CN111744005B - 一种女性下生殖道粘膜保护、再生喷剂及其制备方法 - Google Patents
一种女性下生殖道粘膜保护、再生喷剂及其制备方法 Download PDFInfo
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- CN111744005B CN111744005B CN202010593962.8A CN202010593962A CN111744005B CN 111744005 B CN111744005 B CN 111744005B CN 202010593962 A CN202010593962 A CN 202010593962A CN 111744005 B CN111744005 B CN 111744005B
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Abstract
一种女性下生殖道粘膜保护、再生喷剂及其制备方法,它涉及一种再生喷剂及其制备方法,属于生物技术领域范畴。本发明的目的是要解决现有妇科类护理产品仅注重遮盖异味、针对瘙痒表面症状进行治疗,没有起到对女性下生殖道粘膜保护和粘膜再生修护的问题。产品由乳酸、库拉索芦荟叶提取物、丁二醇、甘油、PDGF‑AB、TGF‑B、1,25‑二羟维生素D3、1640培养基、白蛋白、聚乙烯吡咯烷酮、羧甲基纤维素钠、卡波姆、泊洛沙姆407和纯化水制备而成。本发明制备的女性下生殖道粘膜保护、再生喷剂适用于对女性下生殖道粘膜保护和再生修复。
Description
技术领域
本发明涉及一种再生喷剂及其制备方法,属于生物技术领域范畴。
背景技术
人类与病原体斗争,有一套是与生俱来的天然防御体系,用于抵抗和消灭入侵的病原体,同时与身体的正常微生物群达到共生平衡状态。人体的第一道天然防线,就是皮肤和粘膜防线。在人体呼吸道、消化道和泌尿道、生殖道内部都覆盖着粘膜,粘膜表面还有纤毛运动,如鼻腔里的鼻毛可以阻挡部分飞沫和尘埃,同时粘膜组织的局部免疫,包括固有免疫和适应性免疫,可对共生菌产生免疫耐受而对致病菌产生免疫应答,通过黏膜表面的共生菌可调节宿主全身的免疫***。因此这些第一道防御是机体防御体系中很重要的组成部分,一旦失去或大部失去这一屏障,如大面积烧伤、溃烂、糜烂,便将失液、严重感染等使机体生存面临极大威胁,新冠病毒对粘膜组织的首先侵染就是一个最有利的证据。
女性生殖道(female reproductive tract,FRT)黏膜免疫属于黏膜免疫的一部分,女性生殖道固有免疫***包括黏膜上皮的机械屏障、共生菌的微生物屏障、固有免疫细胞及其受体的免疫屏障;适应性免疫包括B细胞介导的体液免疫及T细胞介导的细胞免疫。女性生殖道黏膜免疫不仅参与局部炎症,还可能具有抗肿瘤免疫应答的作用。因此女性生殖道可抵抗致病菌的入侵,还有助于成功受精及妊娠,从而维持女性生殖健康。不健康的女生生殖道会长妇科疾病,包括外阴炎、***炎、***、***、***等。生殖道感染是女性的常见病和多发病,由于各种细菌、病毒、假丝酵母菌、滴虫、衣原体、支原体等病原体的侵袭,引起女性生殖道感染的一大类疾病的总称,患者以炎症性疾病(包括***炎、***、***和泌尿***感染)就诊的人群达到55.6%。在***有关"中国部分城市已婚妇女妇科常见病的流行疾学调查"结果显示:妇科常见病中生殖道感染患病率最高,约42.9%。女性下生殖道感染中常见的感染为细菌性***病(bacterial vaginosis,BV)、外阴***假丝酵母菌病(vulvovaginal candidiasis,VVC)和滴虫性***炎(trichomonasvaginitis,TV),需氧菌性***炎(aerobic vaginitis,AV)在人群中的检出率约为10%。90%的上生殖道感染是由下生殖道感染上行所致。***开始是微生物有害微生物从***侵染宫颈,然后上行感染盆腔,出现炎症反应,由于表现不特异、治愈率低和复发率高状,临床存在盲目应用抗生素治疗造成的***微生态失衡,进一步加剧各种***炎发生,而市场上很多的妇科类护理产品也仅注重遮盖异味、针对瘙痒等表面症状,没有起到对女性下生殖道粘膜保护和粘膜再生修护作用。
