WO2015087755A1 - Timbre adhésif contenant de la clonidine - Google Patents

Timbre adhésif contenant de la clonidine Download PDF

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Publication number
WO2015087755A1
WO2015087755A1 PCT/JP2014/081970 JP2014081970W WO2015087755A1 WO 2015087755 A1 WO2015087755 A1 WO 2015087755A1 JP 2014081970 W JP2014081970 W JP 2014081970W WO 2015087755 A1 WO2015087755 A1 WO 2015087755A1
Authority
WO
WIPO (PCT)
Prior art keywords
clonidine
acid
pharmaceutically acceptable
patch
acceptable salt
Prior art date
Application number
PCT/JP2014/081970
Other languages
English (en)
Japanese (ja)
Inventor
崇 安河内
山本　直樹
Original Assignee
久光製薬株式会社
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 久光製薬株式会社 filed Critical 久光製薬株式会社
Priority to JP2015552401A priority Critical patent/JP6220893B2/ja
Publication of WO2015087755A1 publication Critical patent/WO2015087755A1/fr

Links

Classifications

    • 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
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4168—1,3-Diazoles having a nitrogen attached in position 2, e.g. clonidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • the present invention relates to a clonidine-containing patch.
  • Clonidine is also called 2- (2,6-dichlorophenylimino) imidazolidine and is known as a selective adrenergic ⁇ 2 receptor agonist. Clonidine suppresses sympathetic nerve signaling by stimulating central ⁇ 2 receptor, acts on ⁇ 2 receptor located in the presynaptic membrane of peripheral adrenergic nerve endings, and suppresses norepinephrine release by sympathetic excitation This has the effect of lowering blood pressure.
  • Patent Documents 4 to 7 describe that the skin permeation rate of an ⁇ 2 agonist in a formulation for treating pain is at least 1 ⁇ g / cm 2 / hr.
  • clonidine exhibits local analgesic action at a dose lower than blood pressure lowering action. Therefore, in anticipation of local analgesic action, when using a conventional antihypertensive patch containing clonidine hydrochloride, it exhibits not only the desired local analgesic action but also blood pressure lowering action, There is a possibility of showing hypotension, which is a problem from the viewpoint of user safety and compliance.
  • a patch for local analgesia is required to have a large area that can sufficiently cover the affected area.
  • the patch area of the patch is simply increased, the content of the drug contained in the preparation increases.
  • a clonidine-containing patch for the purpose of local analgesic action if the blood concentration of clonidine increases, the possibility of causing a blood pressure lowering action increases, so it is necessary to reduce the clonidine content in the preparation.
  • an object of the present invention is to provide a clonidine-containing patch that exhibits local analgesic action and is excellent in drug stability.
  • the present invention provides a support or release liner containing a composition containing clonidine or a pharmaceutically acceptable salt thereof, a skin permeation inhibitor, an adhesive, and a solvent for clonidine or a pharmaceutically acceptable salt thereof. It is also understood to provide a method for producing a topical analgesic patch, including spreading.
  • the skin permeation rate of clonidine or a pharmaceutically acceptable salt thereof can be sufficiently suppressed, and only a local analgesic action is exhibited. It is also excellent in the temporal stability of an acceptable salt.
  • a stretchable or non-stretchable material that can be usually used for a patch is used.
  • polyesters such as polyethylene terephthalate, polybutylene terephthalate, and polyethylene naphthalate; polyolefins such as polyethylene, polypropylene, and polybutadiene; synthesis of ethylene vinyl acetate polymer, polyvinyl chloride, nylon, polyurethane, cellulose derivatives, polyacrylonitrile, and the like
