JP2004168734A - Nicotine-containing patch - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a patch being simply produceable, excellent in economical efficiency and enabling release of nicotine in an amount continuously controlled over a long time. <P>SOLUTION: The sustained-release patch is composed of a support, an adhesive layer, a porous hollow fiber and a separator. In the patch, (i) a medicine and a low molecular solid substance are contained in a void part of the porous hollow fiber and (ii) the medicine is nicotine and (iii) the low molecular solid substance is solid at a room temperature and has 50-20,000 molecular weight and (iv) the formulation ratio of the medicine to the low molecular solid substance is (2:1) to (1:20). <P>COPYRIGHT: (C)2004,JPO

Description

【００４８】
表１中、「ニコチン／樹脂比」は、ニコチンと低分子固体物質の重量比を表す。
【図面の簡単な説明】
【図１】実施例１と比較例２のニコチン放出プロファイルである。[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a patch containing nicotine.
[0002]
[Prior art]
Smoking poses health risks, including increased risk of lung cancer and coronary artery disease. Also, so-called passive smoking, which causes health damage to non-smokers, has been pointed out and has become a major social problem. As a method for quitting smoking, there is known a method in which nicotine is administered while being adjusted, and withdrawal from tobacco is suppressed while tobacco withdrawal symptoms are suppressed. As a method for administering nicotine while adjusting nicotine, a method using a patch containing nicotine has been proposed (for example, see Patent Document 1).
[0003]
However, since nicotine is a volatile liquid and exhibits moderate fat-solubility, simply including nicotine in an adhesive makes it difficult to achieve a well-controlled and sustained release of nicotine. There is a problem that side effects occur due to a rapid rise in the temperature. Therefore, as a patch capable of sustained release of nicotine, a method of adsorbing nicotine to an adsorption layer or the like has been proposed (for example, see Patent Documents 2 to 6).
[0004]
However, in this method, when releasing nicotine, a driving force for drug withdrawal is required, and it is difficult to always obtain a stable drug release.
[0005]
Also, patches have been proposed that hold nicotine in a salt state and convert it to a free base upon administration (for example, see Patent Documents 7 and 8).
[0006]
However, this method requires an auxiliary agent or the like for converting to a free base at the time of administration, and when the auxiliary agent or the like is water, it is easily affected by the environment at the time of use and has a problem in terms of stable drug release. .
[0007]
Also, a patch comprising a drug replenishing layer and a permeation control membrane capable of controlling the permeability of nicotine has been proposed (for example, see Patent Document 9). The so-called reservoir-type patch consisting of a drug storage layer and a controlled release membrane is excellent in terms of steady release of the drug, but its structure is complicated and the permeation control membrane differs for each individual drug. Therefore, there is a problem that the production cost is high and the economy is poor. Further, as a patch having improved reservoir type defects, a matrix reservoir type patch has been proposed (for example, see Patent Document 10).
[0008]
However, there is a problem that the complexity of production is not sufficiently solved, and a problem common to matrix preparations is a decrease in drug flow rate due to drug release. On the other hand, a sustained-release preparation using porous hollow fibers has been proposed as a sustained-release preparation that is easy to produce and that allows sustained drug release (for example, see Patent Document 11). Unlike other porous materials, the porous hollow fiber is excellent in that the drug release surface is easily maintained at a constant level, so that the drug is released constantly as in the case of the reservoir type. However, in the case of a volatile liquid drug such as nicotine, it is difficult to obtain sustained drug release required for smoking cessation treatment simply by holding the drug in the porous hollow fiber.
[0009]
[Patent Document 1]
JP-A-61-251619
[Patent Document 2]
Japanese Patent Publication No. 3-505044
[Patent Document 3]
JP-A-8-81364
[Patent Document 4]
Japanese Patent Publication No. Hei 8-502727
[Patent Document 5]
Japanese Patent Publication No. 9-505028
[Patent Document 6]
Japanese Patent Publication No. Hei 9-506110
[Patent Document 7]
JP-A-1-135717
[Patent Document 8]
JP-A-3-197420
[Patent Document 9]
JP-A-2-174714
[Patent Document 10]
Japanese Patent Publication No. 1-503706
[Patent Document 11]
JP-A-61-293911
[0010]
[Problems to be solved by the invention]
SUMMARY OF THE INVENTION An object of the present invention is to provide a patch which is easy to produce, has excellent economical efficiency, and is capable of releasing a volatile liquid drug, nicotine, for a long time and in a controlled amount in a sustained manner. . The present inventors have conducted intensive studies to achieve such an object, and as a result, in a patch comprising a support, an adhesive layer, a porous hollow fiber and a separator, a drug and a It has been found that the object of the present invention is achieved by including a low-molecular-weight solid substance in a specific ratio, and the present invention has been completed.
