CN101664417A - Niclofolan-contained compound sustained-release animal parasiticide - Google Patents

Abstract

The invention discloses a niclofolan-contained compound sustained-release animal parasiticide, aiming at solving the problems of parasitic mixed infection or multiple infection of the livestock and the poultryin the livestock and poultry cultivation. The niclofolan-contained compound sustained-release animal parasiticide comprises the following raw materials by weight percent: 10-50 percent of niclofolan, 3-20 percent of parasite repellent, 10-40 percent of sustained-release matrix material, and the balance of adhesive. The parasite repellent is one of the ivermectin, the avermectins and the albendazole; the sustained-release matrix material is the hydroxypropyl methyl cellulose; and the adhesive is polyvinylpyrrolidone. The niclofolan-contained compound sustained-release animal parasiticide has broad spectrum and good sustained-release effect, can repel different age groups of various parasite larvae parasitized on the livestock and the poultry by over 97.5 percent, is convenient to use and saves the animal treatment cost. The niclofolan-contained compound sustained-release animal parasiticide can prevent the livestock and the poultry against spring weakness death and weight losscaused by the parasites, thereby being an ideal medicament of preventing the livestock and the poultry like the cattle and the sheep against the parasites.

Description

The animal compound slow release anthelmintic that contains nitroclofene

Technical field

The invention belongs to the broad-spectrum anti-parasite veterinary drug that is used for the treatment of on the veterinary clinic and prevents parasitic disease in or out of livestock and fowl body.

Background technology

Verminosis of animal is the common disease of puzzlement livestock breeding industry development, the cause of disease kind is many, have a very wide distribution, can cause various poultry Chronic consumptionss and infectious disease, the normal growth that not only influences poultry is grown, and greatly reduced quality, the quantity of animal products, the economic benefit of livestock breeding industry is badly damaged.Therefore, using regular anthelmintic of effective anti-parasite medicine and parasite killing, is important step in the livestock and poultry parasite integrated control, to develop animal husbandry and aquaculture have important practice significance.

The common parasitic disease of poultry has ectoparasitism entomiasises such as the external Ticks of gastrointestinal tract nematicide, trematodiasis, taeniasis and poultry, louse, acaricide, sometimes be multiple parasite mixed infection, cause parasite multiparasitization phenomenon, because parasite multiparasitization phenomenon is very general, bring very big inconvenience for parasitic control, and the parasitic medicine of tradition control at present, mostly the anthelmintic spectrum is more single, the anthelmintic spectrum is narrower, it is not thorough that anthelmintic easily takes place single drug, often need repeatedly take medicine, the multiparasitization mixed infection of especially concurrent trematodiasis, single drug is powerless especially.

Summary of the invention

The purpose of this invention is to provide a kind of animal compound slow release anthelmintic that contains nitroclofene, to solve the problem of livestock and poultry parasite mixed infection in the existing animal husbandry breed, multiple infection.

Composition in the raw material of the present invention and weight percentage are: nitroclofene accounts for 10-50%, anthelmintic accounts for 3-20%, sustained-release matrix material 10-40%, adding binding agent to total amount is 100%, anthelmintic is selected from a kind of in ivermectin, avilamycin or the albendazole, the sustained-release matrix material is a hydroxypropyl emthylcellulose, and binding agent is a polyvinylpyrrolidone.

The preferred weight percentage composition is in the raw material of the present invention: nitroclofene accounts for 40%, anthelmintic accounts for 4%, sustained-release matrix material 40%, and adding binding agent to total amount is 100%.

Collection analysis according to long-term market exploration and basic unit's clinical data, recognizing in the clinical preventing and treating verminosis of vast basic unit exists consumption big, repeated drug taking, the problem that uncertain therapeutic efficacy is fixed is through all kinds of anthelmintic Comparison of therapeutic, pharmacology analysis, compatibility is analyzed, and data check selects for use safety and high anti-trematodiasis medicine nitroclofene and other broad-spectrum de-worming medicine of stability to carry out compound, add slow-release material and make compound sustained-released anthelmintic formulation, reach killing parasite adult and each instar larvae.

