CN105025908A - 针对肿瘤、获得性免疫缺陷综合征和白血病的化疗治疗的支持疗法 - Google Patents
针对肿瘤、获得性免疫缺陷综合征和白血病的化疗治疗的支持疗法 Download PDFInfo
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Abstract
本发明涉及用作抗肿瘤化疗治疗、获得性免疫缺陷综合征治疗和白血病治疗中的支持疗法的组合物。所述组合物包含属于戊糖乳杆菌物种且具有抗病毒和抗细菌活性的细菌菌株，以及内化在间歇灭菌的细菌细胞内的生物利用率高的锌，且混有至少一种橡胶、优选藻酸盐和/或凝胶、优选凝胶。
Description
本发明涉及用作抗肿瘤化疗治疗、获得性免疫缺陷综合征治疗和白血病治疗中的支持疗法的组合物。所述组合物包含属于戊糖乳杆菌物种且具有抗病毒和抗细菌活性的细菌菌株，以及内化在经间歇灭菌的细菌细胞内的生物利用率高的锌，且混有至少一种橡胶、优选藻酸盐和/或凝胶、优选凝胶。
已知化疗会导致免疫系统活性的减低，而有缺损的免疫系统无法保护生物体免受细菌和病毒感染。
而且已知化疗(chemo)对于肿瘤具有优势性效果，然而不幸的是其对健康组织、对所有组织(虽然主要是对其中的某一些，如小肠)具有副作用，导致粘膜炎、恶心、呕吐、腹泻、营养吸收困难和由此所致的营养不良。
除非实施了能够借助支持疗法来抵消(当然是在某种限度内)化疗的副作用的疗法，否则无法施用有效的化疗剂量。
因此，对于针对化疗的支持疗法，特别是针对对食道、胃和小肠粘膜造成的损伤的支持疗法仍然有需求，且因此对这些粘膜进行适当保护是绝对必要的。
而且，对于针对化疗的支持疗法，特别是针对免疫系统的支持疗法仍然有需求，这是因为化疗意味着免疫系统有效性的减低，这导致生物体对细菌和病毒的易感性，从而导致细菌和病毒感染的发生。
在经过长期深入的研究工作后，申请人已鉴定并选出具有强抗病毒活性的细菌菌株。申请人所选出的细菌菌株除具有显著的抗病毒活性外，还具有强抗细菌活性，这是因为其能够产生细菌素和/或过氧化氢和/或具有抗细菌活性的代谢物。
因此，申请人所选出的菌株具有独特性，因为其能够同时发挥抗病毒和抗细菌活性。
申请人所选出的细菌菌株显示出对免疫系统的显著刺激性活性，从而导致白细胞介素17、特别是白细胞介素17A(IL-17A)和γ-干扰素的内源性生产。
白细胞介素IL-17A能够对在肿瘤细胞所处的区域中的血管发挥血管生成活性。血管中更强的血循环或血管生成使得能够抑制肿瘤转移的产生，因为肿瘤细胞更为局域化并且更为紧凑。而且，前述的促血管新生效应使得化疗治疗能更好地穿透肿瘤团块，并使得治疗更为有效且局域化。此外，γ-干扰素具有抗病毒能力。
申请人已发现，选出的细菌菌株能够激活并刺激免疫系统(IS)从而导致更高的白细胞介素17、特别是白细胞介素17A(IL-17A)和γ-干扰素的内源性生产。
本发明的一个目标在于属于物种戊糖乳杆菌(Lactobacillus pentosus)且具有抗病毒活性(细胞因子生成)和抗细菌活性(细菌素生成)的细菌菌株。
在一个实施方式中，属于物种戊糖乳杆菌且具有抗病毒活性和抗细菌活性的细菌菌株是保藏号为DSM 21980的菌株戊糖乳杆菌LPS01，其由Probiotical SpA遵照布达佩斯条约于2008年11月14日保藏。
而且，申请人已发现，借助生物利用率极高的锌能够进行IS激活，所述生物利用率极高的锌通过内化在经间歇灭菌(tyndalized)的细菌细胞内的锌而获得，所述细胞属于物种乳双歧杆菌(B.lactis)中的菌株、优选于2005年12月23日保藏于DSMZ的菌株乳双歧杆菌(Bifidobacterium lactis)Bb 1 DSM 17850，后者是欧洲专利申请08789404号的主体，本文通过援引将其并入。
在实践中，申请人已发现，内化在经间歇灭菌(灭活)的细胞内的高生物可利用性的锌使IS激活，特别是使被认为产生T-淋巴细胞(其产生如白细胞介素IL-17A和γ干扰素等非毒性内源细胞因子)的胸腺激活。这一机制受益于保藏号为DSM 21980的细菌菌株戊糖乳杆菌LPS01而整体被激活。
保藏号为DSM 21980的菌株戊糖乳杆菌LPS01适用于治疗因革兰氏阴性菌(如肠球菌、大肠菌群和大肠杆菌)所致的感染。事实上，菌株戊糖乳杆菌LPS01 DSM 21980经测试以大约1×108CFUs/g的载量通过产生过氧化氢、细菌素和代谢物而成功抵抗了以下靶病原体：大肠杆菌ATCC 8739、大肠杆菌ATCC 10536、大肠杆菌ATCC 35218和大肠杆菌ATCC 25922。
测试保藏号为DSM 21980的菌株戊糖乳杆菌LPS01以评估其对来自健康供体的PBMC细胞的细胞因子的体外增殖和释放进行调节的能力。PBMC细胞分离自人外周血，并与菌株戊糖乳杆菌LPS01 DSM 21980共培养。分别借助FACS和ELISA监测不同免疫细胞群体的特异性刺激和内源性细胞因子的分泌。具有统计价值的结果表明，菌株戊糖乳杆菌LPS01 DSM 21980诱导了内源性Th1细胞因子的显著分泌，且IL-17A(表A)和IFN-γ(表B)明显增加。
