JP2001514220A - Improved compositions and methods for smoking control - Google Patents

Abstract

  (57) [Summary] Disclosed are compositions for controlling smoking. The composition comprises (a) a xanthine oxidase inhibitor, (b) a phosphate or a compound capable of releasing phosphate upon administration to a subject, and optionally (c) a sugar, and optionally further (d) one or more thereof. It contains the above pharmaceutically acceptable carriers or excipients. The present invention also describes a method of controlling smoking comprising administering the composition to a subject in need of such treatment.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001] The present invention relates to compositions and methods for use in controlling smoking, and in particular, reducing the need for smoking.

[0002] It is widely accepted that smoking has significant implications for health risks. When smokers are compared to members of other populations, there is an increase in morbidity and mortality in all age groups. Smoking is associated with asthma, emphysema, and cancerous conditions such as the mouth, larynx, tongue, and lungs. According to Glynn and Sussman, many smokers believe that smoking harms their health, and despite the conviction of this crime, a relatively large percentage of Westerners or other groups continue to smoke. (S, M. Glynn and S. Su
ssmann, 1990, Hospital and Community Psychiatry, 41, 9, 1027-1028). Almost all successful approaches to smoking control, such as hypnosis, acupuncture, "naturopathic" and nicotine-based interventions, have not been successful. Chronic smokers generally find it very difficult to stop their habits.

In our pending application PCT / AU95 / 00621, we describe compositions and methods for controlling smoking. Quite surprisingly, we minimize the two different classes of compounds that are effective in combination to reduce the smoker's desire to smoke and thereby provide control of smoking It has been found that a composition can be prepared.

In a first aspect of the present invention, (a) a xanthine oxidase inhibitor,
(B) a phosphate or compound capable of releasing phosphate upon administration to a subject, and optionally (c) a sugar, and optionally (d) one or more pharmaceutically acceptable carriers. Alternatively, there is provided a composition for controlling smoking, comprising an excipient.

In another embodiment of the present invention, (a) a xanthine oxidase inhibitor,
b) phosphate or a compound capable of releasing phosphate upon administration to a subject, and optionally (c) a sugar, and optionally (d) one or more pharmaceutically acceptable carriers or A method of controlling smoking is provided which comprises administering a composition comprising an excipient to a subject in need of such treatment.

In another aspect of the invention, in the manufacture of a medicament for controlling smoking, (a) a xanthine oxidase inhibitor, (b) a phosphate or a compound capable of releasing phosphate upon administration to a subject, and optionally It relates to the use of a composition comprising (c) a sugar and, optionally, (d) one or more pharmaceutically acceptable carriers or excipients.

In a further aspect of the invention, (a) a xanthine oxidase inhibitor, (b) a phosphate or a compound capable of releasing phosphate upon administration to a subject, and optionally (c) a sugar, and further optionally Accordingly, there is provided (d) a smoking control agent comprising one or more pharmaceutically acceptable carriers or excipients.

[0008] The compositions and methods of the present invention have surprisingly been found to control smoking. This is especially surprising, as it was previously considered by the present inventor that all of the components described in PCT / AU95 / 00621 are required for smoking control. Controlling smoking can substantially reduce the number of cigarettes that an individual smokes or can quit smoking. Various tests performed by chronic smokers described below show that the compositions of the present invention suppress the need and need for smoking.

[0009] Xanthine oxidase inhibitors can inhibit the activity of xanthine oxidase (including xanthine dehydrogenase and xanthine oxidoreductase) by a variety of mechanisms (competitive inhibition (if the compound acts as an antagonist), by binding xanthine oxidase at or near the active site). Alter the conformation of xanthine oxidase by binding the active site of the xanthine oxidase enzyme generally outside, binding or inactivating free radical agents produced by the xanthine oxidase, or other (Including the mechanism). Xanthine oxidase inhibitors are well known in the art. Examples of xanthine oxidase inhibitors include Eupatorium Purpureum (Gra
vel Root), plant extracts from plants such as allopurinol, oxypurinol, purpurogallin, and Trolox (e.g., Zeng and Wu, 1992, Cell. Biol., 70, 684-690). Described vitamin E analog).

