WO2001026690A1 - Agents de regulation de la permeabilite percutanee et composition d'electroporation contenant ces agents - Google Patents

Agents de regulation de la permeabilite percutanee et composition d'electroporation contenant ces agents Download PDF

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Publication number
WO2001026690A1
WO2001026690A1 PCT/JP2000/002241 JP0002241W WO0126690A1 WO 2001026690 A1 WO2001026690 A1 WO 2001026690A1 JP 0002241 W JP0002241 W JP 0002241W WO 0126690 A1 WO0126690 A1 WO 0126690A1
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WO
WIPO (PCT)
Prior art keywords
electroporation
composition
drug
present
weight
Prior art date
Application number
PCT/JP2000/002241
Other languages
English (en)
Japanese (ja)
Inventor
Yoshihiro Tokudome
Koji Owaku
Kenichi Goto
Kenji Sugibayashi
Original Assignee
Pola Chemical Industries Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Pola Chemical Industries Inc. filed Critical Pola Chemical Industries Inc.
Priority to JP2001529751A priority Critical patent/JP4801863B2/ja
Priority to AU36718/00A priority patent/AU3671800A/en
Publication of WO2001026690A1 publication Critical patent/WO2001026690A1/fr

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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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A61K9/0009—Galenical forms characterised by the drug release technique; Application systems commanded by energy involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis

