CN107308115A - A kind of fumaric acid tiamulin soluble powder - Google Patents
A kind of fumaric acid tiamulin soluble powder Download PDFInfo
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- CN107308115A CN107308115A CN201710543182.0A CN201710543182A CN107308115A CN 107308115 A CN107308115 A CN 107308115A CN 201710543182 A CN201710543182 A CN 201710543182A CN 107308115 A CN107308115 A CN 107308115A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
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Abstract
It is as made from the raw material of following parts by weight the invention discloses a kind of fumaric acid tiamulin soluble powder：50 60 parts of fumaric acid tiamulin, 20 30 parts of Pul polyglutamic acid cross-linked polymer, 10 15 parts of garlic polysaccharide solid dispersions, 59 parts of soluble starch, 46 parts of sodium alginate, 23 parts of sodium tripolyphosphate, 1 1.6 parts of disodium ethylene diamine tetraacetate, 0.3 0.5 parts of citric acid.The present invention fumaric acid tiamulin soluble powder even particle size distribution, with stronger high temperature resistant, high wet performance, stability is good.Preparation technology of the present invention is simple, efficiency high, and alcohol solvent recoverable used, recovery process is ripe, and energy-conserving and environment-protective are adapted to industrialized production, had broad application prospects.
Description
Technical field
The invention belongs to field of veterinary medicine preparation, and in particular to a kind of fumaric acid tiamulin soluble powder.
Background technology
Tiamulin (tiamulin) is also known as Tiamulin, safe wonderful mycin, safe wonderful spirit, the former net, Thailand of branch and herds mycin, actual use
Mostly Tiamulin fumarate.Tiamulin is animal specific antibiotic, and its antibacterial action is suppression sensitivity bacterium egg
The synthesis of white matter, the ribosomes acted in bacterial body is mainly shown as bacteriostasis, just there is bactericidal action in higher concentrations.
Tiamulin has special efficacy to a variety of gram positive bacterias and mycoplasma, particularly to S. aureus L-forms, streptococcus, a variety of mould and some spirals
Body has stronger effect.Tiamulin is used to prevent and treat by mycoplasma infection and Escherichia coli, salmonella, spiral
The disease that the infection such as body triggers, to porcine mycoplasmal pneumonia, haemophilus pleura pneumonia, region pneumonia (asthma) and pig dysentery
Disease has special efficacy, has good treatment to diseases such as mycoplasmal arthritis, actinomyces bacillus pleuropneumoniae, ileitis, colitis, oedemas
Effect.Tiamulin is widely used all over the world, is recommended as controlling the choice drug of porcine mycoplasmal infection by expert in the U.S..
Fumaric acid tiamulin is that the hydrogenation for the primary Shandong nut woods extracted in the nutrient solution of the northern phoenix bacterium of Agaricaceae is prolonged recklessly
Rope salt, is a kind of semi-synthetic special antibiotic of diterpene alkenes livestock and poultry, and nineteen fifty-one is proposed first by Australian Kavangh, 60 years
Generation beginning is widely studied, and it has special efficacy to a variety of gram-positive bacterias and mycoplasma, is mainly used in chicken chronic respiratory disease, pig
Eaton agent pneumonia and haemophilus pleuropneumonia, are one of big veterinary antibiotics in the world ten.
Fumaric acid tiamulin has unpleasant property smell, influences animal Compliance, is brought very very much not to disease prevention and cure
Just.Conventional soluble powder excitant has some producers to be made granule using wet granulation technology and attempted than larger
Reduce excitant, but when the content of fumaric acid tiamulin is higher, because fumaric acid tiamulin viscosity is larger, system
Standby softwood is relatively sticked, it is difficult to be extruded with it is round as a ball, and still there is certain penetrating odor, therefore conventional granulation is unsuitable
Using.
The content of the invention
In view of the deficiencies of the prior art, the present invention provides it is a kind of it is evident in efficacy, can effectively solve the safe wonderful bacterium of fumaric acid
The fumaric acid tiamulin soluble powder of plain penetrating odor problem.
The purpose of the present invention is achieved by the following technical solution：
A kind of fumaric acid tiamulin soluble powder, is as made from the raw material of following parts by weight：Fumaric acid Thailand is wonderful
50-60 parts of rhzomorph, Pul -20-30 parts of polyglutamic acid cross-linked polymer, 10-15 parts of garlic polysaccharide solid dispersions, can
5-9 parts of soluble starch, 4-6 parts of sodium alginate, 2-3 parts of sodium tripolyphosphate, 1-1.6 parts of disodium ethylene diamine tetraacetate, citric acid
0.3-0.5 parts.
