Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/18—Applying electric currents by contact electrodes
  • A61N1/20—Applying electric currents by contact electrodes continuous direct currents
  • A61N1/30—Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis

Definitions

• the present invention relates to a method for administering iontophoresis of a water-soluble steroid. More specifically, a water-soluble steroid exhibiting excellent pharmacological effects in the treatment of rheumatoid arthritis, osteoarthritis, and the like can be obtained by using a pulse depolarized iontophoresis power supply and a conductor having a non-polarizable electrode and a non-polarizable electrode.
• the present invention relates to a method for administering iontophoresis of a water-soluble steroid, which is transdermally administered to a site of trouble such as a joint using a lead. Background art
• the absorption of a drug from the skin of a living body is more effective than oral administration, which is known as a general drug administration method, in that it maintains the blood concentration, reduces the side effects of the drug on the gastrointestinal tract, and further administers the drug. It is known to have a number of advantages such as simplicity. However, due to the low permeability of the skin of the living body, there are only a limited number of drugs capable of delivering an effective dose sufficient for a therapeutic effect in the living body. However, as research on percutaneous absorption preparations has progressed, preparations using chemical absorption enhancement methods have been put on the market.On the other hand, physical absorption enhancement methods using phonophoresis and iontophoresis have been developed. Percutaneous absorption of the drug is expected.
• iontophoresis is an administration method in which an ionized drug is absorbed from the skin by an electric current, and the above-mentioned advantages can be expected.
• USP No. 4 is an alternative to painful injections at the time of administration. No. 2,087,878, USP. No. 4,141,359, and USP. No. 3,991,755.
• DC-type current-carrying methods so safety and practicability such as electrical stimulation of the skin at the time of administration (when power is applied) and charging (or polarization potential) of the skin occur.
• Pulse-type iontophoresis devices have also been developed in addition to the DC-type iontophoresis devices described above. However, similar to the DC-type devices, electrical stimulus to skin frost and the like poses a problem. I have.
• water-soluble steroids having bioactivity are used as injections in various administration routes.
• This water-soluble steroid is obtained by esterifying fat-soluble steroids such as dexamethasone, betamethasone, and prednisolone with phosphoric acid or acetic acid to improve water solubility.
• this water-soluble steroid is administered intra-articularly in the treatment of rheumatoid arthritis and osteoarthritis.
• surface anesthesia such as lidocaine, etc. It may cause infectious disease, and is not a simple, safe and highly pharmaceutical useful and administration method.
• Japanese Patent Publication No. 2-45461 discloses a device for pulse depolarization type iontophoresis with little electrical stimulation to the skin. Using this technology, transdermal absorption of water-soluble steroids is performed. There has been no study on administration, and no disclosure or suggestion that a non-polarizable electrode such as silver / silver chloride is particularly effective for the electrode layer.
• these conventional configurations have the following problems. That is,
• synovium which is the site of inflammation such as osteoarthritis, and deep joints, such as the joint capsule consisting of the synovium and fibrous membrane, and were not effective for drug treatment.
• Water-soluble steroids are administered intra-articularly as injections for the treatment of rheumatoid arthritis, osteoarthritis, etc. Must be administered at an interval, and a hospital visit is required. Therefore, it is not always a simple and highly useful administration method for seeking a therapeutic effect.
• the present invention solves the above-mentioned conventional problems, and provides a water-soluble physiologically active steroid that is transdermally administered with high absorbability without electrical stimulus to the skin during administration.
• the present invention provides a method for administering iontophoresis of a water-soluble steroid having excellent safety and pharmacological effects, which is highly safe and has pharmacological effects.
• the purpose is to: Disclosure of the invention
• a method for iontophoresis administration of a water-soluble steroid according to the present invention has the following configuration. That is,
• a pulse depolarization type iontophoresis power supply device is used as the iontophoresis power supply device, and a non-polarizing electrode is used for the electrode layers of the inductor and the inductor. I have.
• the method for administering iontophoresis of a water-soluble steroid according to claim 2 is the method according to claim 1, wherein the pulse depolarization type iontophoresis power supply is configured to supply a current between the inductor and the non-inductor.
