CN102215839B - 用于人工喂养重病的重症特护患者的脂肪乳剂 - Google Patents
用于人工喂养重病的重症特护患者的脂肪乳剂 Download PDFInfo
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- CN102215839B CN102215839B CN200980145702.6A CN200980145702A CN102215839B CN 102215839 B CN102215839 B CN 102215839B CN 200980145702 A CN200980145702 A CN 200980145702A CN 102215839 B CN102215839 B CN 102215839B
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Abstract
本发明涉及用于预防或治疗危重病性多发性神经病(CIP)和危重病性肌病(CIM)的药物制剂。本发明还涉及包含至少一种甘油三酯的等渗脂肪乳剂,所述甘油三酯包含至少一种具有奇数个碳原子的脂肪酸基团,其中所述脂肪酸基团包含具有5‑15个碳原子的碳链。
Description
技术领域
本发明涉及用于预防和治疗危重病性多发性神经病(critical illnesspolyneuropathy(CIP))和危重病性肌病(critical illness myopathy(CIM))的药物制剂。此外,本发明涉及包含至少一种甘油三酯的等渗脂肪乳剂,所述甘油三酯包括至少一个具有奇数个碳原子的脂肪酸残基,其中所述脂肪酸残基包含具有5-15个碳原子的碳链。另外,本发明涉及所述等渗脂肪乳剂作为饮食产品的应用,且本发明还涉及所述药物制剂/等渗脂肪乳剂在肠胃外营养范围内或作为饮食产品成分的应用,特别是脂肪乳剂在人工喂养脓毒症重症特护患者中的应用。
背景技术
由于近年来以及近几十年来重症特护医学的发展,病情极度严重的重症特护患者的生存时间可以显著延长,所述重症特护医学的发展归因于,除了别的以外,新治疗观念、分类体系和目标明确的干预。然而,因此,在这组患者中观察到以前罕见或未知的临床现象。因此,重症特护患者具有发生脓毒症(sepsis)的特别高的风险,脓毒症可能使其在其更晚的病程中发生严重并发症。其中,在重症特护患者中的神经病学和肌肉疾患的系统研究中确定了危重病性多发性神经病(CIP)和危重病性肌病(CIM)。这两种情形均涉及获得性肌无力,即主要是轴突性的CIP,和主要是肌肉性的CIM。临床上区分CIP与CIM非常困难,因为全身性瘫痪(paralysis)、肌无力(myasthenia)和呼吸机撤离(respiratior weaning)问题是这两种情形的最重要和普遍症状,并且另外,这两种疾病可以一起发生(O.Friedrich,E.Hund,Anaesthesist 2006,55,1271-1280)。关于CIP/CIM的患病率,目前对于患有严重脓毒症和多器官功能衰竭(multiple organ failure)患者所提到的数值为70-80%。尽管可能仅由CIP/CIM单独引起的致死率并不高,但是CIP/CIM的发生延长重症特护治疗,延缓康复并由此导致治疗和整体经济成本的巨大增加。另外,患有例如严重ARDS的患者的肌性肌无力(muscular weakness)和快速疲劳被认为是受限制的生活质量的最重要原因,即使在重症特护医学治疗结束后12个月以后(M.S.Herridge,A.M.Cheung,C.M.Tansey,N.Engl.J.Med.(英国医学杂志)2003,348,683-693)。CIP/CIM的确切原因目前仍不清楚,并仍处于重症特护医学研究中。除了别的以外,将炎症介质、分解代谢、胰岛素抗性、皮质类固醇的应用、增加的胰高血糖素敏感性、能量供给障碍、肌肉松弛剂的应用、氧化应激以及全身微循环和/或炎症反应作为风险因子进行了讨论。由于该原因,关于CIP/CIM的特异性治疗尚未知。由文献可以看出许多作者认为对SIRS和脓毒症的积极治疗(aggressivetherapy)(“早期目标导向治疗”)是CIP/CIM治疗中最重要的部分。此外,强化胰岛素治疗可以降低发病率44%,并且另一种治疗选择是在静脉内施用免疫球蛋白(M.Alb,S.Hirner,T.Luecke,Intensivmed.Notfallmed.Schmerzther.2007,4,250-258)。
