JPH0474328B2 - - Google Patents

Description

[Detailed description of the invention]

<Industrial Application Fields> The present invention improves the immediate effect and sustained release of vaporized drugs into the body through the nose or mouth, and also improves the bioavailability of the drugs. , aiming to reduce side effects caused by drugs,
This invention relates to an immediate-acting sustained-release preparation. <Conventional technology> In the development of pharmaceuticals, in addition to developing new chemical substances with excellent medicinal efficacy, it is also considered to further enhance the medicinal efficacy of these new chemical substances and chemical substances already used as pharmaceuticals. has been done. That is, in order to obtain a sufficient therapeutic effect, various studies have been made to optimize the dosage form, such as changing the dosage form to an immediate-release or sustained-release formulation. Immediate-acting preparations include injections. With this preparation, the drug is directly injected into a vein or artery, and 100% of the injected drug enters the bloodstream, and the effect is immediate. However, the disadvantage of this method is that the drug concentration after injection decreases rapidly based on the half-life of the drug itself, and the drug efficacy decreases accordingly, and the injection must be performed by the doctor himself or in the presence of a doctor. Therefore, administration is limited to a large cloth. Sustained-release preparations are drugs that have a short half-life, which is a parameter for their effective duration in the body, and are prepared at a concentration that is higher than the minimum effective concentration and lower than the maximum safe concentration, in order to extend the duration of the drug. In recent years, sustained-release preparations have been actively developed, which allow the drug to be absorbed into the body over a long period of time within the effective blood concentration range. Examples of such sustained-release preparations include tapes and patches that contain a certain amount of a drug in an adhesive and are molded into a certain size (for example, Japanese Patent Application Laid-Open No. 1983-1999).
116011, JP-A-58-134020).
According to methods using these tapes and patches, drugs can be administered to humans in sustained release over a long period of one day or more, and in the case of drugs that undergo hepatic metabolism, they can be administered to humans without going through the liver. It is possible to increase the bioavailability of drugs to get into the blood. In addition, side effects such as the development of ulcers in the gastrointestinal tract, such as the stomach, which often occur when administered orally, can be avoided, and in the unlikely event that serious side effects occur, administration of the drug can be immediately discontinued. There are advantages to this. However, these tapes and patches have the problem that the types and amounts of drugs that can be absorbed through the skin are limited, and they also have the disadvantage of slow rise in drug concentration, so they can only be used for a limited number of drugs. only industrialized. Another example of sustained-release preparations is when the drug is administered orally, the drug is coated with a multilayer film of excipients, etc., so that the drug is sustainedly released through these films in the gastrointestinal tract. There are so-called sustained-release tablets, such as tablets whose membranes or membranes themselves gradually disintegrate in the gastrointestinal tract, resulting in sustained drug release. These sustained-release tablets are effective to a certain extent because the effect lasts longer for the patient simply by ``taking the medicine'' in exactly the same way as conventional tablets. However, even in this case, no improvement in bioavailability can be expected for drugs that undergo hepatic metabolism. Furthermore, it is extremely difficult to prevent gastrointestinal disorders. Furthermore, the sites where orally administered drugs are absorbed are mainly the stomach and small intestine, and the effective time of ordinary extended-release tablets is limited, except for drugs with extremely long half-lives.