• the method for administering iontophoresis of a water-soluble steroid according to claim 3 is the method according to claim 1, wherein the non-polarizable electrode is made of silver, silver chloride, or the like. It has a configuration.
• the method for administering iontophoresis of a water-soluble steroid according to claim 4 is the method according to any one of claims 1 to 3, wherein the inductor is a non-polarizable electrode and a drug storage layer. And a configuration in which an ion-exchange membrane is provided between them.
• the method for administering iontophoresis of a water-soluble steroid wherein the water-soluble steroid is dexamethasone sodium phosphate, dexamethasone acetate, It has a composition consisting of dexamethasone metasulfobenzoate sodium, hydrocortisone sodium succinate, sodium hydrocortisone phosphate, predniblone sodium succinate, mesonadium sodium phosphate and the like, or a mixture thereof.
• the pulse depolarization type iontophoresis power supply includes A power supply unit that supplies a current z voltage between the electrode layers of the indifferent inductor, a pulse oscillator that pulse-modulates the current Z voltage output from the power supply unit, and a pulse voltage output from the pulse oscillator that is related to the rest of the pulse voltage And a switch portion for depolarizing the polarization potential between the element and the unrelated element are preferably used.
• the pause of the pulse voltage output from the pulse oscillator refers to the period excluding the pulse width in the pulse interval (or pulse period).
• a pulse depolarization type iontophoresis power supply is formed by integrating a conductor and a conductor, or separating a conductor and a conductor to separate the conductor and the conductor.
• the child may be connected by a connection cord or the like.
• Current value of the pulse depolarized type iontophoresis power supply is preferably 0. 0 l ⁇ lm AZcm 2, the output currents and skin although it depends on the contact area with the conductor and the non-conductor, it is approximately 0.5 to 18 V, preferably 3 to 9 V. Therefore, if necessary, a plurality of light-weight batteries, which will be described later, as a power supply unit may be provided or stacked, or a combination of chipped amplification elements may be used. Further, if necessary, a constant current element, a light emitting element for indicating conduction, or the like may be added.
• the pulse depolarization type iontophoresis power supply is used when the condition of the living body changes according to the dose of the water-soluble steroid or when the dose of the water-soluble steroid needs to be controlled according to the condition of the living body.
• a feed knock mechanism for automatically controlling the output current while monitoring the state of the living body may be provided.
• the power supply unit may be separated from the iontophoresis device and connected with a connection cord or the like, or may be integrated with the device.
• the pulse depolarization type iontophoresis power supply when used in combination with the inductor and the non-inductor, the manganese dry battery, the alkaline dry battery, the lithium battery, the tunicad battery, and the silver oxide are used as the power supply unit.
• a rechargeable battery, a sheet battery, or the like is preferably used.
• the pulse oscillator performs pulse modulation of the current and voltage from the power supply unit.
• the pulse generator may appropriately use a pulse voltage, such as a periodic pulse or an aperiodic pulse, depending on the dose of the water-soluble steroid, the state of the living body, and the like.
• the pulse oscillator may be provided with an output limiting circuit for limiting a large peak current flowing through the human body when the pulse voltage rises and falls.
• the switch removes the polarization potential (or polarization voltage) accumulated between the conductor and the non-conductor in the pause of the pulse voltage, that is, the skin or the like of the living body.
• a transistor switch such as an FET switch is preferably used as the switch unit.
• the guide wire includes a drug storage layer to which a water-soluble steroid is adhered, dispersed, or impregnated, an electrode layer electrically connected to a non-guide wire on the opposite side via skin or the like, A backing layer for supporting the electrode layer; and the non-inductive element includes a conductive layer, an electrode layer electrically connected to the counter electrode-side inductor, and a conductive layer or an electrode layer. And a support layer for supporting.
• the size of the backing layer and the like and the area of the drug storage layer and the like are determined so that an effective blood concentration set in advance when applied to a patient can be obtained for an effective time.
• a material that is impermeable to at least a water-soluble steroid is used as the backing layer and the support layer. This is to prevent leakage of the water-soluble steroid ⁇ additives and the like.
