CN105748533B - 副干酪乳杆菌制剂及其应用 - Google Patents
副干酪乳杆菌制剂及其应用 Download PDFInfo
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Classifications
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- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2400/00—Lactic or propionic acid bacteria
- A23V2400/11—Lactobacillus
- A23V2400/165—Paracasei
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
本发明涉及副干酪乳杆菌制剂及其应用,具体涉及副干酪乳杆菌作为主要活性成份制成微生态制剂,及该微生态制剂在治疗相关疾病中的应用,属于生物药领域。
Description
技术领域
本发明涉及副干酪乳杆菌制剂及其应用,具体涉及副干酪乳杆菌作为主要活性成份制成微生态制剂,及该微生态制剂在治疗相关疾病中的应用,属于生物药领域。
背景技术
副干酪乳杆菌在预防和治疗疾病方面发挥越来越重要的作用,但目前已经上市的含有副干酪乳杆菌的产品效果不理想,因此筛选高效副干酪乳杆菌菌种是目前亟需解决的问题,尤其筛选到具有显著抗过敏作用的副干酪乳杆菌菌种。
近年来,过敏疾病的发生率呈上升趋势,根据世界卫生组织的数据,目前全球有22%的人患过敏性疾病,并且发病率迅猛增长,截止到2015年,全球已有40-50%的人患有过敏症,WHO已把过敏性疾病列为21世纪需要重点研究和防治的三大疾病之一。据统计我国过敏性疾病的发病率高达37.3%,主要影响人群为婴幼儿。
寻找有效的过敏防治措施迫在眉睫。目前针对治疗过敏性疾病比较普遍的方法是使用药物治疗。如组胺拮抗剂,可通过堵塞组胺感受器来抑制组胺反应,以及类固醇和抑制肥大细胞释放发炎物质的药物、气管扩张剂药物等。但是这类药物仅提供暂时的症状缓解,无法真正改变过敏免疫反应,治标不治本。
本发明副干酪乳杆菌微生态制剂防治过敏等疾病疗效显著,效果显著优于其他副干酪乳杆菌,并可作为药品、保健品、食品、兽药和饲料添加剂等应用,社会意义巨大,且未见相关研究报道,特申请此发明专利。
发明内容
本发明的目的是提供一种微生态制剂,该微生态制剂的活性成分为副干酪乳杆菌DH068,保藏编号CGMCC No.11225,该微生态制剂具有预防或治疗机体过敏反应等作用。
根据菌株的菌落、菌体形态特征,16SrDNA序列分析及API细菌鉴定系统分析结果来确认菌株在分类学地位,发现编号DH068的菌株为副干酪乳杆菌;该株菌在形态学及一般性质上的特征如下:
1、菌体及菌落形态
菌体形态:菌体在显微镜下呈短杆状,单个或成对排列,长1.5-3微米,宽0.6-0.8微米,不运动,无芽孢,革兰氏染色阳性。
菌落形态:固体培养基上菌落形态均为圆形,光滑,边缘整齐,隆起,乳白色不透明。菌落直径大小一般为0.8-1.4mm。
2、生理生化特征:
最适生长温度为35-38℃,兼性厌氧,耐NaCl浓度10%(质量分数)。菌株的最适生长pH值5.5-6.2。不具有致病性,不产毒素。
在糖发酵中,苦杏仁苷、纤维二糖、七叶苷、果糖、半乳糖、葡萄糖、乳糖、麦芽糖、甘露醇、甘露糖、鼠李糖、核糖、水杨苷、山梨醇、蔗糖、海藻糖;不发酵阿拉伯糖、松三糖、蜜二糖、棉籽糖、海藻糖、木糖。精氨酸水解不产NH3,发酵葡萄糖不产气,接触酶阴性。