The present invention has the ideal effect of killing to multiple parasites such as cattle and sheep gastrointestinal tract nematicide, distoma hepaticum, vermins, and effect is better than the folk prescription antiparasitic, once takes to kill multiple common parasite, and is easy to use, simple to operate.But all kinds of nematicides of animal repelling body Mao Yuanke, circular section, back circle section, Rhabditidae, Ascaridae, Oxyuridae, Trichocephalidae and the net tail section often sent out clinically, cysticercosis, all kinds of trematodiasis and thread lungworm, and respectively belong to the different parasitic stages of nematicide and comprise larva, in addition the multiple epizoa that parasitizes the poultry body surface such as Ticks, demodicid mite, louse, flea, fly, maggot etc. are also killed effect.

The present invention has following characteristics: 1, anthelmintic wide spectrum covers poultry and often sends out the multiple class of parasite multiple.2, had good sustained release effect is killed each instar larvae of parasite comprehensively, drives clean rate and reaches more than 97.5%.3, easy to use.4, save the treatment cost.Weary death of the spring that this product can prevent the poultry endoparasite to cause and body weight loss are animal anthelmintic desirable anti-parasite medicines in spring and autumn such as cattle and sheep.

The present invention is as follows through the clinical efficacy test of animal medicine institute of Gansu Agriculture University:

Test one

1, materials and methods

(1) trial drug nitroclofene-ivermectin sheet, lot number: 20040601, Wuwei Hongniu Agricultural ﹠ Animal Husbandry Technology Co., Ltd. produces, and uses for clinical trial; Ivermectin injection, Zhongmu Stocks Trading Co. Chengdu medical instruments factory provides lot number: 20040301; Levamisole, animal drug factory in Shandong Province's produces, lot number: 20031203.

(2) experimental animal select for use sheep raising field, Yuzhong County, Gansu Province clinical symptoms obviously, the faecal egg inspection infects 280 serious sheep of gastrointestinal nematode and differs as a subjects sheep age in days, and stud ram, ewe and young sheep are arranged, the test sheep searches for food normally.

(3) test is grouped under the same raising condition, will test sheep and be divided into 4 groups at random, and 70 every group, the A group is medication therapy groups, B, and the C group is the medicine matched group, the D group is the blank group.

(4) medication A group is pressed 0.3mg/kg body weight oral dose nitroclofene-ivermectin sheet; The B group is pressed the disposable intramuscular injection ivermectin injection of 0.2mg/kg body weight dosage; The C group is pressed 7.5mg/kg body weight oral dose levamisole; The D group is blank group, not administration.

2, result of the test

(1) efficacy determination method.

1. clinical observation is selected 5 goats at random from every group respectively and is surveyed its body temperature, P﹠R number, gets its meansigma methods, compares before and after the test.

2. worm's ovum is checked 1d before dispensing, gastrointestinal nematode worm's ovum number (EPG) the dispensing back of using Me Master ' s method counting to calculate in every gram feces was counted EPG in the 10th day and the 21st day again, before calculating 20 sheep anthelmintics, anthelmintic after 10 days, the nematicide worm's ovum meansigma methods of anthelmintic after 21 days, and calculate worm's ovum slip and worm's ovum negative conversion rate.

The worm's ovum slip=[average EPG value before (the average EPG value in average EPG value one test back before the test)/test " * 100%

Worm's ovum negative conversion rate=(experimental animal turn out cloudy a number/confession examination number of animals) * 100%

3. result of the test

Have no adverse reaction behind the drug administration of A, B, C group, sheep body temperature, P﹠R number are normal, appetite, drinking-water, discharge feces, urinate all no abnormal, the mental status was observed in good the 21st day, originally became thin, the sheep growth of livestock of anemia, dysentery is clearly better the feces of discharging in pelletized form, appetite strengthens, good bloom.

