CN1248912A - 用于预防和治疗螺杆菌属感染的口服制剂 - Google Patents
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Abstract
本发明公开了用于预防和/或治疗由螺杆菌属(特别是幽门螺旋杆菌)感染引起的哺乳动物胃肠道粘膜炎症的口服制剂。该制剂含有预防和/或治疗有效量的至少一种叶黄素类化合物。首选的叶黄素是可溶于油的虾青素,优选与脂肪酸成酯的天然虾青素。该口服制剂还可包含糖结构,例如从红球藻属藻生成的细胞壁衍生的糖。该制剂还可含有预防和/或治疗有效量的水溶性抗氧剂,例如抗坏血酸(维生素C)。该口服制剂以独立的单位剂量或以与食物的混合物存在。
Description
本发明涉及用于预防和/或治疗由螺杆菌属感染引起的哺乳动物胃肠道粘膜炎症的口服制剂。该制剂含有至少一种叶黄素类化合物，优选天然虾青素。发明背景
近几年来，幽门螺旋杆菌被确认为是人B型胃炎的主要病因。
不同的螺杆菌属感染不同的动物，并且必须穿透胃表面的粘膜层[0’Toole PW等，分子微生物学(Mol Microbiol)1994，14：691-703]以定居于胃上皮和粘膜下层[Wadstrm T等，食物药理学治疗(Aliment Pharmacol Ther)1996，10(第1补编)：17-28；ValkonenKH等，感染免疫学(Infect Immun)1994，62：3640-3648；Moran AP等，应用细菌学杂志(J Appl Bacteriol)1993，75：184-189；Wadstrm T等，Eur J Gastroenterol Hepatol 1993，5(第2补编)：512-515]。螺杆菌属是一种有鞭毛的游动生物，其可能以与该病原体独特螺旋形状有关的螺旋运动迅速高效地穿透胃粘膜层(螺杆菌源自于含义为螺旋的拉丁文helix)。
幽门螺旋杆菌可以在早期感染(即B型胃炎)中造成胃粘膜屏障功能的剧烈变化并破坏胃上皮的疏水性内层。这会造成酸和胃蛋白酶从胃腔回流到粘膜内，在胃和十二指肠引起消化性溃疡。这种粘膜屏障的破坏似乎还会影响胃粘膜对食物中的多种物质如某些与食物有关的致癌物质的摄取。
叶黄素、包括虾青素是一大组在分子中除碳和氢外还含有氧的胡萝卜素类化合物。胡萝卜素类化合物由植物、真菌和某些细菌重新产生[Johnson E.A.和Schroeder W.A.，1995，生物化学工程和生物技术进展(Adv In Biochem Engin.Biotechn.)53：119-178]。生物学试验证实，虾青素的抗氧特性明显优于其它胡萝卜素类化合物[MikiW.，1991，纯粹和应用化学(Pure and Appl Chem)63(1)：141-146]。
目前，对由螺杆菌属感染引起的哺乳动物胃肠道粘膜炎症的治疗主要是采用所谓的质子泵抑制剂例如Losec(奥美拉唑)，以及在胃溃疡时使用各种抗生素(可能会引起抗药性菌株的出现)。
本发明的描述
本发明提供用于预防和/或治疗由螺杆菌属感染引起的哺乳动物胃肠道粘膜炎症的口服制剂，该制剂含有预防和/或治疗有效量的至少一种叶黄素类化合物。
本发明的口服制剂可以含有不同种类的叶黄素化合物或同一种叶黄素的不同形式的混合物，例如合成虾青素和天然虾青素的混合物。
在本发明的具体实施方案中，哺乳动物胃肠道是人的胃，螺杆菌属是幽门螺旋杆菌。
叶黄素类化合物在治疗由螺杆菌属感染引起的哺乳动物胃肠道粘膜炎症中的预防和治疗作用的机制还不清楚，但据信可溶于脂肪/油的叶黄素类化合物的抗氧化性在保护粘膜的疏水性内层中起重要作用，从而使螺杆菌属无法定居。
在本发明的优选实施方案中，叶黄素是溶于食品级的油中。
在另一个优选的实施方案中，叶黄素的类型是虾青素、特别是被脂肪酸酯化了的虾青素。
在又一个优选的实施方案中，虾青素是从天然来源、特别是从红球藻属藻的培养物中得到[Renstrm B等，1981，植物化学(Phytochem20(11)：2561-2564]。
本发明的口服制剂还可包含糖结构，例如脂多糖、多糖和糖蛋白。
目前，本发明的首选实施方案含有藻粉，所述藻粉含有溶于小滴天然油和部分破裂的细胞壁中的天然糖结构中的被脂肪酸酯化了的虾青素。
本发明的口服制剂还可含有在预防和/或治疗应用中无活性或有活性的其它可药用成分，例如调味剂，以及预防和/或治疗有效量的水溶性抗氧剂，特别是抗坏血酸(维生素C)。
口服制剂以独立的单位剂量或以与食物的混合物存在。独立的单位剂量的例子是片剂、明胶胶囊和预定量的溶液，例如油溶液，或乳液，例如油包水或水包油乳液。可掺入本发明制剂的食物的例子是奶产品如酸奶、巧克力和谷类食品。
本发明的另一方面涉及预防和/或治疗由螺杆菌属感染引起的哺乳动物胃肠道粘膜炎症的方法，该方法包括向所述哺乳动物施用本发明的口服制剂。
对人而言，以虾青素的量计算的本发明活性成分的每日剂量通常为0.01-10mg/kg体重，但实际剂量取决于哺乳动物的种类以及具体的物种特异性生物学效应。
实验
用于该实验的口服制剂是叶黄素虾青素，该物质是由AstaCarotene AB(Gustavsberg，Sweden)通过培养红球藻属生产的商品。
预计其它来源的虾青素以及其它的叶黄素同样可用于本发明的目的。但是，使用来自藻类的虾青素的优点是，该虾青素是以与脂肪酸形成的酯的形式存在[Renstrm B等，文献出处同上]，酯化的虾青素比游离的虾青素在使用和储藏过程中更为稳定。
除藻类外，还可以从真菌和甲壳纲动物得到天然虾青素[JohnsonE.A.和Schroeder W.A.，文献出处同上]。
通过胃管向胃中施用含108cfu幽门螺旋杆菌的磷酸盐缓冲液来感染50只重量为28-30g的6-8周龄Balb/cA小鼠。以一天的间隔重复处理3次[Aleljung P.等，1996，FEMS Immunol Med Microbiol.13：303-309]。