It is preferred that, a kind of fumaric acid tiamulin soluble powder is as made from the raw material of following parts by weight：Corydalis tuber
It is sour 55 parts of Tiamulin, Pul -25 parts of polyglutamic acid cross-linked polymer, 13 parts of garlic polysaccharide solid dispersions, solvable
7 parts of starch of property, 5 parts of sodium alginate, 2.5 parts of sodium tripolyphosphate, 1.3 parts of disodium ethylene diamine tetraacetate, 0.4 part of citric acid.
Described, Pul-polyglutamic acid cross-linked polymer is as made from following methods：Pul is molten
Liquid is added drop-wise in polyglutamic acid solution with 5 drops/s speed, stirring reaction 2h under the conditions of 30 DEG C, absolute ethyl alcohol precipitation mixed liquor,
Vacuum filtration collects precipitation, by precipitation deionized water dissolving, is placed in bag filter the 2h that dialyses, and it is dry that dialysis is retained into liquid freezing
It is dry, obtain Pul-polyglutamic acid cross-linked polymer.
Described, the mass ratio of polyglutamic acid solution and Pul solution is 1：1；The Pul solution
Concentration is 6mg/ml, and pH is 4.0；The concentration of the polyglutamic acid solution is 60mg/ml, and pH is 4.5.
Described, garlic polysaccharide solid dispersions are prepared via a method which by garlic polysaccharide and Hydrolyzed Collagen
Arrive；Will be soluble in water under garlic polysaccharide and Hydrolyzed Collagen stirring, in air velocity 0.8m/min, pressure 0.5MPa, enter
It is spray-dried under the conditions of 170 DEG C of draught temperature to water content≤5.0%, obtains garlic polysaccharide solid dispersions.
Described, garlic polysaccharide solid dispersions are according to 1 by garlic polysaccharide and Hydrolyzed Collagen：8 weight is than system
；The weight of the water is twice of garlic polysaccharide and Hydrolyzed Collagen gross weight.
Described, the molecular weight of Hydrolyzed Collagen is 7000-9000.
The preparation method of the fumaric acid tiamulin soluble powder of the present invention, is as made from following steps：
1) soluble starch is added in distilled water, 50-55 DEG C of water-bath makes its complete swelling, add Pul-
Polyglutamic acid cross-linked polymer, is well mixed, obtains mixed solution；
The step 1) in, the weight ratio of soluble starch and distilled water is 1：10；
2) fumaric acid tiamulin is dissolved in the ethanol of concentration 95%, obtains fumaric acid tiamulin solution；
The step 2) in, the weight ratio of fumaric acid tiamulin and ethanol is 1：0.7；
3) under 50-55 DEG C of water bath condition, fumaric acid tiamulin solution uniform speed slow is dropped in mixed solution, stirred
More than 5h is mixed, it is fully included, inclusion liquid is obtained；
4) inclusion liquid is cooled to room temperature, the ethanol of concentration 95% is added rapidly in inclusion liquid, precipitation is slowly stirred
Precipitation, obtains precipitated liquid；
The step 4) in, the addition of ethanol is 20 times of fumaric acid tiamulin weight；
5) by precipitated liquid suction filtration, filter cake is obtained；Filter cake is washed for 95% ethanol with concentration again, suction filtration is repeated twice；Finally
Filter cake is vacuumized into 40 DEG C of dryings to constant weight, fumaric acid tiamulin inclusion compound is obtained；
The step 5) in, each consumption of ethanol is 2 times of fumaric acid tiamulin weight；
6) by fumaric acid tiamulin inclusion compound, garlic polysaccharide solid dispersions, sodium alginate, sodium tripolyphosphate, second
Edetate disodium and citric acid are well mixed, obtain fumaric acid tiamulin soluble powder.
Beneficial effects of the present invention：
1. Pul-polyglutamic acid cross-linked polymer of the present invention can not only improve fumaric acid tiamulin inclusion
The bag and property of thing, cover the penetrating odor of fumaric acid tiamulin, it is to avoid medicine is directly contacted with taste bud, without bad mouth
Sense, improves the biddability of animal medication, can also be acted synergistically with garlic polysaccharide solid dispersions, significantly improves fumaric acid safe
The bioavilability of wonderful rhzomorph, it is evident in efficacy.
2. the present invention fumaric acid tiamulin soluble powder even particle size distribution, with stronger high temperature resistant, high humidity
Performance, stability is good.
3. the fumaric acid tiamulin soluble powder preparation technique of the present invention is simple, efficiency high, alcohol solvent used can
Recycle, recovery process is ripe, energy-conserving and environment-protective, be adapted to industrialized production, have broad application prospects.
