CN1923179A - Slow release agent for preventing and treating rabbit and chicken coccidiosis and chicken leucocytozoonosisin and preparing method thereof - Google Patents

Abstract

The invention relates to a slow-release agent for treating coccidiosis. Wherein, it uses primachin phosphate and beta cyclodextrin as materials, while their mass ratio is 1:1.5-3.5; and the production comprises (1), dissolving the primachin phosphate at 1g:3-5ml into distilled water; (2), mixing beta cyclodextrin with distilled water at 1g:2-3ml, to be grinded into paste; (3), adding primachin phosphate solution into paste, to be mixed, dried, broken, screened, packed and sealed into slow-release agent; (4), mixing the powder slow-release agent with normal saline at 0.75g-1.34g:20, l, into injection. The invention has high safety and simple operation.

Description

Control coccidiosis of chicken and rabbit and chicken leucocytozoonosisin slow releasing agent and preparation method thereof

Technical field

The present invention relates to livestock and poultry parasite disease Prevention Technique field, especially relate to medicinal slow release agent of control rabbit and chicken coccidiosis and chicken leucocytozoonosisin and preparation method thereof.

Background technology

Rabbit and chicken coccidiosis are to be parasitized in the epithelial cell of the intestinal tube of rabbit and chicken and bile duct by coccidiosis, cause dysentery and dystrophic a kind of protozoacide.The coccidiosis of chicken and rabbit infection rate of 30～60 ages in days reaches 57.3～93.5%, and mortality rate reaches 39.7～85.9%.The common drug of treatment coccidiosis has Robenidine, clopidol, diclazuril, sulphaquinoxaline, sulfadimidine etc., the said medicine mix fodder taken 3～15 days continuously, and drug withdrawal 5～7 days, and then take.Have research report Robenidine, clopidol, sulphaquinoxaline, sulfadimidine often to develop immunity to drugs, especially sulfonamides such as sulphaquinoxaline, sulfadimidine very easily develops immunity to drugs.

Live the leukocyte parasitosis and be called for short leucocytozoonosisin, be that parasite by the Plasmodiidae Leucocytozoon parasitizes in the leukocyte of birds and birds, cause that suffering from the serious anemia of fowl, diarrhoea and biped collapses from physical exhaustion etc. and to be the protozoacide of cardinal symptom, 40～60 mouthfuls age chicken leucocytozoonosisin infection rate reach 27.3～73.5%, mortality rate reaches 19.7～68.9%.This disease is mainly sent out main in southern province, medicine sulphaquinoxaline commonly used or pyrimethamine and sulfadimethoxine etc. adopt medicine mix fodder continuous use after 5 days, drug withdrawal 2～3 days, and then the method for taking, but such medicine also has the problem that easily develops immunity to drugs.

In above-mentioned two kinds of protozoacide, normal mixed infection coccidiosis of chicken and leucocytozoonosisin; Rabbit mainly infects coccidiosis; Sick chicken and the normal skeletonize of sick rabbit, anemia and cause death, these two kinds of parasitic disease are one of diseases the most expensive during poultry industry is produced, and cause heavy economic losses.

At present, prevent and treat with the effect of control coccidiosis and leucocytozoonosisin very undesirable for a long time with oral medicine.Oral medicine is short in the gastrointestinal tract time of staying on the one hand, and metabolism is fast, and consumption is big, control cost height, time-consuming again, interim therapeutical effect (phase of generally preventing and treating only has 1～2 day) is only arranged, and do not have the long-term insecticidal effect that continues, so in application need repeated multiple times or take for a long time and can take effect; The opposing party and, take similar medicine for a long time, inevitable at the poultry body accumulation, quicken to develop immunity to drugs, people are edible also dangerous.Therefore, the culturist of rabbit and chicken urgently wishes to have the new drug of a kind of long lasting control coccidiosis of chicken and rabbit and chicken leucocytozoonosisin.