[0011]
[Means for Solving the Problems]
That is, the present invention comprises a support, an adhesive layer, a porous hollow fiber and a separator,
(I) a drug and a low-molecular-weight solid substance are contained in a void portion of the porous hollow fiber;
(Ii) the drug is nicotine,
(Iii) the low-molecular-weight solid substance is solid at room temperature and has a molecular weight of 50 to 20,000;
(Iv) The compounding ratio of the drug and the low-molecular-weight solid substance is 2: 1 to 1:20.
It is intended to provide a sustained-release patch.
[0012]
BEST MODE FOR CARRYING OUT THE INVENTION
In the present invention, the drug is contained in the void portion of the porous hollow fiber together with the low molecular weight solid substance. If only the drug is contained in the porous hollow fiber or if the drug is only present on the outer surface of the porous hollow fiber together with the low molecular weight solid substance, a sustained and controlled release of the drug over a long period of time Becomes difficult. The porous hollow fiber referred to here has pores on the wall surface of the hollow fiber having a hollow portion along the fiber axis direction, and at least a part of the pores penetrates to the hollow portion of the fiber. Refers to fiber. If none of the pores on the hollow fiber wall penetrates into the hollow part, it is not easy to easily contain the drug in the hollow part, and it is difficult to release a controlled amount of the drug continuously. It becomes.
[0013]
In addition, the porous hollow fiber used in the present invention preferably has a single yarn thickness of 1 μm to 500 μm, more preferably 3 μm to 250 μm, and a porosity of pores on the porous hollow fiber wall surface. Is 0.1% to 70%, more preferably 1% to 60%, and the porosity of the hollow portion of the porous hollow fiber is preferably 3% to 90%, more preferably 5% to 80%. Further, the total porosity of the hollow portion and the pores of the porous hollow fiber is preferably from 10% to 95%, more preferably from 20% to 85%. If the thickness of the single yarn is less than 1 μm, the strength of the single yarn is not sufficient, and a portion of the porous hollow fiber may be damaged by an external force when applied to the skin, making it difficult to control the release of the drug. On the other hand, if the thickness of the single yarn exceeds 500 μm, the skin feels uncomfortable when applied to the skin and further causes skin irritation, which is not preferable. When the porosity of the pores on the wall surface of the porous hollow fiber is less than 0.1%, it becomes difficult to contain a drug and a low-molecular-weight solid substance. On the other hand, when the porosity of the pores exceeds 70%. As the drug is released, the release of the drug is reduced, and it becomes difficult to release a controlled amount of the drug continuously. When the porosity of the hollow portion of the porous hollow fiber is less than 3%, it is difficult to continuously release the drug. On the other hand, when the porosity of the hollow portion exceeds 90%, the strength of the porous hollow fiber decreases. Or controlled release of drug is difficult. Furthermore, if the total porosity of the hollow portion and the pores of the porous hollow fiber is less than 10%, it becomes difficult to continuously release the drug, while the total porosity of the hollow portion and the pores exceeds 95%. In this case, the strength of the porous hollow fiber is reduced, and it is difficult to release a controlled amount of the drug.
[0014]
In the present invention, the porosity of the hollow portion of the porous hollow fiber and the porosity of the pore are calculated as the volume of the hollow portion of the porous hollow fiber and the volume of the pore relative to the volume of the porous hollow fiber. Here, the volume of the hollow portion and the volume of the pores of the porous hollow fiber can be measured by a mercury intrusion method.
[0015]
In addition, the size of the pores on the wall surface of the porous hollow fiber depends on the ease of impregnation of the drug and the low-molecular-weight solid substance, the strength of the porous hollow fiber, and the continuous release of the drug in a controlled amount. It is preferably smaller than the size of the cross section of the hollow portion of the conductive hollow fiber. The pore size mentioned here usually has a distribution, and thus means an average pore size. More specifically, 0.01 μm to 100 μm is preferable, and 0.1 μm to 50 μm is more preferable.
