JP2007260275A - Iontophoresis device and composition for iontophoresis administration - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an iontophoresis device and a composition for iontophoresis administration which can be stored for a long period of time while preventing the lowering of transporting efficiency of a drug to be originally transported even when e.g. epinephrine is used. <P>SOLUTION: The iontophoresis device 10 is constituted of a DC power source 12, an action side electrode structure 20 connected to the anode of the DC power source, and a nonaction side electrode structure 40 connected to the cathode, and administers a drug held in the action side electrode structure 20 to a living body by the voltage from the DC power source 12, cysteine hydrochloride as an antioxidant the drug is held in the action side electrode structure 20 being mixed with the drug. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to the technical field of iontophoresis in which a drug is introduced into a living body non-invasively using an electric driving force.

  Conventionally, anesthetics have been used for the purpose of avoiding or relieving pain when performing treatments such as surgery and injection on living organisms such as animals and human bodies. Anesthesia is roughly classified into general anesthesia and local anesthesia. In recent years, local anesthesia is often desired from the viewpoint of the burden on the body of a patient and the ease of treatment.

  A wide range of drug administration methods including anesthetics are generally administered by injection, orally, or applied (sprayed) to the skin surface. However, in the case of local anesthetics, it is difficult to apply anesthesia to the extent necessary only for the intended local area by mouth, and even when applied (sprayed), the drug is sufficient due to the presence of skin, etc. Does not penetrate. Therefore, it is often administered locally by injection, but naturally there is a problem that the patient is painful.

  In order to solve this problem, as shown in Patent Document 1 and Patent Document 2 below, a drug such as an anesthetic is applied non-invasively from the surface of the living body (skin, mucous membrane, etc.) using an electric driving force. A method and apparatus for locally administering the drug, and a composition for administration have been proposed.

  Patent Document 1 includes, for example, “electrically assisted transcutaneous containing about 1 to 10% lidocaine, about 0.01 to 0.2% epinephrine, and one or more antioxidants or metal chelating agents. On the other hand, Patent Document 2 discloses, for example, “anode assembly having a first electrode and a donor hydrolyzer containing epinephrine electrically connected to the first electrode”. A sealed electrode assembly for an electrically assisted drug delivery device comprising a gel, wherein the sealed anode assembly is physically, chemically, electrically at 25 ° C for at least 12 months Such an assembly is disclosed which is electrochemically, microbially stable.

JP-T-2001-505197 JP 2005-319288 A

  As described in both of the above-mentioned documents, epinephrine is often administered simultaneously when an anesthetic such as lidocaine is administered. This is to prevent the anesthetic agent administered into the living body from diffusing from the local area due to blood flow due to the vasoconstrictive action of epinephrine. The purpose is to demonstrate.

  This epinephrine substance is rapidly decomposed in the presence of oxygen due to its characteristics, and thus cannot be stored for a long time. In order to improve this point, both Patent Document 1 and Patent Document 2 described above employ sodium sulfite (sodium pyrosulfite (sodium metabisulfite), sodium bisulfite, sodium sulfite, etc.) as an antioxidant for epinephrine. Mixing.

  Certainly, by mixing sodium sulfite, the effect of preventing oxidation of epinephrine to some extent by the reducing power of sodium sulfite is recognized. However, this idea does not fully consider the demerit when applied to an iontophoresis device that attempts to transport a drug (drug ion) into a living body by using an electric driving force.

  In iontophoresis, a drug in an ionic state is driven by electricity having the same polarity as that of the ion to transport the drug into the living body. For example, since lidocaine as an anesthetic becomes a cation when ionized, the working electrode structure holding the lidocaine ion is connected to the anode of the power source and driven. At this time, the purpose of the iontophoresis device is to efficiently transport a predetermined drug into the living body, not to transport an antioxidant of the drug into the living body. However, as long as the components of the antioxidant are ionized, the electric driving force is also consumed for the ions derived from the antioxidant, and the transport efficiency of the drug that is the original transport target decreases accordingly. End up. In particular, the amount of ion movement that is electrically driven is substantially proportional to the electric charge and inversely proportional to the molecular weight. Therefore, when sodium sulfite is easily used as an antioxidant, it is derived from the sodium sulfite. The monovalent sodium ion (molecular weight 23) is also efficiently transported relative to the monovalent lidocaine ion (molecular weight 230). This is nothing but a decrease in the transport efficiency of lidocaine ions, which is the original transport target.