It is 12 hours. Moreover, in the case of oral extended-release tablets,
Even if serious side effects occur after oral administration, there is a problem in that the drug cannot be easily taken out of the body, for example, immediately. <Problems to be Solved by the Invention> As described above, in the prior art, immediate-acting preparations such as injections have problems in that the duration of drug efficacy and administration are limited. In addition, among sustained-release preparations, tapes and patches have limited applicable drugs, and tablets have problems such as bioavailability and side effects such as gastrointestinal disorders. . In view of the problems of the prior art, the purpose of the present invention is to provide a drug that has immediate effect and sustained release, that is, maintains the blood concentration of the drug continuously in a safe treatment range, and furthermore, The object of the present invention is to provide a preparation that can be quickly removed. <Means for Solving the Problems> The present inventors have conducted intensive studies on preparations that have immediate effect and sustained release. As a result, as a means of administering drugs, liver metabolism can be improved by supplying drugs in a gaseous state to the lungs, which have countless capillaries and have an extremely high ability to absorb substances, such as oxygen absorption from gases. It was discovered that the drug effectively enters the bloodstream without causing any damage, and that the drug's efficacy appears extremely quickly. However, in order to overcome the drawbacks of conventional formulations, simply relying on the above-mentioned administration method was still insufficient in terms of safety. That is, even if a drug is once vaporized, if the drug re-solidifies on its way to the lungs, it may cause various side effects. Therefore, in order to overcome the drawbacks of conventional formulations and prevent the occurrence of such side effects, the present inventors conducted further intensive studies and developed a portable formulation that can be worn near the nose, thereby making it easier for the drug to be absorbed. The present invention was achieved based on the finding that a formulation designed to be heated and vaporized at body temperature or exhalation temperature is optimal. Therefore, the present invention provides a preparation for inhaling a vaporized drug into the body through the nose or mouth, which is characterized in that the drug is contained in a fibrous material made of microporous hollow fibers. This is a sustained-release formulation. The drug of the present invention may be any drug as long as it can be vaporized.
Moreover, the degree of vaporization may be extremely small. Whether or not a particular compound has vaporizability depends on the organic nature (number of carbon atoms) of the compound, as reviewed in literature such as the Organic Concept Diagram (Sankyo Publishing, published in 1980). and inorganicity (number of substituents), and can be selected from those within the volatility limit line. In this conceptual diagram, compounds that are within the odor limit line are particularly preferred, but the effective dose of a drug varies markedly depending on the type of drug, and even a very small amount is often effective against a specific disease. It may not be within the line. Examples of such compounds include the following. (1) General anesthetic agents such as halothane, anesthetic ether, methoxyflurane, and enflurane; (2) Hypnotic and sedative agents such as bromovalerylurea, glutethimide, barbital, and ethinamate; (3) Fenacemide, acetylphenetride, ethotoin, trimethadione, metalbital,
Anti-epileptic agents such as primidone and ethosuximide; (4) aspirin, salicylic acid, methyl salicylate, ethyl salicylate, glycol salicylate, camphor, thymol, acetaminophen, phenacetin, phenyl acetylglycine dimethylamide, mefenamic acid, Antipyretic, analgesic, and antiinflammatory agents such as flufenamic acid, aminopyrine, antipyrine, alclofenac, ibuprofen, naproxen, flurbiprofen, ketoprofen, fenbufuene, pentazocine, clidanac, torfenamic acid, and diflunisal; (5) Stimulants and stimulants such as benagride; ( 6) Antidepressants such as thiethylperazine; (7) Neuropsychiatric agents such as metazepam and pemoline; (8) Local anesthetics such as ethyl aminobenzoate; (9) such as chlorzoxazone, fuenprobamate, chlormezanone, and baclofen. Skeletal muscle relaxants; (10) Autonomic nerve agents such as carpronium chloride, bethanechol chloride, and akratonium napadisylate; (11) Antispasmodics such as phloroglucin; (12) Antiparkinsonian agents such as biperiden chloride; (13) Ophthalmological agents such as methazolamide. (14) Antihistamines such as diphenhydramine and dimethindene maleate; (15) Stimulants such as D-penicillamine; (16) Cardiotropes such as trans-pi-oxocamphor and apooxocamphor; (17) Diuretics such as polythiazide and benzthiazide; (18) Antihypertensive agents such as mebutamate, pindolol, captryl, and guanhuacine hydrochloride; (19) Amyl nitrite, nitroglycerin, pentaerythritol tetranitrate, trol nitrate phosphate, isosorbide nitrate, ethaphenone hydrochloride,
