viscosity. Many of the sulfhydryl groups contained in the currently used quinone molecules reduce the disulfide group, thereby reducing the cross-linking of mucin molecules. As a result of the reaction, the viscosity of the solution is greatly reduced, so that it can be used to solve the symptoms of lung diseases and respiratory diseases. This is the effect of amino acid cystine, methionine and its esters and ethers (Takatsuka S et al., Int. J. Pharm. 349 (2008) 94-100).

There are many other non-antimony-based phlegm agents, each acting in a different mechanism. A variety of enzymes have a depolymerization effect on mucin (Rubin B K, Respiratory Care, 52 (2007) 859-865). Treatment practices have traditionally used electrolyte solutions such as ammonium chloride and sodium chloride to cause partial dehydration of the macromolecular coating of mucin, thereby reducing the viscosity of the solution. The use of the treated seawater as an aerosol type tanning agent is the technique disclosed in the prior patent (U.S. Patent No. 7,078,852). In traditional and alternative medicine, pediatrics mainly use a combination of a high-tension solution of a sugar (honey, fig, etc.) or a polyol (mannitol, sorbitol, xylitol, pentaerythritol) and an electrolyte.

Many plant complexes derived from extracts of various parts of the plant are also widely used in therapeutic practice. The flowers or root extracts of plants such as the yellow-flowered or high-flowered spring flowers have long been used. These plants contain triterpenoid saponins and phenolic sugars (Anon.: Assessment report on Primula veris, Primula elatior (L.), radix EMEA (HPMC/144474/2006). Saponins have a significant effect on the surface activity mechanism in aqueous solution. The use of plant saponins and sapogenins to reduce human saliva viscosity for microbiological analysis is a patented technology (US Patent No. 4053363) Triterpenoid saponins contained in ivy leaves have similar effects (Kraft K, Zeitschr. Phytotherap. 25 (2004) 179-181; Fazio S et al., Phytomedicine 16 (2009) 17-24). Eucalyptus Essential oils mainly contain eucalyptol (1,8-cineol) and various other substances, such as hydrazine, sesquiterpene and sesquiterpene alcohol, each acting in a different mechanism, which also contains quinones (Tibballs J, Med. J. Aust. 163 (1995) 177-180). Licorice root also provides a variety of surface active substances, which can exert phlegm-removing effects after removing glycyrrhizin (Guslandi M, Int. J. Clin. Parmacol. Ther. Toxicol., 23 (1985) 398-402). Combination of Icelandic moss and hollyhock inclusions and local anesthetics WO/2006/032364. The flowers of the winter and the genus Verbascum contain a variety of substances, especially flavonoids and saponins, and also have a phlegm effect (Newall CA, Anderson LA, Phillipson JD, Herbal Medicines, Pharmaceutical Press, London 1996). Many other plant complexes are also used for therapeutic purposes with alleged phlegm effects such as crushed grass, oregano, anise, thyme and clover.

Nicotine is a relatively stable substance that decomposes when exposed to air and accelerates decomposition by light. A strong receptor for electrons catalyzes the reaction, while a substance capture group inhibits the reaction. The decomposition reaction mainly produces alkylpyrrolidine oxynitrides (Suffredini HB et al., Anal. Letters 38 (2005) 1587-1599) and similar amounts of pyrrolidone (Beckwith ALJ et al., Austral. J. Chem. 36). (1983) 719-739). Nicotine absorbed in various celluloses contains cotinine, ketone-(1-methyl-3-pyrrolidinyl)-3-pyridyl and other degradation products (Mihranyan A, Andersson SB, Ek R, Eur J. Pharm. Sci. 22 (2004) 279-286). One method of stabilizing nicotine is to absorb nicotine from cellulose of algae, bacteria or fungi (WO/2005/023227). The main metabolic site of nicotine in the human body is the lungs, which are known to produce dozens of metabolites (Moyer TP et al., Clin. Chem. 48 (2002) 1460-1471). To stabilize nicotine, water soluble antioxidants must be added.

