CN103908428A - Ponazuril nanosuspension and preparing method thereof - Google Patents

Abstract

The invention belongs to the technical field of veterinary medicine, and relates to a preparing method of a ponazuril nanosuspension. The suspension can be administered through water drinking, and can be uniformly dispersed in water to form a stable solution system after being diluted. The nanosuspension has the characteristics of convenient administration, waste reduction and ensured dosage, and does not block a water fountain.

Description

Ponazuril nano suspension and preparation method thereof

Technical field

The invention belongs to field of veterinary, particularly a kind of ponazuril nano suspension and preparation method thereof.

Background technology

Chicken coccidiosis is the parasitic disease of being produced by the caused serious harm aviculture of Eimeria (Eimeria).The Eimeria parasitizing in Intestinum Gallus domesticus road has 7 kinds, is respectively Eimeria tenella (E.tenella), heap type Eimeria (E.acervulina), Eimeria Necatrix (E.necatrix), Eimeria maxima (E.maxima), Eimeria mitis (E.mitis), E.brunetti (E.brinetti) and precocious Eimeria (E.praecox).Various coccidiosiss are in the entozoic position of chicken digestive tract difference, Eimeria tenella parasitizes caecum, heap type Eimeria parasitizes duodenum, and Eimeria maxima and Eimeria Necatrix parasitize small intestinal, and E.brunetti parasitizes small intestinal hypomere and rectum.

Chicken coccidiosis Distribution Area is extensive, and the place of nearly all poultry has chicken coccidiosis to occur.According to the literature, the sickness rate of whole world chicken coccidiosis is up to 50%～70%.The economic loss that the whole world causes because of chicken coccidiosis every year exceedes 2,000,000,000 dollars.Poultry husbandry is one of the most general aquaculture in China, and especially south China, Southeastern China, Sw China, Central China, due to warmer climate humidity, is more conducive to existence and the propagation of coccidian oocyst, more serious to the harm of poultry husbandry.

The in the past multiple spring and autumn joint of being born in of this disease, along with the development of poultry husbandry, hatching changes long-term hatching into by seasonality, humiture becomes Artificial Control from natural regulating rotary, and along with the expansion of modern times cultivation scale, the increase of cultivation density, the space of also having created existence and having propagated to coccidian oocyst.This pathogen not only life cycle long, resistance is strong, general disinfecting drug is difficult to be killed, and suffers from chicken and still may have pathogen to discharge in several months after being ill, thereby pollutes cycle stretch-out.

Along with poultry environmental change, being widely used of coccidiosis medicine, and use coccidiostat lack of standardization, cause the drug resistance of coccidiosis to strengthen, and the infection scope of coccidiosis is also developed into into chicken and planted chicken by chickling gradually.Chicken coccidiosis infects into chicken, although majority is recessive symptom, can cause the growth promoter that is bred as chicken to be obstructed, and the rate of fertilization of survival rate, laying rate and hatching egg on kind of chicken etc. all can cause corresponding impact.

In recent years, modern poultry is already gradually to industrialization future development, intensive production in enormous quantities, intensive feeding manner and Artificial Control are suitable for the living environment of poultry husbandry development, although greatly promoted the production efficiency of poultry husbandry, but chicken group's high density, manually operated suitable humiture is also given the mutual propagation of chicken coccidiosis and is spread and created advantage.As can be seen here, chicken coccidiosis has become one of significant threat of current poultry husbandry.

Ponazuril is the main metabolites of toltrazuril, has another name called Ponazuril, has good protozoacide effect.Ponazuril (ponazuril) is the novel animal special-purpose medicaments of Triazinone of German Bayer AG late 1990s exploitation, for the ancillary drug of serious clinical response as alleviating the horse protozoacide encephalomyelitis (EPM) being caused by sarcocyst neuron; Its biological half-life is long, and bioavailability is high, and the EPM viruses such as horse are had to specially good effect.Its therapeutic effect is good, toxicity is low, is widely used for many years in states such as America and Europe, Asia.U.S. FDA has been ratified the ponazuril oral paste of the protozoacide encephalomyelitis that is used for the treatment of horse of Bayer AG and has been produced July calendar year 2001, content specification is 15%(w/w), adopted name is: Ponazuril Antiprotozoal Oral Paste is 141-188 in the relevant number of logging in of NADA.Simultaneously Bayer AG has obtained the patent (U.S.'s patent of invention, the patent No.: 5833095, in July, 1997 application time) of said preparation.

