CN1832760B - 基于羟乙基纤维素的生物粘附性凝胶 - Google Patents

基于羟乙基纤维素的生物粘附性凝胶 Download PDF

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CN1832760B
CN1832760B CN200480022719XA CN200480022719A CN1832760B CN 1832760 B CN1832760 B CN 1832760B CN 200480022719X A CN200480022719X A CN 200480022719XA CN 200480022719 A CN200480022719 A CN 200480022719A CN 1832760 B CN1832760 B CN 1832760B
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M·普里尼
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Abstract

本发明公开了生物粘附性凝胶形式的组合物，其粘附于粘膜、特别是阴道粘膜，用于应用活性成分和/或要素，其包含羟乙基纤维素作为唯一的胶凝剂。

Description

基于羟乙基纤维素的生物粘附性凝胶
本发明涉及生物粘附性凝胶形式的组合物，其粘附于粘膜、特别是阴道粘膜，用于应用活性成分和/或要素。
生物粘附性是一些水凝胶藉此粘附于生物组织、特别是被粘液覆盖的上皮如胃、口腔、阴道和直肠粘膜的特性。
该特性已被开发用于研制药物递送系统，尤其是为了增加药物保持与治疗所关注部位或区域接触的时间，产生全身效应(由此增加经粘膜吸收)或局部效应。
最常使用的能够形成水凝胶并赋予生物和/或粘膜粘附性的聚合物是可能为交联的丙烯酸或甲基丙烯酸聚合物，以及脱乙酰壳多糖或其衍生物。
具体而言，对于设计用于妇科的药物，能够确保活性成分和阴道粘膜之间的接触延长并且随时间逐渐释放该成分的生物粘附性凝胶提供了就功效和患者依从性而言的理想的解决方案。
因此，生物粘附性阴道凝胶已例如在US 6159491、US 2002012674、US 2003091642、WO 200047144、WO 200203896、WO 200143720和WO9610989中公开。在所有这些情况下，使用丙烯酸聚合物(卡波母或聚卡波非)作为粘度控制或生物粘附剂。
WO 200015192描述了其中使用脱乙酰壳多糖代替丙烯酸聚合物的生物粘附性制剂。
但是，获得具有以下优势和特性的生物粘附性制剂的问题仍然没有得到解决：
-释放药物达约24小时；
-不存在胶凝/生物粘附剂，所述胶凝/生物粘附剂的特征为存在酸基团，因此对介质的离子强度敏感，有时需要用碱中和；
-携带具有不同化学物理性质的药物的可能性，尤其是水溶性药物和基本不溶于水的脂溶性药物；
-减少治疗的时间和成本。
现已发现，所述目的可以通过粘附于粘膜、特别是阴道粘膜、包含羟乙基纤维素作为唯一生物粘附聚合物的生物粘附性凝胶制剂来实现。该胶凝赋形剂不具有酸基团，因此不依赖于介质的离子强度，其还具有基质效应，允许特别缓慢、逐渐释放活性成分达24小时。
本发明因此涉及水凝胶形式的组合物，用于阴道内递送活性成分，包含羟乙基纤维素作为唯一的胶凝和生物粘附剂。
本发明的组合物还可含有甘油、二乙二醇单乙醚、表面活性剂、防腐剂、酸化剂和其他常用于此处所考察递送形式的赋形剂。
本发明的组合物优选含有1至5重量％的羟乙基纤维素、25至90重量％的水、5至25重量％的甘油、5至50重量％的二乙二醇单乙醚、0.01至10重量％的表面活性剂、0.05至1重量％的防腐剂和0.01至1重量％的酸化剂。
优选地，羟乙基纤维素的含量高于2％且低于4％。
羟乙基纤维素自多种来源市售可得，优选取代度约1.5(对应于每两个糖单元具有3个羟乙基)且特性粘度测量所估计的分子量为1.0至1.3×106的羟乙基纤维素。具有所述特征的羟乙基纤维素可以以Hercules Inc.UK的商品名Natrosol 250HX获得。
活性成分的百分比显然将依赖于所选药物的特征，并且可在宽范围内变化，例如0.01至10重量％。
可有利地根据本发明配制的活性成分包括抗真菌药、消毒剂(antiseptics)和抗微生物剂、抗生素、镇痛药、局部麻醉药、抗组胺药、抗炎剂、避孕药、激素和它们的组合。
这些活性成分的实例包括益康唑、咪康唑、氟康唑、环吡酮胺、硝呋拉太、制霉素、氯己定、布洛芬、酮洛芬、萘普生、苄达明、苯扎氯铵和其他季铵消毒剂、壬苯聚醇-9和所有其他妇科应用所关注的活性成分。
以下实施例更详细地阐明本发明。
实施例1
组成                             百分比
纯化水                           81.9％
甘油                             12.9％
二葡萄糖酸氯己定，20％溶液w/v    2.7％
羟乙基纤维素(Natrosol 250HX)     2.5％
实施例2-布洛芬阴道凝胶
组成                             百分比
布洛芬                           0.100％
苯扎氯铵                         0.150％
聚氧乙烯-20-单鲸蜡基醚(Brij 58)  0.500％
羟乙基纤维素(Natrosol 250HX)     2.500％
二乙二醇单乙酯(Transcutol P)     10.000％
纯化水                           86.750％
实施例3-硝酸益康唑阴道凝胶
组成                             百分比