Each organizes in the sheep dung before the anthelmintic, anthelmintic after 10 days, anthelmintic after 21 days gastrointestinal nematode worm's ovum meansigma methods and worm's ovum slip and the worm's ovum negative conversion rate after the dispensing, see following table for details:

Test one table treatment sheep gastrointestinal nematode clinical trial

The result shows: can effectively drive away the sheep gastrointestinal nematode by middle dosage 0.3mg/kg body weight oral dose medicine nitroclofene of the present invention-ivermectin sheet, curative effect obviously is better than B group matched group to be organized by 7.5mg/kg body weight oral dose Ergamisole by disposable intramuscular injection ivermectin injection of 0.2mg/kg body weight dosage and C, and difference is (P＜0.01) extremely significantly.

Test two

1, materials and methods

(1) laboratory animal

Wuwei, Gansu Province several sheep raising factory amounts to 6 groups 319, chooses 120 of goats that truly have fasciola hepatica infection through the inspection of the faecal egg sedimentation method, does not infect 20 of distoma hepaticum sheep, amounts to 140.Wherein male 62, female 78; Body weight 15-40kg; Age 0.5-3 year.

(2) experiment medicine

Medicine nitroclofene-ivermectin sheet, by our company's development, lot number is 20040601,

Shake magnificent animal pharmaceutical factory of control drug ALBENDAZOLE, Kunming, Yunnan Province produces, and lot number is 20040312, and specification is the 50mg/ sheet, and recommended dose is oral, 10mg/kg.

(3) experimental technique

1. 7d after preceding 1d of medication and the medication before the worm's ovum inspection is distinguished, 14d, 21d adopts excrement from the goat rectum, carries out quantitative check with the precipitation worm's ovum.Being about to the new sheep stool of gathering weighs, adding little water smashs to pieces with Glass rod or wooden chopsticks, adding water again shakes up in right amount, 80 mesh sieves filter, and the filtrate repeated precipitation is washed to clear, and supernatant inclines, measure the hypostasis volume, shake up the back and be added in 2 1mL or 4 the 0.5mL egg count chambers,, calculate every gram faecal egg number with formula EPG=N ÷ V * L ÷ G in microscopic counting with suction pipe.Wherein N is the worm's ovum sum in 2 1mL or 4 the 0.5mL egg count chambers; L is the hypostasis volume; G is alleged feces gram number; V is counting chamber cumulative volume=2 * 1 or 4 * 0.5.

2. polypide is checked after medication 21 days and cuts open and kills each group experiment goat, or dead goat is cutd open inspection, checks and the distoma hepaticum situation of record liver and gall and intestinal.

2, result of the test

(1) deworming rates is calculated respectively in following three formula and is calculated the essence deworming rates of each group experiment sheep respectively, slightly counts deworming rates and drive clean rate.

Worm's ovum number * 100% before smart meter deworming rates=(worm's ovum number after the preceding several administrations of worm's ovum of administration) ÷ administration

Thick meter deworming rates=(the average residual polypide number of the several experimental grouies of the average residual polypide of matched group) the average residual polypide number of ÷ matched group * 100%

Drive clean rate=(driving the whole laboratory animal numbers of clean polypide number of animals ÷) * 100%

(2) treatment is grouped on the basis of the 1st excrement inspection egg count, has confirmed to have fasciola hepatica infection and 20 goats numberings that do not infect distoma hepaticum with 120, is divided into 4 groups, positive controls, each 20 of negative control group, each 50 of medicine groups.Concrete outcome sees the following form:

Test two table treatment sheep distoma hepaticum clinical trials

Group	Size of animal	Drive net amount	Drive clean rate (%)	Average infection intensity	Deworming rates
						Medicine matched group (Albendazole)	??50	??35	??70	??0.30	??72.3
Test group (oral the present invention)	??50	??46	??92**	??0.05	??97**
						Normal healthy controls group (not administration)	??10

The result shows: nitroclofene-ivermectin sheet is pressed 0.3mg/kg body weight oral dose, drives clean rate and slightly count deworming rates to be respectively 92%, 97%; Relatively have utmost point significant difference (P＜0.01) with positive controls, Albendazole commonly used clinically at present will be got well.

