CN106267158A - 一种促进创面愈合和修复宫颈粘膜的凝胶 - Google Patents
一种促进创面愈合和修复宫颈粘膜的凝胶 Download PDFInfo
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- CN106267158A CN106267158A CN201610665254.4A CN201610665254A CN106267158A CN 106267158 A CN106267158 A CN 106267158A CN 201610665254 A CN201610665254 A CN 201610665254A CN 106267158 A CN106267158 A CN 106267158A
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- growth factor
- wound healing
- triclosan
- carbomer
- gel
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Abstract
本发明公开了一种促进创面愈合和修复宫颈粘膜的凝胶，成分由卡波姆、三氯生、透明质酸、碱性成纤维细胞生长因子、转化生长因子β、氢氧化钠、纯水组成，卡波姆1％‑3％、三氯生0.1％‑0.5％、透明质酸0.05％‑0.1％、碱性成纤维细胞生长因子0.000001％‑0.00005％、转化生长因子β0.000001％‑0.00005％、氢氧化钠0.05％‑0.1％、纯水余量。本发明产品可以促进伤口愈合又具有高效抗菌、抑菌性能，生物安全无毒，性能稳定，对阴道炎(细菌性阴道病、念珠菌性阴道炎、混合性阴道炎、外阴炎)和宫颈糜烂等妇科疾病具有治疗作用，并且可清洁护理女性阴部、止血止痛、消炎抑菌和促进创面愈合作用。
Description
技术领域
本发明涉及凝胶剂，具体涉及一种促进创面愈合和修复宫颈粘膜的凝胶。
背景技术
阴道炎和慢性宫颈炎(宫颈糜烂)是当前妇科临床上最常见的两大妇科炎症疾病，具有明显的高发病率、低治愈率的特点。据统计，我国女性整体发病率约41％(约2.8亿人)，已婚育龄妇女发病率70％，由于不规范的治疗和细菌耐药性的产生使得妇科炎症疾病的复发率高达50％。由于阴道炎和慢性宫颈炎患者在感染细菌等致病菌的同时，常伴有出血、阴道、宫颈粘膜的不同程度的受损而形成创面，因此治疗妇科炎症疾病，不仅要杀灭细菌等病原菌，同时要止血、滋养保护受损粘膜，促进创面愈合。
中国专利201010135036.2公开了一种用于修复皮肤创面或宫颈粘膜的诱导凝胶，成分包括卡波姆、三氯生、重组人表皮生长因子，解决皮肤伤口、切口及溃疡创面的治疗问题，同时改善阴道微生态，修复阴道微损伤，对宫颈糜烂进行良好治疗。然而其对创面愈合的效果并不十分显著。
发明内容
本发明旨在提供一种促进创面愈合和修复宫颈粘膜的凝胶。
本发明是采用如下技术方案实现的：一种促进创面愈合和修复宫颈粘膜的凝胶，成分由卡波姆、三氯生、透明质酸、碱性成纤维细胞生长因子、转化生长因子β、氢氧化钠、纯水组成，卡波姆1％-3％、三氯生0.1％-0.5％、透明质酸0.05％-0.1％、碱性成纤维细胞生长因子0.000001％-0.00005％、转化生长因子β0.000001％-0.00005％、氢氧化钠0.05％-0.1％、纯水余量。上述浓度均为质量百分比。
