CN1140990A - 用于防止不希望的宫缩的硝化甘油经皮给药 - Google Patents
用于防止不希望的宫缩的硝化甘油经皮给药 Download PDFInfo
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- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
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- 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
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- 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
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- 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
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- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
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- 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
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Abstract
本发明涉及硝化甘油以一种经皮使用形式的药用，硝化甘油也称作甘油三硝酸酯，化学命名为1，2，3-丙三醇三硝酸酯，所述的应用是防止妊娠的哺乳动物不希望的宫缩。所述药用预防早产。
Description
本发明涉及硝化甘油的应用，它以经皮使用形式用于防止哺乳动物不希望的宫缩。
硝化甘油也称为甘油三硝酸酯(GTN)，是一种很久以前人们就熟悉的具有多种用途的化学物质。GTN的化学命名为1，2，3-丙三醇三硝酸酯。硝化甘油尤其是一种名贵的用于治疗冠心病的高效物质。基于这种意义，现在有许多医药工业方案可使用。这种物质的盖伦氏制剂目前包括片剂、胶囊、软膏、注射液、喷雾剂和用于经皮使用的有效物质的膏药。
意外地发现，硝化甘油以经皮应用形式使用时可以防止哺乳动物的不希望宫缩。
对于动物和人的研究表明，通过硝化甘油的盖伦氏制剂形式，对每批研究对象有针对性的使用硝化甘油可以中止宫缩。
下面以对人进行的研究，对本发明作进一步阐述。
研究包括18名怀孕的妇女，她们总是出现提前宫缩。她们的怀孕期已经是怀孕后期，因为她们已经怀孕25和34周之间。 她们总是使用GTN膏代替利托君，后者是一种宫缩抑制的有效物质。全部怀孕者表现如下特征：
-胎膜囊还没有破裂；
-没有过早地出血；
-胎儿没有表现出异常。
病人每天接受至多2个GTN膏药，相当于10及10.8mg 1，2，3-丙三醇三硝酸酯。膏药的面积当用DEPONIT10时为32cm2，当用Fa.SCHWARZ PHARMA AG产的一种新型的GTN膏药时为16cm2。后者含有硝化甘油，其粘接材料以交联的丙烯酸酯-乙酸乙烯酸共聚物为基础。
两种膏药的使用结果没有差别。两种膏药可防止过早的宫缩、中止过早的宫缩以及停止不规则的宫缩。
表1和2表明，在经皮使用的盖伦氏制剂中的硝化甘油防止怀孕哺乳动物不希望的过早宫缩。
从表可知，使用膏药以后宫缩将被中止。病人当中没有人发生不希望的早产。经根据剂量给予含有硝化甘油的膏药，可以中止剧烈的宫缩或控制不规则的宫缩，直至所希望的产期。
实施例1
膏药的制法如同EP 0 144 486 B1中的实施例1所详细描述的方法。
本发明所述的药物产品具有三层储存结构，按下列方法制备：
一种含有硝化甘油的粘附材料由以下组分制备：
0.175kg聚异丁烯(平均分子量为900,000至1,400,000，商品为OPPANOL B100)，
0.157kg固体的脂肪族碳氢化合物树脂(商品为PICCOTAC CBHT)，
0.157kg氢化的松香树脂(商品为ABITOL)，
0.0105kg 5％硝化甘油在一种中等链长的甘油三酸酯中的溶液(商品为MIGLYOL-812)，
1.174kg特种汽油80-110，作为溶剂。
该产物将涂在一个一面用铝镀膜另一面具有粘附性的保护膜上，当溶剂挥发以后得到大约20g/m2的涂层。在这个得到的粘附层上贴上单位面积重量为大约20g/m2的第一个储存层。
储存层的制备是通过沉积一种分散体而完成的，该分散体的组成如下：
0.05kg 10％(G/G)的硝化甘油-乳糖研磨物，
0.153kg聚异丁烯(平均分子量为900,000-1,400,000，商品名为OPPANOLB100)
0.137kg固体的脂肪族碳氢化合物树脂(商品名为PICCOTAC CBHT)，
0.137kg氢化的松香树脂(商品名为ABITOL)
0.01kg甘油三酸酯，作为溶剂(商品名为MIGLYOL812)，
1.148kg特种汽油80-110，作为溶剂。
该产物将沉积在一个分离纸(Trennpapier)上，然后分散体溶剂被挥发掉。
用同样方法将制备一个单位面积重量为大约50g/m2的第二个储存层，其组分为：
0.6kg10％(G/G)硝化甘油-乳糖研磨物，
0.2kg固体的脂肪族碳氢化物树脂(商品名为PICCOTAC CBHT)，
0.2kg氢化的松香树脂(商品名为ABITOL)，
0.025kg甘油三酸酯，作为溶剂(商品名为MIGLYOL812)，
1.876kg特种汽油80-110，作为溶剂，
将第二个储存层贴在第一个储存层上。
用同样的方法由以下组分制备第三个储存层：
2.5kg 10％(G/G)硝化甘油-乳糖研磨物，
0.657kg聚异丁烯(平均分子量为900,000-1,400,000；商品名为OPPANOLB100)，