Definitions

  • the present invention relates to a transdermally permeable control agent, and a composition for election poration containing the same.
  • the present invention relates to a transdermally permeable control agent useful for adjusting the transdermally permeating amount of a drug in an electoral poration and a composition for electroporation containing the same.
  • the present invention is useful in the field of medicine. Conventional technology
  • the percutaneous absorption route is less prone to pain than injections, and has less forgotten administration than oral administration. It is difficult to absorb the skin because of its defensive function, and it has not yet been established as a drug delivery method.
  • a so-called electoral poration in which a voltage is applied to create a pore in the skin structure, and a drug is transported through the pore, is exemplified. Improving transdermal permeability is one of the major themes in drug transport in such electroporation, but in addition to this, controlling permeability and controlling drug concentration in the blood are also important.
  • One of the major themes is to control the transdermal permeability immediately after the electric field load and to adjust the absorption characteristics of the drug, and the construction of such a control technology has been desired. It has recently become apparent that the behavior of the drug in electoral poration is different from that of normal administration, and a composition for transdermal administration suitable for electroporation, including such de-collection, has been recently developed. Development was desired.
  • the present invention has been made under the above circumstances, and has as its object to provide means for controlling a drug permeation rate in an election portion.
  • the present inventors have sought to find a means of controlling the drug permeation rate in election poration, and as a result of intensive research efforts, have found such an effect on phospholipids.
  • the inventors have found that such control can be performed by appropriately adding this to a composition for election port poisoning, and have completed the invention. That is, the present invention provides a composition for electoral poration containing a phospholipid, and a drug for external use on the skin, which is obtained by combining the composition with an electoral poration device.
  • Phospholipid which is an essential component of the composition for electroporation of the present invention
  • the composition for electoral port poration of the present invention is characterized by containing a phospholipid.
  • lipids that can be contained in the composition for electroporation of the present invention any lipids that are usually used in external preparations for skin and the like can be used without any particular limitation.
  • Preferable examples include fatty acid phosphatidic acid and salts thereof.
  • difatty acid compounds are preferable, and difatty acid phosphatidylglycerol is particularly preferable.
  • constituent fatty acids unsaturated fatty acids are preferred, and oleic acid is particularly preferred. That is, phosphatidylglycerol dioleate is particularly preferred as the phospholipid contained in the composition for electoral poration of the present invention. These may contain only one kind, or may contain two or more kinds in combination. In the composition for election port poration of the present invention, these phospholipids are oriented to the pore portion to adjust the size of the pore formed by the electoportion poration, so that drug permeation occurs at one time, Is considered to have the effect of preventing instantaneous blockage.
  • the content of the phospholipid in the composition (1) varies depending on the control pattern of the drug permeability, it is generally about 0.1 to 10% by weight, more preferably 0.5 to 5% by weight. This is because if the control is overkill, the required amount may not be permeated; if the control is not enough, the drug permeation may be biased, resulting in impaired sustainability or transiently increasing drug concentrations, with side effects. This is because they may be expressed.
  • composition for electroporation of the present invention may contain, in addition to the essential component, a lipid, an optional component for formulation usually used in a composition for electoral poration.
  • optional components include, for example, hydrocarbons such as squalane, petrolatum, and microcrystalline wax, jojoba oil, esters such as carnauba wax, octyldodecyl oleate, olive oil, tallow, coconut oil, and the like.
  • Fatty acids such as triglycerides, stearic acid, oleic acid, and ritinoleic acid; higher alcohols such as oleyl alcohol, stearyl alcohol, octyldodecanol; anionic surfactants such as sulfosuccinates and sodium polyoxyethylene alkyl sulfate; alkyls Amphoteric surfactants such as benzoin salt, cationic surfactants such as dialkylammonium salts, sorbitan fatty acid esters, fatty acid monoglycerides, their polyoxyethylene adducts, polyoxetylene alkyl esters Le, nonionic surface active agents such as poly O key Chez Ji Ren fatty acid esters, thickening-gelling agents, antioxidants, ultraviolet absorbers, coloring materials, preservatives, powders and the like can be preferably exemplified.
  • the drug to be transdermally administered by such an electroporation can be applied without any particular limitation as long as it is usually used as a pharmaceutical.
  • examples of such a drug include, but are not limited to, codin, morphine, and Defoam morphone, oxycodone, pethidine, buflenolfin hydrochloride, pentadyne, tramadol hydrochloride, and other analgesic and anti-inflammatory drugs, insulin, calcitonin, elcatonin, corticotropin (ACTH), parathyroid hormone (PTH), selectin, oxotosine, Angiotensin, 5-endorphin, vasopressin, glucagon, somatosustin, luteinizing hormone-releasing hormone (LH_RH), enkephalin, neurotensin, atrial natriuretic peptide (ANP), growth hormone, bradykinin, substance P , Dynolph Thyrin, thyroid stimulating
  • the composition for electroporation of the present invention is obtained by treating the above essential components, preferred components, optional components and active ingredients according to a conventional method to adjust the physical properties of the active ingredients, etc. Processed into dosage forms, semi-solid dosage forms, solid dosage forms, etc., and used for electroporation. That is, by using the composition of the present invention, the drug of the active ingredient can be transdermally administered by electroporation. For electroporation, it is used together with a device for electoral poration.
  • preferred dosage forms include aqueous dosage forms, and particularly preferred examples include aqueous solution dosage forms, aqueous gel dosage forms, and emulsified dosage forms.
  • the drug administration unit for external use on the skin of the present invention is obtained by combining the above-described composition for electroporation of the present invention with the device for election port poration.
  • the device for the election port location There are no particular restrictions on the device for the election port location as long as it is normally used for such use.
  • Japanese Patent Application Publication No. 11-507341, Japanese Patent Application Publication No. 11-505445 The devices described in JP-A No. 10-502827, JP-A No. 11-503349, JP-A No. 08-51 1680, JP-A No. 03-502416 may be used.
  • commercially available devices for such electoral port por- tions include devices such as £ CM-600 manufactured by 8 companies and GENE PULSER manufactured by BI0-RAD, and these devices are used.
  • FIG. 1 is a diagram showing an apparatus used in a transmission experiment of Example 2. The present invention will be described in more detail below with reference to examples, but it is needless to say that the present invention is not limited to only these examples.
  • a composition for electroporation of the present invention was prepared. That is, the formulation components were stirred and solubilized to obtain a composition for election port poration.
  • the transdermal absorption promoting effect of the composition for electroporation of Example 1 was measured by a transdermal permeability test using Franz cells. That is, a skin specimen 2 from the abdomen of a hairless rat, from which the subcutaneous fat was removed, was attached to the Franz cell 1 as a septum with the stratum corneum facing the donor side, and a saline solution was placed on the receiver side. Water 3 was filled, and the donor side was charged with 3 mL of the composition 4 for electroporation of the present invention. The receiver side was stirred with a stirrer 6 at 1200 rpm using a silver head type stirrer 5.
  • a composition for electoral port poration of the present invention was prepared according to the following prescription. That is, a prescription component was stirred and solubilized to obtain a composition for electoral port poration.
  • a composition for electroporation of the present invention was prepared. That is, the formulation components were stirred and solubilized to obtain a composition for election port poration.
  • a composition for electoral port poration of the present invention was prepared according to the following prescription. That is, the ingredients were stirred and solubilized to obtain a composition for electoral port poration.
  • composition for electroporation of the present invention was prepared according to the following prescription. That is, the components were stirred and solubilized to obtain a composition for election port poisoning.
  • composition for electroporation of the present invention was prepared according to the following formulation (that is, the formulation components were solubilized by stirring to obtain a composition for electoral poration).
  • a composition for electroporation of the present invention was prepared. That is, the prescription component A was stirred, dispersed and solubilized, and the mixture was added to the mouth and neutralized to obtain a composition (gel) for elect mouth poration.
  • Lithium hydroxide 0.4 parts by weight
  • control means of the drug permeation rate in election poration can be provided, and it is useful in the pharmaceutical field.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Radiology & Medical Imaging (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biomedical Technology (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne des agents de régulation de la perméabilité percutanée, destinés à une électroporation et comprenant des phospholipides. En ajoutant ces agents à des compositions d'électroporation, on peut réguler la quantité de perméation percutanée de médicaments.
PCT/JP2000/002241 1999-10-13 2000-04-06 Agents de regulation de la permeabilite percutanee et composition d'electroporation contenant ces agents WO2001026690A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP2001529751A JP4801863B2 (ja) 1999-10-13 2000-04-06 経皮透過性コントロール剤及びそれを含有するエレクトロポーレーション用の組成物
AU36718/00A AU3671800A (en) 1999-10-13 2000-04-06 Percutaneous permeability-controlling agents and compositions for electroporation containing the same