一种促进创面愈合和修复宫颈粘膜的凝胶，成分由卡波姆、三氯生、透明质酸、碱性成纤维细胞生长因子、转化生长因子β、氢氧化钠、纯水组成，各成分的最佳浓度为，卡波姆2％、三氯生0.3％、透明质酸0.08％、碱性成纤维细胞生长因子0.000005％、转化生长因子β0.000005％、氢氧化钠0.07％、纯水余量。
上述成分中：
卡波姆是一类聚烯基聚醚交联的丙烯酸聚合物，在水中溶胀后形成具有三维网络结构的聚合物，经碱中和后形成清晰透明的凝胶，与羧甲基纤维素(CMC)、甲基纤维素(MC)等水凝胶基质相比，卡波姆凝胶具有用量低，手感好，产品清晰度好，是水凝胶制剂中最常用的基质。卡波姆因其广泛的用途，现有技术中，已有相关产品采用卡波姆为原料，制成凝胶产品，用于妇科疾病的治疗上。
三氯生，是一种极难溶于水的物质，又名“三氯新”、“三氯沙”等，化学名2,4,4'-三氯-2'-羟基二苯醚，是一种安全的广谱抑菌剂。对引起感染或病原性革兰式阳性菌、真菌、酵母菌及病毒等都具有广泛的杀灭及抑制作用。三氯生广泛应用于高效药皂/卫生香皂、卫生洗液、除腑臭/脚气雾剂、消毒洗手液、伤口消毒喷雾剂、医疗器消毒剂、卫生洗面奶/膏、空气清新剂及冰箱除臭剂等，也用于卫生织物的整理和塑料的防腐和处理，更高纯度的三氯生还广泛用于治疗牙龈炎、牙周炎及口腔溃疡等疗效牙膏及漱口水中。长期广泛的动物毒理实验也证明了三氯生在建议使用范围及用量下，能够达到当今世界对化学毒性的国际标准，是目前国际上推崇的安全高效广谱抗菌剂。
透明质酸(Hyaluronan；HA)，又称玻尿酸，是一种酸性粘多糖，1934年美国哥伦比亚大学眼科教授Meyer等首先从牛眼玻璃体中分离出该物质。透明质酸是一种高分子的聚合物，由直链(1→3)-2-乙酰氨基-2-脱氧-β-D葡糖-(1→4)-O-β-D葡糖醛酸双糖重复单位组成的直链多糖。透明质酸以其独特的分子结构和理化性质在机体内显示出多种重要的生理功能，如调节血管壁的通透性，调节蛋白质，水电解质扩散及运转，润滑修复，促进创伤愈合等。
碱性成纤维细胞生长因子(Basic fibroblast growth factor，简写为bFGF)在体内可参与多种组织的创伤修复过程，是重要的创伤愈合因子之一，它能诱导微血管的形成、发育和分化，同时直接刺激成纤维细胞和细胞外基质的蛋白合成，以形成胶原纤维，增加创面的抗张力强度，并促进真皮细胞的移行、分裂、分化，以完成皮肤的修复过程，并能促进皮肤软骨组织、骨组织和神经组织损伤修复和肢体再生。大量基础研究和临床试验证实，bFGF对烧伤、外伤及各种慢性难愈合创面具有显著的促修复作用，并且安全、有效、无不良反应。
创伤愈合是一复杂的过程，分为3个阶段：炎症期、肉芽组织形成期、瘢痕形成期，整个过程涉及细胞、ECM及细胞因子间的相互作用。转化生长因子β是创伤愈合过程中重要的调控因子，组织损伤后，转化生长因子β首先由血小板脱颗粒释放到伤口周围，通过与ECM相结合，转化生长因子β被活化，活化的转化生长因子β具有单核细胞、中性粒细胞、成纤维细胞的强烈化学趋化作用，从而导致伤口处的炎症反应，而这些细胞又可产生、分泌更多转化生长因子β。转化生长因子β对上皮细胞也有趋化作用，促进上皮细胞分裂、增殖，增加角质细胞的运动能力，刺激角质细胞表达特异的角蛋白。转化生长因子β作用于损伤组织的成纤维细胞，促使其合成大量的Ⅰ，Ⅲ型胶原蛋白、FN、弹性蛋白、整合素、蛋白多糖等多种ECM成分，抑制基质降解酶的产生、促进该酶降解物的合成并加强基质与细胞的结合，促使伤口张力增加和局部纤维化，从而促进创伤的愈合。
