CN1251496A - 用于促进骨骼肌适应剧烈运动和对抗虚弱个体疲劳过度的营养增补剂 - Google Patents
用于促进骨骼肌适应剧烈运动和对抗虚弱个体疲劳过度的营养增补剂 Download PDFInfo
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Abstract
本发明公开了一种能促进进行剧烈运动的个体的骨胳肌的适应,和对抗虚弱个体的疲劳过度和疲倦的营养增补剂,它包含L-肉碱、乙酰L-肉碱和丙酰L-肉碱的混合物作为基本活性成分。选择性成分包括异戊酰L-肉碱、支链氨基酸和肌酸和/或磷酸肌酸。
Description
本发明涉及一种营养增补剂,它包含作为基本活性成分的“肉碱类”的混合物,其中“肉碱类”是指L-肉碱和系列低级(短链)脂酰L-肉碱的首项,或它们的药理学上可接受的盐。
该营养增补剂特别适于调节参加紧张、持续体育活动的个体的骨胳肌和肝的适应作用,还适于对抗肌疲劳感,以及身体虚弱的人即使在没有进行任何类型的或多或少的强烈体育活动的情况下仍表现出的疲倦感。
参加体育活动的人,无论是作为专业人员还是业余爱好者,都希望最大程度地使骨胳肌在较短的时间里与支持长期剧烈体育运动的能力相适应,并使这一能力保持尽可能长的时间。寻求这种最佳程度的身体适应性,可导致药物、特别是类固醇类药物的滥用。众所周知,这样的药物可以增加蛋白质的合成,由此使肌肉块的生长增强到比通过训练和饮食所能达到的更高的程度。然而,使用这些药物无疑是有害的,并且在职业体育领域中使用这些药物是非法的。
因此,很清楚,正确地达到上述目的的唯一方法是,适当的训练安排与合适的、用适宜营养增补剂强化的饮食相结合。
虚弱的含义是代表当今生活压力状况、特别是在大都市中流行并影响大量人群的一组弥散性的特定症状,大半与年龄和社会状况的因素无关,其特征是肌肉强度不够或丧失、疲倦、易疲劳、对刺激的反应不充分。
本发明的目的是提供一种可用于上述类型消费者的营养增补剂。
线粒体基质是长链脂肪酸进行氧化的部位,L-肉碱作为长链脂肪酸穿过线粒体内膜进入线粒体基质的载体而发挥独特的重要生理学作用,自从这一基本原理被发现以来已过去了数十年(FritzI.B.:肉碱对长链脂肪酸氧化影响的代谢结果。载于《细胞区室化和脂肪酸代谢的控制》。F.C.Gran编著,纽约,学院出版社,1968年,第39-63页)。自从首次确认(Engel和Angelini,科学,1973年,179:899-902)原发性L-肉碱缺乏是严重的,有时是致命的(尽管很少见)肌病形式(脂质贮积性肌病)的原因以来,我们关于原发性和继发性L-肉碱缺乏的病理学结果的知识,以及反过来说,对于肉碱的外源性供给的治疗和营养价值的知识已有了巨大的增长。
肉碱在所有生物组织中以游离肉碱形式存在时浓度相当高,以脂酰肉碱形式存在时浓度较低,脂酰肉碱是以下可逆反应的代谢产物:
脂酰辅酶A+肉碱脂酰肉碱+CoASH该反应是由三组酶催化的,它们是转移酶,主要是根据它们对反应底物的特异性进行区别的:以短链酰基(如乙酰基和丙酰基)作为底物的肉碱乙酰转移酶(CAT)组,以中链酰基作为底物的肉碱辛酰转移酶(COT)组,和以长链酰基作为底物的肉碱棕榈酰转移酶(CPT)组。
肉碱在中间代谢中的重要作用,特别是在其有限的生物合成方面,可以说明在涉及不同器官和装置的病理学功能中,肉碱缺乏可以怎样作为继发性事件而发生。临床范围的增宽已伴随着与该自然产生的化合物的效能有关的治疗机会数量的增加:采用L-肉碱的替代疗法逆转了脂质贮积性肌病患者的显著临床表现,这一观察结果显示出其在各个方面都有潜在的功效。美国食品及药品管理局(FDA)不仅已给予了L-肉碱孤立药品的地位,而且已将其列入救生药品名单中。
与我们对涉及原发性和继发性肉碱缺乏的病理学关系的更深了解相一致,已出现了令人印象深刻的、主要针对L-肉碱,实质上更小范围而言,是针对大量脂酰肉碱类,的科学和专利出版物。
让我们来对此情形进行部分回顾。有人建议,在心血管领域,L-肉碱可用于治疗心律不齐和充血性心力衰竭(US 4,656,191),心肌缺血和缺氧(US 4,649,159);在脂质代谢性疾病方面,可用于治疗高脂血症和高脂蛋白血症(US 4,315,944),使HDL与LDL+VLDL的异常比率正常化(US 4,255,449);可用于全胃肠外营养领域(US4,254,147和4,320,145);在肾病学上,可用于对抗肌无力和因在进行定期血液透析治疗的慢性尿毒症患者的透析液中肉碱丧失而引起的肌痉挛的发作(US 4,272,549);可对抗因抗癌剂,如阿霉素(US 4,400,371和US 4,713,379),和含卤麻醉剂,如卤烷(US4,780,308)导致的毒性作用;用于治疗静脉停滞(US 4,415,589);对抗老年患者许多生化和行为参数的恶化(US 4,474,812);用于AIDS患者和无症状的HIV-血清阳性患者的甘油三酯和肿瘤坏死因子(TNF)水平的正常化(US 5,631,288)。
L-肉碱也被建议与其他活性成分结合使用,如L-肉碱加上辅酶Q10,有更宽的代谢/抗动脉粥样硬化活性谱(US 4,599,232)。
至于脂酰肉碱类,众所周知,乙酰L-肉碱可用于治疗中枢神经系统疾病,特别是早老性痴呆(US 4,346,107),治疗糖尿病神经病(US 4,751,242),而丙酰L-肉碱已被建议用于治疗外周血管病(US 4,343,816)和充血性心力衰竭(US 4,194,006)。
虽然是以简明而部分的方式对上述专利进行了描述,但从中仍可以清楚地看出一点,与其脂酰衍生物相比,L-肉碱有明显更大的份量和重要性。