Summary of the invention

A composition in which nicotine is absorbed into the system by the oral cavity and distributed in the central nervous system for the purpose of quitting smoking or nicotine replacement for smoking exemption, characterized by comprising a concentration of 0.01 to 8.00% by weight, more preferably 0.10. To a 4.00% by weight, the most preferred is a 0.20 to 1.00% by weight solution of nicotine, the form of which is a salt of a base and/or a base and an organic acid; further comprising a substance having a pupation effect, the pupae The effect substance is 3.0 to 30.0% by weight of acetylated cystine and/or 0.50 to 15.00% by weight of the quinone effect plant complex, and the plant complex with the phlegm effect is extracted from yellow flower Nine-round grass, high-grade spring flowers, ivy, eucalyptus or licorice.

The composition may further comprise 0.05 to 1.50% by weight of an antioxidant compound plant complex, and the antioxidant effect plant complex is selected from the group consisting of flavonoids, flavonoids, flavanones, flavonols, isoflavones, new Flavonoids, anthocyanins, proanthocyanidins and their oligomers, as well as polymers extracted from plants such as green tea, turmeric, rosemary, milk thistle, grape, ginkgo, acai, mulberry, eucalyptus, and West Indian cherry.

The composition may preferably further comprise a buffer or an acid adjusting substance to adjust its pH range to 6.0 to 9.5, more preferably 7.0 to 9.0, and most preferably 8.5.

The composition comprises a solvent which is 50 to 99% by weight of water, or a mixture of water and 2 to 50% by weight of a polyol, wherein the polyol is glycerin, propylene glycol and/or sugar. And the saccharide is selected from the group consisting of mannitol, xylitol, glucose, levulose, and sucrose.

The composition also preferably comprises at least one of the following: a substance that adjusts taste perception, a substance that adjusts olfactory perception, an antibacterial agent, a release agent, an antioxidant, a co-solvent, and a wettability enhancer, and improves physical parameters of the applied composition ( Viscosity and surface tension) and substances that improve the condition of the oral surface (mucosa or teeth).

The composition of the present invention is applied to the oral cavity in a gel form or a heterogeneous air dispersion generated by a spraying device, and the single use dose of the composition is 50 microliters to 2000 microliters, preferably 150 microliters. Rose to 500 microliters.

The single-use dose of the composition comprises from 0.05 to 3.00 mg of nicotine, more preferably from 0.10 mg to 2.00 mg, and most preferably from 0.25 mg to 1.00 mg.

A composition in which nicotine is absorbed into the system by the oral cavity and distributed in the central nervous system for the purpose of quitting smoking or nicotine replacement for smoking exemption, characterized by comprising a concentration of 0.01 to 8.00% by weight, more preferably 0.10. To a 4.00% by weight, the most preferred is a 0.20 to 1.00% by weight solution of nicotine, the form of which is a salt of a base and/or a base and an organic acid; further comprising a substance having a pupation effect, the pupae The effect substance is 3.0 to 30.0% by weight of acetylated cystine and/or 0.50 to 15.00% by weight of the quinone effect plant complex, and the plant complex with the phlegm effect is extracted from yellow flower Nine-round grass, high-grade spring flowers, ivy, eucalyptus or licorice.

The composition may further comprise 0.05 to 1.50% by weight of an antioxidant compound plant complex, and the antioxidant effect plant complex is selected from the group consisting of flavonoids, flavonoids, flavanones, flavonols, isoflavones, new Flavonoids, anthocyanins, proanthocyanidins and their oligomers, as well as polymers extracted from plants such as green tea, turmeric, rosemary, milk thistle, grape, ginkgo, acai, mulberry, eucalyptus, and West Indian cherry.

The composition may preferably further comprise a buffer or an acid adjusting substance to adjust its pH range to 6.0 to 9.5, more preferably 7.0 to 9.0, and most preferably 8.5.

The composition comprises a solvent which is 50 to 99% by weight of water, or a mixture of water and 2 to 50% by weight of a polyol, wherein the polyol is glycerin, propylene glycol and/or sugar. And the saccharide is selected from the group consisting of mannitol, xylitol, glucose, levulose, and sucrose.

The composition also preferably comprises at least one of the following: a substance that adjusts taste perception, a substance that adjusts olfactory perception, an antibacterial agent, a release agent, an antioxidant, a co-solvent, and a wettability enhancer, and improves physical parameters of the applied composition ( Viscosity and surface tension) and substances that improve the condition of the oral surface (mucosa or teeth).

The composition of the present invention is applied to the oral cavity in a gel form or a heterogeneous air dispersion generated by a spraying device, and the single use dose of the composition is 50 microliters to 2000 microliters, preferably 150 microliters. Rose to 500 microliters.