• the material include a woven fabric, a nonwoven fabric, a paper, a synthetic paper, or a composite thereof formed of a polymer film or sheet, or a film or fiber made of a natural fiber or a float, a synthetic resin, or a composite thereof. Laminated synthetic resin films are used.
• polyethylene polypropylene, polyethylene terephthalate, polyvinyl chloride, polyvinylidene chloride, plasticized vinyl acetate copolymer, plasticized vinyl acetate-vinyl chloride copolymer, and polyamide.
• Films or sheets made of synthetic resin such as cellulose, cellophane, cellulose acetate, ethyl cellulose and the like are used alone or in a multilayer structure. Further, as these synthetic resin films / sheets, it is possible to use a laminate of aluminum foil, aluminum vapor deposition or ceramic coating, or a laminate of these materials.
• the backing layer and the support layer may form a depression for holding the preparation if necessary.
• the backing layer—the shape of the support layer and the shape of the depression are not particularly limited, but are generally preferably formed in a circular, elliptical, or substantially rectangular shape.
• Electrode layer a non-polarizable material such as silver / silver chloride is preferable.
• An electrode protective layer made of a conductive material may be partially or entirely laminated between the electrode layer and the drug storage layer in order to prevent the influence of the water-soluble steroid depending on the type of the electrode layer. .
• the durability of the electrode layer can be improved.
• the electrode layers are preferably laminated so as not to come into direct contact with each other. This is because electrical stimulation can be further reduced.
• the formation of the electrode layer on the backing layer or the support layer may be performed by mixing the material with a printing ink for electric wiring or the like, coating and drying the material, or spreading and fixing the material, or depositing the material.
• a known method such as a method of forming the electrode layer by photoetching is used.
• ion exchange membrane As the ion exchange membrane, a cation exchange membrane is used when the drug ion is an anion, and an anion exchange membrane is used when the drug ion is a cation.
• Preferred ion-exchange membranes include Neocebu-Yu CMS (manufactured by Tokuyama Soda Co., Ltd.) for the cation-exchange membrane, and Neosep-Yu ACM (Made by Tokuyama Soda Co., Ltd.) for the anion-exchange membrane.
• the ion exchange membrane By using the ion exchange membrane, it is possible to prevent the permeation of the ion from the electrode material released from the electrode layer at the time of energization, and to remarkably improve the percutaneous absorption of the water-soluble steroid.
• the conductive layer is made of natural wood such as karaya gum, tragacanth gum, and xanthan gum. Fatty polysaccharides or polyvinyl alcohol and its partial genated products, polyvinyl formal, polyvinyl methyl ether and its copolymers, polyvinyl resins such as polyvinyl pyridine, polyvinyl methacrylate, polyacrylic acid and its sodium salt, polyacrylamide and its parts Various hydrophilic or natural resins, such as hydrolysates, partially saponified polyacrylates, and acrylic resins such as poly (acrylic acid-acrylamide), can be prepared by adding water, ethyl alcohol, ethylene diol, Flexible plasticized with polyhydric alcohols such as glycerin or a mixture thereof and used as a flexible film or sheet gel having self-retaining property and skin adhesiveness o
• the conductive layer is in the form of a flexible film or sheet and can adhere to the skin, so it has low skin contact resistance and is effective not only for percutaneous penetration of water-soluble steroids, but also for adhesive tapes and other materials. It also has an advantage in use that it can be adhered and supported without the need for a means for bonding the skin.
• a natural resin polysaccharide such as calayagum
• pH buffering property or skin protection property due to its natural polymer acid structure, remarkably high water retention, moderate skin adhesion, etc. Thus, more suitable suitability for skin is obtained.
• a required amount (usually about 1 to 15%) of an electrolyte such as sodium chloride, sodium carbonate, or potassium citrate may be added to impart sufficient conductivity.
• an electrolyte such as sodium chloride, sodium carbonate, or potassium citrate
• the composition of these conductive layers is mainly determined by electrochemical considerations such as the type and required dosage of the water-soluble steroid used, the application time of application, the output of the battery used, and the skin contact area. The ion mobility or conductivity is appropriately determined so as to be a required value.