  • a film or sheet made of a synthetic resin such as resin or cotton, or a laminate thereof, a porous membrane, a foam, a fabric such as a woven fabric or a nonwoven fabric, a porous membrane, a foam, or a paper material is preferably used. be able to.
  • Clonidine is also called 2- (2,6-dichlorophenylimino) imidazolidine and is a compound having a structure represented by the following chemical formula (1). Clonidine is known as a selective adrenergic ⁇ 2 receptor agonist.
  • the skin permeation rate of clonidine is preferably 0.5 ⁇ g / cm 2 / hr or less.
  • the blood concentration of clonidine is unlikely to increase when a patch is applied, and side effects such as blood pressure lowering effects are unlikely to occur.
  • concentration can be ensured in order to exhibit a local analgesic effect in it being 0.002 microgram / cm ⁇ 2 > / hr or more.
  • local concentration means the drug concentration in the tissue that has permeated through the skin at the site (affected site) where the patch is applied.
  • the content of the skin permeation inhibitor relative to clonidine or a pharmaceutically acceptable salt thereof is preferably 0.1 to 10% by mass based on the total amount of the pressure-sensitive adhesive layer. It is more preferably 3 to 9% by mass.
  • the blood concentration of clonidine is not easily increased when a patch is applied, and side effects such as blood pressure lowering effects are unlikely to occur.
  • sufficient local concentration can be ensured in order to exhibit a local analgesic effect as it is 10 mass% or less.
  • the polyisobutylene-based pressure-sensitive adhesive is one obtained by adding a plasticizer or the like to polyisobutylene (PIB) to impart adhesiveness.
  • Fillers include silicates such as aluminum silicate and magnesium silicate, aluminum hydroxide, aluminum carbonate, magnesium carbonate, silicic acid, barium sulfate, calcium sulfate, calcium zincate, zinc stearate, zinc oxide, titanium oxide Etc. can be illustrated.
  • silicates such as aluminum silicate and magnesium silicate, aluminum hydroxide, aluminum carbonate, magnesium carbonate, silicic acid, barium sulfate, calcium sulfate, calcium zincate, zinc stearate, zinc oxide, titanium oxide Etc. can be illustrated.
  • ultraviolet absorbers examples include p-aminobenzoic acid derivatives, anthranilic acid derivatives, salicylic acid derivatives, coumarin derivatives, amino acid derivatives, imidazoline derivatives, pyrimidine derivatives, dioxane derivatives and the like.
  • tocopherol and its ester derivatives Ascorbic acid and its ester derivatives, dibutylhydroxytoluene, butylhydroxyanisole, pyrophosphoric acid and its salts can be preferably used.
  • the adhesive layer of the present embodiment may be coated with a release liner.
  • the release liner is peeled and removed when the patch is used.
  • styrene-isoprene-styrene block copolymer (SIS), polyisobutylene (PIB), tackifying resin, liquid paraffin, additive A and toluene are mixed using a mixer, and uniform.
  • Bases 1-4 were prepared.
  • the numerical value in Table 1 means mass (g).
  • any one of the above-mentioned bases 1 to 4, clonidine, and, if necessary, additive B were mixed to obtain adhesive solutions.
  • the obtained pressure-sensitive adhesive solution was spread on a release-treated film (release liner), and the solvent was dried and removed to form a pressure-sensitive adhesive layer. Then, a support was laminated thereon, and the support and A patch was obtained by pressure bonding the pressure-sensitive adhesive layer. Therefore, the obtained patch was laminated
  • the receptor solution was sampled up to 24 hours later, the flow rate was measured, and the clonidine concentration in the receptor solution was measured using HPLC.
  • the drug permeation rate per hour was calculated from the obtained measured values, and was defined as the skin permeation rate of the drug per unit area in a steady state.

