CN1266369A - 地塞米松凝胶 - Google Patents

地塞米松凝胶 Download PDF

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Publication number
CN1266369A
CN1266369A CN98808109A CN98808109A CN1266369A CN 1266369 A CN1266369 A CN 1266369A CN 98808109 A CN98808109 A CN 98808109A CN 98808109 A CN98808109 A CN 98808109A CN 1266369 A CN1266369 A CN 1266369A
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preparation
dexamethasone
weight
carbopol
active component
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CN98808109A
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CN1142782C (zh
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冈瑟·贝尔曼
古德朗·克劳斯－赫茨
克里斯托夫·凯斯勒
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Dr Gerhard Mann Chem Pharm Fabrik GmbH
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    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0048—Eye, e.g. artificial tears
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/14—Decongestants or antiallergics

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

Abstract

本发明涉及眼科用制剂,它含地塞米松活性成分,任选地也含常规添加剂和水,其特征在于:含有至少一种形成凝胶的药物可接受的物质,其含量足以调节凝胶制剂的粘度。

Description

地塞米松凝胶
本发明涉及一种眼科用制剂，它们含地塞米松(Dexamethasone)活性成分，任选地也含常规的添加剂和水。
众所周知，地塞米松制剂是眼药水和眼药膏。眼药水中地塞米松的浓度一般为0.05-0.1％，而眼药膏通常含约0.05％的地塞米松磷酸钠。
人们常将已知的含地塞米松酯活性成分的眼药水制剂调节成弱碱性的pH值。例如，目前市场销售的眼药水溶液的pH值一般约为7.3。之所以选择弱碱性值，是因为地塞米松酯在该弱碱性范围内的稳定性明显地增大，而强的松龙(prednisolone)的情况也是如此。
在这种情况下，通常尽可能地选择pH值接近中性，因为碱度较高有可能会刺激眼睛并带来其他的耐药量问题。
众所周知，眼药水的消炎效果要比眼药膏显著。试验表明：眼药膏的生物利用率基本上比眼药水溶液的差，即使延长接触时间也是如此(Cox等人，Arch.Ophthalmol.91，373(1972)；Kupferman等人，Arch Opthalmol.91.373(1974))。
尽管眼药水的生物利用率明显地高于眼药膏，但是当使用眼药水溶液时，要求的停留时间常常难以达到。眼药水溶液常被泪液迅速冲掉，结果活性成分的浓度迅速降低。
对于许多应用来说，如果在一次用药后，能延长活性成分的恒定浓度在眼中的滞留时间，那么将是有利的。在这方面，不得不求助于眼药膏，由于存在已知的生物利用率问题，因此代价是相当显著的。
本发明的目的是提供一种眼科用制剂，不存在这些困难。
本发明的目的由所附的主权利要求限定的特征实现。
其他有益的改进和实施方式由从属权利要求限定。
根据已知的眼药水溶液，设法配制一种本发明凝胶制剂，加入一种合适的胶凝剂，导致了意想不到的困难。
当根据已知的眼药水溶液将pH值调节到7-7.3时，令人惊奇地是，添加聚羧乙烯(carbomer)制剂导致活性成分仅在短时间后大量分解，以致于不能达到所需的稳定性。
很显然，要增强地塞米松二氢磷酸二钠(“地塞米松磷酸钠”)向游离碱的转化。
令人惊奇地是，通过选择较高的pH值可防止这种分解。诸如Carbopol(R)类的胶凝剂对在酸性至中性范围以及弱碱性范围内的地塞米松磷酸盐水溶液的耐久性有明显的副作用，同时令人惊奇地是，在较高的碱性范围内，所述的耐久性明显地得到改进。
因此，当使用聚羧乙烯制剂，特别是使用Carbopol 980NF型或类似的Carbopol产品作为本发明凝胶的胶凝剂时，pH范围达7.3以上时才具有要求的稳定性。
在pH值7.3以上，优选约7.6，更优选约7.8和7.8以上可得可存储、稳定的凝胶制剂，其聚羧乙烯，特别是使用Carbopol 980 NF型时的浓度为0.05-约1％(重量)，优选0.1-0.6％(重量)，更优选约3％(重量)，而活性成分的浓度约为0.1％(重量)。其上限取决于制剂的眼科相容性，因为极高的碱度会导致刺激。因此，临床使用的pH值不超过8，或仅在例外情况下才超过该值。
通常用药物可接受的碱例如氢氧化钠将本发明制剂调节到要求的pH值。
所述制剂除了活性成分，胶凝剂和调节碱度的碱外，还可含有防腐剂，例如氯化苄基十二烷基二甲基铵(BAC C12)，它选自包括洁尔灭类。另外，制剂优选地含有等渗剂，例如山梨糖醇，和螯合剂，例如乙二胺四乙酸钠。使用水作为制剂的溶剂。
本发明100kg批量的典型制剂含有下列组分：
名称                                  用量地塞米松二氢磷酸二钠                      0.0985kg氯化苄基十二烷基二甲基铵(BAC C12)         0.0100kgCarbopol 980 NF                           0.3000kg山梨糖醇                                  4.9000kg氢氧化钠，固体                            0.1460-0.1540kg乙二胺四乙酸钠                            0.0100kg注射用水                                  94.5275-94.5355kg
令人惊奇地是，这种制剂的稳定性与眼药水相同，即2或3年。与眼药水溶液相比，当施用时，这种制剂具有极好的容忍性，不会对眼睛产生刺激(在这方面，由所选择的防腐剂起作用)，并且按要求延长接触时间，在此期间，不会对活性成分的生物利用率产生负面影响。

