CN104784167B - A kind of medicine for treating animal eperythrozoonosis and preparation method thereof - Google Patents
A kind of medicine for treating animal eperythrozoonosis and preparation method thereof Download PDFInfo
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- CN104784167B CN104784167B CN201510153271.5A CN201510153271A CN104784167B CN 104784167 B CN104784167 B CN 104784167B CN 201510153271 A CN201510153271 A CN 201510153271A CN 104784167 B CN104784167 B CN 104784167B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
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Abstract
The invention belongs to field of veterinary, a kind of medicine for treating animal eperythrozoonosis specifically disclosed, the active ingredient of the medicine count by weight including：0.25 2.5 parts of Artesunate；0.1 1 parts of arteether；0.25 2.5 parts of Artemether.The medicine of the present invention belongs to natural drug, has the advantages that pollution-free, toxic side effect is small, it is few to remain amount of poisons, has good therapeutic action to eperythrozoonosis, can avoid using antibiotic medicine.
Description
Technical field
The invention belongs to field of veterinary, and in particular to a kind of medicine for treating animal eperythrozoonosis and its preparation side
Method.
Background technology
Eperythrozoonosis is by eperythrozoon（Eperythrozoon, EH）Parasitize humans and animals red blood cell table
It is caused a kind of with the infecting both domestic animals and human for main clinic symptoms such as anaemia, jaundice, heating in face, plasma tissue liquid and marrow
Infectious disease.Near-spherical Tubifex body is found from rodent from Schilling and Dinger in 1928 etc.
（E.coccoides）Since, various countries report eperythrozoonosis in succession；1934, Adler etc. was found that shape in Niu Tizhong
State and microorganism as near-spherical Tubifex body phase, are named as Wen Shi Tubifex bodies（E.wenyoni）；Later in succession in pig, ox, silk floss
Infection is confirmed in animal and the birds such as sheep, goat, horse, rabbit, dog, cat, monkey, camel, fox class, donkey, deer, gnu, vigone and human body
Eperythrozoon.So far, it has been found that and the eperythrozoon named has tens of kinds.Eperythrozoon can pass through placenta, blood
The approach such as liquid, wound are propagated.This sick pathogenesis is that eperythrozoon can change the penetrating of erythrocyte membrane in blood
Property, cause film to be recessed and cavity, it is easy to dissolving and rupture, reduce red blood cell number, hemoglobin reduction can also result in body poor
Blood, jaundice, acid-base imbalance etc. are showed, infected red blood cell oxygen carrying capacity reduction.Because red blood cell also has immunologic function, therefore
Infect after eperythrozoon, red blood cell is destroyed, Abwehrkraft des Koepers is declined and is occurred mixed infection or scabies secondary infection, this disease
Latent infection rate is high.Up to the present also without preferable eperythrozoon vaccine, currently prevent and treat the disease or be by medicine
It is main, this situation can be significantly improved using antibiotic, but generated while huge effect is brought to antibiotic product
Drug resistance and the problems such as medicament residue.Shown according to many reports for treating and preventing eperythrozoonosis in recent years, it is used " special
Effect " medicine reaches as many as tens of kinds, but clinical effectiveness has very big difference.
The medicine of conventional preventing and treating eperythrozoon has " Tubifex is net " etc. at present, and the disease is treated in addition to medicine, simultaneously
Supporting treatment is taken, ORS drinking-water carries out glucose infusion liquid, plus sodium acid carbonate if necessary.If necessary to piglet, chronic
Chalybeate is injected by infected pigs.During mixed infection, it should be noted that the other pathogenic factors of control.Being tested through drug sensitive test and drug therapy confirms
The medicines such as penicillin, streptomysin, gentamicin, sulfa drugs, analgin are invalid to eperythrozoon.After " Tubifex is net " use
Attached corpus hemorrhagicum is set to be come off from red blood cell, attached corpus hemorrhagicum stops swinging in blood plasma.But due to being used for a long time, its effect is increasingly paid no attention to
Think, therefore it is very eager to find new medicine.
The content of the invention
It is an object of the invention to provide a kind of pharmaceutical composition for treating Eperythrozoon wenyonii disease.
The present invention realizes that the technical scheme that above-mentioned purpose is used is as follows：
A kind of medicine for treating animal eperythrozoonosis, the active ingredient of the medicine count by weight including：
0.25-2.5 parts of Artesunate；
0.1-1 parts of arteether；
0.25-2.5 parts of Artemether.
Further, the active ingredient of the medicine count by weight including：
1.25-2.5 parts of Artesunate；
0.8-1 parts of arteether；
0.25-1.25 parts of Artemether.