发明内容
本发明的目的是要解决现有妇科类护理产品仅注重遮盖异味、针对瘙痒表面症状进行治疗,没有起到对女性下生殖道粘膜保护和粘膜再生修护的问题,而提供一种女性下生殖道粘膜保护、再生喷剂及其制备方法。
一种女性下生殖道粘膜保护、再生喷剂由乳酸、库拉索芦荟叶提取物、丁二醇、甘油、PDGF-AB、TGF-B、1,25-二羟维生素D3、1640培养基、白蛋白、聚乙烯吡咯烷酮、羧甲基纤维素钠、卡波姆、泊洛沙姆407和纯化水制备而成。
一种女性下生殖道粘膜保护、再生喷剂的制备方法,是按以下步骤完成的:
一、称取:按质量分数称取0.5~1.5%乳酸、0.4~1.4%库拉索芦荟叶提取物、1.2~3.1%丁二醇、2~4%甘油、3~8×10-4%PDGF-AB、1~3×10-4%TGF-B、100~300IU 1,25-二羟维生素D3、40~50%1640培养基、0.5~1.1%白蛋白、2~3%聚乙烯吡咯烷酮、0.6~1.2%羧甲基纤维素钠、0.3~0.5%卡波姆、0.1~0.2%泊洛沙姆407和余量纯化水;
二、将纯化水分为4份,再将乳酸和泊洛沙姆407分别制成微粉,将乳酸微粉和泊洛沙姆407微粉加入到第一份纯化水中,得到A溶液;将A溶液的pH值调节至4~6,得到A相;
三、将卡波姆加入到第二份纯化水中,磁力搅拌后溶胀18h~24h,得到B相;
四、将甘油、库拉索芦荟叶提取物、聚乙烯吡咯烷酮、羧甲基纤维素钠加入到第三份纯化水中,再在水浴锅中加热,得到C相;
五、将A相、B相和C相依次加入到磁力搅拌机中进行磁力搅拌,得到D相;
六、将丁二醇和1,25-二羟维生素D3依次加入到D相中,得到混合物;调节混合物的pH值至4~5,得到E相;
七、将PDGF-AB、TGF-B和白蛋白加入到1640培养基中,完全溶解后得到F相;将F相加入到E相中,再加入第四份纯化水中,降温至室温,得到女性下生殖道粘膜保护、再生喷剂。
本发明的有益效果:
一、本发明为了解决对女性下生殖道粘膜保护和再生作用,提供了一种女性下生殖道粘膜保护、再生喷剂及其制备方法,本发明制备的女性下生殖道粘膜保护、再生喷剂是一种可长效、缓释的喷剂,可形成保护膜,起到隔绝下生殖道有害微生物作用的同时,对下生殖道粘膜的再生,重建粘膜免疫***还起到了作用;
二、本发明无化学抗菌抑菌成分,通过几种成膜剂在酸性环境下,不破坏进度菌群的正常微生态,隔离作用,形成物理屏障,防止有病微生物侵害;
三、通过PDGF-AB、TGF-B细胞因子,促进***粘膜的再生;
四、通过1,25-二羟维生素D3、白蛋白和1640培养基,促进免疫细胞增加,改善局部粘膜免疫;
五、本发明以创新为基点突破传统工艺、集成缓释和成膜制剂技术、采用先进的微分溶解、低共熔混合、分相定溶及磁力剪切等多项国际先进的制剂技术来完成本品的工艺制备;
六、本发明制备的女性下生殖道粘膜保护、再生喷剂各原料的作用:乳酸—酸碱平衡;库拉索芦荟叶提取物—植物因子:保湿,促进粘膜保护;丁二醇—保湿;甘油—保湿,促进粘膜保护;PDGF-AB—促进粘膜细胞再生;TGF-B—促进粘膜细胞再生;1,25-二羟维生素D3—激活粘膜免疫;1640培养基—激活粘膜免疫;白蛋白—激活粘膜免疫;聚乙烯吡咯烷酮—成膜,隔离保护;羧甲基纤维素钠—成膜,隔离保护;卡波姆—成膜,吸收,抗菌,促进细胞再生;泊洛沙姆407—变温,成膜;纯化水—溶剂。