本发明的另一个背景是通过用于静脉内施用的脂肪乳剂或通过含脂质的饮食产品人工喂养重症特护患者的领域。
如果不可能进行或在医学上禁忌正常的口服喂养,则使用用于肠胃外营养的脂肪乳剂来以静脉内可接受剂型提供脂肪。现有技术中常见的脂肪乳剂由植物油,诸如红花油或大豆油制备;在一些情形中,它们另外含有中链脂肪酸的甘油三酯(也称为中链甘油三酯(MCT))和/或海洋来源的油(鱼油,大多数来自于冷水鱼类)。
因此DE-OS-37 21 137描述了用于肠胃外营养的脂质乳剂,其包含二十碳五烯酸甘油三酯和/或二十二碳六烯酸甘油三酯,或含有所述甘油三酯的鱼油,以及含有Ω-6脂肪酸的植物油,和MCT。
EP 0 120 169 B1公开了合成的甘油三酯,其可以在甘油分子的中心碳原子处携带多不饱和脂肪酸(优选二十碳五烯酸)。根据该定义制备的甘油酯可以用于营养,作为用于治疗营养的食物补充剂或药物。
US-4,526,902描述了包含25-75重量%二十碳五烯酸和Ω-6脂肪酸的混合物,所述Ω-6混合物用作药物或含脂肪食物诸如黄油等的成分。
US 6,740,679描述了正庚酸,其作为对于患有长链脂肪酸降解障碍的患者的能量来源。
US 2008/0132571 A1描述了用于治疗患者中分解代谢作用的制剂和方法,其中应用奇数脂肪酸及其甘油酯,以提高细胞内AMP与ATP的比率并增强AMP激活的蛋白激酶(AMPK)的活性。
几乎不知道关于CIP和CIM的有效治疗方法。另外,至今几乎不知道用于治疗脓毒症和重症特护治疗的继发性并发症,诸如CIP和/或CIM的有效营养方法。
因此,存在对用于重症特护患者的人工喂养及其伴随的营养治疗的物质和制剂的需要,并存在对用于预防和治疗CIP和/或CIM的制剂和方法的迫切需要。
在这样的背景前,本发明的目的是提供用于患危重病的,例如患脓毒症的重症特护患者的伴随营养治疗和用于预防和治疗重症特护治疗的继发性并发症,诸如CIP和/或CIM的药物制剂。
令人意外地,已经发现通过提供含具有奇数个碳原子的脂肪酸残基的甘油三酯的脂肪乳剂,可以减少所述并发症的发生频率,或减轻疾病的严重性,或缩短其病程。
发明内容
因此,本发明涉及用于预防或治疗CIP和/或CIM的药物制剂,其包含含有至少一种式(I)的甘油三酯(A)的脂肪乳剂:
其中基团R1,R2或R3中的至少一个独立地是具有5-15范围内的奇数个碳原子的烷酰基。
根据本发明要使用的脂肪乳剂的甘油三酯(A)由用脂肪酸酯化的甘油组成,所述脂肪酸中至少一个具有5-15个碳原子范围内的奇数个碳原子。
根据本发明,所述奇数烷酰基具有5-15个碳原子的链长。优选地,它们是源自以下脂肪酸中的一种或多种的烷酰基,所述脂肪酸选自由以下各项组成的组:戊酸(pentanoicacid)(C5:0,正戊酸(n-valeric acid)),庚酸(heptanoic acid)(C7:0,庚酸(enanthicacid)),壬酸(nonanoic acid)(C9:0,壬酸(pelargonic acid)),十一烷酸(undecanoicacid)(C11:0,十一酸(undecylic acid)),十三烷酸(tridecanoic acid)(C13:0,十三酸(tridecylic acid))和十五烷酸(pentadecanoic acid)(C15:0,十五酸(pentadecylicacid))。
优选地,甘油三酯(A)中的基团R1,R2或R3中的至少一个独立地具有5-9个碳原子的链长。
更优选地,甘油三酯(A)中的基团R1,R2或R3中的至少一个独立地是正庚酰基,即由酯化的甘油组成的甘油三酯,其中至少1个,优选至少2个羟基被庚酸酯化。
具体地,甘油三酯(A)是三庚酸甘油酯(triheptanoin),即,其中三个羟基被正庚酸酯化的甘油。
