CN104203225A - 增强宠物的抗氧化、肠道菌群和免疫力的组合物和方法 - Google Patents
增强宠物的抗氧化、肠道菌群和免疫力的组合物和方法 Download PDFInfo
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Abstract
本发明的组合物和方法有效地增强宠物的抗氧化、肠道菌群和免疫刺激。所述组合物包含二氢槲皮素和西伯利亚或兴安落叶松阿拉伯半乳糖的组合，更具体地，其中，落叶松阿拉伯半乳糖具有约9.5kDa到约37kDa之间的分子量。该组合物可为以下形式：片剂、咀嚼片、胶囊、树脂、油状物、液体、微脂囊、粉末或栓剂，并且可进一步包括药学可接受的载体；或可被掺入到主体饲料或饲料补充剂中。
Description
技术领域
本发明和本公开内容涉及用于宠物的保健和营养组合物，并且更具体地，涉及一种二氢槲皮素和西伯利亚兴安落叶松阿拉伯半乳糖的组合物，该组合物为以下形式：片剂、咀嚼片、粉末、液体、树脂或油状物；还涉及一种待添加至宠物食物的预混合组合物，以及一种通过给予所述保健和营养组合物而增强宠物的抗氧化、肠道菌群和免疫力的方法。
背景技术
氧化应激和人类健康之间的关系，尤其是关于循环功能和恶性肿瘤的风险之间的关系是现今广为接受的科学，Harmon,D,1067Ann N Y Acad Sci 10-21(2006)。数以千计的已发表的研究表明游离自由基与退行性疾病的发展和加速老化有关，Knight JA.28(6)Ann Clin Lab Sci.(1998)；Huang H.Manton KG.91100-17Front Biosci.(2004)。年轻人自然地产生抗氧化酶即超氧化物歧化酶(SOD)、过氧化氢酶以及谷胱甘肽过氧化物酶，这些抗氧化酶降低和抵消在正常生理过程期间产生的游离自由基。SOD和其它重要的抗氧化酶的水平随着年龄的增长而下降，从而造成了与年龄相关疾病和衰退的根源。
与人类相似，宠物显示出显著的遗传多样性，这就影响了它们的整体健康和营养需求。游离自由基是在暴露于环境时或在正常代谢期间所形成的，其可对细胞膜、蛋白质和遗传物质有害，这就可能基于食物的质量而产生不良的结果，并且游离自由基也可能对机体有害。因此，本发明的制剂包括抗氧化剂的均衡共混物，所述均衡共混物是指相对于溶解度(脂溶或水溶性)、该抗氧化剂发生作用的酸败阶段(去氧剂、自由基终止剂)、该抗氧化剂在机体内浓缩至的组织的均衡共混物。
抗氧化剂为用于帮助患有各种医学病症的宠物最常用的补充剂之一。抗氧化剂为用于维持健康的特定维生素(诸如维生素C和维生素E)以及植物化合物和动物化合物(生物类黄酮，诸如二氢槲皮素、葡萄籽提取物、槲皮素、辅酶Q-10、银杏)。从技术上来说，他们并不增强免疫系统，而是清理细胞损伤的产物以及所产生的氧化的化学物质。抗氧化剂还降低导致细胞损伤的各种化学物质(组胺、白介素、肿瘤坏死因子)的水平。由于抗氧化剂最大限度地降低了对细胞的损伤，因而无论是患有疾病时还有需要免疫支持时，抗氧化剂均是有用的。
对于任何生病的宠物，在患病时利用营养补充剂来增强免疫系统是重要的。虽然补充剂在任何患病期间可被用于支持免疫系统，然而兽医往往被要求对存在以下问题的宠物开出药方：任何传染病，尤其是猫科动物的呼吸系统疾病、犬窝咳、犬瘟热和细小病毒(parvo)；癌症；兽疥癣；以及老年宠物中“不太正常”的任何病症。使用用于宠物的营养补充剂越来越受到欢迎，并且在一些宠物食物中含有这种补充剂。
Paluch在美国专利号6,312,746中记载了一种改进了适口性的多组分食品，其可含有抗氧化维生素，诸如原维生素A胡萝卜素、维生素C、维生素E和它们的混合物。Zicker等人在美国专利号6,914,071教导了使用抗氧化维生素即维生素C、L-左旋肉碱以及α-硫辛酸中的一种来抑制7岁以上的伴侣宠物的精神衰退的方法。Rapisarda在美国专利号6,974,841和XX中记载了一种尤其用于狗的抗氧化保健和营养制剂，包括抗氧化维生素、复合维生素B、生物类黄酮、螯合矿物质、消化酶、草本植物、营养成分和必需脂肪酸；并且同样也是Rapisarda在美国专利号7,368,481中记载了一种用于猫的特定配方，该配方包含多种抗氧化维生素诸如复合维生素A、C、E、B，叶黄素，L-左旋肉碱，脂肪酸以及消化酶。Hayek在美国专利号6,946,488中教导了猫的消炎食物，包含ω-6脂肪酸和ω-3脂肪酸。Shields在美国专利号6,156,355中教导了用于特定种群的品种的狗的若干冗长且详尽的制剂。Young在美国专利号7,211,280中记载了一种改进病症和/或增加年老猫的寿命的方法，该方法利用维生素D、维生素E和维生素K和β-胡萝卜素来给予钙质。Inpanbutr在美国专利号7,129,230中记载了一种利用若干种维生素D类似物或它们的立体异构体来治疗犬鳞状细胞癌的方法。
Sergheraert在美国专利号7,399,481中教导了一种驯养的食肉动物的食物组合物，利用动物蛋白或植物蛋白、脂肪类物质、碳水化合物以及至少5重量％的酪氨酸来治疗毛皮的颜色和质量。Decuypere等人在美国专利号7,261,888中教导了一种饲料组合物，用作抗微生物剂和预防消化不良，包括甘油三酯、中链脂肪酸和外源性活性脂肪分解酶。Hodge在美国专利号7,258,879中记载了包装的治疗型号的宠物食品，利用植物碳和丝兰属植物提取物或丝兰天麻提取物来降低胃胀气。Wadsworth在美国专利号7,244,463中教导了山竹(garciniamangostana L.)在宠物食品中的用途。Abene在美国专利号6,669,975中教导了预制的粗磨的美容性宠物食品和以下功能性成分的混合物：绿唇贻贝提取物、琉璃苣油、向日葵油、亚麻籽油、亚麻籽、鱼油、L-左旋肉碱、共轭亚油酸、低聚果糖、维生素E油、经研磨的菊苣(ground chicory)、维生素C、SAM-E、γ-亚油酸、月见草油、大豆异黄酮、肌酸、草本植物、甘露寡糖以及抗氧化剂。Axelrod在美国专利号7,332,188中公开了一种利用发酵的大豆强化的动物咀嚼玩具。
