CN105012328A - Application of clarithromycin in manufacture of anti-fatigue disease medicine - Google Patents

Application of clarithromycin in manufacture of anti-fatigue disease medicine Download PDF

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Publication number
CN105012328A
CN105012328A CN201510445838.6A CN201510445838A CN105012328A CN 105012328 A CN105012328 A CN 105012328A CN 201510445838 A CN201510445838 A CN 201510445838A CN 105012328 A CN105012328 A CN 105012328A
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China
Prior art keywords
clarithromycin
fatigue
application
health
glycogen
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CN201510445838.6A
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Chinese (zh)
Inventor
苏定冯
刘霞
雷虹
孙旸
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Second Military Medical University SMMU
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Second Military Medical University SMMU
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Priority to CN201510445838.6A priority Critical patent/CN105012328A/en
Publication of CN105012328A publication Critical patent/CN105012328A/en
Pending legal-status Critical Current

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Abstract

The present invention relates to application of clarithromycin in manufacture of an anti-fatigue disease medicine, has the advantage that: for the first time, anti-fatigue effect of the macrolide antibiotic clarithromycin is found, animal test results show that the clarithromycin can significantly prolong swimming time of weight bearing mice, decreases serum urea ammonia level after strenuous exercise suppresses rising of blood lactate, maintains or increases the content of hemoglobin, enhances lactate dehydrogenase vitality, increases glycogen reserving amount, reduces the consumption of glycogen during exercises, and has significant effects of reducing fatigue and increasing exercise tolerance.