硝酸益康唑                       1.000％
苯扎氯铵                         0.150％
羟乙基纤维素(Natrosol 250HX)     2.500％
聚山梨酯80(Tween 80)             4.000％
甘油                             10.000％
二乙二醇单乙酯(Transcutol P)     40.000％
纯化水                           42.350％
实施例4-阴道凝胶的生物粘附性研究
使用适当修改的Lloyd肌力计于体外测量生物粘附性。将测量底物(兔胃粘膜或聚丙烯)用粘附剂固定于上支持物，再将其与活动的横杆连接，将200mg供试制剂放置于下支持物，以均匀覆盖表面。使制剂和底物进行密切接触(30秒)后，将横杆以确定的恒定速度提升，直到两个表面分离。
使用20N负载传感器(load cell)进行测量[J.Y.Chang，Y-K.Oh，H.S.Kong，E.J.Kim等，J.Control.Release 82(2002)39-50；S.Skulason，T.Kristmundsdottir，W.P.Holbrook，Bio-Gels Pharmaceuticals]。
每份样品测量5次，所考察的参数是最大断裂负载(ML)和粘附功(W)。
研究中所用的操作条件报告如下。
仪器        Lloyd LRX张力计
            装备有用于粘附试验的夹具
试验条件    横杆速度：0.1mm/s
            负载传感器：20N
            底物和凝胶的接触时间：30秒
            接触表面：兔胃粘膜/聚丙烯
结果
结果示于表1
表1
Figure G200480022719XD00041
实施例5-实施例1、2和3凝胶的pH4.0扩散试验
扩散介质：乳酸盐缓冲液，pH4.0
扩散体积：50ml
温度：37±0.5℃
搅拌速度：50rpm
样品量：1.5g
释放面积：4.5cm2
释放膜：醋酸纤维素0.45μm
药物自凝胶的释放试验采用扩散池进行，醋酸纤维素膜的表面为4.5cm2。所应用的凝胶量为1.5g。在给定的时间，自动化系统将获取预定的样品等分试样，并立即用UV分光光度计在254nm处读数。
图1显示氯己定的扩散曲线，为8份样品的平均值±标准偏差。
图2显示8份样品中氯己定的扩散曲线。
表2显示8份氯已定样品的释放百分比。
表2
时间  样品   样品    样品    样品    样品    样品    样品    样品    平均  SD
      1      2       3       4       5       6       7       8
 0       0       0       0       0       0       0       0       0       0    0
10   12.89   8.532   11.94   10.37   11.54   4.473   12.28   9.514   10.19 2.74
20   20.05   19.09   19.92   19.39   18.9    17.3    20.35   18.51   19.19 0.98
30   25.29   23.73   26.29   24.53   23.49   22.86   25.73   24.65   24.57 1.17
40   29.94   28.16   31.35   29.54   27.11   27.24   29.5    27.47   28.79 1.53
60   37.63   33.33   39.02   38.09   34.48   35.99   37.73   35.43   36.46 1.97
90   48.43   45.46   51.11   50.36   42.11   40.69   45.84   43.93   45.99 3.76
120  57.25   53.77   59.81   60.04   49.54   51.69   53.37   51.09   54.57 4.01
150  64.1    60.13   65.16   64.99   56.34   60.75   62.1    60.35   61.74 2.99
180  69.83   65.88   70.99   72.06   59.42   64.05   65.88   63.19   66.41 4.31
210  75.2    72.57   76.17   79.41   66.23   70.77   71.62   69.9    72.73 4.10
240  78.71   74.61   79.33   82.52   69.97   3.52    74.98   73.03   75.83 4.07
270  81.79   78.38   81.54   84.88   72.61   77.04   77.86   74.84   78.62 3.99
300  84.36   81.24   83.65   87.96   76.38   79.6    80.6    79.33   81.64 3.58
图3显示布洛芬的扩散曲线，为8份样品的平均值±标准偏差。
表3显示8份布洛芬样品的释放百分比。
表3
时间  样品 样品  样品   样品    样品   样品  样品   样品  平均  SD
(min) 1    2     3      4       5      6     7      8
