CN101677583A - 用于治疗特应性皮炎的瑞士乳杆菌组合物 - Google Patents
用于治疗特应性皮炎的瑞士乳杆菌组合物 Download PDFInfo
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Abstract
本发明提供用于治疗人特应性皮炎的瑞士乳杆菌组合物。
Description
技术领域
本发明涉及用于治疗人特应性皮炎的瑞士乳杆菌(Lactobacillushelveticus)组合物。
背景技术
特应性皮炎(AD)是一种慢性炎性搔痒性皮肤病，影响着工业化国家中的众多儿童和成人。
有多种方式治疗特异性皮炎，例如通过使用抗组胺剂、局部或全身性类固醇进行治疗。参见例如“Allergy 2006：61：969-987”中的2006综述文章。
使用不同的乳酸细菌(LAB)治疗不同的过敏问题如特应性皮炎，也已有描述。
US2006/0088513A1总结了有关这方面的技术。
US2006/0088513A1的描述的相关部分在下文讨论。
众所周知，鼠李糖乳酸杆菌(L.rhamnosus)GG菌株是一种抗过敏乳酸细菌。据报道，将它给予孕妇可抑制婴儿特应性皮炎的发展。
乳酸细菌作为抗过敏药物的用途在几个现有技术文献中有公开。可以一提的公开的实例，有诸如嗜酸乳杆菌(L.acidophilus)、短乳杆菌(L.brevis)、布氏乳杆菌(L.buchnerii)、干酪乳酸杆菌(L.casei)、路氏乳杆菌(Lactobacillus leuteri)的乳酸细菌作为诸如过敏性支气管哮喘、慢性过敏性鼻炎、特应性皮炎等的I型过敏症的抑制剂的用途。
最近，已进行了许多旨在通过特殊食品/饮料产品抑制过敏症的研究。结果，描述或公布了各种食品或饮料的特殊成分如日本罗勒油、鱼油、独特茶多酚等的抗过敏作用。一些乳酸细菌发酵酸奶或乳酸细菌饮料实际上被用作据称具有抗过敏作用的食品或饮料。
在现有技术中(如在US2006/0088513A1中)通常描述到，乳酸细菌应优选作为活的/有存活力(live/viable)的乳酸细菌细胞给予，以获得积极的相关抗过敏作用。
但是，在WO02/28402(Nestlé)中描述到，乳酸细菌也可作为死的/失活的(dead/deactivated)细胞或者作为所谓的乳酸细菌“培养物上清液”[包含相关的代谢物]给予，并仍对皮肤相关过敏反应如特应性皮炎有一定的改善作用。
如US2006/0088513A1的段落[0006]中所说明，要说所有的乳酸细菌都具有相关的抗过敏作用那是不恰当的，因此鉴定/筛选新的有用的乳酸细菌菌株仍十分重要。
发明内容
本发明所要解决的问题是，鉴定可用来制作用于治疗特应性皮炎(AD)的食品/饲料产品或药物的替代乳酸细菌(LAB)。
解决方案是基于本发明人对WO2004/015125和WO2006/125441(两者的申请人均为Chr.Hansen A/S)中描述的注册/检索号为DSM 14998的瑞士乳杆菌的进一步分析。注册号为DSM 14998的这个乳酸细菌在本文中也可称为“Cardi-
”或“CHCC5951”。
在WO2004/015125和WO2006/125441中描述到Cardi-
具有良好的降血压特性，但并没有描述或者暗示Cardi-
对特应性皮炎的作用。
如在本文的工作实施例1中可见，本发明人鉴定到，成人口服Cardi-
发酵乳组合物后，他的特异性皮炎事实上消失了。如在工作实施例1中可见，该人患特应性皮炎很长时间，之前试图用各种药品、天然草药或不同的洗剂治疗，
在实施例1中使用了Cardi-
发酵乳。不受理论局限，不过认为一些Cardi-
代谢物/肽具有抗特应性皮炎作用。肽可例如是由乳酸细菌的蛋白水解活性从乳中的酪蛋白释放出肽所得到的肽。
但是，客观上没有理由认为Cardi-
本身，即作为活的/有存活力的细胞给予人，以获得良好的特应性皮炎治疗效果。如上所述，给予活的/有存活力的乳酸细菌以治疗特应性皮炎，这在现有技术中已广泛描述。
如上所述，Cardi-
是瑞士乳杆菌。
因此，本发明的第一方面涉及瑞士乳杆菌用于制造供治疗人特应性皮炎的产品的用途，其中所述产品包含：
(i)：活的/有存活力的或者死的瑞士乳杆菌；
(ii)：瑞士乳杆菌发酵乳；或者
(iii)：(i)和(ii)两者的混合物。
定义
在对本发明的详细实施方案进行论述之前，先提供与本发明主要方面有关的具体术语的定义。
术语“特异性皮炎”是技术人员公知的术语，医生懂得如何诊断一个人以鉴别该人是否患有特异性皮炎。根据公知的Medical Encyclopedia ofMedlinePlus(NIH，USA)，特应性皮炎与皮肤的炎性反应有关，所述炎性反应由接触过敏原或刺激物、暴露于阳光引起，或者由循环不良甚至应激引起。特应性皮炎的实例有特应性湿疹，这是一种引起发红、水泡和起屑的搔疹。抓挠皮疹可使炎症散播，导致感染甚至留下疤痕。
以下仅以举例方式描述本发明的实施方案。