Test three

1, material and method

(1) trial drug

Nitroclofene-ivermectin sheet, our company's development, lot number: 20040601.Ivermectin sheet (2mg/ sheet) middle peasant Hua Wei company provides lot number: 20031202

(2) experimental animal

Cattle is that Lanzhou sheep cattle self-employed entrepreneurs raises, and ox head portion, back, abdominal part, pars inguinalis are come off by hair, and cattle rubs everywhere, that the skin that has has frayed is hemorrhage _ and, through check natural infection acaricide.Therefrom select 30 (to have several calves to be with in addition, do not do data statistics by the suckling cattle.) typical person, random packet is for examination.

(3) test method

1. divide into groups and offer medicine: be divided into three groups at random for the sick cattle of examination. do not isolabeling.

First group 10 cattle (finished cattle) are nitroclofene-ivermectin sheet group. oral by every kg body weight 0.3mg.After the medication the 7th day, repeated drug taking once.

Second group 10 cattle (finished cattle) are the ivermectin group. by every kg body weight 0.2mg, oral.After the medication the 7th day, repeated drug taking once.

The 3rd group of 10 cattle are that matched group (duration of test isolated rearing) is not done treatment.

2. anthelminthic effect is observed: observe in the process of the test cattle clinical symptoms comprise very itch, the variation of affected part focus, diet desire, mental status etc. preceding the 0th day of medication), after the medication the 7th, 14,21,28 days, by head behind ear, the strong intersection in extremity inboard, back, abdominal part, inguinal disease picks 50% glycerine water solution and scrapes the bark fetching bits perpendicular to skin with dissecting knife, till oozing of blood, a little scurf is placed on the microscope slide.The glycerine water solution of Dropwise 5 0% adds coverslip, test under microscope.If do not find polypide, scurf is put in 10% sodium hydroxide solution, heated and boiled 10Min, per minute 2000 leave heart 5Min and get and be deposited in test under microscope.If do not find then to be judged as feminine gender by polypide; If find that polypide then is judged as the positive.It is identical that duration of test is respectively organized cattle breeding management, and each cowshed is after medication the 4th, 7,10 days simultaneously, and ground is thoroughly swept, and metope thoroughly whitewashes with lime water.Handle observed result and calculate the polypide negative conversion rate, formula is as follows:

Polypide negative conversion rate (%)=(after the anthelmintic polypide turn out cloudy the positive ox head number of polypide before ox head number/anthelmintic) * 100%

2, result of the test

Each test group is before anthelmintic. and ox head portion, cervical region, back are come off by hair. and big diameter has 25cm, little of the disme size. skin has red scar rash. the cattle friction everywhere of very itching. the skin that has frayed hemorrhage _. skin knot in many places is silly, hard solid, forms gauffer and be full of cracks. drink is off one's feed. become thin. thick disorderly, contrary upright, matt by hair.

After test group was used nitroclofene-ivermectin sheet and ivermectin respectively, the 2nd Anoplophorae seu Aprionae apparent friction reduced. and the cattle friction condition almost disappears after the 7th day. and focus is dwindled gradually subsequently. and silly skin comes off gradually. and the 28th day skin has had virgin wool to grow to the medication.Cause of disease inspection in the scurf.Used for the first time behind nitroclofene-ivermectin sheet and the ivermectin the 7th day, two groups all have cattle to detect cause of disease, but polypide all is a larva.Three inspections of the 14th, 21,28 days all do not find the cause of disease (check result sees the following form).

Acaricide check result (male/female) before and after the cattle treatment

Review time	First group (clothes the present invention)	Second group (ivermectin group)	The 3rd group (not treating)
				Before the medication	??10/0	??10/0	??10/0
After the medication the 7th day	??3/7	??5/5	??10/0
				After the medication the 14th day	??0/10	??0/10	??10/0
After the medication the 21st day	??0/10	??0/10	??10/0
				After the medication the 28th day	??0/10	??0/10	??10/0

Test shows, gets nitroclofene-ivermectin sheet by 0.3mg/kg body weight oral dose for first group, the 7th day repeated drug taking once, for the first time the 14th, 21,28 days polypide negative conversion rates all can reach 100% after the medication.As seen, nitroclofene-ivermectin sheet has the effect of well killing to Sarcoptes bovis.