对专利文献的分析表明,在某些情形下,对于给定的适应征,L-肉碱和一些低级脂酰肉碱的作用是等价的。对此等价进行更深的审视发现,它更多是出于获得最宽的保护范围的专利动机,而不是源于适当的药理学/临床研究的结果。上述肉碱与脂酰肉碱之间的可逆平衡反应,或许也揭示了这种行为的“等价”。
从对科学和专利文献的审查也可看出,研究者的注意力总是特定集中在单个肉碱,如已说过的,主要集中在L-肉碱上。这样就形成了一种单一化合物培养,实际上,这是一种技术偏见,它已妨碍了对“肉碱类”混合物功效的研究。事实上,没有证据表明含有L-肉碱、乙酰L-肉碱和丙酰L-肉碱(或它们的药理学上可接受的盐)的混合物曾被建议作为基本活性成分,用于治疗或营养目的。很明显,以前从未公开过任何这样的混合物,其中L-肉碱、乙酰L-肉碱和丙酰L-肉碱是以明确确定的重量比(下文将详述)存在的。为了获得预期的治疗/营养作用,此重量比是至关重要的。
现已发现,L-肉碱、乙酰L-肉碱和丙酰L-肉碱(或其药理学上可接受的盐)的混合物,与单个“肉碱”相比,产生了未曾预料的强大协同作用,这些已被各种试验所证明。在这些试验中,L-肉碱、乙酰L-肉碱和丙酰L-肉碱的混合物的功效和它们单独给药时的功效进行了对比。
这三种“肉碱”的联合作用能影响脂肪酸糖酵解和氧化路径,这不足以为奇。并且,丙酰L-肉碱这一能在三羧酸循环中增加琥珀酰辅酶A浓度(添补作用)的物质的存在,提高了其整体速度。显然,通过补充足够的乙酰单位可以促进这种速度的提高。这后一种作用是由乙酰L-肉碱完成。实际上,由于线粒体肉碱乙酰转移酶的存在,乙酰L-肉碱的乙酰基可转移到辅酶A上,以合成乙酰辅酶A,这是三羧酸循环中的一种关键化合物。最后,肉碱通过其已知的将脂肪酸转移到线粒体基质中的作用,增强了脂肪酸自身的氧化。肌肉收缩过程所需的大部分能量是从脂肪酸类化合物中提取的。
但是,这些明显的原因至多会使人想到“肉碱”的混合物的“加和”作用,而不是令人吃惊的、显著的协同作用,此作用表现为下文将详述的临床研究中显示的ATP产率的增强。ATP是细胞的主要能量来源。
作为使得有可能确定该协同作用的研究结果,本发明提供了一种营养增补剂,它包含下列组合:(a)L-肉碱;(b)乙酰L-肉碱;(c)丙酰L-肉碱;或其药理学上可接受的盐;和药理学上可接受的赋形剂。(a)∶(b)∶(c)的重量比范围是1∶1∶1至1∶0.1∶0.1,其中前述重量比是指以内盐表示的L-肉碱、乙酰L-肉碱和丙酰L-肉碱。
同时也发现,除了该混合物的必需成分(L-肉碱、乙酰L-肉碱和丙酰L-肉碱或其药理学上可接受的盐)以外,本发明的营养增补剂还可有利地包含另外的脂酰L-肉碱,如异戊酰L-肉碱,必需氨基酸的混合物以及肌酸和/或磷酸肌酸。
L-肉碱、乙酰L-肉碱、丙酰L-肉碱和异戊酰L-肉碱的重量比范围是1∶1∶1∶1至1∶0.1∶0.1∶0.1,优选为1∶0.5∶0.5∶0.5。
所有氨基酸,不管是必需的还是非必需的,都是肌细胞为蛋白质合成所需的底物。众所周知,超出蛋白质合成所需的过量氨基酸和其他大分子既不能被排泄,也不能贮存,这一点与脂肪酸和葡萄糖不同。另一方面,过量氨基酸被用作能量物质。当α-氨基被除去后,剩余的碳原子骨架转化为基础代谢中间产物。这些过量氨基酸的大多数氨基转变为脲,而碳骨架转化为乙酰辅酶A、乙酰乙酰辅酶A、丙酮酸盐或是柠檬酸循环的中间产物之一。这样,就从这些氨基酸形成了脂肪酸、酮体和葡萄糖。
优选而言,必需氨基酸混合物包括支链氨基酸缬氨酸、亮氨酸和异亮氨酸。
本发明的营养增补剂也可有利地包含非必需氨基酸,特别是谷氨酰胺、L-谷氨酸、L-天冬氨酸和L-天冬酰胺。
本发明的营养增补剂的一个实例包含:(i)40%至60%重量的L-肉碱、乙酰L-肉碱、丙酰L-肉碱或其药理学上可接受的盐的混合物;(ii)10%至15%重量的缬氨酸;
10%至15%重量的亮氨酸;
10%至15%重量的异亮氨酸;和(iii)8%至12%重量的肌酸或磷酸肌酸。
如果存在非必需氨基酸,它们将占该营养增补剂的10%至30%重量。
针对本发明的所有功效和目的而言,L-肉碱、乙酰L-肉碱、丙酰L-肉碱和异戊酰L-肉碱是指内盐形式的这些化合物。
L-肉碱、乙酰L-肉碱、丙酰L-肉碱或异戊酰L-肉碱的药理学上可接受的盐,是指这些肉碱与不会产生不需要的毒性或副作用的酸形成的任何盐。这些酸是药理学家和药学专家所熟知的。
这些盐的非限制性实例有:氯化物;溴化物;碘化物;天冬氨酸盐;酸式天冬氨酸盐;柠檬酸盐;酸式柠檬酸盐;酒石酸盐;磷酸盐;酸式磷酸盐;延胡索酸盐;酸式延胡索酸盐;甘油磷酸盐;葡糖磷酸;乳酸盐;苹果酸盐;酸式苹果酸盐;乳清酸盐;草酸盐;酸式草酸盐;硫酸盐;酸式硫酸盐;三氯乙酸盐;三氟乙酸盐和甲磺酸盐。
国际药学杂志第33期(1986)第201-217页列出了FDA批准的药理学上可接受的盐的名单;该出版物结合在此作为参考。
延胡索酸盐是特别优选的,例如,延胡索酸L-肉碱对蛋白质代谢施加双重保护作用;通过在中间代谢中的直接增加,它间接地刺激了蛋白质的生物合成,同时,作为脂肪酸转移的结果,它诱导了对肌肉蛋白组分的节省/保护作用。
进行剧烈运动的个体和虚弱的个体,都可以通过服用以下物质而获得最好的效果:约500mg/天L-肉碱,50-500mg/天乙酰L-肉碱和50-500mg/天丙酰L-肉碱,或它们相当重量的药理学上可接受的盐。
该营养增补剂还可以含有无机盐,如柠檬酸二钠,磷酸一钾,乳酸钙和牛磺酸镁。
本发明的营养增补剂适于口服。
本营养增补剂不得用作日常基础上的唯一或主要营养源。
因此,饮食的补充部分将包括适当的氨基酸、碳水化合物、脂肪、维生素和矿物质。