本微生态制剂制成固体组合物包含的总活菌数不低于1×106CFU/g,一般在1×109CFU/g以上,最高可达到1×1011CFU/g或1×1011CFU/g以上;制成液体组合物包含的总活菌数不能低于1×106CFU/mL,一般在1×109CFU/mL以上,最高可达到1×1011CFU/mL或1×1011CFU/mL以上。
本微生态制剂可用于预防或治疗机体过敏反应等多种人体疾病,进一步治疗湿疹、过敏性鼻炎、异位性皮炎、过敏性哮喘或食物过敏等疾病。
本微生态制剂可制成药品组合物、保健品、食品、兽药或饲料添加剂等。
本微生态制剂所述副干酪乳杆菌指活的生物个体。
具体实施方式
制备例说明:这里通过副干酪乳杆菌DH068保藏编号CGMCC11225散剂为例进行具体说明,其他副干酪乳杆菌菌种制剂的制备方法本领域技术人员通过本实施例很容易掌握,其他剂型的制备方法本领域技术人员通过本实施很容易掌握,在此不再一一叙述说明。制备方法并不局限于本发明实施例所述,公知的能够达到制备目的的方法均可以,实施例的制备说明只是对本发明的说明,并不是对本发明保护范围的限制。
制备实施例 副干酪乳杆菌散剂的制备
1菌粉的制备和菌种的鉴定
用无菌容器收集自然排出的新鲜粪便5-10g,迅速放入厌氧罐中,带回实验室进行菌种分离。取粪便样品1.5g,用15mlPBS缓冲液悬浮混匀,400g离心5min收集上清浊液,再加入适量PBS缓冲液8000g离心10min,收集上清浊液,即得到供试样品。吸取1ml上浊液加入一支装有9mlPBS稀释液(含有5‰L-半胱氨酸)的试管中涡旋混匀,作为10-2稀释液,用同样方法稀释至10-3,分别取粪便原液、10-2稀释液、10-3稀释液各0.1ml涂布于MRS平板上,置于37℃恒温培养箱中培养24小时后,选择培养基上呈圆形,光滑,边缘整齐,隆起,乳白色不透明,直径大小在0.8-1.4mm的菌落,接种于MRS液体培养基中,37℃培养24h后,将所得培养液离心(12000rpm)分离出菌体后,将菌体冷冻真空干燥,调制出干燥菌粉,活菌数均为1×109CFU/g以上。同时对菌株展开生理生化特征鉴定。通过对分离获得的菌株分别进行接触酶实验及凝乳实验,去除接触酶阳性及无凝乳现象之菌株,排除非目的菌株后,对其余的菌株继续通过BIOLOG及API 50CH进行生理生化特征鉴定,最后通过提取DNA测序,进一步明确菌株的分类地位。经鉴定为副干酪乳杆菌DH068、副干酪乳杆DH052、副干酪乳杆DH077、副干酪乳杆DH026、副干酪乳杆DH127、副干酪乳杆DH103。
2毒性试验
2.1动物及分组取70只SPF级别小鼠,6~8周龄,体重15~19g,随机分入各副干酪乳杆菌组和未给药组,每组10只。
2.2制备菌液将上述副干酪乳杆菌菌粉分别用纯化水调制为含菌数均为1×107CFU/mL的菌液。
2.3方法副干酪乳杆菌组和未给药组均给予相同的基础饲料,且饲养条件均一致,副干酪乳杆菌组每天灌服副干酪乳杆菌菌液0.5mL,未给药组每天灌服纯化水0.5mL,饲喂6个月,观察毒性反应。
2.4结果
各组小鼠均未出现异常情况,未发生振颤、痉挛、运动失调、姿态异常,无眼球突出,排尿正常,皮肤、呼吸正常,无死亡情况,表明副干酪乳杆菌不存在毒性。
3制备成散剂等剂型
根据上述步骤和方法分离鉴定后,经实验检验无毒性,就可将副干酪乳杆菌菌种制成菌粉,然后按照需要添加相关辅料制成各种剂型,优选根据副干酪乳杆菌菌粉的活菌数,制成散剂,使活菌数不低于1×107CFU/g,然后装袋。
应用效果实施例说明:本发明以副干酪乳杆菌DH068保藏编号CGMCC11225为代表说明副干酪乳杆菌的应用效果,但不是对本发明的限制。
应用效果实施例1:副干酪乳杆菌缓解过敏试验研究
1材料与方法
1.1材料