甘油三酯(A)的合成是技术人员所熟悉的。获得的奇数脂肪酸(戊酸、庚酸、壬酸、十一烷酸、十三烷酸和十五烷酸)可商购自例如西格玛化学公司(Sigma Chemicals Co)。而且,存在许多关于甘油三酯(A)的不同变体的商业供应来源,例如,三庚酸甘油酯可作为Special Oil 107购自Condea Chemie GmbH(Witten,德国)。三壬酸甘油酯(Trinonanoin)、十一碳酸甘油三酯或十五碳酸甘油三酯可以例如由Chemos GmbH(Regenstauf,德国)供应。除根据本发明具有5-15的奇数碳数的必需脂肪酸残基以外,甘油三酯(A)还可以包含其他,偶数脂肪酸残基。在该情形中,含有这样的甘油三酯(A)的脂肪乳剂在根据本发明的药物制剂中是优选的,所述甘油三酯(A)中至少一个脂肪酸残基由Ω-3脂肪酸和/或Ω-6脂肪酸衍生。Ω-3脂肪酸和Ω-6脂肪酸是生物学必需的结构单元/营养物,其是人类生物体自身完全不能产生并起前列腺素、类二十烷酸和细胞膜的结构组分的前体的作用。植物来源的多种油包括大豆油和红花油起Ω-6脂肪酸来源的作用;现有技术包括它们用于制备静脉内脂肪乳剂的应用。现有技术还包括静脉内脂肪乳剂中作为Ω-3脂肪酸来源的海洋来源的油(“鱼油”)的加工(EP-A-0 298 293),其中高度纯化的鱼油浓缩物是优选的,其获自冷水鱼类,诸如鲑鱼、鲱鱼、沙丁鱼或鲭鱼。它们的Ω-3脂肪酸含量优选是40%以上。
进一步优选的是这样的甘油三酯(A),其中至少一个脂肪酸残基选自由以下各项组成的组:中链脂肪酸(例如,辛酸C8:0,癸酸C10:0,月桂酸C12:0),长链饱和脂肪酸(例如,肉豆蔻酸C14:0,棕榈酸C16:0,硬脂酸C18:0),单不饱和脂肪酸(棕榈油酸C16:1,油酸C18:1),Ω-3型和Ω-6型多不饱和脂肪酸,例如,二十碳五烯酸(EPA,C20:5 Ω-3),二十二碳六烯酸(DHA,C22:6 Ω-3),亚油酸(LA,C18:2 Ω-6)或γ-亚麻酸(GLA,C18:3 Ω-6)。
在本发明的进一步优选的实施方案中,甘油三酯(A)为随机结构化的脂质的形式,具有奇碳数的烷酰基残基和具有偶碳数的烷酰基残基随机分布在甘油三酯分子(A)的sn-1,sn-2和sn-3位置中。备选地和特别优选地,甘油三酯(A)为化学定义结构化的脂质的形式,即存在具有奇碳数的烷酰基残基在甘油三酯分子的sn-1和sn-3位置和具有偶碳数的烷酰基残基在sn-2位置的化学定义的分布。
在其中根据本发明使用的脂肪乳剂整体或部分地包含化学定义的或随机结构化的脂质的情况下,植物油优选起作为Ω-6脂肪酸来源的作用,且鱼油起作为Ω-3脂肪酸来源的作用,从而制备所述结构化的脂质。随机结构化的甘油三酯可以,例如,通过用由链长为5-15的奇数脂肪酸组成的甘油三酯化学转酯化所需植物油和/或鱼油的混合物而获得。在化学定义结构化的脂质的情形中,转酯化由相同的基材酶促地实现。
在本发明的进一步优选的实施方案中,根据本发明的药物制剂包含脂肪乳剂,所述脂肪乳剂包含至少一种与(A)不同的另外的甘油三酯(B)。
优选地,甘油三酯(B)包括海洋或植物来源的甘油三酯。由于一方面由鱼油或植物油回收纯Ω-3或Ω-6脂肪酸或化学合成这些脂肪酸非常复杂和昂贵,同时另一方面所述的海洋或植物来源的油具有高含量的相应的脂肪酸,所以根据本发明不需要从这些油中分离Ω-3或Ω-6脂肪酸或含有Ω-3或Ω-6脂肪酸的甘油三酯,而是这些油可以原样地用于制备根据本发明要使用的脂肪乳剂。
鱼油的使用和特别是大豆油或红花油的使用也自然地提供长链饱和脂肪酸,诸如如上所述的代表性的肉豆蔻酸、棕榈酸和硬脂酸,以及还有油酸,其是单不饱和的并包含在海洋油中并且也以特别高的浓度包含在橄榄油中。
中链脂肪酸或甘油三酯作为辛酸和癸酸,即以超过90%(基于总脂肪酸含量)包含在半合成的MCT油(Miglyol oil)中。在该形式中,它们特别适合于用作根据本发明要使用的脂肪乳剂中的甘油三酯(B)。
在优选的实施方案中,根据本发明的药物制剂包括这样的乳剂,所述乳剂除甘油三酯(A)外还包含至少一种其他的甘油三酯(B),所述甘油三酯(B)包含选自由以下各项组成的组的至少一个脂肪酸残基:中链脂肪酸(例如,辛酸C8:0,癸酸C10:0,月桂酸C12:0),长链饱和脂肪酸(例如,肉豆蔻酸C14:0,棕榈酸C16:0,硬脂酸C18:0),单不饱和脂肪酸(棕榈油酸C16:1,油酸C18:1),型和型多不饱和脂肪酸,例如,二十碳五烯酸(EPA,C20:5Ω-3),二十二碳六烯酸(DHA,C22:6 Ω-3),亚油酸(LA,C18:2 Ω-6)或γ-亚麻酸(GLA,C18:3 Ω-6)。
在本发明的进一步优选的实施方案中,甘油三酯(A)的量是基于乳剂中全部甘油三酯的总重量的50-80重量%,更优选60-70重量%。