Embodiment
The present invention is described in further detail below in conjunction with specific embodiment.
Raw material used in the present invention is that market is commercially available.
Embodiment 1
A kind of fumaric acid tiamulin soluble powder, is as made from the raw material of following parts by weight：Fumaric acid Thailand is wonderful
60 parts of rhzomorph, Pul -20 parts of polyglutamic acid cross-linked polymer, 10 parts of garlic polysaccharide solid dispersions, soluble starch 9
Part, 4 parts of sodium alginate, 3 parts of sodium tripolyphosphate, 1.6 parts of disodium ethylene diamine tetraacetate, 0.3 part of citric acid.
Described, Pul-polyglutamic acid cross-linked polymer is as made from following methods：Pul is molten
Liquid is added drop-wise in polyglutamic acid solution with 5 drops/s speed, stirring reaction 2h under the conditions of 30 DEG C, absolute ethyl alcohol precipitation mixed liquor,
Vacuum filtration collects precipitation, by precipitation deionized water dissolving, is placed in bag filter the 2h that dialyses, and it is dry that dialysis is retained into liquid freezing
It is dry, obtain Pul-polyglutamic acid cross-linked polymer.
Described, the mass ratio of polyglutamic acid solution and Pul solution is 1：1；The Pul solution
Concentration is 6mg/ml, and pH is 4.0；The concentration of the polyglutamic acid solution is 60mg/ml, and pH is 4.5.
Described, garlic polysaccharide solid dispersions are prepared via a method which by garlic polysaccharide and Hydrolyzed Collagen
Arrive；Will be soluble in water under garlic polysaccharide and Hydrolyzed Collagen stirring, in air velocity 0.8m/min, pressure 0.5MPa, enter
It is spray-dried under the conditions of 170 DEG C of draught temperature to water content≤5.0%, obtains garlic polysaccharide solid dispersions.
Described, garlic polysaccharide solid dispersions are according to 1 by garlic polysaccharide and Hydrolyzed Collagen：8 weight is than system
；The weight of the water is twice of garlic polysaccharide and Hydrolyzed Collagen gross weight.
Described, the molecular weight of Hydrolyzed Collagen is 7000.
The preparation method of the fumaric acid tiamulin soluble powder of the present invention, is as made from following steps：
1) soluble starch is added in distilled water, 55 DEG C of water-baths make its complete swelling, adds Pul-poly-
Glutamic acid cross-linked polymer, is well mixed, obtains mixed solution；
The step 1) in, the weight ratio of soluble starch and distilled water is 1：10；
2) fumaric acid tiamulin is dissolved in the ethanol of concentration 95%, obtains fumaric acid tiamulin solution；
The step 2) in, the weight ratio of fumaric acid tiamulin and ethanol is 1：0.7；
3) under 50-55 DEG C of water bath condition, fumaric acid tiamulin solution uniform speed slow is dropped in mixed solution, stirred
More than 5h is mixed, it is fully included, inclusion liquid is obtained；
4) inclusion liquid is cooled to room temperature, the ethanol of concentration 95% is added rapidly in inclusion liquid, precipitation is slowly stirred
Precipitation, obtains precipitated liquid；
The step 4) in, the addition of ethanol is 20 times of fumaric acid tiamulin weight；
5) by precipitated liquid suction filtration, filter cake is obtained；Filter cake is washed for 95% ethanol with concentration again, suction filtration is repeated twice；Finally
Filter cake is vacuumized into 40 DEG C of dryings to constant weight, fumaric acid tiamulin inclusion compound is obtained；
The step 5) in, each consumption of ethanol is 2 times of fumaric acid tiamulin weight；
6) by fumaric acid tiamulin inclusion compound, garlic polysaccharide solid dispersions, sodium alginate, sodium tripolyphosphate, second
Edetate disodium and citric acid are well mixed, obtain fumaric acid tiamulin soluble powder.
Embodiment 2
A kind of fumaric acid tiamulin soluble powder, is as made from the raw material of following parts by weight：Fumaric acid Thailand is wonderful
55 parts of rhzomorph, Pul -25 parts of polyglutamic acid cross-linked polymer, 13 parts of garlic polysaccharide solid dispersions, soluble starch 7
Part, 5 parts of sodium alginate, 2.5 parts of sodium tripolyphosphate, 1.3 parts of disodium ethylene diamine tetraacetate, 0.4 part of citric acid.