• the material for forming the drug storage layer is a polymer film or sheet to which water-soluble steroids can be attached, dispersed or impregnated.L is made of natural fibers, felts, synthetic resin films and fibers, etc. The formed woven or nonwoven fabric is used. As these materials, widely known water-soluble polymer materials, hydrophilic synthetic polymer materials, hydrophobic polymer materials, natural materials, and composites thereof are used.
• Films made of synthetic resins such as polyethylene, polypropylene, polyethylene terephthalate, polyvinyl chloride, polyvinylidene chloride, plasticized vinyl acetate copolymer, plasticized vinyl acetate-vinyl chloride copolymer, polyamide, cellophane, cellulose acetate, and ethyl cellulose.
• a sheet or an ion exchange resin membrane or the like is used alone or in a multilayer structure.
• a conventionally known plasticizer may be used by mixing a softener.
• paper materials such as water-absorbing paper, cloth materials such as gauze, fiber materials such as absorbent cotton, synthetic resin continuous foam such as sponge, water-absorbing resin or porous material, etc. It is also possible to enclose the member.
• water-soluble steroids examples include dexamethasone sodium phosphate, dexamethasone acetate, dexamethasone sodium metasulfobenzoate, hydrocortisone sodium succinate, sodium hydrocortisone phosphate, sodium blednibron succinate, and sodium metazone sodium phosphate. It can be used but is not limited to these.
• a reservoir type, a matrix type, or the like can be used as the shape of the iontophoresis device containing the water-soluble steroid.
• an aqueous solution storage layer for storing an aqueous solution may be provided adjacent to a backing layer or a support layer, an electrode layer, a drug storage layer, or a conductive layer of a reservoir-type preparation or a matrix-type preparation.
• the aqueous solution storage layer include paper materials such as water-absorbing paper, cloth materials such as gauze, fiber materials such as a degreased surface, synthetic resin continuous foam such as sponge, water-absorbing resin or
• a water-absorbing member for impregnating a chemical such as a porous material, a nonwoven fabric, and the like.
• the amount of water-soluble steroids contained or deposited in the drug reservoir is determined so that when applied to a patient, a preset, effective blood concentration is obtained for an effective time.
• an electrolyte such as sodium chloride, sodium carbonate, potassium citrate or the like in order to impart sufficient conductivity.
• additives include solvents such as water and ethanol as required, emulsifiers such as phosphazidonic acid derivatives, lecithin, cephaline, and polyalkylene glycol, methyl laurate, methyl carboxylate, aison, and oleic acid.
• solvents such as water and ethanol as required
• emulsifiers such as phosphazidonic acid derivatives, lecithin, cephaline, and polyalkylene glycol, methyl laurate, methyl carboxylate, aison, and oleic acid.
• Pyrothiodecane 1 Clotamiton
• an absorption enhancer such as menthol, limonene, and heart oil
• Ethylene glycol diethylene glycol, triethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, dimethyl sulfoxide, dimethylformamide, dimethylacetamide, dimethylperylamide, isosorbitol, olive oil, castor oil, squalene , Lanolin and other solubilizers or solubilizers, as well as thickeners such as cellulose acetate, methylcellulose, hydroxymethylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose and stearyl alcohol, glycerin monooleic acid, glycerin mono.
• Irritation reducing agents such as laurate, sorbitan monolaurate, karaya gum, tragacanth gum, polyvinyl alcohol and That portion Gen product, dextran, albumin, polyamino acids, poly Binirupirori pyrrolidone, It is also possible to add hydrophilic and water-absorbing polymers such as poly (meth) acrylate, polyacrylic acid and its sodium salt, polyacrylamide and its partial hydrolyzate, and plasticizers such as glycerin.
• hydrophilic and water-absorbing polymers such as poly (meth) acrylate, polyacrylic acid and its sodium salt, polyacrylamide and its partial hydrolyzate, and plasticizers such as glycerin.
• additives are determined for each type of water-soluble steroid to the extent that the type and concentration appear to be optimal, as long as they are therapeutically beneficial and pharmacologically acceptable.
• the drug storage layer or the conductive layer may have an adhesive layer on its surface.