Coronary vasodilators such as nicorandil; (20) Peripheral vasodilators such as cyclanderate and nicamethate citrate; (21) Other circulating vasodilators such as meclofenoxate hydrochloride, pentoxifylline, and dI-alpha-tocopherol nicotinate. (22) Antitussive and expectorant agents such as oxelazine citrate, isoaminyl citrate, guaifuenesin, cloperastine, L-ethylcysteine hydrochloride, L-methylcysteine hydrochloride, acetylcysteine; (23) Antitussive expectorants such as povidone-iodine, sodium guaiazulene sulfonate, etc. Dental and oral preparations; (24) Peptic ulcer treatment agents such as gephalnate and teprenone; (25) Other gastrointestinal agents such as phenipentol; (26) Antithyroid hormone agents such as propylthiouracil and thiamazole; (27) Other hormonal agents such as cyclophenyl; (28) Analgesic, antipruritic, astringent, and antiinflammatory agents such as Cantharis, dimethylisopropyl azulene, Bufexamac, crotamiton, isoprofenpiconol, and butyl flufenate; (29) L-tinol palmitate, Ergo Vitamins such as calciferol, difudrotaxerol, cichotiamine hydrochloride, nicotinic acid, nicotinamide, biotin, tocopherol calcium succinate; (30) Hemostatic agents such as tranexamic acid; (31) Thioctic acid, thioctic acid amide (32) Antidotes such as dimercaprol, disulfiram, malotylate; (33) Metabolic drugs not elsewhere classified such as L-cysteine; (34) Cyclophosphamide, thiotepa, pipobroman (35) Antibiotics such as bacampicillin hydrochloride, cycloserine; (36) Chemistry such as isoniazid, ethionamide, prothionamide, etc. Therapeutic agents; (37) propranolol, oxprenolol,
A β-blocker obtained by liberating hydrochloric acid from a drug commonly used as the hydrochloride of indenolol. These drugs may be used alone or in an appropriate combination of two or more. Among these drugs, in particular, antipyretic, analgesic, and antiinflammatory agents such as flurbiprofen, clidanac, ibuprofen, pentazocine, alclofenac, and phenacetin; antihistamines such as diphenhydramine; and coronary vasodilators such as nitrites and nicorandil. ; Dental and oral agents such as sodium guaiazulene sulfonate; Neuropsychiatric agents such as pemoline and metazepam; Skeletal muscle relaxants such as chlormethasone and baclofen; Antihypertensive agents such as pindolol; β-blockers such as propranolol; Citric acid Peripheral vasodilators such as nicamethate; antithyroid agents such as thiamazole are suitable. The amount of the drug to be used is appropriately determined depending on the strength of the pharmacological action of the drug used and the difficulty of vaporization. In the present invention, such a drug is a preparation that is contained in a fibrous material made of microporous hollow fibers, and is placed around the human nose (external nose) or within the nostrils, or is attached to it or adhered to it. It can be applied by fixing it with tape, etc., or by attaching it inside an existing mask. As described below, the fibrous material of the present invention is made of microporous hollow fibers having holes penetrating in the outer circumferential direction, and by incorporating a drug into the fiber, the vaporization of the drug is significantly promoted. , it becomes easier to control drug release, and therefore the range of drugs that can be applied to the formulation of the present invention is greatly expanded;
It has the great advantage of being able to increase the dosage of the same drug. The microporous hollow fiber of the present invention is a hollow fiber having countless micropores over the entire surface of the fiber, at least some of which communicate with the hollow portion. Both the outer shape and the shape of the hollow portion in the cross section of such hollow fibers may be arbitrary. For example, the outer shape and the hollow part may both be substantially circular, one of the outer shape and the hollow part may be substantially circular and the other an irregular shape, or both the outer shape and the hollow part may have similar or dissimilar irregular shapes. . Further, there is no particular restriction on the size of the external shape. The hollowness ratio of the microporous hollow fiber of the present invention may be arbitrary, but it is particularly preferably 5% or more, and the proportion of the pores communicating from the fiber surface to the hollow part in the cross-sectional area of the fiber is 0.001 to 70% of the removed fiber cross-sectional area is preferable, particularly 0.01 to 50%,
Furthermore, 1 to 50% is preferable. In the present invention, such hollow fibers may be used as long fibers, may be used rolled up like a ball, or may be used after being cut into a length of 5 to 1000 mm, or It may also be used as a sheet material such as cloth, paper, or nonwoven fabric. These planar bodies may be further folded and used. Both are defined as fibrous substances in the present invention. It may also be in a mixed state with other fibers.