At present, the main purposes of ponazuril is the protozoacide encephalomyelitis that is used for the treatment of horse, and is the administering mode with oral paste.Domestic aspect, Hubei Long Xiang company has obtained the patent in the purposes of ponazuril crude drug in prevention and treatment coccidiosis, patent CN 102697787 A, on October 03rd, 2012 is open, disclose ponazuril expection and there is good anticoccidial effect, but because of its poorly water-soluble, be made generally in pre-mixing agent spice and use, for chicken medication, clinical use is extremely inconvenient.

Summary of the invention

The object of the present invention is to provide a kind of suspensoid that contains ponazuril and preparation method thereof, the administration of clinical practice drinking-water, easy to use.

Described ponazuril suspensoid, is take ponazuril as principal agent, and suitable pharmaceutic adjuvant in addition, the nano suspension of making after ultramicronising.

Described ponazuril suspensoid mainly comprises following composition:

Described surfactant is one or both in PEG-4000, Tween-80.

Described organic solvent is ethanol, N,N-dimethylacetamide combination, and both usage ratio are 9: 1.

Described ponazuril nano suspension is realized by following technical step:

(1) first sodium hydrogen citrate, anhydrous sodium sulfite are dissolved in a small amount of purified water, stirring and dissolving obtains solution A;

(2) get recipe quantity N,N-dimethylacetamide, add recipe quantity ponazuril to stir it is dissolved, obtain solution B;

(3) get purified water appropriate, add recipe quantity sodium carboxymethyl cellulose, heating for dissolving, after letting cool solution C;

(4) recipe quantity Tween-80, PEG-4000 are slowly added to mix homogeneously in solution B, then add wherein ethanol, add solution C after stirring and dissolving, solution D stirs to obtain;

(5) solution A is mixed with solution D, stir, be settled to recipe quantity by purified water;

(6) solution is passed through to high pressure homogenizer, pressure 700bar twice, obtains ponazuril nano suspension.

The invention has the beneficial effects as follows:

The nano suspension of the present invention administration of can drinking water, and can be dispersed in water after stock solution dilution, and keep stable suspended state, facilitate administration, cut the waste, guarantee dosage, do not stop up the advantages such as water fountain, simultaneously, said preparation has adhesion to the mucous membrane tissue in body, extend the medicine holdup time in vivo, improved the bioavailability of medicine, made this medicine can fully play drug effect in the time for the treatment of chicken coccidiosis.

The specific embodiment

Embodiment 1:

Prescription:

Compound method is

(1) first sodium hydrogen citrate, anhydrous sodium sulfite are dissolved in 200ml purified water, stirring and dissolving obtains solution A;

(2) get N,N-dimethylacetamide, ponazuril stirs it is dissolved, and obtains solution B;

(3) get purified water 2000ml, add recipe quantity sodium carboxymethyl cellulose, heating for dissolving, obtains solution C after letting cool;

(4) recipe quantity Tween-80 is slowly added to mix homogeneously in solution B, then add ethanol, add solution C after stirring and dissolving, solution D stirs to obtain;

(5) solution A is mixed with solution D, stir, be settled to 10000ml by purified water;

(6) solution is passed through to high pressure homogenizer, pressure 700bar twice, to obtain final product.

Embodiment 2:

Prescription:

 

Compound method is:

(1) first sodium hydrogen citrate, anhydrous sodium sulfite are dissolved in 500ml purified water, stirring and dissolving obtains solution A;

(2) get N,N-dimethylacetamide, add ponazuril to stir it is dissolved, obtain solution B;

(3) get purified water 3000ml, add recipe quantity sodium carboxymethyl cellulose, heating for dissolving, obtains solution C after letting cool;

(4) recipe quantity Tween-80, PEG-4000 are slowly added to mix homogeneously in solution B, then add wherein ethanol, add solution C after stirring and dissolving, solution D stirs to obtain;

(5) solution A is mixed with solution D, stir, be settled to recipe quantity by purified water;

(6) solution is passed through to high pressure homogenizer, pressure 700bar twice, obtains nanoscale ponazuril suspension.

