CN104473942A - 一种抗帕金森氏病的药物组合物 - Google Patents

一种抗帕金森氏病的药物组合物 Download PDF

Info

Publication number
CN104473942A
CN104473942A CN201410759728.2A CN201410759728A CN104473942A CN 104473942 A CN104473942 A CN 104473942A CN 201410759728 A CN201410759728 A CN 201410759728A CN 104473942 A CN104473942 A CN 104473942A
Authority
CN
China
Prior art keywords
rasagiline
parkinson disease
resistance
medicine composition
mice
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201410759728.2A
Other languages
English (en)
Inventor
侯琳
张峥
张金玉
律玉强
王月华
马千会
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Qingdao University
Original Assignee
Qingdao University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Qingdao University filed Critical Qingdao University
Priority to CN201410759728.2A priority Critical patent/CN104473942A/zh
Publication of CN104473942A publication Critical patent/CN104473942A/zh
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A61K31/661—Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
    • A61K31/6615—Compounds having two or more esterified phosphorus acid groups, e.g. inositol triphosphate, phytic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

本发明属于医药技术领域，具体涉及一种抗帕金森氏病的药物组合物。一种抗帕金森氏病的药物组合物，由六磷酸肌醇和雷沙吉兰按30～300：1的比例组成。本发明的用于抗帕金森氏病的药物组合物可用于早期和中晚期的帕金森氏病患者，加强神经元的保护作用，缓解运动障碍，延缓症状的发展，并且副作用小，安全可靠。