Landscapes

  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Epidemiology (AREA)
  • Pain & Pain Management (AREA)
  • Dermatology (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne un timbre adhésif pour le soulagement d'une douleur locale, qui est muni d'un corps de support et d'une couche adhésive qui est stratifiée sur le corps de support. La couche adhésive contient de la clonidine ou l'un de ses sels pharmaceutiquement acceptable, un agent réduisant la pénétration cutanée pour la clonidine ou un de ses sels pharmaceutiquement acceptables et un adhésif. L'agent réduisant la pénétration cutanée pour la clonidine ou son sel pharmaceutiquement acceptable est composé d'au moins une substance choisie dans l'ensemble consistant en acide citrique, acide oléique, acide stéarique, acide isostéarique, acide malique, acide lactique, un copolymère d'acide méthacrylique et d'un ester d'acide méthacrylique et un polyéthylène glycol. La teneur en clonidine ou son sel pharmaceutiquement acceptable est inférieure ou égale à 0,9 % en masse par rapport à la masse totale de la couche adhésive.
PCT/JP2014/081970 2013-12-09 2014-12-03 Timbre adhésif contenant de la clonidine WO2015087755A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2015552401A JP6220893B2 (ja) 2013-12-09 2014-12-03 クロニジン含有貼付剤

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2013253882 2013-12-09
JP2013-253882 2013-12-09

Publications (1)

Publication Number Publication Date
WO2015087755A1 true WO2015087755A1 (fr) 2015-06-18

Family

ID=53371063

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2014/081970 WO2015087755A1 (fr) 2013-12-09 2014-12-03 Timbre adhésif contenant de la clonidine

Country Status (3)

Country Link
JP (1) JP6220893B2 (fr)
TW (1) TWI636800B (fr)
WO (1) WO2015087755A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110354104A (zh) * 2019-07-30 2019-10-22 苏州盈得来医药科技有限公司 一种盐酸可乐定透皮贴剂及其制备方法

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS58190444A (ja) * 1982-02-10 1983-11-07 ベ−リンガ−・インゲルハイム・コマンデイツト・ゲゼルシヤフト ポリアクリレ−トフイルムの形における医薬製剤の製造法
JPS60199834A (ja) * 1984-03-23 1985-10-09 Takeda Chem Ind Ltd 経皮吸収外用製剤
JPH01287024A (ja) * 1988-05-11 1989-11-17 Nitto Denko Corp クロニジンを含有する粘着テープ製剤
JPH04103528A (ja) * 1990-08-23 1992-04-06 Sekisui Chem Co Ltd 経皮吸収製剤
JPH05503539A (ja) * 1990-02-26 1993-06-10 エイアールシー　１，インコーポレイテッド 交感神経性持続性痛みの治療のための組成物および方法
JP2011020997A (ja) * 2009-03-19 2011-02-03 Kyoritsu Yakuhin Kogyo Kk 外用貼付剤
JP2012140407A (ja) * 2010-12-13 2012-07-26 Hisamitsu Pharmaceut Co Inc 経皮吸収促進剤、ならびにそれを含有する医薬組成物および貼付剤

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS58190444A (ja) * 1982-02-10 1983-11-07 ベ−リンガ−・インゲルハイム・コマンデイツト・ゲゼルシヤフト ポリアクリレ−トフイルムの形における医薬製剤の製造法
JPS60199834A (ja) * 1984-03-23 1985-10-09 Takeda Chem Ind Ltd 経皮吸収外用製剤
JPH01287024A (ja) * 1988-05-11 1989-11-17 Nitto Denko Corp クロニジンを含有する粘着テープ製剤
JPH05503539A (ja) * 1990-02-26 1993-06-10 エイアールシー　１，インコーポレイテッド 交感神経性持続性痛みの治療のための組成物および方法
JPH04103528A (ja) * 1990-08-23 1992-04-06 Sekisui Chem Co Ltd 経皮吸収製剤
JP2011020997A (ja) * 2009-03-19 2011-02-03 Kyoritsu Yakuhin Kogyo Kk 外用貼付剤
JP2012140407A (ja) * 2010-12-13 2012-07-26 Hisamitsu Pharmaceut Co Inc 経皮吸収促進剤、ならびにそれを含有する医薬組成物および貼付剤

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110354104A (zh) * 2019-07-30 2019-10-22 苏州盈得来医药科技有限公司 一种盐酸可乐定透皮贴剂及其制备方法

Also Published As

Publication number Publication date
JP6220893B2 (ja) 2017-10-25
TW201605498A (zh) 2016-02-16
JPWO2015087755A1 (ja) 2017-03-16
TWI636800B (zh) 2018-10-01

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