CN105727372A - 一种温敏性宫腔修复凝胶及其制备方法 - Google Patents

一种温敏性宫腔修复凝胶及其制备方法 Download PDF

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CN105727372A
CN105727372A CN201610100804.8A CN201610100804A CN105727372A CN 105727372 A CN105727372 A CN 105727372A CN 201610100804 A CN201610100804 A CN 201610100804A CN 105727372 A CN105727372 A CN 105727372A
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高秀岩
李利明
任孝敏
敖强
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YANTAI JUNXIU BIOLOGICAL SCIENCE & TECHNOLOGY Co Ltd
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Abstract

本发明提供了一种温敏性宫腔修复凝胶及其制备方法，该方法通过对来源于动物的细胞外基质进行低温酶解、中和、过滤、浓缩、冷冻干燥、乳化等一系列处理，制备成均一的粘稠液体产品。当该产品注射到使用部位时，液体慢慢升温至体温，在使用部位形成原位凝胶，对损伤部位形成屏障保护；凝胶中所含的胶原及多糖成分，能促进受损组织修复，加速伤口愈合。

Description

一种温敏性宫腔修复凝胶及其制备方法
技术领域
本发明涉及生物组织工程材料领域，具体涉及到一种温敏性宫腔修复凝胶及其制备方法。
背景技术
改革开放30多年以来，随着人们生活理念和生活环境的改变，宫腔手术已成为临床中极为常见的手术。以人工流产手术为例，据中青报报道，国家人口计生委科学技术研究所在2013年发布的一组数据显示，我国每年人工流产多达1300万人次，居世界第一。不管何种类型的宫腔手术，在手术过程中都会其对宫腔造成一定的手术性创伤，术后都有可能出现诸如出血、穿孔、栓塞、感染、粘连等并发症，其中绝大部分问题是在宫腔组织修复过程中产生的。
宫腔手术中面临的最大问题来自于术后恢复过程中创面组织的增生和粘连。目前国内外用于预防宫腔术后粘连的方法有很多，包括采用宫腔防粘连产品以及采用激素类药物等。
目前临床上用于宫腔防粘连的产品均为液体，易于使用，但其存在屏障不充分、降解吸收过快、不能有效修复受损组织等问题；而激素类药物尽管可促使子宫内膜再生与修复，但缺乏屏障作用，易引起创面组织瘢痕化，不利于术后恢复。理想的宫腔修复产品应便于使用并且尽可能模拟人体组织，能够诱导组织细胞再生分化，促进损伤组织的再生修复。基于这种临床现状，有必要研发一种既便于使用，能有效隔离创面防止粘连形成，又能促进受损组织修复的产品。
发明内容
本发明的目的在于提供一种温敏性宫腔修复凝胶，产品在使用前为粘稠液体状态，当注射到使用部位后，液体慢慢升温至体温，在使用部位形成原位凝胶，对损伤部位形成屏障保护；凝胶中所含的胶原及多糖成分，能促进受损组织修复，加速伤口愈合。
为得到上述温敏性宫腔修复凝胶，本发明采取以下方案：取来自于动物的细胞外基质经低温酶解、中和、过滤、浓缩、冷冻干燥、乳化等一系列处理，制成所需的凝胶产品，具体步骤如下：
（1）取来自于动物的细胞外基质，在20~30℃、pH值1~3的条件下，用0.1~2%胃蛋白酶溶液酶解24~72h；
（2）用0.01~1mol/L的氢氧化钠溶液中和酶解液至pH值6~8；
（3）加压梯度过滤，过滤目数依次为100目、200目、300目、400目、500目；
（4）过滤后的料液在20~30℃下真空浓缩24~72h；
（5）对真空浓缩后的料液进行冷冻干燥24~72h；
（6）按冻干粉与pH值7.2~7.4的PBS缓冲液（0.1~2）：100（W/V）的比例进行乳化制备凝胶。
本发明的优点：
1.本发明提供的温敏性宫腔修复凝胶的整个制备过程都是在30℃以下的低温环境中进行，该方法最大限度地保留了细胞外基质的活性成分，所制备的凝胶安全性高，有效性好；
2.本发明提供的温敏性宫腔修复凝胶在使用前为液体状态，便于使用；当注射到使用部位后，在使用部位形成原位凝胶，对损伤部位形成屏障保护，较目前临床上使用的液体类产品防护效果更佳；凝胶中所含的胶原及多糖成分，能促进受损组织修复，加速伤口愈合；
3.本发明提供的温敏性宫腔修复凝胶在防止粘连及促进组织修复的同时，可在4个周内被人体缓慢降解吸收，符合宫腔受损的正常修复周期。
具体实施方式
下面通过实施例对本发明作出进一步的详细说明，旨在用于说明本发明而非限定本发明。应当指出，对于本领域技术人员而言，在不脱离本发明原理的前提下，还可以对本发明进行若干改进和修饰，这些改进和修饰也同样处于本发明的保护范围之内。
实施例1：
在20℃下，用0.001mol/L的盐酸溶液1000ml溶解1g胃蛋白酶制成pH值为3的0.1%胃蛋白酶溶液。取来自于动物的细胞外基质10g，用配制好的胃蛋白酶溶液20℃下酶解72h后，用0.01mol/L的氢氧化钠溶液中和酶解液pH值至8.0。采用板框过滤器进行加压梯度过滤，过滤目数依次为100目、200目、300目、400目、500目，过滤后的料液在20℃下真空浓缩72h后的进行冷冻干燥72h。取冻干后的产品0.1g加入pH值7.2的PBS缓冲液100ml乳化制备凝胶。
实施例2：
在25℃下，用0.01mol/L的盐酸溶液1000ml溶解10g胃蛋白酶制成pH值为2的1%胃蛋白酶溶液。取来自于动物的细胞外基质10g，用配制好的胃蛋白酶溶液25℃下酶解48h后，用0.1mol/L的氢氧化钠溶液中和酶解液pH值至7.0。采用板框过滤器进行加压梯度过滤，过滤目数依次为100目、200目、300目、400目、500目，过滤后的料液在25℃下真空浓缩48h后的进行冷冻干燥48h。取冻干后的产品1g加入pH值7.3的PBS缓冲液100ml乳化制备凝胶。
实施例3：
在30℃下，用0.1mol/L的盐酸溶液1000ml溶解20g胃蛋白酶制成pH值为1的2%胃蛋白酶溶液。取来自于动物的细胞外基质10g，用配制好的胃蛋白酶溶液30℃下酶解24h后，用1mol/L的氢氧化钠溶液中和酶解液pH值至6.0。采用板框过滤器进行加压梯度过滤，过滤目数依次为100目、200目、300目、400目、500目，过滤后的料液在30℃下真空浓缩24h后的进行冷冻干燥24h。取冻干后的产品2g加入pH值7.4的PBS缓冲液100ml乳化制备凝胶。