  The present invention has been made in order to solve such problems, and even if epinephrine that is easily oxidized is used as a drug, for example, while preventing a decrease in the transport efficiency of the drug that is the original transport target. An iontophoresis device that can be stored for a long period of time and a composition for its administration are provided.

  As will be described in detail in the following embodiments, the DC power source, the working electrode structure connected to the anode of the DC power source, and the non-working electrode structure connected to the cathode, the function An iontophoresis device for administering a drug held in a side electrode structure to a living body by a voltage from the DC power source, wherein the working side electrode structure has hydrochloric acid as an antioxidant for the drug. The above-mentioned problem is solved by configuring the iontophoresis device so that cysteine is mixed and held with the drug.

  The molecular weight of the cation (cysteine ion) when cysteine hydrochloride is ionically dissociated is 180. This figure is relatively close to the molecular weight 230 of lidocaine ion compared to the molecular weight 23 of sodium ion. That is, even if cysteine ions are present, the reduction in lidocaine ion transport efficiency can be minimized. In addition, cysteine hydrochloride has an excellent reducing power as compared with conventionally used sodium sulfite (see experimental results) and has superior characteristics as an antioxidant.

  In addition to the above configuration, the drug may be configured as epinephrine. With such a configuration, even if epinephrine that is easily oxidized is present, it can be stored for a long period of time.

  In addition to the above-described configuration, the drug may further include lidocaine. With such a configuration, the use of the apparatus can exert the effect of lidocaine as an anesthetic locally for a long time by epinephrine, and further, long-term storage even when using epinephrine that is easily oxidized. Is possible.

  The present invention also provides an iontophoretic composition containing epinephrine that functions as a vasoconstrictor and cysteine hydrochloride that functions as an antioxidant for the epinephrine. Even when cysteine hydrochloride is dissociated into ions, the molecular weight of cysteine ions, which are cations thereof, is 180. This value is relatively very large compared to the molecular weight 23 of sodium ions. That is, even if cysteine ions are present, the decrease in drug transport efficiency can be suppressed to a very small extent. In addition, cysteine hydrochloride has an excellent reducing power as compared with conventionally used sodium sulfite and has superior characteristics as an antioxidant. Thus, the composition can be stored for a long period of time without reducing the transport efficiency of the drug administered by iontophoresis.

  Further, in addition to the above-described configuration, it may be configured as an iontophoretic administration composition containing lidocaine that functions as an anesthetic. If comprised in this way, the effect as an anesthetic agent of lidocaine can be exhibited locally for a long time by epinephrine, and also long-term preservation | save becomes possible even if it uses the epinephrine which is easy to oxidize.

  According to the present invention, the usable period of a drug containing epinephrine can be prolonged. In addition, when a drug is administered in vivo by iontophoresis, it is possible to prevent a decrease in drug transport efficiency.

  Hereinafter, an example of an embodiment of the present invention will be described in detail with reference to the accompanying drawings.

  First, a device to which the present invention is applied will be described, and an experimental result of cysteine hydrochloride and sodium sulfite as an antioxidant will be shown and described.

<Description of device example>
This will be described with reference to FIGS.

  The iontophoresis device 10 includes a DC power source 12, a working electrode structure 20 connected to the anode of the DC power source 12, and a non-working electrode structure 40 connected to the cathode. Lidocaine ions held in the electrode structure 20 are administered to a living body by a voltage from the DC power supply 12. In this embodiment, explanation is given by taking lidocaine as an anesthetic as an example, but the drug is not limited to lidocaine.

  In the iontophoresis device 10, the working electrode structure 20 and the non-working electrode structure 40 are configured such that a proximal support 14, an intermediate support 16, and a distal support 18 are stacked.

  The intermediate support 16 is obtained by forming the working-side intermediate support 21 and the non-working-side intermediate support 41 into a single continuous sheet-like member.

  Similarly, the tip support 18 is a continuous sheet-like material made up of the working tip support 22 and the non-working tip support 42.