 0      0      0      0      0     0      0       0      0     0    0
30  15.56  17.83  18.96  18.96  4.18   3.22   17.06  11.26 13.38 6.05
60  24.34  26.60  26.88  19.53  33.15  24.14  26.71  19.95 25.16 4.06
90  30.56  28.02  32.26  28.02  34.44  36.37  30.57  37.01 32.16 3.28
120 40.19  33.39  45.28  30.56  36.05  44.74  42.16  39.59 38.99 4.94
150 47.26  47.54  45.56  56.60  47.63  44.74  43.77  43.77 47.11 3.89
180 57.45  41.60  53.49  46.69  47.31  44.74  44.09  44.41 47.47 4.99
240 57.73  54.62  54.62  59.71  52.11  51.81  53.03  52.11 54.47 2.70
300 68.20  61.69  59.99  63.67  68.88  61.87  69.49  62.17 64.49 3.52
360 70.18  66.79  64.24  59.71  76.80  74.67  69.79  71.31 69.19 5.17
420 61.98  74.99  65.65  73.30  77.41  84.72  77.71  76.50 74.03 6.73
480 78.39  72.16  71.60  71.31  81.98  84.72  81.07  80.15 77.67 4.93
图4显示益康唑的扩散曲线，为8份样品的平均值±标准偏差。
表3显示8份益康唑样品的释放百分比。
时间  样品  样品  样品  样品  样品  样品  样品  样品  平均  SD
      1     2     3     4     5     6     7     8
1     8.9   8.9   10.7  11.7  9.1   8.8   10.3  12    10.1  1.3
2     12.3  15.5  18.4  19.1  14.4  15    17.3  19.5  16.4  2.5
3     24.1  21.6  24    25    22.1  25.3  21.1  23.6  23.4  1.6
4     29    26.2  28.8  30.1  30.4  28.2  25.8  32.1  28.8  2.1
5     34.1  30.4  32.8  34.5  36    33.4  30.2  33.7  33.1  2.0
6     40    34.2  35.4  37.6  38.4  36.5  34    36.3  36.6  2.1
7     40.5  36.8  37.4  39.9  41    39.2  37    38.4  38.8  1.6
8     44.4  39.3  38.6  41.3  43.2  40.2  39.6  41.2  41.0  2.0
9     45.2  40.6  40    43    45.8  42.1  42.3  44.2  42.9  2.1
10    46.1  41.8  40.9  44    47.3  44    45    45.4  44.3  2.1
11    47.2  42.8  41.4  44.8  48    45.3  46.3  46.7  45.3  2.3
12    48.6  43.6  42.6  45.8  49.2  47.1  48.2  48.1  46.7  2.4
13    49.2  44.3  43.1  46.4  50.3  49.6  50.2  49.2  47.8  2.8
14    50.2  45.2  43.6  46.9  51    49.8  50.8  50.1  48.5  2.8
15    50.7  45.4  43.7  47.6  51.1  50    51.1  50.6  48.8  2.9
16    51.3  46    44.3  47.4  51.3  50.3  51.4  50.8  49.1  2.8
17    51.9  46.3  44.7  47.7  51.5  50.4  51.7  50.9  49.4  2.8
18    52.6  46.3  45    47.7  51.7  50.7  51.9  51.1  49.6  2.9
19    53.1  46.8  46.7  48.2  52    51.1  52    51.3  50.2  2.5
20    53.3  46.9  49.3  50.1  52.2  51.2  52.3  51.5  50.9  2.0
21    53.1  47    52.2  50.3  52.3  51.4  52.6  51.7  51.3  1.9
22    53.9  47.8  54.2  51.2  52.5  51.6  52.7  51.9  52.0  2.0
23    54.1  48.3  55.3  51.9  52.7  51.8  52.9  52.2  52.4  2.0
24    55.2  50.1  56.1  52    53.2  52.4  53.1  52.4  53.1  1.9