本发明制备的女性下生殖道粘膜保护、再生喷剂适用于对女性下生殖道粘膜保护和再生修复。
附图说明
图1为实施例一制备的女性下生殖道粘膜保护、再生喷剂在37℃培养后经显微镜下放大40倍的图;
图2为实施例一制备的女性下生殖道粘膜保护、再生喷剂在25℃培养后经显微镜下放大40倍的图;
图3为使用实施例一制备的女性下生殖道粘膜保护、再生喷剂对黏膜免疫水平修复和激活效果的第一幅图;
图4为使用实施例一制备的女性下生殖道粘膜保护、再生喷剂对黏膜免疫水平修复和激活效果的第二幅图;
图5为放置不同时间的实施例一制备的女性下生殖道粘膜保护、再生喷剂在243nm波长处的吸光度。
具体实施方式
本发明技术方案不局限于以下所列举具体实施方式,以下所列举具体实施方式,仅用于说明本发明而并非受限于本发明实施例所描述的技术方案。本领域的普通技术人员应当理解,仍然可以对本发明进行修改或等同替换,以达到相同的技术效果。只要满足使用需要,都在本发明的保护范围内。
具体实施方式一:本实施方式是一种女性下生殖道粘膜保护、再生喷剂由乳酸、库拉索芦荟叶提取物、丁二醇、甘油、PDGF-AB、TGF-B、1,25-二羟维生素D3、1640培养基、白蛋白、聚乙烯吡咯烷酮、羧甲基纤维素钠、卡波姆、泊洛沙姆407和纯化水制备而成。
具体实施方式二:本实施方式与具体实施方式一不同点是:一种女性下生殖道粘膜保护、再生喷剂按质量分数由0.5~1.5%乳酸、0.4~1.4%库拉索芦荟叶提取物、1.2~3.1%丁二醇、2~4%甘油、3~8×10-4%PDGF-AB、1~3×10-4%TGF-B、100~300IU 1,25-二羟维生素D3、40~50%1640培养基、0.5~1.1%白蛋白、2~3%聚乙烯吡咯烷酮、0.6~1.2%羧甲基纤维素钠、0.3~0.5%卡波姆、0.1~0.2%泊洛沙姆407和余量纯化水制备而成。其它步骤与具体实施方式一相同。
具体实施方式三:本实施方式与具体实施方式一或二之一不同点是:一种女性下生殖道粘膜保护、再生喷剂按质量分数由0.5~1%乳酸、0.4~1%库拉索芦荟叶提取物、1.2~2.1%丁二醇、2~3%甘油、3~5×10-4%PDGF-AB、1~2×10-4%TGF-B、100~200IU1,25-二羟维生素D3、40~45%1640培养基、0.5~0.8%白蛋白、2~2.5%聚乙烯吡咯烷酮、0.6~0.9%羧甲基纤维素钠、0.3~0.4%卡波姆、0.1~0.15%泊洛沙姆407和余量纯化水制备而成。其它步骤与具体实施方式一或二相同。
具体实施方式四:本实施方式与具体实施方式一至三之一不同点是:一种女性下生殖道粘膜保护、再生喷剂按质量分数由1~1.5%乳酸、1~1.4%库拉索芦荟叶提取物、2.1~3.1%丁二醇、3~4%甘油、5~8×10-4%PDGF-AB、2~3×10-4%TGF-B、200~300IU1,25-二羟维生素D3、45~50%1640培养基、0.8~1.1%白蛋白、2.5~3%聚乙烯吡咯烷酮、0.9~1.2%羧甲基纤维素钠、0.4~0.5%卡波姆、0.15~0.2%泊洛沙姆407和余量纯化水制备而成。其它步骤与具体实施方式一至三相同。
具体实施方式五:本实施方式与具体实施方式一至四之一不同点是:一种女性下生殖道粘膜保护、再生喷剂按质量分数由1%乳酸、1%库拉索芦荟叶提取物、2.1%丁二醇、3%甘油、5×10-4%PDGF-AB、2×10-4%TGF-B、200IU 1,25-二羟维生素D3、45%1640培养基、0.8%白蛋白、2.5%聚乙烯吡咯烷酮、0.9%羧甲基纤维素钠、0.4%卡波姆、0.15%泊洛沙姆407和余量纯化水制备而成。其它步骤与具体实施方式一至四相同。
具体实施方式六:本实施方式是一种女性下生殖道粘膜保护、再生喷剂的制备方法是按以下步骤完成的:
一、称取:按质量分数称取0.5~1.5%乳酸、0.4~1.4%库拉索芦荟叶提取物、1.2~3.1%丁二醇、2~4%甘油、3~8×10-4%PDGF-AB、1~3×10-4%TGF-B、100~300IU 1,25-二羟维生素D3、40~50%1640培养基、0.5~1.1%白蛋白、2~3%聚乙烯吡咯烷酮、0.6~1.2%羧甲基纤维素钠、0.3~0.5%卡波姆、0.1~0.2%泊洛沙姆407和余量纯化水;
二、将纯化水分为4份,再将乳酸和泊洛沙姆407分别制成微粉,将乳酸微粉和泊洛沙姆407微粉加入到第一份纯化水中,得到A溶液;将A溶液的pH值调节至4~6,得到A相;
三、将卡波姆加入到第二份纯化水中,磁力搅拌后溶胀18h~24h,得到B相;
四、将甘油、库拉索芦荟叶提取物、聚乙烯吡咯烷酮、羧甲基纤维素钠加入到第三份纯化水中,再在水浴锅中加热,得到C相;
五、将A相、B相和C相依次加入到磁力搅拌机中进行磁力搅拌,得到D相;
六、将丁二醇和1,25-二羟维生素D3依次加入到D相中,得到混合物;调节混合物的pH值至4~5,得到E相;
七、将PDGF-AB、TGF-B和白蛋白加入到1640培养基中,完全溶解后得到F相;将F相加入到E相中,再加入第四份纯化水中,降温至室温,得到女性下生殖道粘膜保护、再生喷剂。
本实施方式的有益效果:
一、本实施方式为了解决对女性下生殖道粘膜保护和再生作用,提供了一种女性下生殖道粘膜保护、再生喷剂及其制备方法,本实施方式制备的女性下生殖道粘膜保护、再生喷剂是一种可长效、缓释的喷剂,可形成保护膜,起到隔绝下生殖道有害微生物作用的同时,对下生殖道粘膜的再生,重建粘膜免疫***还起到了作用;
二、本实施方式无化学抗菌抑菌成分,通过几种成膜剂在酸性环境下,不破坏进度菌群的正常微生态,隔离作用,形成物理屏障,防止有病微生物侵害;
三、通过PDGF-AB、TGF-B细胞因子,促进***粘膜的再生;
四、通过1,25-二羟维生素D3、白蛋白和1640培养基,促进免疫细胞增加,改善局部粘膜免疫;
五、本实施方式以创新为基点突破传统工艺、集成缓释和成膜制剂技术、采用先进的微分溶解、低共熔混合、分相定溶及磁力剪切等多项国际先进的制剂技术来完成本品的工艺制备;
六、本实施方式制备的女性下生殖道粘膜保护、再生喷剂各原料的作用:乳酸—酸碱平衡;库拉索芦荟叶提取物—植物因子:保湿,促进粘膜保护;丁二醇—保湿;甘油—保湿,促进粘膜保护;PDGF-AB—促进粘膜细胞再生;TGF-B—促进粘膜细胞再生;1,25-二羟维生素D3—激活粘膜免疫;1640培养基—激活粘膜免疫;白蛋白—激活粘膜免疫;聚乙烯吡咯烷酮—成膜,隔离保护;羧甲基纤维素钠—成膜,隔离保护;卡波姆—成膜,吸收,抗菌,促进细胞再生;泊洛沙姆407—变温,成膜;纯化水—溶剂。
本实施方式制备的女性下生殖道粘膜保护、再生喷剂适用于对女性下生殖道粘膜保护和再生修复。
具体实施方式七:本实施方式与具体实施方式六的不同点是:步骤二中所述的乳酸微粉的粒径为150目~250目;所述的泊洛沙姆407微粉的粒径为250目~350目。其它步骤与具体实施方式六相同。
具体实施方式八:本实施方式与具体实施方式六至七之一不同点是:步骤三中所述的磁力搅拌的速度为8000r/min~10000r/min,磁力搅拌的时间为20min~30/min。其它步骤与具体实施方式六至七相同。
具体实施方式九:本实施方式与具体实施方式六至八之一不同点是:步骤四中所述的水浴锅的温度为75℃~80℃,加热时间为30min~40min;步骤五中所述的磁力搅拌的速度为8000r/min~10000r/min,磁力搅拌的时间为20min~30min。其它步骤与具体实施方式六至八相同。
