CN103054040B - Pharmaceutical composition for increasing hypoxia tolerance - Google Patents

Pharmaceutical composition for increasing hypoxia tolerance Download PDF

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CN103054040B
CN103054040B CN201310010730.5A CN201310010730A CN103054040B CN 103054040 B CN103054040 B CN 103054040B CN 201310010730 A CN201310010730 A CN 201310010730A CN 103054040 B CN103054040 B CN 103054040B
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pharmaceutical composition
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漆又毛
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HANGZHOU ADAMERCK MEDICINE TECHNOLOGY Co Ltd
Zhejiang Adamerck Biopharmlabs Inc
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HANGZHOU ADAMERCK MEDICINE TECHNOLOGY Co Ltd
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Abstract

The invention provides a pharmaceutical composition for increasing hypoxia tolerance, which is composed of natural amino acids, natural extracts and alpha-lipoic acid. The natural amino acids in the composition comprise ornithine or salts thereof and citrulline or salts thereof. The natural extracts are one or more substances selected from a safflower extract, a gingko extract or a Chinese-date extract. The pharmaceutical composition disclosed by the invention is capable of obviously increasing acute cerebral ischemic hypoxia survival time and increasing the oxygen utilization rate of tissue cells and has the function of increasing hypoxia tolerance. The pharmaceutical composition disclosed by the invention is prepared into troches or granules, which are applied to being taken by students, brain workers, the old and weak and sub-healthy people caused by hypoxia.

