JPS5984818A - Pharmaceutical for prolonged release of chemical - Google Patents

Abstract

PURPOSE:The titled pharmaceutical having a backing member, a chemical storage layer provided on one surface of the backing member, a chemical-permeable layer containing the chemical storage layer and chemical paths, surrounded by chemical-impermeable walls, and having one end thereof communicated to the chemical storage layer and the other end communicated to the chemical-permeable layer. CONSTITUTION:A pharmaceutical for prolonged release of a chemical having a backing member 1, a chemical storage layer 2 provided on one surface of the backing member 1, a chemical-permeable layer 3 containing the chemical storage layer 2 and zigzag chemical paths 5, formed by chemical-impermeable partition walls 4, and having one end thereof communicated to the above-mentioned chemical storage layer 2 and the other end extending and communicated to the surface of the above-mentioned chemical-permeable layer 3. The zigzag chemical paths 5 surrounded by the partition walls 4 are the same as the thick chemical- permeable resin layer, and the chemical is released for a long term to keep the concentration in blood in the body at a constant value, and the release rate of the chemical can be controlled by adjusting the shape or cross-sectional area of the paths 5.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to sustained release drug formulations that release pharmacologically active drugs at a controlled rate over an extended period of time.

To achieve the desired therapeutic effect by administering a drug, it is desirable to maintain the drug at an effective concentration or higher in the diseased area or the circulatory system for a long period of time, and for this reason it is conventional to release the drug at a controlled rate. Various sustained release drugs have been proposed. Typically, as described in Japanese Patent Publication No. 54-1'6566 (1), a backing member forming the outer surface, a pressure-sensitive adhesive layer forming the adhesive surface to the skin or mucous membrane, This is a laminate including a drug storage layer containing a drug between the backing member and the adhesive layer. The storage layer consists of a resin layer that is permeable to the drug and controls its release rate; diffuses through the adhesive layer from the storage layer, is released slowly from the surface at a controlled rate, and is absorbed into the body through the skin or mucous membranes applied to the adhesive surface. In some cases, a control layer in which the diffusion rate of the drug is lower than that of the storage layer may be interposed between the storage layer and the adhesive layer.

However, in such sustained-release preparations, the drug diffuses in the thickness direction of the preparation, so the period during which the drug can be released is not necessarily long enough. The release wall is not completely satisfactory.

Furthermore, it is difficult to vary and control the release rate depending on the type of drug, and the release rate is often limited.

The present invention has been made to solve the above-mentioned problems, and the present invention is to release a drug at a substantially constant rate over a long period of time, thereby substantially reducing the blood concentration of the drug absorbed into the body from the application surface. It is an object of the present invention to provide a sustained release preparation that has excellent sustained release properties that maintain a constant drug release rate, and that also allows the release rate of a drug to be controlled over a wide range.

The sustained release preparation of the present invention includes a lining member, a drug storage layer provided on one surface of the lining member, a drug permeable layer that includes the drug storage layer, and a drug impermeable layer in the drug permeable layer. It is characterized by comprising a drug passage surrounded by a partition wall, one end of which communicates with the drug storage layer, the other end of which communicates with the surface of the drug permeable layer and extends in a bent manner.

FIG. 1 shows an example of a sustained drug release formulation of the present invention.

The backing member 1 may be either non-flexible or flexible, but is preferably flexible and drug-impermeable because many sustained-release preparations are applied on the skin or mucous membranes by adhesion. Preferred specific examples include resin sheets or films of cellulose acetate, ethyl cellulose, cellophane, polyethylene terreslate, plasticized vinyl acetate-vinyl chloride copolymer, polyamide, polyethylene, polyvinylidene chloride, and aluminum foil. metal foil, etc.
and a laminate of two or more of these.

In the sustained release preparation of the present invention, a drug storage layer 2 is provided on one surface of this lining member 1 .

This storage layer is made of a drug-permeable resin layer containing a drug, and the mode in which the drug is contained in the drug-permeable resin is not particularly limited. For example, by melt-mixing tit fat and a drug,
It may be formed into a sheet shape, or it may be one in which the drug is uniformly dispersed in the resin layer in powder or liquid form.

