CN1222282C - 注入堆积密度为0.28～0.38g/ml的含有布地奈德的吸入用新配方 - Google Patents
注入堆积密度为0.28～0.38g/ml的含有布地奈德的吸入用新配方 Download PDFInfo
- Publication number
- CN1222282C CN1222282C CNB988018985A CN98801898A CN1222282C CN 1222282 C CN1222282 C CN 1222282C CN B988018985 A CNB988018985 A CN B988018985A CN 98801898 A CN98801898 A CN 98801898A CN 1222282 C CN1222282 C CN 1222282C
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- China
- Prior art keywords
- bulk density
- compositions
- budesonide
- carrier mass
- inhalation
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired - Lifetime
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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
-
- 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
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
-
- 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
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
Abstract
一种干粉剂组合物，其中包含布地奈德和一种载体物质，这两种物质都呈微细形式，其中该配方的注入堆积密度为0.28～0.38g/ml。这种干粉剂组合物在治疗呼吸系统疾病方面是有用的。
Description
发明领域
本发明提供一种新药物配方、其制备及其用途。
发明背景
吸入法给药用的强效药因其制备精确剂量的问题，一般是与乳糖等载体相缔合来配制的。当这样的药物稀释时，配方重量的差异导致与它们未被稀释时比较更小的药物剂量差异。这些配方一般由载体的粗大颗粒和药物的微细颗粒组成，这种组合一般称为订做的混合物。
本发明提供一种改进的配方，在为模仿吸入而设计的系统中，已发现该配方能改善药物的分散。
本发明说明
按照本发明，提供的是一种干粉剂组合物，其中包含布地奈德和一种载体物质，这两种物质都呈微细形式，其中该配方的注入堆积密度为0.28～0.38g/mL，较好为0.30～0.36g/mL。
按照本发明的注入堆积密度是用已知技术测定的，例如“粉末测试指南：散装粉末物理性能测定方法”L.Svarovsky，ElsevierApplied Science 1987，pp 84-86中描述的那些。
载体物质较好的是一种单糖、二糖或多糖，一种糖醇或一种多醇。适用的载体是诸如乳糖、葡萄糖、棉子糖、松三糖、乳糖醇、麦牙糖醇、茧蜜糖、蔗糖、甘露糖；和淀粉。乳糖是特别好，特别是其一水合物形式。
按照本发明的配方的各组分必须均呈微细形式，即它们的质量中值直径一般应当小于10μm，较好的是1～7μm，是用激光衍射仪或coulter计数器测定的。这些组分可以用有本门技术技能的人员已知的方法例如研磨、微粉化或直接沉淀，以所希望的粒度产生。
按照本发明的组合物最好配制成含有20～4300μg布地奈德(优选80～2150μg)作为日剂量。更好是，将该组合物配制成能提供200μg或400μg布地奈德的单元剂量。该组合物配制成每单元剂量优选包含50μg～25mg，更优选50μg～10mg，最优选100～4000μg的载体物质。
按照本发明，进一步提供的是按照本发明的一种组合物的制备方法，包括
(a)将布地奈德和载体物质进行微粉化；
(b)任选地调理该产品；和
(c)球形化直至得到所希望的堆积密度。
本工艺在步骤(b)之后较好进一步包含一个低能量再微粉化步骤。
按照本发明的配方可以用本身已知的常用技术制作。这样的生产工艺一般包括使这些组分微粉化成所需要的粒度，用诸如WO92/18110或WO 95/05805中所述的方法除去所得到颗粒上的任何无定形区域，然后将所得到的粉末造粒、球形化和过筛。所得到团粒的粒度较好在100～2000μm的范围内，更好的是在100～800μm。所生产配方的堆积密度可以根据经验通过改变成分和工艺来调节，例如，可以通过延长颗粒在球形化装置中翻滚的时间来提高堆积密度。
在固-固混合中，最重要的特色之一是确保含量均匀。微细粉末的粉末混合中遇到的主要问题是混合机不能使粉末团粒破碎。已经发现，微细粉末调理步骤之后用低能量输入的再微粉化步骤是有利的。它一般应当用足以使粉末团粒破碎的能量进行，但不要用如此多的能量，以致影响颗粒本身的粒度。这样一个步骤给出一种组合物，其中，活性物质和载体物质大体上均匀分布，例如相对标准偏差小于3％(较好小于1％)，且不影响微细颗粒的结晶性。
按照本发明的配方可用任何已知干粉吸入器给药，例如该吸入器可以是单剂量或多剂量吸入器，还可以是一种呼吸驱动干粉吸入器，例如Turbuhaler(商品名)。本发明进一步提供按照本发明的组合物在制造用于治疗的药物方面的用途。按照本发明的组合物在治疗呼吸系统疾病，特别是气喘病方面是有用的。本发明也提供治疗受呼吸系统疾病困扰的病人的方法，该方法包括对患者施用治疗有效量的按照本发明的组合物。
下列实例说明，但不限制本发明。
实例
9份布地奈德和91份乳糖一水合物在约6～7巴压力下分别在螺旋喷射磨中单独进行微粉化，得到小于3μm的颗粒尺寸，然后在Turbula混炼机中充分混合。混合之前，乳糖一水合物粉末按WO 95/05805所述方法进行处理。混合物在仅约1巴的压力下在螺旋喷射磨中再次进行微粉化，以便得到均匀的混合物。然后将该粉末喂入双螺杆进料机(K-Tron)中使粉末聚集，在振动筛(0.5mm目径)中过筛，在圆周速度0.5m/s的旋转盘中进行球形化4分钟，然后再用同样的筛子过筛，随后再球形化6分钟，最后再过筛(目径1.0mm)，得到堆积密度为0.35g/ml的粉末。
Claims (6)
1.一种干粉剂组合物，其中包含
a)布地奈德，和
b)一种选自单糖、二糖和多糖的载体物质，其中活性物质和载体物质的质量中值直径小于10μm，且其中组合物的注入堆积密度为0.28～0.38g/ml。