[0016]
The shape of the outer diameter and the inner diameter of the cross section of the porous hollow fiber is not particularly limited, and may be any of a circle, a triangle, and a star.
[0017]
Further, the material of the porous hollow fiber is not particularly limited, for example, polyethylene terephthalate, polyester such as polybutylene terephthalate, for example, nylon 6, polyamide such as nylon 66, for example, polyethylene, polyolefin such as polypropylene, for example, Examples include celluloses such as cellulose, cellulose ester and cellulose ether, polyvinyl chloride, polyacrylonitrile, polyurethane and the like. Polyethylene terephthalate is particularly preferred from the viewpoints of inertness to nicotine, chemical stability, and the like.
[0018]
In addition, as a method for obtaining a porous hollow fiber, it can be obtained by a conventionally known method. For example, a hollow fiber material such as polyester is melted, discharged from a double-slit spinneret, and cooled to produce a hollow fiber. Thereafter, the hollow fiber wall surface is formed by chemical treatment such as alkali treatment or laser processing. By forming pores in the hollow fiber, a porous hollow fiber can be obtained.
[0019]
The porous hollow fiber is used in the form of a knitted fabric, a woven fabric, a nonwoven fabric, or the like for the purpose of improving the handleability when manufacturing a patch, improving the handleability of the patch when applied to the skin, and improving the feel to the skin. Can be used as
[0020]
As a method for containing a drug and a low-molecular-weight solid in the porous hollow fiber, a solution in which the drug and the low-molecular-weight solid substance are dissolved in a common solvent or a solution in which the low-molecular-weight solid substance is dissolved in a solvent and the drug are used. Conventional methods include immersing porous hollow fibers in the mixed solution, bringing them into contact, removing the solvent, melting the drug and low-molecular-weight solid substance, and then contacting or immersing the porous hollow fibers. A known method can be adopted. Further, in order to help impregnate the drug and the low-molecular-weight solid substance into the porous hollow fiber, means such as heating, pressurization, vacuum, and ultrasonic treatment can be used.
[0021]
In addition, conventionally known stabilizers, antioxidants, fragrances, pH adjusters, and the like can be added to the drug and the low-molecular-weight solid substance to be contained in the porous hollow fiber, if necessary. Specifically, for example, stabilizers such as citric anhydride, dibutylhydroxytoluene, for example, ascorbic acid, tocopherol acetate, antioxidants such as vitamin E, for example, fragrances such as menthol, camphor, peppermint oil, lemon oil, For example, pH adjusters such as sodium citrate, sodium dihydrogen citrate, sodium hydrogen phosphate, sodium hydrogen phosphate and the like can be mentioned. These may be used alone or in combination of two or more.
[0022]
The drug in the present invention refers to nicotine, which is a volatile liquid at room temperature, and corresponds to the present invention if it is in the form of nicotine when the drug is released. In other words, even if the drug is in the form of a nicotine salt in the state of retention and storage, a substance having the form of nicotine at the time of drug release and whose release is controlled by the porous hollow fiber falls under the present invention. I do. In addition, the content of nicotine in the patch comprising the porous hollow fiber of the present invention as a component is not particularly limited, and in consideration of the purpose of treatment and safety, the necessary minimum amount of nicotine is 1 mg. -100 mg is preferred.
[0023]
The low molecular weight solid substance in the present invention refers to a substance which is solid at room temperature and has a molecular weight of 50 to 20,000, more preferably has a molecular weight of 100 to 10,000, and excludes ionic crystalline inorganic substances. If it is not solid at room temperature, such as a liquid, it will be difficult to sustainably release the controlled amount of drug required for smoking cessation therapy. In addition, even when solid at room temperature, in the case of an inorganic substance of ionic crystals, when a patch using the porous hollow fiber of the present invention is applied to the skin, it may cause discomfort and further cause skin irritation. Is not preferred. If the low-molecular-weight solid substance has a molecular weight of less than 50, the crystallinity is strong. On the other hand, when a solid substance having a molecular weight of more than 20,000, for example, a polymer substance such as cellulose ester is used, it is not preferable because it is difficult to impregnate the porous hollow fiber due to its high viscosity.