Description

The application of clarithromycin in preparation resisting fatigue disease medicament
Technical field
The present invention relates to medical art, specifically, is the application of a kind of macrolide antibiotics clarithromycin in preparation resisting fatigue disease medicament.
Background technology
Macrolide be a class have ten binary to two ten-rings not wait basic lipophilic antibiotic.Wherein erythromycin represents medicine for its classics.Clinical and experimental study finds, erythromycin be treatment légionaires' disease the most effectively and safe drugs.Also effective in this external some other bacteriological infection, such as helicobacter pylori.Recently existing increasing report finds that macrolides compound is not only a kind of antibiotic, also there is other biologic activity: research finds fourteen-ring derivant (erythromycin, Roxithromycin, clarithromycin) stem cell of Monocytes/Macrophages is had to the effect stimulated proliferation; Anssers finds that erythromycin can accelerate the Rythmic contractions characteristic of gastrointestinal, promotes gastric emptying and colon running, increases gastric emptying number of times.Its mechanism is that erythromycin is the agonist of Motilin receptor; In addition, erythromycin also has good effect to chronic asthma, and this effect and its antimicrobial acivity have nothing to do.But about the resisting fatigue effect of macrolide antibiotics clarithromycin, yet there are no report.
Summary of the invention
First object of the present invention is for deficiency of the prior art, provides the application of clarithromycin in preparation resisting fatigue disease medicament.
Second object of the present invention is, provides clarithromycin preparing the application in anti-fatigue health-product containing.
For achieving the above object, the technical scheme that the present invention takes is: the application of clarithromycin in preparation resisting fatigue disease medicament.Clarithromycin is preparing the application in anti-fatigue health-product containing.
Anti-fatigue active composition in described resisting fatigue disease medicament or anti-fatigue health-product containing is clarithromycin.
Other adjuvants are also comprised in described resisting fatigue disease medicament or anti-fatigue health-product containing.
Described medicine or health product reach the effect of resisting fatigue by one or more modes following: reduce serum urea ammonia level after strenuous exercise, blood lactase acid is suppressed to raise, maintain or increase the content of hemoglobin, strengthen Ldh Activity, the consumption of hepatic glycogen when improving liver glycogen reserves amount and reduce motion.
The effective dose of described clarithromycin is 5-60mg/kg.
The invention has the advantages that:
The Late Cambrian of the present invention antifatigue effect of macrolide antibiotics clarithromycin, animal test results shows, clarithromycin can the swimming time of significant prolongation heavy burden mice, reduce serum urea ammonia level after strenuous exercise, suppress blood lactase acid to raise, maintain or increase the content of hemoglobin, strengthen Ldh Activity, when improving liver glycogen reserves amount and reduce motion, the consumption of hepatic glycogen, has the effect of the exercise tolerance that lessens fatigue significantly, increases.
Detailed description of the invention
Below in conjunction with embodiment, detailed description of the invention provided by the invention is elaborated.
Embodiment 1 anti-fatigue active is studied
One, materials and methods
(1) reagent
Chinese English name company
The pharmacy of clarithromycin Clarithromycin Jinhua, Zhejiang
Carboxymethyl cellulose sodium CMC-Na traditional Chinese medicines
(2) main solution configuration
1. 0.8% Carboxymethyl cellulose sodium solution
Reagent name consumption
Carboxymethyl cellulose sodium 0.8g
Single steaming water 1000ml
2. clarithromycin suspension (Mouse oral)
Reagent name consumption
Clarithromycin 0.01g
CMC-Na solution 0.8ml
(3) laboratory animal
Animal feeding: C57 mice, male, 18-22g, takes from The 2nd Army Medical College Experimental Animal Center.Experimental session, Animal House temperature stabilization is at about 22 degree, and relative humidity 70%, lighting hours, from morning 8 to late 8 points, continues 12 hours.Animal can ad lib, freely drinks water.The use of animal is all through the agreement of the care of animal mechanism of The 2nd Army Medical College.
1. swimming test
Mice is inserted in the rustless steel cylinder of 48 × 36 × 29 centimetres, depth of water 20cm, water temperature about 22 degree, the safety pin cord being equivalent to himself body weight 8% is put on and is fixed on its root of the tail portion, then start to record swimming time, freely can not float for fatigue criteria more than 8 seconds with the mice sinking water surface, stop experiment.
2. administration (clarithromycin)
Laboratory mice is divided at random matched group (n=8 only) and administration group (n=24,8/each dosage group), respectively to each group of administration: press 5mg/kg respectively, 15mg/kg, the dosage of 60mg/kg carries out oral administration, and matched group gives the CMC-Na solution of same dosage.Continuous three days, carried out swimming test at the 4th day, when all mices all bear a heavy burden 8% record its swimming time.
(4) statistical analysis
Compare between the group of many groups during homogeneity of variance and check with LSD-t.Compare between many groups group during heterogeneity of variance with Dunnett T3 inspection.Two samples during homogeneity of variance compare employing two independent samples t test.With p<0.05, there is statistical significance.
Two, result
1. clarithromycin can extend the swimming time of mice dose-dependant
To divide into groups in the manner described administration, terminate relief mice in experiment and swim and detect swimming time.We find, clarithromycin can extend the swimming time of mice dose-dependant, and in table 1, (LSD-t checks, and its corresponding P value is respectively compared with last group: 0.005,0.000,0.000).
Table 1 clarithromycin is on the impact of mice burden swimming time
Group Swimming time (minute) P value (comparing with matched group)
Matched group 16.9±3.0
Clarithromycin (5mg/kg) 22.1±5.6 0.005
Clarithromycin (15mg/kg) 31.7±2.7 <0.0001
Clarithromycin (60mg/kg) 40.1±2.9 <0.0001
The raising of exercise tolerance is that anti-fatigue ability strengthens the strongest macro manifestations, and the length of walking weight load can reflect the degree of animal movement fatigue.From above experimental result, clarithromycin low dose group, middle dosage group, high dose group swimming time are obviously longer than matched group, illustrate that clarithromycin can the walking weight load of dose-dependant ground significant prolongation mice, improve exercise tolerance, there is significant antifatigue effect.