2.按照权利要求1的组合物，其中所述堆积密度是0.30～0.36g/ml。
3.按照权利要求1或2的组合物，其中所述载体物质是乳糖一水合物。
4.制备按照权利要求1的组合物的方法，该方法包括：
(a)将布地奈德和载体物质进行微粉化；
(b)任选地调理该产品；和
(c)球形化直至得到所希望的堆积密度。
5.按照权利要求4的方法，该方法还包括在步骤(b)之后的低能量再微粉化步骤。
6.按照权利要求1-3中任何一项的组合物在制造用于治疗呼吸系统疾病的药物方面的用途。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE97001333 | 1997-01-20 | ||
| SE9700133A SE9700133D0 (sv) | 1997-01-20 | 1997-01-20 | New formulation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1243434A CN1243434A (zh) | 2000-02-02 |
| CN1222282C true CN1222282C (zh) | 2005-10-12 |
Family
ID=20405452
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB988018985A Expired - Lifetime CN1222282C (zh) | 1997-01-20 | 1998-01-13 | 注入堆积密度为0.28～0.38g/ml的含有布地奈德的吸入用新配方 |
Country Status (35)
| Country | Link |
|---|---|
| US (1) | US6027714A (zh) |
| EP (1) | EP1019033B1 (zh) |
| JP (1) | JP2010059179A (zh) |
| KR (1) | KR100528418B1 (zh) |
| CN (1) | CN1222282C (zh) |
| AT (1) | ATE389390T1 (zh) |
| AU (1) | AU726916B2 (zh) |
| BE (1) | BE1011400A5 (zh) |
| BR (1) | BR9806892A (zh) |
| CA (1) | CA2277914C (zh) |
| CZ (1) | CZ295083B6 (zh) |
| DE (1) | DE69839275T2 (zh) |
| DK (1) | DK1019033T3 (zh) |
| EE (1) | EE03998B1 (zh) |
| ES (2) | ES2302348T3 (zh) |
| FR (1) | FR2759908B1 (zh) |
| GR (1) | GR1003290B (zh) |
| HK (1) | HK1025516A1 (zh) |
| HU (1) | HU228312B1 (zh) |
| ID (1) | ID22883A (zh) |
| IE (1) | IE980024A1 (zh) |
| IL (1) | IL130840A (zh) |
| IS (1) | IS2563B (zh) |
| NL (1) | NL1008019C2 (zh) |
| NO (1) | NO327451B1 (zh) |
| NZ (1) | NZ336592A (zh) |
| PL (1) | PL191569B1 (zh) |
| PT (1) | PT1019033E (zh) |
| RU (1) | RU2180563C2 (zh) |
| SE (1) | SE9700133D0 (zh) |
| SI (1) | SI1019033T1 (zh) |
| SK (1) | SK283948B6 (zh) |
| TR (1) | TR199901691T2 (zh) |
| UA (1) | UA57762C2 (zh) |
| WO (1) | WO1998031350A1 (zh) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9803770D0 (sv) * | 1998-11-05 | 1998-11-05 | Astra Ab | Dry powder pharmaceutical formulation |
| EP1129705A1 (en) | 2000-02-17 | 2001-09-05 | Rijksuniversiteit te Groningen | Powder formulation for inhalation |
| GB0008660D0 (en) * | 2000-04-07 | 2000-05-31 | Arakis Ltd | The treatment of respiratory diseases |
| GB0012261D0 (en) * | 2000-05-19 | 2000-07-12 | Astrazeneca Ab | Novel process |
| FR2809692A1 (fr) | 2000-05-31 | 2001-12-07 | Ecia Equip Composants Ind Auto | Ensemble de masquage d'un coussin gonflable de securite pour vehicule automobile, procede de fabrication et planche de bord correspondante |
| US20020141946A1 (en) * | 2000-12-29 | 2002-10-03 | Advanced Inhalation Research, Inc. | Particles for inhalation having rapid release properties |
| US20030055026A1 (en) * | 2001-04-17 | 2003-03-20 | Dey L.P. | Formoterol/steroid bronchodilating compositions and methods of use thereof |
| US6681768B2 (en) | 2001-06-22 | 2004-01-27 | Sofotec Gmbh & Co. Kg | Powder formulation disintegrating system and method for dry powder inhalers |
