JP2004149447A - Nicotine-containing ointment - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To prepare a nicotine-containing ointment capable of giving an excellent non-smoking effect, by a simple and safe method. <P>SOLUTION: This nicotine-containing ointment is characterized by comprising nicotine or its salt and an ointment base material comprising water, a wetting agent, and a thickener. <P>COPYRIGHT: (C)2004,JPO

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to an ointment containing nicotine or a nicotine salt, which has an excellent smoking cessation effect.
[0002]
[Prior art]
BACKGROUND ART Conventionally, smoking cessation therapy in which a nicotine-containing composition is administered to a person who desires to quit smoking for the purpose of reducing nicotine craving is known. Examples of such a composition include a chewable composition described in Patent Documents 1 and 2, a high-viscosity nicotine nasal composition described in Patent Document 3, a nicotine-containing saliva-soluble ointment described in Patent Document 4, and Patent Document 5 Low-viscosity nicotine-containing composition suitable for nasal spray administration described in Patent Documents 6 and 7, inhalation aerosols described in Patent Documents 6 and 7, liquid aerosol preparations described in Patent Documents 8 and 9, nicotine drug drops described in Patent Document 10 and the like. No.
However, these nicotine preparations may not be able to obtain a sufficient smoking cessation effect because the absorption rate of nicotine into the body is lower than when actually smoking.
[0003]
In order to solve this problem, Patent Document 11 proposes a nicotine-containing pharmaceutical composition for delivering nicotine having a melting point range of about 25 ° C to about 45 ° C, preferably about 33 ° C to about 45 ° C. . This pharmaceutical composition can be applied to the skin by, for example, pressing a nicotine-containing tablet between the mucous membrane of the cheek and the gums to rapidly absorb nicotine from the inside of the cheek, or as a nicotine-containing patch (sheet-like material). It is intended to allow nicotine to be absorbed percutaneously to achieve a nicotine absorption rate comparable to that of actual smoking.
[0004]
However, in this method, if the person to be treated for smoking cessation chews too much on the nicotine-containing tablet, nicotine may elute and cause sore throat or stomach pain. Also, when a patch is applied to the skin, the skin may be rash, which has been a problem.
Therefore, the development of a nicotine-containing preparation that can be used more easily and safely and that does not cause skin irritation or the like and that can obtain an excellent smoking cessation effect has been demanded.
[0005]
[Patent Document 1]
USP. 3,845,217 [Patent Document 2]
WO88 / 03803 [Patent Document 3]
USP. 4,579,858 [Patent Document 4]
USP. No. 5,525,351 [Patent Document 5]
USP. No. 5,656,255 [Patent Document 6]
USP. 4,920,989 [Patent Document 7]
USP. 4,953,572 [Patent Document 8]
BP. No. 1,528,391 [Patent Document 9]
BP. Japanese Patent No. 2,030,862 [Patent Document 10]
UK patent application GB. 2230439A
[Patent Document 11]
JP 2002-530335 A
[Problems to be solved by the invention]
The present invention has been made in view of the above-mentioned prior art, and has as its object to provide a nicotine-containing ointment capable of obtaining an excellent smoking cessation effect by a simple and safe method.
[0007]
[Means for Solving the Problems]
As a result of intensive studies to solve the above-mentioned problems, the present inventors have prepared a nicotine-containing ointment containing nicotine or a nicotine salt and an ointment base. Then, when this ointment is applied to human skin, especially on a thin part of the skin, the nicotine is absorbed into the body in a very short time, and it has been found that an excellent smoking cessation effect can be obtained, and the present invention has been completed. I came to.
[0008]
Thus, according to the present invention, there is provided a nicotine-containing ointment comprising nicotine or a salt of nicotine and an ointment base.
In the ointment of the present invention, the ointment base preferably contains at least water, a wetting agent and a thickener.
In the ointment of the present invention, the content of nicotine or a nicotine salt is more preferably 1 to 5% by weight based on the whole ointment.
[0009]
BEST MODE FOR CARRYING OUT THE INVENTION
Hereinafter, the nicotine-containing ointment of the present invention will be described in detail.
The nicotine-containing ointment of the present invention is characterized by containing nicotine or a nicotine salt, and an ointment base.
The ointment of the present invention is in so-called nicotine poisoning, and by rapidly absorbing nicotine or a salt of nicotine into the body of a person who wants to quit smoking, it is possible to reduce smoking craving and obtain an excellent smoking cessation effect. Things.
[0010]
(1) Nicotine or nicotine salt The ointment of the present invention contains nicotine or a nicotine salt as an essential component.