In particular, when used in the form of a tissue such as fiber, knitted fabric, or nonwoven fabric, it is preferable because it provides good handling properties, a good feel on the skin, and an excellent effect on sustained drug release. Among these, knitted fabrics are particularly preferred because they have high elasticity and cause less discomfort when applied to humans in the form of preparations. The weight of knitting is 5~
2000 g/m ² , especially 10 to 1000 g/m ² is preferred. Materials for the hollow fibers used in the present invention include, for example, polyesters such as polyethylene terephthalate; polyolefins such as polyethylene and polypropylene; polyamides such as nylon 6 and nylon 66; polyurethane, cellulose acetate, polyacrylonitrile, polyvinyl chloride, polyvinyl acetate, etc. , you can choose any one. Among these, polyester is preferred, and polyethylene terephthalate is particularly preferred from the viewpoint of good thermal stability, chemical stability, little interaction with drugs, and safety as a formulation. The hollow fiber used in the present invention is, for example,
-20612 Publication, JP-A-56-20613, JP-A-Sho
It can be produced by the method described in JP 56-43420 and the like. The immediate-acting sustained release preparation of the present invention can be obtained by incorporating a drug into the micropores and hollow portions of the microporous hollow fibers described above.
The drug may be present alone in the micropores and hollow portions, or may be present together with commonly used excipients, solubility aids, diffusion aids, absorption enhancers, and the like. The drug can be filled into the micropores and hollow portions of the hollow fibers by any method. For example, into a solution containing a drug,
After soaking the hollow fibers, the solvent is removed, or the drug is mixed with excipients, dissolution aids, diffusion aids, absorption enhancers, etc., and then made into a solution, ointment, etc. A method of dipping or contacting the hollow fibers is used. Means such as heating, pressurization, vacuum depressurization, ultrasonic vibration, etc. can also be used to aid in the entry of the drug or drug mixture into the micropores and hollow portions of the hollow fibers. When applying the immediate-acting sustained-release preparation of the present invention to humans, it is necessary to attach it around the nose so that the drug vaporized from the preparation can be inhaled into the body via the nose or mouth. You can sew it directly onto the mask, formulate the entire mask, or
The formulation may further include an adhesive layer to secure it to the skin or mask. In order to control the release of the drug, all or part of the drug-containing moiety may be made of a polyolefin such as polyethylene or polypropylene; a polyester such as polyethylene terephthalate; a polyamide such as nylon 6 or nylon 66; polyvinyl alcohol or chloride. vinylidene, polyurethane,
It may be coated with a sheet, film, woven fabric, knitted fabric, nonwoven fabric, foil, etc. of ethylene-vinyl acetate copolymer, metal foil, rubber, etc. In particular, it is preferable to newly provide an adhesive layer because it is effective in controlling the release of the drug and making it easier to attach the preparation to the nasal area. The present invention will be explained in more detail with reference to Examples below. Parts in Examples and Reference Examples indicate parts by weight. Reference example 1 Preparation of hollow fiber sample 297 parts of dimethyl terephthalate, 265 parts of ethylene glycol, 53 parts of sodium 3,5-di(carbomethoxy)benzenesulfonate (11.7 mol% based on dimethyl terephthalate), manganese acetate 4 water 0.084 parts of salt and 1.22 parts of sodium acetate trihydrate were placed in a glass flask equipped with a rectifying column, and a transesterification reaction was carried out according to a conventional method. After the theoretical amount of methanol had been distilled off, the reaction product was placed in a glass flask equipped with a rectifying column. Add 0.090 56% aqueous solution of orthophosphoric acid to the condensation flask as a stabilizer.
0.135% and antimony trioxide as polycondensation catalyst
30 mmHg for 20 minutes at a temperature of 275°C and normal pressure. The resulting copolymer had an intrinsic viscosity of 0.405 and a softening point of 200°C. After the reaction was completed, the copolymerized polymer was made into chips according to a conventional method. 15 parts of chips and intrinsic viscosity of this copolymer
0.640 polyethylene terephthalate chips 85
5 in a Nauta mixer (manufactured by Hosokawa Iron Works).
After mixing for 2 minutes at 110°C in a nitrogen stream,
After further drying at 150°C for 7 hours, the mixture was melt-kneaded at 290°C using a twin-screw extruder to form chips. This chip had an intrinsic viscosity of 0.520 and a softening point of 262°C. The chips are dried in a conventional manner and placed in a spinneret.