该营养增补剂的每日摄取量可在较宽的幅度内变化,例如,这取决于服用者的年龄和体重,以及训练日程的强度和复杂性,或根据具体情况,取决于服用者所从事的体育运动。不过,一般说来,从该营养增补剂摄入的蛋白质的量不应超过服用者每天正常摄入的蛋白质总量的30-35%重量。
合理地长期使用本发明的营养增补剂能产生下列积极的功效:
(a)能保存肌肉蛋白,特别是骨胳肌中存在的支链氨基酸;
(b)刺激骨胳肌和肝中的蛋白质合成;
(c)可获得用于丙氨酸和谷氨酰胺合成的氨基,丙氨酸和谷氨酰胺均参加糖异生作用;
(d)促进丙酮酸盐代谢转化为丙氨酸而不是乳酸盐;和
(e)促进氢离子经谷氨酸盐向谷氨酰胺的转化而从骨胳肌流出,以维持最佳肌内pH值。
下面给出了本发明营养增补剂的一个非限制性的实例。该组合物适当地溶于足量的水,如200-300ml水后,适于以液体形式口服。基本活性成分 每日剂量-延胡索酸L-肉碱 200mg(=143mg L-肉碱内盐)-乙酰L-肉碱 75mg-丙酰-肉碱 75mg支链氨基酸和非必需氨基酸-异亮氨酸 50mg-亮氨酸 50mg-缬氨酸 50mg-天冬氨酸 150mg-谷氨酸 200mg-天冬酰胺 100mg磷酸肌酸 50mg维生素-维生素C 250mg无机盐-柠檬酸二钠(=7.8mg钠) 40mg-磷酸一钾(=8.6mg钾) 30mg-乳酸钙(=20mg钙) 110mg-牛磺酸镁(=73.0mg镁) 820mg活性成分总量 2250mg-赋形剂 2750mg总重量 5000mg
对于药学专家来说,很明显,通过使用合适的赋形剂,能将本发明的组合物配制成固体形式,从而制成片剂、咀嚼片剂、胶囊等。
下文给出的大量研究证明了与单独使用的L-肉碱、乙酰L-肉碱和丙酰L-肉碱相比,它们的混合物具有协同作用。混合物对运动表现的影响
为了评估与单独服用L-肉碱、乙酰L-肉碱和丙酰L-肉碱相比,它们的混合物(COMB)对持久运动员(研究1)和进行非紧张的、娱乐性体育锻炼的受试者(研究2)的表现的影响,我们进行了两项研究。研究1
人群:40位健康男性志愿者,他们已从事了至少4年的长距离赛跑(如马拉松)。
研究设计:随机、双盲、平行、与安慰剂对照,期限为45天。
包含标准:-性别:男-年龄:20-40岁-体重:不超过正常体重的10%-呼吸交换率:0.8
排除标准:-有胃肠、心血管、骨胳肌和神经系统疾病-肾和肝机能不全
在研究过程中,所有受试者都没有承受不正常的身体和营养压力。治疗
为确保研究的盲性,所有受试者每天口服6片药(2×3,饭后)。通过改变每个治疗组服用的活性片剂和安慰剂片剂的数量来实现研究设计。这种改变根据要服用的具体物质而定,如下:-8名受试者,每天服用1.5g COMB(3×500mg片剂,每片由167mgLC、167mg PLC和167mg ALC组成,+3片安慰剂),服用45天;-8名受试者,每天服用2g L-肉碱(LC)(4×500mg片剂+2片安慰剂),服用45天;-8名受试者,每天服用2.5g丙酰L-肉碱(PLC)(5×500mg片剂+1片安慰剂),服用45天;-8名受试者,每天服用3g乙酰L-肉碱(ALC)(6×500mg片剂),服用45天;-8名受试者,每天服用安慰剂(PLA,6片),服用45天。
在研究过程中,要求运动员每周的训练距离保持相对稳定。功效的评估:每位运动员在完成一项渐进式踏车测试(0°梯度)直至精疲力竭后,记录各自的氧消耗量(VO2,ml/分)和踏车跑速峰值(km/小时)。运动员起初跑速为8km/小时,每3分钟提高2km/小时,直至达到16km/小时。之后,每2分钟提速1km/小时,直至体力耗尽,其有两个测量标准:1-VO2稳定;2-呼吸交换率超过1.1。踏车跑速峰值为运动员在测试过程中能达到的、持续60秒的最高跑速。
所有受试者都在基线(T0)和治疗后45天(T45)进行评估。另外,测定血液化学和尿参数,以监控负作用。
利用方差分析(ANOVA)对数据,包括受试者、时间和治疗等因素进行分析。利用t检验评价不同治疗组之间得分的差异。显著性为P<0.05。结果
运动员的身体特征为:年龄(岁)27.5±3.8;身高(厘米)175±6.5;体重(Kg)69.9±7。有关效能参数的结果如下:
数据为平均值±标准误差*与PLA比较,P<0.05;$与LC比较,P<0.05;°与ALC比较,P<0.05;^与PLC比较,P<0.05。
组(n=8) | 最高跑速(km/小时) | VO2(ml/分) | ||
T0 | T45 | T0 | T45 | |
PLA | 19.7±0.7 | 20.1±0.8 | 3108.7±325.4 | 3071.2±245.4 |
COMB | 19.6±0.7 | 23.0±0.7*$°^ | 3025.0±110.2 | 2551.2±146.5*°^ |
LC | 19.5±0.9 | 21.4±0.7*° | 2916.2±166.7 | 2850.0±119.5 |
ALC | 19.6±0.7 | 20.0±0.7^ | 2950.6±96.0 | 2685.0±105.1* |
PLC | 19.6±0.7 | 21.5±0.5* | 2953.1±97.3 | 2907.5±115.0 |
在T0时,各治疗组之间没有统计学上的显著差异。
在T45时,COMB组的最高跑速显著高于其他各组,但并未伴随VO2的上升。
因此,很明显,用COMB治疗积极地影响了持久运动员的身体表现。
没有负作用的报道。
研究2
人群:40位从事非紧张的、娱乐性体育锻炼的健康志愿者(23名男性和17名女性)。