Description

A kind of Pharmaceutical composition that improves anoxia endurance
Technical field
The invention belongs to field of health care food, relate to a kind of Pharmaceutical composition that can improve anoxia endurance, it is made up of natural amino acid and natural extract and alpha-lipoic acid.
Background technology
Keen competition, nervous rhythm, excessive requires mental skill and unbalanced dietary structure, and environmental pollution, cause that body declines to the ability of utilizing of oxygen, presents more than one three performances of going down, tired many, vigor goes down, and respond goes down, and adaptive capacity goes down.Show as " Hypoxic syndrome " phenomenons such as weak, fatiguability, emotional instability, aging, impotence, insomnia.
Arginine has the effect of the anoxia endurance of raising, treats the diseases such as Hypoxic Pulmonary Hypertension in Rats as can be used for.But because the arginine half-life of taking in is very short, only 1 hour, therefore directly supplement arginine and fail effectively to increase the arginine concentration in body inner blood and cell.Only have by taking citrulling, make its rapid delivery profile to various cells in blood and body, under enzymatic, constantly produce endogenous arginine, make arginine-level in body be able to obvious rising, remain in higher foundation level simultaneously, improved the tolerance of body to anoxic.
Date is the ripening fruits of Rhamnaceae plant jujube tree, contain polysaccharide, protein, fat, carbohydrate, vitamin A, B1, B2, C, E, P, and oleanolic acid, cyclic adenosine monophosphate, flavonoids and selenium and other trace elements, energy diastole smooth muscle, hemangiectasis, improves ischemia and hypoxia state.
Safflower main component is carthamic acid, carthamin yellow, safflower quinone etc.Research shows, Flos Carthami extract can significantly be eliminated the muscular fatigue degree that mouse movement causes, significantly strengthens muscle power, endurance, hypoxia-bearing capability and the nonspecific resistance of mouse.
Ginkgo leaf is by reducing Ca 2+level blocking-up NO abnormal metabolism, anti-glutamate neurotoxicity, and energy antagonism platelet activating factor, have protective effect to the brain tissue of hypoxic-ischemic encephalopathy (HIE).Experimental results show that, the GINKGO BILOBA EXTRACT containing in ginkgo biloba p.e has extremely strong antioxidation, can eliminate the harmful substance of organism surplus (various free radical), stops body lipid peroxidating, improve collective's immunity, improve heart and brain blood circulation, promote study, improve memory, delay senility etc.
Alpha-lipoic acid and the reduzate dihydrolipoic acid forming in vivo thereof are powerful antioxidant.Lipoic acid can be known hydroxyl free radical, hypochlorous acid, peroxynitrite and singlet oxygen.Dihydrolipoic acid can be removed superoxides, hydroperoxyl radical, renewable thioredoxin.Have and report that alpha-lipoic acid has obvious prevention and Neurotherapeutic effect to Brain Ischemia-reperfusion Injury.
summary of the invention
The object of the present invention is to provide a kind of Pharmaceutical composition that can improve anoxia endurance, described Pharmaceutical composition is made up of natural amino acid, natural extract and alpha-lipoic acid, wherein Pharmaceutical composition main active is natural amino acid, formed by two kinds of ornithine or its esters and citrulling or its esters, the two weight ratio with 3:1 to 1:3 is mixed, wherein preferred 1:2.125; Natural extract is one or more in safflower extract, ginkgo biloba extract or Fructus Jujubae extract.Natural amino acid: the weight ratio of natural extract and alpha-lipoic acid is 4:1.Natural extract mixes with the weight ratio of 1:1 with alpha-lipoic acid.
In the time selecting three kinds of natural extracts, be take safflower extract with alpha-lipoic acid: ginkgo biloba extract: Fructus Jujubae extract: alpha-lipoic acid mixes as the weight ratio of 1:1:1:1 simultaneously.
Preferred Pharmaceutical composition formula is natural amino acid: natural extract+alpha-lipoic acid is to mix with 4:1 weight ratio, is specifically made up of ornithine hydrochloride, citrulling, safflower extract, ginkgo biloba extract, Fructus Jujubae extract and alpha-lipoic acid.Wherein safflower extract, ginkgo biloba extract, Fructus Jujubae extract and alpha-lipoic acid are to mix with the weight ratio of 1:1:1:1, ornithine hydrochloride: the ratio of citrulling is 1:2.125.
Above-mentioned Pharmaceutical composition and pharmaceutic adjuvant are made the one in tablet, capsule or granule, and wherein pharmaceutic adjuvant is selected hydroxypropyl cellulose, superfine silica gel powder, dolomol and 80% ethanol.
Recommended doses of the present invention is taken orally as per unit dosage is 250 milligrams, 500 milligrams, 1000 milligrams, 1500 milligrams or 2000 milligrams containing described composition and is waited or not for the mankind, can, with 2 times or 3 times, also can do dosage adjustment with user's age and body weight every day.
Pharmaceutical composition provided by the invention can significantly increase Ischemia Injury in Brain the survival time under hypoxic condition, improves the utilization rate of histocyte to oxygen, has the function that improves anoxia endurance.Described Pharmaceutical composition is made to the one in tablet, capsule or granule, be applicable to student and mental worker, the old and the weak body void person and the sub-health population that causes due to anoxic is taken.The raw material sources of the present composition are natural component, prepare easy, be easy to absorb, have no side effect, safe, can long-term taking.
The specific embodiment
The present invention is described further in conjunction with the embodiments.
Embodiment 1 different formulations chmice acute cerebral ischemia the survival time under hypoxic condition
Dosage: 800mg/kg/ days/group.Given the test agent is prepared with redistilled water, per os gavage, continuous 7 days.
The method of inspection: last gavage after 1 hour by mouse respectively from neck by broken end only, record after mouse broken end to the dwell time of breathing of dehiscing with stopwatch.The results are shown in Table 1.
Figure 2013100107305100002DEST_PATH_IMAGE001
Embodiment 2 tablet preparations
1. table 2 Raw, replenishers and auxiliary material are crossed respectively to 80 mesh sieves, for subsequent use;
2. take raw material by formula ratio: the hydroxypropyl cellulose of citrulling, ornithine hydrochloride, safflower extract, ginkgo biloba p.e, Fructus Jujubae extract and alpha-lipoic acid and 1/2nd formula ratios is dry mixed and closes 10~15 minutes, add 80% ethanolic solution and prepare in right amount softwood;
3. granulate through 16 mesh sieves; In 60 ℃~65 ℃ oven dry, after adding glidant superfine silica gel powder, magnesium stearate lubricant and remaining disintegrant hydroxypropyl cellulose, whole grain mixes compressing tablet, dressing.
Figure 276165DEST_PATH_IMAGE002
Embodiment 3 improves the resistance to anoxic experiment of one of anoxia tolerant function experiment normal pressure
Animal used as test: select 144 of Healthy female ICR kind secondary mouse, be divided at random 4 groups by body weight, 12 every group.
Dosage design: establish 400mg/kg/d (be equivalent to be grown up per kg body weight per day recommended intake 10 times), 800mg/kg/d and tri-dosage groups of 1200mg/kg/d, establish a Normal group simultaneously.Sample is prepared with distilled water, respectively organizes the amount per os gavage of every day with 20ml/kgb wt, continuously 30d.Normal group gavage every day equivalent distilled water.
Experimental technique: last gavage is put into mouse respectively the 250ml port grinding bottle (capacity error ± 1ml) that fills 5g soda lime after 1 hour, be coated with vaseline sealing bottleneck, and timing immediately, to cease breathing as index, observe and record the resistance to the survival time under hypoxic condition of mouse normal pressure, initial data adopts SPSS statistical software first to carry out homogeneity test of variance, and variance is neat, then is used in the comparative statistics between two of mean between multiple experimental group and a control group.
Experimental result: before and after each treated animal experiment, body weight and time-to-live are in table 3.
From table 3: the weight of animals is without group difference (P>0.05) before test and after test.The resistance to the survival time under hypoxic condition of high dose group animal, higher than control group, has utmost point significant difference (P<0.01) compared with control group.
Embodiment 4 improves the poisoning survival experiment of two natrium nitrosums of anoxia tolerant function experiment
Dosage design: establish 400mg/kg/d (be equivalent to be grown up per kg body weight per day recommended intake 10 times) 800mg/kg/d and tri-dosage groups of 1200mg/kg/d, establish a Normal group simultaneously.Sample configures with distilled water, respectively organizes the amount per os gavage of every day with 20ml/kgb wt, continuously 30d.Normal group gavage every day equivalent distilled water.
Experimental technique: last gavage after 1 hour by each group of mouse respectively by 220mg/kg bw dosage by a lumbar injection natrium nitrosum (injection volume is 0.1ml/10g body weight), timing immediately, take breath stopped as index, records the mouse survival time.
Experimental result: before and after each treated animal experiment, body weight and time-to-live are in table 4.
Figure 786781DEST_PATH_IMAGE004
From table 4: before test and test afterwards the weight of animals all extend without group difference (P>0.05) each dosage group time-to-live compared with control group but there are no significant difference (P>0.05).
Embodiment 5 improves three Ischemia Injury in Brain anoxic experiments of anoxia tolerant function experiment
Dosage design: establish 400mg/kg/d (be equivalent to be grown up per kg body weight per day recommended intake 10 times)
Tri-dosage groups of 800mg/kg/d and 1200mg/kg/d, establish a Normal group, sample configures with distilled water, respectively organizes the amount per os gavage of every day with 20ml/kgb wt simultaneously, continuously 30d. Normal group gavage every day equivalent distilled water.
Experimental technique: last gavage after 1 hour by each group of mouse respectively from neck by broken end only, record after mouse broken end to the dwell time of breathing of dehiscing with stopwatch.
Before and after each treated animal experiment, after body weight and broken end, breathe dwell time in table 5 to dehiscing.
Figure DEST_PATH_IMAGE005
From table 5: the weight of animals is without group difference (P>0.05) before test and after test.Control group is compared the dwell time of breathing to dehiscing after each dosage treated animal broken end all increase, in and the high dose group dwell time of breathing all there is utmost point significant difference (P<0.01).
Brief summary: from embodiment, show 3-5, each dosage group and control group comparison, starting weight, eventually heavy difference there are no significant meaning (P>0.05), shows that this Pharmaceutical composition has no significant effect the weight of animals.
Pharmaceutical composition of the present invention can extend the time of the resistance to anoxic survival of mouse normal pressure, and result is positive.
Pharmaceutical composition of the present invention can extend the time-to-live of the poisoning anoxic of mouse natrium nitrosum, and result is positive.
Pharmaceutical composition of the present invention can extend the breathing time of chmice acute cerebral ischemia anoxic, and result is positive.
The standard judgement that improves anoxia endurance according to Ministry of Public Health's " health food check and assessment technique standard (2003) year version ", capsule of the present invention has raising anoxia tolerant function.