[0024]
Specific examples of the low molecular weight solid substance of the present invention include, for example, rosin-based resins such as gum rosin, wood rosin, hydrogenated rosin, hydrogenated rosin glycerin ester, for example, α-pinene resin, β-pinene resin, terpene phenol Terpene resins such as resins, for example, aliphatic (C5) petroleum resins, aromatic (C9) petroleum resins, alicyclic petroleum resins, petroleum resins such as cumarone / indene resins, styrene resins, for example, cetyl Alcohol, stearyl alcohol, higher alcohols such as behenyl alcohol, for example, higher fatty acids such as stearic acid, lauric acid, behenic acid, hydroxystearic acid, for example, sorbitan monopalmitate, sorbitan monostearate, glycerin monolaurate, hexadecyl lactate, etc. Fatty acid esters, for example, polyethylene glycos Such as polyethylene glycol (23) monocetyl ether, polyethylene glycol (20) behenyl ether, and polyethylene glycol (160) polypropylene glycol (30). Examples thereof include polypropylene glycols such as polypropylene glycol 3000 and polypropylene glycol 4000. Among these, resins such as rosin-based resin, terpene-based resin, petroleum resin, and styrene-based resin are preferable from the viewpoint of skin safety and economy. These may be used alone or in combination of two or more.
[0025]
In the present invention, the compounding ratio of the drug and the low molecular weight solid substance is preferably 2: 1 to 1:20, more preferably 1: 1 to 1:10, and particularly preferably 1: 2 to 1 by weight. : 10. If the compounding ratio of the low-molecular-weight solid substance to the drug is less than 0.5, sustained drug release becomes difficult, while if the compounding ratio of the low-molecular-weight solid substance to the drug exceeds 20, the drug and the low-molecular-weight solid substance Is not easily contained in the porous hollow fiber, or the porous hollow fiber containing the drug and the low-molecular-weight solid substance becomes hard, and when a patch containing this as a component is applied to the skin, a feeling of discomfort is felt. It also causes skin irritation, which is not preferred.
[0026]
The pressure-sensitive adhesive constituting the pressure-sensitive adhesive layer in the present invention is not particularly limited as long as it has adhesiveness to the skin, and conventionally known pressure-sensitive adhesives can be used. For example, an acrylic adhesive mainly containing an alkyl (meth) acrylate having 2 to 20 carbon atoms such as 2-ethylhexyl (meth) acrylate and pentyl (meth) acrylate, for example, mainly containing polydimethylsiloxane Silicone-based adhesives, for example, rubber-based adhesives containing polyisoprene rubber, styrene-butadiene copolymer rubber, acrylic rubber, natural rubber, etc. as main components, hydrogel-based adhesives containing gelatin, carrageenan, hydroxyethylcellulose, etc. as main components Agent, a vinyl-based adhesive such as polyvinyl alcohol, polyacrylic acid, and polyvinyl acetate, and the like. These may be used alone or in combination of two or more. Among these adhesives, acrylic adhesives, silicone-based adhesives, and rubber-based adhesives are more preferable from the viewpoint of adhesiveness to the skin, and acrylic adhesives containing 2-ethylhexyl acrylate as a main component are applied to the skin. It is particularly preferable from the viewpoint of low irritation and economy.
[0027]
Further, for the purpose of adjusting the adhesive strength and suppressing the irritation to the skin, a liquid component can be mixed with the adhesive, or a crosslinking treatment can be performed. Examples of such a liquid component include alcohols such as ethyl alcohol, lauryl alcohol, and benzyl alcohol; for example, polyhydric alcohols such as propylene glycol, butanediol, hexanetriol, and glycerin; for example, monoacetin, triacetin, sorbitan monooleate, and the like. Polyhydric alcohol derivatives such as isopropyl myristate, isooctyl palmitate, ethyl oleate, diethyl sebacate, isopropyl adipate and the like, for example, linolenic acid, linoleic acid, oleic acid, higher fatty acids such as capric acid, For example, fats and oils such as olive oil and castor oil, for example, monoethanolamine, diethanolamine, triethanolamine, diisopropanolamine, triisopropanolamine Amines such emissions, for example, dimethyl sulfoxide, dimethyl acetamide, N- aprotic polar organic materials such as methylpyrrolidone, for example liquid paraffin, and hydrocarbons such as squalane and the like. These may be used alone or in combination of two or more. In addition, as a method of the crosslinking treatment, a method of crosslinking by adding a crosslinking agent such as ultraviolet light or γ-ray, or a crosslinking agent such as silicic anhydride, a polyisocyanate compound, an organic metal salt, or a metal chelate compound can be used. .
