CN1456350A - Eye cyclosporin gel - Google Patents

Eye cyclosporin gel Download PDF

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Publication number
CN1456350A
CN1456350A CN 02117619 CN02117619A CN1456350A CN 1456350 A CN1456350 A CN 1456350A CN 02117619 CN02117619 CN 02117619 CN 02117619 A CN02117619 A CN 02117619A CN 1456350 A CN1456350 A CN 1456350A
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gel
cyclosporine
methyl
containing
formulation
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CN 02117619
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Chinese (zh)
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刘继东
姚东民
高峨
宋长海
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刘继东
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Abstract

A cyclosporin eye gel for treating the rejection reaction of corneal transplantation, keratoconjunctival xerosis, catarrhal conjunctivitis, and chemical burn of eye is prepared from cyclosporin, boric acid, borax, trichloro-tert-butanol, etc. Its advantages are long stay time in eye and high curative effect.

Description

环孢素眼用凝胶 Cyclosporine ophthalmic gel

所属技术领域本发明涉及一种药物有效成分——环孢素——首次制成眼用凝胶,应用于眼部疾病的治疗,主要治疗以下眼科疾病:1、角膜移植排斥反应,2、角、结膜干燥症(KC),3、春季卡他性结膜炎,4、眼部化学烧伤(2度至4度)。 The present invention relates to the art a pharmaceutically effective ingredient - cyclosporin - first made ophthalmic gel, applied to the treatment of eye diseases, eye diseases the following main treatment: 1, corneal graft rejection, 2, angle , sicca (KC), 3, vernal conjunctivitis, 4, ocular chemical burns (2 degrees to 4 degrees).

本发明的技术方案是:环孢素药物成分与卡泊姆膏体基质形成稳定的透明膏体,施用后在眼表形成一层透气的网状膜,作用持久。 Aspect of the present invention are: cyclosporin pharmaceutical ingredient and the matrix-forming paste carbomers stable transparent paste, net-like film is formed after the administration of the ocular surface layer of breathable, lasting effect. 其具体特征如下:环孢素眼用凝胶单方制剂,其通用名为环孢素眼用凝胶;化学名为环[[(E)-(2S,3R,4R)-3-羟基-4-甲基-2-(甲氨基)-6-辛烯酰]-L-2氨基丁酰-N-甲基甘氨酰-N-甲基-L-亮氨酰-L-缬氨酰-N-甲基-L-亮氨酰-L-丙氨酰-D-丙氨酰-N-甲基-L-亮氨酰-N-甲基-L-亮氨酰-N-甲基-L-缬氨酰]眼用凝胶;英文名为CiclosporinOphthalmic Gel;汉语拼音为Huanbaosu Yanyong Ningjiao;药物与主要辅料成分及其按下列比例组成的应用于眼科疾患的制剂:其中含环孢素为2.0%(w/w),含卡泊姆为0.4%(w/w),含硼砂为1.0%(w/w),含硼酸为0.5%(w/w),含三氯叔丁醇为0.3%(w/w);应用于角膜移植排斥反应、角膜结膜干燥症(KC)、春季卡他性结膜炎、眼部化学烧伤(2度至4度)等眼科疾患的治疗;其制备工艺过程为:取处方量的三氯叔丁醇用900ml注射用水溶解,将卡波姆浸泡其中,过夜。 Specific characteristics are as follows: cyclosporine ophthalmic gel formulations unilateral, the generic name of cyclosporine ophthalmic gel; chemical name ring [[(E) - (2S, 3R, 4R) -3- hydroxy-4 - methyl-2- (methylamino) -6-octyloxy-enoyl] -L-2-methyl-aminobutyryl-glycyl -N- -N- methyl -L- leucyl -L- valyl - N- methyl -L- leucyl-alanyl -D- -L- alanyl -L- -N- methyl -N- methyl -L- leucyl-leucyl -N- methyl - L- valyl] ophthalmic gel; English name CiclosporinOphthalmic gel; pinyin Huanbaosu Yanyong Ningjiao; primary pharmaceutical excipients and their formulations ingredients used in ophthalmology disorders consisting of the following proportions: 2.0 which contains cyclosporine % (w / w), of carbomers containing 0.4% (w / w), borax containing 1.0% (w / w), containing boric acid was 0.5% (w / w), containing chlorobutanol 0.3 % (w / w); applied to corneal graft rejection, corneal sicca (KC), ophthalmic disorders vernal conjunctivitis treating him, ocular chemical burns (2 degrees to 4 degrees) and the like; the preparation process as follows: the formulation amounts chlorobutanol was dissolved with 900ml water for injection, wherein the carbomer soaking overnight. 取处方量的硼砂、硼酸加入其中,搅拌均匀,制成透明凝胶基质;将处方量环孢素研成极细粉,过9号筛,加热条件下分次研入基质中,补水至全量,充分搅拌均匀;用220目筛布过滤,热压灭菌,分装,即得。 The formulation amounts of borax, boric acid was added thereto, followed by stirring uniformly to prepare a transparent gel matrix; the amount of the cyclosporine formulation research into a very fine powder, passed through a No. 9 sieve fractionation under heating RESEARCH into the host, to pay the full amount , stir; filtered with a 220 mesh screen, autoclaving, packaging, i.e., too. 另外,药物有效成分与羟丙甲基纤维素系列、甲基纤维素系列、聚乙烯醇系列等基质均可形成凝胶,卡泊姆系列基质效果最好。 Further, the pharmaceutical active ingredient is mixed with hydroxypropyl methylcellulose series, cellulose series, a polyvinyl alcohol series can form a gel matrix, the matrix carbomers series best. 上述制备工艺中,其核心技术是:(1)环孢素药物成分研磨成极细粉(过9号筛),(2)与辅料成分研磨加热(温度范围60-80℃)混合溶解是保证膏体透明的关键,(3)卡泊姆溶涨(浓度范围0.5-5.0%)制成透明乳膏,(4)热压灭菌(115℃,30分钟)。 The above-described manufacturing process, the core technology is: (1) cyclosporin pharmaceutical ingredient ground to a very fine powder (sieve through a No. 9), (2) heating the abrasive component materials (temperature range 60-80 deg.] C) were mixed and dissolved ensure a transparent paste key, (3) swelling carbomers (concentration range 0.5 to 5.0%) made of a transparent cream, (4) autoclaving (115 ℃, 30 minutes).