Claims (2)

1. one kind is improved the Pharmaceutical composition of anoxia endurance, it is characterized in that, described Pharmaceutical composition is made up of natural amino acid, natural extract and alpha-lipoic acid, wherein natural amino acid is made up of ornithine or its salt and citrulling or its salt, natural extract is selected one or more in safflower extract, ginkgo biloba extract or Fructus Jujubae extract, natural amino acid: the weight ratio of natural extract and alpha-lipoic acid is 4:1, natural extract mixes with the weight ratio of 1:1 with alpha-lipoic acid; Wherein in natural amino acid, ornithine or its salt mix with the weight ratio of 3:1 to 1:3 with citrulling or its salt.
2. a kind of Pharmaceutical composition that improves anoxia endurance according to claim 1, it is characterized in that, described Pharmaceutical composition and pharmaceutic adjuvant are made tablet, capsule or granule, and wherein pharmaceutic adjuvant is selected hydroxypropyl cellulose, superfine silica gel powder, dolomol and 80% ethanol.
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CN101433314B (en) * 2007-11-13 2012-05-30 蒋爱芳 Health care food with fatigue resistance and oxidation resistance functions
CN101215307B (en) * 2008-01-08 2010-11-10 山西大学 Method for preparing hydroxyl carthamus tinctorius yellow color A
WO2011051742A1 (en) * 2009-10-28 2011-05-05 Modutech S.A. Preparation comprising amino acids and plants and its activity in the alcohol detoxification
CN102058694B (en) * 2010-12-24 2012-09-05 漆又毛 Application of pharmaceutical composition consisting of amino acids and extracts
CN102349941A (en) * 2011-10-19 2012-02-15 石家庄藏诺生物科技有限公司 Traditional Chinese medicine composition for relieving fatigue and improving anoxia endurance and preparation method thereof
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黄勇超等.α-硫辛酸对缺氧应激肝癌细胞线粒体呼吸率和产能代谢的影响.《生物物理学报》.2007,第23卷(第6期),436-442.

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