• a pressure-sensitive adhesive or a gel adhesive is suitably used as the adhesive layer.
• the pressure-sensitive adhesive or gel adhesive can hold a device for iontophoresis or a conductor or an inducible conductor on the patient's skin, and is not limited as long as it is perceptually acceptable.
• acrylic adhesives such as poly (2-ethylhexyl acrylate), methacrylic adhesives such as polybutyl methacrylate, and silicone adhesives such as polydimethyl siloxane.
• Polyisoprene rubber Polybutylene rubber, polybutadiene rubber, rubber-based adhesives such as natural rubber, polyvinyl alcohol, gelatin, polyvinylpyrrolidone, carboxyvinyl polymer, sodium polyacrylate, and cross-linked products thereof And sodium alginate and its crosslinked products, cellulose derivatives and the like.
• the adhesive layer may be added with a required amount (usually about 15%) of an electrolyte such as sodium chloride, sodium carbonate, potassium citrate or the like in order to impart sufficient conductivity thereto.
• the adhesive layer may be provided with a hole for allowing the passage of ionized water-soluble steroids from the drug storage layer, if necessary.
• the shape of the pressure-sensitive adhesive layer and the holes formed in the pressure-sensitive adhesive layer is not particularly limited, but is generally formed in a circular shape, an elliptical shape, a substantially rectangular shape, or the like. desirable.
• the pulsed depolarization type iontophoresis power supply and the inductor or non-inductor having a non-polarizing electrode are used for the method of administering the water-soluble steroid, so that the water-soluble steroid can be removed from the skin.
• the body especially rheumatoid arthritis and osteoarthritis It is possible to highly absorb a therapeutically effective amount of a drug sufficient for a therapeutic effect up to the deep part of the joint where an inflammation site such as a symptom or a joint capsule is present.
• it can suppress electrical stimulation and electrification on the skin during administration.
• an ion exchange membrane is provided, the adverse effect of ions of the electrode material can be prevented, and the transport number of the water-soluble steroid can be significantly increased.
• FIG. 1 is a block circuit diagram showing a device for pulse depolarization type iontophoresis used in a method for administering iontophoresis of a water-soluble steroid in a first embodiment of the present invention.
• FIG. 2 (a) is a perspective view showing the guide element.
• FIG. 2 (b) is a perspective view showing an unrelated inductor.
• FIG. 3 is an exploded perspective view showing a conductor for an electrical stimulation test.
• FIG. 4 is an exploded perspective view showing an unrelated inductor for an electrical stimulation test.
• FIG. 5 is a schematic view showing a mounted state of a conductor and an open conductor for an electrical stimulation test.
• FIG. 6 is a characteristic diagram showing a current value at which an electric stimulus is sensed.
• FIG. 7 (a) is an exploded perspective view showing a 2-chamber-diffusion cell for a permeation experiment.
• FIG. 7 (b) is a sectional view showing a 2-chamber-diffusion cell for a permeation experiment.
• FIG. 8 is a characteristic diagram showing the accumulated permeation amount of the steroid after 6 hours.
• Fig. 9 is a characteristic diagram showing the concentration of dexamethasone sodium phosphate in the joint capsule.
• Fig. 10 is a characteristic diagram showing the increase and decrease of the joint circumference based on the joint circumference on the 11th day.
• FIG. 1 is a block diagram showing a block diagram of a device for pulse depolarization iontophoresis used in a method for administering iontophoresis of a water-soluble steroid according to a first embodiment of the present invention.
• 1 is a device for pulse depolarization type iontophoresis
• 2 is a conductor containing water-soluble steroid
• 3 is a non-inductor
• 4 is a power supply unit 5, a pulse oscillator 6, and a switch unit 7 described later.
• 5 is a power supply such as a dry battery for applying a current Z voltage between each electrode layer of the inductor 2 and the non-inductor 3
• 6 is supplied from the power supply 5
• 7 is a pulse oscillator that is output from the pulse oscillator 6, and at the same time the pulse voltage is paused.
• a switch part for depolarizing the polarization potential of the unrelated inductor 3 8 is an administration site such as a joint, and 9 and 10 are connection terminals such as jacks.