研究设计:随机、双盲、平行、与安慰剂对照,期限为15天。
包含标准:-性别:男性与女性-年齿龄:18-40岁-体重:不超过正常体重10%-呼吸交换率:0.8
排除标准:-有胃肠、心血管、骨胳肌和神经系统疾病-肾和肝机能不全
在研究中,所有受试者都没有承受不正常的身体和营养压力。治疗
为确保研究的盲性,所有受试者每天口服6片药(2×3,饭后)。通过改变每个治疗组服用的活性片剂和安慰剂片剂的数量来实现研究设计。这种改变根据要服用的具体物质而定,如下:-8名受试者,每天服用1.5g COMB(3×500mg片剂,每片包括167mgLC、167mg PLC和167mg ALC,+3片安慰剂),服用15天;-8名受试者,每天服用2g L-肉碱(LC)(4×500mg片剂+2片安慰剂),服用15天;-8名受试者,每天服用2.5g丙酰L-肉碱(PLC)(5×500mg片剂+1片安慰剂),服用15天;-8名受试者,每天服用3g乙酰L-肉碱(ALC)(6×500mg片剂),服用15天;-8名受试者,每天服用安慰剂(PLA,6片),服用15天。
功效评估:测定最大氧消耗量(VO2max,ml/kg/分)和总工作负荷(kgm/小时),以评估治疗功效。
在基线(T0)和治疗后15天(T15),对所有受试者进行最大动力肺活量(ergospirometric effort)测试(三角踏车),工作负荷根据Bruce方案确定(每3分钟7步,10-22%的倾斜度,速度为1.7-6.5Mph)。
另外,测定血液化学和尿参数,以监控负作用。
利用方差分析(ANOVA)对数据,包括受试者、时间和治疗等因素进行分析。利用t检验评价各治疗组之间得分的差异。显著性为P<0.05。结果
受试者的身体特征为:年龄(岁)29±5.1;体重(Kg)74±5.2;身高(厘米)174.5±6.8。
有关效能参数结果如下:
数据为平均值±标准误差*与PLA比较,P<0.05;$与LC比较,P<0.05;°与ALC比较,P<0.05;^与PLC比较,P<0.05。
组(n=8) | 总工作负荷(kgm/小时) | VO2max(ml/kg/分) | ||
T0 | T15 | T0 | T15 | |
PLA | 9600.9±1600.4 | 9800.4±910.0 | 62.1±4.9 | 61.8±4.4 |
COMB | 10390.2±1400.5 | 13280.5±700.1*$° | 61.5±4.3 | 75.9±3.3*$°^ |
LC | 10200.5±1510.1 | 11400.2±700.2* | 60.6±4.2 | 67.5±2.5 |
ALC | 10020.5±1500.2 | 11100.4±1100.8 | 617±5.1 | 64.4±4.9 |
PLC | 10800.2±10015.9 | 12100±900.4* | 62.6±4.8 | 69.0±3.0* |
在T0时,各组间没有统计学上的显著差异。
在T15时,COMB组的总工作负荷明显高于PLA、LC和ALC组。并且,VO2max明显高于其他各组。结果,用COMB治疗的受试者有更有效的身体表现。
没有负作用的报道。混合物对虚弱个体的影响
本研究的目的是评估与单独使用L-肉碱、乙酰L-肉碱和丙酰L-肉碱相比,它们的混合物(COMB)对虚弱个体的影响。
本研究设计为COMB与L-肉碱或乙酰L-肉碱或丙酰L-肉碱或安慰剂之间的随机的、双盲的、平行组间比较,期限为30天。
本研究的受试者为18岁至60岁之间的男性或女性,他们为手术后(n=19)和传染病(n=15)导致的虚弱以及“自发性”虚弱(n=26)。排除标准包括心血管、骨胳肌和神经系统病史,肝和肾机能不全以及抑郁(用Beck抑郁表诊断)。
在开始试验前征得所有受试者的同意。治疗
为确保研究的盲性,所有受试者每天服用6片药(2×3,饭后)。通过改变各治疗组服用的活性片剂和安慰剂片剂的数量来实现研究设计。这种改变根据要服用的具体物质而定,如下:-12名受试者,每天服用1.5g COMB(3×500mg片剂,每片包含167mg LC、167mg PLC和167mg ALC,+3片安慰剂),服用30天;-12名受试者,每天服用2g L-肉碱(LC)(4×500mg片剂+2片安慰剂),服用30天;-12名受试者,每天服用2.5g丙酰L-肉碱(PLC)(5×500mg片剂+1片安慰剂),服用30天;-12名受试者,每天服用3g乙酰L-肉碱(ALC)(6×500mg片剂),服用30天;-12名受试者,每天服用安慰剂(PLA,6片),服用30天。
功效评估:在基线(T0)和治疗后30天(T30)时,利用20项自我报告评估表(MFI-20表,Smets E.M.A.等,身心研究杂志39:315-325,1995;英国癌症杂志73:241-245,1996)测定虚弱情况。该评估表包括一般意义上的疲劳、身体疲劳、活力减弱、动机减弱以及精神疲倦。总分在20至40之间表明不存在虚弱,40以上(直至最大100)表明了虚弱的逐步严重性。
用方差分析法(ANOVA)分析数据。用t检验评价各治疗组之间分数的差异。显著性为P<0.05。结果
获得以下结果:
数据为平均值±标准误差*与PLA比较,P<0.05;$与LC比较,P<0.05;°与ALC比较,P<0.05;^与PLC比较,P<0.05。
组(n=12) | MFI-20表得分 | |
T0 | T30 | |
PLA | 73.2±2.5 | 74.0±3.5 |
COMB | 70.4±4.1 | 24.2±2.2*$°^ |
LC | 75.2±6.2 | 52.5±4.7*°^ |
