CN1113433A - Antiparasitic medicine - Google Patents
Antiparasitic medicine Download PDFInfo
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- CN1113433A CN1113433A CN 95101027 CN95101027A CN1113433A CN 1113433 A CN1113433 A CN 1113433A CN 95101027 CN95101027 CN 95101027 CN 95101027 A CN95101027 A CN 95101027A CN 1113433 A CN1113433 A CN 1113433A
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Abstract
The antiparasitic medicine prepared with macrolide antibiotics and in the form of powder, tablet, ointment, cream, or paste uses an 8-component oily mixture as main active component, as well as imidazole drug for high parasite-expelling effect to tapeworm, blood fluke, etc., and it is safe less consumption of B1, and easy to use.
Description
The present invention relates to prepare animal anthelmintic field with microorganism synthetic ten hexa-atomic macrolide antibiotics.
Avilamycin (Avermectins) is the metabolite of streptomycete Streptomyces Avermitilis, have wide spectrum, anti-insect activity efficiently, found this material in 76 years, the eighties U.S. Merok company successively succeeds in developing insecticide, anti-post the worm medicine and put on market.The mixture that avilamycin (Avermectins) is made up of eight quite similar homologues of structure, i.e. Avermeotin A
1a, A
1b, A
2a, A
2b, B
1a, B
1b, B
2aAnd B
2b, the avilamycin structural formula is as follows:
Avermectin R
5R
20C
22-X-C
23
A
1aCH
3C
2H
5-CH=CH-
A
1bCH
3CH
3-CH=CH-
B
1aH C
2H
5-CH=CH-
B
1bH CH
3-CH=CH-
A
2aCH
3C
2H
5 
A
2bCH
3CH
5 
B
2aH C
2H
5
B
2bCH
3C
2H
5 
Eight components of avilamycin are divided into two groups of a, b or A again habitually
1, A
2, B
1, B
2Four pairs; Wherein a group is a large amount of components, accounts for more than 85%, and the b group is a small amount of component, accounts for below 15%; 8 components all have different insecticidal activities, B
1aComponent is the widest component of insecticidal activity height, insecticidal spectrum (1. Wu Lian sweet smell etc. wherein, new antibiotic Avermectin of gang and derivative I vermectin thereof " external medical antibiotic fascicle ", 13(3)-191,1992: 2. Richard, W.Burg, et al.Avermectins, New Family of Potent Anthelmintic Agents:Produing Organism and Fermentation " Antimicrob.Agents Chemother. " 15(3) 361-367,1979; 3. Egerton, T.R.et al.Avermectin, New Family Poten Anthelmintic Agents:Efficacy of the Bla Component " Antimicrob.Agents Chemother. " 15(3) 372-378,1979) but because of B
1aAnd B
1bIn suitability for industrialized production, be difficult to separate effectively, so that be widely used now is B
1aAnd B
1bRespectively account for certain proportion (B
1aAccount for more than 80% B
1bAccount for below 20%) mixture B
1And B
1Hydrogenating reduction product ivermectin H
2B
1(Ivermectin), B
1And H
2B
1Be widely used in the prophylactic treatment of the parasitic disease of animal in plant protection in the agricultural production and the animal husbandry.The chemical improvement of each component of avilamycin has now become one of emphasis of this antibiotic deep development.Relevant this antibiotic patent reaches hundreds of, but great majority have for Merck ﹠ Co.Inc..Use B
1And H
2B
1The injection of preparation is present the most common dosage form, and also useful mycelium directly prepares the scheme of tablet and powder.
Prior art has following weak point: the first, use B
1Or H
2B
1, the preparation injection because of extraction process has increased cost and price greatly than complexity, is restricted its promotion and application, especially in developing country; Its two, B in extraction not only
1There is more loss (being generally about 50%), and A
1, A
2, B
2Can not be used effectively Deng composition, cause waste with insecticidal activity.Though tablet and the powder price made with mycelium are low, the composition (polyenoid class material and few enzyme element etc.) that has big side effect in the mycelium also is brought in the preparation in the lump, gives to take animal and cause in various degree toxic and side effects.