The primaquine phosphate anti-malaria medicaments is usually used in people's plasmodial control, and this medicine has stronger killing action to infrared phase of plasmodium and gametocyte.The malaria protozoacide action principle of this medicine may be that its metabolite has oxidizing property, disturbs the reduction process of the infrared phase codehydrogenase II of plasmodium, influences plasmodial energy metabolism and breathing and causes death.Data introduction (HighPower king Jansen carrier pigeon research center www.hpw-js.com whole world racing homer pigeon information network) is arranged, select the haematozoon of primaquine phosphate and Arechin (Polfa) alternating treatment racing homer pigeon HAEMOPROTEUS for use, wherein, primaquine phosphate is 13.2mg ()/1000 ml waters, 21 days courses of treatment, effect is comparatively satisfied.But do not see the document announcement of using primaquine phosphate control rabbit and chicken coccidiosis and chicken leucocytozoonosisin is arranged.For this reason, the inventor at first adopts primaquine phosphate, in spice oral administration mode, rabbit and chicken coccidiosis and chicken leucocytozoonosisin has been done the test of preparation property prevention effect, and clearly this medicine all has better therapeutic effect to rabbit and chicken coccidiosis and chicken leucocytozoonosisin; But also find to exist following problem: the one, though medicine spice oral administration mode is convenient concerning feed lot in enormous quantities, due to illness and feed intake reduces but because wherein sick rabbit and sick chicken, especially sick rabbit that is in a bad way and sick chicken even stop to eat feedstuff, the requirement that this does not just reach feed effective dose medicine also just is difficult to reach therapeutic effect; The 2nd, though the primaquine phosphate drug effect is high, its toxicity is bigger, therefore, often occurs in same raising colony, and healthy chicken, rabbit cause because of feed intake is excessive and poison even dead, and morbidity chicken, rabbit therapeutic effect are relatively poor even invalid; The 3rd, though the primaquine phosphate regular dosage form has short term therapy effect preferably, but it is the same with above-mentioned sulfonamides, does not have to continue insecticidal effect for a long time, in case drug withdrawal easily repeated infection coccidiosis, leucocytozoonosisin again, and take this medicine for a long time continuously, then certainly lead to drug-fast problem again; Simultaneously in the process of this medicinal slow release agent of development, a difficult problem that runs into is that the medicine inclusion rate is low, only about 63%, and with phenomenon such as effect instability in application test.

Summary of the invention

The objective of the invention is problem at above-mentioned existence, find a kind of new worm and live the tapeworm medicine of efficiently killing, and utilize beta cyclodextrin can improve medicine dissolution, reduce toxicity, slowly discharge medicine, prolong advantages such as drug effect, be optimized proportioning, provide a kind of cost low, pharmaceutical release time is long, can prevent and treat the medicinal slow release agent product of rabbit and chicken coccidiosis and chicken leucocytozoonosisin or wherein any parasite disease simultaneously; Another object of the present invention is the preparation method that proposes this slow releasing agent.

The present invention seeks to be achieved by following technical proposals:

Control coccidiosis of chicken and rabbit and chicken leucocytozoonosisin slow releasing agent are raw material with primaquine phosphate and beta cyclodextrin, and 1: 1.5 by weight～3.5 is formulated.

The optimization formula of described slow releasing agent, primaquine phosphate and beta cyclodextrin 1: 2.34 by weight are formulated.

A kind of method for preparing control coccidiosis of chicken and rabbit and chicken leucocytozoonosisin slow releasing agent, carry out as follows:

(1) will kill worm medicament primaquine phosphate and distilled water, volume ratio is 1 gram by weight: 3～5 milliliters of mixing, be stirred to medicine and dissolve fully, standby;

(2) with beta cyclodextrin and distilled water, volume ratio is 1 gram by weight: 2～3 milliliters of mixing, grind 20～30 minutes one-tenth pasty states, and standby;

(3) step (1) primaquine phosphate solution is poured in step (2) the pasty state beta cyclodextrin, stirred 30～60 minutes, moisture natural evaporation or vacuum drying under 30～40 ℃ of temperature are pulverized, and 80～90 orders sieve, the powdering slow releasing agent;

(4) with the packing of step (3) powdery slow releasing agent, sealing is powdering slow releasing agent product;

(5) with step (4) powdery slow releasing agent and normal saline by weight volume ratio be 0.75～1.34 gram: 20 milliliters are mixed with slow-release injection.

Beneficial effect of the present invention:

The one, by the inventive method will kill worm medicine primaquine phosphate by the proper proportion enclose in beta cyclodextrin glycosidic bond circulus, form ultra micro cryptomere clathrate, the inclusion rate of medicine by in the past about 63% bring up to 97.9～99.3%, make the internal energy accurate quantification of this slow releasing agent ground include medicament contg index by designing requirement; The 2nd, the results showed, this slow releasing agent is done subcutaneous intramuscular injection by 0.14ml/kg body weight dosage, in a short time coccidiosis or leucocytozoonosisin and both mixed infection persons all there is excellent curative, general 1～3 day promptly takes effect, its effective control phase reaches 2 months and does not have repeated infection in the long term, saves control medication expense 97.6%; The 3rd, this slow releasing agent dosage is few, the wherein contained primaquine phosphate of injection shot is the 2mg/kg body weight, only be half of oral once a day primaquine phosphate (4mg/kg body weight) dosage, reduce primaquine phosphate drug cost 50～95% (are 21 days by a course of treatment); And safe, reduced the toxic and side effects of the former drug form of primaquine phosphate, when the dose of injection primaquine phosphate slow releasing agent during greater than 1 times of stomodaeum dosage, rabbit and chicken still do not have any side reaction (seeing the routine table 1 of test); Four are to use conveniently, are easy to apply; The 5th, promote growth of animals or poultry, body weight obviously increases behind the injecting drug use, and prevention effect is seen the routine table 2 of test.