Embodiment 2 is on the impact of biochemical indicator after mouse movement
One, materials and methods
1. reagent and laboratory animal
With embodiment 1, by laboratory mice 80, be divided into 2 batches at random, carry out serum urea nitrogen determination, blood lactase acid mensuration, hemoglobinometry, determination of lactate dehydrogenase experiment and hepatic glycogen determination experiment respectively.Often criticize animal and be divided into again 4 groups, be respectively clarithromycin low dose group, dosage group in clarithromycin, clarithromycin high dose group and matched group, every treated animal 10, press clarithromycin 5mg/kg respectively, the dosage of clarithromycin 15mg/kg, clarithromycin 60mg/kg carries out gastric infusion, and matched group gives the CMC-Na solution of same dosage, mice conventional illumination, drinking-water, 25 DEG C of raisings.Every day gavage 1 time, gavage amount is 1% of mice quality, surveys indices after continuous 30d.
2. main agents and instrument
Blood urea nitrogen (BUN) measures test kit, glycogen measures test kit, lactic acid (LD) measures test kit, lactic acid dehydrogenase (LDH) measures test kit, micro free hemoglobin (FHb) measures test kit: build up biological engineering company limited purchased from Nanjing; Hitachi L-8900 automatic amino acid analyzer: group of HITACHI Hitachi product; Electronic analytical balance: Shanghai precision instrument science company limited product; Swimming trunk, High speed refrigerated centrifuge: power & light company of U.S. product; Electric-heated thermostatic water bath: the permanent Science and Technology Ltd. in Shanghai one product; Vortex oscillator: Industrial Co., Ltd. of upper Nereid section product; UV-2450 ultraviolet-uisible spectrophotometer: Japanese Shimadzu Corporation product.
3. the mensuration of mice serum blood urea nitrogen, blood lactase acid, hemoglobin, lactic acid dehydrogenase
After last gives tested material 30min, mice is put in not swimming with a load attached to the body 90min in swimming trunk, water temperature (30 ± 1) DEG C, plucks eyeball after rest 60min and gets blood, blood sample with the centrifugal 5min of 3000r/min with separation of serum.Kit measurement serum urea nitrogen is measured with blood urea nitrogen (BUN), kit measurement blood lactase acid is measured with lactic acid (LD), measure kit measurement hemoglobin by micro free hemoglobin (FHb), measure kit measurement lactic acid dehydrogenase with lactic acid dehydrogenase (LDH).
4. hepatic glycogen measures
Last is de-cervical vertebra execution after giving tested material 30min.Get liver, to blot with filter paper after normal saline rinsing, measure kit measurement hepatic glycogen with glycogen.
5. statistical analysis
Date processing and statistical analysis adopt Excel and SPSS 17.0 software, and result is with average ± standard deviation represent.
Two, result
1. the impact that various sample is heavy on the whole opisthosoma of mice
After continuous irrigation feeds 30d, the growth there was no significant difference (P > 0.05) of each group Mouse Weight, show clarithromycin low dosage, dosage in clarithromycin, clarithromycin high dose does not make significant difference to Mouse Weight.
2. on the impact of biochemical indicator after mouse movement
As shown in Table 2, oral administration 30d, compares with matched group, clarithromycin low dosage, and middle dosage and high dose all significantly can reduce the content of the rear mice serum blood urea nitrogen of swimming.In clarithromycin, dosage and high dose significantly can reduce the content of the rear Mouse Blood lactic acid of swimming, clarithromycin low dosage DeGrain.In clarithromycin, dosage and high dose all significantly can increase the content of the rear Mouse Blood Lactoferrin of swimming, and wherein clarithromycin high dose effect is the most obvious.Clarithromycin high dose significantly can increase the content of Mouse Lactate Dehydrogenase, and low dosage and middle dosage also can increase the content of Mouse Lactate Dehydrogenase, but DeGrain.In clarithromycin, the hepatic glycogen content of dosage and high dose significantly raises, and high dose effect is more obvious.
Table 2 different disposal group is on the impact of mice biochemical indicator
Serum urea nitrogen is the end-product of protein metabolism, that evaluation body is to one of important indicator of motor fitness, body serum urea nitrogen content with work and sports load increase and increase, body is poorer to load performance, and serum urea nitrogen increase is more obvious.Experimental result shows, and clarithromycin can serum urea ammonia level after dose-dependent obvious reductions mice strenuous exercise, the excessive decomposition protecting protein in strenuous exercise is described, improves the adaptive capacity of body to strenuous exercise, endurance is increased.Blood lactase acid is the important symbol thing evaluating organism fatigue, body is after long-time strenuous exercise, in body, overheap lactic acid is the major reason causing sports fatigue, because lactic acid accumulation too much can affect normal metabolic processes in the relatively stable of organismic internal environment and body in body.The present invention finds that clarithromycin can have and suppresses blood lactase acid rising effect, illustrates that clarithromycin can eliminate the lactic acid produced due to strenuous exercise in time, thus lessens fatigue.The major function of hemoglobin is transports oxygen, its content directly affects the exercise tolerance of body, experimental result shows, clarithromycin can maintain or increase the content of Mouse Blood Lactoferrin, ensure that body oxygen supply is sufficient, and then promote the carrying out of body aerobic metabolism and the elimination of lactic acid, improve exercise tolerance.By improving Ldh Activity to reduce one of approach that blood lactase acid level is raising body resisting fatigue ability.Experiment records clarithromycin and can strengthen Ldh Activity significantly, and the amount that after effectively reducing motion, blood lactase acid produces, strengthens mouse movement endurance.Hepatic glycogen is the storage vault of blood glucose, can decompose rapidly be released into blood when body blood glucose reduces, to maintain the stable of blood sugar level.Experimental result shows, the consumption of hepatic glycogen when clarithromycin can improve liver glycogen reserves amount and reduce motion, for body provides more energy to reach the object of resisting fatigue.
The above is only the preferred embodiment of the present invention; it should be pointed out that for those skilled in the art, under the prerequisite not departing from the inventive method; can also make some improvement and supplement, these improve and supplement and also should be considered as protection scope of the present invention.