The salt of nicotine is not particularly limited, and examples thereof include salts of inorganic acids, salts of organic acids, double salts, and hydrates thereof. Specific examples of nicotine salts include salts of inorganic acids of nicotine such as hydrochloride, nitrate, sulfate, phosphate; acetate, lactate, citrate, tartrate, malate, succinate, etc. Salts of aromatic carboxylic acids such as benzoate, salicylate, and phthalate; double salts with zinc chloride; and the like. Among these, salts of organic acids are preferred, salts of aromatic carboxylic acids are more preferred, and salicylates are particularly preferred from the viewpoint of less irritation to human skin and excellent smoking cessation effects. As nicotine or nicotine salts, commercially available ones can be used as they are. As the nicotine salt, those produced by reacting nicotine with a corresponding acid can also be used.
[0011]
The content of nicotine or a salt of nicotine in the ointment is not particularly limited, but from the viewpoint of forming a stable paste and obtaining an excellent smoking cessation effect, the content is usually 0.1 to 10 with respect to the whole ointment. % By weight, preferably 1 to 5% by weight, more preferably 1.5 to 3% by weight, particularly preferably 2 to 3% by weight.
[0012]
(2) Ointment base The ointment of the present invention contains an ointment base as an essential component. The ointment base is a raw material for dissolving or kneading the active ingredient (nicotine or a nicotine salt).
The components of the ointment base are important, and it is necessary to select one suitable for the condition of the skin. Ointment bases, oily bases, emulsion bases, water-soluble bases, etc., can be classified, but by applying the ointment to the skin, in order to quickly transdermally absorb nicotine or nicotine salts, Emulsion bases or water-soluble bases having excellent skin penetration are preferred, and emulsion bases are more preferred.
[0013]
Among these, the ointment base used in the present invention particularly preferably contains at least water, a wetting agent and a thickener. By using such an ointment base material, there is no irritation to the skin, good elongation, and nicotine or a nicotine salt is rapidly transdermally absorbed, and an ointment exhibiting an excellent smoking cessation effect can be obtained. .
[0014]
Wetting agents are compounds that promote retention of moisture and are also called humidifiers. Examples of the wetting agent include ethoxydiglycol, sorbitol, glycerin, glycereth 5 lactate, glyceres 7-triacetate, glyceres 7 diisonanoate, hexanetriol, hexylene glycol, propylene glycol, alkoxylated glucose, and D-pan. Tenol and derivatives thereof, hyaluronic acid, propylene oxide of glycerin, hydrolyzed corn starch, hydrolyzed wheat protein / wheat oligosaccharide, hydrolyzed corn protein, hydrolyzed wheat gluten, hydrolyzed yeast protein, hydrolyzed plant protein, hydrolyzed soy protein , Hydrolyzed rice protein, hydrolyzed potato protein and the like. These wetting agents can be used alone or in combination of two or more.
[0015]
Thickeners are polymeric substances that become viscous when dissolved or dispersed in water. Examples of the thickener include cellulose derivatives such as hydroxyethylcellulose, methylcellulose, hydroxypropylcellulose and carboxymethylcellulose; locust bean gum, guar gum, hydroxypropyl guar gum, xanthan gum, polyacrylic acid or a salt thereof, lanolin, gilcerol poly (meth) acrylate Polymer, polyvinylpyrrolidone, polyvinyl alcohol, crosslinked polymer of acrylamide and ammonium acrylate, crosslinked polymer of acrylamide and 2-acrylamido-2-methylpropanesulfonic acid and partially or completely neutralized product thereof, acrylamide and methacryloyloxyethyltrimethylammonium Crosslinked polymer with chloride, homopolymer or copolymer derived from acrylic acid Rimmer, such as a polyurethane latex, and the like. These thickeners can be used alone or in combination of two or more.
[0016]
The content of water in the ointment base is 5 to 50% by weight, preferably 10 to 40% by weight, more preferably 15 to 30% by weight, based on the whole ointment.
The content of the wetting agent is usually 1 to 30% by weight, preferably 10 to 25% by weight, based on the whole ointment. When the content of the wetting agent is within this range, an ointment having high affinity with the skin and good elongation can be obtained.
The content of the thickener is usually 0.1 to 10% by weight, preferably 1 to 5% by weight, based on the whole ointment.
When the content of water, humectant and thickener is in these ranges, it has excellent moisturizing properties, high affinity with the skin, good elongation, and percutaneous absorption of nicotine or nicotine salt. An excellent ointment can be obtained.
[0017]
The ointment base may contain other components as desired in addition to water, a wetting agent and a thickener. As other components, those used in ordinary ointments and cosmetics, for example, benzoic acid esters, higher fatty acid esters, polysiloxane compounds, alcohols, synthetic polymers, inorganic salts, vitamins, plant-derived substances, fragrances , Amino acids, oils, surfactants (emulsifiers) and the like.