ALC | 69.8±7.1 | 39.4±5.5* |
PLC | 70.9±6.0 | 65.2±6.6* |
在T0时,各治疗组间没有显著差异。
在T30时,COMB组受试者已从虚弱中恢复。LC、PLC和ALC组的受试者比安慰剂组的受试者具有明显低的平均得分,但仅有ALC组的受试者达到了大体正常的平均值。
Claims (15)
1、一种营养增补剂,它包含以下物质的混合物:
(a)L-肉碱;
(b)乙酰L-肉碱;
(c)丙酰L-肉碱;或其药理学上可接受的盐,和药理学上可接受的赋形剂。
2、权利要求1所述的营养增补剂,其中(a)∶(b)∶(c)的重量比为1∶1∶1至1∶0.1∶0.1。
3、权利要求2所述的营养增补剂,它进一步包含:
(d)异戊酰L-肉碱或其药理学上可接受的盐,其中(a)∶(b)∶(c)∶(d)的重量比为1∶1∶1∶1至1∶0.1∶0.1∶0.1。
4、上述任一项权利要求所述的营养增补剂,它进一步包含必需氨基酸或其混合物。
5、权利要求4所述的营养增补剂,其中必需氨基酸选自支链氨基酸缬氨酸、亮氨酸和异亮氨酸或其混合物。
6、权利要求4所述的营养增补剂,其中L-肉碱、乙酰L-肉碱、丙酰L-肉碱的混合物与必需氨基酸或其混合物的重量比为3∶1至1∶1。
7、权利要求4-6任-项所述的营养增补剂,它进一步包含谷氨酰胺、L-谷氨酸、L-天冬氨酸和L一天冬酰胺。
8、上述任一项权利要求所述的营养增补剂,它进一步包含选自肌酸和磷酸肌酸的肌酸。
9、上述任一项权利要求所述的营养增补剂,它包含:
(i)40%至60%重量的L-肉碱、乙酰L-肉碱和丙酰L-肉碱或其药理学上可接受的盐的混合物;
(ii)10%至15%重量的缬氨酸;
10%至15%重量的亮氨酸;
10%至15%重量的异亮氨酸;和
(iii)8%至12%重量的肌酸或磷酸肌酸。
10、权利要求9所述的营养增补剂,它进一步包含10%至30%重量的非必需氨基酸。
11、前述任一项权利要求所述的营养增补剂,其中药理学上可接受的盐选自:氯化物;溴化物;碘化物;天冬氨酸盐;酸式天冬氨酸盐;柠檬酸盐;酸式柠檬酸盐;酒石酸盐;磷酸盐;延胡索酸盐;酸式延胡索酸盐;甘油磷酸盐;葡糖磷酸;乳酸盐;苹果酸盐;酸式苹果酸盐;乳清酸盐;草酸盐;酸式草酸盐;硫酸盐;酸式硫酸盐;三氯乙酸盐和甲磺酸盐。
12、前述任一项权利要求所述的营养增补剂,它包含:基本活性成分 每日剂量-延胡索酸L-肉碱 200mg(=143mg L-肉碱内盐)-乙酰L-肉碱 75mg-丙酰L-肉碱 75mg支链氨基酸和非必需氨基酸-异亮氨酸 50mg-亮氨酸 50mg-缬氨酸 50mg-天冬氨酸 150mg-谷氨酸 200mg-天冬酰胺 100mg磷酸肌酸 50mg维生素-维生素C 250mg无机盐-柠檬酸二钠(=7.8mg钠) 40mg-磷酸一钾(=8.6mg钾) 30mg-乳酸钙(=20mg钙) 110mg-牛磺酸镁(=73.0mg镁) 820mg活性成分总量 2250mg-赋形剂 2750mg总重量 5000mg
13、促进进行剧烈体育运动的个体的骨胳肌的适应和对抗虚弱个体的疲劳过度和疲倦的方法,该方法包含给予需要的个体服用营养增补剂,该营养增补剂包含以下物质的混合物:(a)L-肉碱;(b)乙酰L-肉碱;(c)丙酰L-肉碱;或其药理学上可接受的盐。
14、权利要求13所述的方法,其中(a)∶(b)∶(c)的重量比为1∶1∶1至1∶0.1∶0.1。
15、权利要求14所述的方法,它包含给予所需个体500mg/天L-肉碱,50-500mg/天乙酰L-肉碱和50-500mg/天丙酰L-肉碱或相当重量的其药理学上可接受的盐。
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IT97RM000185A IT1291127B1 (it) | 1997-04-01 | 1997-04-01 | Integratore alimentare per soggetti dediti ad intensa e prolungata attivita' fisica |
ITRM97A000185 | 1997-04-01 |
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CN1251496A true CN1251496A (zh) | 2000-04-26 |
CN1074912C CN1074912C (zh) | 2001-11-21 |
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CN98803848A Expired - Fee Related CN1074912C (zh) | 1997-04-01 | 1998-03-27 | 用于促进骨骼肌适应剧烈运动和对抗虚弱个体疲劳过度的营养增补剂 |
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US (1) | US6245378B1 (zh) |
EP (1) | EP0973415B1 (zh) |
JP (1) | JP2001517085A (zh) |
KR (1) | KR20010005865A (zh) |
CN (1) | CN1074912C (zh) |
AT (1) | ATE202675T1 (zh) |
AU (1) | AU729412B2 (zh) |
BR (1) | BR9807905A (zh) |
CA (1) | CA2285332C (zh) |