优选地,根据本发明的药物制剂包括基于总药物制剂的5-30重量%,更优选10-20重量%的量的甘油三酯。
除甘油三酯(A)和任选地其他甘油三酯/脂质以外,根据本发明的药物制剂的脂肪乳剂有利地包含注射用水以及与制备静脉内脂肪乳剂的技术发展水平相对应的另外的辅剂和添加剂,例如乳化剂、辅助乳化剂、稳定剂和用于调节等渗压性的合适物质。
生理学良好耐受的乳化剂,诸如动物或植物来源的磷脂,作为所述乳化剂使用。优选采用纯化的卵磷脂,诸如大豆卵磷脂或蛋黄卵磷脂或由其获得的部分级分。根据本发明使用的乳剂的磷脂含量分别基于乳剂总重量优选为0.4-2.0重量%,优选0.6-1.5重量%。
此外,可以使用辅助乳化剂,诸如长链脂肪酸的碱性盐(诸如硬脂酸钠,油酸钠等),或,作为单独的辅助乳化剂或与其他,胆固醇或胆固醇酯(例如,胆固醇乙酸酯)组合使用。如果长链脂肪酸的碱性盐作为辅助乳化剂使用,并且也在单独或与其他辅助乳化剂组合使用胆固醇或胆固醇酯的情形中,它们的浓度分别基于乳剂总重量为0.01重量%-0.1重量%,优选0.02-0.04重量%。
特别地,如果其含有多不饱和脂肪酸,诸如Ω-3或Ω-6脂肪酸,则根据本发明的药物制剂的脂肪乳剂可以富含抗氧化剂,其保护以防止不希望的过氧化物的形成。首先,维生素E(α-,β-或γ-生育酚)和维生素C(例如,作为抗坏血酸棕榈酸酯)可以用作抗氧化剂,其中维生素E和C或它们的异构体或衍生物可以是单独的或组合的。取决于根据本发明的制剂中的长链脂质,特别是多不饱和脂质的含量,抗氧化剂的重量比例是分别基于根据本发明要使用的乳剂的总重量为0.002-0.03%(α-生育酚)或0.001-0.015%(抗坏血酸棕榈酸酯)。
在特殊实施方案中,根据本发明的药物制剂中的根据本发明要使用的脂肪乳剂另外含有分别基于乳剂的总重量优选0.01-0.1重量%的量的L-肉毒碱。
在另外的实施方案中,根据本发明的制剂可以另外包含维生素生物素和/或钴胺素。它们的浓度是1-10mg生物素或0.1-1mg钴胺素/100g制剂的脂质级分。
脂肪乳剂的等渗化作用优选借助于多元醇,诸如甘油,木糖醇或山梨糖醇实现,所述多元醇以分别基于乳剂总重量优选2-3重量%的量应用。甘油起优选的等渗剂的作用。
根据本发明的药剂以药学有效量施用。优选地,药学有效量,即为了避免严重的疾病,例如,脓毒症,的并发症和它们的重症特护医学治疗,为了减轻其强度和缩短其持续时间而与根据本发明的药物制剂一起供应的甘油三酯(A)的量是1-2g/kg体重/日。该供应优选地在24小时内/日连续实施,但是也可以分配为若干部分,其中不应该超过0.25g脂质/kg体重/小时的输注速度。一般需要若干天的中长期施药,以获得根据本发明的效果。
根据本发明的药物制剂作为完全肠胃外或组合肠胃外/肠内营养的成分来应用,如适用于严重疾病,例如脓毒症重症特护患者,所述患者显示出复杂的疾病过程或明显的或危急的神经病。根据本发明的乳剂的高能量含量在肠胃外或组合肠内/肠胃外营养的总热量供应中要加以考虑。取决于根据本发明的脂肪乳剂的实施方案,即与或不与一定比例的必需脂肪酸(Ω-3或Ω-6)一起应用的实施方案,后者不需要另外补充。尤其是因为乳剂中特别优选存在Ω-3脂肪酸残基及其抗炎症特征,可以获得协同效果,并且另外促进康复过程。
本发明还涉及包含式(I)的甘油三酯(A)的等渗脂肪乳剂:
其中基团R1,R2或R3中的至少一个是具有5-15范围内的奇数个碳原子的烷酰基,所述等渗脂肪乳剂包含至少一种与(A)不同的另外的甘油三酯(B)并具有选自由以下各项组成的组的至少一个脂肪酸残基:中链脂肪酸包括辛酸,癸酸或月桂酸,长链饱和脂肪酸包括肉豆蔻酸,棕榈酸或硬脂酸,单不饱和脂肪酸包括棕榈油酸或油酸,以及Ω-3型和Ω-6型多不饱和脂肪酸包括二十碳五烯酸,二十二碳六烯酸,亚油酸和γ-亚麻酸。
根据本发明的等渗脂肪乳剂的其他优选实施方案与根据本发明的药物制剂中的根据本发明要使用的脂肪乳剂相对应。
本发明还涉及根据本发明的等渗脂肪乳剂作为饮食产品的应用。为了该目的,等渗脂肪乳剂优选用于肠内营养。
本发明还涉及一种饮食产品,其包含至少一种式(I)的甘油三酯(A)。优选地,所述饮食产品包含根据本发明的等渗脂肪乳剂。
本发明还涉及根据本发明的等渗脂肪乳剂或包含至少一种式(I)的甘油三酯(A)的脂肪乳剂或根据本发明的药物制剂在人工喂养脓毒症重症特护患者和/或在肠胃外营养中的应用。