[0010] One group of xanthine oxidase inhibitors is the flavonoids (also known as bioflavonoids) (eg, edited by Harborne et al., The Flavonoids, Ac
ademic Press, New York, 1975, Harborne et al., The Flavonoids, Advances in Researc
h Since 1986, 1994; Princemail et al., 1987, `` Ginkgo Biloba extract inhibits oxyg
en specles production generated by phorbol myristate acetate stimulated
human leukocytes, Experientia, February 15, 43 (2), 181-184, Frage et al. (1987), Flav
onoids as antioxidants evaluated in vitro and in situ liver chemilumines
cence ", Biochem. Pharmacol., March 1, 36 (5), 717-720, Schmeda-Hirschmann et al., (19
87), `` Preliminary pharmacological studies on Eugenia uniflora leaves: xa
nthine oxidase activity '', J. Ethnopharmacol., November 21 (2), 183-186, Zeng LH
And Wu TW, (1992), `` Purpurogallin is a more powerful protector of ki
dney cells than Trolux and allopurinol ", Biochemistry and Cell Biology, 70
, 604-709, Siggins FM, (1888), `` Analysis of the levels of Eupatorium Pur
purem '', Am. J. of Pharm., 60, 121-122, Manger CC, (1984), `` Euparin '', Am. J.
of Pharm., 66, 120-124, Trimble H., 1890, "Eupatorium Purpurem", Am. J. of Ph.
arm., February, 62, 73-80).

[0011] Flavonoids are a large group of plant secondary metabolites derived from flavan. The basic structure of flavonoids is flavanone (flavan-4-one), which is a derivative of flavonoids, flavonol (flavan-3-ol),
Derived from flavone and flavonol. Anthocyanins and catechol are derived from flavans and should be considered as flavonoids for the present invention (Concise Encyclopaedia of Chemistry, de Gruyter, 1994; specifically, 77,
190 and 411-431). Examples of anthocyanins are cyanine, pelargonin, delphin, delaein, malvin, petunin, petunin, keracyanin, micocyanin, micocyanin, frasarin, ぺ onin ( paeonin), oenin, and chyrsanthemin. These compounds can be hydrolyzed by acids and glycosidases to the corresponding aglycones (anthocyanins). The sugar residue may be linked to position 3 or 5 of the anthocyanin. Catechol tannins are a group of tannins whose monomer unit is flavan-3-ol (catechol) or flavan-3,4-diol. Catechol is 5,7,3 ', 4'-tetrahydroxyflavan-3-ol. The above compounds should be considered as flavonoids for the purpose of the present invention.

The most widely occurring flavonoids are the flavones. Flavones are yellow pigments of the flavonoid group containing a flavone, isoflavone or flavonone skeleton. Flavones are widely found in nature, for example, in flowers, trees and roots, usually as glycosides or esters of tannic acid, and The Flavonoids, Advances in Research
It can be easily extracted from these natural sources using long-established and well-known techniques, such as those described in Since 1986, Harborne et al., 1994 and the like. Examples of flavonoids include apigenin, chrysin, eupatorin, fisetin (fiseti
n), genistein, hesperitin, kaempherol
Luteolin, morin, myricetin and quercetin. Flavonoid compounds within the scope of the present invention and other xanthine oxidase inhibitors Eupa torium Purpureum (aka Gravel Root, Queen of the Meadow or known as Jo Pye Weed,), (known as an alias Agrimony) Eupatorium Coenobium, Eupatorium Fortun ei (Peil (related extracts known as lan or Peilan), Ginkgo Biloba, and can be extracted from a wide variety of plant species. Examples of preferred compounds are euparin and eupatorin, or plant extracts containing these substances. Eupatorium Purpurem- containing extract contains Euparin from Blackmores' Gravel Root Extrac
t "(Blackmores Pty, Balgowlah, New South Wales, Australia). Flavonoids can be provided as plant extracts prepared according to standard procedures such as alcohol extraction.