Claims (8)

1.一种温敏性宫腔修复凝胶，其特征在于，所述温敏性宫腔修复凝胶是由动物的细胞外基质经低温酶解、中和、过滤、浓缩、冷冻干燥、乳化等一系列处理制成的。
2.权利要求1所述的动物的细胞外基质，其特征在于，所用的动物的细胞外基质是由猪、牛、羊的皮肤、心脏、肌腱、韧带、神经和膀胱等组织经脱细胞处理制得。
3.权利要求1所述的低温酶解，其特征在于，所用酶为胃蛋白酶，酶解温度为20~30℃，酶解液浓度为0.1~2%，pH值范围为1~3，所用pH调节剂为0.001~0.1mol/L的盐酸溶液，酶解时间为24~72h。
4.权利要求1所述的中和，其特征在于，所用中和剂为0.01~1mol/L的氢氧化钠溶液，中和后pH值为6~8。
5.权利要求1所述的过滤，其特征在于，所述过滤为加压梯度过滤，过滤目数依次为100目、200目、300目、400目、500目。
6.权利要求1所述的浓缩，其特征在于，所述浓缩为低温真空浓缩，浓缩温度为20~30℃，浓缩时间为24~72h。
7.权利要求1所述的冷冻干燥，其特征在于，所述冷冻干燥的料液为权利要求6中真空浓缩后制得的浓缩液，冻干时间为24~72h。
8.权利要求1所述的乳化，其特征在于，所述乳化的分散质为权利要求7中所制得的冻干粉，分散剂为pH值7.2~7.4的磷酸缓冲盐溶液（PBS），其中分散质与分散剂的比例为（0.1~2）：100（W/V）。
CN201610100804.8A 2016-02-25 2016-02-25 一种温敏性宫腔修复凝胶及其制备方法 Pending CN105727372A (zh)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106496608A (zh) * 2016-11-02 2017-03-15 四川大学 胶原基复配非离子型多糖构建复合水凝胶的制备方法
CN106880871A (zh) * 2017-01-18 2017-06-23 烟台正海生物科技股份有限公司 一种用于促进子宫内膜修复的胶原蛋白真皮材料及其制备方法
CN110812529A (zh) * 2019-10-17 2020-02-21 易小玉 一种可注射水凝胶及其制备方法
WO2022055974A1 (en) * 2020-09-08 2022-03-17 Xylyx Bio, Inc. Tissue-derived matrikine compositions and methods therefor

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1777437A (zh) * 2003-02-21 2006-05-24 Uab研究基金会 生物活性天然生物基质组合物
CN102227225A (zh) * 2008-09-30 2011-10-26 加利福尼亚大学董事会 用于组织修复的使用细胞外基质的组合物和方法
CN104971380A (zh) * 2014-04-11 2015-10-14 烟台隽秀生物科技有限公司 一种脱细胞基质修复凝胶及其制备新方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1777437A (zh) * 2003-02-21 2006-05-24 Uab研究基金会 生物活性天然生物基质组合物
CN102227225A (zh) * 2008-09-30 2011-10-26 加利福尼亚大学董事会 用于组织修复的使用细胞外基质的组合物和方法
CN104971380A (zh) * 2014-04-11 2015-10-14 烟台隽秀生物科技有限公司 一种脱细胞基质修复凝胶及其制备新方法

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106496608A (zh) * 2016-11-02 2017-03-15 四川大学 胶原基复配非离子型多糖构建复合水凝胶的制备方法
CN106496608B (zh) * 2016-11-02 2018-12-07 四川大学 胶原基复配非离子型多糖构建复合水凝胶的制备方法
CN106880871A (zh) * 2017-01-18 2017-06-23 烟台正海生物科技股份有限公司 一种用于促进子宫内膜修复的胶原蛋白真皮材料及其制备方法
CN110812529A (zh) * 2019-10-17 2020-02-21 易小玉 一种可注射水凝胶及其制备方法
WO2022055974A1 (en) * 2020-09-08 2022-03-17 Xylyx Bio, Inc. Tissue-derived matrikine compositions and methods therefor

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