关于提供了二氢槲皮素和西伯利亚或兴安落叶松阿拉伯半乳糖的独特性质的宠物用饲料或保健和营养组合物，上述教导中均没有记载，也不能从市场上购得。
二氢槲皮素
二氢槲皮素是一种生物类黄酮。类黄酮天然产物显示出广泛的生物化学性质和药理学性质，其中最充分表征的效果之一是化学预防活性，而化学预防活性由作为筛选潜在药剂的标记物来说的化学预防指数来进行测量。二氢槲皮素也被称为紫杉叶素，显示出高解毒能力但在细胞中较低的细胞毒性，是高化学预防指数的代表。已经表明其调节若干基因的表达，该若干基因包含编码解毒酶、细胞周期调节蛋白、生长因子和DNA修复蛋白的基因。最近的微阵列结果表明，在紫杉叶素的存在下，阶段II解毒酶、NQO1和GSTM1上调，而阶段I解毒酶，CYP2E1下调，Lee,SB,等人，30(6)Biol Pharm Bull 1074-1079(2007)。对于对人肺胚胎成纤维细胞(TIG-1)和脐静脉内皮(HUVE)细胞的毒性的测量进行检验，二氢槲皮素显示出了在十种(10)测试的类黄酮中最小的细胞毒性：对于50％致死浓度，在TIG-1中为>300微摩尔，在HUVE细胞中为>200微摩尔，Matsuo,M,等人,28(2)Biol Pharm Bull 253-9(2005)。
二氢槲皮素是维生素的优异增效剂并且是催化给出电子的酶抗氧化系统的共因子，其具有高的氧自由基吸收能力(ORAC)值，通过脂质过氧化物抑制氢的给出，并且其酶的形式是金属螯合剂。二氢槲皮素能在血液中迅速代谢成酶的形式并且作为人类抗氧化系统的催化剂。与维生素A、C和E相比，二氢槲皮素是一种远远更强有力的抗氧化剂，这可通过其ORAC的USDA排名和另外的研究得到证实。
常用的过氧化物自由基涉及脂肪酸和其它脂质的氧化损伤，并且证实了为何自由基(诸如过氧化物和羟基自由基)引起的损伤远远超出预期。根据所涉及的化学反应，主要的抗氧化能力测定法基本上可分为两大类：(1)基于氢原子转移(HAT)反应的测定法和(2)基于单电子转移(ET)反应的测定法。
大多数的基于HAT的测定法采用竞争性反应方案，其中，抗氧化剂和底物为了偶氮化合物的分解而热法产生的过氧自由基进行竞争。ORAC是对于被诱导的低密度脂蛋白氧化的抑制和氧自由基吸收能力的测定法。该ORAC氢测试二氢槲皮素产生的氢原子转移(HAT)争夺热法产生的过氧自由基和羟自由基的能力。对于后者，必须使用ORAC测定法试验。与测量抗氧化剂的还原能力的基于电子转移的测定法不同，基于HAT的测定法检测给出氢原子的能力。氢原子转移是自由基链式反应的关键步骤。因此，基于HAT的测定法与使自由基链断裂的抗氧化能力更相关。在所有基于HAT的测定法中，ORAC采用AUC(曲线下面积)技术来量化的抗氧化能力。AUC方法的优点是其同样良好地适用于显示出明显的滞后期的抗氧化剂和不具有滞后期的那些样品。该方法与滞后时间方法和初始速率方法一致，并且其尤其用于食物样品，其中食物样品通常含有多种成分并且具有复杂的反应动力学。因此，ORAC测定法在学术界和食物和补充剂产业中已被广泛地选择用作量化抗氧化能力的方法。事实上，通过组合使用ORAC和总酚测定法，已经建立了抗氧化剂数据库。已经测定了二氢槲皮素的ORAC氢值，其至少为300微摩尔Trolox(水溶性维生素E)当量每420mg胶囊或800微摩尔Trolox当量每克。
二氢槲皮素是一种强有力的抗氧化剂，并且是食物中的一种能够显著地降低活性氧和活性氮的不利影响的物质，Valko,M等人,39(1)Int J Biochem CellBiol.44-84(2007)；Kostyuk VA,Potapovich AI,355(1)Arch Biochem Biophys43-8(1998)；Soliman KF & Mazzio EA,218(4)Proc Soc Exp Biol Med 390-7(1998)。已经发现其是用于形成槲皮素、低聚原花色素(OPC)和儿茶素的类黄酮生物合成途径中的必需分子中间体，并且已经多次证实了其作为抗氧化剂的优越性，Tiukavkina NA,Rulenko IA,Kolesnik IA,6Vopr Pitan.12-5(1997)；Teselkin,IO,等人,41(3)Biofizika.620-4(1996)。
二氢槲皮素保护细胞膜免受游离自由基损伤，提高毛细血管的活性并且支持遍及全身的血液微循环的恢复。证实了在细胞水平上降低了氧化应激，例如在培养的肾细胞中降低了氧化应激，Areias,FM等人,62(1)Biochem Pharmacol.111-8(2001)。由于二氢槲皮素进入人类细胞(包含血细胞)的渗透性，从而证实二氢槲皮素在细胞水平上可靠地保护免受各种活性游离自由基的损伤。
由于二氢槲皮素不会被机体内的酶分解为在量上与槲皮素接近的较低活性的化合物，所以与普通的槲皮素相比，二氢槲皮素的血浆水平保持较高并且时间较长。此外，其诱变性比槲皮素的诱变性少400倍，槲皮素的最小诱变剂量为4nml，二氢槲皮素为1626nmol，Jurado,J.,25等人,6(4)Mutagenesis 289-95(1991)。
已经表明，二氢槲皮素通过活化的人类嗜中性粒细胞来抑制鲁米诺(luminol)依赖的化学发光(CLlum)的产生“T Hart Chem Biol Interact.1990；73(2-3):323-35”，以及抑制其在炎症过程的吸附“Wang,YH等人，67(12)Biochem Pharmacol 2251-62(2004)”。已经报道了二氢槲皮素保护吞噬细胞免受氧化硅诱发的损伤，Kostyuk VA,Potapovich AI.355(1)Arch Biochem Biophys43-8(1998)。已经积极地表明，二氢槲皮素是作为由肥大细胞释放的组胺的抑制剂，Bronner C,Landry Y.,16(3)Agents Actions 147-51(1985)。