Described, Pul-polyglutamic acid cross-linked polymer is as made from following methods：Pul is molten
Liquid is added drop-wise in polyglutamic acid solution with 5 drops/s speed, stirring reaction 2h under the conditions of 30 DEG C, absolute ethyl alcohol precipitation mixed liquor,
Vacuum filtration collects precipitation, by precipitation deionized water dissolving, is placed in bag filter the 2h that dialyses, and it is dry that dialysis is retained into liquid freezing
It is dry, obtain Pul-polyglutamic acid cross-linked polymer.
Described, the mass ratio of polyglutamic acid solution and Pul solution is 1：1；The Pul solution
Concentration is 6mg/ml, and pH is 4.0；The concentration of the polyglutamic acid solution is 60mg/ml, and pH is 4.5.
Described, garlic polysaccharide solid dispersions are prepared via a method which by garlic polysaccharide and Hydrolyzed Collagen
Arrive；Will be soluble in water under garlic polysaccharide and Hydrolyzed Collagen stirring, in air velocity 0.8m/min, pressure 0.5MPa, enter
It is spray-dried under the conditions of 170 DEG C of draught temperature to water content≤5.0%, obtains garlic polysaccharide solid dispersions.
Described, garlic polysaccharide solid dispersions are according to 1 by garlic polysaccharide and Hydrolyzed Collagen：8 weight is than system
；The weight of the water is twice of garlic polysaccharide and Hydrolyzed Collagen gross weight.
Described, the molecular weight of Hydrolyzed Collagen is 8000.
The preparation method of the fumaric acid tiamulin soluble powder of the present invention, is as made from following steps：
1) soluble starch is added in distilled water, 53 DEG C of water-baths make its complete swelling, adds Pul-poly-
Glutamic acid cross-linked polymer, is well mixed, obtains mixed solution；
The step 1) in, the weight ratio of soluble starch and distilled water is 1：10；
2) fumaric acid tiamulin is dissolved in the ethanol of concentration 95%, obtains fumaric acid tiamulin solution；
The step 2) in, the weight ratio of fumaric acid tiamulin and ethanol is 1：0.7；
3) under 50-55 DEG C of water bath condition, fumaric acid tiamulin solution uniform speed slow is dropped in mixed solution, stirred
More than 5h is mixed, it is fully included, inclusion liquid is obtained；
4) inclusion liquid is cooled to room temperature, the ethanol of concentration 95% is added rapidly in inclusion liquid, precipitation is slowly stirred
Precipitation, obtains precipitated liquid；
The step 4) in, the addition of ethanol is 20 times of fumaric acid tiamulin weight；
5) by precipitated liquid suction filtration, filter cake is obtained；Filter cake is washed for 95% ethanol with concentration again, suction filtration is repeated twice；Finally
Filter cake is vacuumized into 40 DEG C of dryings to constant weight, fumaric acid tiamulin inclusion compound is obtained；
The step 5) in, each consumption of ethanol is 2 times of fumaric acid tiamulin weight；
6) by fumaric acid tiamulin inclusion compound, garlic polysaccharide solid dispersions, sodium alginate, sodium tripolyphosphate, second
Edetate disodium and citric acid are well mixed, obtain fumaric acid tiamulin soluble powder.
Embodiment 3
A kind of fumaric acid tiamulin soluble powder, is as made from the raw material of following parts by weight：Fumaric acid Thailand is wonderful
50 parts of rhzomorph, Pul -30 parts of polyglutamic acid cross-linked polymer, 15 parts of garlic polysaccharide solid dispersions, soluble starch 5
Part, 6 parts of sodium alginate, 2 parts of sodium tripolyphosphate, 1 part of disodium ethylene diamine tetraacetate, 0.5 part of citric acid.
Described, Pul-polyglutamic acid cross-linked polymer is as made from following methods：Pul is molten
Liquid is added drop-wise in polyglutamic acid solution with 5 drops/s speed, stirring reaction 2h under the conditions of 30 DEG C, absolute ethyl alcohol precipitation mixed liquor,
Vacuum filtration collects precipitation, by precipitation deionized water dissolving, is placed in bag filter the 2h that dialyses, and it is dry that dialysis is retained into liquid freezing
It is dry, obtain Pul-polyglutamic acid cross-linked polymer.
Described, the mass ratio of polyglutamic acid solution and Pul solution is 1：1；The Pul solution
Concentration is 6mg/ml, and pH is 4.0；The concentration of the polyglutamic acid solution is 60mg/ml, and pH is 4.5.