  The working electrode structure 20 includes a proximal support 14, a working electrode 24 connected to the anode of the DC power source 12, and a drug solution holding the administration composition that is disposed in front of the working electrode 24. The part 30 and the working side biological contact layer 32, which is disposed on the front surface of the drug solution holding part 30 and is impregnated with a non-woven fabric, is laminated in this order.

  The working side electrode 24 is connected to the DC power source 12 and has a working side current collector 24A made of carbon formed by printing on the front surface of the base end support 14, and an electric current on the front side of the working side current collector 24A. And a working-side polarizable electrode 24B arranged in a connected manner.

  The working side intermediate support 21 is made of a resin material having a thickness substantially equal to that of the working side polarizable electrode 24B, and has a working side intermediate through hole 21A having substantially the same shape as the planar shape of the working side polarizable electrode 24B. The working side polarizable electrode 24B is accommodated in the working side intermediate through hole 21A.

  Further, the working side tip support 22 is made of a resin material having a thickness substantially equal to that of the chemical solution holding part 30, and has a working side tip through-hole 22A having substantially the same shape as the planar shape of the working side polarizable electrode 24B. The chemical solution holding unit 30 is accommodated in the working side distal end through hole 22A.

  The non-working side electrode structure 40 includes a non-working side electrode 44 connected to the cathode of the DC power source 12 from the base support 14 side, and an electrolysis that holds an electrolytic solution on the front side of the non-working side electrode 44. A liquid holding part 48, an ion selective membrane 50 that selectively allows anions to pass through, and a non-working-side biological contact layer formed by applying the same electrolytic solution as the electrolytic solution held in the electrolytic solution holding part 48 52 are laminated in this order.

  The non-working side electrode 44 includes a base end support 14, a non-working side current collector 44 </ b> A made of carbon printed away from the current collector 24 </ b> A of the working side electrode 24, and the non-working side current collector 44 </ b> A. The non-working-side polarizable electrode 44B is provided in electrical connection with.

  The non-working-side intermediate support 41 is made of a resin material having a thickness equal to that of the non-working-side polarizable electrode 44B, and is formed with a non-working-side intermediate through-hole 41A having a size for accommodating the non-working-side polarizable electrode 44B. Has been. Further, the non-working-side tip support 42 is formed with a non-working-side tip through-hole 42A made of a resin material having the same thickness as the electrolyte solution holding part 48 and having a size for accommodating the electrolyte solution holding part 48. ing.

  In this embodiment, the four through holes 22A, 21A, 41A, and 42A are all circular, and the working electrode 24, the drug solution holding unit 30, and the biological contact layer 32 are also circular membranes or sheets. ing.

  Similarly, the non-working side electrode 44, the electrolyte solution holding unit 48, the ion selective membrane 50, and the non-working side biological contact layer 52 are also formed into a circular membrane or a sheet shape.

  The living body contact layer 32 is made larger than the working tip through-hole 22A of the outer diameter, and held by the adhesive of the tip support 18 at the outer peripheral edge of the working tip through-hole 22A at the circular outer peripheral edge. The chemical solution holding part 30 accommodated in the working side distal end through hole 22A is supported so as not to drop downward in FIG.

  The working side current collector 24A in the working side electrode 24 and the non-working side current collector 44A in the non-working side electrode 44 are printed on the proximal support 14 as shown in FIGS. The working side conducting wire 19A and the non-working side conducting wire 19B made of a provided metal film are connected to each other. These working-side conducting wire 19A and non-working-side conducting wire 19B are connected to the DC power source 12 via a connector 19C at their tips.

  Further, the connection portions of the working side current collector 24A and the non-working side current collector 44A of the working side conducting wire 19A and the non-working side conducting wire 19B are shown in an enlarged manner in FIG. The working current collectors 24 </ b> A and 44 </ b> A are in contact with and connected to the tapered surfaces 25 and 45.

  In this embodiment, as shown in FIGS. 1 and 4, circular members are arranged in the thickness direction in each of the working electrode structure 20 and the non-working electrode structure 40, and FIG. The iontophoresis device 10 is integrally formed as shown in FIG.