Examples of further flavonoids or bioflavonoids that can be used in the present invention include citrus bioflavonoids, vitamin P, vitamin P complex, rutin, bioflavonoids from orange peel, bioflavonoids from grapefruit peel , Lemon bioflavonoids, lime bioflavonoids,
Narigenin (narigenin), naringin (naringin), naringenis (naringenis), delphinidin (delphinidin), phloretin (phloretin), cyanic (cyanic),
Catechin, morin, phlorizin, phloretin, 3-hydroxyflavone, 3-deoxyflavonol, isorhamnetin, tricine,
Chrysoeriol, chlosoeriol, erlodictyon, techtrochrysin, silybin, taxifolin, pinocembrim, galangin, robinin, diosmetin, diosmetin (kaempferide), rhamnetin
) And 3-O-methylcatechin.

Xanthine oxidase inhibitors include plant extracts (eg, water and / or alcohol extracts) of plants such as Eupatorium Purpurem, which have xanthine oxidase inhibitory activity, common tea-derived extracts, and oak bark or husk. It may contain an extract derived from tomato. Synthetically produced flavonoid compounds such as euparin having xanthine oxidase inhibitory activity or analogs thereof are within the scope of the present invention.

[0015] Other xanthine oxidase inhibitors that can be used in the present invention include plant extracts, such as modified tannins, or those that can exhibit xanthine oxidase inhibitory activity, common tea-derived extracts, and oak bark or husk Includes extract from tofu. Examples of other xanthine oxidase inhibitors include purine analogs (caffeine, theobromine, theophylline, ethophylline (et
ofylline), quinazoline (including metacaron hydrochloride), triazine (1,2,3-triazine, 1,3,5-triazine, cyanuric acid, cyanuric chloride, etc.)
, Pyrazaro (3,4-d) pyrimidines such as allopurinol and oxypurinol, and benzocycloheptenone such as purprogalin.

[0016] Xanthine oxidase (XO) inhibitory activity was measured using Biochem. Biophys. Acta., 1992.
, 1112 (2), 178-182, which are incorporated herein by reference, and can be readily assessed by standard biological assays.

Compounds that bind to or inactivate free radicals produced by xanthine oxidase should be considered inhibitors of xanthine oxidase. Such compounds include butylated hydroxyanisole, butylated hydroxytoluene, propyl gallate, sodium benzoate, pterin (FEBS Lett., 19
92, 304, 2-3, 163-166), flavonoid compounds, iron-eliminating compounds such as superoxide dismutase, desferrioxamine, plasma antioxidants such as glutathione, bilirubin, ubiquinone, albumin, ascorbic acid, etc. Water-soluble antioxidants, fat-soluble antioxidants such as tocipherol, heme release antioxidants such as salts of haptoglobulin, aspartic acid zinc, magnesium, chromium, manganese, etc. .

As mentioned above, xanthine oxidase inhibitors are, for example, British He
rbal Pharmacopeia, 1990, Volume 1, British Herbal Medicine Association, United
Kingdom, and The Flavonoidds, Advances in Reseach Since 1986, Harborne et al.,
It can be provided as a plant / plant component extract produced according to standard techniques, such as the technique described in 1994.

Examples of phosphates or compounds that can release phosphate (PO43−) when administered to a subject include phosphoric acid, orthophosphoric acid salts (depending on the number of hydrogen groups replaced, eg, sodium, magnesium, and Primary phosphate (dihydrogen phosphate), secondary phosphate (monohydrogen phosphate) or tertiary phosphate (such as magnesium phosphate, sodium phosphate and potassium phosphate) including potassium salt, phosphorus Organic esters, such as C1-10 esters of acids, as well as herbal extracts that release phosphate or phosphorus when administered to human subjects. Phosphates are phytostigmine, minaprin
It should be considered within the scope of organophosphorus, including compounds including e) and Ethelin. Preferably, the compositions of the present invention include one or more of such substances. For example, in one aspect of the invention, the composition may include a compound that includes inorganic phosphorus, such as magnesium phosphate, and an organic phosphorus compound, such as phytostigmine.