Described, garlic polysaccharide solid dispersions are prepared via a method which by garlic polysaccharide and Hydrolyzed Collagen
Arrive；Will be soluble in water under garlic polysaccharide and Hydrolyzed Collagen stirring, in air velocity 0.8m/min, pressure 0.5MPa, enter
It is spray-dried under the conditions of 170 DEG C of draught temperature to water content≤5.0%, obtains garlic polysaccharide solid dispersions.
Described, garlic polysaccharide solid dispersions are according to 1 by garlic polysaccharide and Hydrolyzed Collagen：8 weight is than system
；The weight of the water is twice of garlic polysaccharide and Hydrolyzed Collagen gross weight.
Described, the molecular weight of Hydrolyzed Collagen is 9000.
The preparation method of the fumaric acid tiamulin soluble powder of the present invention, is as made from following steps：
1) soluble starch is added in distilled water, 50 DEG C of water-baths make its complete swelling, adds Pul-poly-
Glutamic acid cross-linked polymer, is well mixed, obtains mixed solution；
The step 1) in, the weight ratio of soluble starch and distilled water is 1：10；
2) fumaric acid tiamulin is dissolved in the ethanol of concentration 95%, obtains fumaric acid tiamulin solution；
The step 2) in, the weight ratio of fumaric acid tiamulin and ethanol is 1：0.7；
3) under 50-55 DEG C of water bath condition, fumaric acid tiamulin solution uniform speed slow is dropped in mixed solution, stirred
More than 5h is mixed, it is fully included, inclusion liquid is obtained；
4) inclusion liquid is cooled to room temperature, the ethanol of concentration 95% is added rapidly in inclusion liquid, precipitation is slowly stirred
Precipitation, obtains precipitated liquid；
The step 4) in, the addition of ethanol is 20 times of fumaric acid tiamulin weight；
5) by precipitated liquid suction filtration, filter cake is obtained；Filter cake is washed for 95% ethanol with concentration again, suction filtration is repeated twice；Finally
Filter cake is vacuumized into 40 DEG C of dryings to constant weight, fumaric acid tiamulin inclusion compound is obtained；
The step 5) in, each consumption of ethanol is 2 times of fumaric acid tiamulin weight；
6) by fumaric acid tiamulin inclusion compound, garlic polysaccharide solid dispersions, sodium alginate, sodium tripolyphosphate, second
Edetate disodium and citric acid are well mixed, obtain fumaric acid tiamulin soluble powder.
Comparative example 1
A kind of fumaric acid tiamulin soluble powder, is as made from the raw material of following parts by weight：Fumaric acid Thailand is wonderful
55 parts of rhzomorph, 13 parts of garlic polysaccharide solid dispersions, 7 parts of soluble starch, 5 parts of sodium alginate, 2.5 parts of sodium tripolyphosphate, second
1.3 parts of edetate disodium, 0.4 part of citric acid.
Described, garlic polysaccharide solid dispersions are prepared via a method which by garlic polysaccharide and Hydrolyzed Collagen
Arrive；Will be soluble in water under garlic polysaccharide and Hydrolyzed Collagen stirring, in air velocity 0.8m/min, pressure 0.5MPa, enter
It is spray-dried under the conditions of 170 DEG C of draught temperature to water content≤5.0%, obtains garlic polysaccharide solid dispersions.
Described, garlic polysaccharide solid dispersions are according to 1 by garlic polysaccharide and Hydrolyzed Collagen：8 weight is than system
；The weight of the water is twice of garlic polysaccharide and Hydrolyzed Collagen gross weight.
Described, the molecular weight of Hydrolyzed Collagen is 8000.
The preparation method of the fumaric acid tiamulin soluble powder of the present invention, is as made from following steps：
1) soluble starch is added in distilled water, 53 DEG C of water-baths make its complete swelling, obtain mixed solution；
The step 1) in, the weight ratio of soluble starch and distilled water is 1：10；
2) fumaric acid tiamulin is dissolved in the ethanol of concentration 95%, obtains fumaric acid tiamulin solution；
The step 2) in, the weight ratio of fumaric acid tiamulin and ethanol is 1：0.7；
3) under 50-55 DEG C of water bath condition, fumaric acid tiamulin solution uniform speed slow is dropped in mixed solution, stirred
More than 5h is mixed, it is fully included, inclusion liquid is obtained；
4) inclusion liquid is cooled to room temperature, the ethanol of concentration 95% is added rapidly in inclusion liquid, precipitation is slowly stirred
Precipitation, obtains precipitated liquid；
The step 4) in, the addition of ethanol is 20 times of fumaric acid tiamulin weight；
5) by precipitated liquid suction filtration, filter cake is obtained；Filter cake is washed for 95% ethanol with concentration again, suction filtration is repeated twice；Finally
Filter cake is vacuumized into 40 DEG C of dryings to constant weight, fumaric acid tiamulin inclusion compound is obtained；
The step 5) in, each consumption of ethanol is 2 times of fumaric acid tiamulin weight；
6) by fumaric acid tiamulin inclusion compound, garlic polysaccharide solid dispersions, sodium alginate, sodium tripolyphosphate, second
Edetate disodium and citric acid are well mixed, obtain fumaric acid tiamulin soluble powder.
