JPS6232167B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a physiologically active substance supplying member (hereinafter referred to as a supplying member) that continuously supplies a contact body surface capable of adsorbing and/or absorbing a physiologically active substance. The supply member of the present invention is used for administering an active drug systemically or locally, for example by contacting with the outer skin or mucous membrane of the body, and for other uses, it can be applied to any application site as described above. Used for purposes such as arranging a member, attracting small harmful animals with a vaporizable attractant and bringing them into contact with the supply member, and killing small animals or preventing reproduction depending on the type of physiologically active substance in the member. It is something that will be done. For example, systemic or local administration of active drugs through the body's outer skin or mucous membranes can be achieved by applying a drug solution in which the drug is dissolved in a solvent, or by mixing the drug with a soft substance and applying it as a cream-like ointment. Alternatively, it is usually inserted or implanted in the form of a suppository or tablet. One of the unavoidable drawbacks of these administration methods is that drug levels in the circulatory system increase each time the drug is applied, but over a short period of time the drug concentration in the blood or other parts of the body decreases and is quantitatively reduced. This means that it cannot be retained. In order to solve these drawbacks, methods have been developed in which systemically or locally active drugs are continuously administered through the outer skin or mucous membranes of the body, and some attempts have been made to put them into practical use. One is a pressure-sensitive adhesive tape or film-like drug dosage article formed on a carrier of a mixture of active drugs in a selected pressure-sensitive adhesive composition. However, since the adhesive composition of the lever-dosed product effectively prevents the temporary release of the drug to the skin surface, the drug is administered continuously, but the dose does not change over time. and does not serve the purpose of quantitative continuous dosing. The other is a drug administration product consisting of a laminate of a backing member, a drug storage layer, a polymer film layer that controls the transfer rate of the drug, and a pressure-sensitive adhesive layer.
In this drug, the drug diffuses through a polymer film layer and a pressure-sensitive adhesive layer and is administered to the skin surface.The drug diffusion rate is controlled by the diffusion rate in the polymer substance. Because of the method, control factors for drug permeation occur in the polymeric film and also in the adhesive. Therefore, it is complicated to select the type of polymer material and adhesive depending on the structure of the drug, and the adhesive properties of the adhesive to the skin must also be taken into consideration. This makes it difficult to apply to drugs. The supply member of the present invention solves these problems and is capable of adsorbing and/or absorbing physiologically active substances.
or by contacting or causing to come into contact with an absorbable body, animal or article, the active substance in the supply member is adsorbed and/or absorbed by the body, animal or article and the efficacy of the substance is enhanced. It is used for the purpose of functioning effectively. This purpose consists of a physiologically active substance retention layer and an impermeable base material layer formed on one side of this layer, and the retention layer is a membrane-like material having countless micropores. This is achieved by constructing a structure in which the following three components are retained in the pores, and these three components are a liquid material supporting a physiologically active substance, a physiologically active substance, and a water-swellable substance. That is, the supply member of the present invention is a method for continuously supplying physiologically active substances contained in micropores to the surface of the member, using moisture from sweat from the body's outer skin and/or mucous membranes, moisture in the air, and artificially. A novel method is adopted in which water such as water is supplied to a water-swellable substance in the retention layer to swell the substance, and this swelling pushes out the physiologically active substance in the pores along with the liquid to the pore surface, By employing this method, a physiologically active substance is continuously supplied to the surface of the member, and is continuously adsorbed and/or absorbed by the body, animal, or other biological article that is in contact with the surface of the member. FIG. 1 shows an enlarged partial cross-section of the supply member of the present invention, in which the member 1 shows a film-like material 12 having numerous fine pores 11 uniformly distributed throughout.
and a liquid substance, a physiologically active substance, and a water-swellable substance held in the pores 11. In this example, a composite film 14 made of a water-swellable substance is formed on the wall surface 13 forming the hole 11, and the coating 1
A mixture 1 of a liquid substance and a physiologically active substance dissolved and/or dispersed in the liquid substance in the pores 11 covered by 4.
5 is maintained. In the figure, reference numeral 2 denotes an impermeable base material layer made of a base material that substantially does not allow physiologically active substances to pass through, such as aluminum foil or polyester film. In the above, the shape of the hole 11 is not particularly limited, but the hole diameter is 100μ or less, practically 10μ or less, more preferably 0.01 to 5μ; if it is 100μ or more, if strong external pressure is applied to the supply member 1, the mixture 15 Even if the viscosity of the material is made considerably high, it may be extruded, which is not preferable. The thickness of the membranous material 12 is determined by the amount of physiologically active substance to be retained in the pores, but is generally about 10
~1000μ, practically 50 to 400μ is preferably used. Further, the water-swellable substance can be retained in the pores by coating the wall surface 13 of the pore 11 in a conventional manner as described above, or alternatively, for example, a fine powder of the substance can be preliminarily prepared in the form of an aqueous dispersion in the pores. Alternatively, the material and the mixture may be mixed and filled into the pores. FIGS. 2 and 3 show typical examples of applying the supply member of the present invention to the outer skin of the body,
In FIG. 2, an adhesive film 3, which is larger than the member 1 and provides an adhesion area for sufficiently closely fixing the member 1 to the outer skin of the body, is pasted through the base material layer 2. In the figure, 4 is an impermeable release film. In FIG. 3, an adhesive layer 5 for fixing the member 1 is provided in the shape of a frame on the opposite side of the base material layer 2 of the member 1. The shape of the adhesive layer is not particularly limited. In carrying out this invention, any active drug as a physiologically active substance that is adsorbed and/or absorbed systemically or locally by the body surface to which the supply member is applied may be used without particular limitation. For example, systemically active drugs include anti-inflammatory agents such as indomethacin and diclofenac, anticardiac drugs such as nitroglycerin, nitroglycol, and dipyridamole, clonidine, mecadylamine,