[0020] Optionally, the compositions of the present invention may comprise fructose, sucrose, or any other sugar (either a monosaccharide, disaccharide or polysaccharide). Such sugar components are
It can promote uric acid production in humans. Examples of suitable sugars include glucose, fructose, galactose, xylose, arabinose, fucose, rhamnose, starch or other sugars including polymers. In particular, fructose is preferred.

[0021] The compositions of the present invention comprise from about 0.1% to about 40% w / w, more particularly from about 10% to 25%.
w / w xanthine oxidase inhibitor, about 0.2% to about 20%, more preferably about 0.5% to about 5% w / w, and more particularly about 0.5% to about 4% w / w phosphate Or it may comprise a compound capable of releasing phosphate. The balance of the composition can include pharmaceutically acceptable carriers or excipients described below. Optionally, the composition in an embodiment of the present invention further comprises about 10% to about 50% sugar.
/ W, more particularly about 15% to about 40% w / w, even more particularly about 15% to about 30%
Includes w / w amounts.

The compositions of the present invention can be administered orally, topically (including buccal and sublingual), parenteral (including subcutaneous, intramuscular, intravenous, intraperitoneal and intradermal), vaginal or rectal administration or implantation (eg, , Slow release molecules). The compositions may conveniently be presented in unit dosage form and may be prepared by any of the methods well-known in the art of pharmacology.
Such methods include the step of bringing into association the main component with the carrier which constitutes one or more accessory ingredients. In general, the compositions are prepared by uniformly and intimately bringing into association the active ingredient with the liquid carrier or finely divided solid carrier or both, and then, if necessary, shaping the product.

[0023] Depending on the rate of administration, the active ingredient may need to be coated with an agent to protect the active ingredient from the action of enzymes, acids and other natural conditions which may inactivate the ingredient.

For oral administration, the pharmaceutical compositions include tablets, lozenges, pills, troches, capsules, elixirs, powders, granules, aqueous solutions, suspensions, emulsions, syrups and tinctures. It can be in the form. Forms for slow release or delayed release may also be prepared, for example, in the form of coated particles, multilayer tablets or finely divided powders.

[0025] Solid forms for oral administration can include pharmaceutically acceptable binders, sweeteners, disintegrants, diluents, flavors, coatings, preservatives, lubricants and / or time delay agents. Suitable binders include acacia gum, gelatin, corn starch, tragacanth gum,
Includes sodium alginate, carboxymethyl cellulose or polyethylene glycol. Suitable sweeteners include sucrose, lactose, glucose, aspartame or saccharin. Suitable disintegrants include corn starch, methylcellulose, polyvinylpyrrolidone, xanthan gum, bentonite,
Includes alginic acid or agar. Suitable diluents include lactose, sorbitol, mannitol, dextrose, kaolin, cellulose, calcium carbonate,
Includes calcium silicate or dicalcium phosphate. Suitable fragrances include peppermint oil, oil palm, cherry, orange or raspberry scented oils. Suitable coatings include acrylic and / or methacrylic acid polymers or copolymers and / or their esters, waxes, fatty alcohols, zein, shellac or gluten. Suitable preservatives include sodium benzoate, vitamin E, α-tocopherol, ascorbic acid,
Includes methyl paraben, propyl paraben or sodium disulfate. Suitable lubricants include magnesium stearate, stearic acid, sodium oleate, sodium chloride or talc. Suitable time delay agents include glycerol monostearate or glycerol distearate.

Liquid forms for oral administration can contain a liquid carrier in addition to the active ingredient. Suitable liquid carriers include water, oils (olive oil, peanut oil,
Sesame oil, sunflower oil, safflower oil, arachis oil, coconut oil, etc.),
Includes liquid paraffin, ethylene glycol, propylene glycol, polyethylene glycol, ethanol, propanol, isopropanol, glycerol, fatty alcohols, triglycerides or mixtures thereof.