DE (1) | DE69801047T2 (zh) |
DK (1) | DK0973415T3 (zh) |
ES (1) | ES2159179T3 (zh) |
GR (1) | GR3036777T3 (zh) |
HK (1) | HK1026124A1 (zh) |
IL (1) | IL131857A (zh) |
IT (1) | IT1291127B1 (zh) |
PT (1) | PT973415E (zh) |
SK (1) | SK282907B6 (zh) |
WO (1) | WO1998043499A2 (zh) |
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CN101524155B (zh) * | 2009-04-20 | 2012-10-10 | 北京康比特体育科技股份有限公司 | 一种氨基酸组合物 |
CN104415043B (zh) * | 2013-09-03 | 2017-03-15 | 上海华拓医药科技发展有限公司 | 一种磷酸肌酸二钠盐在制备抗癌因性疲乏药物中的用途 |
CN118638020A (zh) * | 2024-08-08 | 2024-09-13 | 杭州海尔希畜牧科技有限公司 | L-天门冬氨酸l(-)肉碱(1:1)的制备方法 |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2146555B1 (es) * | 1999-01-22 | 2001-03-01 | Helsint S A L | Empleo de formulaciones a base de fracciones hidrosolubles de phlebodium decumanum (exply-37) y/o polypodium leucotomos como complemento nutricional en la prevencion y reversion del sindrome de sobresfuerzo fisico. |
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Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4400371A (en) * | 1972-11-06 | 1983-08-23 | Biocarn Ltd. | Carnitine and its use in reducing cardiac toxicity and as a synergist with cytostats |
FR2384751A1 (fr) * | 1977-03-23 | 1978-10-20 | Francaise Coop Pharma | Nouveaux derives de la taurine a activite neuro-musculaire renforcee |
AU518617B2 (en) * | 1977-04-29 | 1981-10-08 | Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. | Therapeutic application of acetyl-d, 1-carnitine |
DE2903558C2 (de) * | 1978-02-03 | 1994-09-01 | Sigma Tau Ind Farmaceuti | Verwendung von L-Carnitin |
IT1156769B (it) * | 1978-05-25 | 1987-02-04 | Sigma Tau Ind Farmaceuti | Applicazione terapeutica della carnitina e di altri acil derivati della carnitina |
US4346107A (en) | 1979-02-12 | 1982-08-24 | Claudio Cavazza | Pharmaceutical composition comprising acyl-carnitine for the treatment of impaired cerebral metabolism |
IT1206954B (it) * | 1979-02-12 | 1989-05-17 | Sigma Tau Ind Farmaceuti | Agenti terapeutici a base di un acil derivato della carnitina per la cura di vasculopatie periferiche |
IT1119853B (it) * | 1979-09-21 | 1986-03-10 | Sigma Tau Ind Farmaceuti | Composizione farmaceutica comprendente l-carnitina per il trattamento delle dislipidemie ed iperlipo proteinemie |
IT1119854B (it) * | 1979-09-21 | 1986-03-10 | Sigma Tau Ind Farmaceuti | Composizione farmaceutica comprendente l-carnitina per il trattamento di disfunzioni cardiache |