Develop and a kind ofly can overcome above-mentioned pure B
1The place that the insufficient new prescription of preparation and mycelium preparation is a purpose of the present invention.
The foregoing invention purpose is by with containing avilamycin A
1, A
2, B
1, B
2The oily mixture of four pairs of components adds that as main effective ingredient adjuvant makes that the anthelmintic drug of different dosage form realizes, below is relevant detailed description of the present invention.
One, avilamycin oily mixture (hereinafter to be referred as AVM grease)
Avilamycin oily mixture (hereinafter to be referred as AVM grease) through PROCESS FOR TREATMENT such as decolourings and get, is main anthelmintic ingredient by lixiviating solution, this mixture consist of A
13～10%, A
28-15%, B
16-15%, B
23～10%, 14-18 carbon fatty acid: 35-40%, water: 10-15%.Its preparation technology is as follows:
Producing bacterial strain decolours → concentrates → AVM grease with acetone or ethyl acetate lixiviate → filtration (or centrifugal) → lixiviating solution through 10-11 days fermentation → filtration → mycelium.
Most side effect compositions can be removed through technologies such as decolourings.
Two, form formula and technology
The present invention includes the prescription and the production technology thereof that prepare powder, tablet, unguentum, ointment, five kinds of dosage forms of paste with AVM grease.
1. powder:
(1) prescription (w/w)
AVM grease 1-10%+CaCO
330-49%+ starch 50-60%(starch can use equivalent wheat bran, Semen Maydis powder or corn cob to substitute).
(2) technology
A. according to B in the concentration for preparing powder and each batch AVM grease
1Content and single batch of output calculate various raw material consumptions;
B. take by weighing AVM grease, CaCO
3And starch, earlier with AVM grease and CaCO
3Mixing in premixing device adds starch (wheat bran, Semen Maydis powder, corn cob) abundant mixing, dries, sieves again, and check gets final product by the design specification packing.
(3) purposes, usage: be mainly used in inside and outside verminates such as the nematicide of killing animals such as parasitizing pig, cattle, sheep, chicken, rabbit, demodicid mite, Ticks, louse, fly larvae.Usage: add water and gavage or mix in feedstuff and all can.
2. tablet:
(1) prescription (w/w)
AVM grease 10-20%+CaCO
320-50%+ starch 50～60%+ magnesium stearate 2%+ dextrin 15%
(2) technology
A. according to B in tablet specification and the AVM grease
1The various composition consumptions of cubage;
B. earlier with AVM grease and CaCO
3Mixing;
C. starch is added, fully mixing is made soft material again;
D. use 12 mesh sieve wet granulations, the grain that will wet is put drying room (about 80 ℃) aeration-drying;
E. add magnesium stearate, dextrin mixing, be tablet with the tablet machine tabletting.
The specification size of tablet and content etc. can be decided according to concrete conditions such as treatment targets, and the addition of AVM grease is with B
1Cubage.
(3) purposes, usage: but inside and outside verminate such as the nematicide of prophylactic treatment pig, cattle, sheep, chicken, rabbit etc., demodicid mite, Ticks, louse, fly larvae.Directly oral or water-soluble admixing thrown clothes in feedstuff or the drinking-water and all can.
3. ointment:
(1) prescription (w/w)
AVM grease 2～20%+ hexadecanol, octadecanol mixture 30-60%+ white vaseline 30-60%+ lanoline 1-10%
(2) technology
AVM grease, lanoline, white vaseline are heated to 80 ℃ of dissolvings, and with they mix homogeneously under constantly stirring, and then add and 16, the octadecanol mixture, mixing, check, fill gets final product.
(3) purposes, usage:
Be applied in the cattle, sheep mouth on the mucosa, be mainly used in and kill the nematicide that parasitizes cattle, sheep inside and outside, demodicid mite, Ticks, louse, fly larvae etc.Press B
1Cubage, ampoule are that 0.1～0.3mg/kg.b.w. can reach the anthelminthic effect more than 95%.