Further, the active ingredient of the medicine count by weight including：
1.25 parts of Artesunate；
0.8 part of arteether；
1.25 parts of Artemether.
The applicable animal of the medicine includes pig, ox, sheep, horse, rabbit, dog, cat, monkey, camel, fox, donkey, deer, gnu, vigone
Deng.
The method for preparing the medicine of above-mentioned treatment animal eperythrozoonosis, including, by Artesunate, arteether, Hao Jia
Ether, alkaline conditioner and cosolvent are added in solvent, after stirring, sterilization, that is, obtain the medicine.
Further, the alkaline conditioner is ethylenediamine.
Further, cosolvent is Tween-80, and solvent is 1,3-PD.
Artesunate that the present invention is selected, methyl ether, arteether belong to natural drug, have to eperythrozoonosis good
Curative effect, and without recurrence.
Brief description of the drawings
Fig. 1 is the treatment results curve map of piglet eperythrozoonosis.
Fig. 2 is the treatment results curve map of eperythrozoonosis in dairy cow.
Fig. 3 is the treatment results curve map of eperythrozoon ovis disease.
Embodiment
The present invention is described in further details below in conjunction with specific embodiment.
Embodiment 1
Raw material is as follows：
Artesunate 0.25g
Arteether 0.5g
Artemether 2.5g
The ml of ethylenediamine 0.2
The ml of Tween-80 5
Above-mentioned Artesunate, arteether, Artemether, ethylenediamine and Tween-80 are added to 50ml 1,3-PD, often
Temperature stirring 1 hour, then mended with 1,3-PD to 100ml, stir 0.5 hour, dispense, sterilizing, you can, below by medicine letter
Referred to as Tubifex kills injection 1.
Embodiment 2
Raw material is as follows：
Artesunate 1.25g
Arteether 0.8g
Artemether 1.25g
The ml of ethylenediamine 0.2
The ml of Tween-80 5
Above-mentioned Artesunate, arteether, Artemether, ethylenediamine and Tween-80 are added to 50ml 1,3-PD, often
Temperature stirring 1 hour, then mended with 1,3-PD to 100ml, stir 0.5 hour, dispense, sterilizing, you can, below by medicine letter
Referred to as Tubifex kills injection 2.
Embodiment 3
Artesunate 2.5g
Arteether 1g
Artemether 0.25g
Ethylenediamine 0.2ml
The ml of Tween-80 5
Above-mentioned Artesunate, arteether, Artemether, ethylenediamine and Tween-80 are added to 50ml 1,3-PD, often
Temperature stirring 1 hour, then mended with 1,3-PD to 100ml, stir 0.5 hour, dispense, sterilizing, you can, below by medicine letter
Referred to as Tubifex kills injection 3.
Reference examples 1
Artesunate 4g
The ml of ethylenediamine 0.2
Tween-80 5ml
Above-mentioned Artesunate, ethylenediamine and Tween-80 be added to 50ml 1,3-PD, stirring at normal temperature 1 hour, then
Mended to 100ml, stirred 0.5 hour with 1,3-PD, dispensed, sterilizing, you can, the medicine is referred to as Artesunate note below
Penetrate agent.
Reference examples 2
Arteether 4g
The ml of ethylenediamine 0.2
The ml of Tween-80 5
Above-mentioned arteether, ethylenediamine and Tween-80 are added to 50ml 1,3-PD, stirring at normal temperature 1 hour, then used
1,3-PD is mended to 100ml, is stirred 0.5 hour, is dispensed, sterilizing, you can, the medicine is referred to as arteether injection below
Agent.
Reference examples 3
Artemether 4g
The ml of ethylenediamine 0.2
Tween-80 5ml
Above-mentioned Artemether, ethylenediamine and Tween-80 are added to 50ml 1,3-PD, stirring at normal temperature 1 hour, then used
1,3-PD is mended to 100ml, is stirred 0.5 hour, is dispensed, sterilizing, you can, the medicine is referred to as Artemether injection below
Agent.
。
The formulation of medicine of the present invention is not limited to injection, also can be by active ingredient Artesunate, arteether and Artemether
The formulations such as eclegm, tablet, pulvis, capsule are mixed and made into other conventional pharmaceutic adjuvants.
Effect experiment
1. materials and methods
1.1 material
1.1.1 pathogen selection has the milk cow of classical symptom, sterile to take its anticoagulation（Anticoagulant heparin）, examined through laboratory
Look into（The iodine retardation test of blood pressed disc method, Wright Stain and characteristic）, it is determined that there is Infected with Eperythrozoon, person is the positive, is received
Collect anticoagulation of the infection rate more than 90%, saved backup in 4 DEG C of refrigerators.
