Summary of the invention
For overcoming the defective of prior art, the object of the present invention is to provide a kind of amoxicillin sulphuric acid colistin granule, both can evenly be mixed, the dissolubility of product in water improves, and drug effect is enhanced, and guarantees curative effect, the quick rehabilitation of favourable animal, have to be easy to preserve and fall, side effect is low, and what drug combination heightened the effect of a treatment has a few; Can not only treat the mixed infection of pig, and use dispensing also very convenient clinically, be convenient to the compoundanimal diseases prevention and treatment to alleviate the animal stress and to alleviate the labor intensity of artificial medication.
Another object of the present invention is to provide the preparation method of a kind of amoxicillin sulphuric acid colistin granule, this method granulating process is simple, and less energy consumption is implemented easily.
The technical solution adopted in the present invention is as follows for achieving the above object:
A kind of amoxicillin sulphuric acid colistin granule, it comprises the following component in weight portion:
Amoxicillin 1-25 part
Colistine sulfate 0.5-50 part
Adjuvant 50-90 part;
It also comprises the binding agent that accounts for above-mentioned several composition weight sum 0.5-8 parts; Described adjuvant be dextrin, sucrose, glucose, lactose, soluble starch, sorbitol, mannitol, Polyethylene Glycol, polyvidone, poloxamer, carbomer a kind of or two or more with any than mixing.The present invention can also realize by following preferred version:
As a preferred embodiment of the present invention, described amoxicillin sulphuric acid colistin granule comprises the following component in weight portion:
Amoxicillin 5-15 part
Colistine sulfate 1-20 part
Adjuvant 70-90 part;
It also comprises the binding agent that accounts for above-mentioned several composition weight sum 1-5 parts.
As a preferred embodiment of the present invention, described amoxicillin sulphuric acid colistin granule comprises the following component in weight portion:
10 parts of amoxicillin
1 part of colistine sulfate
89 parts of adjuvants;
It also comprises the binding agent that accounts for 2.5 parts of above-mentioned several composition weight sums.
In the such scheme, described binding agent be one or more of Polyethylene Glycol, polyvidone, poloxamer, sodium carboxymethyl cellulose, gelatin, starch slurry, syrup, dextrin, carbomer with any than mixing.
The preparation method of a kind of amoxicillin sulphuric acid colistin granule, it may further comprise the steps:
1) sieve: the amoxicillin in will filling a prescription, colistine sulfate, adjuvant are respectively with 80-200 purpose sieve sieving for standby;
2) dissolve: binding agent is dissolved in obtains the binder solution that mass concentration is 2-10% in water or the alcoholic solution;
3) mix: the amoxicillin in the step 1) is mixed earlier fully with partial supplementary material, get mixture A; With colistine sulfate and the abundant mix homogeneously of remaining adjuvant, get mixture B; Then with mixture A and mixture B mix homogeneously, and add binder solution, be prepared into soft material;
4) dry, pelletize: the soft material for preparing is crossed the 20-30 mesh sieve, and dry back is after 10-15 mesh sieve granulate, and packing namely.
In said method, earlier partial supplementary material is mixed earlier with the amoxicillin, can effectively improve the amoxicillin dissolubility, the amoxicillin can be well dispersed in the adjuvant, prevent its moisture absorption caking.
As preferred scheme, the drying described in the step 4) of above-mentioned preparation method is to adopt 50-70 ℃ of forced air drying.
Compared to existing technology, beneficial effect of the present invention is:
1. amoxicillin of the present invention sulphuric acid colistin granule has improved the dissolubility of amoxicillin in water, and because having made the low dried particles of water content, avoided amoxicillin and sulphuric acid colistin simply to mix the easily problem of caking of back, and side effect is low;
2. amoxicillin of the present invention sulphuric acid colistin granule complements each other amoxicillin and the medication combined use of sulphuric acid colistin, promotes every component property of medicine performance mutually, has double effects, can reduce medication number of times and dosage;
3. sulphuric acid colistin granule clinical dispensing in amoxicillin of the present invention is convenient, adds drinking-water and gets final product, and alleviates labor intensity that artificial dispensing brings and the stress of animal greatly;
4. amoxicillin of the present invention sulphuric acid colistin preparation method of granules technology is simple, less energy consumption, and production safety, various veterinary drug manufacturing enterprise realizes easily, meets most veterinary drug enterprise production status.