本发明的积极效果:环孢素眼用凝胶的研制与开发有以下优点:(1)、环孢素眼用凝胶直接作用于患处,能充分有效地发挥作用,可减少口服药物引起的胃肠道刺激和其他副作用。 The positive effect of the invention: cyclosporine ophthalmic gel research and development has the following advantages: (1), cyclosporine ophthalmic gel acts directly on the affected area, sufficiently to function effectively, reduce drug-induced oral gastrointestinal irritation and other side effects. (2)、相对于其它眼用制剂,凝胶剂具有无可比拟的优点。 (2), relative to the other eye has incomparable advantages preparations, gels. 和滴眼液相比环孢素眼用凝胶不易被泪液稀释,在眼内停留时间长,有利于主要的充分吸收和利用;和凡士林基质的眼膏相比,环孢素眼用凝胶水溶性好,容易清洗,不污染衣物,使用方便。 And cyclosporine ophthalmic drops can not easily be diluted with tear gel, a long residence time in the eye, a major beneficial compared to fully absorb and use; and petrolatum ointment matrix compared to cyclosporine ophthalmic gel good water solubility, easy to clean, not contaminated clothing, and easy to use. 另一方面,环孢素眼用凝胶不造成视野模糊,使用后在眼表形成一层透气的网状膜,昼夜都可使用。 On the other hand, cyclosporine ophthalmic gel does not cause blurry vision, after the film is formed using a layer of air-permeable mesh ocular surface, it can be used day and night. 本产品的开发成功,不仅可填补国内眼科用药的一项空白,还可带来很好的社会效益和经济效益。 The successful development of this product, not only to fill a gap in the domestic ophthalmic drugs, but also bring good social and economic benefits. (3)、我们企业是国内专业的眼科用药生产厂家,30多年来一直致力于眼药的生产、研制、开发,积极参加社会公益事业,眼科用药占总产值的90%以上。 (3), our business is the professional manufacturer of ophthalmic drugs, 30 years has been dedicated to the production of ophthalmic drugs, research and development, and actively participate in social welfare undertakings, ophthalmic drugs accounted for 90% of GDP.