具体实施方式十:本实施方式与具体实施方式六至九之一不同点是:所述的第一份纯化水、第二份纯化水、第三份纯化水和第四份纯化水的体积比为1:1:2:6。其它步骤与具体实施方式六至九相同。
采用以下实施例验证本发明的有益效果:
实施例一:一种女性下生殖道粘膜保护、再生喷剂的制备方法,是按以下步骤完成的:
一、称取:按质量分数称取1%乳酸、1%库拉索芦荟叶提取物、2.1%丁二醇、3%甘油、5×10-4%PDGF-AB、2×10-4%TGF-B、200IU 1,25-二羟维生素D3、45%1640培养基、0.8%白蛋白、2.5%聚乙烯吡咯烷酮、0.9%羧甲基纤维素钠、0.4%卡波姆、0.15%泊洛沙姆407和余量纯化水;
二、将纯化水分为4份,再将乳酸和泊洛沙姆407分别制成微粉,将乳酸微粉和泊洛沙姆407微粉加入到第一份纯化水中,得到A溶液;将A溶液的pH值调节至4,得到A相;
步骤二中所述的乳酸微粉的粒径为300目;所述的泊洛沙姆407微粉的粒径为300目;
三、将卡波姆加入到第二份纯化水中,磁力搅拌后溶胀20h,得到B相;
步骤三中所述的磁力搅拌的速度为10000r/min,磁力搅拌的时间为25min;
四、将甘油、库拉索芦荟叶提取物、聚乙烯吡咯烷酮、羧甲基纤维素钠加入到第三份纯化水中,再在水浴锅中加热,得到C相;
步骤四中所述的水浴锅的温度为80℃,加热时间为35min;
五、将A相、B相和C相依次加入到磁力搅拌机中进行磁力搅拌,得到D相;
步骤五中所述的磁力搅拌的速度为10000r/min,磁力搅拌的时间为25min;
六、将丁二醇和1,25-二羟维生素D3依次加入到D相中,得到混合物;调节混合物的pH值至5,得到E相;
七、将PDGF-AB、TGF-B和白蛋白加入到1640培养基中,完全溶解后得到F相;将F相加入到E相中,再加入第四份纯化水中,降温至室温,得到女性下生殖道粘膜保护、再生喷剂。
所述的第一份纯化水、第二份纯化水、第三份纯化水和第四份纯化水的体积比为1:1:2:6。
有益效果验证:
(1)、成膜试验:
将0.5mL实施例一制备的女性下生殖道粘膜保护、再生喷剂喷涂在25.4mm×76.2mm载玻片上,再在置于37℃的培养箱中使其变温后成膜,然后将载玻片置于Leica正置显微镜下,物镜4倍,目镜选择10倍,调整光圈和焦距,并对表明形态结构进行拍照分析。
本发明实施例一制备的女性下生殖道粘膜保护、再生喷剂经37℃孵育后镜下观察结果见图1;图1为实施例一制备的女性下生殖道粘膜保护、再生喷剂在37℃培养后经显微镜下放大40倍的图;
图1中箭头所指为实施例一制备的女性下生殖道粘膜保护、再生喷剂成膜边缘,可见喷剂边缘整齐,成膜均匀致密,膜中无可见物质分布不均状态。
本发明实施例一制备的女性下生殖道粘膜保护、再生喷剂经25℃孵育后镜下观察结果见图2;
图2为实施例一制备的女性下生殖道粘膜保护、再生喷剂在25℃培养后经显微镜下放大40倍的图;
图2中箭头所指为实施例一制备的女性下生殖道粘膜保护、再生喷剂边缘,只有液滴的边缘线,无明显可见的膜结构。结果显示喷剂可在37℃左右形成膜结构。
(2)、喷剂刺激性试验:
取体重为180g~220g SD雌性大鼠,随机分5组:大剂量喷剂组(1g/kg)、中剂量喷剂组(0.5g/kg)、小剂量喷剂组(0.1g/kg),及其阴性基质对照和壬苯醇醚阳性对照组(0.1g/kg)。大剂量喷剂组(1g/kg)、中剂量喷剂组(0.5g/kg)、小剂量喷剂组(0.1g/kg)使用的喷剂为实施例一制备的女性下生殖道粘膜保护、再生喷剂;每组6只,每日向***轻柔喷洒对应计量喷剂,连续10天。最后一次用药次日处死各组所有动物,立即剔取***粘膜。其组织病理形态学分析采用EoKstein法评分。具体评价以***壁的病理改变的上皮脱落、白细胞浸润、固有膜水肿、充血等四项指标从轻到重以0~4级打分,每只动物各项目分值为***上、中、下三段组织的均分,每只动物总分为各项目分值的总和。总分为0~8分者为临床能接受;8~10分为边缘值;10分以上为临床不能接受,实验结果见表1和表2所示。