Examples include antihypertensive agents such as guanethidine, antibiotics such as erythromycin, and locally active drugs such as glycol salicylate,
Examples include anti-inflammatory analgesics such as methyl salicylate, camphor, l-menthol, and thymol, steroidal anti-inflammatory agents, hemostatic agents such as semicarpazides, antihistamines such as chlorpheniramine, and bactericidal agents such as Hibitene. In addition, small harmful animals, such as pests such as flies, mosquitoes, and oil ants, or animals such as rats and rabbits, are brought into contact with the feeding member through the path of the harmful small animals, or by using an attractant, and the physiologically active substance is adsorbed and/or
Examples of active drugs as physiologically active substances used to kill, prevent or repel these insects by absorption include organophosphate insecticides and pyrethroid insecticides such as permethrin. Examples of repellents include rodent repellents such as anti-inflammatory agents, tetranactin, rodent repellents such as creosote oil, and insect repellents such as 2-4-diethyltoluamide. Liquid materials used to support these physiologically active substances in the pores include vegetable oils such as olive oil, salad oil, rapeseed oil, soybean oil, cottonseed oil, coconut oil, jojoba oil, and safflower oil, lanolin,
Animal fats and oils such as squalene, lard, and fish oil, alcohols and their derivatives such as ethyl alcohol, propylene glycol, polyethylene glycol, glycerin, and sorbitol, stearic acid, myristic acid, palmitic acid, oleic acid,
Higher fatty acids such as linoleic acid and sepacic acid and their derivatives, solvents such as dimethylformamide and dimethylacetamide, and waxes such as paraffin are used. The combination of the physiologically active substance and the liquid supporting the substance is determined depending on the solubility of the physiologically active substance, its affinity for the target substance, safety, etc. Although the content varies depending on the efficacy of the substance and the porosity of the membrane used, it is generally preferably 0.1 to 10% by weight. The water-swellable substance held in the pore together with these liquid substances and physiologically active substances swells with water supplied by various methods, increases in volume, and transfers the liquid substance containing the physiologically active substance in the pore to the pore surface. A material is selected that is extruded to provide a physiologically active substance on the surface of the member and has a water absorption rate of at least 500% by weight, preferably 1000% by weight, and more preferably 10000% by weight. Water-swellable substances used include acrylic acid/vinyl acetate copolymer, acrylic acid/vinyl acetate/ethylene terpolymer, three-dimensionally crosslinked acrylic acid/acrylamide copolymer, and acrylic acid added to starch. Graft products neutralized by graft polymerization, crosslinked polyvinyl alcohol, etc. are preferably used, but for example, polyacrylic salt calcium salt, carboxymethyl cellulose aluminum salt, etc. can also be used. Such active substance-containing liquid materials and membrane materials holding water-swellable materials include cellulose acetate, ethylene-borivinyl alcohol copolymer, polyacrylonitrile, fluorinated polyethylene sulfonated polystyrene, polyethylene, polypropylene,
Films made from materials such as polyvinyl alcohol and mainly composed of polyacrylonitrile, for example, are produced by dissolving a copolymer containing a large amount of polyacrylonitrile in a solvent to create a concentrated solution and casting it on the liner. It can be obtained by immersing it in a solvent to remove the solvent, and then drying it. Further, as for a film-like material mainly composed of polyethylene, a film made of phosphoronized polyethylene can be obtained by, for example, treating polyethylene with phosphorus trichloride and oxygen gas to convert it into chlorofluorinated fluorine and hydrolyze it. The material or manufacturing method of these membranes is arbitrary, but 95% or more of the pore diameters are 10μ or less, and the porosity is at least 30%, preferably 70% or more. . The combination of a film-like material and the physiologically active substance-containing liquid material is such that at least the film-like material contains a physiologically active substance and/or a physiologically active substance.
Alternatively, each is selected so that it will not be dissolved or highly swollen by the liquid. Then, for example, by applying a physiologically active substance-containing liquid material containing a water-swellable substance to the surface of the membrane-like material under reduced pressure, or by immersing the membrane-like material in a liquid bath, the physiologically active substance is added to the pores. A supply member can be made by filling a substance-containing liquid material. Alternatively, it can be produced by applying a solution of the water-swellable substance to a previously formed membrane to form a film on the inner wall of the pores, and then filling it with a liquid substance containing a physiologically active substance. The size of the supply member of the present invention depends on the degree of activity of the physiologically active substance and the desired physiologically active response, but is generally 1 to 100 cm ² . The supply member configured in this manner can be used for many purposes, such as treating diseased areas, administering drugs for the circulatory system, killing insects, repelling or preventing the breeding of harmful small animals, preserving wood, and preventing feeding damage by pests. I can do it. Therefore, those skilled in the art will understand that it is easy to develop applications by selecting various physiologically active substances. Examples of the present invention will be shown below. Example 1 An ethylene-polyvinyl alcohol copolymer film having a thickness of 60μ, an average pore diameter of 0.2μ, and a porosity of 120% is prepared. On the other hand, sodium acrylate vinyl acetate copolymer 1
After swelling g in 1000 ml of distilled water, heat at 130°C for 30 minutes to obtain a solution. Next, the solution is absorbed into the pores of the film and dried under 10 mgHg to form a sodium acrylate/vinyl acetate copolymer coating on the pore walls. Then, onto the film processed in this way, a liquid containing bioactive substances prepared by dissolving 1 g of erythromycin in 10 g of dimethylformamide was added to 0.1 g of the liquid.
ml is absorbed into the pores of a 9 cm ² film to make a device, and a 25 μm thick polyester film is attached to one side of the device to prepare the biologically active substance supplying member of the present invention. obtain. Example 2 An ethylene-polyvinyl alcohol copolymer film with a thickness of 150 μm, an average pore diameter of 3 μm, and a porosity of 100% is prepared, and an aluminum foil with a thickness of 10 μm is laminated on one side of the film. On the other hand, a fine powder of the grafted material obtained by craft polymerizing starch with acrylic acid and neutralizing it is pulverized into ultra-fine powder using a vibration mill, made into a suspension with cyclohexane, and incorporated under pressure from the non-amminium foil side of the film to form a film. Wipe the surface and dry under reduced pressure. Next, dissolve 1 g of erythromycin in 10 g of dimethylformamide, and add 0.1 g of this to 9 cm ² of film.
ml of a physiologically active substance-containing liquid material is adjusted and absorbed into the pores to obtain a physiologically active substance supplying member of the present invention. Table 1 shows the amount of excretion into urine after a specified time period measured by applying the feeding member of the present invention to Wistar rats.