  Here, the working side and non-working side intermediate through holes 21A, 41A of the working side and non-working side intermediate supports 21, 41 accommodate the working side polarizable electrode 24B and the non-working side polarizable electrode 44B, respectively. In the state, it is sandwiched by other members from above and below, and similarly, the working solution and non-working side tip through-holes 22A and 42A in the working side and non-working side tip support bodies 22 and 42 are also filled with the chemical solution holding unit 30 and electrolysis. In a state where the liquid holding portions 48 are respectively stored, the liquid holding portions 48 are sandwiched by other members from above and below, and further, between the proximal support 14 and the intermediate support 16 and between the intermediate support 16 and the biological contact layer 32. These members are sandwiched between them and positioned and fixed.

  The outer diameters of the working side current collector 24A and the non-working side current collector 44A in the working side electrode 24 and the non-working side electrode 44 are slightly smaller than the diameters of the working side and non-working side intermediate through holes 21A and 41A. Each of the side polarizable electrode 24B and the non-working side polarizable electrode 44B can be pressed.

  Reference numeral 56 in FIG. 4 indicates an adhesive, which is an intermediate portion between the working side and non-working side current collectors 24A and 44A in the resin sheet 36, and the working side and non-working in the intermediate support 16. It adheres to a portion between the working side intermediate through-holes 21A and 41A to isolate the working side and non-working side electrodes 24 and 44 from each other.

  Further, reference numeral 58 in FIG. 1 denotes a release liner that is detachably attached to the distal end support 18 covering the working side biocontact layer 32 and the non-working side biocontact layer 52.

  Both the working side polarizable electrode 24B in the working side electrode 24 and the non-working side polarizable electrode 44B in the non-working side electrode 44 are mainly made of a conductive base material formed of activated carbon, preferably carbon fiber or carbon fiber paper. Configured as an ingredient. When only the activated carbon fiber is used as the working side and non-working side polarizable electrodes 24B and 44B, a cloth and felt made of activated carbon fiber may be combined. In this case, it is preferable to impart viscosity to the electrolytic solution and impregnate the activated carbon fiber.

For example, a layer in which activated carbon is dispersed in a binder polymer may be laminated on the conductive substrate. The activated carbon may have a specific surface area of 10 m ² / g or more.

  In this embodiment, the working side polarizable electrode 24B is impregnated with a liquid containing lidocaine, and the non-working side polarizable electrode 44B is the same as the electrolyte retained in the electrode side electrolyte retaining part 46. The liquid containing the electrolytic solution is impregnated.

  Both the working current collector 24A in the working electrode 24 and the non-working side current collector 44A in the non-working side electrode 44 are obtained by printing a PET (polyethylene terephthalate) material mixed with carbon and an adhesive. It is a printed electrode.

  In addition to the carbon described above, a conductive metal such as gold, platinum, silver, copper, or zinc may be used as the material for the printed electrode. In addition, a conductive material itself such as carbon or gold may be used as the current collector without printing.

  The electrolyte solution impregnated in the non-working side polarizable electrode 44B has an electrolyte as a main component, and this electrolyte is an electrolyte that is more easily reduced than the water electrolysis, such as lactic acid, oxalic acid, malic acid, succinic acid, fumaric acid. It is particularly preferable to use an organic acid such as a salt thereof and / or a salt thereof, whereby it is possible to suppress generation of hydrogen gas, and a plurality of combinations of combinations that become buffer electrolytes when dissolved in a solvent. By blending the electrolyte, it is possible to suppress a change in pH during energization.

  The drug solution holding unit 30 is obtained by impregnating a PP (polypropylene) non-woven fabric with a liquid containing a composition for administration whose main component is lidocaine. Further, the medicinal component dissociates into cations in the administration composition impregnated in the drug solution holding unit 30 when dissolved in a solvent such as water. The component of the chemical solution contained in the chemical solution holding unit 30 is mainly lidocaine hydrochloride. However, not only lidocaine hydrochloride is dissolved in a solvent such as water but also other substances for assisting the medicinal effect of lidocaine hydrochloride. These drugs and antioxidants are also included. The composition for administration in the present embodiment includes, for example, lidocaine hydrochloride 10.00% (weight percent, the same applies hereinafter) as an anesthetic, epinephrine 0.10% as a vasoconstrictor, and cysteine hydrochloride as an antioxidant. The composition is 0.10%, glycerin 10%, citric acid 0.02%, 0.1% paraben solution 79.78%.