本发明还涉及一种药物,其包含至少一种式(I)的甘油三酯(A)和至少一种与(A)不同的其他甘油三酯(B):
在式(I)中基团R1,R2或R3中的至少一种独立地是具有5-15范围内的奇数个碳原子的烷酰基。优选地,所述药物包含根据本发明的等渗脂肪乳剂。
为了制备根据本发明的药物制剂和根据本发明的等渗脂肪乳剂以及根据本发明的药物,将如下表中所示的亲脂性成分1-9(根据制备实施例的需要)通过Ultra-Turrax均质器粗略地混合和分散。随后,加入亲水性成分10-13,利用油酸钠或硬脂酸钠和NaOH作为水性溶液,并利用较后提到的成分将该初始混合物的pH调节至8.0-9.0的值。所述混合物的实际均质化作用随后在高压均质器中,在约400kg/cm2压力下实现。将形成的乳剂填充至合适的玻璃或塑料容器中并通过通常应用于肠胃外制剂的方法进行加热灭菌。由此产生的是无菌、无热原且稳定的脂肪乳剂,其具有小于0.5μm的平均粒度和在室温下至少24个月的保存期。
实施例
1)对于中链甘油三酯(辛酸/癸酸甘油三酯)的部分,使用可商购的混合物(Miglyol812,Sasol Germany GmbH,Witten,德国)。
2)作为结构化脂质,采用由在甘油三酯的sn-1和sn-3位置中被庚酸酯化的甘油和在sn-2位置中的二十碳五烯酸(EPA;C20:5 Ω-3)组成的甘油三酯(A)。
Claims (11)
1.药物制剂在制备用于预防或治疗危重病性多发性神经病和/或危重病性肌病的药物中的应用,所述药物制剂包含含有至少一种式(I)的甘油三酯(A)的脂肪乳剂:
其中基团R1,R2或R3中的至少一个独立地是具有5-15范围内的奇数个碳原子的烷酰基。
2.根据权利要求1的应用,其特征在于所述脂肪乳剂包含至少一种与(A)不同的另外的甘油三酯(B)并具有选自由中链脂肪酸、长链饱和脂肪酸、单不饱和脂肪酸以及Ω-3型和Ω-6型多不饱和脂肪酸组成的组的至少一个脂肪酸残基,其中所述中链脂肪酸是辛酸、癸酸或月桂酸,所述长链饱和脂肪酸是肉豆蔻酸、棕榈酸或硬脂酸,所述单不饱和脂肪酸是棕榈油酸或油酸,并且所述Ω-3型和Ω-6型多不饱和脂肪酸是二十碳五烯酸、二十二碳六烯酸、亚油酸或γ-亚麻酸。
3.根据权利要求1的应用,其特征在于甘油三酯(A)中的基团R1,R2或R3中的至少一个独立地具有5-9个碳原子的链长。
4.根据权利要求1的应用,其特征在于甘油三酯(A)中的基团R1,R2或R3中的至少一个独立地是正庚酰基。
5.根据权利要求1的应用,其特征在于所述甘油三酯(A)是三庚酸甘油酯。
6.根据权利要求1-5中任一项的应用,其特征在于所述甘油三酯的量是基于总药物制剂的5-30重量%。
7.根据权利要求6的应用,其特征在于所述甘油三酯的量是基于总药物制剂的10-20重量%。
8.根据权利要求1-5中任一项的应用,其特征在于甘油三酯(A)的量是基于所述脂肪乳剂中全部甘油三酯的总重量的50-80重量%。
9.根据权利要求1-5中任一项的应用,其特征在于甘油三酯(A)的量基于所述脂肪乳剂中全部甘油三酯的总重量的是60-70重量%。
10.包含式(I)的甘油三酯(A)的脂肪乳剂或如权利要求1-9中任一项定义的药物制剂在制备用于人工喂养脓毒症重症特护患者的肠胃外营养中的应用:
在式(I)中基团R1,R2或R3中的至少一个是具有5-15范围内的奇数个碳原子的烷酰基。
11.包含式(I)的甘油三酯(A)的脂肪乳剂或如权利要求1-9中任一项定义的药物制剂在制备肠胃外营养剂中的应用:
在式(I)中基团R1,R2或R3中的至少一个是具有5-15范围内的奇数个碳原子的烷酰基。
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CN200980145702.6A Ceased CN102215839B (zh) | 2008-11-18 | 2009-11-09 | 用于人工喂养重病的重症特护患者的脂肪乳剂 |
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US (2) | US20110207819A1 (zh) |
EP (1) | EP2355813B1 (zh) |
JP (1) | JP2012509292A (zh) |
KR (1) | KR20110084513A (zh) |
CN (1) | CN102215839B (zh) |