Comparative example 2
A kind of fumaric acid tiamulin soluble powder, is as made from the raw material of following parts by weight：Fumaric acid Thailand is wonderful
55 parts of rhzomorph, Pul -25 parts of polyglutamic acid cross-linked polymer, 7 parts of soluble starch, 5 parts of sodium alginate, tripolyphosphate
2.5 parts of sodium, 1.3 parts of disodium ethylene diamine tetraacetate, 0.4 part of citric acid.
Described, Pul-polyglutamic acid cross-linked polymer is as made from following methods：Pul is molten
Liquid is added drop-wise in polyglutamic acid solution with 5 drops/s speed, stirring reaction 2h under the conditions of 30 DEG C, absolute ethyl alcohol precipitation mixed liquor,
Vacuum filtration collects precipitation, by precipitation deionized water dissolving, is placed in bag filter the 2h that dialyses, and it is dry that dialysis is retained into liquid freezing
It is dry, obtain Pul-polyglutamic acid cross-linked polymer.
Described, the mass ratio of polyglutamic acid solution and Pul solution is 1：1；The Pul solution
Concentration is 6mg/ml, and pH is 4.0；The concentration of the polyglutamic acid solution is 60mg/ml, and pH is 4.5.
The preparation method of the fumaric acid tiamulin soluble powder of the present invention, is as made from following steps：
1) soluble starch is added in distilled water, 53 DEG C of water-baths make its complete swelling, adds Pul-poly-
Glutamic acid cross-linked polymer, is well mixed, obtains mixed solution；
The step 1) in, the weight ratio of soluble starch and distilled water is 1：10；
2) fumaric acid tiamulin is dissolved in the ethanol of concentration 95%, obtains fumaric acid tiamulin solution；
The step 2) in, the weight ratio of fumaric acid tiamulin and ethanol is 1：0.7；
3) under 50-55 DEG C of water bath condition, fumaric acid tiamulin solution uniform speed slow is dropped in mixed solution, stirred
More than 5h is mixed, it is fully included, inclusion liquid is obtained；
4) inclusion liquid is cooled to room temperature, the ethanol of concentration 95% is added rapidly in inclusion liquid, precipitation is slowly stirred
Precipitation, obtains precipitated liquid；
The step 4) in, the addition of ethanol is 20 times of fumaric acid tiamulin weight；
5) by precipitated liquid suction filtration, filter cake is obtained；Filter cake is washed for 95% ethanol with concentration again, suction filtration is repeated twice；Finally
Filter cake is vacuumized into 40 DEG C of dryings to constant weight, fumaric acid tiamulin inclusion compound is obtained；
The step 5) in, each consumption of ethanol is 2 times of fumaric acid tiamulin weight；
6) by fumaric acid tiamulin inclusion compound, sodium alginate, sodium tripolyphosphate, disodium ethylene diamine tetraacetate and lemon
Acid is well mixed, obtains fumaric acid tiamulin soluble powder.
Comparative example 3
A kind of fumaric acid tiamulin soluble powder, is as made from the raw material of following parts by weight：Fumaric acid Thailand is wonderful
55 parts of rhzomorph, 7 parts of soluble starch, 5 parts of sodium alginate, 2.5 parts of sodium tripolyphosphate, 1.3 parts of disodium ethylene diamine tetraacetate, lemon
0.4 part of acid.
The preparation method of the fumaric acid tiamulin soluble powder of the present invention, is as made from following steps：
1) soluble starch is added in distilled water, 53 DEG C of water-baths make its complete swelling, obtain mixed solution；
The step 1) in, the weight ratio of soluble starch and distilled water is 1：10；
2) fumaric acid tiamulin is dissolved in the ethanol of concentration 95%, obtains fumaric acid tiamulin solution；
The step 2) in, the weight ratio of fumaric acid tiamulin and ethanol is 1：0.7；
3) under 50-55 DEG C of water bath condition, fumaric acid tiamulin solution uniform speed slow is dropped in mixed solution, stirred
More than 5h is mixed, it is fully included, inclusion liquid is obtained；
4) inclusion liquid is cooled to room temperature, the ethanol of concentration 95% is added rapidly in inclusion liquid, precipitation is slowly stirred
Precipitation, obtains precipitated liquid；
The step 4) in, the addition of ethanol is 20 times of fumaric acid tiamulin weight；
5) by precipitated liquid suction filtration, filter cake is obtained；Filter cake is washed for 95% ethanol with concentration again, suction filtration is repeated twice；Finally
Filter cake is vacuumized into 40 DEG C of dryings to constant weight, fumaric acid tiamulin inclusion compound is obtained；
The step 5) in, each consumption of ethanol is 2 times of fumaric acid tiamulin weight；
6) by fumaric acid tiamulin inclusion compound, sodium alginate, sodium tripolyphosphate, disodium ethylene diamine tetraacetate and lemon
Acid is well mixed, obtains fumaric acid tiamulin soluble powder.