②.硼砂、硼酸加入①中,制成透明凝胶基质。 ②. Borax, boric acid was added in ①, made of a transparent gel matrix.

③.环孢素研磨成极细粉,过9号筛,加热条件下分次研入②中。 ③. Cyclosporin ground into a very fine powder, passed through a No. 9 screen, divided into RESEARCH ② under heating.

④.220目筛布过滤,热压灭菌,分装,包装,即得。 ④.220 mesh screen filtration, autoclaving, packaging, packing, ie.

处方2:环孢素 0.5-10.0g卡泊姆 0-4.0g硼砂 0-10.0g硼酸 0-5.0g三氯叔丁醇 0-3.0g制成 100.0g操作过程:①.适量水,溶解三氯叔丁醇,加入卡泊姆溶解,过夜。 Prescription 2: cyclosporine 0.5-10.0g carbomers 0-4.0g borax 0-10.0g acid 0-5.0g chlorobutanol 0-3.0g made 100.0g operation:. ① amount of water, dissolved three chloro tert-butanol, Jia Ruka carbomers dissolve overnight.

②.硼砂、硼酸加入①中,制成透明凝胶基质。 ②. Borax, boric acid was added in ①, made of a transparent gel matrix.

③.环孢素研磨成极细粉,过9号筛,加热条件下分次研入②中。 ③. Cyclosporin ground into a very fine powder, passed through a No. 9 screen, divided into RESEARCH ② under heating.

④.220目筛布过滤,热压灭菌,分装,包装,即得。 ④.220 mesh screen filtration, autoclaving, packaging, packing, ie. 本发明的创造性,通过临床、毒理药理数据来实现,实质审查时一并提供。 Inventive present invention, is achieved by clinical pharmacology toxicological data, provided together during substantive examination.

图1为环孢素眼用凝胶制备工艺流程图。 Figure 1 is a process flow diagram for preparation of a gel cyclosporine ophthalmic.

Claims (2)