BR (1) | BRPI0921917B8 (zh) |
CA (1) | CA2739390C (zh) |
DE (1) | DE102008057867A1 (zh) |
ES (1) | ES2561207T3 (zh) |
MX (1) | MX338223B (zh) |
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DE102009013914B4 (de) * | 2009-03-19 | 2011-05-05 | Bruker Daltonik Gmbh | Kalibriersubstanzen für Atmosphärendruck-Ionenquellen |
AU2012211854A1 (en) * | 2011-01-31 | 2013-08-08 | Nagoya Industrial Science Research Institute | Prophylactic or therapeutic drug for peripheral neuropathy caused by anticancer agent |
US8183227B1 (en) | 2011-07-07 | 2012-05-22 | Chemo S. A. France | Compositions, kits and methods for nutrition supplementation |
US8168611B1 (en) | 2011-09-29 | 2012-05-01 | Chemo S.A. France | Compositions, kits and methods for nutrition supplementation |
CN106900888B (zh) * | 2015-12-23 | 2021-12-24 | 丰益(上海)生物技术研发中心有限公司 | 含有奇数碳脂肪酸结构脂的油脂组合物及其应用 |
NZ749389A (en) * | 2016-06-08 | 2022-12-23 | Sunregen Healthcare Ag | Lipids with odd number of carbon atoms and their use as pharmaceutical composition or nutritional supplement |
CN109602704A (zh) * | 2019-01-23 | 2019-04-12 | 广东嘉博制药有限公司 | 丁酸氯维地平脂肪乳注射液及其制备工艺 |
CN110326789A (zh) * | 2019-06-11 | 2019-10-15 | 上海互众药业有限公司 | 一种脂肪乳食品补充液及其制备方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20030162833A1 (en) * | 2001-08-01 | 2003-08-28 | Roe Charles R. | Fatty acid treatment for cardiac patients |
US6740679B1 (en) * | 1999-02-05 | 2004-05-25 | Baylor University Medical Center | Nutritional supplement or pharmaceutical preparation comprising triglycerides with seven-carbon fatty acid |
WO2004103307A2 (en) * | 2003-05-20 | 2004-12-02 | Baylor Research Institute | Method of use of five and fifteen carbon fatty acids |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2515174A1 (fr) | 1981-10-23 | 1983-04-29 | Roussel Uclaf | Nouveaux triglycerides, procede de preparation et d'applications en dietetique et en therapeutique |