由于这些性质还可能有助于这种类型的化合物的抗氧化性能，所以测定仿生系统(胶束)中的儿茶素和紫杉叶素的分配系数。测定的log P值取决于化合物与不同电荷的胶束之间的静电作用(最高值由两性离子胶束和阳离子胶束获得)。通过铜催化、费顿反应诱导的2'-脱氧鸟苷的氧化来评估化合物的助氧化行为。所得到的数据反映了在该具体系统中，所研究的类黄酮并不存在促氧化活性，Teixeiria,S,39(8)Free Radic Biol Med 1099-108(2005)。
类黄酮尤其是二氢槲皮素还支持心血管功能。已经表明其能够抑制脂肪氧合酶，该酶使脂肪酸中的脂类氧化，Wheeler,EL和Berry,DL,7(1)Carcinogenesis 33-6(1986)。二氢槲皮素与维生素C的结合能够提高红细胞变形能力并且降低红细胞的聚集，Plotnikov,MB等人,104(12)Zh Nevrol PsikhiatrIm S S Korsakova 33-7(2004)。还已经证实了二氢槲皮素能够改善微粒体对脂质过氧化的抗性，Kravchenko LV,Morozov SV,Tutel'yan VA,136(6)Bull ExpBiol 572-5(2003)。
公认的是，西伯利亚或兴安落叶松(俗称为蒙古落叶松树)均是用于市场容量的二氢槲皮素的优良来源。
阿拉伯半乳糖
具有公认的免疫力增强性质的许多草本植物，如紫锥菊(Echinaceapurpurea)、赝靛(Baptisia tinctoria)、金钟柏(Thuja occidentalis)、当归(Angelicaacutiloba)和姜黄(Curcuma longa)也含有显著量的AG。通常在用于增强免疫力的药用草本植物(包括紫锥菊和黄芪(Astragalus))中发现多糖。阿拉伯半乳糖是一类长且具有分支密集的多糖，分子量范围为6000至120,000并且存在于在多种可食用和不可食用的木本植物的细胞壁中。阿拉伯半乳糖是一种精细干燥的近白色粉末，具有温和的甜味并且能够与液体良好地混合。这种安全有效的植物化学品由FDA批准用作膳食纤维，甚至可以大剂量使用，并且批准用作食品添加剂，5(5)Altern Med Rev 463-6(2000)(未列出作者)。唯一报道的副作用是在食用阿拉伯半乳糖的小比例人群中出现偶尔腹胀和胃肠胀气。
阿拉伯半乳糖粉末通过增加血流中存在的免疫细胞的数量、增强天然杀伤细胞和巨噬细胞活化作用并且限制不健康细胞的复制，从而增强免疫系统。阿拉伯半乳糖粉末通过缓和肠道中的酸性积聚从而支持免疫系统和结肠健康。纤维是非过敏性的并且不刺激胰岛素响应。
阿拉伯半乳糖在落叶松树(落叶松种)中最丰富。落叶松阿拉伯半乳糖可以从西部落叶松(粗皮落叶松(Larix occidentalis))、或西伯利亚落叶松或兴安落叶松(Laix Sibirica或Larix gmelinni)中提取，兴安落叶松俗称为蒙古落叶松。最常使用的是西部落叶松。由于其潜在的生物活性和免疫力增强性质，该独特的膳食纤维作为临床有用的保健品受到越来越多的关注。
肠道菌群
落叶松在药学上利用这些多糖对肠道和免疫系统的影响。落叶松阿拉伯半乳糖是一种不易消化的可溶性膳食纤维，对由酶导致的分解有耐受性并且完整地进入大肠，在大肠中其通过结肠细菌进行发酵。
很多食用的植物和非食用的植物是阿拉伯半乳糖的丰富来源，这些食用的植物和非食用的植物包含韭菜籽、胡萝卜、萝卜、黑豆、梨、玉米、小麦、红酒、多花黑麦草、西红柿、豚草、高粱、竹草、椰子肉和奶。
西伯利亚或兴安落叶松阿拉伯半乳糖被认为作为益生元起作用；其刺激提供一定保健功效的细菌(诸如双歧杆菌和乳酸杆菌)的结肠生长。落叶松阿拉伯半乳糖的摄入对增强有益肠道微生物，尤其是增加厌氧菌(诸如乳酸菌)具有显著的效果，Robinson RR,Feirtag J,Slavin JL,20(4)J Am Coll Nutr 279-85(2001)。
所有的慢性疾病中百分之九十是由不健康的肠道所引起的。在对狗体内若干种形式的阿拉伯半乳糖(AG)的研究(Cohasset，MN)中：研究了未加工的AG(AG100)、Laraceutical(AG1000)和松木多糖(Fiberaid)分别在1.65g/天和0.55g/天的影响，其中，与对照组狗相比，低剂量AG1000和高剂量AG3000导致了排泄物中的乳酸杆菌浓度更高(P＝0.04)以及排泄物中的双歧杆菌浓度更高(P0.16)的趋势。与对照组的狗相比，饲喂低剂量AG3000的狗趋向于在排泄物中具有较低浓度的产气荚膜梭菌(Clostridium perfringens)(P＝0.10)，Greishop,132J Nutr 478-482(2002)。阿拉伯半乳糖粉末能通过刺激免疫细胞的活化作用而限制的疾病的恶化。
短链脂肪酸(主要是乙酸，丙酸，丁酸)是在结肠中通过食物中的碳水化合物的发酵、尤其是从耐降解的淀粉和膳食纤维的发酵而产生的，并且在肠道健康中起着重要的作用。这些酸是结肠上皮细胞的主要的能量来源。阿拉伯半乳糖的非吸收纤维通过末端肠道微生物被快速地发酵，导致更多地产生短链脂肪酸(主要是丁酸，其次是丙酸)。氨作为结肠中通过蛋白和其它含氮物质的细菌发酵的副产物而产生。研究表明，低至5mmol/L的氨水平可对排列在结肠上的上皮细胞具有有害的影响。氨对于结肠上皮细胞的毒性可能导致细胞被破坏并且导致这些细胞的周转期增加。