4. ointment:
(1) prescription (w/w)
AVM grease 2-20%+ diformazan gathers silicon 40-80%+ stearyl alcohol 5-10%+ peregal 201-2%+ softener sg 2-4%+ ethyl hydroxybenzoate 0.5-1%+ distilled water 10-30%
(2) technology:
After getting the poly-silicon of oil-phase component-AVM grease, diformazan, stearyl alcohol and water-phase component-peregal 20, softener sg, glycerol, mud moor gold ethyl ester and water respectively and being heated to 80 ℃ of dissolvings, divide water and oil phase mixing respectively; Oil phase thing with mixing joins in the aqueous-phase material again, mixing, cooling, and pick test gets final product by the specification packing.
(3) usage, purposes:
The same ointment of usage is applied in ointment in the mouth of cattle, sheep, horse and gets final product on the mucosa.Be mainly used in parasites such as killing the inside and outside nematicide of animal body, demodicid mite, Ticks, louse, fly larvae.Press B
1Amount calculating 0.1～0.3mg/kg.b.w dosage can reach the preventive effect more than 95%.
5. paste:
(1) prescription (w/w)
AVM grease 10%+ starch 10～20%+ glycerol 60%+ distilled water 10～20%+ peregal 201%+ softener sg 1%+ sodium benzoate 0.5%(starch can replace with cellulose derivative or sodium alginate).
(2) technology
A. at first water with starch furnishing pasty state;
B. AVM grease is heated to 80 ℃ of dissolvingizations;
C. glycerol, peregal 20, softener sg heating are mixed.
D. the mixture with above-mentioned dissolved AVM grease and glycerol etc. mixes earlier, and pasty state starch mixing is paste afterwards.
(3) usage, purposes
Paste is applied in the mouth of horse, cattle, sheep and gets final product on the mucosa.Be mainly used in and kill parasites such as parasitizing the inside and outside nematicide of animal body, demodicid mite, Ticks, louse, fly larvae.
More than all can add B in five kinds of form formulas
1The imidazoles that 30-60 doubly measures, as albendazole, benzene sulfur imidazoles, several class parasites of not killing in order to avilamycin such as hold concurrently killing cestode and trematodiasis simultaneously.
Above-mentioned various dosage form shows that through the clinical practice on Xinjiang and other places to the most parasites in the control spectrum, its repelling and killing efficacy reaches more than 95%.
The present invention compared with prior art has following good effect
1. and B
1Crystallization product preparation is compared has identical curative effect, B still less
1Loss, lower cost, cost can reduce 50%-70%, and technology is simple, and is easy and simple to handle, aspect side effect such as toxicity and B
1The elaboration preparation is suitable.
2. compare with the mycelium preparation, it is close to have price, the characteristics higher to animal safety, and safety index is greater than more than 10 times of medicine regulation.
3. because of the equal tool insecticidal activity of its four pairs of components, on insecticidal spectrum, has complementary action, therefore at B
1Under the identical situation of concentration, because the effect of other component, anthelminthic effect is better.
Described below is several examples of five kinds of dosage form preparations:
Each embodiment takes from the AVM grease that same jar lixiviating solution processing obtains (lot number is: 940309).A in this batch grease
1, B
1, A
2, B
2Composition as follows:
A
110% A
214% water 11%
B
115% B
211% 14～18 carbon fatty acid 39%
Embodiment 1: powder:
A. take by weighing AVM grease (lot number: 940309) 100 grams, CaCO respectively
3300 grams, starch 600 grams.
B. earlier with AVM grease and CaCO
3Fully mixing adds starch abundant mixing again, dries, sieves, check, get final product B
1Content is 1.5% powder 1000 grams.
Embodiment 2: powder:
A. take by weighing AVM grease (lot number: 940309) 100 grams, CaCO respectively
3300 grams, wheat bran 600 grams.
B. earlier with AVM grease and CaCO
3Fully mixing adds starch abundant mixing again, dries, sieves, check, get final product B
1Content is 1.5% powder 1000 grams.
Embodiment 3: powder:
A. take by weighing AVM grease (lot number: 940309) 100 grams, CaCO respectively
3300 grams, Semen Maydis powder 600 grams.