Claims (3)

1.用于递送活性成分的水性生物粘附性凝胶形式的组合物，包含1至5重量％的羟乙基纤维素作为唯一的胶凝和生物粘附剂、5至25重量％的甘油、5至50重量％的二乙二醇单乙醚、0.01至10重量％的表面活性剂、0.05至1重量％的防腐剂、0.01至1重量％的酸化剂和25至90重量％的水。
2.权利要求1所述的组合物，含有作为活性成分的抗真菌药、消毒剂和抗微生物剂、抗生素、镇痛药、局部麻醉药、抗组胺药、抗炎剂、避孕药、激素或它们的组合。
3.权利要求2所述的组合，其中活性成分选自益康唑、咪康唑、氟康唑、环吡酮胺、硝呋拉太、制霉素、氯己定、布洛芬、酮洛芬、萘普生、苄达明、苯扎氯铵或其他季铵消毒剂，以及壬苯聚醇-9。
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Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100394919C (zh) * 2006-03-01 2008-06-18 杨军 一种用于治疗阴道疾病的药物组合物
US8433851B2 (en) 2007-08-16 2013-04-30 International Business Machines Corporation Reducing wiring congestion in a cache subsystem utilizing sectored caches with discontiguous addressing
US9452173B2 (en) 2013-01-31 2016-09-27 Merz Pharmaceuticals, Llc Topical compositions and methods for making and using same
US9446131B2 (en) 2013-01-31 2016-09-20 Merz Pharmaceuticals, Llc Topical compositions and methods for making and using same
US9433680B2 (en) * 2013-01-31 2016-09-06 Merz Pharmaceuticals, Llc Topical compositions and methods for making and using same
US8778365B1 (en) 2013-01-31 2014-07-15 Merz Pharmaceuticals, Llc Topical compositions and methods for making and using same
CN106310266A (zh) * 2015-07-09 2017-01-11 王强 一种预防或治疗粘膜疾病的组合物及制备方法
CN106038477A (zh) * 2016-06-14 2016-10-26 上海通用药业股份有限公司 一种含有噻康唑的阴道用凝胶的制备方法
CN106109398A (zh) * 2016-06-14 2016-11-16 上海通用药业股份有限公司 一种含有噻康唑的阴道用凝胶
EA037435B1 (ru) * 2016-07-08 2021-03-26 Ацьенде Кимике Рьюните Анджелини Франческо А.К.Р.А.Ф. С.П.А. Фармацевтическая композиция, содержащая бензидамин
IT201900000388A1 (it) * 2019-01-10 2020-07-10 L N Age S R L Composizione per l'uso nel trattamento di lesioni vaginali, del glande ed anali
EA202290122A1 (ru) * 2019-06-21 2022-03-17 Альфасигма С.П.А. Фармацевтические композиции в форме геля, содержащие ксилоглюкан и спирты, для регулируемого высвобождения активных ингредиентов
CN111557897B (zh) * 2020-07-07 2023-06-23 温州海鹤药业有限公司 一种含有硝呋太尔的药物组合物及其制备方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1248906A (zh) * 1997-02-28 2000-03-29 加拿大吉勒特公司 具有改进的存留性的氟化亚锡凝胶