Furthermore, the drug may be dispersed in the resin layer as microcapsules.

The drug used in the present invention is not particularly limited as long as it is absorbed into the body through the skin or mucous membrane and exerts the desired pharmacological effect. Cardiac drugs, anticonvulsants such as atropin and scopolamine, antibiotics such as penicillin, tetracycline, chlorotetracycline, oxytetracytalline, and sulfonamides, barbiturates, phenobarbital, bendoparvicur, α-bromoisovaleryl Analgesic hypnotics such as urea and codine, anti-inflammatory analgesics such as indomethacin, mefenamic acid, diclofenac, alclofenac, and phenylbutacin, tranquilizers such as chloropromacine, thioridazine, diacepam, reserpine, and hacoperidol, 3-2 ( Psychoactive agents such as 2-aminobutyl) indole acetate, prednisolone, hydrocortisone, fluocinolone acetonide,
triamcinolone acetonide, methyltestosterone,
Megesterol acetate, fluoximesterone, esterone, estradiol, ethinyl estradiol, 17α-hydroxyprogesterone acetate, 1
Contains steroid hormones such as 9-norprogesterone and methoxyprogesterone acetate, antipyretic agents such as acetylsalicylic acid, salicylamide, and sodium salicylate. In addition, when these drugs are absorbed through the skin or mucous membranes, they should be prepared as a pharmaceutically acceptable solution.
Moreover, it may be made into a pharmaceutically acceptable derivative if necessary.

The resin for constituting the drug storage layer is not particularly limited as long as it has drug permeability, but examples include silicone resins such as boridimethylsiloxane, polyhydroxylethyl (meth)acrylate, polymethylacrylate, and polyester. Poly(meth)acrylic esters such as butyl acrylate, polyacrylic acid, its salts, polyvinyl alcohol, polyvinyl acetate, polyethylene wax, polyethylene oxide, polyvinylpyrrolidone, hydroxyethylcellulose, carboxymethylcellulose,
Synthetic or natural resins and rubbers such as plasticized polyvinyl chloride, plasticized polyamide, polyurethane, polyisobutylene, styrene-butadiene rubber, ethylene-carbon oxide copolymer, collagen, gelatin, gum acacia, and gum tragacanth are preferably used.

To adjust the permeation rate of the drug in the drug storage layer,
The drug storage layer may be formed by containing a drug in a mixture of the above resin and an appropriate solvent.

The solvent is appropriately selected depending on the type of drug used and the release rate of the drug, but examples include mineral oil, silicone oil,
Glycols such as diethylene glycol, propylene glycol, and polyethylene glycol, oils and fats such as olive oil, squalene, and lanolin are preferably used.

In the sustained-release preparation of the present invention, a drug-permeable resin layer 3 is laminated on the drug storage layer 2 configured as described above, and within this drug-permeable resin layer is a drug-impermeable partition wall. 4
A drug passage 5 surrounded by the drug passage 5 is formed by bending, and one end of this passage communicates with the drug storage ii2, and the other end communicates with the surface of the drug permeable resin layer 3. In the embodiment shown in FIG. 1, drug-impermeable partition walls 4 are laminated in parallel in a drug-permeable resin layer 3 at intervals, and curved passages 5 are formed between the partition walls.
is configured.

FIG. 2 shows another embodiment of the sustained-release preparation of the present invention, in which a drug storage M2 is included inside the drug-permeable resin layer 3, and a partition wall 4 is spirally wound from this storage layer. A curved passage 5 is formed between them.

In the embodiment shown in FIG. 2, the partition walls are exposed on the surface of the preparation and can also serve as a lining member.

In addition to the sheet made of the material constituting the above-mentioned backing member, the above-mentioned partition wall can be made of, for example, polypropylene, ethylene-vinyl acetate copolymer, polyvinyl chloride, vinyl chloride-
Sheets made of ethylene copolymer, polysulfone, polyphenylene oxide, polycarbonate, aromatic polyamide, polyacetal, polyfluoroethylene, etc. are used.