14天后，处死10只小鼠并在胃活体组织上培养以分离幽门螺旋杆菌。培养时间为7天。
用幽门螺旋杆菌感染21天后，对剩余动物中的半数每只动物每天给予添加有相当于0.3mg虾青素的藻粉的饲料，共进行10天。
在第30天，将各组中的半数动物处死并按照上述的类似方法进行培养。
在第40天，处死剩余的动物并按照上述的类似方法进行培养。
结果列于表1。
表1
幽门螺旋杆菌呈阳性的动物数/处死的动物数
天数 处理的动物 对照动物
14 - 8/10
30 0/8 8/10
40 0/1 7/10
表1的结果证实，含有虾青素的藻粉具有治疗作用并可用于预防的目的。
Claims (13)
1.用于预防和/或治疗由螺杆菌属感染引起的哺乳动物胃肠道粘膜炎症的口服制剂，所述制剂含有预防和/或治疗有效量的至少一种叶黄素类化合物。
2.根据权利要求1的口服制剂，其中的哺乳动物胃肠道是人胃，螺杆菌属是幽门螺旋杆菌。
3.根据权利要求1或2的口服制剂，其中的叶黄素溶于食品级的油中。
4.根据权利要求1-3中任意一项的口服制剂，其中的叶黄素的类型是虾青素。
5.根据权利要求4的口服制剂，其中的虾青素是被脂肪酸酯化了的形式。
6.根据权利要求4或5的口服制剂，其中的虾青素是从天然来源得到的。
7.根据权利要求6的口服制剂，其中的天然来源是红球藻属藻的培养物。
8.根据权利要求1-7中任意一项的口服制剂，其中还含有糖结构。
9.根据权利要求7和8的口服制剂，该制剂含有藻粉，所述藻粉含有溶于小滴天然油和部分破裂的藻细胞壁中的天然糖结构中的被脂肪酸酯化了的虾青素。
10.权利要求1-9中任意一项的口服制剂，其中还含有预防和/或治疗有效量的水溶性抗氧剂。
11.根据权利要求10的口服制剂，其中的水溶性抗氧剂是抗坏血酸(维生素C)。
12.根据权利要求1-11中任意一项的口服制剂，该制剂以独立的单位剂量或以与食物的混合物存在。
13.预防和/或治疗由螺杆菌属感染引起的哺乳动物胃肠道粘膜炎症的方法，该方法包括向所述哺乳动物施用权利要求1-12中任意一项所述的口服制剂。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9700708A SE522246C2 (sv) | 1997-02-27 | 1997-02-27 | Oralt preparat för profylaktisk och terapeutisk behandling av Helicobacter Sp. infektion |
| SE97007082 | 1997-02-27 |
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| Publication Number | Publication Date |
|---|---|
| CN1248912A true CN1248912A (zh) | 2000-03-29 |
| CN1119994C CN1119994C (zh) | 2003-09-03 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN98802850A Expired - Fee Related CN1119994C (zh) | 1997-02-27 | 1998-02-05 | 用于预防和治疗螺杆菌属感染的口服制剂 |
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| Country | Link |
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| US (1) | US6262316B1 (zh) |
| EP (1) | EP0981338B1 (zh) |
| JP (3) | JP4267076B2 (zh) |
| KR (1) | KR100569908B1 (zh) |
| CN (1) | CN1119994C (zh) |
| AT (1) | ATE243030T1 (zh) |
| AU (1) | AU719090B2 (zh) |
| CA (1) | CA2280715C (zh) |
| DE (1) | DE69815677D1 (zh) |
| IL (1) | IL131129A (zh) |
| NO (1) | NO327303B1 (zh) |
| NZ (1) | NZ337080A (zh) |
| PL (1) | PL335370A1 (zh) |
| SE (1) | SE522246C2 (zh) |
| WO (1) | WO1998037874A1 (zh) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1324989C (zh) * | 2005-10-10 | 2007-07-11 | 华南理工大学 | 含虾青素营养食品及其制备方法 |
| CN114732130A (zh) * | 2022-04-07 | 2022-07-12 | 云南雨藻生物科技有限公司 | 含雨生红球藻且抑制胃粘膜受损的组合物及其应用 |
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| SE524337C2 (sv) * | 1998-10-16 | 2004-07-27 | Astacarotene Ab | Användning av åtminstone en typ av xantofyller för framställning av ett läkemedel för profylaktisk och/eller terapeutisk behandling av matsmältningsbesvär |