在培养5天后，从受三种单独细菌菌株刺激的PBMC培养物的上清液制备IL-17A细胞因子制剂，所述三种单独细菌菌株为：唾液乳杆菌DLV1 DSM 25138、唾液乳杆菌LS01 DSM 22775和戊糖乳杆菌LPS01 DSM 21980。以IL-17A(pg/ml)表达的具有统计价值的结果如下表A所示。
表A
所分析的三种细菌菌株展现出不同的调节IL-17A细胞因子的能力，特别是唾液乳杆菌DLV1 DSM 25138和唾液乳杆菌LS01 DSM 22775没有效果，而戊糖乳杆菌LPS01 DSM 21980则相对于基线情况(Basal)极大提高了IL-17A的分泌。
从分离自人外周血并与菌株植物乳杆菌LP01(LMG P-21021)和与菌株戊糖乳杆菌LPS01 DSM 21980共培养的PBMC制备γ-干扰素制剂。以IFN-γ(pg/ml)表达的具有统计价值的结果如下表B所示。
表B
菌株戊糖乳杆菌LPS01 DSM 21980显示出比对照高10倍的刺激γ-干扰素的能力。
有利的是，内源性细胞因子的生产不涉及毒性，这与通过灌注施用的外源性细胞因子不同。
本发明的一个目的在于具有所附权利要求中所要求的特征的药物组合物或食品组合物、或者包含食品补剂的组合物或包含医疗装置的组合物(下文称作根据本发明所述的组合物)。
根据本发明所述的组合物可有用地作为抗肿瘤化疗治疗、获得性免疫缺陷综合征治疗和白血病治疗中的支持疗法。
根据本发明所述的组合物包含橡胶(优选藻酸盐或其衍生物)和/或凝胶(优选芦荟凝胶或其衍生物)。
所述藻酸盐或其衍生物优选为藻酸钠。
芦荟类产物或其衍生物优选为木立芦荟；优选为冻干形式。木立芦荟优选处于冻干形式。
藻酸盐和芦荟类产物一旦与唾液或用于吞咽片剂或胶囊或者溶解颗粒或粉末组合物的水相接触，则两者均会产生凝胶。
凝胶形式的藻酸盐或芦荟类产物能够具有机械效应或保护食道、胃和胃肠道中的粘膜。
藻酸盐、优选藻酸钠具有机械性抗反流、抗食道炎和抗胃炎活性，并能使罹患肿瘤疾病的患者更易耐受化疗治疗的副作用。
冻干形式的芦荟类产物、优选木立芦荟具有物理保护食道、胃和小肠粘膜的机械功能。而且，冻干形式并重建为凝胶形式的芦荟类产物、优选木立芦荟能够降低病原性菌株、特别是有鞭毛的病原性菌株在食道和胃肠道中的附着能力。最后，冻干形式并重建为凝胶形式的芦荟类产物、优选木立芦荟能够降低胃和小肠的透过性。
通过涂覆食道、胃和小肠粘膜并且降低有鞭毛的病原体的附着能力，冻干形式并重建为凝胶形式的芦荟类产物、优选木立芦荟能使罹患肿瘤疾病的患者更易耐受化疗治疗的副作用(细菌感染)。
在一个实施方式中，根据本发明所述的组合物包含重量比为1:50(藻酸盐:芦荟)至50:1、优选1:30(藻酸盐:芦荟)至30:1的藻酸钠和冻干形式的木立芦荟。
根据本发明所述的组合物还包含与藻酸盐、优选藻酸钠和/或冻干形式的芦荟类产物、优选木立芦荟组合的某些细菌菌株。
在一个实施方式中，根据本发明所述的组合物包含与藻酸盐、优选藻酸钠和/或冻干形式的芦荟类产物、优选木立芦荟组合的以下细菌菌株：所述细菌菌株属于具有抗病毒和抗细菌活性的戊糖乳杆菌物种；所述菌株是由Probiotical SpA于2008年11月14日保藏的保藏号为DSM 21980的戊糖乳杆菌LPS01菌株。
在另一个实施方式中，根据本发明所述的组合物包含与藻酸盐、优选藻酸钠和/或冻干形式的芦荟类产物、优选木立芦荟组合的细菌菌株戊糖乳杆菌LPS01 DSM21980，且还组合有内化于经间歇灭菌的细菌细胞内的生物利用率高的锌。
申请人已经选出处于经间歇灭菌(灭活)的细胞形式的一些细菌菌株，这些细菌菌株能使锌具有高的生物利用率(内化)。此种形式的锌具有高的生物利用率，并因此更易被生物体同化(assimilated)。生物可利用且易于被生物体同化的锌离子具有重要作用，并具有对胸腺的作用，其负责淋巴细胞的形成/生成。
使锌离子内化的所述细菌菌株选自包括于2007年7月13日保藏于DSMZ的嗜热链球菌ST16 BM DSM 19526菌株和于2005年12月23日保藏于DSMZ的乳双歧杆菌Bb 1 DSM 17850菌株的组，或者作为选择选自由这些菌株构成的组。
在另一个实施方式中，所述组合物包含与藻酸盐、优选藻酸钠和/或冻干形式的芦荟类产物、优选木立芦荟组合的戊糖乳杆菌LPS01 DSM 21980菌株，且还组合有内化于经间歇灭菌的细菌细胞内的生物利用率高的锌；所述经间歇灭菌的细菌细胞选自包括于2007年7月13日保藏于DSMZ的嗜热链球菌ST16 BM DSM 19526菌株和于2005年12月23日保藏于DSMZ的乳双歧杆菌Bb 1 DSM 17850菌株的组，或者作为选择选自由这些菌株构成的组。
本发明的一个目的在于用作抗肿瘤化疗治疗、获得性免疫缺陷综合征治疗和白血病治疗中的支持疗法的组合物；所述组合物包含保藏号为DSM 21980的细菌菌株戊糖乳杆菌LPS01，其由Probiotical SpA保藏于2008年11月14日。所述组合物以1x108至1x1011CFUs/g组合物的量包含所述菌株。
在一个实施方式中，所述组合物还包含内化于经间歇灭菌的细菌细胞内的具有高度生物利用率的锌。优选地，所述经间歇灭菌的细菌细胞选自包括于2007年7月13日保藏于DSMZ的嗜热链球菌ST16 BM DSM 19526菌株和于2005年12月23日保藏于DSMZ的乳双歧杆菌Bb 1 DSM 17850菌株的组。
在另一个实施方式中，所述组合物还包含至少一种橡胶，优选植物橡胶。优选地，所述植物橡胶是至少一种藻酸盐，优选藻酸钠。