Below in conjunction with concrete embodiment the present invention is described in further detail.
The specific embodiment
Below introduce the present invention in detail by several embodiment respectively and prevent and treat amoxicillin sulphuric acid colistin granule of the multiple infection of animal and preparation method thereof.
Embodiment 1
A kind of amoxicillin sulphuric acid colistin granule, it comprises effective ingredient and adjuvant, and wherein effective ingredient is composed of the following components, and the weight portion concentration of each component is:
10 parts of amoxicillin;
1 part of colistine sulfate;
15 parts of Polyethylene Glycol-6000
74 parts of lactose
Wherein binding agent is to account for 2.5 parts of said components gross weights and mass concentration 5% 30 POVIDONE K 30 BP/USP 30 alcoholic solution.
Described amoxicillin sulphuric acid colistin granule prepares by the following method:
1) but the amoxicillin in will writing out a prescription, colistine sulfate, Polyethylene Glycol-6000, lactose use 80 orders with the top sieve sieving for standby respectively;
2) it is an amount of to take by weighing 30 POVIDONE K 30 BP/USP 30, and it is dissolved in 50% the ethanol liquid fully, obtains the alcoholic solution of 5% 30 POVIDONE K 30 BP/USP 30, and it is standby to make binder solution;
3) load weighted amoxicillin is mixed earlier fully with Polyethylene Glycol-6000 obtain mixture A, again colistine sulfate and the abundant mix homogeneously of lactose obtained mixture B, it is an amount of mixture A and B to be mixed and add the binder solution that has prepared, is prepared into soft material;
4) soft material for preparing is crossed 24 mesh sieves, 60 ℃ of dryings, packing is namely behind the 12 mesh sieve granulate again.
Embodiment 2
A kind of amoxicillin sulphuric acid colistin granule, it comprises with the following component of weight portion:
5 parts of amoxicillin;
10 parts of colistine sulfates;
30 10 parts of 30 POVIDONE K 30 BP/USPs
75 parts of lactose
Wherein binding agent is to account for the alcoholic solution that 2 parts of said components gross weights and mass concentration are 5% Polyethylene Glycol-6000.
Described amoxicillin sulphuric acid colistin granule prepares by the following method:
1) but the amoxicillin in will writing out a prescription, colistine sulfate, 30 POVIDONE K 30 BP/USP 30, lactose use 80 orders with the top sieve sieving for standby respectively;
2) it is an amount of to take by weighing Polyethylene Glycol-6000, and it is dissolved in 50% the ethanol liquid fully, obtains 5 parts of Polyethylene Glycol-6000 alcoholic solution, and it is standby to make binder solution;
3) load weighted amoxicillin is mixed earlier fully with 30 POVIDONE K 30 BP/USP 30 obtain mixture A, again colistine sulfate and the abundant mix homogeneously of lactose are obtained mixture B, it is an amount of mixture A and B to be mixed and add the binder solution that has prepared, is prepared into soft material;
4) soft material for preparing is crossed 24 mesh sieves, 60 ℃ of dryings, packing is namely behind the 12 mesh sieve granulate again.
Embodiment 3
A kind of amoxicillin sulphuric acid colistin granule, it comprises with the following component of weight portion:
2 parts of amoxicillin;
15 parts of colistine sulfates;
188 5 parts of poloxamers
78 parts of glucoses
Wherein binding agent is to account for 5 parts of said components gross weights and mass concentration is 6% poloxamer 188.
Described amoxicillin sulphuric acid colistin granule prepares by the following method:
1) but the amoxicillin in will writing out a prescription, colistine sulfate, poloxamer 188, glucose use 80 orders with the top sieve sieving for standby respectively;
2) take by weighing poloxamer 188 it is dissolved in the water fully, obtain 6% poloxamer, 188 solution, it is standby to make binder solution;
3) load weighted amoxicillin is mixed earlier fully with poloxamer 188 obtain mixture A, again colistine sulfate and the abundant mix homogeneously of glucose are obtained mixture B, it is an amount of mixture A and B to be mixed and add the binder solution that has prepared, is prepared into soft material;
4) soft material for preparing is crossed 24 mesh sieves, 60 ℃ of dryings, packing is namely behind the 12 mesh sieve granulate again.