Description

一种抗帕金森氏病的药物组合物
技术领域
本发明属于医药技术领域，具体涉及一种抗帕金森氏病的药物组合物。
背景技术
雷沙吉兰（Rasagiline），一种单胺氧化酶的不可逆抑制剂，作为早期帕金森病的治疗单药和作为中、晚期帕金森病与左旋多巴（Levodoba）联合用药。化学名为(R)-2，3-二氢-N-2-炔丙基-1H-茚-1-胺甲磺酸盐，分子式：C12H13N·CH3SO3H，分子量：267.34。本药为不可逆性、选择性单胺氧化酶(MAO)-B抑制药。MAO为一种参与脑内多巴胺代谢性降解的酶，该酶受抑后，多巴胺的传递信号增强，对帕金森氏病有益，也可增强左旋多巴的作用。但长期使用或剂量增大会导致较强的副作用，包括1. 心绞痛等心血管系统症状；2.可见头痛、眩晕、抑郁等中枢神经系统症状。3.呼吸系统：可见鼻炎。4.肌肉骨骼系统：可见颈痛、关节痛、关节炎。5.泌尿生殖系统：可见尿急。6.胃肠道：可见消化不良、食欲缺乏。7. 血液：可见白细胞减少。8.皮肤：可见皮疹、黑色素瘤。9.眼：可见结膜炎。
发明内容
本发明的目的是克服现有用于抗帕金森氏病（PD）药物长期使用副作用较大的不足，提供一种副作用较小，适合长期使用且疗效更强的用于抗帕金森氏病的药物组合物。
为了实现上述目的，本发明采用的技术方案是：一种用于抗帕金森氏病的药物组合物，由六磷酸肌醇和雷沙吉兰按30～300：1的比例组成。
六磷酸肌醇是天然植物中的活性成分，又名植酸，因为体内也含有肌醇，故长期服用副作用较小。六磷酸肌醇作为二价金属离子螯合剂，对于铁离子、铜离子等有极强的螯合作用，在铁沉积为重要发病机理的帕金森氏病中，植酸具有积极的抗帕金森氏病作用，同时植酸还有抗炎、提高机体免疫力等作用，均可预防和延缓PD的发生，是一种副作用极小的药物。与单胺氧化酶抑制剂雷沙吉兰联合使用可具有协同作用，同时减少雷沙吉兰的剂量，减少雷沙吉兰的副反应，适合长期使用。
本发明的一种用于抗帕金森氏病的药物组合物，将六磷酸肌醇和单胺氧化酶抑制剂雷沙吉兰按一定比例配合，可更好地保护神经元细胞，延缓病情的发展，同时减少常规雷沙吉兰的用量，从而减轻雷沙吉兰的副作用，可有效地缓解帕金森氏病动物模型中黑质多巴胺细胞的损伤，作用强于单独使用雷沙吉兰组，并且未观察到明显的副作用。
附图说明
图1是采用本发明的用于抗帕金森氏病的药物组合对帕金森氏病模型小鼠行为学影响；
图2是帕金森氏病模型小鼠酪氨酸羟化酶免疫组化染色结果。
具体实施方式
实施例1 一种用于抗帕金森氏病的药物组合物，由六磷酸肌醇和雷沙吉兰按30：1的比例组成。
实施例2一种用于抗帕金森氏病的药物组合物，由六磷酸肌醇和雷沙吉兰按100：1的比例组成。
实施例3一种用于抗帕金森氏病的药物组合物，由六磷酸肌醇和雷沙吉兰按300：1的比例组成。
实施例4 采用实施例1和3的用于抗帕金森氏病的药物组合物作用于小鼠帕金森氏病模型的行为学效果实验观察。
实验动物：雄性C57/BL6小鼠，8周龄，体重20～25g；小鼠每笼3只，7～9只/组，均侍养于室温22～25℃的环境中，12h昼夜节律，自由进食和饮水，适应5天。
用转棒法(rotarod法)观察MPTP诱发帕金森氏病(PD)模型小鼠的行为学改变：C57/BL6小鼠提前用转棒法训练3天，将运动不协调的小鼠剔除后，随机分为5组，每组9只。除正常对照组腹腔注射生理盐水外；MPTP组，每日固定时间腹腔注射MPTP；雷沙吉兰组，雷沙吉兰灌胃，同时腹腔注射MPTP；药物组合组1、2，分别给予实施例1和3的药物组合灌胃，同时腹腔注射MPTP。以上处理每天1次，连续4天，于第1、2、3、4、5天在腹腔注射MPTP1h后将各组小鼠用转棒法进行行为学检测。具体方法如下：将小鼠置于正在运转的转棒仪上，开始计时。记录小鼠在转棒上停留的时间作为潜伏期(即第一次掉落的时间)和2min内掉落的次数，以此表示其运动协调能力。每只小鼠测定3次，每次间隔30min，取平均值。数据用均数标准差表示，采用SPSS13.0统计软件进行单因素方差分析。
结果如图1所示，第5天转棒法检测各组小鼠行为学结果显示，MPTP帕金森氏模型组小鼠旋转时间明显低于正常对照组，***等于P〈0.001；添加了雷沙吉兰的小鼠旋转时间高于MPTP帕金森氏模型组，**等于P〈0.01；添加了本发明的药物组合物的小鼠旋转时间分别高于雷沙吉兰组，**等于P〈0.01。
实施例5本发明的用于抗帕金森氏病的药物组合物作用于小鼠帕金森氏病模型的小鼠酪氨酸羟化酶免疫组化染色。
实验方法：将上述实施例4的受试小鼠脑组织块进行冠状连续切片，片厚10μm ，0.3%的H2O2稀释100倍，37℃孵育15min，以去除内源性过氧化物酶。0.01M的PBS 冲洗3次，每次5min；加入抗原抗体修复液微波炉高火修复5min后冷却至室温；10%山羊血清37℃孵育15min，吸去封闭血清后，滴加TH抗体(1：200稀释液)置于湿盒中37℃ 孵育2h，PBS冲洗3次，每次5min；滴加辣根过氧化物酶标记的二抗37℃孵育40 min；PBS冲洗3次，每次5min；DAB显色10～15 min；酒精梯度脱水，二甲苯透明，中性树胶封片。镜检显色后进行TH阳性细胞计数，分别计数每张切片上注射侧和未注射侧的TH阳性细胞总数。染色过程中做替代对照实验，用PBS取代一抗，其他染色步骤都相同，实验结果为阴性。
小鼠酪氨酸羟化酶免疫组化染色结果如图2显示，MPTP帕金森氏病模型组（MPTP组）黑质细胞染色数量明显减少，表明黑质多巴胺细胞与对照组相比明显减少，而添加了雷沙吉兰或本发明的药物组合物的小鼠在MPTP损伤时黑质多巴胺细胞数量与MPTP损伤组相比显著增多，表明雷沙吉兰和本发明的药物组合物对MPTP损伤的神经细胞有保护作用，并且本发明的药物组合组的黑质多巴胺细胞的数量多于雷沙吉兰组，说明本发明的药物组合物对神经细胞的保护作用优于雷沙吉兰。
综上所述，本发明的用于抗帕金森氏病的药物组合物可用于早期和中晚期的帕金森氏病患者，加强神经元的保护作用，缓解运动障碍，延缓症状的发展，并且副作用小，安全可靠。

Claims (1)

1.一种用于抗帕金森氏病的药物组合物，其特征在于：由六磷酸肌醇和雷沙吉兰按30～300：1的比例组成。
CN201410759728.2A 2014-12-12 2014-12-12 一种抗帕金森氏病的药物组合物 Pending CN104473942A (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201410759728.2A CN104473942A (zh) 2014-12-12 2014-12-12 一种抗帕金森氏病的药物组合物

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201410759728.2A CN104473942A (zh) 2014-12-12 2014-12-12 一种抗帕金森氏病的药物组合物

Publications (1)

Publication Number Publication Date
CN104473942A true CN104473942A (zh) 2015-04-01

Family

ID=52748646

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201410759728.2A Pending CN104473942A (zh) 2014-12-12 2014-12-12 一种抗帕金森氏病的药物组合物

Country Status (1)