  1. 1.一种用于角膜移植排斥反应、角膜结膜干燥症(KC)、春季卡他性结膜炎、眼部化学烧伤(2度至4度)等眼科疾患治疗的环孢素眼用凝胶单方制剂,其通用名为环孢素眼用凝胶;化学名为环[[(E)-(2S,3R,4R)-3-羟基-4-甲基-2-(甲氨基)-6-辛烯酰]-L-2氨基丁酰-N-甲基甘氨酰-N-甲基-L-亮氨酰-L-缬氨酰-N-甲基-L-亮氨酰-L-丙氨酰-D-丙氨酰-N-甲基-L-亮氨酰-N-甲基-L-亮氨酰-N-甲基-L-缬氨酰]眼用凝胶;英文名为Ciclosporin Ophthalmic Gel;汉语拼音为Huanbaosu Yanyong Ningjiao;药物与主要辅料成分及其按下列比例组成的应用于眼科的制剂:其中含环孢素为2.0%(w/w),含卡泊姆为0.4%(w/w),含硼砂为1.0%(w/w),含硼酸为0.5%(w/w),含三氯叔丁醇为0.3%(w/w);制备工艺过程:取处方量的三氯叔丁醇用900ml注射用水溶解,将卡波姆浸泡其中,过夜。 Cyclosporin A eye for corneal graft rejection, corneal sicca (KC), vernal conjunctivitis, ocular chemical burns (2 degrees to 4 degrees) and other eye diseases treated with unilateral gel formulation, the generic name of cyclosporine ophthalmic gel; chemical name ring [[(E) - (2S, 3R, 4R) -3- hydroxy-4-methyl-2- (methylamino) -6- oct-enoyl] -L-2-methyl-aminobutyryl-glycyl -N- -N- methyl -L- leucyl -L- valyl -N- methyl -L- leucyl -L- -D- alanyl-alanyl -L- -N- methyl -N- methyl -L- leucyl-leucyl -N- methyl -L- valyl] ophthalmic gel; English of ciclosporin ophthalmic Gel; pinyin Huanbaosu Yanyong Ningjiao; primary pharmaceutical excipients and their formulations ingredients used in ophthalmology according to the following composition ratio: wherein cyclosporine containing 2.0% (w / w), containing 0.4 carbomers % (w / w), borax containing 1.0% (w / w), containing boric acid was 0.5% (w / w), containing chlorobutanol was 0.3% (w / w); preparation process: The formulation the amount of chlorobutanol dissolved in 900ml water for injection, wherein the carbomer soaking overnight. 取处方量的硼砂、硼酸加入其中,搅拌均匀,制成透明凝胶基质;将处方量环孢素研成极细粉,过9号筛,加热条件下分次研入基质中,补水至全量,充分搅拌均匀;用220目筛布过滤,热压灭菌,分装,即得。 The formulation amounts of borax, boric acid was added thereto, followed by stirring uniformly to prepare a transparent gel matrix; the amount of the cyclosporine formulation research into a very fine powder, passed through a No. 9 sieve fractionation under heating RESEARCH into the host, to pay the full amount , stir; filtered with a 220 mesh screen, autoclaving, packaging, i.e., too. 另外,环孢素药物有效成分与羟丙甲基纤维素系列、甲基纤维素系列、聚乙烯醇系列等基质均可形成凝胶,卡泊姆系列基质效果最好。 Moreover, pharmaceutical active ingredient with cyclosporine hydroxypropyl methylcellulose series, cellulose series, a polyvinyl alcohol series can form a gel matrix, the matrix carbomers series best. 上述制备工艺中,其核心技术是:(1)环孢素药物成分研磨成极细粉(过9号筛),(2)与辅料成分研磨加热(温度范围60-80℃)混合溶解是保证膏体透明的关键,(3)卡泊姆溶涨(浓度范围0.5-5.0%)制成透明乳膏,(4)热压灭菌(115℃,30分钟)。 The above-described manufacturing process, the core technology is: (1) cyclosporin pharmaceutical ingredient ground to a very fine powder (sieve through a No. 9), (2) heating the abrasive component materials (temperature range 60-80 deg.] C) were mixed and dissolved ensure a transparent paste key, (3) swelling carbomers (concentration range 0.5 to 5.0%) made of a transparent cream, (4) autoclaving (115 ℃, 30 minutes).
  2. 2.按照权利要求1所述的环孢素眼用凝胶,其特征在于该药物有效成分环孢素首次制成眼用凝胶剂,药物与主要辅料成分及其按下列比例组成的应用于眼科疾患治疗的制剂:其中环孢素为其药效成分,浓度为0.5-10.0%(w/w),主要辅料含卡泊姆为0-4.0%(w/w),含硼砂为0-10.0%(w/w),含硼酸为0-5.0%(w/w),含三氯叔丁醇为0-3.0%(w/w)。 2. applied according to the cyclosporine ophthalmic gel claim 1, characterized in that the pharmaceutical active ingredient cyclosporine ophthalmic gel first formed, the pharmaceutical ingredients and the excipients mainly composed of the following proportions ophthalmic disorders treatment formulation: wherein cyclosporine its medicinal ingredient, a concentration of 0.5-10.0% (w / w), adjuvant mainly comprising carbomers of 0-4.0% (w / w), containing from 0 to borax 10.0% (w / w), containing boric acid is 0-5.0% (w / w), containing chlorobutanol was 0-3.0% (w / w).
CN 02117619 2002-05-10 2002-05-10 Eye cyclosporin gel CN1456350A (en)