Animal medicine institute of Gansu Agriculture University, conclusion: confirm through clinical trial, nitroclofene-ivermectin compound recipe sheet (worm demodicid mite KUAIKE) by Wuwei Hongniu Agricultural ﹠ Animal Husbandry Technology Co., Ltd.'s development and production, the corresponding parasite condition of disease of domestic animal is played the effectively preventing effect, with its anthelmintic wide spectrum, easy and simple to handle, evident in efficacy, and be better than like product.

The specific embodiment

The following examples can make those skilled in the art more fully understand the present invention, but do not limit the present invention in any way.

Embodiment 1 " nitroclofene+avilamycin " prescription type

Method for making: take by weighing nitroclofene 50% (W/W), avilamycin 5% (W/W) and hydroxypropyl emthylcellulose 20% (W/W) and cross 80 mesh sieves respectively, by the equivalent method mixing that progressively increases, with the polyvinylpyrrolidone ethanol solution is that binding agent 25% (W/W) is made tablet, every contains nitroclofene 125mg, avilamycin 12.5mg.

Using method is for oral administration swallows or pulverizes spice and once measure every 1kg body weight cattle, sheep 0.3mg (by avilamycin).Lucifuge, airtight is preserved in the cool.

Case: Wuwei animal and veterinary station, town home town Liu that sees and treat patients of radically reforming raises 17 beef cattles, suffer from the skin itch mite after diagnosing, the disturbance of cattle body is uneasy, has and grinds the phenomenon that bites of itching, and the fur large tracts of land comes off, scrape the bark fetching bits on one's body from sick cattle before the medication and do micrography, be diagnosed as the cattle acaricide, the compound recipe nitroclofene sheet (" nitroclofene+avilamycin " prescription type) of selecting for use our factory to produce, after the medication 1 day, 14 beef cattles symptom of scratching where it itches obviously alleviates, and throws clothes once more with identical dosage after 7 days, continues to observe.After 28 days, all beef cattles be can not check the itch mite of controlling substantially, and dead demodicid mite is rare.At this moment, the equal rehabilitation of sick cattle also grows virgin wool, after 56 days, continues to check, suffers from cattle and returns to one's perfect health, and does not detect demodicid mite alive.

Embodiment 2 " nitroclofene+albendazole " prescription type

Method for making: take by weighing nitroclofene 10% (W/W), albendazole 20% (W/W) and hydroxypropyl emthylcellulose 20% (W/W) and cross 80 mesh sieves respectively, by the equivalent method mixing that progressively increases, with the polyvinylpyrrolidone ethanol solution is that binding agent 50% (W/W) is made tablet, every contains nitroclofene 25mg, albendazole 50mg.

Using method is for oral administration swallows or pulverizes spice and once measure every 1kg body weight cattle, sheep 10～15mg (by albendazole).Lucifuge, airtight is preserved in the cool.

Case: Wuwei following pair of township sheep raising rich and influential family sheep anthelmintic in autumn, use the compound recipe nitroclofene sheet (" nitroclofene+albendazole " prescription type) of our factory development to do clinical trial, selected 27 sheep all have parasitic infection symptom in various degree before test, sneeze frequently, hit wall, shake the head, bite, the per rectum stool examination, every gram feces on average detects 852 of worm's ovums, be diagnosed as the concurrent multiple infection of sheep gastrointestinal nematode and trematodiasis, the part sheep only has loose bowels seriously, disorderly thick by hair, the growth of livestock seriously descends, take compound recipe nitroclofene sheet after 7 days with the dosage of the oral a slice of per 10 kg body weight, sheep only stops to have loose bowels, and feed intake is gone up, after 12 days, hair color bleaches and brightens, and the growth of livestock takes a turn for the better, and the every gram of feces detects 4 of worm's ovums, the sheep of testing only there is no toxic and side effects in this test, and the result shows compound recipe nitroclofene sheet, and to kill multiple sheep parasite effect very remarkable to disposable.