US4526902A (en) | 1983-10-24 | 1985-07-02 | Century Laboratories, Inc. | Combined fatty acid composition for treatment or prophylaxis of thrombo-embolic conditions |
DE3721137A1 (de) | 1987-06-26 | 1989-01-05 | Dietl Hans | Fettemulsion zur intravenoesen anwendung |
DE3722540A1 (de) | 1987-07-08 | 1989-01-19 | Fresenius Ag | Fettemulsion, verfahren zu ihrer herstellung und ihre verwendung |
DE3734147C2 (de) * | 1987-10-09 | 1998-10-29 | Braun Melsungen Ag | Isotone omega-3-fettsäurenhaltige Fettemulsion und ihre Verwendung |
AU682894B2 (en) * | 1993-10-28 | 1997-10-23 | Institut National De La Recherche Agronomique | Composition based on amino acids intended for the treatment of sepsis or of an attack bringing about an inflammatory reaction, in animals and man |
RU2155612C2 (ru) * | 1997-01-30 | 2000-09-10 | Скрипченко Наталия Викторовна | Способ лечения острых инфекционных заболеваний периферической нервной системы |
IL144645A0 (en) * | 1999-02-05 | 2002-05-23 | Baylor University Medical Ct | Nutritional supplement or pharmaceutical preparation comprising triglycerides with seven-carbon fatty acid |
BR0213183A (pt) * | 2001-10-11 | 2004-08-31 | Applied Research Systems | Uso de ativadores gp130 em neuropatia diabética |
WO2006014353A2 (en) * | 2004-07-02 | 2006-02-09 | Baylor Research Institute | Glycogen or polysaccharide storage disease treatment method |
EP1723944B1 (de) * | 2005-02-16 | 2007-04-04 | Dr. Streatmans Chemische Produktion GmbH | Kosmetische und dermatologische Lichtschutzformulierungen mit einem Gehalt an chemischen UV-Filtern und Triheptanonin |
KR20150038525A (ko) | 2006-09-26 | 2015-04-08 | 베일러 리서치 인스티튜트 | 영양물 센서 |
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2008
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- 2009-11-09 ES ES09760502.6T patent/ES2561207T3/es active Active