The single-use dose of the composition comprises from 0.05 to 3.00 mg of nicotine, more preferably from 0.10 mg to 2.00 mg, and most preferably from 0.25 mg to 1.00 mg.

The composition of the present invention contains, in addition to nicotine and its salt as an active substance, a phlegm-removing agent, such as acetylated cystine and/or a plant complex having a phlegm-removing effect, the plant complex having a phlegm-removing effect. It is extracted from plants and acts to increase nicotine bioavailability. The composition of the present invention may further comprise an antioxidant derived from a natural plant to enhance the stability of nicotine and prevent oxidation thereof, and water is used as a solvent in the composition. The composition of the present invention may also contain various stabilizers such as antibacterial agents, release agents, and free radical quenchers; and sensory property adjusting substances may also be added. The composition of the present invention may also contain a substance which improves physical parameters such as viscosity and surface tension at the time of application of the composition, and a substance which improves oral surface conditions such as mucosa or teeth.

Nicotine is an extremely potent alkaloid that dissolves easily in water-to-strong alkaline solutions. The oral mucosa is well tolerated, and it can fully enter the systemic circulation after being absorbed by the oral mucosa. The pH of the nicotine solution is preferably below 9.0 and above 7.0. The pH of the nicotine aqueous solution can be easily lowered by adding a salt such as citric acid, malic acid, tartaric acid, lactic acid, glycolic acid or phosphoric acid. The concentration of nicotine in the solution will depend on the dosage administered; it may range from 0.01% to 8.00%, more preferably from 0.10% to 4.00%, and most preferably from 0.20% to 1.00%. The dose of nicotine for a single administration may range from 0.05 mg to 3.00 mg, more preferably from 0.10 mg to 2.00 mg, and most preferably from 0.25 mg to 1.00 mg.

The phlegm-removing agent is a highly hydrophilic substance which can reduce the viscosity of mucin, which contains mucin-like substances. Decreasing the viscosity of mucins allows nicotine molecules to spread faster to the surface of the mucosal barrier, thus accelerating and enhancing the absorption of nicotine. Acetylcysteine is a highly hydrophilic substance. The carboxyl group can interact with the basic nitrogen of the pyrrolidine ring of nicotine. It has an antioxidant effect, and the sulfhydryl group can be an electron donor. It is an important bismuth agent that interacts with disulfide bonds to reduce the viscosity of aqueous mucoprotein solutions.

A natural plant-derived tanning agent capable of increasing the nicotine bioavailability of the composition of the present invention is the same as a phlegm-removing agent conventionally used for promoting sputum excretion, and such a substance is particularly commonly used in pediatrics. Applicable to the extraction of a complex from a medicinal plant, such as the yellow flower of the genus Hydrangea or the high-grade spring flower or the root water or alcohol extract, which comprises triterpenoid saponin and phenolic sugar. Triterpenoid saponins contained in the leaves of ivy also have similar effects. The composition of the present invention may also comprise an essential oil derived from eucalyptus leaves, which particularly contains eucalyptol (1,8-cineol) and various other substances such as hydrazine, sesquiterpene and sesquiterpene alcohol. The plant complex obtained by extracting from the licorice root can provide a surface active substance and has a phlegm-removing effect after removing the glycyrrhizin. Another component suitable for use in the compositions of the present invention is a combination of the materials contained in the Icelandic moss and the hollyhock, and the contents of the winter cultivar and the genus. There are many other plant complexes that provide the desired quinone effects, such as crushed grass, oregano, anise, thyme, clover, and the like. When the plant complex having the pupation effect is used as a component of the composition of the present invention, the concentration thereof is 0.5% by weight to 15% by weight, more preferably 0.5% by weight to 5% by weight, and most preferably 1 % by weight to 2% by weight.