Country Link
CN (1) CN104473942A (zh)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5206226A (en) * 1990-10-24 1993-04-27 Robert Sabin Method of treatment of Parkinsons's disease using phytic acid
CN102105169A (zh) * 2008-06-06 2011-06-22 图必制药公司 用于治疗帕金森病的药物组合物
CN103127121A (zh) * 2011-12-02 2013-06-05 苏州法莫生物技术有限公司 雷沙吉兰/叶酸类化合物的药物组合物及其用途

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5206226A (en) * 1990-10-24 1993-04-27 Robert Sabin Method of treatment of Parkinsons's disease using phytic acid
CN102105169A (zh) * 2008-06-06 2011-06-22 图必制药公司 用于治疗帕金森病的药物组合物
CN103127121A (zh) * 2011-12-02 2013-06-05 苏州法莫生物技术有限公司 雷沙吉兰/叶酸类化合物的药物组合物及其用途

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
QI XU 等: "Neuroprotective effect of the natural iron chelator, phytic acid in a cell culture model of Parkinson’s disease", 《TOXICOLOGY》 *
QI XU 等: "Phytic Acid Protects against 6-Hydroxydopamine-Induced Dopaminergic Neuron Apoptosis in Normal and Iron Excess Conditions in a Cell Culture Model", 《PARKINSON’S DISEASE》 *

Similar Documents

Publication Publication Date Title
Suárez et al. Mediterranean diet and multi-ingredient-based interventions for the management of non-alcoholic fatty liver disease
Bond et al. Tea compounds and the gut microbiome: findings from trials and mechanistic studies
Conlon et al. The impact of diet and lifestyle on gut microbiota and human health
Wang et al. Inhibition of LPS-induced oxidative damages and potential anti-inflammatory effects of Phyllanthus emblica extract via down-regulating NF-κB, COX-2, and iNOS in RAW 264.7 cells
Ortega et al. Gut microbiota metabolites in major depressive disorder—Deep insights into their pathophysiological role and potential translational applications
Hu et al. Triterpenoid saponins from Stauntonia chinensis ameliorate insulin resistance via the AMP-activated protein kinase and IR/IRS-1/PI3K/Akt pathways in insulin-resistant HepG2 cells
Liu et al. Research advances on hepatotoxicity of herbal medicines in China
Wang et al. The antidepressant-like effect of flavonoids from Trigonella foenum-graecum seeds in chronic restraint stress mice via modulation of monoamine regulatory pathways
Peralta-Marzal et al. The impact of gut microbiota-derived metabolites in autism spectrum disorders
Kadali et al. Antidepressant activity of brahmi in albino mice
Tam et al. Intestinal inflammation and alterations in the gut microbiota in cystic fibrosis: a review of the current evidence, pathophysiology and future directions
Wang et al. Diagnosis analysis of 4 TCM patterns in suboptimal health status: a structural equation modelling approach
Han et al. Gastrointestinal dysfunction in Parkinson’s disease: current and potential therapeutics
Guo et al. Effects of refined xiaoyaosan on depressive-like behaviors in rats with chronic unpredictable mild stress through neurosteroids, their synthesis and metabolic enzymes
Tian et al. Wushenziye Formula Improves Skeletal Muscle Insulin Resistance in Type 2 Diabetes Mellitus via PTP1B‐IRS1‐Akt‐GLUT4 Signaling Pathway
An et al. Ginsenosides Rg5 and Rk1 enriched cultured wild ginseng root extract bioconversion of Pediococcus pentosaceus HLJG0702: Effect on scopolamine-induced memory dysfunction in mice
Xu et al. Poria cocos polysaccharide ameliorated antibiotic-associated diarrhea in mice via regulating the homeostasis of the gut microbiota and intestinal mucosal barrier
Shi et al. Bile acids, intestinal barrier dysfunction, and related diseases
Arie et al. Grape seed extract eliminates visceral allodynia and colonic hyperpermeability induced by repeated water avoidance stress in rats
Tizabi et al. Interaction of heavy metal lead with gut microbiota: implications for autism spectrum disorder
Ilich Nutritional and behavioral approaches to body composition and low-grade chronic inflammation management for older adults in the ordinary and COVID-19 times
Chen et al. Natural garlic organosulfur compounds prevent metabolic disorder of lipid and glucose by increasing gut commensal Bacteroides acidifaciens
Akter et al. The effect of COVID-19 on gut microbiota: Exploring the complex interplay and implications for human health
Stummer et al. Role of hydrogen sulfide in inflammatory bowel disease
Ferrari et al. The Role of Bifidobacterium bifidum novaBBF7, Bifidobacterium longum novaBLG2 and Lactobacillus paracasei TJB8 to improve mechanisms linked to neuronal cells protection against oxidative condition in a gut-brain axis model

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
WD01 Invention patent application deemed withdrawn after publication

Application publication date: 20150401