表1
表2
从表1和表2可知,采用Eoksetin评分进行病理形态学分析,结果表明,大剂量组总分值5.33、中剂量组总分值4.55、小剂量组总分值4.66,均属于临床可接受范围(8分以内),说明其短期刺激作用不明显。
(3)、动物***粘膜完整性试验:
镜下观察喷剂刺激性试验各组剔取的***粘膜及宫颈组织的形态学变化。结果显示阴性对照组***粘膜上皮未见明显细胞增生,未见明显的水肿、炎细胞浸润等病理改变,疏松***排列正常。阳性对照组***粘膜可见粘膜表层上皮细胞增生、空泡变性、伴炎性细胞浸润,纤维组织增生,宫颈粘膜未见病理性改变。大剂量组***粘膜上皮出现轻微增生,上皮过度角化、部分淋巴组织浸润,宫颈粘膜未见病理性改变。中剂量组主要表现为粘膜上皮轻度细胞增生,其它改变与阴性对照相类似。小剂量组与阴性对照组比较无明显差异。
(4)、大鼠***微生态试验:
(4.1)实施例一制备的女性下生殖道粘膜保护、再生喷剂对***细菌生态影响:
为验证实施例一制备的女性下生殖道粘膜保护、再生喷剂对***各种细菌的生长影响,现进行四组试验检测。
第一组取***正常菌群中的优势菌-卷曲乳酸杆菌进行实施例一制备的女性下生殖道粘膜保护、再生喷剂对***有益菌影响实验,将卷曲乳酸杆菌接种到液体培养基中,37℃培养24-48小时之后,取菌液接种于固体琼脂培养基中,无可见液体后使用实施例一制备的女性下生殖道粘膜保护、再生喷剂喷洒、成膜,继续37℃培养,培养72小时,同时观察菌落生长状态。
第二组将卷曲乳酸杆菌接种到液体培养基中,37℃培养24-48小时之后,取菌液接种于固体琼脂培养基中,不使用私密喷剂参与,直接在37℃条件下培养,培养72小时,同时观察菌落生长状态。
第三组将卷曲乳酸杆菌接种到液体培养基中,37℃培养24-48小时之后,取菌液接种于固体琼脂培养基中,无可见液体后使用实施例一制备的女性下生殖道粘膜保护、再生喷剂喷洒、成膜后将培养的金黄葡萄球菌菌液均匀喷涂在私密喷剂膜上,继续37℃培养,培养12-24小时,将平板上生长的菌落接种至适宜体积胰酪大豆胨液体培养基中,混匀后30~35℃培养18~24小时。取上述培养物划线接种于甘露醇氯化钠琼脂培养基上,30~35℃培养18~72小时,观察生长状态。若甘露醇氯化钠琼脂培养基平板上有黄色菌落或外周有黄色环的白色菌落生长,则应进行鉴定试验,确证是否为金黄色葡萄球菌;若平板上没有与上述形态特征相符或疑似的菌落生长则鉴定结果为阴性,未检出金黄色葡萄球菌。
第四组试验步骤除将实施例一制备的女性下生殖道粘膜保护、再生喷剂替换为无菌生理盐水外与第三组相同。
实验结果显示,第一组和第二组平板均有大量菌落生成,使用PCR检测结果显示均为卷曲乳酸杆菌。第三组平板有大量菌落生成,挑取菌落进行鉴别培养基检测,无符合金黄色葡萄球菌特征菌落出现,随机PCR检测无金黄色葡萄球菌基因检出。第四组平板有大量菌落生成,挑取菌落进行鉴别培养基检测,出现符合金黄色葡萄球菌特征菌落,PCR检测结果显示为金黄色葡萄球菌。
综上可以得出结论,实施例一制备的女性下生殖道粘膜保护、再生喷剂可以有效的遏制金黄色葡萄球菌的生长,但是对于***有益菌不存在破坏作用。
(4.2)实施例一制备的女性下生殖道粘膜保护、再生喷剂病毒隔离试验:
采用96孔培养板培养***上皮细胞,培养成单层细胞后,分为两组,分别加入0.5mL的纯培养基和5%实施例一制备的女性下生殖道粘膜保护、再生喷剂,继续培养4小时,换液后加入100TCID50的HPV病毒液1.2×1012PFU/mL,培养两小时后换液,继续培养三天,期间持续观察细胞病变情况。