| SE9903336D0 (sv) * | 1999-09-17 | 1999-09-17 | Astacarotene Ab | DNA construct and its use |
| SE9903619D0 (sv) * | 1999-10-07 | 1999-10-07 | Astacarotene Ab | Use and method of treatment |
| SE0001071D0 (sv) * | 2000-03-27 | 2000-03-27 | Astacarotene Ab | Method of inhibiting the expression of inflammatory cytokines and chemokines |
| US7078040B2 (en) | 2000-03-27 | 2006-07-18 | Fuji Chemical Industry Co., Ltd. | Method of inhibiting the expression of inflammatory cytokines and chemokines |
| KR100481880B1 (ko) * | 2001-12-05 | 2005-04-11 | (주)바이오벤 | 목이버섯으로부터 헬리코박터 파이로리의 부착억제성분을추출하는 방법 및 그 헬리코박터 파이로리의 부착억제성분 |
| CA2473698A1 (en) * | 2002-01-16 | 2003-07-31 | Natural Alternatives International, Inc. | Anti-inflammatory formulations |
| WO2004021798A1 (es) * | 2002-09-03 | 2004-03-18 | Centro De Investigacion En Alimentacion Y Desarrollo A.C. | Metodo de preparacion de microcapsulas de astaxantina en quitosano y producto obtenido |
| US20040151761A1 (en) * | 2003-02-05 | 2004-08-05 | The Procter & Gamble Company | Methods and compositions utilizing astaxanthin |
| GB0314624D0 (en) | 2003-06-23 | 2003-07-30 | Advanced Bionutrition Europ Lt | Inflammatory disease treatment |
| WO2005025586A1 (en) | 2003-09-12 | 2005-03-24 | Access Business Group International Llc | Cytokine modulators and related method of use |
| JP4933097B2 (ja) * | 2003-12-19 | 2012-05-16 | 株式会社メニコン | 糖尿病および糖尿病合併症の治療・改善方法 |
| WO2005102356A1 (en) | 2004-04-14 | 2005-11-03 | Hawaii Biotech, Inc. | Carotenoid analogs or derivatives for the inhibition and amelioration of inflammation |
| US20090118229A1 (en) * | 2007-11-07 | 2009-05-07 | Bristol-Myers Squibb Company | Carotenoid-containing compositions and methods |
| US20090118228A1 (en) * | 2007-11-07 | 2009-05-07 | Bristol-Myers Squibb Company | Carotenoid-containing compositions and methods |
| US20090118227A1 (en) * | 2007-11-07 | 2009-05-07 | Bristol-Myers Squibb Company | Carotenoid-containing compositions and methods |
| JP5497372B2 (ja) * | 2009-08-19 | 2014-05-21 | バイオジェニック株式会社 | 非ステロイド性抗炎症薬起因性潰瘍の予防・治療薬 |
| WO2014074772A1 (en) | 2012-11-09 | 2014-05-15 | Heliae Development, Llc | Mixotrophic, phototrophic, and heterotrophic combination methods and systems |
| WO2014074770A2 (en) | 2012-11-09 | 2014-05-15 | Heliae Development, Llc | Balanced mixotrophy methods |
| CN107691751A (zh) * | 2017-11-12 | 2018-02-16 | 张雅萍 | 一种美容、香体的虾青素夹心凝胶糖果及其制备方法 |