IT1120033B (it) * | 1979-10-05 | 1986-03-19 | Sigma Tau Ind Farmaceuti | Composizione farmaceutica comprendente-carnitina adatta per l'alimentazione parenterale |
IT1142934B (it) * | 1981-11-06 | 1986-10-15 | Sigma Tau Ind Farmaceuti | Uso della carnitina e delle acilcarnitine inferiori nel trattamento terapeutico della patologia delle vene |
IT1157238B (it) * | 1982-10-29 | 1987-02-11 | Sigma Tau Ind Farmaceuti | Impiego di 1-carnitina per migliorare i paramenti biochimici e comportamentali dell'eta' senile |
CH655005A5 (it) * | 1983-02-16 | 1986-03-27 | Sigma Tau Ind Farmaceuti | Composizione farmaceutica ad azione metabolica ed energetica utilizzabile in terapia cardiaca e vascolare. |
DE3463261D1 (en) * | 1983-12-28 | 1987-05-27 | Sigma Tau Ind Farmaceuti | Salts of l-carnitine and alkanoyl l-carnitines and process for preparing same |
DE3420828A1 (de) * | 1984-06-05 | 1985-12-05 | Bayer Ag, 5090 Leverkusen | Fungizide mittel |
US4604286A (en) * | 1984-09-17 | 1986-08-05 | Daigo Nutritive Chemicals, Ltd. | Infusion solution for parenteral nutrition |
IT1196564B (it) * | 1986-08-04 | 1988-11-16 | Sigma Tau Ind Farmaceuti | Impiego di acetil l-carnitina nel trattamento terapeutico delle neuropatie periferiche |
ATE88631T1 (de) * | 1986-09-17 | 1993-05-15 | Clintec Nutrition Co | Zusatznahrung bzw. therapie fuer personen mit risiko oder in behandlung fuer arteriosklerotische vaskulaere, kardiovaskulaere und/oder thrombotische erkrankungen. |
IT1245699B (it) * | 1991-05-29 | 1994-10-14 | Sigma Tau Ind Farmaceuti | Derivati della l-carnitina quali agenti terapeutici per il trattamento delle miopatie, della degenarazione neuronale e per inibire la proteolisi |
IT1258491B (it) * | 1992-09-24 | 1996-02-26 | Sigma Tau Ind Farmaceuti | Impiego di l-carnitina e acil l-carnitine nel trattamento di pazienti affetti da aids e sindromi correlate e di pazienti asintomatici hiv- sieropositivi. |
US5817329A (en) * | 1997-02-28 | 1998-10-06 | Gardiner; Paul T. | Nutritional supplement for increased muscle size and strength for body builders |
-
1997
- 1997-04-01 IT IT97RM000185A patent/IT1291127B1/it active IP Right Grant
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1998
- 1998-03-27 IL IL13185798A patent/IL131857A/en not_active IP Right Cessation
- 1998-03-27 ES ES98912704T patent/ES2159179T3/es not_active Expired - Lifetime