In the sustained-release preparation of the present invention, a pressure-sensitive adhesive N6 is usually provided on the drug-permeable resin layer in order to apply the preparation to the skin or mucous membrane. This adhesive may be any adhesive as long as it is dermatologically and mucosologically acceptable and is permeable to the drug used, but specific examples include acrylic resin adhesives, silicone resin adhesives, and other adhesives. , natural rubber, polyurethane, polyisoprene, polyisobutylene,
Rubber adhesives such as polyptadiene, vinyl adhesives such as polyvinylpyrrolidone and polyvinyl acetate, and cellulose adhesives such as ethylcellulose and methylcellulose are used. If necessary, on top of this adhesive layer,
A suitable release sheet 7 such as a resin film coated with silicone resin is attached.

As described above, according to the sustained release preparation of the present invention, since the drug passage surrounded by the partition wall is formed in a curved manner, it is the same as if the drug permeable resin layer is formed with a large thickness. Yes, therefore the drug is released over a long period of time and
The blood concentration of the drug absorbed into the body can be kept approximately constant, and the drug penetration rate can be controlled in various ways by changing the shape and cross-sectional area of the passage.

The present invention will be explained below with reference to Examples, but the present invention is not limited to these Examples in any way.

Example 1 Room-temperature curing type boridimethylsiloxane elastomer was coated on one side of a polyethylene film with a thickness of 0.1 tm.
This was cut into a size of 10 x 9 cm. Next, the long sides were aligned, the short sides were alternately shifted left and right by 10, and the periphery was heat-sealed to a width of about 21 to form a square laminated film. In this laminated film, the polyethylene film forms the partition wall, and the silicone resin elastomer on the film forms the drug passage.

Next, 10 parts by weight of 30% isosorbide nitrate lactose mixture, 1 part by weight of polyethylene glycol (molecular weight 400), and 89 parts by weight of hydroxymethacrylate-ethyl acrylate (weight ratio 7/3) copolymer were dissolved in a methanol-acetone mixed solvent. A uniform solution was obtained, and this was applied onto an aluminum foil and dried to form a drug storage layer with a thickness of 0.2 mm.

The above-mentioned polyethylene film was laminated on the drug storage layer so that the silicone-filled elastomer coating layer was in contact with the drug storage layer, and the periphery was heat-sealed to obtain a sustained release preparation of the present invention.

This preparation was applied to the hairless back of a rabbit weighing 3.7 kg, and the blood concentration of isosorbide nitrate was measured. The results are shown in the table. The method for measuring blood concentration is as follows. After applying the preparation as above, apply 3 times at specified intervals.
Blood was collected in ml portions, and plasma was separated and extracted with 4 ml of hexane. Next, this was evaporated to dryness in an inert gas,
It was dissolved in 100 μβ of ethyl acetate and measured by ECD-gas chromatography.

Example 2 In Example 1, octyl acrylate-acrylic acid (weight ratio 96/'4) copolymer was coated on a polyethylene film and dried to form drug passages, and 2% indomethacin was coated on a polyethylene terephthalate film. A sustained release preparation was obtained in exactly the same manner as in Example 1, except that the polyoctyl acrylate contained therein was applied to form a drug storage layer.

[Brief explanation of the drawing]

FIG. 1 is a sectional view of a main part showing one embodiment of the sustained release preparation of the present invention, and FIG. 2 is a sectional view of a main part showing another embodiment. l... Lining member, 2... Drug storage layer, 3... Drug permeable resin layer, 4... Partition wall, 5... Drug passage, 6
... Adhesive layer, 7... Peeling layer. Patent applicant Mototoshi Fujinuma, representative of Sekisui Chemical Co., Ltd.

Claims (1)

[Claims] (1) A lining member, a drug storage layer provided on one surface of the lining member, a drug-permeable layer that includes the drug-storage layer, and a drug-impermeable partition surrounded by a drug-impermeable partition within the drug-permeable layer. 1. A sustained-release preparation comprising a drug passage whose one end communicates with the drug storage layer and whose other end communicates with the surface of the drug permeable layer and extends in a bent manner.