| US7931022B2 (en) * | 2001-10-19 | 2011-04-26 | Respirks, Inc. | Method and apparatus for dispensing inhalator medicament |
| SE0200657D0 (sv) * | 2002-03-04 | 2002-03-04 | Astrazeneca Ab | Novel Formulation |
| TWI359675B (en) * | 2003-07-10 | 2012-03-11 | Dey L P | Bronchodilating β-agonist compositions |
| GB0327723D0 (en) * | 2003-09-15 | 2003-12-31 | Vectura Ltd | Pharmaceutical compositions |
| US20070020299A1 (en) | 2003-12-31 | 2007-01-25 | Pipkin James D | Inhalant formulation containing sulfoalkyl ether cyclodextrin and corticosteroid |
| US20070020298A1 (en) * | 2003-12-31 | 2007-01-25 | Pipkin James D | Inhalant formulation containing sulfoalkyl ether gamma-cyclodextrin and corticosteroid |
| CN100333727C (zh) * | 2004-11-25 | 2007-08-29 | 天津药业研究院有限公司 | 布地奈德靶向微丸及其制备方法 |
| ES2493641T3 (es) * | 2007-06-28 | 2014-09-12 | Cydex Pharmaceuticals, Inc. | Administración nasal de soluciones acuosas de corticosteroides |
| DE102007049931A1 (de) | 2007-10-18 | 2009-04-23 | Pharmatech Gmbh | Vorrichtung und Verfahren zur kontinuierlichen Herstellung von sphärischen Pulveragglomeraten |
| WO2011110852A1 (en) | 2010-03-10 | 2011-09-15 | Astrazeneca Ab | Polymorphic forms of 6- [2- (4 -cyanophenyl) - 2h - pyrazol - 3 - yl] - 5 -methyl - 3 - oxo - 4 - (trifluoromethyl - phenyl) 3,4-dihydropyrazine-2-carboxylic acid ethylamide |
| EP2821062A1 (en) | 2013-07-01 | 2015-01-07 | Arven Ilac Sanayi Ve Ticaret A.S. | Novel dry powder inhaler formulations |
| AU2018318123A1 (en) | 2017-08-15 | 2020-03-19 | Nephron Pharmaceuticals Corporation | Aqueous nebulization composition |
| JP2022549445A (ja) | 2019-09-24 | 2022-11-25 | キエシ・フアルマチエウテイチ・ソチエタ・ペル・アチオニ | 吸入用乾燥粉末製剤のための新規担体粒子 |
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| GB1429184A (en) * | 1972-04-20 | 1976-03-24 | Allen & Hanburys Ltd | Physically anti-inflammatory steroids for use in aerosols |
| GB1571629A (en) * | 1977-11-30 | 1980-07-16 | Fisons Ltd | Pharmaceutical compositions containing beclomethasone dipropionate |
| SE438261B (sv) * | 1981-07-08 | 1985-04-15 | Draco Ab | Anvendning i dosinhalator av ett perforerat membran |
| ATE23272T1 (de) * | 1981-07-08 | 1986-11-15 | Draco Ab | Pulverinhalator. |
| DE3268533D1 (en) * | 1981-07-24 | 1986-02-27 | Fisons Plc | Inhalation drugs, methods for their production and pharmaceutical formulations containing them |
| EP0705614B1 (en) * | 1989-04-28 | 2002-09-25 | Riker Laboratories, Inc. | Dry powder inhalation device |
| US5176132A (en) * | 1989-05-31 | 1993-01-05 | Fisons Plc | Medicament inhalation device and formulation |
| US5192548A (en) * | 1990-04-30 | 1993-03-09 | Riker Laboratoires, Inc. | Device |
| SE9100342D0 (sv) * | 1991-02-04 | 1991-02-04 | Astra Ab | Novel steroid esters |
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| IS1736B (is) * | 1993-10-01 | 1999-12-30 | Astra Ab | Aðferð og tæki sem stuðla að aukinni samloðun agna |