- 2009-11-09 US US13/126,245 patent/US20110207819A1/en not_active Abandoned
- 2009-11-09 CN CN200980145702.6A patent/CN102215839B/zh not_active Ceased
- 2009-11-09 WO PCT/EP2009/064839 patent/WO2010057804A1/de active Application Filing
- 2009-11-09 KR KR1020117010418A patent/KR20110084513A/ko not_active Application Discontinuation
- 2009-11-09 BR BRPI0921917A patent/BRPI0921917B8/pt active IP Right Grant
- 2009-11-09 RU RU2011124887/15A patent/RU2528108C2/ru active
- 2009-11-09 CA CA2739390A patent/CA2739390C/en active Active
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6740679B1 (en) * | 1999-02-05 | 2004-05-25 | Baylor University Medical Center | Nutritional supplement or pharmaceutical preparation comprising triglycerides with seven-carbon fatty acid |
US20030162833A1 (en) * | 2001-08-01 | 2003-08-28 | Roe Charles R. | Fatty acid treatment for cardiac patients |
WO2004103307A2 (en) * | 2003-05-20 | 2004-12-02 | Baylor Research Institute | Method of use of five and fifteen carbon fatty acids |
Also Published As
Publication number | Publication date |
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JP2012509292A (ja) | 2012-04-19 |
CA2739390A1 (en) | 2010-05-27 |
CA2739390C (en) | 2016-05-03 |
BRPI0921917B1 (pt) | 2020-08-25 |
DE102008057867A1 (de) | 2010-05-20 |
MX338223B (es) | 2016-04-08 |
US20110207819A1 (en) | 2011-08-25 |
ES2561207T3 (es) | 2016-02-25 |
US20160051506A1 (en) | 2016-02-25 |
MX2011005201A (es) | 2011-06-01 |
WO2010057804A1 (de) | 2010-05-27 |
EP2355813A1 (de) | 2011-08-17 |
EP2355813B1 (de) | 2015-11-04 |
KR20110084513A (ko) | 2011-07-25 |
CN102215839A (zh) | 2011-10-12 |
RU2528108C2 (ru) | 2014-09-10 |
BRPI0921917A2 (pt) | 2015-12-29 |
RU2011124887A (ru) | 2012-12-27 |
BRPI0921917B8 (pt) | 2021-05-25 |
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