在另一个实施方式中，所述组合物还包含至少一种凝胶。优选地，所述凝胶是芦荟凝胶，优选木立芦荟凝胶。更优选地，所述芦荟凝胶是冻干形式的木立芦荟凝胶。
在一个实施方式中，所述组合物包含：保藏号为DSM 21980的细菌菌株戊糖乳杆菌LPS01；内化有锌离子的至少一种细菌菌株，其选自包括保藏号为DSM 19526的嗜热链球菌ST16 BM菌株和保藏号为DSM 17850的乳双歧杆菌Bb 1菌株的组；藻酸盐、优选藻酸钠；以及基于木立芦荟(优选处于冻干形式)的产物。
Claims (9)
1.一种用作抗肿瘤化疗治疗、获得性免疫缺陷综合征治疗和白血病治疗中的支持疗法的组合物，所述组合物包含保藏号为DSM 21980的戊糖乳杆菌LPS01细菌菌株，该菌株于2008年11月14日由Probiotical SpA保藏。
2.根据权利要求1所述的组合物，其中，所述组合物还包含被内化在经间歇灭菌的细菌菌株内的生物利用率高的锌。
3.根据权利要求2所述的组合物，其中，所述经间歇灭菌的细菌细胞选自包含嗜热链球菌ST16BM DSM 19526菌株和乳双歧杆菌Bb 1DSM 17850菌株的组，其中嗜热链球菌ST16BM DSM 19526于2007年7月13日保藏于DSMZ，乳双歧杆菌Bb 1DSM 17850于2005年12月23日保藏于DSMZ。
4.根据权利要求1至3中任一项所述的组合物，其中，所述组合物还包含至少一种橡胶，优选植物橡胶。
5.根据权利要求4所述的组合物，其中，所述植物橡胶为至少一种藻酸盐，优选藻酸钠。
6.根据权利要求1至5中任一项所述的组合物，其中，所述组合物还包含至少一种凝胶。
7.根据权利要求6所述的组合物，其中，所述凝胶是芦荟类凝胶，优选基于木立芦荟的凝胶。
8.根据权利要求7所述的组合物，其中，所述芦荟类凝胶是冻干形式的基于木立芦荟的凝胶。
9.根据权利要求1至8中任一项所述的组合物，其中，所述组合物包含：保藏号为DSM 21980的戊糖乳杆菌LPS01细菌菌株；内化有锌离子的至少一种细菌菌株，该细菌菌株选自包含保藏号为DSM 19526的嗜热链球菌ST16BM菌株和保藏号为DSM 178505的乳双歧杆菌Bb 1菌株的组；藻酸盐，优选为藻酸钠；以及基于木立芦荟的产物，该产物优选处于冻干形式。
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| PCT/IB2013/002890 WO2014102595A1 (en) | 2012-12-31 | 2013-12-31 | Composition for use as a support therapy for treatment of tumours, aids and leukaemia |
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| CN107105747A (zh) * | 2014-09-23 | 2017-08-29 | 韩国韩医学研究院 | 包含间歇灭菌的乳酸菌死菌体作为有效成分的用于皮肤保湿或改善皱纹的组合物 |
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| ITMI20122270A1 (it) | 2012-12-31 | 2014-07-01 | Giovanni Mogna | Terapia di supporto ai trattamenti di chemioterapia per i tumori, per la sindrome da immunodeficienza acquisita e per le leucemie. |
| KR102244492B1 (ko) * | 2020-10-21 | 2021-04-26 | 대한민국(관리부서:국립수산과학원) | 신규 락토바실러스 속 균주 및 그의 용도 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5292511A (en) * | 1992-07-03 | 1994-03-08 | Pulmuwon Food Co., Ltd. | Process for manufacturing a health-supplementary food containing aloe as an active ingredient |
| US20040175389A1 (en) * | 2003-01-14 | 2004-09-09 | Porubcan Randolph Stanley | Formulations to increase in vivo survival of probiotic bacteria and extend their shelf-life |
| US20060134238A1 (en) * | 2004-12-16 | 2006-06-22 | Dnyaneshwar Agashe M | Process of manufacturing clear juice from the leaves of the aloe vera plant |