具体实施方式
瑞士乳杆菌
特别优选的瑞士乳杆菌菌株CHCC5951/Cardi-
的样品保存在DSMZ(德国微生物菌种保藏中心，Deutsche Sammlung vonMikroorganismen und Zellkulturen GmbH，Mascheroder Weg 1b，38124Braunschweig，德国)，保藏号DSM 14998，保藏日期2002年5月15日。该保存是按国际承认用于专利程序的微生物保存布达佩斯条约(Budapest Treatyon the International Recognition of the Deposit of Microorganisms for thePurposes of Patent Procedure)的条件作出的。
因此，在一个优选的实施方案中，瑞士乳杆菌是注册号为DSM 14998的瑞士乳杆菌。
产品
产品可以是任何食品或药物产品，或者供口服或局部应用的化妆品。食品或药物产品的实例有乳、酸奶、凝乳、奶酪、发酵乳、乳基发酵产品、冰淇淋、发酵谷物基产品、乳基粉末、婴儿配方、宠物食品、片剂、液体细菌悬浮液、干口服补剂、湿口服补剂、干管饲喂(dry tube-feeding)或湿管饲喂(dry tube-feeding)。对于化妆品，有洗液、香波、霜(如保湿霜、防晒霜、日晒后用霜或抗衰老霜)和/或油膏，其中细菌可以以活的形式、半活性形式或失活形式包含，例如作为冻干粉包含。
产品——包含活的/有存活力的或死的瑞士乳杆菌
如上所述，根据第一方面的第(i)点，产品可以是包含活的/有存活力的或死的瑞士乳杆菌的产品。
技术人员知道(参见例如WO02/28402)，当作为细菌给予个人时，益生菌的平衡活性(balancing activity)将是依赖于剂量的。因此，设想到包含多达105-1012个细菌/g产品，其中细菌可以是活的或死的。优选地，它们是活的/有存活力的。
产品——包含瑞士乳杆菌发酵乳
如上所述，根据第一方面的第(ii)点，产品可以是包含瑞士乳杆菌发酵乳的产品。
技术人员知道如何进行乳的乳酸细菌发酵。参考例如WO2004/015125，其详细描述了乳酸细菌乳发酵。
如本文所述使用乳酸细菌，在发酵后即能提供有用数量的具有良好特应性皮炎减轻性能的肽或其他活性成分。因此，可不必进一步从发酵乳纯化或浓缩肽或其他活性成分。发酵食品乳可直接包装和提供到市场，例如作为食品产品，优选功能食品产品，或者食品产品添加剂，例如冷冻干燥的形式。
此外，可将冷冻干燥的发酵乳悬浮于中性乳中，从而得到合适的食品产品。冷冻干燥的发酵乳因此可视为合适的食品添加剂产品。
术语“功能食品”在本文中表示消费者以某种方式获悉其具有与特应性皮炎减轻性能有关的有用功能的食品产品。
在一些情形中，可能优选进行从发酵食品乳后续纯化肽或其他活性成分。例如当肽或其他活性成分要用于药品如药物片剂时，需要非常高浓度的具有特应性皮炎减轻性能的肽或其他活性成分，就可这样进行纯化。因此，在本发明的一个实施方案中，产品是药品。
本发明的一个实施方式涉及本文所述的用途，其中发酵乳以具有特应性皮炎减轻性能的肽或其他活性成分得以纯化或浓缩的方式进行进一步加工。
进行浓缩的一个合适方式是，将含有具有特应性皮炎减轻性能的肽或其他活性成分的发酵乳进行离心，回收所得的包含所述肽或其他活性成分的上清液。
当进行乳发酵时，这种上清液组合物称为乳清。如实施例1中可见，乳清是具有极好的特应性皮炎减轻性能的产品。因此，在一个优选的实施方案中，产品/组合物是乳清。
离心可优选例如在2,000-20,000rpm下进行1-20分钟。离心还可在离心机中进行。
所得的上清液可用反相树脂进行进一步的纯化处理，以获得其中具有减少心速性能的肽或其他活性成分的含量得到增加的样品。反相树脂纯化处理可通过用反相树脂吸收和洗脱肽或其他活性成分进行，和/或通过反相色谱进行，从而增加肽或其他活性成分的纯度。
如本文工作实施例1中所示，成人在口服了Cardi-
发酵乳组合物后，他的特应性皮炎事实上消失了。如实施例1中所说明，发酵乳产品以150ml/天的体积给予男性成人，持续8个星期的时间。
技术人员知道，获得所需医疗效果的药物相关剂量可因人而异，且可根据所要治疗的实际疾病的严重程度而变。
因此，在本发明的一个实施方案中，将发酵乳以5ml/天-1000ml/天、更优选25ml/天-500ml/天的体积给予人。优选地，发酵乳给予1天至1年的时间，更优选1个星期至25个星期的时间。
人
人可以是儿童或成人。在一个优选的实施方案中，人是成人。
实施例
实施例1：用发酵乳治疗特应性皮炎的人
用来进行乳发酵的瑞士乳杆菌是Cardi-
乳发酵和随后离心获取乳清是按WO2004/015125的工作实施例所述进行。
将这个发酵乳产品以150ml/天的体积给予男性成人，持续8个星期的时间。
试验人员在给本专利申请的发明人的信件中总结了结果。该信件大体上说道：
我参加了你们的Cardi-