1.1.2 medicine：Medicine prepared by above-described embodiment 1-3 and reference examples 1-3.
1.1.3 complete medium RPMI-1640（LIFE TECHNOLONGIES companies of the U.S. produce）With calf blood
It is clear to press 8：2 ratio is mixed.
1.2 method
1.2.1 extracorporeal culturing method is carried out with reference to Eperythrozoon wenyonii extracorporeal culturing method.Complete medium and anti-freezing
Blood is according to 7：1 ratio mixing, loaded in 50ml centrifuge tubes, then is sub-packed in through in autoclaved penicillin bottle, pressing
Mixed liquor final volume is set to be 1ml according to the concentration addition medicine of test requirements document, selection standard incubator is cultivated with 37 DEG C.
1.2.2 the selection of drug concentration according to dosage requires to be diluted medicine with physiological saline, every kind of medicine according to
The method of equal difference sets 4 different concentration, after the drug concentration that wherein Tubifex kills is by its contained three kinds of active ingredient addition
Amount calculate, it is 1ml to make liquid mixture cumulative volume, and drug concentration is reached required concentration（ 2μg/ml、4μg /ml、6μg
/ ml, 8 μ g/ml are respectively 2 when being scaled actual therapeutic dosage, 4,6,8mg/kg）.Every 6 hours are observed once respectively,
Continuous Observation 5 times.
1.2.3 each sample of the judgement of infected Erythrocytes rate takes 5 μ l to do tabletting inspection respectively every time, in 400 power microscopes
Under 10 visuals field of each observation, each visual field observes 50 red blood cells, averages, be used as sample infected Erythrocytes rate.
2. result
The result of the test that 2.1 Tubifexs kill injection 1-3 is shown in Table 1-3
The Tubifex of table 1 kills injection 1 and kills result to E.wenyoni suppression
The Tubifex of table 2 kills injection 2 and kills result to E.wenyoni suppression
The Tubifex of table 3 kills injection 3 and kills result to E.wenyoni suppression
As can be seen from the above results, suppression is killed effect and is followed successively by from high to low：Tubifex kills the ＞ Tubifexs of injection 2 and kills injection
The ＞ Tubifexs of agent 3 kill injection 1.
2.2 reference examples 1-3 result of the test is shown in Table 4-6
The Artesunate injection of table 4 kills result to E.wenyoni suppression
The arteether injection of table 5 kills result to E.wenyoni suppression
The Artemether injection of table 6 kills result to E.wenyoni suppression
。
3. discuss
More than 3.1 result of the tests show, under identical condition of culture, each treated according to medicine this it is sick when used connect
Nearly concentration（mg/kg）Although there is certain inhibitory action to E.wenyoni, their action effect is different, and suppression is killed
Effect is Artesunate injection ＞ Artemether injection ＞ arteether injections successively from high to low, this with we are actual gives birth to
Produce medication effect in work basically identical, but its effect is still well below the blood being made up of Artesunate, Artemether and arteether
Worm kills injection, illustrates there is synergy well in medicine of the present invention between each active ingredient, and suppression kills effect from high to low
It is followed successively by：Tubifex, which kills the ＞ Tubifexs of injection 2 and kills the ＞ Tubifexs of injection 3, kills the ＞ Artesunate injections of injection 1.
3.2 in incubation it was found that culture to 24h when, begin with the color of nutrient solution by scarlet discoloration
Into kermesinus, red blood cell is pointed out to be destroyed, the color of small part nutrient solution becomes kermesinus by cerise when 30h, in
It is that we finish experiment.
Clinical test
Clinical Treatment Test treats Infected with Eperythrozoon using at most and effect most definite medicine is net for Tubifex at present.
The animal that eperythrozoon is infected in injection treatment is killed in this experiment with the Tubifex of the present invention, and using commercially available Tubifex it is net as pair
According to.
Infection 3 monthly age of eperythrozoon piglet 100 is confirmed to Henan area, body in Zhangjiakou Area, Hebei Province confirms infection eperytozoa
Body milk cow 50, Gansu Wu Sheyi plants confirm that the sheep 50 of infection eperythrozoon is treated.Every kind of animal is equal at random
It is divided into 5 groups, the 1st group is infection not treatment group, and as a control group, remaining 4 groups respectively with the net injection of Tubifex（Gansu Zheng Feng medicines
Industry Co., Ltd）, Tubifex kills injection 1, Tubifex and kills injection 2, Tubifex and kill injection 3, dosage：2mg/kg body weight, continuously
Medication 7 days.Blood sample is stayed to carry out eperythrozoon detection, Continuous Observation 15 days daily to experimental animal.