实验结果显示未使用安全浓度实施例一制备的女性下生殖道粘膜保护、再生喷剂孵育的***上皮细胞大量病变,而使用实施例一制备的女性下生殖道粘膜保护、再生喷剂孵育组细胞生长状态良好,细胞形态完整,与未侵染病毒组对比,细胞存活率可以达到90%以上。
(5)喷剂对黏膜免疫水平修复和激活:
取体重为180g~220g SD雌性大鼠,随机分2组:实施例一制备的女性下生殖道粘膜保护、再生喷剂给药组(0.5g/kg)及对照组,每组6只,每周向***轻柔喷洒对应计量喷剂三次,分别于治疗前,治疗一个月,治疗三个月时取***分泌物及静脉血。取材方法为充分暴露***后,取后穹隆***分泌物检测免疫球蛋白E(immunoglobulin E,IgE)、分泌型IgA(secretory IgA,sIgA)、γ干扰素(interferon-γ,IFN-γ)表达水平;静脉血离心后取血清检测IL-2、IL-10抗体IgG、IgA、IgM含量,结果如图3~图4所示;
图3为使用实施例一制备的女性下生殖道粘膜保护、再生喷剂对黏膜免疫水平修复和激活效果的第一幅图;
图4为使用实施例一制备的女性下生殖道粘膜保护、再生喷剂对黏膜免疫水平修复和激活效果的第二幅图;
从图3和图4可知,各因子存在不同程度降低,并趋向正常数值,显示机体的炎性反应有所好转。
(6)实施例一制备的女性下生殖道粘膜保护、再生喷剂成分长效、缓释作用:
随机抽取3批实施例一制备的女性下生殖道粘膜保护、再生喷剂,按照释放度测定法(中国药典2005)按照溶出度测定法进行,将实施例一制备的女性下生殖道粘膜保护、再生喷剂分别放置10、30、60、90、120min,以蒸馏水为供试品溶液。用紫外-可见分光光度计,在243nm波长处分别测定吸收度。分别计算不同时间的释放度,见图5所示;
图5为放置不同时间的实施例一制备的女性下生殖道粘膜保护、再生喷剂在243nm波长处的吸光度;
从图5可知,实施例一制备的女性下生殖道粘膜保护、再生喷剂成分释放随时间推移由少量逐渐增加,逐渐释放。
(7)***黏膜巨噬细胞及RAT-1细胞检测:
取12只大鼠,分为两组,每组6只,分别为未给药组和采用中剂量实施例一制备的女性下生殖道粘膜保护、再生喷剂给药组,未给药组使用生理盐水替代,分别处理一个月后,使用棉签轻柔的***大鼠***中,轻轻旋转数下后拔出,将棉签在适量生理盐水中充分浸泡,采用流式细胞技术检测样品中的巨噬细胞(Macrophages,)及RAT-1细胞,比对巨噬细胞及RAT-1细胞在两组中的含量差别,结果如表3所示,使用实施例一制备的女性下生殖道粘膜保护、再生喷剂后***黏膜中巨噬细胞及RAT-1细胞的含量明显增加。
表3
Claims (9)
1.一种女性下生殖道粘膜保护、再生喷剂,其特征在于一种女性下生殖道粘膜保护、再生喷剂按质量分数由0.5~1.5%乳酸、0.4~1.4%库拉索芦荟叶提取物、1.2~3.1%丁二醇、2~4%甘油、3~8×10-4%PDGF-AB、1~3×10-4%TGF-B、100~300IU 1,25-二羟维生素D3、40~50%1640培养基、0.5~1.1%白蛋白、2~3%聚乙烯吡咯烷酮、0.6~1.2%羧甲基纤维素钠、0.3~0.5%卡波姆、0.1~0.2%泊洛沙姆407和余量纯化水制备而成。
2.根据权利要求1所述的一种女性下生殖道粘膜保护、再生喷剂,其特征在于一种女性下生殖道粘膜保护、再生喷剂按质量分数由0.5~1%乳酸、0.4~1%库拉索芦荟叶提取物、1.2~2.1%丁二醇、2~3%甘油、3~5×10-4%PDGF-AB、1~2×10-4%TGF-B、100~200IU1,25-二羟维生素D3、40~45%1640培养基、0.5~0.8%白蛋白、2~2.5%聚乙烯吡咯烷酮、0.6~0.9%羧甲基纤维素钠、0.3~0.4%卡波姆、0.1~0.15%泊洛沙姆407和余量纯化水制备而成。