[0028]
In the present invention, a drug may be contained in the adhesive in addition to the void portion of the porous hollow fiber.
[0029]
Furthermore, conventionally known stabilizers, antioxidants, fragrances, pH adjusters, and the like can be added to the pressure-sensitive adhesive of the present invention, if necessary. Specifically, for example, stabilizers such as citric anhydride, dibutylhydroxytoluene, for example, ascorbic acid, tocopherol acetate, antioxidants such as vitamin E, for example, fragrances such as menthol, camphor, peppermint oil, lemon oil, For example, pH adjusters such as sodium citrate, sodium dihydrogen citrate, sodium hydrogen phosphate, sodium hydrogen phosphate and the like can be mentioned. These can be used alone or in combination of two or more.
[0030]
The thickness of the pressure-sensitive adhesive layer in the present invention is not particularly limited, but is preferably 5 μm to 200 μm, and particularly preferably 10 μm to 100 μm.
[0031]
The support used in the present invention is not particularly limited as long as it can adhere an adhesive layer and has a self-shape retaining property, and its material and shape are not particularly limited. For example, polymer films such as polyesters, polyolefins, polyurethanes, and cellulose esters; woven, knitted, nonwoven fabrics and papers made of fibers such as polyesters, polyolefins, polyurethanes, cellulose esters, and polyamides; and polyesters, polyolefins, cellulose esters, polyurethanes, and polyamides. Porous membrane; and a laminate comprising a combination of two or more of these. The thickness of the support is not particularly limited, but is preferably 100 μm to 2000 μm, and particularly preferably 200 μm to 1000 μm.
[0032]
The separator used in the present invention is not particularly limited as long as it has a shape-retaining property and the pressure-sensitive adhesive layer can be easily peeled off, but a film, woven fabric, knitted fabric, or nonwoven fabric made of polyester, polyamide, polyolefin, polyurethane, cellulose, or the like Further, it is preferable that the surface of paper or the like is subjected to a release treatment such as a fluoro resin or a silicone resin. The thickness of the separator is not particularly limited as long as it can be handled, but is preferably from 10 μm to 2000 μm.
[0033]
The patch in the present invention has a support, a pressure-sensitive adhesive layer, a porous hollow fiber and a separator as essential components, and in addition to these, a backing material or the like for preventing generation of wrinkles during application is provided. You can also. The method of combining the components is not particularly limited.For example, an adhesive layer, a porous hollow fiber, and a separator are sequentially laminated on a support, or a porous hollow fiber, an adhesive layer, and a separator are laminated on a support. Alternatively, a patch can be prepared by laminating a pressure-sensitive adhesive layer, a porous hollow fiber, a pressure-sensitive adhesive layer, and a separator on a support. In addition, in order to suppress the adhesiveness to the skin and the loss of the drug to the atmosphere, it is preferable that the porous hollow fiber be configured to have an area smaller than that of the pressure-sensitive adhesive layer or to be configured so as not to directly contact the atmosphere.
[0034]
【The invention's effect】
As described above, in a patch comprising a support, a pressure-sensitive adhesive layer, a porous hollow fiber, and a separator, nicotine and a low-molecular-weight solid substance having a molecular weight of 50 to 20,000 at room temperature are filled with nicotine in voids of the porous hollow fiber. By containing it in a blending ratio of 2: 1 to 1:20, a patch is obtained which is easy to manufacture, is excellent in economic efficiency, and can release a controlled amount of nicotine continuously over a long period of time.
[0035]
【Example】
Hereinafter, the present invention will be described with reference to examples. In Examples,% means% by weight. Further, the "thickness of single yarn of porous hollow fiber", "porosity of porous hollow fiber", "nicotine release rate" and "nicotine content" in the examples were measured by the following methods. is there.