0.77kg固体的脂肪族碳氢化物树脂(商品名为PICCOTAC CBHT)，
0.77kg氢化的松香树脂(商品名为ABITOL)，
7.507kg特种汽油80-110，作为溶剂。
其中，为了达到单位面积重量为大约200g/m2，分散体在分离纸上的沉积要经过三次相继的步骤才能实现。如此得到的第三层储存层被贴在第二层储存层上。
用同样的方法，由下列组分制备单位面积重量为大约20g/m2的粘附中间层：
0.179kg聚异丁烯(平均分子量为900,000-1,400,000；商品名为OPPANOLRB100)，
0.16kg固体的脂肪族碳氢化物树脂(商品名为PICCOTAC CBHT)，
0.16kg氢化的松香树脂(商品名为ABITOL)。
1.167kg特种汽油80-110，作为溶剂。
将粘附中间层贴在第三层储存层上。
粘附中间层用一种不透气的覆盖膜盖上以后，得到的层状物将按治疗的要求分割成单一的小块。
硝化甘油-膏药具有以下结构：它是一个矩形体系，由一个多层构造的、充满药物的接触膜，由聚异丁烯、固体的脂肪族碳氢化物树脂和氢化的松香树脂构成，最外层由一个聚酯薄膜覆盖上。一个32cm2的膏药含有32mg硝化甘油。有效物质在皮肤上的平均释放量为10mg/24小时。经皮体系的释放表面将用一个硅化处理的和金属镀膜的聚酯薄膜保护起来，在使用之前再将此膜揭掉。
实施例2
膏药的制备方法如PCT/EP 92/01169＝WO 92/22292 A1中的实施例3所详细描述的那样。
这种硝化甘油-膏药具有以下构造：它是一个矩形体系，它是由一个含有硝化甘油的、由一种交联的丙烯酸酯-乙酸乙烯酯共聚物为基础的粘附材料构成，最外层由一种聚酯薄膜所覆盖。
这种16cm2的膏药含有40mg硝化甘油。有效物质对皮肤的平均释放量为10.8mg/24小时。这种经皮体系的释放表面用一种聚酯薄膜保护起来，在使用之前再把它揭掉。
表1
| 子宫颈膨胀 | 妊娠期 | 宫缩 | 用Deponit1010mg TN | 宫缩终止 |
| 5cm | 32周 | 每3分钟收缩2次 | 每日同时2剂 | 3小时之内.+ |
| 4cm | 32周 | 每3分钟收缩1次 | 每日同时2剂 | 3小时之内.+ |
| 2cm | 25周 | 不规则 | 每日用1剂 | 5小时之内.+ |
表2
| 子宫颈膨胀 | 妊娠期 | 宫缩 | 用GTN-丙烯酸酯膏药10.8mg GTN | 宫缩终止 |
| 5cm | 32周 | 每3分钟收缩2次 | 每日同时2剂 | 3小时之内.+ |
| 4cm | 32周 | 每3分钟收缩1次 | 每日同时服2剂 | 3小时之内.+ |
| 2cm | 25周 | 不规则 | 每日用1剂 | 5小时之内.+ |
Claims (3)
1. 1，2，3-丙三醇三硝酸酯以一种经皮使用形式用于防止哺乳动物不希望的宫缩的应用。
2. 1，2，3-丙三醇三硝酸酯以一种经皮使用形式用于防止哺乳动物早产的应用。
3. 1，2，3-丙三醇三硝酸酯以一种经皮使用形式用于调节哺乳动物宫缩的应用。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP4406332.6 | 1994-02-28 | ||
| DE4406332A DE4406332C1 (de) | 1994-02-28 | 1994-02-28 | Pharmazeutische Verwendung von Nitroglycerin zur Verhinderung unerwünschter Wehentätigkeit bei Säugern in einer transdermalen Applikationsform |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1140990A true CN1140990A (zh) | 1997-01-22 |
| CN1069522C CN1069522C (zh) | 2001-08-15 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN95191680A Expired - Fee Related CN1069522C (zh) | 1994-02-28 | 1995-02-23 | 用于防止不希望的宫缩的硝化甘油经皮给药 |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US5817697A (zh) |
| EP (1) | EP0804176B1 (zh) |
| JP (1) | JP2823700B2 (zh) |
| KR (1) | KR100334372B1 (zh) |
| CN (1) | CN1069522C (zh) |
| AT (1) | ATE200732T1 (zh) |
| CA (1) | CA2184201A1 (zh) |
| DE (2) | DE4406332C1 (zh) |
| DK (1) | DK0804176T3 (zh) |
| ES (1) | ES2156938T3 (zh) |
| FI (1) | FI963329A (zh) |
| GR (1) | GR3035785T3 (zh) |
| NO (1) | NO961724D0 (zh) |
| PT (1) | PT804176E (zh) |
| WO (1) | WO1995022964A1 (zh) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020015951A1 (en) * | 2000-01-06 | 2002-02-07 | Bader Joel S. | Method of analyzing a nucleic acid |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU560710B2 (en) * | 1983-04-27 | 1987-04-16 | Lohmann Gmbh & Co. Kg. | Pharmaceutical product |