本发明将上述几种成分按照最佳比例制成凝胶制剂，经化学修饰，使其生物相容性大大增强，具有良好的组织相容性，首先针对糜烂创面形成隔离保护，起到生物屏障作用，同时凝胶具有较强的吸附作用，能吸附大量的组织渗出液，为组织细胞的修复提供良好的生长环境。
本发明凝胶产品可以促进伤口愈合又具有高效抗菌、抑菌性能，生物安全无毒，性能稳定，对阴道炎(细菌性阴道病、念珠菌性阴道炎、混合性阴道炎、外阴炎)和宫颈糜烂等妇科疾病具有治疗作用，并且可清洁护理女性阴部、止血止痛、消炎抑菌和促进创面愈合作用；该凝胶为酸性聚合物，释放于阴道内层细胞，调节阴道PH值水平，并且在阴道内具有良好的抑菌活性，对金黄色葡萄球菌、白色念珠菌等多种病原体均有明显的抑制作用，可用于预防和治疗细菌性阴道炎症，并减少阴部异味，缓解瘙痒、疼痛等症状，使女性阴道环境不受损伤。本配方产品不仅具有现在市场上相关产品的杀菌功能，同时具有治愈时间短、恢复迅速、减少瘢痕等优点，对皮肤及粘膜无毒、无刺激性、无超敏反应，具有护肤作用，值得推广应用。
具体实施方式
下面结合实施例对本发明的实施方式作进一步详细描述。以下实施例用于说明本发明，但不能用来限制本发明的范围。
实施例1
一种促进创面愈合和修复宫颈粘膜的凝胶，成分由卡波姆、三氯生、透明质酸、碱性成纤维细胞生长因子、转化生长因子β、氢氧化钠、纯水组成，卡波姆2％、三氯生0.3％、透明质酸0.08％、碱性成纤维细胞生长因子0.000005％、转化生长因子β0.000005％、氢氧化钠0.07％、纯水余量。
实施例2
一种促进创面愈合和修复宫颈粘膜的凝胶，成分由卡波姆、三氯生、透明质酸、碱性成纤维细胞生长因子、转化生长因子β、氢氧化钠、纯水组成，卡波姆1％、三氯生0.1％、透明质酸0.05％、碱性成纤维细胞生长因子0.000001％、转化生长因子β0.000001％、氢氧化钠0.05％、纯水余量。
实施例3
一种促进创面愈合和修复宫颈粘膜的凝胶，成分由卡波姆、三氯生、透明质酸、碱性成纤维细胞生长因子、转化生长因子β、氢氧化钠、纯水组成，卡波姆3％、三氯生0.5％、透明质酸0.1％、碱性成纤维细胞生长因子0.00005％、转化生长因子β0.00005％、氢氧化钠0.1％、纯水余量。
实施例4
一种促进创面愈合和修复宫颈粘膜的凝胶，成分由卡波姆、三氯生、透明质酸、碱性成纤维细胞生长因子、转化生长因子β、氢氧化钠、纯水组成，卡波姆2.5％、三氯生0.2％、透明质酸0.07％、碱性成纤维细胞生长因子0.00003％、转化生长因子β0.00002％、氢氧化钠0.07％、纯水余量。
对比例1
中国专利201010135036.2实施例1凝胶剂。
实验例1：创伤实验
1，对照组设计：实施例产品和对比例1产品。
2，模型的制备及治疗方法：
创伤模型：将小鼠背部皮肤剃毛，用细砂纸轻轻摩擦造成直径为2cm的圆形创伤，皮肤表皮完全破损，并出血。将所列各组所述物质在小鼠的破损皮肤上均匀涂敷，每天早晚两次清洗创面并涂药，观察小鼠皮肤愈合情况。
3，实验结果：见下表。
表1：创伤模型2天治疗情况
表2：创伤模型5天治疗情况
实验例2：烧烫伤实验
1，对照组设计：实施例产品和对比例1产品。
2，模型的制备及治疗方法：