B. earlier with AVM grease and CaCO
3Fully mixing adds starch abundant mixing again, dries, sieves, check, get final product B
1Content is 1.5% powder 1000 grams.
Embodiment 4: powder:
A. take by weighing AVM grease (lot number: 940309) 100 grams, CaCO respectively
3300 grams, corn cob 600 grams.
B. earlier with AVM grease and CaCO
3Fully mixing adds starch abundant mixing again, dries, sieves, check, get final product B
1Content is 1.5% powder 1000 grams.
Embodiment 5. tablets:
A. take by weighing AVM grease (lot number: 940309) 100 grams, CaCO respectively
3200 grams, starch 530 grams, magnesium stearate 20 grams, dextrin 150 grams.
B. earlier with AVM grease and CaCO
3Mixing;
C. starch is added, fully mixing is made soft material again;
D. use 12 mesh sieve wet granulations, the grain that will wet is put drying room (about 80 ℃) aeration-drying;
E. add magnesium stearate, dextrin mixing, can obtain B with tablet machine tabletting (100mg/ sheet)
1Content is 1.5% tablet 1000 grams.
Embodiment 6. ointments:
A. take by weighing AVM grease (lot number: 940309) 100 grams, hexadecanol, octadecanol mixture 400 grams, white vaseline 450 grams, lanoline 50 grams respectively.
B. AVM grease, lanoline, white vaseline are heated to 80 ℃ of dissolvings, and with they mix homogeneously under constantly stirring, and then add and 16, the octadecanol mixture, mixing, check, get final product B
1Content is 1.5% ointment 1000 grams.
Embodiment 7. ointments:
A. take by weighing AVM grease (lot number: 940309) 100 grams, poly-silicon 600 grams of diformazan, stearyl alcohol 60 grams, peregal 2012 grams, softener sg 25 grams, ethyl hydroxybenzoate 3 grams, distilled water 200 grams respectively.
B. after getting the poly-silicon of oil-phase component-AVM grease, diformazan, stearyl alcohol and water-phase component-peregal 20, softener sg, glycerol, mud moor gold ethyl ester and water respectively and being heated to 80 ℃ of dissolvings, divide water and oil phase mixing respectively: the oil phase thing with mixing joins in the aqueous-phase material again, mixing, cooling, pick test can obtain B
1Content is 1.5% ointment 1000 grams.
Embodiment 8. pastes:
A. take by weighing AVM grease (lot number: 940309) 100 grams, starch 180 grams, glycerol 550 grams, distilled water 145 grams, peregal 2010 grams, softener sg 10 grams, sodium benzoate 5 grams respectively.
B. first water is with starch furnishing pasty state;
C. AVM grease being heated to 80 ℃ dissolves;
D. glycerol, peregal 20, softener sg heating are mixed.
E. the mixture with above-mentioned dissolved AVM grease and glycerol etc. mixes earlier, adds pasty state starch mixing afterwards and can obtain B
1Content is 1.5% paste 1000 grams.
Embodiment 9. pastes:
A. take by weighing AVM grease (lot number: 940309) 100 grams, methylcellulose 190 grams that contract, glycerol 550 grams, distilled water 135 grams, peregal 2010 grams, softener sg 10 grams, sodium benzoate 5 grams respectively.
B. the first water methyl fiber rhzomorph furnishing pasty state that will contract;
C. AVM grease is heated to 80 ℃ of dissolvingizations;
D. glycerol, peregal 20, softener sg heating are mixed.
E. the mixture with above-mentioned dissolved AVM grease and glycerol etc. mixes earlier, adds pasty state starch mixing afterwards and can obtain B
1Content is 1.5% paste 1000 grams.
Embodiment 10. pastes:
A. take by weighing AVM grease (lot number: 940309) 100 grams, sodium alginate 180 grams, glycerol 550 grams, distilled water 145 grams, peregal 2010 grams, softener sg 10 grams, sodium benzoate 5 grams respectively.