研究项目，留意到了非常奇特的事情。从小到大，我备受特应性湿疹的折磨。为了治愈它，我用尽各种药品、天然草药、不同的洗剂等等。直到在过去几个星期里，我才差不多摆脱湿疹的困 扰。除了参加你们的研究项目以外，我的生活方式还有饮食习惯没有发生什么变化。
结论：
本结果证明，Cardi-
具有非常良好的抗过敏作用，从而使特应性湿疹得到有效治疗。
参考文献：
1：Allergy 2006：61：969-987
2：US2006/0088513A1
3：WO02/28402(Nestlé)
4：WO2004/015125(Chr.Hansen A/S)
5：WO2006/125441(Chr.Hansen A/S)
Claims (10)
1.瑞士乳杆菌用于制造供治疗人特应性皮炎(AD)的产品的用途，其中所述产品包含：
(i)：活的/有存活力的或者死的瑞士乳杆菌；
(ii)：瑞士乳杆菌发酵乳；或者
(iii)：(i)和(ii)两者的混合物。
2.权利要求1的用途，其中所述特应性皮炎(AD)是特应性湿疹。
3.权利要求1或2的用途，其中所述瑞士乳杆菌是登记号为DSM14998的瑞士乳杆菌(本文也称为“
”)。
4.根据前述权利要求中任一项的用途，其中所述产品是供口服或局部应用的食品、药品或者化妆品。
5.权利要求4的用途，其中
-所述食品或药品是乳、酸奶、凝乳、奶酪、发酵乳、乳基发酵品、冰淇淋、发酵谷物基产品、乳基粉末、婴儿配方或宠物食品，或者片剂、液体细菌悬浮液、干口服补剂、湿口服补剂、干管饲喂或湿管饲喂；或者
-所述化妆品是洗剂、香波、霜。
6.根据前述权利要求中任一项的用途，其中所述产品是食品(例如酸奶)，且它包含瑞士乳杆菌发酵乳。
7.根据权利要求6的用途，其中所述发酵乳是乳清。
8.权利要求6或7的用途，其中所述发酵乳是冷冻干燥的，所述产品是食品添加剂产品。
9.根据权利要求1-6中任一项的用途，其中所述产品包含105-1012个活的/有存活力的细菌/g产品。
10.根据前述权利要求中任一项的用途，其中所述人是儿童或成人，优选其中所述人是成人。
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| DKPA200700932 | 2007-06-27 | ||
| PCT/EP2008/058134 WO2009000875A2 (en) | 2007-06-27 | 2008-06-26 | Lactobacillus helveticus bacterium composition for treatment of atopic dermatitis |
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| CN101677583A true CN101677583A (zh) | 2010-03-24 |
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| JP (1) | JP2010531840A (zh) |
| CN (1) | CN101677583A (zh) |
| WO (1) | WO2009000875A2 (zh) |
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| GB2472790A (en) * | 2009-08-18 | 2011-02-23 | Laurence Christian Hayes | Dermatological preparations comprising microbes. |
| EP2449890A1 (en) * | 2010-11-05 | 2012-05-09 | Nestec S.A. | Powdered cereal compositions comprising non-replicating probiotic microorganisms |
| EP2617296A1 (en) * | 2012-01-19 | 2013-07-24 | Nestec S.A. | A composition comprising specific Lactobacillus helveticus strains and reducing food and/or respiratory allergy symptoms |
| US10111829B2 (en) | 2017-03-03 | 2018-10-30 | Alpha Pet Tech, Inc. | Probiotic-containing animal shampoo and methods of use |
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|---|---|---|---|---|