Embodiment 4
A kind of amoxicillin sulphuric acid colistin granule, it comprises with the following component of weight portion:
15 parts of amoxicillin;
25 parts of colistine sulfates;
5 parts in mannitol
55 parts of sucrose
Wherein binding agent is to account for 1 part of said components gross weight and mass concentration is 5 parts of starch slurries.
Described amoxicillin sulphuric acid colistin granule prepares by the following method:
1) but the amoxicillin in will writing out a prescription, colistine sulfate, mannitol, sucrose use 80 orders with the top sieve sieving for standby respectively;
2) take by weighing starch, be added to the water while stirring, make it be dissolved in the hot water fully and sieve, obtain 5 parts of starch slurries, it is standby to make binder solution;
3) load weighted amoxicillin is mixed earlier fully with mannitol obtain mixture A, again colistine sulfate and the abundant mix homogeneously of sucrose are obtained mixture B, it is an amount of mixture A and B to be mixed and add the binder solution that has prepared, is prepared into soft material;
4) soft material for preparing is crossed 24 mesh sieves, 60 ℃ of dryings, packing is namely behind the 12 mesh sieve granulate again.
Embodiment 5
A kind of amoxicillin sulphuric acid colistin granule, it comprises with the following component of weight portion:
25 parts of amoxicillin;
50 parts of colistine sulfates;
25 parts of Polyethylene Glycol-6000
Wherein binding agent is to account for 2 parts of said components gross weights and mass concentration is 5% 30 POVIDONE K 30 BP/USP, 30 alcoholic solution.
Described amoxicillin sulphuric acid colistin granule prepares by the following method:
1) but the amoxicillin in will writing out a prescription, colistine sulfate, Polyethylene Glycol-6000 use 80 orders with the top sieve sieving for standby respectively;
2) take by weighing 30 POVIDONE K 30 BP/USP 30 it is dissolved in 50% the ethanol liquid fully, obtain the alcoholic solution of 5% 30 POVIDONE K 30 BP/USP 30, it is standby to make binder solution;
3) load weighted amoxicillin is mixed earlier fully with Polyethylene Glycol-6000 obtain mixture A, again the abundant mix homogeneously of colistine sulfate is obtained mixture B, it is an amount of mixture A and B to be mixed and add the binder solution that has prepared, is prepared into soft material;
4) soft material for preparing is crossed 24 mesh sieves, 60 ℃ of dryings, packing is namely behind the 12 mesh sieve granulate again.
Comparative Examples 1: the comparison of amoxicillin sulphuric acid colistin granule and general formulation dissolubility in water
Experimental technique: take by weighing respectively that (principal agent is 5 parts amoxicillin and 10 parts colistine sulfate according to the amoxicillin sulphuric acid colistin granule of embodiment 2 preparation and general formulation, adjuvant is 85 parts of glucoses, principal agent simply evenly mixes with adjuvant, namely) each 2g puts into the beaker with capacity, add in about 100ml80 ℃ of left and right sides water respectively earlier and stir, add room temperature water again to 500ml and stirring, both mixings time are identical, place 5 minutes.
Experimental result: amoxicillin sulphuric acid colistin granule dissolves substantially, and common then have obvious a large amount of not molten thing to float on the surface.Show that thus said preparation and technology have solved the water solublity problem of amoxicillin preferably.
Comparative Examples 2: amoxicillin sulphuric acid colistin granule and general formulation heat in water-bath relatively
Experimental technique: (principal agent is 5 parts amoxicillin and 10 parts colistine sulfate to take by weighing amoxicillin sulphuric acid colistin granule, the general formulation for preparing according to embodiment 2 respectively, adjuvant is 85 parts of glucoses, principal agent simply evenly mixes with adjuvant, namely) each 100g puts into the aluminium foil bag with capacity, puts in 80 ℃ of left and right sides water-baths 2 hours.
Experimental result: amoxicillin sulphuric acid colistin particle appearance does not have any variation, and common then have an agglomerating phenomenon of obvious adhesion.Show that thus said preparation has solved both preferably with technology and mixed the easily problem of caking of using.
Below clinical efficacy by zoopery explanation amoxicillin of the present invention sulphuric acid colistin granule.