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Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7083803B2 (en) 2003-09-19 2006-08-01 Advanced Ocular Systems Limited Ocular solutions
US7083802B2 (en) 2003-07-31 2006-08-01 Advanced Ocular Systems Limited Treatment of ocular disease
US7087237B2 (en) 2003-09-19 2006-08-08 Advanced Ocular Systems Limited Ocular solutions
US7354574B2 (en) 2002-11-07 2008-04-08 Advanced Ocular Systems Limited Treatment of ocular disease
US7833966B2 (en) 2005-07-18 2010-11-16 Peyman Gholam A Enhanced ocular neuroprotection and neurostimulation
US8222271B2 (en) 2006-03-23 2012-07-17 Santen Pharmaceutical Co., Ltd. Formulations and methods for vascular permeability-related diseases or conditions
US8367097B2 (en) 2005-02-09 2013-02-05 Santen Pharmaceutical Co., Ltd. Liquid formulations for treatment of diseases or conditions
US8492400B2 (en) 2006-02-09 2013-07-23 Santen Pharmaceutical Co., Ltd. Stable formulations, and methods of their preparation and use
US8663639B2 (en) 2005-02-09 2014-03-04 Santen Pharmaceutical Co., Ltd. Formulations for treating ocular diseases and conditions
CN103656617A (en) * 2012-09-26 2014-03-26 沈阳兴齐眼药股份有限公司 Preparation method of ciclosporin ophthalmic solution
CN103735495A (en) * 2014-01-23 2014-04-23 兆科药业(合肥)有限公司 Ciclosporin eye gel and preparation method thereof
CN104039308A (en) * 2011-11-15 2014-09-10 阿勒根公司 Autoclavable suspensions of cyclosporin a form 2

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7354574B2 (en) 2002-11-07 2008-04-08 Advanced Ocular Systems Limited Treatment of ocular disease
US7083802B2 (en) 2003-07-31 2006-08-01 Advanced Ocular Systems Limited Treatment of ocular disease
US7083803B2 (en) 2003-09-19 2006-08-01 Advanced Ocular Systems Limited Ocular solutions
US7087237B2 (en) 2003-09-19 2006-08-08 Advanced Ocular Systems Limited Ocular solutions
US9387165B2 (en) 2005-02-09 2016-07-12 Santen Pharmaceutical Co., Ltd. Rapamycin formulations and methods of their use
US9381153B2 (en) 2005-02-09 2016-07-05 Santen Pharmaceutical Co., Ltd. Liquid formulations for treatment of diseases or conditions
US8927005B2 (en) 2005-02-09 2015-01-06 Santen Pharmaceutical Co., Ltd. Liquid formulations for treatment of diseases or conditions
US8367097B2 (en) 2005-02-09 2013-02-05 Santen Pharmaceutical Co., Ltd. Liquid formulations for treatment of diseases or conditions
US8663639B2 (en) 2005-02-09 2014-03-04 Santen Pharmaceutical Co., Ltd. Formulations for treating ocular diseases and conditions
US8637070B2 (en) 2005-02-09 2014-01-28 Santen Pharmaceutical Co., Ltd. Rapamycin formulations and methods of their use
US8202840B2 (en) 2005-07-18 2012-06-19 Minu L.L.C. Enhanced ocular neuroprotection and neurostimulation
US7833966B2 (en) 2005-07-18 2010-11-16 Peyman Gholam A Enhanced ocular neuroprotection and neurostimulation
US8492400B2 (en) 2006-02-09 2013-07-23 Santen Pharmaceutical Co., Ltd. Stable formulations, and methods of their preparation and use
US8658667B2 (en) 2006-02-09 2014-02-25 Santen Pharmaceutical Co., Ltd. Stable formulations, and methods of their preparation and use
US9452156B2 (en) 2006-03-23 2016-09-27 Santen Pharmaceutical Co., Ltd. Formulations and methods for vascular permeability-related diseases or conditions
US8222271B2 (en) 2006-03-23 2012-07-17 Santen Pharmaceutical Co., Ltd. Formulations and methods for vascular permeability-related diseases or conditions
US8486960B2 (en) 2006-03-23 2013-07-16 Santen Pharmaceutical Co., Ltd. Formulations and methods for vascular permeability-related diseases or conditions
CN104039308B (en) * 2011-11-15 2018-06-05 阿勒根公司 2 may be in the form of a cyclosporin hot suspension of
CN104039308A (en) * 2011-11-15 2014-09-10 阿勒根公司 Autoclavable suspensions of cyclosporin a form 2
CN103656617A (en) * 2012-09-26 2014-03-26 沈阳兴齐眼药股份有限公司 Preparation method of ciclosporin ophthalmic solution
CN103735495A (en) * 2014-01-23 2014-04-23 兆科药业(合肥)有限公司 Ciclosporin eye gel and preparation method thereof

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