Embodiment 3 " nitroclofene+ivermectin " prescription type

Method for making: take by weighing nitroclofene 30% (W/W), ivermectin 3% (W/W) and hydroxypropyl emthylcellulose 40% (W/W) and cross 80 mesh sieves respectively, by the equivalent method mixing that progressively increases, with the polyvinylpyrrolidone ethanol solution is that binding agent 27% (W/W) is made tablet, every contains nitroclofene 75mg, ivermectin 7.5mg.

Using method is for oral administration swallows or pulverizes spice and once measure every 1kg body weight cattle, sheep 0.3mg (by ivermectin).Lucifuge, airtight is preserved in the cool.

Case: Wuwei sheep raising rich and influential family sheep anthelmintic in autumn, use the compound recipe nitroclofene sheet (" nitroclofene+ivermectin " prescription type) of our factory development to do clinical trial, selected 38 sheep all have parasitic infection symptom in various degree before test, sneeze frequently, hit wall, shake the head, bite, the per rectum stool examination, every gram feces on average detects 713 of worm's ovums, be diagnosed as the sheep distoma hepaticum multiple infection that disappears, the part sheep only has loose bowels seriously, disorderly thick by hair, the growth of livestock seriously descends, take compound recipe nitroclofene sheet after 7 days with the dosage of the oral a slice of per 10 kg body weight, sheep only stops to have loose bowels, and feed intake is gone up, after 12 days, hair color bleaches and brightens, and the growth of livestock takes a turn for the better, and the every gram of feces detects 4 of worm's ovums, the sheep of testing only there is no toxic and side effects in this test, and the result shows compound recipe nitroclofene sheet, and to kill multiple sheep parasite effect very remarkable to disposable.

Embodiment 4 " nitroclofene+ivermectin " prescription type

Method for making: take by weighing nitroclofene 40% (W/W), ivermectin 4% (W/W) and hydroxypropyl emthylcellulose 40% (W/W) and cross 80 mesh sieves respectively, by the equivalent method mixing that progressively increases, with the polyvinylpyrrolidone ethanol solution is that binding agent 16% (W/W) is made tablet, every contains nitroclofene 100mg, ivermectin 10mg.

Using method is for oral administration swallows or pulverizes spice and once measure every 1kg body weight cattle, sheep 0.3mg (by ivermectin).Lucifuge, airtight is preserved in the cool.

Case: Wuwei sheep raising rich and influential family sheep anthelmintic in spring, use the compound recipe nitroclofene sheet (" nitroclofene+ivermectin " prescription type) of our factory development to do clinical trial, selected 23 sheep all have parasitic infection symptom in various degree before test, the per rectum stool examination, every gram feces on average detects 671 of worm's ovums, be diagnosed as the concurrent multiple infection of sheep gastrointestinal nematode and trematodiasis, the part sheep only has loose bowels seriously, thick disorderly the growth of livestock seriously descends by hair, with oral this product after 7 days, sheep only stops to have loose bowels, feed intake is gone up, and after 12 days, hair color bleaches and brightens, the growth of livestock takes a turn for the better, the every gram of feces detects 4 of worm's ovums, and the sheep of testing only there is no toxic and side effects in this test, and the result shows nitroclofene-ivermectin sheet, and to kill multiple sheep parasite effect very remarkable to disposable.

Claims (2)

1, a kind of animal compound slow release anthelmintic that contains nitroclofene, it is characterized in that composition and weight percentage in the raw material are: nitroclofene accounts for 10-50%, anthelmintic accounts for 3-20%, sustained-release matrix material 10-40%, adding binding agent to total amount is 100%, anthelmintic is selected from a kind of in ivermectin, avilamycin or the albendazole, the sustained-release matrix material is a hydroxypropyl emthylcellulose, and binding agent is a polyvinylpyrrolidone.

2, according to the described animal compound slow release anthelmintic that contains nitroclofene of claim 1, it is characterized in that composition and the weight percentage in the raw material is: nitroclofene accounts for 40%, anthelmintic accounts for 4%, sustained-release matrix material 40%, and adding binding agent to total amount is 100%.