烧烫伤模型：将小鼠背部皮肤剃毛，用90℃开水烫伤5秒，制造直径为2cm的圆形II度烧烫伤模型。将所列各组所述物质在小鼠的破损皮肤上均匀涂敷，每天早晚两次清洗创面并涂药，观察小鼠皮肤愈合情况。
3，实验结果：见下表
表3：烧烫伤模型2天治疗情况
表4：烧烫伤模型5天治疗情况
实验例3：阴道用药刺激性试验结果：
实施例1凝胶剂给大鼠塞阴道局部用药，实验观察期间动物进食、活动、大小便等均未见异常，7天内大鼠全部存活，无一死亡。阴道内肉眼所见粘膜面完整，阴道壁未见缺损、穿孔、出血改变。病理组织学检查镜下示：涂敷阴道24小时、48小时实施例组上皮各层细胞形态结构正常，无角化不全现象，鳞状上皮未见明显增生，各层细胞未见变性坏死。真皮浅层轻度水肿，有少量淋巴细胞浸润。涂敷阴道7天阴道粘膜鳞状上皮各层细胞形态正常，未见增生、坏死，真皮无明显水肿或呈细胞浸润。上述结果表明该药塞阴道局部用药未引起明显毒性及不良反应。
实验例4：治疗宫颈糜烂效果
患者常规消毒外阴、阴道，用窥器充分暴露宫颈并消毒，用无菌干纱布擦净宫颈表面分泌物，将本发明实施例1涂抹在糜烂面。视糜烂程度而定，7-10天为一个疗程。
治疗684例，总有效率达100％，治愈680例，治愈率达99％。用药前宫颈糜烂程度及治疗情况见下表。
表5：用药前宫颈糜烂程度及类型分布
表6：宫颈糜烂用药后的疗效
总有效率＝治愈+显效+有效
表7：宫颈糜烂疗效与疗程的关系
Claims (2)
1.一种促进创面愈合和修复宫颈粘膜的凝胶，其特征在于，成分由卡波姆、三氯生、透明质酸、碱性成纤维细胞生长因子、转化生长因子β、氢氧化钠、纯水组成，卡波姆1％-3％、三氯生0.1％-0.5％、透明质酸0.05％-0.1％、碱性成纤维细胞生长因子0.000001％-0.00005％、转化生长因子β0.000001％-0.00005％、氢氧化钠0.05％-0.1％、纯水余量。
2.根据权利要求1所述的一种促进创面愈合和修复宫颈粘膜的凝胶，其特征在于，成分由卡波姆、三氯生、透明质酸、碱性成纤维细胞生长因子、转化生长因子β、氢氧化钠、纯水组成，卡波姆2％、三氯生0.3％、透明质酸0.08％、碱性成纤维细胞生长因子0.000005％、转化生长因子β0.000005％、氢氧化钠0.07％、纯水余量。
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| CN108452293A (zh) * | 2018-04-12 | 2018-08-28 | 广西达庆生物科技有限公司 | 一种妇科用凝胶及其制备方法 |
| CN114272205A (zh) * | 2021-12-30 | 2022-04-05 | 广州朗圣药业有限公司 | 一种具有宫颈表面保护作用的凝胶 |
| CN114272205B (zh) * | 2021-12-30 | 2023-09-08 | 广州朗圣药业有限公司 | 一种具有宫颈表面保护作用的凝胶 |
| CN114344452A (zh) * | 2022-02-18 | 2022-04-15 | 深圳市第二人民医院(深圳市转化医学研究院) | 一种抗瘢痕烧伤药膏及其制备方法和应用 |
| CN114344452B (zh) * | 2022-02-18 | 2023-09-19 | 深圳市第二人民医院(深圳市转化医学研究院) | 一种抗瘢痕烧伤药膏及其制备方法和应用 |
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