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP29053499 1999-10-13
JP11/290534 1999-10-13

Publications (1)

Publication Number Publication Date
WO2001026690A1 true WO2001026690A1 (fr) 2001-04-19

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ID=17757280

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2000/002241 WO2001026690A1 (fr) 1999-10-13 2000-04-06 Agents de regulation de la permeabilite percutanee et composition d'electroporation contenant ces agents

Country Status (3)

Country Link
JP (1) JP4801863B2 (fr)
AU (1) AU3671800A (fr)
WO (1) WO2001026690A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1989006555A1 (fr) * 1988-01-21 1989-07-27 Massachusetts Institute Of Technology Transport de molecules a travers les tissus par electroporation
WO1996033771A2 (fr) * 1995-04-28 1996-10-31 Alza Corporation Composition et procede pour ameliorer l'apport d'un agent par electrotransport
JPH09255561A (ja) * 1996-03-26 1997-09-30 Hisamitsu Pharmaceut Co Inc エレクトロポレーション用マイクロエマルション製剤

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1989006555A1 (fr) * 1988-01-21 1989-07-27 Massachusetts Institute Of Technology Transport de molecules a travers les tissus par electroporation
WO1996033771A2 (fr) * 1995-04-28 1996-10-31 Alza Corporation Composition et procede pour ameliorer l'apport d'un agent par electrotransport
JPH09255561A (ja) * 1996-03-26 1997-09-30 Hisamitsu Pharmaceut Co Inc エレクトロポレーション用マイクロエマルション製剤

Also Published As

Publication number Publication date
JP4801863B2 (ja) 2011-10-26
AU3671800A (en) 2001-04-23

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