The specific embodiment

The present invention is described in further detail by following examples, but this is not specifically to place restrictions on of the present invention:

Primaquine phosphate: the Changshu Nanhu Industrial Chemical Plant produces, content 99%;

Beta cyclodextrin: Liquan chemical industry limited industrial corporation in Shaanxi Province's produces.

The preparation method 1 of embodiment 1:(control rabbit and chicken coccidiosis and chicken leucocytozoonosisin slow releasing agent)

(1) powdery is killed worm and live 200 milliliters of tapeworm medicament primaquine phosphate 50 gram+distilled water → be stirred to medicine to be dissolved into transparency liquid fully;

(2) in the pasty state with 234 milliliters of powdery beta cyclodextrin 117 gram+distilled water → grinding 20 minutes;

(3) primaquine phosphate solution is poured in the pasty state beta cyclodextrin, stirred after 30 minutes, put under 30～40 ℃ until drying, after the pulverizing, 80～90 orders sieve, i.e. powdering slow releasing agent 167 grams;

(4) the powdery slow releasing agent is pressed 1 gram/every bottle of packing, sealing is powdering slow releasing agent product.

(5) every bottle of powdery slow releasing agent is added the 20ml normal saline, shake, be the slow releasing agent injection to the whole moistening one-tenth suspensions of medicine.

The preparation method 2 of embodiment 2:(control rabbit and chicken coccidiosis and chicken leucocytozoonosisin slow releasing agent)

(1) powdery is killed worm and live 150 milliliters of tapeworm medicament primaquine phosphate 50 gram+distilled water → be stirred to medicine to be dissolved into transparency liquid fully;

(2) in the pasty state with 225 milliliters of powdery beta cyclodextrin 75 gram+distilled water → grinding 30 minutes;

(3) primaquine phosphate solution is poured in the pasty state beta cyclodextrin, stirred after 40 minutes, put under 30～40 ℃ until drying, after the pulverizing, 80～90 orders sieve, i.e. powdering slow releasing agent 125 grams;

(4) the powdery slow releasing agent is pressed 0.75 gram/every bottle of packing, seal, i.e. powdering slow releasing agent product;

(5) every bottle of powdery slow releasing agent is added the 20ml normal saline, shake, be the slow releasing agent injection to the whole moistening one-tenth suspensions of medicine.

The preparation method 3 of embodiment 3:(control rabbit and chicken coccidiosis and chicken leucocytozoonosisin slow releasing agent)

(1) powdery is killed worm and live 250 milliliters of tapeworm medicament primaquine phosphate 50 gram+distilled water → be stirred to medicine to be dissolved into transparency liquid fully;

(2) in the pasty state with 525 milliliters of powdery beta cyclodextrin 175 gram+distilled water → grinding 40 minutes;

(3) primaquine phosphate solution is poured in the pasty state beta cyclodextrin, stirred after 50 minutes, put under 30～40 ℃ until drying, after the pulverizing, 80～90 orders sieve, i.e. powdering slow releasing agent 225 grams;

(4) the powdery slow releasing agent is pressed 1.34 gram/every bottle of packing, seal, i.e. powdering slow releasing agent product;

(5) every bottle of powdery slow releasing agent is added the 20ml normal saline, shake, be the slow releasing agent injection to the whole moistening one-tenth suspensions of medicine.

Test example: (slow releasing agent control and gaining effect contrast test)

Each 150 of test coccidiosis rabbits (30 age in days) and leucocytozoonosisin chicken (30 age in days), respectively be divided into 3 groups, every group 50, be divided into slow releasing agent injection group: adopt embodiment 1,2 or 3 prepared slow releasing agent injections to press the injection of 0.14ml/kg body weight, wherein contained primaquine phosphate dose is the 2mg/kg body weight; Oral group: the primaquine phosphate dosage is a 4mg/kg body weight spice; Not medication matched group.In (0 day) and the test (10,20,30,40,50,60,70 days), rabbit is adopted excrement and looks into the coccidian oocyst number with the saturated brine floating method, calculates egg reduction rate % before test; Chicken blood sampling smear fast staining microscopy is lived the tapeworm number, calculates worm reduction rate %.Each group is weighed before the test, weigh during off-test, and relatively 3 groups of rabbits and chicken weightening finish situation, it the results are shown in Table 1, table 2.