许多临床医师使用益生元作为肠道病症的补充支持剂，其中肠道病症包含憩室病、漏肠、肠易激综合症以及诸如克罗恩病和溃疡性结肠炎的炎性肠疾病。研究表明：落叶松阿拉伯半乳糖的消耗减少肠道中氨的生成，Robinson RR,Feirtag J,Slavin JL,20(4)J Am Coll Nutr 279-85(2001)。由于即使是低的氨水平也可能对肠的结肠细胞具有损伤作用，所以落叶松阿拉伯半乳糖可支持不能对氨进行解毒的患者。当暴露于在健康的肠道中发现的双歧杆菌时，与衍生自阿拉伯半乳糖的寡糖相反，阿拉伯半乳糖的发酵较低，Degnan,BA,McFarlane,GT,1(2)Anaerobe 103-12(1995)。寡糖也是膳食纤维的来源，Gray,J.,Dietary Fiber,ILSI Europe Concise Monograph Series(2006)。
免疫调节
阿拉伯半乳糖支持健康的免疫系统功能，Schepetkin,IA,5(13-14)IntImmunopharmacol 1783-99.(2005)。具体地，落叶松阿拉伯半乳糖增加了有益的免疫细胞(诸如白细胞)的水平[25]而不刺激促炎性免疫细胞的产生或活化作用，Kelly,GS,4(2)Altern Med Rev 96-103(1999)。落叶松阿拉伯半乳糖降低骨髓中淋巴细胞的产生，Currier,NL,10(2-3)Phytomedicine:145-53(2003)。阿拉伯半乳糖高度有效地在体内和体外促进巨噬细胞的增殖，并且显示出抗炎性、抗补体和抗过敏作用，Kim LS,Waters RF,Burkholder PM.,7(2)Altern MedRev 138-49(2002)。
若干研究表明：落叶松阿拉伯半乳糖在动物中具有抗癌活性。1987年在癌研究与临床肿瘤学(the Journal of Cancer Research and Clinical Oncology)杂志中报道的研究中，研究人员检验了他们的理论：器官特异性凝集素(表示一种蛋白质)有助于确定在动物中恶性细胞的转移位置。注射阿拉伯半乳糖显示出其能够有效地阻止小鼠肝脏中的这些凝集素从而防止小鼠癌症的扩散，Beuth,J,10113(1)J Cancer Res Clin Oncol 51-5(1987)。
在德国科隆的研究者成功重复了该研究，并发表于1988年，Beuth,J,6(2)Clin Exp Metastasis 115-20(1988)。在瑞典于1991年进行的相似的研究中发现在实验动物中用阿拉伯半乳糖进行预处理降低了肝脏亚态的数目并且延长了存活时间，Hagmar B,Ryd W,Skomedal H,11(6)Invasion Metastasis 348-55(1991)。
1999年发表于在非传统医学评论(Alternative Medicine Review)中的落叶松阿拉伯半乳糖研究的综述中报道了该物质能够刺激自然杀伤细胞活性并且还增强免疫功能的其它方面，Kelly,GS,4(2)Altern Med Rev 96-103(1999)。
由于落叶松阿拉伯半乳糖能够增强部分的免疫响应，这在某种程度上是由于其能够刺激作为健康的功能性标记物的“自然杀伤(NK)”细胞的细胞毒性。在医学文献将NK细胞的活性降低与多种慢性疾病联系起来，这些慢性疾病包含慢性疲劳综合征、病毒性肝炎、HIV/AIDS、和诸如多发性硬化症等自身免疫性疾病。改性柑橘果胶(citrus pectin)在动物中具有与落叶松阿拉伯半乳糖相同的抗转移作用机制，但是改性柑橘果胶并不提供免疫调节效果。
在严格控制的研究中，落叶松阿拉伯半乳糖诱导干扰素γ(IFNγ)、肿瘤坏死因子α、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)的释放增加。这就导致了使免疫系统的两种强有力的细胞活化：巨噬细胞和NK细胞。已经发现，IFNγ是观察到NK细胞毒性增强的主因，Hauer J,Anderer FA.,36(4)Cancer Immunol Immunother 237-44(1993)。
其它报道表明：落叶松阿拉伯半乳糖还显示出有助于降低由革兰氏阴性杆菌、尤其是大肠杆菌和肺炎克雷伯氏菌所引起的小儿中耳炎的频率和严重性，D’Adamo P.,6J Naturopathic Med 33-37(1996)。
来自粗皮落叶松的落叶松阿拉伯半乳糖已被分离和被表征为低分子量的9kDa的阿拉伯半乳糖片段和37kDa的经纯化的阿拉伯半乳糖，其由具有相似的分子量和组成的重复单元组成。9kDa的阿拉伯半乳糖可以从37kDa的阿拉伯半乳糖中通过在121℃下高压灭菌或通过暴露于在硼氢化钠存在下的碱性溶液来以高收率获得。重均分子量37kDa的阿拉伯半乳糖通过强烈光散射和沉降平衡(sedimentation equilibrium)被分别测定为37kDa和38kDa。重均分子量9kDa的阿拉伯半乳糖通过强烈光散射和沉降平衡被分别测定为6kDa和9.5kDa。对于阿拉伯半乳糖(9kDa)，MALDI-TOF质谱法在分布的峰值处得到8.3kDa的分子量。阿拉伯半乳糖(37kDa)和阿拉伯半乳糖(9kDa)均呈现出窄分子量分布(Mw/Mn约为1.2)。阿拉伯半乳糖25(37kDa)和阿拉伯半乳糖(9kDa)呈现出几乎相同的13C-NMR谱图、单糖组成、以及糖苷键。有人提出阿拉伯半乳糖(37kDa)由阿拉伯半乳糖(9kDa)的共价结合的亚单元组成。阿拉伯半乳糖(37kDa)和阿拉伯半乳糖(9kDa)同等良好地与分离的肝细胞糖蛋白受体结合。因此，阿拉伯半乳糖(9kDa)是用于肝细胞定向的药物递送的候选物质以及可能比阿拉伯半乳糖(37kDa)更适用于此用途。粉末形式的落叶松阿拉伯半乳糖通常用茶匙和汤匙以每匙为大约3克的浓度给药。
由于其在水或果汁中温和的口感以及优异的溶解性，其易于与自制的宠物食物(诸如酸奶)进行混合。这可根据紧急程度定期进行、或当宠物需要肠道微生物的免疫刺激和保护时进行。
发明内容
本发明人发现了有效的抗氧化剂和强有力的免疫调节剂的结合将维持并提高宠物的免疫系统的健康，其中有效的抗氧化剂为二氢槲皮素，强有力的免疫调节剂为落叶松阿拉伯半乳糖，尤其是低分子量的西伯利亚或兴安落叶松阿拉伯半乳糖。其通常被提供作为宠物普通膳食和补充食物的一部分，但它也可以在不利的情况下用于有效增强抗氧化、肠道菌群和免疫系统。