Fumaric acid tiamulin inclusion compound and fumaric acid tiamulin prepared by embodiment 1-3 and comparative example 1-3
Pure powder carries out size distribution, stability and therapeutic effect and is measured, and result of the test is as follows：
1. particle size distribution
The granularity of fumaric acid tiamulin inclusion compound prepared by embodiment 1-3 and comparative example 2 is bigger than normal, relatively concentrates, particle diameter
Concentrate on 50-90 μm；The granularity of fumaric acid tiamulin inclusion compound prepared by comparative example 1 and comparative example 3 is slightly smaller, does not concentrate；
The granularity of the pure powder of fumaric acid tiamulin is less than normal and does not concentrate, and particle diameter accounts for 43% for 10-25 μm of particle.
Pul-polyglutamic acid cross-linked polymer in embodiment 1-3 and comparative example 2 is remarkably improved fumaric acid
The particle size uniformity of Tiamulin inclusion compound, is conducive to preparation to mix, and the uniformity is greatly improved after mixing, it is to avoid medicament contg is taken out
Sample detection is uneven.Prepared fumaric acid tiamulin soluble powder adapts to long-distance transport and jolted, will not be because of medicine
It is big and pulvis occur seriously uneven with the particle size differences of auxiliary material, or even lamination.Meanwhile, medicinal powder granularity increase, proportion adds
Greatly, medicinal powder is difficult to fly away, and reduces the loss of preparation and the medicine using link.
2. Stability Determination
2.1 hot test
Fumaric acid tiamulin soluble powder prepared by embodiment 1-3 and comparative example 1-3 is under 60 DEG C of temperature conditionss
Place 10 days, respectively at the 0th day, the 5th day, sampling detection in the 10th day, its character is detected by ocular estimate, passes through high-efficient liquid phase color
Spectrum detection fumaric acid tiamulin content, as a result as shown in table 1.
The hot test testing result of table 1
2.2 high wet tests
Fumaric acid tiamulin soluble powder prepared by embodiment 1-3 and comparative example 1-3 is in 25 DEG C, 95% ± 5%
Placed 10 days under damp condition, respectively at the 0th day, the 5th day, sampling detection in the 10th day, its character is detected by ocular estimate, passed through
High performance liquid chromatography detection fumaric acid tiamulin content, as a result as shown in table 2.
The high humidity testing inspection result of table 2
2.3 stability test
Fumaric acid tiamulin soluble powder prepared by embodiment 1-3 and comparative example 1-3 in 40 DEG C ± 2 DEG C of temperature,
Placed 6 months under the conditions of humidity 75% ± 5%, detected respectively at the 0th, 1,2,3, sampling in 6 months, its property is detected by ocular estimate
Shape, by high performance liquid chromatography detection fumaric acid tiamulin content, as a result as shown in table 3.
The stability test testing result of table 3
3. Eaton agent pneumonia therapeutic effect is tested
The piglet of individual raiser's natural occurrence 480, a sick pig standing a corner or the breathing of dog shape sitting posture, breathe, cough, exhale
Inhale number of times to increase severely, occur spasmodic cough or even vomiting predominantly in abdominal respiration, when serious.Sick pig spirit is depressed, is reluctant to walk
It is dynamic, poor appetite, lean body mass, slightly disorderly, happiness is sleeping cold for fur, body temperature and appetite change less growth retardation.Cut open inspection
It can be seen that lung has different degrees of oedema and wind-puff, the sharp leaf and lobus cardiacus of two lungs are in symmetry, confluent bronchopneumonia lesion.
The sharp leaf of sick pig lung, lobus cardiacus, the leading edge of middle leaf and lobus diaphragmaticus are in meat sample or shrimp sample consolidation, and hilus pulumonis and vertical phrenic lymph nodes are obvious
Enlargement, matter are hard, canescence, tangent plane succulence.Pass through the diagnosis such as clinical symptoms, serodiagnosis, cut open inspection symptom, the inspection of x-ray fluoroscopy piece
It is positive that method is diagnosed as mycoplasma hyopneumoniae.