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| SE9603669D0 (sv) * | 1996-10-08 | 1996-10-08 | Astra Ab | New combination |
-
1997
- 1997-01-20 SE SE9700133A patent/SE9700133D0/xx unknown
-
1998
- 1998-01-09 US US09/004,894 patent/US6027714A/en not_active Expired - Lifetime
- 1998-01-13 EP EP98901616A patent/EP1019033B1/en not_active Expired - Lifetime
- 1998-01-13 CA CA002277914A patent/CA2277914C/en not_active Expired - Lifetime
- 1998-01-13 SK SK957-99A patent/SK283948B6/sk not_active IP Right Cessation
- 1998-01-13 IL IL13084098A patent/IL130840A/xx not_active IP Right Cessation
- 1998-01-13 DE DE69839275T patent/DE69839275T2/de not_active Expired - Lifetime
- 1998-01-13 PT PT98901616T patent/PT1019033E/pt unknown
- 1998-01-13 ID IDW990664A patent/ID22883A/id unknown
- 1998-01-13 TR TR1999/01691T patent/TR199901691T2/xx unknown
- 1998-01-13 HU HU0000841A patent/HU228312B1/hu unknown
- 1998-01-13 PL PL334493A patent/PL191569B1/pl unknown
- 1998-01-13 DK DK98901616T patent/DK1019033T3/da active
- 1998-01-13 CN CNB988018985A patent/CN1222282C/zh not_active Expired - Lifetime
- 1998-01-13 CZ CZ19992555A patent/CZ295083B6/cs not_active IP Right Cessation
- 1998-01-13 AU AU57857/98A patent/AU726916B2/en not_active Expired
- 1998-01-13 EE EEP199900320A patent/EE03998B1/xx unknown
- 1998-01-13 WO PCT/SE1998/000038 patent/WO1998031350A1/en active IP Right Grant
- 1998-01-13 KR KR10-1999-7006412A patent/KR100528418B1/ko active IP Right Grant
- 1998-01-13 NZ NZ336592A patent/NZ336592A/xx not_active IP Right Cessation
- 1998-01-13 UA UA99074042A patent/UA57762C2/uk unknown
- 1998-01-13 RU RU99118589/14A patent/RU2180563C2/ru active
- 1998-01-13 NL NL1008019A patent/NL1008019C2/nl not_active IP Right Cessation
- 1998-01-13 BR BR9806892-0A patent/BR9806892A/pt not_active Application Discontinuation
- 1998-01-13 SI SI9830910T patent/SI1019033T1/sl unknown
- 1998-01-13 AT AT98901616T patent/ATE389390T1/de active
- 1998-01-13 ES ES98901616T patent/ES2302348T3/es not_active Expired - Lifetime
- 1998-01-14 GR GR980100021A patent/GR1003290B/el unknown
- 1998-01-15 BE BE9800029A patent/BE1011400A5/fr not_active IP Right Cessation
- 1998-01-16 IE IE980024A patent/IE980024A1/en not_active Application Discontinuation
- 1998-01-16 FR FR9800458A patent/FR2759908B1/fr not_active Expired - Lifetime
- 1998-01-16 ES ES009800078A patent/ES2148059B1/es not_active Expired - Fee Related
-
1999
- 1999-07-06 IS IS5110A patent/IS2563B/is unknown
- 1999-07-19 NO NO19993537A patent/NO327451B1/no not_active IP Right Cessation
-
2000
- 2000-08-01 HK HK00104815A patent/HK1025516A1/xx not_active IP Right Cessation
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2009
- 2009-11-06 JP JP2009255051A patent/JP2010059179A/ja active Pending
Also Published As
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