例如，对于病毒性传染病，例如细小病毒症，可对宠物给予过量剂量的二氢槲皮素和西伯利亚或落叶松阿拉伯半乳糖来增强免疫力并增强肠道菌群的活性。该组合物可以以以下形式来给予：胶囊、片剂、咀嚼片、液体、树脂、油状物、粉末、微脂囊、栓剂或预混合物；或者该组合物可以作为完整饲料的一部分被销售，或者被加入至自制的或制造的宠物食物中，并且可进一步包括药学可接受的载体。
西伯利亚或兴安落叶松独有地在俄罗斯的东西伯利亚和远东地区发现，并且从其树皮和根段原木中分离出二氢槲皮素。这两种原料均购自美国FLAVITPURE有限公司。二氢槲皮素被认为是一种饮食中的抗氧化剂，并且是食物中的一种显著地降低活性氧的不利影响的物质。已经发现其是负责形成槲皮素、低聚原花色素(OPC)和儿茶素的类黄酮生物合成途径中的必需分子中间体。
保健和营养组合物提供用于在动物的消化道中促进有益细菌同时减少致病细菌，用于内部抗氧化剂再循环的内源性抗氧化防御和催化作用，用于必需维生素C、E、A的协同作用，增强短链脂肪酸；所有这些都将有助于使动物更健康。该二氢槲皮素中断过氧化反应中氧化的链，并且增强身体的内部酶的抗氧化系统和维生素的再循环。
当添加到饲料中时，该组合物提高饲料有效性并且使得体重增加，降低每只动物的饲喂成本，减少或消除腹泻的发生、并且减少对抗生素的依赖。其也是有效的饲料添加剂，能够容易地掺入到自制制剂或现有的制剂中。
具体实施方式
在下面的描述中，阐述了多个具体细节以便提供对本发明的更透彻的描述。然而，对于本领域技术人员显而易见的是本发明可以在没有这些具体细节的情况下进行实施。另一方面，为避免使本发明不清楚，没有对众所周知的特征进行详细的描述。
对于上述发明内容、本发明的说明书、后附的权利要求和摘要，可参照本发明的具体特征(包含方法步骤)。应当理解的是，此公开内容包含这些具体特征的可能组合。例如，当在本发明的具体方面或实施方式或具体权利要求的上下文中公开了一个具体特征时，在可能的程度上，该特征也可与本发明的其它具体方面和实施方式组合，或在本发明的其它具体方面和实施方式的情况下应用，以及可以一般性地在本发明中应用。
本文中所使用的术语“包括”及其语法上等同的表达是指其它组分、成分、步骤等是可选地存在的。例如，“包括”(或“其包括”)组分A、B和C的表达是指可以由组分A、B和C组成(即仅含有)，或者不仅仅含有组分A、B和C，还含有一种或多种其它组分。
在本文中所使用的后面跟有数字的术语“至少”或不定冠词“a(一个)”(表示“1”)表示由该数字开始的范围的起始(该范围可能未具有上限或没有上限，这取决于所限定的变量)。
本发明人发现一种保健和营养组合物，其有效地增强宠物的抗氧化、15种肠道菌群和免疫刺激，该保健和营养组合物包括二氢槲皮素和西伯利亚或落叶松阿拉伯半乳糖。具体地，落叶松阿拉伯半乳糖具有约9.5kDa到约37kDa之间的分子量，并且该制剂可为片剂、咀嚼片、胶囊、树脂、油状物、液体、微脂囊、粉末或栓剂的形式，并且可进一步包括药学可接受的载体。
在一个具体的实施方式中，二氢槲皮素以约3重量％至约30重量％的量存在，更特别地，以约5重量％至约20重量％的量存在；并且最特别地，以5重量％的量存在或10重量％的量存在。在一个具体实施方式中，所述组合物的重量为每匙约3克。
还提供了一种通过给予保健和营养组合物来增强宠物、尤其是狗的抗氧化、肠道菌群和免疫刺激的方法。含5％的二氢槲皮素的组合物可以以约0.6g(0.2匙)的量给予到体重小于10kg的狗。含10％的二氢槲皮素的组合物也重为每匙约3g，并且可以以约0.9g(0.3匙)的量给予到体重在约10kg到约50lbs之间的狗，以约1.5g(0.5匙)的量给予到体重在约50lbs到约100lbs之间的狗，以及以约2.4g(0.8匙)的量给予到体重超过100lbs的狗。增强宠物的抗氧化、肠道菌群和免疫刺激的方法也适用于猫，具体地，该方法以0.1匙的量施用含5％的二氢槲皮素的组合物。
在本发明的另一实施方式中，保健和营养组合物在与犬类动物的主体饲料(bulk feed)混合并成为主体饲料的一部分之前，要进行预混合，该主体饲料包括肉类、谷物、纤维、用于天然风味的草本植物和香料，以及维生素混合物；该维生素混合物包括生育酚、维生素C、类胡萝卜素、有机矿物质和ω脂肪酸。在该实施方式中，以全部饲料重量计，预混合的二氢槲皮素和落叶松阿拉伯半乳糖以约0.5重量％至约5重量％的量存在，其中肉类以约10重量％至约50重量％的量存在，谷物以约10重量％至约80重量％的量存在，纤维以约0.1重量％至约20重量％的量存在，草本植物和香料以约0.01重量％至约0.5重量％的量存在，并且生育酚以约0.01重量％至约1重量％的量存在，维生素C以约0.1重量％至约5重量％的量存在，类胡萝卜素以约0.2重量％至约1重量％的量存在，有机矿物质以约0.01重量％至约0.5重量％的量存在，以及ω-脂肪酸以1重量％至约5重量％的量存在。
在更具体的实施方式中，以饲料重量计，预混合的二氢槲皮素和落叶松阿拉伯半乳糖以约1重量％至约2重量％的量存在，肉类以约20重量％至约25重量％的量存在，谷物以约25重量％至约45重量％的量存在，纤维以约0.5重量％至约4重量％的量存在，草本植物和香料以约0.01重量％至约0.2重量％的量存在，并且混合的生育酚以约0.025重量％至约0.05重量％的量存在，所述维生素C以约0.2重量％的量存在，类胡萝卜素以约0.54重量％的量存在，有机矿物质以约0.01重量％至约0.02重量％的量存在，ω-脂肪酸以2重量％的量存在。肉类可为牛肉、山羊肉、家禽肉和鱼肉；ω-脂肪酸可以是一种或多种ω-3脂肪酸10酸，ω-6脂肪酸和ω-9脂肪酸，并且以ω-6脂肪酸与ω-3脂肪酸的比例为约5:1至约10:1之间存在，并且所述ω-9脂肪酸以约4mg的量存在。最具体地，类胡萝卜素为β-胡萝卜素或叶黄素。