Claims (6)

1. the application of clarithromycin in preparation resisting fatigue disease medicament.
2. clarithromycin is preparing the application in anti-fatigue health-product containing.
3. according to the arbitrary described application of claim 1 or 2, it is characterized in that, the anti-fatigue active composition in described resisting fatigue disease medicament or anti-fatigue health-product containing is clarithromycin.
4. application according to claim 3, is characterized in that, also comprises other adjuvants in described resisting fatigue disease medicament or anti-fatigue health-product containing.
5. according to the arbitrary described application of claim 1 or 2, it is characterized in that, described medicine or health product reach the effect of resisting fatigue by one or more modes following: reduce serum urea ammonia level after strenuous exercise, blood lactase acid is suppressed to raise, maintain or increase the content of hemoglobin, strengthen Ldh Activity, the consumption of hepatic glycogen when improving liver glycogen reserves amount and reduce motion.
6., according to the arbitrary described application of claim 1 or 2, it is characterized in that, the effective dose of described clarithromycin is 5-60mg/kg.
CN201510445838.6A 2015-07-27 2015-07-27 Application of clarithromycin in manufacture of anti-fatigue disease medicine Pending CN105012328A (en)

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2493239C1 (en) * 2012-05-10 2013-09-20 Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Уфимский государственный нефтяной технический университет" Composition of lead-free ecologically clean high-octane petrol

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2493239C1 (en) * 2012-05-10 2013-09-20 Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Уфимский государственный нефтяной технический университет" Composition of lead-free ecologically clean high-octane petrol

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
于丽婷: "基于α-1-酸性糖蛋白的抗疲劳药物筛选", 《万方数据知识服务平台》 *

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Inventor after: Su Dingfeng

Inventor after: Liu Xia

Inventor after: Lei Hong

Inventor after: Sun Yang

Inventor after: Wan Jingjing

Inventor after: Qin Zhen

Inventor after: Wang Pengyuan

Inventor before: Su Dingfeng

Inventor before: Liu Xia

Inventor before: Lei Hong

Inventor before: Sun Yang

RJ01 Rejection of invention patent application after publication
RJ01 Rejection of invention patent application after publication

Application publication date: 20151104