[0018]
Examples of the benzoic acid ester include an alkyl ester of benzoic acid having 1 to 20 carbon atoms. Among them, alkyl esters of benzoic acid having 12 to 15 carbon atoms are preferred. Specific examples of the alkyl ester of benzoic acid having 12 to 15 carbon atoms include dodecyl benzoate, tridecyl benzoate, tetradecyl benzoate, pentadecyl benzoate, and mixtures thereof.
[0019]
Examples of higher fatty acid esters include glycerol and cholesterol esters of long-chain fatty acids having 12 or more carbon atoms. Examples include esters of saturated fatty acids such as lauric acid, myristic acid, palmitic acid, and stearic acid; esters of unsaturated fatty acids such as oleic acid, linoleic acid, and linolenic acid (α and γ isomers).
[0020]
The polysiloxane compound is a polymer having a siloxane bond (—Si—O—) in the main chain. For example, polydimethylsiloxane, polymethylphenylsiloxane, polydiphenylsiloxane, and the like can be given.
[0021]
As alcohols, for example, ethanol, phenoxyethanol, decanol, undecanol, dodecanol, tridecanol, tetradecanol, pentadecanol, hexadecanol (cetyl alcohol), heptadecanol, octadecanol, cetearyl alcohol (Cetearyl Alcohol) And the like.
[0022]
Examples of the synthetic polymer include polyacrylamide and polyamide.
Examples of the inorganic salts include magnesium silicate, aluminosilicate, wuslanite, potassium titanate, basic magnesium sulfate, sepiolite, zonotlite, zinc oxide, mica, and the like.
Examples of the vitamins include vitamin A palmitate, vitamin E acetate (tocopheryl acetate), vitamin C palmitate, and the like.
[0023]
As the plant-derived material, those that can be used for ordinary cosmetics can be used. For example, aloe vera (or extract), grape berry extract (Vitis Vinifera seed extract), wheat germ oil (Triticum Vulgare Germ Oil), wheat extract, red grape extract, asenyaku extract, avocado oil, altea Extract, arnica extract, gougon extract, spinach extract, oryzanol, chamomile extract, quince seed extract, cornflower extract, ashitaba extract, carrot extract and the like.
[0024]
Various flavors such as vegetable flavors, animal flavors, and synthetic flavors can be used as the flavors. For example, pinene, linenemol, anethole, cineole, green leaf alcohol, geraniol, citronellol, terpineol, phenethyl alcohol, menthol, linalool, eugenol, cinnamylaldehyde, citral, citronellal, cinnamylaldehyde, liral, ionon, jasmon, coumarin and the like. Can be
[0025]
Amino acids include hydroxymethylglycine sodium salt, glycine, methionine, isoleucine, arginine and the like.
Examples of oils include kernel oil, almond oil, olive oil, camellia oil, castor oil, coconut oil, macadamian nut oil, mink oil, coconut oil, lanolin, sesame oil, squalane oil, and the like.
[0026]
As the surfactant (emulsifier), various types of anionic surfactant, cationic surfactant, nonionic surfactant, and amphoteric surfactant can be used depending on their properties. Examples include cetearyl glucoside, tetrasodium EDTA, ethanolamine, diethanolamine, diisopropanolamine, triethanolamine, polyethylene glycol, polyoxyethylene fatty acid ester, lauryl sulfate, sodium lauryl sulfate, and the like.
These other components can be used alone or in combination of two or more.
[0027]
The total content of these other components is 1% by weight or less, preferably 0.5% by weight or less, more preferably 0.4% by weight or less based on the whole ointment. The content of each of the other components is preferably 0.1% by weight or less.
[0028]
(3) Preparation method of ointment The ointment of the present invention can be prepared by mixing a predetermined amount of nicotine or a nicotine salt with a predetermined amount of an ointment base, and kneading the mixture sufficiently. The kneading method is not particularly limited, and can be performed using a known kneading machine. In the case of a small amount, for example, a predetermined amount of nicotine or a salt of nicotine and a predetermined amount of an ointment base may be put in a mortar or a mixer and kneaded sufficiently until the whole becomes uniform.
[0029]
The ointment obtained as described above is an external preparation to be applied to the skin, which is formulated into a homogenous semi-solid (semi solid) having an appropriate consistency.
[0030]
The ointment of the present invention is quickly applied to nicotine by applying (applying) a predetermined amount to the skin of a human who wants to quit smoking, particularly to a thin part of the skin such as the inside of the upper arm, under the chin, and the lower eyelid. Or nicotine salts are absorbed into the body. A person with a condition called so-called nicotine addiction craves nicotine (i.e., desires to smoke) when the level of nicotine in the blood drops. It is considered that when the ointment of the present invention is applied to the skin, the blood concentration is increased to the same level as when smoking, and thus the craving for smoking can be reduced.