可选地，与主体饲料预混合和混合的保健和营养组合物可进一步包括以下物质中的一种或多种：镁、铁、锰、锌、铜、碘、硒、维生素A、混合的生育酚、维生素D-3、硫胺素、核黄素、烟酸、D-泛酸、吡哆醇、生物素、叶酸、胆碱、维生素B-12。最具体地，这些营养物质在每千克的膳食补充剂和饲料组合物中以下列量充分存在：600mg镁、124mg铁、58.4mg锰、233mg锌、42.2mg铜、2.6mg碘、200.34mg硒、27,900IU的维生素A、139.1IU的维生素E、1,826IU的维生素D-3、17.7mg硫胺素、41.0mg核黄素、69.5mg烟酸、35.3mg的D-泛酸、10.0mg吡哆醇、0.57mg生物素、1.93mg叶酸、2416mg胆碱以及0.28mg维生素B-12。
还提供了一种使用与主体饲料预混合和混合的保健和营养组合物来增强宠物中抗氧化、肠道菌群和免疫刺激的方法。保健和营养组合物可以与主体饲料一起以下列量给予：如果狗的体重为5kg或以下，则以约20gm至约70gm给予至所述狗；如果所述狗的体重在约5kg至约10kg，则以约70gm至约110gm给予至所述狗；并且如果所述狗的体重在约10kg以上，则以每千克约10gm给予至所述狗。
在另一实施方式中，有效增强抗氧化、肠道菌群和免疫刺激的保健和营养组合物进一步包括蛋白质、粗脂肪、粗纤维、水分、钙、钠、氯化物和镁，并且以适用于被加入至自制宠物食物或市售宠物食物中可用于迅速增强抗氧化、肠道菌群和免疫刺激的形式提供。在该实施方式中，在加入蛋白质、粗脂肪、粗纤维、水分、钙、钠、氯化物和镁之前，二氢槲皮素与西伯利亚或兴安落叶松阿拉伯半乳糖进行预混合。具体地，落叶松阿拉伯半乳糖具有在约9.5kDa到约37kDa之间的分子量；预混合的二氢槲皮素和落叶松阿拉伯半乳糖以约5重量％至约95重量％的范围的量存在，蛋白质以约5重量％至约95重量％的范围的量存在，粗脂肪以至少0.01重量％的量存在，粗纤维以至多10重量％的量存在，水分以至多10重量％的量存在，钙以不少于0.02重量％的量存在，钠以约0.02重量％至约0.1重量％的范围的量存在，氯化物以约0.005重量％至约0.02重量％的范围的量存在，以及镁以约0.05重量％至约0.2重量％的范围的量存在。在本发明最特定的实施方案中，预混合的二氢槲皮素和落叶松阿拉伯半乳糖以约10重量％的量存在，蛋白质以约80重量％的量存在，粗脂肪以至少0.5重量％的量存在，粗纤维以至多3重量％的量存在，水分以至多5重量％的量存在，钙以不少于0.05重量％的量存在，钠以约0.05重量％的量存在，氯化物以约0.01重量％的量存在，以及镁以约0.1重量％的量存在。该保健和营养组合物可包装提供，最特定地为约10gm的包装，其用于与自制宠物食物或市售宠物食物混合从而用于迅速增强抗氧化、肠道菌群和免疫刺激。在特定实施方式中，二氢槲皮素以约0.5重量％和约1重量％的量存在。
还提供了一种迅速增强宠物的抗氧化作用、肠道菌群和免疫刺激的方法，所述方法包括：将保健和营养组合物混合到自制饲料或市售饲料中的步骤，以及将所述经混合的组合物和饲料以一餐或多餐提供给所述宠物的步骤。具体而言，对于体重小于约10kg的狗或猫，使用0.5％的二氢槲皮素组合物，如果是体重至多约5kg的狗或猫，在每日一餐中混合1包，而如果是体重在约5kg到约10kg之间的狗或猫，在每日两餐中混合1包。
在另一具体的实施方式中，对于体重超过约10kg的狗，使用1重量％的二氢槲皮素组合物，如果狗的体重在约10kg至约50lbs重量之间，在每日一餐中混合1包；如果狗的体重超过50lbs，在每日两餐中混合1包10。这些方法对于已经暴露于细小病毒的一只或多只够是尤其有利的，这是因为当够非常需要时，抗氧化、肠道菌群和免疫功能能够迅速增强。
在本发明的又一实施方式中，将该保健和营养组合物以片剂提供，形成为能够被宠物咀嚼。二氢槲皮素可为约5重量％或约10重量％，而其中较低的量被用于较小的狗和猫。二氢槲皮素和落叶松阿拉伯半乳糖可以以约250mg至约2000mg范围的量存在，特定地以约500mg至约1000mg范围的量存在，最特定地以约1000mg存在。
该咀嚼片也可用在增强宠物抗氧化、肠道菌群和免疫刺激的方法中。对于体重小于约10kg的狗或猫，使用5％的二氢槲皮素组合物，而对于体重超过10kg的狗，使用10％的二氢槲皮素组合物。
在另一实施方式中，咀嚼片还可以包含维生素A如β胡萝卜素，维生素C如抗坏血酸，维生素D如胆骨化醇，维生素E如生育酚、硫胺素、核黄素、烟酸，维生素B-6如盐酸吡哆醇、泛酸，维生素B-12，生物素和叶酸。具体地，生育酚可为混合的生育酚、DL-生育酚乙酸酯，以及天然的α-生育酚。在非常特定的实施方式中，维生素A如β-胡萝卜素以约1500IU的量存在，维生素C如抗坏血酸以约20mg的量存在，维生素D如胆骨化醇以约150IU的量存在，维生素E如生育酚以约15IU的量存在，硫胺素以4mg的量存在，核黄素以约650mcg的量存在，烟酸以约4mg的量存在，维生素B-6如盐酸吡哆醇以约360mcg的量存在，泛酸以约2mg的量存在，维生素B-12以约8mcg的量存在，生物素以约100mcg的量存在，以及叶酸以约80mcg的量存在。
在相关的实施方式中，咀嚼片无论包括或不包括额外的维生素，均用于增强宠物的抗氧化、肠道菌群和免疫刺激的方法中，通过如下的方式来给予咀嚼片。在体重低于10kg的狗或猫中，使用5％的二氢槲皮素组合物，如果宠物是体重小于10lbs猫或狗，则向宠物给予1片；如果狗的体重在约10lbs到约10kg之间则向狗给予2片。在体重超过约10kg的狗中，使用10％的二氢槲皮素组合物并且按以下方式给予：体重在约10kg至约20kg之间的狗给予1片；体重在20kg至45kg之间的狗给予2片；体重超过45kg的狗给予3片。
实施例1