  The biological contact layer 32 is configured by impregnating a PP nonwoven fabric with the same liquid as that impregnated in the chemical solution holding unit 30. In this case, the electrolyte solution holding part 48 in the non-working side electrode structure 40 is obtained by impregnating the PP non-woven fabric with the same liquid as the non-working side polarizable electrode 44B.

  In addition, the liquid containing the drug or the electrolytic solution shown above is chemically obtained by, for example, water (ion exchange water), hydroxypropyl cellulose (HPC, for example, H-Type of Nippon Soda), or cellulose insoluble in water. A viscous material such as Metroise (for example, 90SH-10000SR manufactured by Shin-Etsu Chemical Co., Ltd.) that has been treated to form a water-soluble polymer may be mixed to produce a viscous material.

  The ion selective membrane 50 is an ion exchange membrane having a function of selectively allowing anion to pass through. For example, Neocepta AM-1, AM-3, AMX, AHA, AMH, ACS, etc. manufactured by Tokuyama Corporation. An anion exchange membrane can be used without particular limitation. Further, an anion exchange membrane of a type in which an anion exchange resin is polymerized in part or all of the pores of a porous film made of a polyolefin resin, a vinyl chloride resin, a fluorine resin, a polyamide resin, or a polyimide resin is particularly preferably used. be able to. In this case, the anion exchange resin is filled after impregnating the pores of the porous film with a solution in which a polymerization initiator is blended with a crosslinking monomer such as styrene-divinylbenzene or chloromethylstyrene-divinylbenzene. The polymerization can be carried out by introducing an anion exchange group such as a primary to tertiary amino group, quaternary ammonium group, pyridyl group, imidazole group, quaternary pyridinium group, or quaternary imidazolium group into the polymer.

  When the iontophoresis device 10 is assembled, in the state shown in FIG. 1 or 4, the constituent members are housed and stacked in the through holes of the intermediate support 16 and the distal support 18, and the proximal support 14, The intermediate support 16 and the tip support 18 are bonded and fixed, and the release contactor 58 covers the living body contact layer 32 and the non-working living body contact layer 52 and attaches to the tip support 18 to complete the assembly. To do.

  Since the intermediate support 16 and the base support 14 are not in close contact with each other at the resin sheet 36, the polarizable electrodes 24B and 44B of the working electrode 24 and the non-working electrode 44 are electrically connected by the drug or the electrolyte. However, in this embodiment, the resin sheet 36 is placed in the intermediate support 16 in the position between the working current collector 24A and the non-working current collector 44A by the adhesive 56 in this embodiment. Adhering to the upper surface prevents conduction between the working electrode 24 and the non-working electrode 44.

  Further, as the DC power source 12, a button battery or a thin battery disclosed in, for example, Japanese Patent Laid-Open No. 11-067236, US Patent Publication No. 2004 / 0185667A1, US Pat. No. 6,855,441, or the like is used. However, it is not limited to the structure of this embodiment.

  Further, the non-acting side biological contact layer 52 is not necessarily provided as long as the ion selective membrane 50 can sufficiently contact the skin and mucous membrane of the living body.

  Next, the operation of the iontophoresis device 10 will be described.

  Since the working electrode structure 20 in which the chemical solution holding unit 30 is disposed is electrically connected to the anode of the DC power source 12, a cation (this embodiment) is present in the chemical solution holding unit 30 when electricity is applied. In this case, lidocaine ions and the like) start to be driven to the living body through the living body contact layer 32. At this time, cysteine hydrochloride is used in place of sodium sulfite as the antioxidant in the chemical solution holding unit 30 of the iontophoresis device 10, so that the transport efficiency of lidocaine ions due to the presence of the antioxidant is reduced. The decline is prevented. More specifically, the movement amount (transport amount) of electrically driven ions is approximately proportional to the charge and approximately inversely proportional to the molecular weight. Therefore, when sodium sulfite is used as an antioxidant, In this case, the monovalent cation sodium ion (molecular weight 23) generated from sodium sulfite is efficiently transported to the monovalent cation lidocaine ion (molecular weight 230). However, the antioxidant in the apparatus is cysteine hydrochloride, and the monovalent cation generated by dissociation of cysteine hydrochloride is a cysteine ion having a molecular weight of 180. Therefore, even if the molecular weight is simply compared, it is compared with sodium ion. In addition, it has characteristics that are very difficult to move (not easily transported). As a result, lidocaine and epinephrine, which are originally intended for transportation, are efficiently transported to the living body side.