| WO2009013709A2 (en) * | 2007-07-26 | 2009-01-29 | Bioman S.R.L. | Zinc-enriched biomass, method for the preparation thereof and pro-biotic, cosmetic, dietary and nutraceutic products comprising the same |
| US20110117210A1 (en) * | 2009-11-17 | 2011-05-19 | Andrey Ugolkov | Therapeutic treatment of human cancers using simple salts of zinc |
| WO2011110918A1 (en) * | 2010-03-08 | 2011-09-15 | Probiotical S.P.A. | Composition comprising probiotic bacteria for use in the treatment of immune disorders |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2286558T5 (es) | 2004-08-24 | 2013-10-15 | N.V. Nutricia | Composición nutritiva que comprende transgalactooligosacáridos indigeribles y sacáridos de galactosa digeribles |
| US20060045887A1 (en) * | 2004-08-25 | 2006-03-02 | Gavish-Galilee Bio Applications Ltd. | Mushroom extracts having anticancer activity |
| US7964571B2 (en) * | 2004-12-09 | 2011-06-21 | Egen, Inc. | Combination of immuno gene therapy and chemotherapy for treatment of cancer and hyperproliferative diseases |
| ITMI20051510A1 (it) | 2005-08-02 | 2007-02-03 | Proge Farm Srl | Uso di specifici batteri lattici per la preparazione di composizioni iunomodulanti |
| ITBA20080008A1 (it) * | 2008-02-22 | 2009-08-23 | Michele Barone | Composizioni comprendenti fitoestrogeni selettivi per il recettore estrogenico beta e fibre dietetiche |
| IT1397566B1 (it) * | 2009-05-27 | 2013-01-16 | Probiotical Spa | Lactobacillus pentosus produttore di batteriocine, composizioni alimentari e farmaceutiche contenenti lo stesso e relativo uso |
| ITMI20122270A1 (it) | 2012-12-31 | 2014-07-01 | Giovanni Mogna | Terapia di supporto ai trattamenti di chemioterapia per i tumori, per la sindrome da immunodeficienza acquisita e per le leucemie. |
-
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- 2013-12-31 US US14/758,211 patent/US10933105B2/en active Active
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-
2020
- 2020-02-27 US US16/803,874 patent/US20200197453A1/en not_active Abandoned
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5292511A (en) * | 1992-07-03 | 1994-03-08 | Pulmuwon Food Co., Ltd. | Process for manufacturing a health-supplementary food containing aloe as an active ingredient |