| US11065269B1 (en) * | 2018-11-15 | 2021-07-20 | Samuel L. Shepherd | Method of using astaxanthin for the treatment of diseases, and more particularly, the treatment of cancer |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL110139A0 (en) * | 1993-06-28 | 1994-10-07 | Howard Foundation | Pharmaceutically-active antioxidants |
| JPH0799924A (ja) | 1993-09-30 | 1995-04-18 | Nippon Suisan Kaisha Ltd | アスタキサンチンを主要成分とするファフィア色素油の安定な粉末化物及びその製造方法 |
| JPH07300421A (ja) | 1994-04-28 | 1995-11-14 | Itano Reitou Kk | 抗炎症剤 |
| WO1996023489A2 (de) * | 1995-02-03 | 1996-08-08 | Basf Aktiengesellschaft | Verwendung von carotinoiden zur herstellung von arzneimitteln zur behandlung von dermatosen |
| JPH09124470A (ja) * | 1995-10-26 | 1997-05-13 | Suntory Ltd | 抗ストレス組成物 |
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1997
- 1997-02-27 SE SE9700708A patent/SE522246C2/sv not_active IP Right Cessation
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- 1998-02-05 WO PCT/EP1998/000628 patent/WO1998037874A1/en active IP Right Grant
- 1998-02-05 AU AU62951/98A patent/AU719090B2/en not_active Ceased
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1324989C (zh) * | 2005-10-10 | 2007-07-11 | 华南理工大学 | 含虾青素营养食品及其制备方法 |
| CN114732130A (zh) * | 2022-04-07 | 2022-07-12 | 云南雨藻生物科技有限公司 | 含雨生红球藻且抑制胃粘膜受损的组合物及其应用 |
| CN114732130B (zh) * | 2022-04-07 | 2024-01-23 | 云南雨藻生物科技有限公司 | 含雨生红球藻且抑制胃粘膜受损的组合物及其应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| AU6295198A (en) | 1998-09-18 |
| KR100569908B1 (ko) | 2006-04-10 |
| US6262316B1 (en) | 2001-07-17 |
| CN1119994C (zh) | 2003-09-03 |
| JP4463773B2 (ja) | 2010-05-19 |
| IL131129A (en) | 2004-06-20 |
| EP0981338A1 (en) | 2000-03-01 |
| IL131129A0 (en) | 2001-01-28 |
| KR20000070973A (ko) | 2000-11-25 |
| NO327303B1 (no) | 2009-06-02 |
| PL335370A1 (en) | 2000-04-25 |
| NO994109L (no) | 1999-10-27 |
| NZ337080A (en) | 2001-03-30 |
| JP2006188526A (ja) | 2006-07-20 |
| JP4267076B2 (ja) | 2009-05-27 |
| ATE243030T1 (de) | 2003-07-15 |
| CA2280715A1 (en) | 1998-09-03 |
| JP2001517213A (ja) | 2001-10-02 |
| SE522246C2 (sv) | 2004-01-27 |
| DE69815677D1 (de) | 2003-07-24 |
| SE9700708L (sv) | 1998-08-28 |
| SE9700708D0 (sv) | 1997-02-27 |
| WO1998037874A1 (en) | 1998-09-03 |
| EP0981338B1 (en) | 2003-06-18 |
| AU719090B2 (en) | 2000-05-04 |
| NO994109D0 (no) | 1999-08-25 |
| CA2280715C (en) | 2008-10-07 |
| JP2010111689A (ja) | 2010-05-20 |
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