Claims (6)

1.眼用制剂，它含地塞米松活性成分，任选地也含常规添加剂和水，其特征在于：含有至少一种形成凝胶的药物可接受的物质，其含量足以调节凝胶制剂的粘度。
2.根据权利要求1的制剂，其特征在于：制剂含有至少一种聚羧乙烯制剂，特别是Carbopol 980 NF型作为胶凝剂。
3.根据权利要求1或2的制剂，其特征在于：制剂含有0.05-1％(重量)，优选0.1-0.6％(重量)，更优选约0.3％(重量)的聚羧乙烯制剂。
4.根据权利要求1-3任一项的制剂，其特征在于：制剂含有地塞米松二氢磷酸二钠作为活性成分，其含量为约0.1％(重量)。
5.根据权利要求1-4任一项的制剂，其特征在于：制剂的pH值高于7.3，优选7.6-8.2，更优选7.8-8.0。
6.根据权利要求1-5任一项的制剂，其特征在于：制剂含有氯化苄基十二烷基二甲基铵(BAC C12)。
CNB988081091A 1997-10-06 1998-10-05 地塞米松凝胶 Expired - Lifetime CN1142782C (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19744113A DE19744113A1 (de) 1997-10-06 1997-10-06 Dexamethason-Gel
DE19744113.0 1997-10-06

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CN1266369A true CN1266369A (zh) 2000-09-13
CN1142782C CN1142782C (zh) 2004-03-24

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JP (1) JP4156793B2 (zh)
KR (1) KR100392481B1 (zh)
CN (1) CN1142782C (zh)
AR (1) AR017170A1 (zh)
AT (1) ATE230601T1 (zh)
BR (1) BR9812849A (zh)
CA (1) CA2300806C (zh)
DE (2) DE19744113A1 (zh)
DK (1) DK1021192T3 (zh)
ES (1) ES2191352T3 (zh)
HK (1) HK1030748A1 (zh)
HU (1) HU224986B1 (zh)
IL (1) IL135001A0 (zh)
MX (1) MXPA00003363A (zh)
PL (1) PL189727B1 (zh)
WO (1) WO1999017780A1 (zh)
ZA (1) ZA989066B (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101190177B (zh) * 2006-11-24 2010-09-01 上海医药工业研究院 醋酸地塞米松局部成膜凝胶组合物及其应用