(1) Thickness of single yarn of porous hollow fiber
The porous hollow fiber was observed with a microscope, and the average value of repeated measurements of n = 5 was determined to be the thickness of a single yarn.
(2) Porosity of porous hollow fiber
The porosity of the hollow portion of the porous hollow fiber and the porosity of the pore are defined as the volume of the hollow portion of the porous hollow fiber and the volume of the pore relative to the volume of the porous hollow fiber, and the volume of the hollow portion of the porous hollow fiber. The pore volume and the pore volume were measured and determined by a mercury intrusion method.
(3) Nicotine release rate
The adhesive layer surface of the patch is exposed, fixed to a stainless steel plate, and placed in 500 mL of a 32 ° C. pH 7.4 phosphate buffer solution. The solution was stirred at a speed of 150 rpm, and after 1 hour, 2 hours, 4 hours, and 8 hours, the solution was sampled, the nicotine concentration was analyzed by HPLC, and the amount of released drug (W1) at each time was determined. Was. The value obtained by dividing the amount of released nicotine by the nicotine content (W2) in the patch before the test was expressed as a percentage, and the average value of n = 3 repetitions was defined as the nicotine release rate.
(4) Nicotine content
To a glass tube having a volume of 50 mL, one patch without the separator and 40 mL of methanol were added, and the mixture was subjected to ultrasonic treatment to extract nicotine. A sample solution was prepared by adding 9 mL of an acetonitrile / water = 1/9 (v / v) solution to 1 mL of this solution, and the nicotine content was determined by analyzing the nicotine concentration by HPLC.
[0036]
[Example 1]
A knitted fabric of a porous hollow fiber (area φ30 mm, 18 μm in thickness of a single yarn, porosity of pores in a porous hollow fiber wall surface of 12%, porosity of a hollow portion of 27%, and total porosity of 39%) (Weight 40 mg) was immersed in a solution consisting of 3.5 g of nicotine, 10.5 g of hydrogenated rosin glycerin ester (ester gum H, manufactured by Arakawa Chemical Industries) and 7 g of acetone, and was impregnated with ultrasonic waves. Thereafter, the knitted fabric of the porous hollow fiber was taken out, the solution attached to the surface was wiped off, and then dried to remove acetone as a solvent. An acrylic pressure-sensitive adhesive (90% 2-ethylhexyl acrylate, 7.5% methyl methacrylate, 2.5% acrylic acid) laminated on a polyester film (12 μm thick) is provided on one side of the knitted fabric of the porous hollow fiber ( A pressure-sensitive adhesive layer having a thickness of 40 μm) was bonded to the other side, and an adhesive pressure-sensitive adhesive layer (thickness of 40 μm) laminated on a silicone-coated release film was bonded to another surface of the pressure-sensitive adhesive. It was cut to size to make a patch.
[0037]
It was 11.9 mg when the content of the obtained patch was measured. A release test was performed using this patch. The results are shown in Table 1 and FIG. As shown in Table 1 and FIG. 1, good nicotine release was sustained over a long period of time.
[0038]
[Comparative Example 1]
A patch having a nicotine content of 10.4 mg was obtained in the same manner as in Example 1, except that a solution consisting of 7.0 g of nicotine and 14 g of acetone, excluding hydrogenated rosin glycerin ester, was used. When the release rate of the obtained patch was measured, as shown in Table 1, the drug was released in a short time, and it was difficult to obtain a sustained drug release.
[0039]
[Comparative Example 2]
In Example 1, a patch having a nicotine content of 10.9 mg was prepared in the same manner as in Example 1 except that gauze was used as a solid yarn fabric instead of the porous hollow fiber knitted fabric. Obtained. When the release rate of the obtained patch was measured, as shown in Table 1 and FIG. 1, it was difficult to obtain sustained drug release over a long period of time.
[0040]
[Example 2]
Example 1 was repeated in the same manner as in Example 1 except that the weight of the knitted fabric of the porous hollow fibers was 80 mg, and a solution consisting of 2.8 g of nicotine, 11.2 g of hydrogenated rosin glycerin ester, and 7 g of acetone was used. A patch having a nicotine content of 17.6 mg was obtained. When the release rate of the obtained patch was measured, as shown in Table 1, good nicotine release was continuously exhibited over a long period of time.