B. first water is with sodium alginate furnishing pasty state;
C. AVM grease is heated to 80 ℃ of dissolvingizations;
D. glycerol, peregal 20, softener sg heating are mixed.
E. the mixture with above-mentioned dissolved AVM grease and glycerol etc. mixes earlier, adds pasty state starch mixing afterwards and can obtain B
1Content is 1.5% paste 1000 grams.
Embodiment 8: the powder that contains imidazoles:
A. take by weighing AVM grease (lot number: 940309) 50 grams, CaCO respectively
3300 grams, starch 500 grams, albendazole 150 grams.
B. earlier with AVM grease, albendazole and CaCO
3Fully mixing adds starch abundant mixing again, dries, sieves, check, get final product B
1Content is 0.75% powder 1000 grams.
Embodiment 11. contains the tablet of imidazoles:
A. take by weighing AVM grease (lot number: 940309) 50 grams, albendazole 180 grams, CaCO respectively
3200 grams, starch 400 grams, magnesium stearate 20 grams, dextrin 150 grams.
B. earlier with AVM grease and CaCO
3Mixing;
C. starch is added, fully mixing is made soft material again;
D. use 12 mesh sieve wet granulations, the grain that will wet is put drying room (about 80 ℃) aeration-drying;
E. add magnesium stearate, dextrin mixing, can obtain B with tablet machine tabletting (100mg/ sheet)
1Content is 0.75% tablet 1000 grams.
Embodiment 12. contains the ointment of imidazoles:
A. take by weighing AVM grease (lot number: 940309) 100 grams, albendazole 500 grams, hexadecanol, octadecanol mixture 400 grams, white vaseline 450 grams, lanoline 50 grams respectively.
B. AVM grease, lanoline, white vaseline are heated to 80 ℃ and dissolve, and they mix homogeneously under constantly stirring, and then add and 16, the octadecanol mixture, mixing, check, get final product B
1Content is 1% ointment 1500 grams.
Embodiment 13. contains the ointment of imidazoles:
A. take by weighing AVM grease (lot number: 940309) 100 grams, benzene sulfur imidazoles 500 grams, poly-silicon 600 grams of diformazan, stearyl alcohol 60 grams, peregal 2012 grams, softener sg 25 grams, ethyl hydroxybenzoate 3 grams, distilled water 200 grams respectively.
B. after getting the poly-silicon of oil-phase component-AVM grease, diformazan, stearyl alcohol and water-phase component-peregal 2020, softener sg, glycerol, mud moor gold ethyl ester and water respectively and being heated to 80 ℃ of dissolvings, divide water and oil phase mixing respectively; Oil phase thing with mixing joins in the aqueous-phase material again, mixing, cooling, and pick test can obtain B
1Content is 1% ointment 1500 grams.
Embodiment 14. contains the paste of imidazoles:
A. take by weighing AVM grease (lot number: 940309) 100 grams, albendazole 450 grams, starch 143 grams, glycerol 600 grams, distilled water 170 grams, peregal 202015 grams, softener sg 15 grams, sodium benzoate 7 grams respectively.
B. first water is with starch furnishing pasty state;
C. AVM grease being heated to 80 ℃ dissolves;
D. glycerol, peregal 20, softener sg heating are mixed.
E. the mixture with above-mentioned dissolved AVM grease and glycerol etc. mixes earlier, adds pasty state starch mixing afterwards and can obtain B
1Content is 1% paste 1500 grams.
Embodiment 15. therapeutic tests:
In Xinjiang, the clinical trial of Inner Mongol shows, all reach more than 95% with above-mentioned five kinds of dosage forms of AVM grease preparation anthelminthic effect the sheep endoparasite and ectoparasite.
Claims (4)
1, a kind of broad-spectrum anti-parasite medicine that contains avilamycin comprises powder, tablet, unguentum, ointment, five kinds of dosage forms of paste, and it is characterized in that: avilamycin is for containing a certain proportion of Avermectin A
1, A
2, B
1, B
2The oily mixture of four pairs of eight components (being called for short AVM grease), AVM grease is to form via prepared such as microbial fermentation, extraction, decolourings.