| US20040175389A1 (en) * | 2003-01-14 | 2004-09-09 | Porubcan Randolph Stanley | Formulations to increase in vivo survival of probiotic bacteria and extend their shelf-life |
| US20060134238A1 (en) * | 2004-12-16 | 2006-06-22 | Dnyaneshwar Agashe M | Process of manufacturing clear juice from the leaves of the aloe vera plant |
| WO2009013709A2 (en) * | 2007-07-26 | 2009-01-29 | Bioman S.R.L. | Zinc-enriched biomass, method for the preparation thereof and pro-biotic, cosmetic, dietary and nutraceutic products comprising the same |
| US20110117210A1 (en) * | 2009-11-17 | 2011-05-19 | Andrey Ugolkov | Therapeutic treatment of human cancers using simple salts of zinc |
| WO2011110918A1 (en) * | 2010-03-08 | 2011-09-15 | Probiotical S.P.A. | Composition comprising probiotic bacteria for use in the treatment of immune disorders |
Non-Patent Citations (3)
| Title |
|---|
| MALCOLM S. MITCHELL: "Combinations of anticancer drugs and immunotherapy", 《CANCER IMMUNOL IMMUNOTHER》 * |
| PAOLO LISSONI ET AL.: "A Randomized Study of Chemotherapy Versus Biochemotherapy with Chemotherapy plus Aloe arborescens in Patients with Metastatic Cancer", 《IN VIVO》 * |
| YECHIEL BECKER: "Molecular Immunological Approaches to Biotherapy of Human Cancers–A Review，Hypothesis and Implications", 《ANTICANCER RESEARCH》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107105747A (zh) * | 2014-09-23 | 2017-08-29 | 韩国韩医学研究院 | 包含间歇灭菌的乳酸菌死菌体作为有效成分的用于皮肤保湿或改善皱纹的组合物 |
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| EP2938349A1 (en) | 2015-11-04 |
| KR20150102102A (ko) | 2015-09-04 |
| RU2015124336A (ru) | 2017-02-06 |
| KR102188696B1 (ko) | 2020-12-09 |
| US20150343004A1 (en) | 2015-12-03 |
| BR112015015393A2 (pt) | 2017-07-11 |
| DK2938349T3 (en) | 2018-05-07 |
| DK3345611T3 (da) | 2020-11-30 |
| RU2018141041A (ru) | 2019-03-21 |
| EP2938349B1 (en) | 2018-02-21 |
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| US10933105B2 (en) | 2021-03-02 |
| RU2674658C2 (ru) | 2018-12-12 |
| ITMI20122270A1 (it) | 2014-07-01 |
| PT2938349T (pt) | 2018-04-26 |
| US20200197453A1 (en) | 2020-06-25 |
| CA2896402A1 (en) | 2014-07-03 |
| WO2014102595A1 (en) | 2014-07-03 |
| ES2668483T3 (es) | 2018-05-18 |
| EP3345611B1 (en) | 2020-09-02 |
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