| DE4020144A1 (de) * | 1990-06-25 | 1992-01-09 | Lohmann Therapie Syst Lts | Pflaster mit hohem gehalt an weichmachenden inhaltsstoffen |
| JP2579729B2 (ja) * | 1991-06-10 | 1997-02-12 | シュバルツ ファルマ アクチェンゲゼルシャフト | ニトログリセリン膏薬及びその製造方法 |
| US5508045A (en) * | 1992-10-09 | 1996-04-16 | The Regents Of The University Of California | Method and agents for control and management of labor during pregnancy |
| JPH1192367A (ja) * | 1997-09-22 | 1999-04-06 | Hoechst Marion Roussel Kk | 妊娠悪阻治療剤 |
-
1994
- 1994-02-28 DE DE4406332A patent/DE4406332C1/de not_active Expired - Fee Related
-
1995
- 1995-02-22 US US08/700,402 patent/US5817697A/en not_active Expired - Fee Related
- 1995-02-23 EP EP95911253A patent/EP0804176B1/de not_active Expired - Lifetime
- 1995-02-23 DK DK95911253T patent/DK0804176T3/da active
- 1995-02-23 AT AT95911253T patent/ATE200732T1/de not_active IP Right Cessation
- 1995-02-23 CA CA002184201A patent/CA2184201A1/en not_active Abandoned
- 1995-02-23 DE DE59509223T patent/DE59509223D1/de not_active Expired - Fee Related
- 1995-02-23 PT PT95911253T patent/PT804176E/pt unknown
- 1995-02-23 WO PCT/EP1995/000654 patent/WO1995022964A1/de active IP Right Grant
- 1995-02-23 JP JP7522126A patent/JP2823700B2/ja not_active Expired - Fee Related
- 1995-02-23 KR KR1019960702455A patent/KR100334372B1/ko not_active IP Right Cessation
- 1995-02-23 ES ES95911253T patent/ES2156938T3/es not_active Expired - Lifetime
- 1995-02-23 CN CN95191680A patent/CN1069522C/zh not_active Expired - Fee Related
-
1996
- 1996-04-29 NO NO961724A patent/NO961724D0/no not_active Application Discontinuation
- 1996-08-27 FI FI963329A patent/FI963329A/fi not_active IP Right Cessation
-
2001
- 2001-04-26 GR GR20010400584T patent/GR3035785T3/el not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| FI963329A0 (fi) | 1996-08-27 |
| US5817697A (en) | 1998-10-06 |
| ES2156938T3 (es) | 2001-08-01 |
| NO961724L (no) | 1996-04-29 |
| FI963329A (fi) | 1996-09-05 |
| KR100334372B1 (ko) | 2002-09-04 |
| KR960705553A (ko) | 1996-11-08 |
| EP0804176A1 (de) | 1997-11-05 |
| NO961724D0 (no) | 1996-04-29 |
| CA2184201A1 (en) | 1995-08-31 |
| ATE200732T1 (de) | 2001-05-15 |
| PT804176E (pt) | 2001-08-30 |
| CN1069522C (zh) | 2001-08-15 |
| GR3035785T3 (en) | 2001-07-31 |
| DE59509223D1 (de) | 2001-05-31 |
| WO1995022964A1 (de) | 1995-08-31 |
| JP2823700B2 (ja) | 1998-11-11 |
| EP0804176B1 (de) | 2001-04-25 |
| JPH09506108A (ja) | 1997-06-17 |
| DK0804176T3 (da) | 2001-05-28 |
| DE4406332C1 (de) | 1995-06-22 |
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