  In addition, as will be described later, cysteine hydrochloride has superior characteristics as an antioxidant alone compared to sodium sulfite, and by using cysteine hydrochloride, the long-term use of devices and administration compositions can be improved. Saving is possible.

  Further, in this iontophoresis device 10, both the working side electrode 24 and the non-working side electrode 44 are composed of a current collector and a polarizable electrode, so that when the current iontophoresis device is energized, It is possible to energize the electrolyte or drug without causing electrode reaction or reducing such electrode reaction, resulting in generation of gas such as oxygen gas, chlorine gas or hydrogen gas. Alternatively, generation of undesirable ions such as hydrogen ions, hydroxyl ions, and hypochlorous acid can be suppressed or reduced.

<Comparison of experimental results between cysteine hydrochloride and sodium pyrosulfite>
Next, referring to FIG. 6 and FIG. 7, the experimental results of examining the properties of cysteine hydrochloride and sodium pyrosulfite as antioxidants will be described.

  Tables 1 and 2 show the composition of the composition for administration that is assumed to be held in the drug solution holding part, and Table 1 is a composition example using sodium pyrosulfite as an antioxidant (Formula A). Table 2 shows a composition example (Formula B) using cysteine hydrochloride (hydrate) as an antioxidant.

  As shown in Table 1, Formula A is obtained by using sodium pyrosulfite as an antioxidant. Sodium pyrosulfite 0.10%, lidocaine hydrochloride 10.00%, epinephrine 0.10%, glycerol 10. 00%, citric acid 0.06%, 0.1% paraben solution 79.74%.

  Further, when each component was collected from a specific sample having the composition, the collected amount was 0.10141 g of sodium pyrosulfite, 10.00057 g of lidocaine hydrochloride, 0.10084 g of epinephrine, 10.0223 g of glycerin, 0 citrate. 0.06075 g and 0.1% paraben solution 79.68 g.

  As shown in Table 2, Formula B uses cysteine hydrochloride as an antioxidant, cysteine hydrochloride 0.10%, lidocaine hydrochloride 10.00%, epinephrine 0.10%, glycerin 10.00%. , Citric acid 0.02%, 0.1% paraben solution 79.78%.

  Further, when each component was collected from a specific sample having the composition, the collected amount was 0.10281 g of cysteine hydrochloride, 10.01061 g of lidocaine hydrochloride, 0.10112 g of epinephrine, 10.0231 g of glycerin, and 0.13 citrate. The amount was 02015 g and 79.83 g of 0.1% paraben solution.

  In addition, in order to clearly see the oxidation state of epinephrine, the above sample was placed in a sealed container in which outside air can enter and exit, and stored under the following storage conditions.

  The first condition is a temperature of 25 ° C. and light-shielded (hereinafter simply referred to as “first condition”), and the second condition is a temperature of 40 ° C. and light-shielded (hereinafter simply referred to as “second condition”). The third condition is a temperature of 25 ° C. and light irradiation (hereinafter simply referred to as “third condition”).

  The test points are 5 points on the 0th day, the 3rd day, the 7th day, the 14th day, and the 28th day.

  The test items are the quantitative value of lidocaine and the quantitative value of epinephrine. Lidocaine and epinephrine were quantified according to the Japanese Pharmacopoeia.

  Next, the result obtained by experiment along the said method is shown.

<Formula A>
Table 3 is a table showing the quantitative results of lidocaine hydrochloride in Formula A.

  Table 4 is a table showing the quantitative results of epinephrine in Formula A.

  A graph of the measurement results in Tables 3 and 4 is attached as FIG.

<Formula B>
Table 5 is a table showing the quantitative results of lidocaine hydrochloride in Formula B.

  Table 6 is a table | surface which shows the fixed_quantity | quantitative_assay result of epinephrine in Formula B.

  In addition, what graphed about the measurement result of these Table 5 and Table 6 is attached as FIG.