[0027] Suspensions for oral administration can further include dispersants and / or suspensions. Suitable suspending agents include sodium carboxymethylcellulose, methylcellulose,
Includes hydroxypropyl methylcellulose, polyvinylpyrrolidone, sodium alginate or cetyl alcohol. Suitable dispersants include polyoxyethylene esters of fatty acids such as lecithin, stearic acid, polyoxyethylene sorbitol mono or dioleate, stearate or laurate, polyoxyethylene sorbitan mono or dioleate, stearate or laurate, and the like. .

[0028] Emulsions for oral administration may further comprise one or more emulsifiers. Suitable emulsifiers include the dispersing agents described above or natural gums such as acacia or tragacanth.

For topical administration, the pharmaceutical composition may be in the form of a cream, ointment, gel, jelly, tincture, suspension or emulsion. Pharmaceutical compositions may include pharmaceutically acceptable binders, diluents, disintegrants, preservatives, lubricants, dispersants, suspending agents and / or emulsifiers as described above.

Pharmaceutical forms suitable for parenteral administration include sterile aqueous solutions (where water soluble) or dispersions and powders for the extemporaneous preparation of sterile injectable solutions or dispersion. The pharmaceutical form must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol and liquid polyethylene glycol, and the like), suitable mixtures thereof, and vegetable oils. The solution or suspension may further include one or more buffers. Suitable buffers include sodium acetate, sodium citrate, sodium borate or sodium tartrate. Proper fluidity can be maintained, for example, by the use of a coating such as lectin, the maintenance of the required particle size when dispersed, and the use of surfactants. The action of microorganisms can be prevented by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, thermelosal, and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars or sodium chloride. Absorption of injectable compositions is
For example, it can be delayed by using a composition of the absorption delaying agents.

Sterile injectable solutions are prepared by mixing the required amount of the active ingredient with a suitable solvent having the required other ingredients from those enumerated above, followed by sterile filtration.

Generally, dispersions are prepared by mixing the various sterilized bases in a sterile vehicle which contains the main dispersion medium and the required other ingredients from those enumerated above.
In the case of sterile powders for the preparation of sterile injectable solutions, the preferred preparation methods are suction drying and freeze-drying techniques, which result in a powder of the active ingredient and any further desired ingredients from the solution, which has been previously sterilized by filtration.

For rectal administration, the active ingredient is suitably administered in the form of an enema or suppository. Suitable suppositories may be made by mixing the active ingredient with a non-inflammatory excipient which is solid at room temperature but which is soluble in the rectum. Suitable such materials are cocoa butter and polyethylene glycol. Suitable enemas may include agents that refer to the above described forms for topical administration.

The above ingredients used to formulate the active ingredient into a suitable dosage form can be referred to collectively as a carrier and excipient.

The compositions of the present invention are preferably suitable for oral administration, more preferably as an aqueous solution. Examples of solutions of the invention may include (i) a water / ethanol flavonoid extract, eg, extracted from Eupatorium Purpure um species, (ii) an aqueous solution of a phosphate compound such as phosphoric acid, and (iii) a fragrance.

[0036] In another embodiment, the composition may further comprise a sugar such as fructose.

In the method of the present invention, the active ingredients may be administered separately or as a composition comprising the active ingredients (ie, a xanthine oxidase inhibitor, a phosphate or a compound capable of releasing phosphate, and optionally a sugar). obtain. Without limiting the invention in general, a suitable dose of a xanthine oxidase inhibitor is 0.5 mg to 10 mg / kg body weight, preferably 3 mg to 6 mg.
/ Kg body weight / day, more preferably in the range of 3 mg to 5 mg / kg body weight / day. Without limiting the invention in general, suitable dosage ranges for the phosphate or a compound capable of releasing phosphate are on the order of 0.01 mg to 0.5 mg / kg body weight per day, preferably 0.06 mg to 0 mg. 0.3 mg / kg body weight / day, more preferably in the range of 0.08 mg to 0.25 mg / kg body weight / day. When a saccharide component according to the optional embodiment of the present invention is contained, the saccharide such as fructose is present in an amount of 0.75 mg to 50 mg / kg body weight, preferably 4.5.
mg to 30 mg / kg body weight / day, more preferably 6 mg to 25 mg / kg
It can be present in the range of weight / day.