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* Cited by examiner, † Cited by third party
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TW200808375A (en) 2006-05-12 2008-02-16 Otsuka Pharma Co Ltd Hydrogel suspension and manufacturing process thereof
US20150190407A1 (en) * 2014-01-07 2015-07-09 Insite Vision Incorporated Methods for treatment of postoperative inflammation with reduced intraocular pressure

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2212392C3 (de) * 1972-03-15 1981-03-19 Avicon Inc., Fort Worth, Tex. Verwendung von mikrokristallinem Collagen zur Herstellung eines wäßrigen pharmazeutischen Mittels für die topische Anwendung am Auge
JPS6056684B2 (ja) * 1977-11-07 1985-12-11 東興薬品工業株式会社 点眼剤
US4271143A (en) * 1978-01-25 1981-06-02 Alcon Laboratories, Inc. Sustained release ophthalmic drug dosage
DE3066859D1 (en) * 1979-10-26 1984-04-12 Smith & Nephew Ass Autoclavable emulsions
JPS63174924A (ja) * 1987-01-14 1988-07-19 Toko Yakuhin Kogyo Kk 軟膏基剤および軟膏剤
US5252318A (en) * 1990-06-15 1993-10-12 Allergan, Inc. Reversible gelation compositions and methods of use
EP0551626A1 (en) * 1991-12-19 1993-07-21 LEK, tovarna farmacevtskih in kemicnih izdelkov, d.d. Thermoreversible gel as a liquid pharmaceutical carrier for a galenic formulation
WO1993017664A1 (en) * 1992-03-02 1993-09-16 Alcon Laboratories, Inc. Combinations of cellulosic polymers and carboxy vinyl polymers and their use in pharmaceutical compositions
DE4209722C3 (de) * 1992-03-25 1997-06-19 Medproject Pharma Entwicklungs Tropfbares Gel für die Augenheilkunde
WO1995005803A1 (en) * 1993-08-20 1995-03-02 Alcon Laboratories, Inc. Topical ophthalmic pharmaceutical vehicles
DE4404990C1 (de) * 1994-02-17 1995-05-04 Mann Gerhard Chem Pharm Fab Verfahren zur Herstellung eines sterilen Prednisolongels
US5683993A (en) * 1995-06-22 1997-11-04 Ciba Vision Corporation Compositions and methods for stabilizing polymers
DE19614823A1 (de) * 1996-04-15 1997-10-16 Mann Gerhard Chem Pharm Fab Ophthalmische Zusammensetzung mit verlängerter Verweilzeit am Auge

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101190177B (zh) * 2006-11-24 2010-09-01 上海医药工业研究院 醋酸地塞米松局部成膜凝胶组合物及其应用

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EP1021192B1 (de) 2003-01-08
KR100392481B1 (ko) 2003-07-23
IL135001A0 (en) 2001-05-20
DE59806884D1 (en) 2003-02-13
DK1021192T3 (da) 2003-05-05
WO1999017780A1 (de) 1999-04-15
PL189727B1 (pl) 2005-09-30
ATE230601T1 (de) 2003-01-15
HU224986B1 (en) 2006-05-29
ES2191352T3 (es) 2003-09-01
JP2001518510A (ja) 2001-10-16
CA2300806A1 (en) 1999-04-15
HK1030748A1 (en) 2001-05-18
AR017170A1 (es) 2001-08-22
DE19744113A1 (de) 1999-04-15
MXPA00003363A (es) 2007-12-07
HUP0003796A2 (hu) 2001-04-28
BR9812849A (pt) 2000-08-08
KR20010030939A (ko) 2001-04-16
HUP0003796A3 (en) 2001-05-28
PL341026A1 (en) 2001-03-26
ZA989066B (en) 1999-06-15
JP4156793B2 (ja) 2008-09-24
CN1142782C (zh) 2004-03-24
CA2300806C (en) 2004-02-03
WO1999017780A8 (de) 2000-01-27
EP1021192A1 (de) 2000-07-26

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