Family Cites Families (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3731255A1 (de) * 1987-09-17 1989-04-06 Boehringer Ingelheim Int Stabilisierung von therapeutisch wirksamen proteinen in pharmazeutischen zubereitungen
DE3741149A1 (de) * 1987-12-04 1989-06-15 Thomae Gmbh Dr K Zubereitungsformen zur verhinderung von adhaesionen von organen und organteilen
JPH04217925A (ja) * 1990-03-27 1992-08-07 Nippon Saafuakutanto Kogyo Kk 新規な解熱消炎鎮痛剤組成物
JPH05178763A (ja) * 1991-02-19 1993-07-20 Nippon Saafuakutanto Kogyo Kk 難溶解性薬物溶解剤組成物
US5667492A (en) 1994-10-07 1997-09-16 Columbia Laboratories, Inc. Use and composition of an anti-sexually transmitted diseases formulation
AT408067B (de) * 1995-03-17 2001-08-27 Gebro Pharma Gmbh Pharmazeutische zusammensetzung zur topischen applizierung und verfahren zu ihrer herstellung
US5849761A (en) * 1995-09-12 1998-12-15 Regents Of The University Of California Peripherally active anti-hyperalgesic opiates
JP3616688B2 (ja) * 1996-03-25 2005-02-02 太田製薬株式会社 医薬組成物
EP0954294A1 (en) * 1996-06-12 1999-11-10 The Procter & Gamble Company Use of h2-antagonists for the manufacture of a topical composition for the treatment of colds
IT1284874B1 (it) 1996-08-02 1998-05-22 Farmigea Spa Complessi bioadesivi di polycarbophil e farmaci antifungini o antiprotozoari azolici
CA2289966A1 (en) * 1997-05-14 1998-11-19 Galen (Chemicals) Limited Topical compositions
US6416779B1 (en) * 1997-06-11 2002-07-09 Umd, Inc. Device and method for intravaginal or transvaginal treatment of fungal, bacterial, viral or parasitic infections
AU3565799A (en) 1998-09-17 2000-04-03 Zonagen, Inc. Methods and materials related to bioadhesive contraceptive gels
US6159491A (en) 1999-02-12 2000-12-12 Biovector Technologies, Inc. Prolonged release bioadhesive vaginal gel dosage form
JP2003512310A (ja) * 1999-10-22 2003-04-02 リーフ−フラウプ イーエイチエフ バイオ−ゲルズ ファーマシューティカルス インコーポレイテッド 粘膜上皮潰瘍および／または糜爛の治療用製薬組成物
FR2802097B1 (fr) 1999-12-14 2002-12-13 Invest S Therapeutiques Essais Composition sous forme de gel prevue pour recevoir un principe actif en solution ou en suspension, notamment pour application sur une muqueuse et procede de fabrication
EP1307232B1 (en) * 2000-08-03 2007-03-07 Antares Pharma IPL AG Novel composition for transdermal and/or transmucosal administration of active compounds that ensures adequate therapeutic levels
IL142037A0 (en) * 2001-03-15 2002-03-10 Agis Ind 1983 Ltd Pharmaceutical compositions containing a non-steroidal anti-inflammatory drug
WO2003020210A2 (en) * 2001-08-29 2003-03-13 Umd, Inc. Vaginal delivery of chemotherapeutic agents and inhibitors of membrane efflux systems for cancer therapy
WO2003066001A2 (en) * 2002-02-07 2003-08-14 The Trustees Of Columbia University In The City Of New York Zinc salt compositions for the prevention of mucosal irritation from spermicides and microbicides
AR039540A1 (es) * 2002-05-13 2005-02-23 Tibotec Pharm Ltd Compuestos microbicidas con contenido de pirimidina o triazina

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1248906A (zh) * 1997-02-28 2000-03-29 加拿大吉勒特公司 具有改进的存留性的氟化亚锡凝胶

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