Each of the compounds of the present invention, when in the form of a composition described herein, may be
It can be administered ten times, more preferably one to five times a day, and at appropriate intervals and at appropriate dosage levels. Administration is for 1 to 10 weeks, preferably at least 2 weeks.
Can be maintained for ~ 4 weeks.

The compositions of the present invention may also provide fatigue, chronic fatigue, concentration difficu
lties), mood disturbances, or a general class of symptoms described in "asthenia" or "neurosis" or "post viral asthenia". Smokers may exhibit one or more of these conditions, which may be due to various metabolic instabilities. Such signs of instability can drive a strong urge to smoke. Treatment or amelioration of one or more of these conditions may reduce the urge or demand for smoking.

The present invention is described below with reference to examples, but is not limited thereto. Example 1 The following active water-soluble composition was prepared. A) Ethanol extract of herb Gravel Root (1: 2 v / v) 400 ml Phosphate ion 10 ml Phosphoric acid or calcium diphosphate 10 g Perfume 30 ml More than 2 liters of water is added to make the total volume 2 liters. B) The composition of A) further comprising 1 kg of a thickening excipient (glucose syrup). C) The composition of A), further comprising 1 kg of fructose. D) further comprising 1 kg of glucose syrup and 1 kg of fructose
Composition. E) Compositions A) and D) when 2-20 g of allopurinol, oxypurinol, purprogalin or Trolox are used instead of the gravel root extract.

Example 2 A series of clinical trials have been conducted in Australia showing that the invention is effective in various aspects. Specific details are briefly described below.

A) Procedure Participants in this study were volunteers who smoked on average more than 30 cigarettes per day. Each study involved daily oral administration of the composition to participants and lasted for 6 weeks. During the last two weeks of each test, no test or placebo composition was administered.

B) Composition The composition described in Example 1 was orally administered in a volume of 10 ml / day.

One of the trials was in the following treatment groups: i) The first group to which the composition D of Example 1 was administered. ii) a second group administered with a composition comprising: an ethanol extract of Gravel Root glucose syrup perfume water each of these compositions is present in the same amount as in Example 1. iii) a third group administered with a composition comprising: fructose, phosphoric acid, flavor, glucose syrup, water, each of these compositions being present in the same amount as in Example 1. iv) Group 4 administered a composition comprising: • an ethanol extract of Gravel Root • glucose syrup • fructose • fragrance • water Each of these compositions is present in the same amount as in Example 1. v) Group 5 to which the composition A) of Example 1 was administered. vi) Group 6 to which a composition comprising: • 30 ml of perfume • 1 kg of full-coose syrup • 2 liters of water.

C) Results (Summary) A small, transient placebo effect was observed in Group 6. There was no significant reduction in smoking during or after the study. Large reductions in the percentage of participants smoking were observed in Groups 1 and 5. However, a small number (less than about 10%) of participants are refractory to treatment, which in no way diminishes the efficacy of the present invention. In the other groups, there was no significant effect on smoking, meaning that the treatment was not effective.

The above detailed example is described below. (Group 1) XAA is a woman in her late thirties who smoked more than 15 cigarettes per day. She did not show a desire to smoke as a result of the treatment program.

(Group 2) Mr XA is a 38-year-old man who smoked 25 cigarettes per day.
The treatment course was not effective. XB is a 46-year-old man who smokes 40 cigarettes per day. The treatment course was not effective.

(Group 3) Mr. XC is a middle-aged man who smokes more than 30 cigarettes per day.
The treatment course was not effective.

Group 4 Mr. XD is a 46-year-old man who smokes more than 30 cigarettes per day. The treatment course was not effective.

Group 5 Mr XE is a 49-year-old man who smokes 15 cigarettes per day. As a result of his cool treatment, he stopped smoking.

Mr XF is a 45-year-old man who smokes more than 30 cigarettes per day.
As a result of his treatment program, he has lost his desire for smoking.