6 groups are randomly divided into, experimental group 1-3 adds the fumaric acid tiamulin soluble powder of embodiment 1-3 preparations respectively,
Per 50kg feeds addition 10g fumaric acid tiamulin soluble powders.Control group 1-3 adds prolonging for comparative example 1-3 preparations respectively
Fumarate Tiamulin soluble powder, per 50kg feeds addition 10g fumaric acid tiamulin soluble powders.It is used in conjunction 7 days, is discontinued
Afterwards observe 3 days, as a result as shown in table 4.
Criterion：
Cure：Clinical symptom disappearance (is coughed, dyspneic symptom stops, spirit takes a turn for the better, and grows extensive in 3 days after drug withdrawal
It is normal etc. again).
Effectively：Clinical symptom relief (cough, dyspneic remission, spirit take a turn for the better, and growth takes a turn for the better etc.).
It is dead：It is dead in (including after drug withdrawal in 3 days) during testing.
The Eaton agent pneumonia therapeutic effect result of the test of table 4
Finally it should be noted that foregoing description is only the preferred embodiments of the present invention, the ordinary skill people of this area
Member on the premise of without prejudice to present inventive concept and claim, can make table as multiple types under the enlightenment of the present invention
Show, such conversion is each fallen within protection scope of the present invention.
Claims (7)
1. a kind of fumaric acid tiamulin soluble powder, it is characterised in that be as made from the raw material of following parts by weight：Prolong recklessly
50-60 parts of Tiamulin of rope acid, Pul -20-30 parts of polyglutamic acid cross-linked polymer, garlic polysaccharide solid dispersions
10-15 parts, 5-9 parts of soluble starch, 4-6 parts of sodium alginate, 2-3 parts of sodium tripolyphosphate, disodium ethylene diamine tetraacetate 1-1.6
Part, 0.3-0.5 parts of citric acid.
2. fumaric acid tiamulin soluble powder according to claim 1, it is characterised in that be by the original of following parts by weight
Material is obtained：55 parts of fumaric acid tiamulin, Pul -25 parts of polyglutamic acid cross-linked polymer, garlic polysaccharide solid
13 parts of dispersion, 7 parts of soluble starch, 5 parts of sodium alginate, 2.5 parts of sodium tripolyphosphate, 1.3 parts of disodium ethylene diamine tetraacetate, lemon
0.4 part of lemon acid.
3. fumaric acid tiamulin soluble powder according to claim 1 or claim 2, it is characterised in that the Pul-
Polyglutamic acid cross-linked polymer is as made from following methods：Pul solution is added drop-wise to poly- paddy with 5 drops/s speed
In propylhomoserin solution, stirring reaction 2h under the conditions of 30 DEG C, absolute ethyl alcohol precipitation mixed liquor, vacuum filtration collects precipitation, precipitation is used
Deionized water dissolving, is placed in bag filter the 2h that dialyses, and dialysis is retained into liquid freeze-drying, obtains Pul-polyglutamic acid and hands over
Linked polymer.
4. fumaric acid tiamulin soluble powder according to claim 3, it is characterised in that the polyglutamic acid solution and
The mass ratio of Pul solution is 1：1；The concentration of the Pul solution is 6mg/ml, and pH is 4.0；The poly- paddy
The concentration of propylhomoserin solution is 60mg/ml, and pH is 4.5.
5. fumaric acid tiamulin soluble powder according to claim 1 or claim 2, it is characterised in that the garlic polysaccharide is consolidated
Body dispersion is prepared via a method which to obtain by garlic polysaccharide and Hydrolyzed Collagen；By garlic polysaccharide and hydrolytic collagen
It is soluble in water under albumen stirring, sprayed under the conditions of air velocity 0.8m/min, pressure 0.5MPa, 170 DEG C of intake air temperature
Mist drying obtains garlic polysaccharide solid dispersions to water content≤5.0%.
6. fumaric acid tiamulin soluble powder according to claim 5, it is characterised in that the garlic polysaccharide solid point
Granular media is according to 1 by garlic polysaccharide and Hydrolyzed Collagen：8 weight is than obtained；The weight of the water be garlic polysaccharide and
Twice of Hydrolyzed Collagen gross weight.
7. fumaric acid tiamulin soluble powder according to claim 5, it is characterised in that the Hydrolyzed Collagen
Molecular weight is 7000-9000.
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