3.根据权利要求1所述的一种女性下生殖道粘膜保护、再生喷剂,其特征在于一种女性下生殖道粘膜保护、再生喷剂按质量分数由1~1.5%乳酸、1~1.4%库拉索芦荟叶提取物、2.1~3.1%丁二醇、3~4%甘油、5~8×10-4%PDGF-AB、2~3×10-4%TGF-B、200~300IU1,25-二羟维生素D3、45~50%1640培养基、0.8~1.1%白蛋白、2.5~3%聚乙烯吡咯烷酮、0.9~1.2%羧甲基纤维素钠、0.4~0.5%卡波姆、0.15~0.2%泊洛沙姆407和余量纯化水制备而成。
4.根据权利要求1、2或3所述的一种女性下生殖道粘膜保护、再生喷剂,其特征在于一种女性下生殖道粘膜保护、再生喷剂按质量分数由1%乳酸、1%库拉索芦荟叶提取物、2.1%丁二醇、3%甘油、5×10-4%PDGF-AB、2×10-4%TGF-B、200IU 1,25-二羟维生素D3、45%1640培养基、0.8%白蛋白、2.5%聚乙烯吡咯烷酮、0.9%羧甲基纤维素钠、0.4%卡波姆、0.15%泊洛沙姆407和余量纯化水制备而成。
5.如权利要求1所述的一种女性下生殖道粘膜保护、再生喷剂的制备方法,其特征在于一种女性下生殖道粘膜保护、再生喷剂的制备方法是按以下步骤完成的:
一、称取:按质量分数称取0.5~1.5%乳酸、0.4~1.4%库拉索芦荟叶提取物、1.2~3.1%丁二醇、2~4%甘油、3~8×10-4%PDGF-AB、1~3×10-4%TGF-B、100~300IU 1,25-二羟维生素D3、40~50%1640培养基、0.5~1.1%白蛋白、2~3%聚乙烯吡咯烷酮、0.6~1.2%羧甲基纤维素钠、0.3~0.5%卡波姆、0.1~0.2%泊洛沙姆407和余量纯化水;
二、将纯化水分为4份,再将乳酸和泊洛沙姆407分别制成微粉,将乳酸微粉和泊洛沙姆407微粉加入到第一份纯化水中,得到A溶液;将A溶液的pH值调节至4~6,得到A相;
三、将卡波姆加入到第二份纯化水中,磁力搅拌后溶胀18h~24h,得到B相;
四、将甘油、库拉索芦荟叶提取物、聚乙烯吡咯烷酮、羧甲基纤维素钠加入到第三份纯化水中,再在水浴锅中加热,得到C相;
五、将A相、B相和C相依次加入到磁力搅拌机中进行磁力搅拌,得到D相;
六、将丁二醇和1,25-二羟维生素D3依次加入到D相中,得到混合物;调节混合物的pH值至4~5,得到E相;
七、将PDGF-AB、TGF-B和白蛋白加入到1640培养基中,完全溶解后得到F相;将F相加入到E相中,再加入第四份纯化水中,降温至室温,得到女性下生殖道粘膜保护、再生喷剂。
6.根据权利要求5所述的一种女性下生殖道粘膜保护、再生喷剂的制备方法,其特征在于步骤二中所述的乳酸微粉的粒径为150目~250目;所述的泊洛沙姆407微粉的粒径为250目~350目。
7.根据权利要求5所述的一种女性下生殖道粘膜保护、再生喷剂的制备方法,其特征在于步骤三中所述的磁力搅拌的速度为8000r/min~10000r/min,磁力搅拌的时间为20min~30/min。
8.根据权利要求5所述的一种女性下生殖道粘膜保护、再生喷剂的制备方法,其特征在于步骤四中所述的水浴锅的温度为75℃~80℃,加热时间为30min~40min;步骤五中所述的磁力搅拌的速度为8000r/min~10000r/min,磁力搅拌的时间为20min~30min。
9.根据权利要求6、7或8所述的一种女性下生殖道粘膜保护、再生喷剂的制备方法,其特征在于所述的第一份纯化水、第二份纯化水、第三份纯化水和第四份纯化水的体积比为1:1:2:6。
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