WO2014046472A1 - 리바스티그민의 안정성이 개선된 의약품 - Google Patents
리바스티그민의 안정성이 개선된 의약품 Download PDFInfo
- Publication number
- WO2014046472A1 WO2014046472A1 PCT/KR2013/008426 KR2013008426W WO2014046472A1 WO 2014046472 A1 WO2014046472 A1 WO 2014046472A1 KR 2013008426 W KR2013008426 W KR 2013008426W WO 2014046472 A1 WO2014046472 A1 WO 2014046472A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- rivastigmine
- package
- less
- oxygen content
- stability
- Prior art date
Links
Images
Classifications
-
- 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
- A61K31/325—Carbamic acids; Thiocarbamic acids; Anhydrides or salts thereof
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/27—Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
-
- 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
-
- 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
- A61K9/7061—Polyacrylates
-
- 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
- A61K9/7069—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. polysiloxane, polyesters, polyurethane, polyethylene oxide
-
- 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
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the present invention relates to a medicament with improved stability of rivastigmine.
- the present invention also relates to a packaging method capable of improving the stability of rivastigmine.
- Rivasstigmine (S) -N-ethyl-3- [1-dimethylamino) ethyl] -N-methyl-phenyl-carbamate, is used for the treatment of Alzheimer's disease, and acetylcholine in the central nervous system. Useful to inhibit esterases.
- Such rivastigmine is commercially available in patch formulations.
- Percutaneous compositions in patch form are disclosed in Example 2 of British Patent No. 2,203,040.
- patches are prepared by mixing rivastigmine with two polymers and a plasticizer to produce a viscous composition and then applying the composition to the foil.
- US Pat. No. 6,335,031 relates to transdermal compositions containing rivastigmine or salts thereof, characterized by the use of stabilizers.
- the transdermal composition containing rivastigmine discloses that it is difficult to secure a storage period necessary for commercial distribution because it is decomposed by oxygen and an oxidation reaction even under a closed storage condition.
- the present invention to solve this problem, such as tocopherol (tocopherol) and esters thereof, ascorbic acid (ascorbic acid), butylhydroxytoluene, butylhydroxyanisole, and propyl gallate (propyl gallate)
- a transdermal composition of rivastigmine containing an antioxidant is disclosed. Tocopherols are used as stabilizers in commercially available rivastigmine transdermal administration products.
- the problem to be solved by the present invention is to provide a rivastigmine-containing medicine with improved stability.
- Another object of the present invention is to provide a method for packaging a rivastigmine-containing pharmaceutical formulation that can improve stability.
- the present invention provides a packaged medicine including a rivastigmine-containing pharmaceutical formulation, the oxygen content in the package is less than 12% by volume, more preferably 11% by volume or less, even more preferably 10% by volume It provides a rivastigmine-containing medicine, characterized in that less than%.
- the present invention provides a rivastigmine-containing medicament, wherein the pharmaceutical formulation in the medicament according to the invention is a rivastigmine free base-containing patch.
- the present invention also provides a method for packaging a rivastigmine-containing pharmaceutical formulation, wherein the air content in the packaging is replaced with nitrogen to reduce the oxygen content to less than 12% by volume, more preferably up to 11% by volume, even more preferably up to 10% by volume It provides a method for improving the stability of rivastigmine, characterized in that the adjustment to.
- the present invention provides a method for improving the stability of rivastigmine, wherein the pharmaceutical formulation in the above method according to the invention is a rivastigmine free base containing patch.
- the present invention provides rivastigmine-containing pharmaceuticals with improved stability and methods for preparing such pharmaceuticals.
- 1 is a graph showing the amount of generation of impurity C, the decomposition product according to the oxygen content in the package.
- a drug adhesive layer solution was prepared by mixing rivastigmine free base, a thickener, and an acrylic adhesive, and then coated on a silicone-coated polyester (PET) film, and dried at 80 ° C. for 10 minutes, and then using polyester (A) as a support layer. PET) film was covered to prepare a drug adhesive layer. Separately from the drug adhesive layer, a silicone adhesive solution was applied / dried to a fluorine-coated polyester (PET) film under the same conditions to prepare a skin adhesive layer. A silicone-coated polyester (PET) film was removed from the drug-adhesive layer, laminated on the skin-adhesive layer, and cut into circular 10 cm 2 to prepare a patch containing rivastigmine free base.
- PET silicone-coated polyester
- the rivastigmine free base patch prepared above was packaged in a packaging material in which polyester and aluminum were laminated, and the residual oxygen concentration in the package was measured while replacing the air in the package with nitrogen. Thereafter, the packaged product was stored at 60 ° C. for 7 days, and then the amount of generation of impurity C, a degradation product of rivastigmine free base, was measured according to the residual oxygen concentration.
- Impurity C is a degradation product resulting from oxidation, and the chemical name is 3-acetylphenyl ethyl (methyl) carbamate.
- UV Detector (217 nm)
- Quality guidelines Q3B (R2) require that the limit of known degradation products in finished products be adjusted to less than 0.5%.