[Table] The amount of excretion in Table 1 is based on a supply material of 9 cm ² .
It was applied using surgical adhesive tape to the hair removal area on the back of Wistar rats, and the amount excreted into the urine over time was measured. In the reference example in Table 1, 1 g of erythromycin was dissolved in 10 g of dimethylformamide, and this was applied directly to the hair-removed area (9 cm ² ) of a rat, and an adhesive polyvinyl chloride film was coated on top of this to remove urine. This is a measurement of excretion amount. In addition, a comparative example is the same as in Example 1, except that the sodium acrylate/vinyl acetate copolymer was not used, and a physiologically active substance-containing liquid material was directly absorbed into the pores.

[Brief explanation of the drawing]

FIG. 1 is a partially enlarged sectional view showing the implementation of this invention, and FIGS. 2 and 3 are sectional views showing other examples. DESCRIPTION OF SYMBOLS 11... Micropore, 12... Membrane-like material, 13... Wall surface of pore, 14... Coating made of water-swellable substance, 15... Liquid material (mixture) containing physiologically active substance, 2... Impermeable base material layer, 3... adhesive film.

Claims (1)

[Claims] 1. Constituent elements include a physiologically active substance retention layer and an impermeable base layer formed on one side of this layer, and the retention layer is a membrane having countless micropores. A physiologically active substance supplying member comprising a liquid substance supporting a physiologically active substance, a physiologically active substance, and a water-swellable substance. 2. The physiologically active substance supplying member according to claim 1, wherein the micropores have a pore diameter of 10 μm or less. 3. The physiologically active substance supplying member according to claim 1, wherein the water-swellable substance has a water absorption rate of at least 500% by weight. 4 Water-swellable substances include three-dimensional crosslinked products of sodium acrylate and vinyl acetate copolymer, sodium acrylate and vinyl acetate-ethylene terpolymer, sodium acrylate and acrylamide copolymer, and graft polymerization of acrylic acid to starch. The physiologically active substance supplying member according to claim 1, which is at least one member selected from the group of neutralized graft products and crosslinked polyvinyl alcohol.