• FIG. 2 (a) is a perspective view showing the inductor
• FIG. 2 (b) is a perspective view showing the non-inductor.
• 2a is a lead wire connected to an electrode layer 2c to be described later
• 2b is a backing layer made of a polyolefin film such as polyester or polyethylene
• 2c is a backing layer 2b.
• An electrode layer formed of silver chloride or the like on one side of the electrode, 2 d is laminated on the electrode layer 2 c and has a slightly larger diameter than the electrode layer 2 c and contains sodium alginate or polyvinyl alcohol containing a water-soluble steroid as a drug.
• a drug storage layer composed of chitin and the like.
• 3a is a lead wire connected to an electrode layer 3c described later
• 3b is a support layer made of a film / sheet of a polyolefin such as polyester or polyethylene
• 3c is a support layer.
• 3b is an electrode layer formed by evaporating silver etc. on one surface
• 3d is a conductive layer formed on the electrode layer 3c and having a diameter slightly larger than the electrode layer 3c Layer.
• the device for pulse depolarization iontophoresis configured as described above, that is, a pulse depolarization type iontophoresis power supply, and a conductor and a non-conductor associated with a non-polarizable electrode
• the method of iontophoresis administration of the water-soluble steroid used will be described based on an example applied to a human joint.
• the inductor 2 and the non-inductor 3 are attached to the administration site 8. Since the drug storage layer 2 d and the conductive layer 3 d are made of a flexible material, the administration site 8 can be brought into close contact with a relatively uneven portion such as a joint without falling.
• the main power supply of the pulse depolarization type iontophoresis power supply 1 is turned on.
• the frequency of the pulse oscillator 6 and the output time of the pulse voltage are adjusted, and the designed dose is administered.
• the administration is terminated after a lapse of a predetermined administration time or the like.
• the switch of the pulse depolarization type iontophoresis power supply 1 is turned off, and the treatment is completed by separating the guide 2 and the guide 3 from the administration site.
• the switch section 7 is automatically turned on and off upon detecting the falling Z rise of the pulse voltage output from the pulse generator 6, and is not related to the inductor 2 when the switch section 7 is turned on.
• the designed amount of the water-soluble steroid was produced without electrical stimulation or electrification at the administration site during the administration period. It can be administered smoothly to the body, for example, to the deep joints where the synovium and the joint capsule composed of the synovium and the fibrous membrane are present. Performance comparison tests were performed on the pulse depolarization type iontophoresis device and the conventional iontophoresis device configured as described above. Hereinafter, the results will be described.
• FIG. 3 is an exploded perspective view showing a conductor for an electrical stimulus test
• FIG. 4 is an exploded perspective view showing an unrelated conductor for an electrical stimulus test
• FIG. 5 is an electrical stimulus.
• FIG. 3 is a schematic view showing a state where a test inductor and an unrelated inductor are attached.
• a polyethylene terephthalate (PET) film 2b ' was prepared as a backing layer.
• silver chloride was applied to one surface of the backing layer (or PET film) 2b 'to form an electrode layer 2c'.
• a nonwoven fabric 2d ' was laminated as a drug storage layer on the upper surface of the electrode layer (or silver chloride) 2c'.
• an acryl-based adhesive 2e ' is attached as an adhesive layer on the upper surface of the drug storage layer (or non-woven fabric) 2d' as an adhesive layer, and the backing layer 2b ', the electrode layer 2c', and the drug The storage layer 2d 'and the adhesive layer 2e' were fixed.
• the drug storage layer 2 d ′ was impregnated with the aqueous solution lml through the pores of the adhesive layer 2 e ′, to prepare a guide 2 ′.
• a PET film 3b ′ was prepared as a support layer.
• silver was applied to one surface of the support layer (or PET film) 3b 'to form an electrode layer 3c'.
• an acrylic pressure-sensitive adhesive 3e ' is adhered in a 0-ring shape as a binding layer on the upper surface of the electrode layer (or silver) 3c', and is adhered to the support layer 3b 'and the electrode layer 3c'.
• Layer 3e ' was fixed.