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Organic Chemistry (AREA)
- Neurosurgery (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Emergency Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
약물점착층 | 피부점착층 | |
리바스티그민 유리염기 | 30 중량% | 실리콘 점착제 |
증점제 | 20 중량% | |
아크릴계 점착제 | 50 중량% |
Claims (8)
- 리바스티그민 함유 약학 제제를 포함한 포장된 의약품에 있어서,상기 포장 내 산소 함량이 12% 미만인 것을 특징으로 하는 리바스티그민 함유 의약품.
- 제1항에 있어서, 상기 포장 내 산소 함량이 11% 이하인 것을 특징으로 하는 리바스티그민 함유 의약품.
- 제2항에 있어서, 상기 포장 내 산소 함량이 10% 이하인 것을 특징으로 하는 리바스티그민 함유 의약품.
- 제1항 내지 제3항 중 어느 한 항에 있어서, 상기 의약품은 약학 제제로 리바스티그민 유리 염기 함유 패취를 포함하는 것을 특징으로 하는 리바스티그민 함유 의약품.
- 리바스티그민 함유 약학 제제를 포장하는 방법에 있어서,포장 내 공기를 질소로 치환하여 산소 함량을 12% 미만으로 조정하는 것을 특징으로 하는 리바스티그민의 안정성을 개선하는 방법.
- 제5항에 있어서, 상기 포장 내 산소 함량을 11% 이하로 조정하는 것을 특징으로 하는 리바스티그민의 안정성을 개선하는 방법.
- 제6항에 있어서, 상기 포장 내 산소 함량을 10% 이하로 조정하는 것을 특징으로 하는 리바스티그민의 안정성을 개선하는 방법.
- 제5항 내지 제7항 중 어느 한 항에 있어서, 상기 방법은 약학 제제로 리바스티그민 유리 염기 함유 패취를 사용하는 것을 특징으로 하는 리바스티그민의 안정성을 개선하는 방법.
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
BR112015006275A BR112015006275A2 (pt) | 2012-09-20 | 2013-09-17 | ''produto de droga contendo rivastigmina e método para aperfeiçoar a estabilidade de rivastigmina'' |
US14/430,106 US20150250758A1 (en) | 2012-09-20 | 2013-09-17 | Medicine having improved rivastigmine stability |
EP13839349.1A EP2898882A4 (en) | 2012-09-20 | 2013-09-17 | MEDICINAL PRODUCT WITH IMPROVED RIVASTIGMINE STABILITY |
JP2015532962A JP6267205B2 (ja) | 2012-09-20 | 2013-09-17 | リバスティグミンの安定性が改善した医薬品 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020120104727A KR20140038237A (ko) | 2012-09-20 | 2012-09-20 | 리바스티그민의 안정성이 개선된 의약품 |
KR10-2012-0104727 | 2012-09-20 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2014046472A1 true WO2014046472A1 (ko) | 2014-03-27 |
Family
ID=50341695
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/KR2013/008426 WO2014046472A1 (ko) | 2012-09-20 | 2013-09-17 | 리바스티그민의 안정성이 개선된 의약품 |
Country Status (6)
Country | Link |
---|---|
US (1) | US20150250758A1 (ko) |
EP (1) | EP2898882A4 (ko) |
JP (1) | JP6267205B2 (ko) |
KR (1) | KR20140038237A (ko) |
BR (1) | BR112015006275A2 (ko) |
WO (1) | WO2014046472A1 (ko) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102933207B (zh) | 2009-10-30 | 2018-02-02 | Ix生物医药有限公司 | 快速溶解固体剂型 |
US20140083878A1 (en) * | 2012-09-21 | 2014-03-27 | Mylan Inc. | Transdermal drug delivery device |
JP7031353B2 (ja) | 2018-02-16 | 2022-03-08 | セイコーエプソン株式会社 | 電解質、電池、電子機器、電解質および電池の製造方法 |
CN116098878A (zh) * | 2023-01-04 | 2023-05-12 | 新领医药技术(深圳)有限公司 | 稳定的透皮给药试剂盒及其制备方法和用途 |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2203040A (en) | 1987-03-04 | 1988-10-12 | Sandoz Ltd | Phenyl carbamates |
JPH10509694A (ja) * | 1994-09-30 | 1998-09-22 | ベクトン・ディッキンソン・アンド・カンパニー | 安定性及び在庫期間を増すためにイオン浸透療法による薬剤投与パッチ等を形成し且つ包装するための方法 |
US6335031B1 (en) | 1998-01-12 | 2002-01-01 | Novartis Ag | TTS containing an antioxidant |
WO2006131931A2 (en) * | 2005-06-10 | 2006-12-14 | Transpharma Medical, Ltd. | Patch for transdermal drug delivery |
WO2007064407A1 (en) * | 2005-12-01 | 2007-06-07 | Novartis Ag | Transdermal therapeutic system |
US20120031047A1 (en) * | 2010-08-03 | 2012-02-09 | Hisamitsu Pharmaceutical Co., Inc. | Method for storing transdermally/transmucosally absorbable preparation and package of transdermally/transmucosally absorbable preparation |
WO2012069820A1 (en) * | 2010-11-22 | 2012-05-31 | Dewan Fazlul Hoque Chowdhury | Multi-layered transdermal patch |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6199698B1 (en) * | 1999-12-03 | 2001-03-13 | Alusuisse Technology & Management, Ltd. | Pharmaceutical packaging with separation means |