Experiment 1Amoxicillin sulphuric acid colistin granule according to embodiment 2 preparations is tested at the clinical application effect of pig
Experimental technique: choose 80 of the piglets that certain large-scale pig farm is basic identical from numerous autotrophy, feeding and management condition, the birth age in days is close, be diagnosed as yellow and white dysentery of piglet, be divided into 2 groups at random, be i.e. experimental group, matched group, 40 every group.Experimental group, the amoxicillin sulphuric acid colistin granule 2g(that adds according to embodiment 2 preparations by every premium on currency pours medicine into the small amount of thermal water dissolution earlier again, dissolution velocity is faster); Matched group adds sulphuric acid colistin soluble powder (adjuvant only the is lactose) 2g for preparing voluntarily with content by every premium on currency, two groups of identical and every day of concentrated administrations 2 times of drinking water respectively sooner or later of feeding and management.
Curative effect is judged
Cure rate: the symptom complete obiteration after 2~3 times of offeing medicine, feces is shaped, and anus does not have redness or sticking wet sense, and appetite, the normal person of body temperature are for curing.Be defined as curing pig quantity only according to these and calculate cure rate;
Effective percentage: offer medicine after 4~5 times, spirit, appetite take a turn for the better, and sx, feces become soft or retrogradation person for effectively, calculate the treatment effective percentage in every treated animal accordingly;
Inefficiency: after death or the medication 6~7 times, symptom does not alleviate or continues and worsens to invalid, calculates the rate of failing to respond to any medical treatment in every group accordingly in the medication.
Experimental result: show through clinical observation on the therapeutic effect statistics: the cure rate of experimental group is 75.0% (30/40), effective percentage is 85.0%(34/40), inefficiency 15.0% (6/40), matched group be respectively 60.0%(24/40), 67.5%(27/40), 32.5%(13/40).
Experiment conclusion: the effective percentage of experimental group is higher by 17.5% than matched group, and difference is (p<0.01) extremely significantly, this shows that amoxicillin sulphuric acid colistin granule is embodying clinical effectiveness preferably aspect the treatment yellow and white dysentery of piglet.
Experiment 2Amoxicillin sulphuric acid colistin granule according to embodiment 2 preparations is tested at the clinical application effect of chicken
Experimental technique: be diagnosed as 160 of the yellow chickens of colibacillosis when choosing certain raiser's 30 age in days, be divided into 2 groups at random, be i.e. experimental group, matched group, 80 every group.Experimental group, the amoxicillin sulphuric acid colistin granule 0.8g(that adds according to embodiment 2 preparations by every premium on currency pours medicine into the small amount of thermal water dissolution earlier again, dissolution velocity is faster); Matched group adds sulphuric acid colistin soluble powder (adjuvant only the is lactose) 0.8g for preparing voluntarily with content by every premium on currency, two groups of identical and every day of concentrated administrations 2 times of drinking water respectively sooner or later of feeding and management.
Curative effect is judged
Mortality rate: all at duration of test, classical symptom and the death of colibacillosis appear, and necropsy heart, liver have typical characteristics of lesion, are judged to be to infect death.Calculate mortality rate according to dead chicken number.
Cure rate: all at duration of test, chicken is after administration, and it is normal that the mental status, appetite etc. are recovered, and all belongs to and curing.Account for the ratio calculating cure rate that whole test chicken number is given according to curing the chicken number.
Effective percentage: after medication, healing and do not have death but have the chicken of clinical symptoms performance to be " effectively "; The ratio that the chicken number of every group of survival accounts for the test chicken number during off-test is effective percentage.
Experimental result: show through clinical observation on the therapeutic effect statistics: the cure rate of experimental group is 78.8% (63/80), effective percentage is 87.5%(70/80), inefficiency 12.5% (10/80), matched group be respectively 58.8%(47/80), 73.4%(59/80), 26.3%(21/80).
Experiment conclusion: the effective percentage of experimental group is higher by 14.1% than matched group, and difference is (p<0.01) extremely significantly, this shows that amoxicillin sulphuric acid colistin granule is embodying better clinical therapeutic efficacy on the more common folk prescription dosage form aspect the treatment chicken colibacillosis.
Above-mentioned embodiment only is preferred implementation of the present invention; can not limit the scope of protection of the invention with this, the variation of any unsubstantiality that those skilled in the art does on basis of the present invention and replacement all belong to the present invention's scope required for protection.