• an aqueous solution of polyvinyl alcohol (PVA) containing 0.9% of sodium chloride was stored in the pores of the adhesive layer 3e ', and these were frozen at 130 ° C to gel the PVA.
• Insulator 3 ' was created.
• the lead wires 2a 'and 3a' were connected to the respective electrode layers 2c 'and 3c' of the prepared inductor 2 'and non-inductor 3', respectively.
• FIG. 6 is a characteristic diagram showing a current value at which an electric stimulus is sensed.
• FIG. 7 (a) is an exploded perspective view showing a 2-chamber-diffusion cell for a permeation experiment
• FIG. 7 (b) is a cross-sectional view showing a 2-chamber-diffusion cell for a permeation experiment.
• the cell 14a on the side of the inductor 2 is filled with dexamethasone sodium phosphate at 1 Omg Zm1, and the cell 14b on the side of the inductor 3 is filled with saline. did.
• unrelated inductor 3 The physiological saline in the cell 14 b on the side was stirred with a stirrer 16.
• FIG. 8 is a characteristic diagram showing the accumulated permeation amount of stelloid after 6 hours.
• a pulsed depolarizing iontophoresis power supply and a lead / insensitive lead having a nonpolarizable electrode layer of silver / silver chloride were used on the isolated skin of the human.
• mA was supplied and 1 O mg Zm 1 of dexamethasone sodium phosphate was permeated, about 40 ⁇ g Zcm 2 of dexamethasone sodium phosphate was transmitted by 6 hours.
• Comparative Example 3 a pulsed depolarized iontophoresis power supply and a conductor having a nonpolarizable electrode layer of silver Z silver chloride and a non-polarized electrode layer were used for 3 m on the human skin.
• Egret Japanese white rabbit was anesthetized with pentobarbital.
• a cylindrical cell having a diameter of 1 cm and fitted with a guide having a silver chloride electrode layer as shown in Fig. 7 (a) was set outside the right rear knee of the egret.
• a conductive layer of PVA gel containing 0.9% of sodium chloride and a silver electrode layer as shown in Fig. 2 (b) were superimposed on the inside of the right knee of the rear of the egret.
• the lead was set.
• the inductor side was used as the anode
• the non-inductor side was used as the cathode.
• the cylindrical cell is filled with radiolabeled dexamethasone sodium phosphate (3 O mg / m 1, 33 33 / C i / m 1) and linked to a pulse depolarization type iontophoresis power supply. After connecting the probe and the unrelated probe, 3 mA was supplied. Two hours later, the egret was exsanguinated and killed. The joint capsule was taken out from the joint of the hind right foot knee, weighed, burned with an oxidizer, and the radioactivity was measured. The results are shown in FIG. FIG. 9 is a characteristic diagram showing the concentration of dexamethasone sodium phosphate in the joint capsule.
• FIG. 7 (a) A non-inductive element in which a conductive layer of a PVA gel containing sodium chloride and a silver electrode layer were superimposed as shown in FIG. 2 (b) was set inside the knee of the rear right foot.
• the side of the conductor was the anode
• the side of the non-conductor was the cathode.
• FIG. 10 is a characteristic diagram showing the increase and decrease of the joint circumference based on the joint circumference on the 11th day.
• a water-soluble steroid having bioactivity is efficiently used in a living body, particularly in a synovial membrane or a joint capsule comprising the synovial membrane and fibrous membrane. It can be absorbed in a large amount, and the electrical stimulation and electrification at the administration site such as the skin can be extremely low, and a clinically excellent method of administering iontophoresis of a water-soluble steroid can be realized. Things.
• the method for administering iontophoresis of a water-soluble steroid of the present invention having such excellent effects can be applied to a site of administration in a living body and applied with a voltage so that the desired excellent effects can be exhibited without any effect. Very useful in industry.

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• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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• 1995
  • 1995-08-21 JP JP08512468A patent/JP3119488B2/ja not_active Expired - Fee Related
  • 1995-08-21 WO PCT/JP1995/001652 patent/WO1996011034A2/fr active Application Filing
  • 1995-08-21 AU AU32313/95A patent/AU3231395A/en not_active Abandoned

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