Fig. 1 is the treatment results curve map of piglet eperythrozoonosis, and Fig. 2 is the treatment results of eperythrozoonosis in dairy cow
Curve map, Fig. 3 is the treatment results curve map of eperythrozoon ovis disease.
Fig. 1-3 result shows that treatment group animal eperythrozoon is not detected and is presented positive in 15 days always（a）；Even
After continuous treatment 7 days, net group of Tubifex（b）Injection 1 is killed with Tubifex（c）Positive rate be down to 10% or so；And Tubifex kills injection 2
（d）, Tubifex kill injection 3（e）Positive rate be 0, all turn out cloudy.Continue attached corpus hemorrhagicum monitoring of infection one week, Tubifex is organized all only
In the presence of a small amount of recurrent infection, Tubifex of the invention kills injection 1-3 treatment groups without recurrence, illustrates that medicine of the invention has good
Good curative effect, therefore the medicine has widely application prospect.
The present invention use natural drug for active ingredient, with pollution-free, toxic side effect it is small, remain amount of poisons lack etc. it is excellent
Point, has good therapeutic action to eperythrozoonosis, so as to avoid using antibiotic medicine.
Claims (7)
1. a kind of medicine for treating animal eperythrozoonosis, is counted by weight, the medicine is made up of following active ingredient：
0.25-2.5 parts of Artesunate；
0.1-1 parts of arteether；
0.25-2.5 parts of Artemether.
2. the medicine of animal eperythrozoonosis is treated according to claim 1, it is characterised in that counted by weight, institute
Medicine is stated to be made up of following active ingredient：
1.25-2.5 parts of Artesunate；
0.8-1 parts of arteether；
0.25-1.25 parts of Artemether.
3. the medicine of animal eperythrozoonosis is treated according to claim 2, it is characterised in that counted by weight, institute
Medicine is stated to be made up of following active ingredient：
1.25 parts of Artesunate；
0.8 part of arteether；
1.25 parts of Artemether.
4. according to the medicine of any treatment animal eperythrozoonosises of claim 1-3, it is characterised in that the animal is
Pig, ox, sheep, horse, rabbit, dog, cat, monkey, camel, fox, donkey, deer, gnu or vigone.
5. the method for the medicine for the treatment of animal eperythrozoonosis described in claim 1 is prepared, including, by Artesunate, wormwood artemisia second
Ether, Artemether, alkaline conditioner and cosolvent are added in solvent, after stirring, sterilization, that is, obtain the medicine.
6. method according to claim 5, it is characterised in that the alkaline conditioner is ethylenediamine.
7. method according to claim 5, it is characterised in that cosolvent is Tween-80, solvent is 1,3-PD.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510153271.5A CN104784167B (en) | 2015-04-02 | 2015-04-02 | A kind of medicine for treating animal eperythrozoonosis and preparation method thereof |
| PCT/CN2015/081207 WO2016155118A1 (en) | 2015-04-02 | 2015-06-10 | Medicine for treating animal eperythrozoonosis and method for preparing same |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510153271.5A CN104784167B (en) | 2015-04-02 | 2015-04-02 | A kind of medicine for treating animal eperythrozoonosis and preparation method thereof |
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| Publication Number | Publication Date |
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| CN104784167A CN104784167A (en) | 2015-07-22 |
| CN104784167B true CN104784167B (en) | 2017-08-15 |
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| CN106166174A (en) * | 2016-07-21 | 2016-11-30 | 河南黑马动物药业有限公司 | Pet dog, pet cat composite artesunate pharmaceutical composition and preparation method thereof |
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| EP1940519B1 (en) * | 2005-09-09 | 2012-03-07 | Dafra Pharma N.V. | Pharmaceutical composition comprising artesunate, sulfamethoxypyrazine and pyrimethamine for use in the treatment of malaria within one day |
| CN101317879B (en) * | 2008-07-08 | 2011-04-13 | 赵志敏 | Medicament for treating eperythrozoon diseases of cattle, sheep and pig |
| CN103181886A (en) * | 2011-12-30 | 2013-07-03 | 上海复星医药产业发展有限公司 | Artemisinin or its derivative sustained release preparation, and preparation method thereof |
| CN102755316A (en) * | 2012-07-16 | 2012-10-31 | 中国科学院武汉病毒研究所 | Application of artemisinin and derivatives thereof in preparation of medicaments for treating hepatitis C viruses |
| CN104288273B (en) * | 2014-10-13 | 2017-06-06 | 天津瑞贝特科技发展有限公司 | Treat Chinese and western medicinal composition of eperythrozoonosis in dairy cow and preparation method thereof |
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| WO2016155118A1 (en) | 2016-10-06 |
| CN104784167A (en) | 2015-07-22 |
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