The antioxidants in the composition of this case are important for maintaining the stability of nicotine in the solution, preventing the oxidation of nicotine, and the antioxidants also have a positive effect on the oral mucosa. The composition of the present invention may comprise a substance derived from a natural plant or a water-soluble mixture thereof, such as ascorbic acid and a salt thereof, various flavonoids such as flavonoids, flavonoids, flavanones, flavonols, isoflavones, new Flavonoids, anthocyanins, proanthocyanidins and their oligomers and polymers. In many plant complexes extracted from plant materials containing known species, the catechin-containing green tea leaf extract is a flavanol, the milk thistle extract contains a milk thistle complex, and the turmeric extract contains turmeric The complex, the rosemary extract comprises rosmarinic acid, the grape extract comprises proanthocyanidins and various other polyphenolic materials, the ginkgo leaves contain flavonoids, and both the mulberry fruit and the acai berry contain anthocyanins. In addition to the epicatechin contained in green tea, quercetin and quercetin are the most commonly used foods. The extract of the French coast P. sylvestris contains a mixture of many bioflavonoid catechins, oligopolymer proanthocyanidins and phenolic fruit acids with antioxidant capacity. Extracts of plants such as eucalyptus and West Indian cherries are the main sources of ascorbic acid and its salts. In the composition concentration of the present invention, the plant complex containing various antioxidants and extracted from the plant has a concentration of about 0.05% by weight to 1.5% by weight, more preferably 0.25% by weight to 1.5% by weight, most preferably It is from 0.50% by weight to 1.0% by weight. Water is the solvent of the individual ingredients in the composition of this case. According to the technical solution of the present invention, the proportion of water in the composition is from 50% to 99%, more preferably from 65% to 90%, and most preferably from 75% to 95%.

Acids or hydroxides can be used to adjust the acidity of the components, such as amine or amino acid and nicotine to produce incomplete salts or better, buffer system acetate, citric acid, triethanolamine, tromethamine, carbonate, etc. Wait. The dicarboxyamino acid can be used singly or in combination, such as glutamic acid or aspartic acid, or a basic amino acid such as an aminic acid or a protein amine. In order to improve the stability and bioavailability of the nicotine, the pH range of the solution should be adjusted to 6.0 to 9.5, more preferably 7.0 to 9.0, and the optimum pH is 8.5.

Other ingredients useful in the compositions of the present invention also include antiseptic additives. Applicable to sorbic acid or benzoic acid and salt. Other antibacterial substances suitable for use in the present invention may include parabens or benzoic acid phenol esters, especially methyl benzoic acid phenol esters. Various essential oils such as clove oil, thyme oil, wild thyme oil, eucalyptus oil or semi-polar solvent extracts of such plants may also be added to the compositions of the present invention. Propylene glycol or ethanol can also provide an antibacterial effect, and it can also be used as an extractant for plant raw materials. Suitable preservatives such as hypericum, Icelandic moss, tartary buckwheat, sage, willow skin and other alcohol or propylene glycol liquid extract.

The substance that adjusts the taste perception is mainly a sweetener. The most common are various sugars and inositol, such as glycerin, propylene glycol, sucrose, glucose, levulose, sorbitol, mannitol, xylitol, honey, and the like. Another class of materials suitable for this purpose are artificial non-nutritive sweeteners such as sweetener salts, acesulfame lactone, aspartame, neohesperidin dihydrochalcone, sucralose, licorice extract, Stevia extract and more. Essential oils can be used to adjust olfactory perception, such as peppermint oil, spearmint oil, anise oil, fennel oil, eucalyptus oil, eucalyptus oil, cumin oil, cinnamon oil, clove oil, thyme oil, wild thyme oil, and water cress oil. , juniper oil, marjoram oil, ginger oil, etc.

The composition according to the invention may further comprise other ingredients for positively adjusting its physical parameters. The addition of ethanol or propylene glycol can reduce the viscosity and surface tension of the aqueous solution, and can also use an surfactant. Substances that have a positive effect on oral surface conditions such as mucous membranes and teeth may contain a variety of vitamins and minerals such as vitamin B and its salts, vitamin C and its salts, esters and glycosides, vitamin H, coenzyme Q10, and zinc and copper. a complex of a substance such as selenium, calcium and manganese, a salt thereof or the like. An anti-inflammatory agent can be used as the bisabolol and allantoin extracted from hypericum, marigold and chamomile.

The composition of the present invention is applied to the oral cavity by spraying, that is, the composition contacts the oral mucosa, the gingival mucosa, the hard palate, and the surface of the tongue in a gas in a heterogeneous or gel-like manner. The air distribution generator can be a pump, or a pressure vessel with a propeller can be used to spray the composition in a gas flow pattern. The propellant gas can be nitrogen or other chemically inert gas, or a mixture of alkanes such as butane, isobutane or propane. The particle size in the ejected aerosol may range from 20 nm to 100 μm, preferably from 500 nm to 5 μm. To control the dose, the air distribution generator is equipped with a dispensing device. The liquid dose for a single administration may range from 50 microliters to 2000 microliters, preferably from 150 microliters to 500 microliters. The listed parameters are for illustrative purposes only and are not the subject of the technical solution in this case.