A circular slit of 0.05 mm and a diameter of 0.6 mm with two closed arcuate openings was used and spun according to a conventional method to obtain hollow fibers (hollow fibers) with a ratio of outer diameter to inner diameter of 2:1. rate of 25%). This raw yarn was 300 denier/24 filaments, and was drawn in a conventional manner at a draw ratio of 4.2 times to obtain a multifilament of 71 denier/24 filaments. This multifilament was knitted into a knitted fabric, refined and dried by a conventional method, and then treated with a 1% caustic soda solution at boiling temperature for 2 hours to achieve an alkali loss rate of 15%, a water absorption rate of 3 seconds, a water absorption rate of 80%, and a basis weight.
A fabric of 38 g/m ² was obtained. Incidentally, the water absorption rate and water absorption rate were measured by the following method. (a) Water absorption rate test method (according to JIS-L1018) The fibers are made into cloth, and the cloth is washed with a 0.3% aqueous solution of anionic detergent Zab (manufactured by Kao Soap Co., Ltd.) at 40℃ for 30 minutes in a household electric washing machine. Repeat the washing a specified number of times, then dry the sample. Place the sample horizontally, and pour 1 drop of water (0.04cm) from a height of 1cm above the sample.
cc) Drop the sample and measure the time until the water is completely absorbed by the sample and no reflected light is observed. (b) Water absorption measurement method A sample obtained by drying a fabric is immersed in water for at least 30 minutes, and then dehydrated for 5 minutes in a dehydrator of a household electric washing machine. It was calculated from the weight of the dry sample and the weight of the sample after dehydration using the following formula. Water absorption rate = Sample weight after dehydration - Dry sample weight / Dry sample weight (%) The hollow fibers obtained by the above method are coated with powder and arranged in the fiber direction over the entire surface of the hollow fibers, and at least a part of the hollow fibers is It was a hollow fiber having fine pores that communicated to the hollow part. Reference Example 2 Creation of adhesive solution and adhesive layer 97.4 parts of 2-ethylhexyl acrylate, 2.5 parts of methacrylic acid, 0.1 part of polyethylene glycol (degree of polymerization 14) dimethacrylate, 1.0 part of benzoyl peroxide and 100 parts of ethyl acetate were cooled under reflux. Place in a reaction vessel equipped with a stirrer and stirrer under nitrogen atmosphere.
Polymerization was continued for 9 hours at 60°C with gentle stirring. The polymerization addition rate was 99.9%. 500 parts of ethyl acetate was added to the obtained polymer solution to adjust the solid content concentration to about 20% to obtain an adhesive solution. An ethyl acetate solution containing the adhesive was applied onto a silicone-coated release paper so that the thickness after drying would be 20 μm, and dried at 90° C. for 10 minutes to obtain an adhesive layer. Example 1 100 parts of the hollow fiber sample obtained in Reference Example 1 was impregnated with 100 parts of an acetone solution containing 45 parts of isosorbide nitrate, and then the acetone was removed by evaporation. Thus, an immediate release sustained release formulation consisting of microporous cloth containing 9.1 g/m ² of isosorbide nitrate was obtained. The cloth containing 9.1 g/ ^m2 of isosorbide nitrate thus obtained was cut into 10 cm x 10 cm pieces and placed in a constant temperature bath at 37°C to examine the amount of isosorbide nitrate released by sublimation over time, and it was found that it was approximately 5.8 mg/day. It was released linearly over two days at a constant rate of . A piece of cloth containing 9.1g/ ^m2 of isosorbide nitrate was cut into pieces of 2cm x 4cm and fixed around the rabbit's nose so that the rabbit's exhalation passed through the cloth. Isosorbide nitrate in 0.5 ml of blood plasma obtained from blood collection was extracted with 5 ml of n-hexane, concentrated, added with 100 μl of ethyl acetate, extracted into a gas chromatograph equipped with an ECD detector, and quantified as shown in Table 1. It became. Comparative Example 1 Isosorbide nitrate obtained in Example 1 9.1g/m ²
The adhesive layer obtained in Reference Example 2 was laminated on both sides of the cloth containing the material, and a polyethylene terephthalate film with a thickness of 5 μm was laminated on the free side of the adhesive layer, and then this molding was performed. The object was cut into 2cm x 4cm pieces. This was applied to the back of a rabbit whose hair had been removed, and blood was collected from the ears of the rabbit over time. Isosorbide nitrate was quantified in the plasma in the same manner as in Example 1. The obtained values are shown in Table 1. Indicated.