From table 1, behind the coccidiosis rabbit injection slow releasing agent 10～70 days, its coccidian oocyst egg reduction rate was 99.7～98.4%.Behind the leucocytozoonosisin chicken injection slow releasing agent 10～70 days, it lives the tapeworm worm reduction rate was 100～98.7%; The oral primaquine phosphate of coccidiosis rabbit (4mg/kg body weight) back 10～70 days, its coccidian oocyst egg reduction rate is 95.6～73.3%.Behind the oral primaquine of leucocytozoonosisin chicken 10～70 days, it lives the tapeworm worm reduction rate was 97.5～75.6%; And not medication of coccidiosis rabbit matched group, its coccidian oocyst increases to 596 from 291, and the increasing egg production of silkworm rate is 8.2～104.8%; It lives the leucocytozoonosisin chicken tapeworm and increases to 483 from 354, and increasing the worm rate is 3.1～36.4%.

Table 1 slow releasing agent is to the prevention effect contrast test of rabbit coccidiosis and chicken leucocytozoonosisin

Group	Name of disease		Before and after the injection (my god)
											0	10	20	30	40	50	60	70
			Injection slow releasing agent group	Coccidiosis	Egg sac number	312	1	3	2	3									3	5	5
Egg reduction rate %	0	99.7									99.0	99.4	99.0	99.0	98.4	98.4
					Live tapeworm	Borer population	371	0	0	0							0	0	1	5
Worm reduction rate %	0	100		100							100	100	100	99.7	98.7
						Oral primaquine group	Coccidiosis	Egg sac number	296	33						17	13	20	35	43	79
Egg reduction rate %	0	88.9	94.3	95.6	93.2						88.2	85.5	73.3
								Live tapeworm	Borer population	365				23	9	11	9	35	67	89
Worm reduction rate %	0	93.7	97.5	97.0	97.5		90.4				81.6	75.6
									Not medication matched group	Coccidiosis			Egg sac number	291	317	375	402	439	493	513	596
Egg reduction rate %	0	+8.2	+28.9	+38.1	+50.9	+69.4	+76.3	+104.8
											Live tapeworm	Borer population	354	365	394	398	412	430	475	483
Worm reduction rate %	0	+3.1	+11.3	+12.4	+16.4	+21.5	+34.2	+36.4

The gaining effect contrast test of table 2 slow releasing agent control rabbit coccidiosis and chicken leucocytozoonosisin

Group	Animal	Only	Starting weight (kg)	End heavy (kg)	Average weight gain (Kg)	With oral medicine than (%)	With not medication than (%)
								The slow releasing agent group	Rabbit	50	0.67	2.85	2.18	59.1	165.9
Chicken	50	0.23	1.32	1.09	39.7	127.1
							The oral medicine group		Rabbit	50	0.67	2.04	1.37		79.3
Chicken	50	0.24	1.02	0.78		62.5
								Not medication group	Rabbit	50	0.69	1.51	0.82
Chicken	50	0.24	0.72	0.48

39.7%, than the weightening finish of raising respectively 165.9%, 127.1% without medical treatment, oral medicine is than the weightening finish of raising respectively 79.3%, 62.5% without medical treatment.

Claims (3)

1, the slow releasing agent of control coccidiosis of chicken and rabbit and chicken leucocytozoonosisin is characterized in that with primaquine phosphate and beta cyclodextrin be raw material, and 1: 1.5 by weight～3.5 is formulated.

2, by the described slow releasing agent of claim 1, it is characterized in that with primaquine phosphate and beta cyclodextrin be raw material, 1: 2.34 by weight formulated.

3, the method for preparing the described slow releasing agent of claim 1 is characterized in that carrying out according to the following steps:

(1) will kill worm medicament primaquine phosphate and distilled water, volume ratio is 1 gram by weight: 3～5 milliliters of mixing, be stirred to medicine and dissolve fully, standby;

(2) with beta cyclodextrin and distilled water, volume ratio is 1 gram by weight: 2～3 milliliters of mixing, grind 20～30 minutes one-tenth pasty states, and standby;

(3) step (1) primaquine phosphate solution is poured in step (2) the pasty state beta cyclodextrin, stirred 30～60 minutes, moisture natural evaporation or vacuum drying under 30～40 ℃ of temperature are pulverized, and 80～90 orders sieve, the powdering slow releasing agent;

(4) with the packing of step (3) powdery slow releasing agent, sealing is powdering slow releasing agent product;

(5) with step (4) powdery slow releasing agent and normal saline by weight volume ratio be 0.75～1.34 gram: 20 milliliters are mixed with slow-release injection.