2, by the described anti-parasite medicine of claim 1., it is characterized in that the percentage ratio of AVM grease constitutes: A
13-10%, A
2: 8～15%, B
16～15%, B
2: 3-10%, 14-18 carbon fatty acid 35-40%, water 10-15%.
3, anti-post the worm medicine by claim 1 is described, it is characterized in that the prescription of five kinds of dosage forms is as follows:
(1) wp formula: AVM grease 1-10%+CaCO
339-49%+ starch 50-60%(starch can use equivalent wheat bran, Semen Maydis powder, corn cob to substitute);
(2) tablet formulation: AVM grease 10-20%+CaCO
320-50%+ starch 50-60%+ magnesium stearate 2% dextrin 15%;
(3) ointment prescription: AVM grease 2-20%+ hexadecanol, octadecanol mixture 30-60%+ white vaseline 30-60%+ lanoline 1-10%;
(4) ointment prescription: AVM grease 2-20%+ diformazan gathers silicon 30-60%+ stearyl alcohol 5-10%+ peregal 201-2%+ softener sg 2-4%+ ethyl hydroxybenzoate 0.5-1%+ distilled water 10-30%;
(5) paste prescription: AVM grease 10%+ starch 10～20%+ glycerol 60%+ distilled water 10～20%+ peregal 201%+ softener sg 1%+ sodium benzoate 0.5%(starch can substitute with equivalent cellulose derivative or sodium alginate).
4, antiparasitic according to claim 3 is characterized in that all can extraordinarily going into imidazoles by the 30-60 of B1 amount in five kinds of form formulas, is prepared into the corresponding dosage form that contains the imidazoles medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 95101027 CN1113433A (en) | 1995-01-06 | 1995-01-06 | Antiparasitic medicine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 95101027 CN1113433A (en) | 1995-01-06 | 1995-01-06 | Antiparasitic medicine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1113433A true CN1113433A (en) | 1995-12-20 |
Family
ID=5073743
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 95101027 Pending CN1113433A (en) | 1995-01-06 | 1995-01-06 | Antiparasitic medicine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1113433A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1044440C (en) * | 1996-11-08 | 1999-08-04 | 王玉万 | Animal anti-parasite oral liquor containing avilamycin or envimycin |
| CN1069033C (en) * | 1998-11-13 | 2001-08-01 | 王玉万 | Anti-parasite oral spray containing evericin and ivermectin for sheep |
| CN1069032C (en) * | 1997-03-27 | 2001-08-01 | 中国农业大学 | Antiparasitic medicine containing avermectin/ivermectin for animals |
| CN1114411C (en) * | 1998-08-07 | 2003-07-16 | 武汉第四制药厂 | Compound prothiphenyl imidazole emulsion for repelling and curing animal endoparasites and ectoparasite, and method for preparing same |
| CN102977167A (en) * | 2012-12-17 | 2013-03-20 | 石家庄市兴柏生物工程有限公司 | Abamectin active pharmaceutical ingredient and pesticide using same as active component |
-
1995
- 1995-01-06 CN CN 95101027 patent/CN1113433A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1044440C (en) * | 1996-11-08 | 1999-08-04 | 王玉万 | Animal anti-parasite oral liquor containing avilamycin or envimycin |
| CN1069032C (en) * | 1997-03-27 | 2001-08-01 | 中国农业大学 | Antiparasitic medicine containing avermectin/ivermectin for animals |
| CN1114411C (en) * | 1998-08-07 | 2003-07-16 | 武汉第四制药厂 | Compound prothiphenyl imidazole emulsion for repelling and curing animal endoparasites and ectoparasite, and method for preparing same |
| CN1069033C (en) * | 1998-11-13 | 2001-08-01 | 王玉万 | Anti-parasite oral spray containing evericin and ivermectin for sheep |
| CN102977167A (en) * | 2012-12-17 | 2013-03-20 | 石家庄市兴柏生物工程有限公司 | Abamectin active pharmaceutical ingredient and pesticide using same as active component |
| CN102977167B (en) * | 2012-12-17 | 2014-11-05 | 石家庄市兴柏生物工程有限公司 | Abamectin active pharmaceutical ingredient and pesticide using same as active component |
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