Embodiment 3:

The prescription that contains ponazuril coccidium-resistant suspension:

 

Compound method is:

(1) first sodium hydrogen citrate, anhydrous sodium sulfite are dissolved in 500ml purified water, stirring and dissolving obtains solution A;

(2) get N,N-dimethylacetamide, add ponazuril to stir it is dissolved, obtain solution B;

(3) get purified water 3000ml, add recipe quantity sodium carboxymethyl cellulose, heating for dissolving, obtains solution C after letting cool;

(4) recipe quantity Tween-80, PEG-4000 are slowly added to mix homogeneously in solution B, then add wherein ethanol, add solution C after stirring and dissolving, solution D stirs to obtain;

(5) solution A is mixed with solution D, stir, be settled to recipe quantity by purified water;

(6) solution is passed through to high pressure homogenizer, pressure 700bar twice, obtains nanoscale ponazuril suspension.

Embodiment 4:

Clinical effect trial

1 material

Ponazuril pre-mixing agent (1%): for ponazuril and the anhydrous glucose equivalent dilution method that progressively increases formulated.

Ponazuril nano suspension prepared by the embodiment of the present invention one

2 methods

Select 20 age in days non-ball worms to infect chickling, be divided into four groups, be respectively mono-group of I group: embodiment, II group ponazuril pre-mixing agent group, III group positive controls infect not administration, IV group normal healthy controls group (not infecting not administration), every group of 20 chickens.Every chicken artificial challenge 5 × 10 ⁴individual Eimeria Tenella egg capsule.Four groups respectively infect and on request medication within 7 days, all catch and kill afterwards, calculate each medicine anticoccidial index (ACI), judge anticoccidial effect.

3 experimental results

Table 1 ponazuril nano suspension, pre-mixing agent divide into groups to chicken coccidiosis clinical trial

Table 2 ponazuril nano suspension, the therapeutic effect of pre-mixing agent to chicken coccidiosis

Experiment conclusion: can find out from the experimental result of table 1: ponazuril nano suspension anticoccidial effect, higher than ponazuril pre-mixing agent, illustrates that preparation of the present invention can obviously improve clinical result of use and convenience.

Claims (5)

1. ponazuril nano suspension, is characterized in that this preparation is take ponazuril as principal agent, and suitable pharmaceutic adjuvant in addition, the nano suspension of making after ultramicronising.

2. ponazuril nano suspension according to claim 1, is characterized in that described ponazuril suspensoid comprises following composition:

3. ponazuril nano suspension according to claim 2, is characterized in that described surfactant is one or both in PEG-4000, Tween-80.

4. ponazuril nano suspension according to claim 3, is characterized in that described organic solvent is ethanol, N,N-dimethylacetamide combination, and both usage ratio are 9: 1.

5. ponazuril nano suspension according to claim 3, is characterized in that it realizes by following technical step:

(1) first sodium hydrogen citrate, anhydrous sodium sulfite are dissolved in a small amount of purified water, stirring and dissolving obtains solution A;

(2) get recipe quantity N,N-dimethylacetamide, add recipe quantity ponazuril to be stirred to dissolve, obtain solution B;

(3) get purified water appropriate, add recipe quantity sodium carboxymethyl cellulose, heating for dissolving, after letting cool solution C;

(4) recipe quantity Tween-80, PEG-4000 are slowly added to mix homogeneously in solution B, then add wherein ethanol, add solution C after stirring and dissolving, solution D stirs to obtain;

(5) solution A is mixed with solution D, stir, be settled to recipe quantity by purified water;

(6) solution is passed through to high pressure homogenizer, pressure 700bar twice, obtains ponazuril nano suspension.