[0041]
[Example 3]
In Example 2, a porous hollow fiber having a single yarn thickness of 15 μm, a porosity of pores on a porous hollow fiber wall surface of 19%, a porosity of a hollow portion of 26%, and a total porosity of 45% was used. A patch having a nicotine content of 18.8 mg was obtained in the same manner as in Example 2 except that a knitted fabric (area φ30 mm, weight 40 mg) was used. When the release rate of the obtained patch was measured, as shown in Table 1, good nicotine release was continuously exhibited over a long period of time.
[0042]
[Example 4]
A patch having a nicotine content of 18.0 mg in the same manner as in Example 2 except that hydrogenated rosin ester (KE-311, manufactured by Arakawa Chemical Industries) was used instead of hydrogenated rosin glycerin ester. Got. When the release rate of the obtained patch was measured, as shown in Table 1, good nicotine release was continuously exhibited over a long period of time.
[0043]
[Example 5]
The knitted porous hollow fiber used in Example 3 was immersed in a solution consisting of 2.0 g of nicotine, 12.0 g of an alicyclic petroleum resin (Alcon P-100, manufactured by Arakawa Chemical Industries) and 12.0 g of chloroform, It was impregnated with ultrasonic waves. Then, in the same manner as in Example 3, a patch having a nicotine content of 9.6 mg was obtained. When the release rate of the obtained patch was measured, as shown in Table 1, good nicotine release was continuously exhibited over a long period of time.
[0044]
[Example 6]
The knitted porous hollow fiber used in Example 3 was immersed in a solution composed of 2.0 g of nicotine, 12.0 g of lauric acid, which is a higher fatty acid, and 12.0 g of acetone, and was impregnated with ultrasonic waves. Then, in the same manner as in Example 3, a patch having a nicotine content of 7.0 mg was obtained. When the release rate of the obtained patch was measured, as shown in Table 1, good nicotine release was continuously exhibited over a long period of time.
[0045]
[Example 7]
Except for using a silicone-based adhesive composed of 95% polydimethylsiloxane (Q7-4501, manufactured by Dow Corning) and 5% of silicone oil (360 medical Fluid, manufactured by Dow Corning) in place of the acrylic-based adhesive in Example 1. In the same manner as in Example 1, a patch with a nicotine content of 11.8 mg was obtained. When the release rate of the obtained patch was measured, as shown in Table 1, good nicotine release was continuously exhibited over a long period of time.
[0046]
Example 8
Example 1 Example 1 was repeated except that a rubber-based pressure-sensitive adhesive composed of 41% of styrene-isoprene-styrene copolymer, 54% of hydrogenated rosin ester, and 5% of liquid paraffin was used instead of the acrylic pressure-sensitive adhesive. In the same manner as in the above, a patch having a nicotine content of 9.4 mg was obtained. When the release rate of the obtained patch was measured, as shown in Table 1, good nicotine release was continuously exhibited over a long period of time.
[0047]
[Table 1]

[0048]
In Table 1, "nicotine / resin ratio" represents the weight ratio of nicotine to the low-molecular-weight solid substance.
[Brief description of the drawings]
FIG. 1 shows nicotine release profiles of Example 1 and Comparative Example 2.

Claims (3)

Support, adhesive layer, consisting of porous hollow fiber and separator,
(I) a drug and a low-molecular-weight solid substance are contained in a void portion of the porous hollow fiber;
(Ii) the drug is nicotine,
(Iii) the low-molecular-weight solid substance is solid at room temperature and has a molecular weight of 50 to 20,000;
(Iv) A sustained-release patch wherein the compounding ratio of the drug and the low-molecular-weight solid substance is 2: 1 to 1:20. The thickness of a single yarn of the porous hollow fiber is 1 μm to 500 μm, the porosity of pores on the wall surface of the porous hollow fiber is 0.1% to 70%, and the void of the hollow portion of the porous hollow fiber is The patch according to claim 1, wherein the porosity of the porous hollow fiber is 10% to 95%. The low-molecular-weight solid substance is at least one selected from rosin-based resins, terpene-based resins, petroleum resins, styrene-based resins, higher alcohols, higher fatty acids, fatty acid esters, polyethylene glycol, polyethylene glycol derivatives, and polypropylene glycol. Item 3. The patch according to item 1 or 2.

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