[Table] From Table 1, in the formulation of the present invention (Example 1),
Compared to the comparative example, it can be seen that isosorbide nitrate is absorbed immediately after application and maintains a blood concentration at a substantially constant level for a long period of time, that is, it has immediate effect and sustained release. Comparative Example 2 100 parts of a hot 10μ polyethylene terephthalate film was impregnated with an acetone solution containing isosorbide nitrate, and then the acetone was removed by evaporation. The thus obtained film to which 9.1 g/m ² of isosorbide nitrate was adhered was cut into 10 cm x 10 cm pieces, placed in a constant temperature bath at 37°C, and the amount of isosorbide nitrate released by sublimation was examined over time. As a result, the average amount was 0.3 mg/m2. The drug was released at a daily rate, but the release was in a tapering pattern. Example 2 33 parts of nitroglycerin was added dropwise to 100 parts of the hollow fiber sample obtained in Reference Example 1, and the mixture was left in a sealed glass container overnight. Nitroglycerin thus obtained 12.5 g/m ²
The adhesive layer obtained in Reference Example 2 was attached to both sides of the cloth containing the material, and a polyethylene terephthalate film with a thickness of 5 μm was attached to the free side of the adhesive layer. The vaporized nitroglycerin was cut into pieces and placed around the rabbit's nose like a mask so that the vaporized nitroglycerin could be inhaled into the rabbit's body. After extracting nitroglycerin with 5 ml of n-hexane, it was concentrated to 100μ under a stream of N ₂ and extracted into a gas chromatography equipped with an ECD detector for quantification. The results are shown in Table 2. Comparative Example 3 Nitroglycerin obtained in Example 2 12.5g/
A 2 cm x 2 cm preparation containing m ² was applied to the back of a dehaired domestic rabbit, blood was collected from the rabbit's ear over time, and nitroglycerin in the blood was determined in the same manner as in Example 3. The values obtained are shown in Table 2.

[Table] From Table 2, it can be seen that when the formulation of the present invention is administered by inhalation (Example 2), it has an immediate effect and also has sustained release properties compared to when the same formulation is administered by patch (Comparative Example 3). It can be seen that Example 3 After adding 100 parts of an acetone solution containing 30 parts of camphor to 100 parts of the hollow fiber sample obtained in Reference Example 1,
Acetone was removed by evaporation. The cloth containing 11.1 g/m ² of camphor thus obtained was cut into 6 cm x 6 cm pieces, placed in a high temperature bath at 37°C, and the amount of camphua released by sublimation was examined over time. Table 3 shows the change in release amount over time. Comparative Example 4 In Example 3, instead of the hollow fiber sample, a 50μ thick ethylene/vinyl acetate copolymer was used.
A film was obtained in the same manner as in Example 3, except that a film of 11.5 g/m ² of camphor was crystallized on the surface in a thin film form. This film was cut into 6 cm x 6 cm and Example 3
At the same time, we investigated the change in release amount over time. 3rd result
Shown in the table.

Table 3 shows that the formulation of the present invention (Example 3) has a good onset of drug release and is linearly released. On the other hand, the comparative formulation (Comparative Example 4) is inferior in terms of start-up and release amount. Example 4 80 parts of an acetone solution containing 3.37 parts of ibuprofen was added to 100 parts of the hollow fiber sample obtained in Reference Example 1, the acetone was evaporated, and the ibuprofen was dissolved.
A fabric containing 1.28 g/m ² was obtained. After cutting this cloth into a size of 20cm x 30cm, fold it to 6cm x 6cm, which is the size of a normal mask.
When the release rate of ibuprofen was examined by placing it in a high temperature bath at 36°C, the drug was released at a constant rate of approximately 3 mg/hour over 24 hours. Comparative Example 5 20.3 mg of ibuprofen was placed in a glass jar.