Throughout this specification, unless required by context, the words “comprise” or “com”
A variant such as "prises" or "comprising" or the term "includes" or a variant thereof includes the inclusion of the listed element or whole or group of elements or whole but refers to any other element or whole or group of elements or whole. It is understood that it does not exclude. In this regard, in interpreting the following claims, if one or more of the essential features of the claimed invention are included in such an embodiment, one or more features may be added to any claim Should be considered within the scope of the present invention.

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Claims (21)

[Claims] 1. A composition for controlling smoking, comprising: (a) a xanthine oxidase inhibitor, (b) a phosphate or a compound capable of releasing phosphate upon administration to a subject, and optionally (c) A) A composition comprising a sugar and, optionally, (d) one or more pharmaceutically acceptable carriers or excipients. 2. The composition of claim 1, wherein said xanthine oxidase inhibitor is selected from flavonoids, purine analogs, quinazolines, triazines, and pyrazaro (3,4-d) pyrimidines. 3. The composition of claim 2, wherein said flavonoid is selected from flavanone, flavonol, flavone, anthocyanin, catechol and catechol tannin. 4. The composition according to claim 2, wherein the flavonoid is in the form of an extract from a plant source comprising one or more flavonoids. 5. The composition according to claim 1, wherein the xanthine oxidase inhibitor is an extract derived from a plant source. 6. The composition according to claim 5, wherein said plant source is Eupatorium Purpureum (Gravel Root). 7. The method of claim 1, wherein the xanthine oxidase inhibitor is euparin (e
The composition of claim 1, which is an uparin). 8. The xanthine oxidase inhibitor comprises allopurinol, oxypurinol, purpurogallin and trolox (tr).
olox). 9. The method according to claim 1, wherein the phosphate or the compound capable of releasing phosphate when administered to a subject is a herbaceous extract which releases phosphoric acid, salts of phosphoric acid, esters of phosphoric acid or phosphate. Composition. 10. The composition according to claim 9, wherein said phosphate source is phosphoric acid or phosphate. 11. The composition of claim 1, wherein said sugar comprises fructose, sucrose, or a sugar that promotes human uric acid production. 12. (a) a xanthine oxidase inhibitor, (b) a phosphate or a compound capable of releasing phosphate upon administration to a subject, and optionally (c) a sugar, and further optionally (d) one or more. A method of controlling smoking, comprising administering a composition comprising a pharmaceutically acceptable carrier or excipient to a subject in need of such treatment. 13. The xanthine oxidase inhibitor comprises a flavonoid, a purine analog, a quinazoline, a triazine, and a pyrazaro (3,4-d).
13. The method of controlling smoking according to claim 12, wherein the method is selected from pyrimidines. 14. The method according to claim 13, wherein the flavonoid is selected from flavanone, flavonol, flavone, anthocyanin, catechol and catechol tannin. 15. The method of controlling smoking according to claim 12, wherein said xanthine oxidase inhibitor is an extract derived from a plant source. 16. The plant source according to claim 15, wherein said plant source is Eupatorium Purpureum.
The described method of controlling smoking. 17. The method according to claim 17, wherein the xanthine oxidase inhibitor is eupalin.
13. The method of controlling smoking craving according to claim 12, which is (euparin). 18. The phosphate or a compound capable of releasing phosphate when administered to a subject is a herbal extract which releases phosphate, salts of phosphate, esters of phosphate or phosphate. How to control smoking. 19. The phosphate source is phosphoric acid or phosphate,
The method for controlling smoking according to claim 18. 20. In the manufacture of a drug for controlling smoking, (a) a xanthine oxidase inhibitor, (b) a phosphate or a compound capable of releasing phosphate upon administration to a subject, and optionally (c) a sugar, and further optionally To (d
) Use of a composition comprising one or more pharmaceutically acceptable carriers or excipients. 21. (a) a xanthine oxidase inhibitor, (b) a phosphate or a compound capable of releasing phosphate upon administration to a subject, and optionally (c) a sugar, and optionally (d) An agent for controlling smoking comprising one or more pharmaceutically acceptable carriers or excipients.