Preferred embodiment example

Preparation procedure: Individual ingredients are gradually added to dissolve in water. The solution is filtered as needed and placed in a pressure vessel with a dispensing valve or a closed vessel with a dispensing valve and driven by a manual pump.

Industrial Applicability: The composition of the present invention can be produced by the pharmaceutical industry. The preparation is suitable for the absorption of nicotine transmucosal for the purpose of quitting smoking.

Claims (8)

A composition in which nicotine is absorbed into the system and distributed in the central nervous system for the purpose of quitting smoking or nicotine replacement for smoking exemption, characterized in that the composition comprises a nicotine solution and a substance having a pupation effect An antioxidant compound plant complex and a buffer or an acid adjusting substance; the nicotine solution is at a concentration of 0.01 to 8.00% by weight, and the form is a salt of a base and/or a base and an organic acid; The effect substance is 3.0 to 30.0% by weight of acetylated cystine and/or a quinone effect plant complex having a concentration of 0.50 to 15.00% by weight, and the plant complex with the phlegm effect is extracted from At least one plant selected from the group consisting of Primula veris, Primula elatior, Hedera helix, Eucalyptus globulus or Liquiritia glabra. One of the antioxidant compound plants is 0.05 to 1.50% by weight, and the antioxidant compound plant complex is selected from the group consisting of flavones and flavonols. , flavanones, flavanonols, isoflavones, neoflavoneoids, anthocyanidins, proanthocyanidins, and oligomers thereof, and at least one extracted from Green tea (Camellia sinensis), Curcuma longa, Rosmarinus officinalis, Sylibium marianum, Vitis vinifera, Ginkgo biloba, Euterpe oleracea, Mulberry a polymer of one of Vaccinium myrtillus), Morinda citrifolia and Malpighia glabra; and the buffer or acid adjusting substance to adjust the pH range of the composition to 7.0 to 9.0. A composition for invoking nicotine into the systemic circulation and distributed in the central nervous system, as described in claim 1, wherein the composition comprises a solvent having a concentration of 50 to 99% by weight of water. Or a mixture of water and a polyol having a concentration of from 2 to 50% by weight, wherein the polyol is glycerin, propylene glycol and/or at least one saccharide selected from the group consisting of mannitol (mannitol), xylitol, glucose, fructose, and saccharose. A composition for invoking nicotine into the systemic circulation and distributed in the central nervous system, as described in claim 1, wherein the composition comprises at least one of the following groups: adjusting taste sensing substances, adjusting Olfactory perception of substances, antibacterial agents, release agents, An antioxidant, a cosolvent and a wettability enhancer, a substance which improves the physical parameters of the composition, and a substance which improves the surface condition of the oral cavity, wherein the physical parameter comprises the viscosity and surface tension of the composition, and the oral surface condition comprises a mucous membrane or The condition of the teeth. A composition for invoking nicotine into the systemic circulation and distributed in the central nervous system as described in claim 2, wherein the composition comprises at least one of the following groups: adjusting taste sensing substances, adjusting Olfactory-aware substances, antibacterial agents, release agents, antioxidants, co-solvents and wettability enhancers, substances which improve the physical parameters of the applied composition, and substances which improve the surface conditions of the oral cavity, wherein the physical parameters include the viscosity of the composition and Surface tension, and the conditions of the oral surface include conditions of mucous membranes or teeth. The composition for invoking nicotine into the systemic circulation and distributed in the central nervous system as described in claim 1, wherein the single-use dose of the composition comprises 0.05 mg to 3.00 mg of nicotine. The composition for invoking nicotine into the systemic circulation and distributed in the central nervous system as described in claim 2, wherein the single-use dose of the composition comprises 0.05 mg to 3.00 mg of nicotine. The composition for invoking nicotine into the systemic circulation and distributed in the central nervous system as described in claim 3, wherein the single-use dose of the composition comprises 0.05 mg to 3.00 mg of nicotine. The composition for invoking nicotine into the systemic circulation and distributed in the central nervous system as described in claim 4, wherein the single-use dose of the composition comprises 0.05 mg to 3.00 mg of nicotine.