- 1998-03-27 SK SK1349-99A patent/SK282907B6/sk unknown
- 1998-03-27 CN CN98803848A patent/CN1074912C/zh not_active Expired - Fee Related
- 1998-03-27 BR BR9807905-0A patent/BR9807905A/pt not_active IP Right Cessation
- 1998-03-27 DK DK98912704T patent/DK0973415T3/da active
- 1998-03-27 WO PCT/IT1998/000069 patent/WO1998043499A2/en not_active Application Discontinuation
- 1998-03-27 EP EP98912704A patent/EP0973415B1/en not_active Expired - Lifetime
- 1998-03-27 CA CA002285332A patent/CA2285332C/en not_active Expired - Lifetime
- 1998-03-27 KR KR1019997008941A patent/KR20010005865A/ko not_active Application Discontinuation
- 1998-03-27 JP JP54137898A patent/JP2001517085A/ja active Pending
- 1998-03-27 AT AT98912704T patent/ATE202675T1/de active
- 1998-03-27 PT PT98912704T patent/PT973415E/pt unknown
- 1998-03-27 DE DE69801047T patent/DE69801047T2/de not_active Expired - Lifetime
- 1998-03-27 US US09/147,179 patent/US6245378B1/en not_active Expired - Lifetime
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101524155B (zh) * | 2009-04-20 | 2012-10-10 | 北京康比特体育科技股份有限公司 | 一种氨基酸组合物 |
CN102512655A (zh) * | 2011-11-30 | 2012-06-27 | 北京康比特体育科技股份有限公司 | 左旋肉碱组合物和制剂,及其制备方法和应用 |
CN104415043B (zh) * | 2013-09-03 | 2017-03-15 | 上海华拓医药科技发展有限公司 | 一种磷酸肌酸二钠盐在制备抗癌因性疲乏药物中的用途 |
CN118638020A (zh) * | 2024-08-08 | 2024-09-13 | 杭州海尔希畜牧科技有限公司 | L-天门冬氨酸l(-)肉碱(1:1)的制备方法 |
Also Published As
Publication number | Publication date |
---|---|
WO1998043499A3 (en) | 1999-01-07 |
SK282907B6 (sk) | 2003-01-09 |
IL131857A (en) | 2002-04-21 |
HK1026124A1 (en) | 2000-12-08 |
IT1291127B1 (it) | 1998-12-29 |
GR3036777T3 (en) | 2002-01-31 |
BR9807905A (pt) | 2000-02-22 |
AU6746298A (en) | 1998-10-22 |
DE69801047T2 (de) | 2001-10-31 |
EP0973415A2 (en) | 2000-01-26 |
WO1998043499A2 (en) | 1998-10-08 |
CA2285332C (en) | 2007-11-27 |
SK134999A3 (en) | 2000-05-16 |
ES2159179T3 (es) | 2001-09-16 |
DE69801047D1 (de) | 2001-08-09 |
CA2285332A1 (en) | 1998-10-08 |
ATE202675T1 (de) | 2001-07-15 |
EP0973415B1 (en) | 2001-07-04 |
US6245378B1 (en) | 2001-06-12 |
ITRM970185A1 (it) | 1998-10-01 |
IL131857A0 (en) | 2001-03-19 |
PT973415E (pt) | 2001-10-30 |
JP2001517085A (ja) | 2001-10-02 |
DK0973415T3 (da) | 2001-09-24 |
CN1074912C (zh) | 2001-11-21 |
AU729412B2 (en) | 2001-02-01 |
KR20010005865A (ko) | 2001-01-15 |
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