在一个家庭的八只狗中的一只狗中罹患并死于细小病毒。其它七只狗是混合品种，包含体重在8lbs至50lbs的西施犬、巴塞特猎犬混种、两只猎浣熊犬混种、可卡犬、小猎犬(small terrier)和幼狼杂交犬(young wolf hybrid)。迅速用保健和营养组合物来治疗这些狗，该保健和营养组合物由30mg的二氢槲皮素、50mg的西伯利亚或兴安落叶松阿拉伯半乳糖以及70mg的维生素C组成，并且被配制在单一凝胶胶囊中。在第二天和四天后，每只狗接受两个凝胶胶囊，每日两次，该凝胶胶囊由30mg二氢槲皮素、500mg的西伯利亚或兴安落叶松阿拉伯半乳糖以及70mg的维生素C组成，使得总剂量为120mg的二氢槲皮素、2000mg的西伯利亚或兴安落叶松阿拉伯半乳糖以及280mg的维生素C。用该组合物治疗的七(7)只狗都没有出现细小病毒感染的信号或症状。
虽然已经参照本发明的优选实施方式具体示出并描述了本发明，但是本领域的技术人员将理解的是，在不脱离由所附权利要求所限定的本发明的精神和范围的情况下，可对本发明在形式和细节上的进行多种改变。本领域的技术人员将认识到或能够仅仅通过常规试验来确认本文中具体描述的本发明的具体实施方式的多个等同方案。这些等同方案涵盖在权利要求的范围内。
Claims (5)
1.一种有效增强动物体内的抗氧化、肠道菌群和免疫刺激的动物保健和营养组合物，包括：
二氢槲皮素；以及
西伯利亚或兴安落叶松阿拉伯半乳糖。
2.根据权利要求1所述的动物保健和营养组合物，其中，所述西伯利亚或兴安落叶松阿拉伯半乳糖具有约9.5kDa到约37kDa之间的分子量。
3.根据权利要求1所述的动物保健和营养组合物，其中，所述组合物为以下形式：片剂、咀嚼片、胶囊、树脂、油状物、液体、微脂囊、粉末或栓剂。
4.根据权利要求1所述的动物保健和营养组合物，进一步包括药学可接受的载体。
5.根据权利要求1所述的动物保健和营养组合物，其中，所述组合物被掺入到主体饲料或饲料补充剂中。
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| EP (1) | EP2822550A1 (zh) |
| JP (1) | JP2015516372A (zh) |
| KR (1) | KR20140141592A (zh) |
| CN (1) | CN104203225A (zh) |
| CA (1) | CA2865891A1 (zh) |
| WO (1) | WO2013133783A1 (zh) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8710027B2 (en) * | 2012-04-10 | 2014-04-29 | Flavitpure, Inc. | Method of using nutritional compounds dihydroquercetin (taxifolin) and arabinogalactan in combination with dihydroquercetin (taxifolin) to reduce and control cardiometabolic risk factors associated with metabolic syndrome and hypercholesterolemia |
| JP6370612B2 (ja) * | 2014-06-05 | 2018-08-08 | 株式会社ファンケル | ジヒドロケルセチンとアスタキサンチン含有組成物 |
| EP3884784A1 (en) | 2015-09-30 | 2021-09-29 | Hill's Pet Nutrition, Inc. | Pet food composition for managing non-food allergies |
| CN108967674B (zh) * | 2018-07-09 | 2021-07-09 | 江西省科学院生物资源研究所 | 一种增强羊免疫机能的饲料添加剂及其制备方法和应用 |
| IL261670B (en) * | 2018-09-06 | 2019-06-30 | Tudu Holdings Ltd | Magnesium-containing formulation and uses thereof |
| KR102470655B1 (ko) * | 2018-12-28 | 2022-11-25 | 주식회사 일화 | 보리 발효추출물을 이용한 면역 증강 및 암 예방 및 치료용 조성물의 제조 방법 |
| KR102470657B1 (ko) * | 2018-12-28 | 2022-11-25 | 주식회사 일화 | 보리 발효추출물을 이용한 알레르기성 질환의 예방, 개선 및 치료용 조성물의 제조 방법 |
| RU2713113C1 (ru) * | 2019-04-22 | 2020-02-03 | Колесник Алексей Юрьевич | Премикс для пищевых продуктов и фармацевтических препаратов |
| KR102270024B1 (ko) | 2019-07-19 | 2021-06-30 | 유한회사 비피코리아 | 반려동물용 고체 유산균 및 이의 제조방법 |
Citations (2)
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|---|---|---|---|---|
| US5614501A (en) * | 1994-07-21 | 1997-03-25 | The University Of Montana | Compositions and methods for animal husbandry and for treating gastrointestinal disorders |