1.1.1试验产品
副干酪乳杆菌活菌DH068、DH052、DH077、DH026、DH123、DH103散剂,活菌数均为1×107CFU/g以上。
1.1.2试验动物
清洁级3周龄断乳雄性BALB/c近交系小鼠56只。
1.2方法
将56只小鼠随机分为8组,每组各7只。将各组的益生菌溶于生理盐水中混匀制成混浊液,使终浓度为1×108cfu/ml。灌胃给予20ml/kg,每日剂量分两次灌胃。阴性对照组:将冻干保护剂溶于生理盐水中制成浑浊液,小鼠每天灌胃20ml/kg,每日剂量分两次灌胃。阳性对照组:选用从市场上同类益生菌产品中分离获得的副干酪乳杆菌,将该菌株菌体溶于生理盐水中制成1×108cfu/ml混浊液,小鼠每天灌胃20ml/kg,每日剂量分两次灌胃。
1.3建立迟发型超敏反应动物模型
首次灌胃第二日小鼠腹部剃毛,3cm×3cm范围,以使致敏部位充分暴露。均匀涂布20μL 0.5%DNFB溶液(溶于4:1丙酮:橄榄油中)致敏。对各组小鼠按上述方法连续灌胃14天,末次给药后1小时,在小鼠左耳两面均匀涂布0.25%DNFB溶液10μL进行攻击,诱发小鼠迟发型超敏反应模型。60min后剪下双耳称重。
1.4观察指标
耳重量:以打孔器取耳中部组织块,分析天平称重,计算左右耳组织块的重量差。比较各组数值,以样本均值差异显著性t检验作统计学处理。
1.5计算公式
肿胀度(mg)=右耳片重量-左耳片重量
抑制率(%)=(空白对照组平均肿胀度-各给药组平均肿胀度)/空白对照组平均肿胀度×100%
2试验结果及分析
2.1试验结果
表1 不同益生菌菌株对小鼠迟发型超敏反应的影响(n=7)
2.2分析
与市场上知名同类产品分离获得的菌株副干酪乳杆菌及从样品中同时分离的其它菌株相比,副干酪乳杆菌DH068能显著抑制由DNFB诱发的小鼠迟发型超敏反应的耳肿胀程度,抑制率为69.09%,差别具有统计学意义(P<0.05)。因此该株益生菌相较于其它菌株具有良好的抑制机体的过敏反应功能。
本发明在实施过程中所使用的微生物菌种已于2015年08年11日在中国微生物菌种保藏管理委员会普通微生物中心(北京市朝阳区北辰西路1号院3号,中国科学院微生物研究所邮编100101)保藏,微生物菌种信息如下。
分类命名:副干酪乳杆菌Lactobacillus paracasei,保存编号11225。
上述微生物菌种经该微生物中心检测,检测结果为存活。
Claims (7)
1.一种微生态制剂,其特征在于该微生态制剂的活性成分为副干酪乳杆菌,所述副干酪乳杆菌为副干酪乳杆菌DH068,保藏编号CGMCC No.11225,所述微生态制剂固体组合物包含的总活菌数不低于1×106CFU/g,或液体组合物包含的总活菌数不低于1×106CFU/mL。
2.按权利要求1所述的微生态制剂,其特征在于固体组合物包含的总活菌数在1×109CFU/g及以上,或液体组合物包含的总活菌数在1×109CFU/mL及以上。
3.按权利要求1所述的微生态制剂,其特征在于固体组合物包含的总活菌数在1×1011CFU/g及以上,或液体组合物包含的总活菌数在1×1011CFU/mL及以上。
4.按权利要求1所述的微生态制剂,其特征在于副干酪乳杆菌指活的生物个体。
5.权利要求1所述的微生态制剂的应用,其特征在于有效剂量的副干酪乳杆菌作为活性成份制成药品组合物、保健品、食品、兽药或饲料添加剂。
6.权利要求1所述的微生态制剂在制备预防或治疗机体过敏反应用组合物中的用途。
7.权利要求1所述的微生态制剂在制备治疗湿疹、过敏性鼻炎、异位性皮炎、过敏性哮喘或食物过敏用组合物中的用途。
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