[0031]
The timing of using the ointment of the present invention is not particularly limited, and a predetermined amount may be applied to the skin when smoking is desired. For example, in the case of a person who has a habit of smoking before going to bed, it is before bedtime, in the case of a person who has a habit of smoking immediately after getting up, immediately after getting up, and in the case of a person who has a habit of smoking after eating, after eating. The amount of the ointment of the present invention to be applied is not particularly limited, and is usually about 0.1 g to 2 g, although it depends on the nicotine dependence of the person who wants to quit smoking.
[0032]
The time after the application of the ointment of the present invention until the state where the desire to smoke disappears (the smoking cessation effect) is recognized is usually within 30 minutes after application, and preferably within 20 minutes after application. The duration of the effect varies from individual to individual, but is usually from 3 hours to 12 hours.
[0033]
By using the ointment of the present invention, it is generally recognized that after using the ointment, the time until the next craving for smoking appears gradually becomes longer. As a result, the amount of smoking (the number of smoking cigarettes) can be reduced to about half or less.
Nicotine addiction must also be cured in order to completely abstain from smoking and achieve complete cessation. For that purpose, by using the ointment of the present invention, first, the smoking habit is stopped, and then the amount of the ointment of the present invention (the amount of application, the number of times of use, etc.) may be gradually reduced. .
[0034]
【Example】
Hereinafter, the present invention will be described in more detail with reference to examples. The present invention is not limited to the following examples, and the type of nicotine salt, the composition of the ointment base, the composition ratio, and the like can be freely changed without departing from the gist of the present invention.
[0035]
Example Production of nicotine-containing ointment 22 parts by weight of water, 75.6 parts by weight of an ointment base, and 2.4 parts by weight of nicotine salicylate were mixed in a mortar, kneaded well and mixed to give a pale yellow color. A nicotine-containing ointment was obtained.
As the ointment base, one composed of the following components was used.
Glycerin 18% by weight, C15-C15 alkyl benzoate 15% by weight, glyceryl stearate 12% by weight, dimethylpolysiloxane 8.75% by weight, cetearyl alcohol 4.5% by weight, cetearyl glucoside 3.5% by weight , Polyacrylamide, 2.5% by weight of hexadecanol, 1.5% by weight of magnesium silicate, 1.5% by weight of ginsan gum (high molecular weight polysaccharide), 1% by weight of aloe extract (Aloe barbadens), acetic acid of vitamin E 0.5% by weight of ester (tocopherol acetate), 0.25% by weight of Planas amigadalus amara (one of flavor herbs), 0.2% by weight of kernel oil, 1.25% by weight of ethoxydiglycol, emulsifier (trade name) : Krisgel 100, Professional Compounding Center of America, Inc.) 0.3 wt%
[0036]
Smoking cessation effect test Thirty women aged 20 to 40 and five men aged 40 to 60 who had a smoking habit were set as subjects. 0.5 g of the nicotine-containing ointment obtained in the example was applied (applied) to the inside of the upper arm of the skin of the subject who had a desire to smoke. Within 15-20 minutes after application of the ointment, all subjects had no craving for smoking. Also, apparently, the frustration of smoking cravings, which are remarkably observed in people with smoking habits, has disappeared.
[0037]
Thereafter, whenever there was a desire to smoke, a nicotine-containing ointment was applied to the skin of each subject. The ointment was applied alternately to the skin portion inside the upper arm of the subject and the skin portion under the chin.
The average interval between the application of the nicotine-containing ointment and the next desire to smoke was 3 to 4 hours. Also, this interval tended to be longer each time the application of the ointment of the example was repeated.
[0038]
As a result of continuing to apply the nicotine-containing ointment every time there was a desire for smoking, the number of cigarettes smoked decreased to less than half for all the test subjects. In addition, there was no difference between men and women in this effect, and there was no person who had an abnormality such as rash on the skin by applying the ointment.
[0039]
【The invention's effect】
According to the ointment of the present invention, an excellent smoking cessation effect can be obtained by a very simple and safe method of applying to the skin.
Further, the ointment of the present invention has excellent affinity with the skin, has good elongation, and allows nicotine or a nicotine salt to be rapidly transdermally absorbed. Therefore, by applying the ointment of the present invention to human skin, particularly to a thin part of the skin, nicotine is absorbed into the body in a very short time, and an excellent smoking cessation effect can be obtained.

Claims (3)

A nicotine-containing ointment comprising nicotine or a salt of nicotine, and an ointment base. 2. The nicotine-containing ointment according to claim 1, wherein the ointment base contains water, a wetting agent and a thickener. The nicotine-containing ointment according to claim 1 or 2, wherein the content of nicotine or a salt of nicotine is 1 to 5% by weight based on the whole ointment.