| WO2007088046A2 (en) * | 2006-02-01 | 2007-08-09 | Nestec S.A. | Nutritional system and methods for increasing longevity |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4006266A (en) * | 1975-10-08 | 1977-02-01 | The Quaker Oats Company | Process for making a dry pet food having a hard component and a soft component |
| EP1453388A1 (en) * | 2001-12-05 | 2004-09-08 | DSM IP Assets B.V. | Methods and compositions for use in pet breeding |
| US6974841B1 (en) * | 2002-09-27 | 2005-12-13 | Rapisarda Family Irrevocable Trust | Pet anti-aging wellness supplement |
| US8309080B2 (en) * | 2007-12-06 | 2012-11-13 | Naidu Lp | Metallo-protein and tocotrienol (MP-T3) compositions and uses thereof |
| WO2009079680A1 (en) * | 2007-12-21 | 2009-07-02 | University Of Graz | Use larch wood material for treating inflammation |
| RU2421215C1 (ru) * | 2010-04-15 | 2011-06-20 | Открытое Акционерное Общество Завод Экологической Техники И Экопитания "Диод" | Композиция с повышенной фармакологической активностью на основе дигидрокверцетина и растительных полисахаридов (варианты) |
-
2012
- 2012-03-09 US US13/416,759 patent/US20130236529A1/en not_active Abandoned
- 2012-08-22 EP EP12870391.5A patent/EP2822550A1/en not_active Withdrawn
- 2012-08-22 KR KR20147026014A patent/KR20140141592A/ko not_active Application Discontinuation
- 2012-08-22 WO PCT/US2012/000366 patent/WO2013133783A1/en active Application Filing
- 2012-08-22 CN CN201280071221.7A patent/CN104203225A/zh active Pending
- 2012-08-22 JP JP2014560893A patent/JP2015516372A/ja active Pending
- 2012-08-22 CA CA2865891A patent/CA2865891A1/en not_active Abandoned
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| US5614501A (en) * | 1994-07-21 | 1997-03-25 | The University Of Montana | Compositions and methods for animal husbandry and for treating gastrointestinal disorders |
| WO2007088046A2 (en) * | 2006-02-01 | 2007-08-09 | Nestec S.A. | Nutritional system and methods for increasing longevity |
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| 无: "LarchVitaTM Super-charged vitamin C with DHQ and LAG capsule", 《HTTP://WEB.ARCHIVE.ORG/WEB/20100419002256/HTTP://WWW.VITALAVITA.US/PRODUCTS.PHP?PAGE=EXTRA》, 14 June 2009 (2009-06-14) * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2013133783A1 (en) | 2013-09-12 |
| US20130236529A1 (en) | 2013-09-12 |
| EP2822550A1 (en) | 2015-01-14 |
| JP2015516372A (ja) | 2015-06-11 |
| KR20140141592A (ko) | 2014-12-10 |
| CA2865891A1 (en) | 2013-09-12 |
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