JP4394873B2 (ja) * | 2001-12-19 | 2010-01-06 | 武田薬品工業株式会社 | 酸素に不安定な化合物を含有する固形組成物およびその安定化方法 |
WO2007084247A2 (en) * | 2005-12-28 | 2007-07-26 | Alza Corporation | Stable therapeutic formulations |
US9585862B2 (en) * | 2011-05-20 | 2017-03-07 | Sk Chemicals Co., Ltd. | Patch containing rivastigmine |
-
2012
- 2012-09-20 KR KR1020120104727A patent/KR20140038237A/ko not_active Application Discontinuation
-
2013
- 2013-09-17 BR BR112015006275A patent/BR112015006275A2/pt not_active IP Right Cessation
- 2013-09-17 US US14/430,106 patent/US20150250758A1/en not_active Abandoned
- 2013-09-17 WO PCT/KR2013/008426 patent/WO2014046472A1/ko active Application Filing
- 2013-09-17 JP JP2015532962A patent/JP6267205B2/ja not_active Ceased
- 2013-09-17 EP EP13839349.1A patent/EP2898882A4/en not_active Withdrawn
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2203040A (en) | 1987-03-04 | 1988-10-12 | Sandoz Ltd | Phenyl carbamates |
JPH10509694A (ja) * | 1994-09-30 | 1998-09-22 | ベクトン・ディッキンソン・アンド・カンパニー | 安定性及び在庫期間を増すためにイオン浸透療法による薬剤投与パッチ等を形成し且つ包装するための方法 |
US6335031B1 (en) | 1998-01-12 | 2002-01-01 | Novartis Ag | TTS containing an antioxidant |
WO2006131931A2 (en) * | 2005-06-10 | 2006-12-14 | Transpharma Medical, Ltd. | Patch for transdermal drug delivery |
WO2007064407A1 (en) * | 2005-12-01 | 2007-06-07 | Novartis Ag | Transdermal therapeutic system |
US20120031047A1 (en) * | 2010-08-03 | 2012-02-09 | Hisamitsu Pharmaceutical Co., Inc. | Method for storing transdermally/transmucosally absorbable preparation and package of transdermally/transmucosally absorbable preparation |
WO2012069820A1 (en) * | 2010-11-22 | 2012-05-31 | Dewan Fazlul Hoque Chowdhury | Multi-layered transdermal patch |
Non-Patent Citations (1)
Title |
---|
See also references of EP2898882A4 |
Also Published As
Publication number | Publication date |
---|---|
EP2898882A1 (en) | 2015-07-29 |
BR112015006275A2 (pt) | 2017-07-04 |
KR20140038237A (ko) | 2014-03-28 |
JP6267205B2 (ja) | 2018-01-24 |
US20150250758A1 (en) | 2015-09-10 |
JP2015529243A (ja) | 2015-10-05 |
EP2898882A4 (en) | 2016-03-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6335031B1 (en) | TTS containing an antioxidant | |
US20200289426A1 (en) | Transdermal Therapeutic System for Administering an Active Substance | |
WO2014046472A1 (ko) | 리바스티그민의 안정성이 개선된 의약품 | |
WO2012161489A2 (ko) | 리바스티그민 함유 패취 | |
AU2010312096B2 (en) | Stable composition of rasagiline | |
EP3146980A1 (en) | Rotigotine-containing transdermal absorption preparation with improved stability | |
EP2870963A1 (en) | Preparation for percutaneous absorption containing rotigotine | |
US6316023B1 (en) | TTS containing an antioxidant | |
EP3943156A1 (en) | Medicinal composition having excellent absorption of drug into living body and excellent chemical stability | |
KR20120130073A (ko) | 리바스티그민 함유 패취 | |
WO2012157921A2 (ko) | 리바스티그민 또는 이의 염을 함유하는 경피 투여 조성물 | |
JP3820103B6 (ja) | 抗酸化剤含有tts | |
JP2002500178A5 (ko) |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 13839349 Country of ref document: EP Kind code of ref document: A1 |
|
ENP | Entry into the national phase |
Ref document number: 2015532962 Country of ref document: JP Kind code of ref document: A |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 14430106 Country of ref document: US |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2013839349 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: BR Ref legal event code: B01A Ref document number: 112015006275 Country of ref document: BR |
|
ENP | Entry into the national phase |
Ref document number: 112015006275 Country of ref document: BR Kind code of ref document: A2 Effective date: 20150320 |