The weight after being placed in a 36℃ high temperature bath and left for 24 hours is
The dose was 20.2 mg, and almost no drug was released. From Example 4 and Comparative Example 5, it can be seen that the formulation of the present invention can also be applied to ibuprofen, which does not exhibit volatility under normal conditions. Example 5 In Example 4, a cloth containing flurbiprofen was prepared in exactly the same manner as in Example 4, except that flurbiprofen was used instead of ibuprofen. When the release rate of Ene was determined, the drug was released at a constant rate of 0.8 mg/hour. Comparative Example 6 In Comparative Example 5, the amount of flurbiprofen released was investigated in the same manner as in Example 5 except that flurbiprofen was used instead of ibuprofen.
The initial weight was 20.2mg, but it remained 20.2mg after 24 hours.
It was hot. Example 6 In Example 4, a fabric containing 1.28 g/m ² of captopril was prepared in the same manner as in Example 4, except that capropril was used instead of ibuprofen, and the release rate of captopril was determined in the same manner as in Example 6. When tested, the drug was released at a constant rate of approximately 0.11 mg/hour. Example 7 A fabric containing 1.28 g/m ² of propranolol was made in the same manner as in Example 4 except that propranolol was used instead of ibuprofen in Example 4, and propranolol was released in the same manner as in Example 4. When the rate was determined, the drug was released at a constant rate of 0.18 mg/hour. Example 8 Acetone solution containing 20 parts of diphenhydramine 80 parts
100 parts of the hollow fiber sample obtained in Reference Example 1, and the acetone was removed by evaporation to obtain a cloth containing 7.3 g/m ² of diphenhydramine. The adhesive layer obtained in Reference Example 2 was laminated on one side of this cloth, and the adhesive layer surface was further covered with a polyethylene terephthalate film with a thickness of 5 μm, and the size was 2.8 cm.
The cloth was cut into 3 cm pieces to obtain an immediate-acting sustained release preparation made of cloth containing 6 mg of diphenhydramine. When this preparation was placed in a high temperature bath at 36°C and the release rate of diphenhydramine was examined, the drug was released at a constant rate of 0.36 mg/hour. Example 9 An immediate-release sustained release preparation made of cloth containing 1.28 g/m ² of indenolol was prepared in exactly the same manner as in Example 4, except that indenolol was used instead of ibuprofen. The drug release rate was determined in the same manner as in 4, and was found to be 2.16 mg/
Drug was released at a constant rate in time. Example 10 An immediate-release sustained release preparation made of cloth containing 1.28 g/m ² of nicorandil was prepared in exactly the same manner as in Example 4 except that nicorandil was used instead of ibuprofen. When the drug release rate was determined in the same manner as above, the drug was released at a constant rate of 0.60 mg/hour.

Claims (1)

[Scope of Claims] 1. A preparation in which a vaporized drug is inhaled into the body through the nose or mouth, in which the drug is contained in a fibrous material made of microporous hollow fibers. Features: Immediate-acting sustained-release formulation. 2 A fibrous material consisting of microporous hollow fibers is
The immediate-acting sustained-release preparation according to claim 1, which is a cotton-like material or a sheet material such as cloth, paper, or nonwoven fabric. 3. The immediate-acting sustained release preparation according to claim 2, which comprises a planar body with an adhesive layer on one or both sides. 4. The immediate-acting sustained release preparation according to any one of claims 1 to 3, wherein the microporous hollow fibers are polyester hollow fibers. 5. Any one of claims 1 to 4, wherein the drug is one or more selected from antipyretic, analgesic, and antiinflammatory agents, coronary vasodilators, antihistamines, and β-blockers. Immediate-acting sustained-release preparations as described in Section 1. 6 Antipyretic, analgesic and anti-inflammatory agents include camphor, methyl salicylate, glycol salicylate, ibuprofen,
The immediate-acting sustained-release preparation according to claim 5, which is any one selected from flurbiprofen, clidanac, and pentazocine. 7. The immediate-acting agent according to claim 5, wherein the coronary vasodilator is any one selected from nitroglycerin, isosorbide nitrate, amyl nitrite, pentaerythritol tetranitrate, trolnitrol phosphate, and nicorandil. sustained release formulation. 8. The immediate-acting sustained release preparation according to claim 5, wherein the antihistamine is diphenhydramine. 9. The immediate-acting sustained release preparation according to claim 5, wherein the β-blocker is propranolol.