| JP2000239175A (ja) * | 1999-02-18 | 2000-09-05 | Calpis Co Ltd | 抗アレルギー剤 |
| AUPS057102A0 (en) * | 2002-02-15 | 2002-03-07 | Vri Biomedical Ltd | Compositions and methods for treatment of skin disorders |
| JP4499564B2 (ja) * | 2002-08-09 | 2010-07-07 | セーホーエル．ハンセン アクティーゼルスカブ | 抗高血圧特性を有するペプチドの製造方法 |
| AU2004233658B2 (en) * | 2003-03-13 | 2009-10-29 | Kirin Holdings Kabushiki Kaisha | Antiallergic composition |
| CA2532489C (en) * | 2003-06-23 | 2012-12-11 | Nestec S.A. | Infant or follow-on formula |
| WO2005060937A1 (en) * | 2003-12-23 | 2005-07-07 | Chr. Hansen A/S | Compressed tablets comprising viable probiotic microorganisms |
| ITMI20041550A1 (it) * | 2004-07-29 | 2004-10-29 | Proge Farm Srl | Uso di batteri probiotici per la preparazione di composizioni topiche per la protezione dell'epidermide |
| KR100479719B1 (ko) * | 2005-01-29 | 2005-03-31 | 주식회사 프로바이오닉 | 유해 병원성 미생물 생육 억제능 및 항알레르기성을 갖는 신규 내산성 락토바실러스 사케이 Ｐｒｏｂｉｏ-65 |
| PL1855550T3 (pl) * | 2005-02-28 | 2012-03-30 | Nutricia Nv | Kompozycje żywieniowe z probiotykami |
| KR20080019059A (ko) * | 2005-06-24 | 2008-02-29 | 칼피스가부시키가이샤 | 표피세포 분화 및 각화 촉진제, 및 표피 각화 촉진용기능성 음식품 |
| FR2889057B1 (fr) * | 2005-08-01 | 2008-07-18 | Oreal | Composition cosmetique et/ou dermatologique pour la prevention et/ou le traitement des peaux sensibles ou seches |
| FR2889958A1 (fr) * | 2005-08-25 | 2007-03-02 | Lyoct Sa Lab | Utilisation d'un symbiotique pour le traitement de la dermatite atopique |
-
2008
- 2008-06-26 EP EP08761381A patent/EP2170088A2/en not_active Withdrawn
- 2008-06-26 US US12/664,963 patent/US20100273239A1/en not_active Abandoned
- 2008-06-26 CN CN200880021245A patent/CN101677583A/zh active Pending
- 2008-06-26 WO PCT/EP2008/058134 patent/WO2009000875A2/en active Application Filing
- 2008-06-26 JP JP2010513916A patent/JP2010531840A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JP2010531840A (ja) | 2010-09-30 |
| WO2009000875A2 (en) | 2008-12-31 |
| US20100273239A1 (en) | 2010-10-28 |
| EP2170088A2 (en) | 2010-04-07 |
| WO2009000875A3 (en) | 2009-12-23 |
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