  As is clear from the comparison of the graphs of FIG. 6 and FIG. 7, focusing on the epinephrine content, one using sodium pyrosulfite (Formula A) as an antioxidant and one using cysteine hydrochloride (Formula) B) shows almost the same residual rate under the first condition and the third condition where the temperature conditions are both 25 ° C, but sodium pyrosulfite is used under the second condition where the temperature conditions are 40 ° C. Formula A showed a marked decrease in epinephrine content compared to Formula B using cysteine hydrochloride. The effect of light irradiation can be easily prevented by light-shielding packaging, but since the effect of temperature cannot be prevented unless conditions for cold storage are set, Formula A using sodium pyrosulfite is used in medical institutions and It is clear that the composition is difficult for the user to store and manage. That is, it can be judged that the use of cysteine hydrochloride is superior in terms of performance and ease of handling from the viewpoint of an antioxidant.

  It has been confirmed that both compositions do not affect the stability of lidocaine.

  Similarly, the drugs to which the present invention can be applied include, for example, pergolide mesylate, levomepromazine hydrochloride, chlorpromazine hydrochloride, perphenazine hydrochloride, levobunolol hydrochloride, ketotifen fumarate, amrinone, ethylephrine hydrochloride, dopamine hydrochloride, aprindine hydrochloride, hydrochloric acid Midodrine, isosorbide nitrate, bromhexine hydrochloride, ambroxol hydrochloride, orciprenaline sulfate, trimethoquinol hydrochloride, azasetron hydrochloride, metoclopramide hydrochloride, ritodrine hydrochloride, indomethacin, epinephrine hydrogen tartrate, propitocaine hydrochloride, pyridoxal phosphate, mitoxantrone hydrochloride, promethazine , Gentamicin sulfate, sisomycin sulfate, micronomycin sulfate, phentolamine mesylate and other drugs that dissociate into cations Both can be expected accordingly.

  The present invention is not limited to the medical field, and can be applied to, for example, an iontophoresis device for cosmetic purposes and a composition for administration thereof.

1 is an exploded perspective view showing an iontophoresis device according to an embodiment of the present invention. The top view which expands and shows the working side electrode and non-working side electrode part in the iontophoresis device Enlarged sectional view taken along line III-III in FIG. Exploded sectional view showing the iontophoresis device Sectional drawing which shows the assembly state of the iontophoresis device The graph which shows the experimental result of Formula A The graph which shows the experimental result of Formula B

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 ... Iontophoresis apparatus 12 ... DC power supply 14 ... Proximal support 16 ... Intermediate support 18 ... End support 19A ... Working side conductor 19B ... Non-acting side conducting wire 20 ... Working side electrode structure 21 ... Working side middle Support 21A ... Working side intermediate through hole 22 ... Working side tip support 22A ... Working side tip through hole 24 ... Working side electrode 24A ... Working side current collector 24B ... Working side polarizable electrode 25, 45 ... Tapered surface 30 ... Chemical solution holding part 32 ... working side biological contact layer 36 ... resin sheet 40 ... non-working side electrode structure 41 ... non-working side intermediate support 41A ... non-working side intermediate through hole 42 ... non-working side tip support 42A ... non-working Side tip through-hole 44... Non-working side electrode 44 A... Non-working side current collector 44 B... Non-working side polarizable electrode 48 ... Electrolyte holding part 50 ... Ion selective membrane 52. 58 ... Release liner

Claims (5)

A drug composed of a DC power supply, a working electrode structure connected to the anode of the DC power supply, and a non-working electrode structure connected to the cathode, the drug held in the working electrode structure, An iontophoresis device for administering to a living body by a voltage from a DC power source,
The iontophoresis device, wherein the working electrode structure holds cysteine hydrochloride mixed with the drug as an antioxidant for the drug. In claim 1,
The iontophoresis device, wherein the drug is epinephrine. In claim 2,
The iontophoresis device, wherein the drug further contains lidocaine.   A composition for iontophoresis administration comprising epinephrine that functions as a vasoconstrictor and cysteine hydrochloride that functions as an antioxidant for the epinephrine. In claim 4,
Furthermore, a composition for iontophoresis administration comprising lidocaine that functions as an anesthetic.

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