CN114748495A - Oil-water-soluble veterinary linke grand scale compound preparation and preparation method and application thereof - Google Patents
Oil-water-soluble veterinary linke grand scale compound preparation and preparation method and application thereof Download PDFInfo
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- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- 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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- A61K9/141—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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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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Abstract
The invention belongs to the field of veterinary antibiotics, and particularly relates to an oil-water double-soluble veterinary linke compound preparation with a large-scale appearance, and a preparation method and application thereof; the compound preparation comprises the following materials in parts by weight: 5-10 parts of polyethylene glycol, 5-12 parts of cyclodextrin derivative, 2-4 parts of poloxamer, 2-7 parts of anhydrous sodium sulfite, 60-100 parts of spectinomycin and/or salifying form, 20-40 parts of lincomycin and/or salifying form and 10-20 parts of lactose; the dissolving amount of the prepared lincomycin grandparent compound preparation in the aqueous vaccine is 370-390 g/L, and the dissolving amount in the oily vaccine is 80-120 g/L, so that the problems of small dissolving amount and unstable solution of the lincomycin and the lincomycin in the aqueous vaccine and the oily vaccine are solved.
Description
Technical Field
The invention belongs to the technical field of veterinary antibiotics, and particularly relates to an oil-water double-soluble veterinary linke compound preparation with a large visual field and a preparation method thereof.
Background
The antibacterial agent is the most important way for treating bacterial diseases, and in livestock and poultry breeding, due to high breeding density and poor breeding environment, multiple pathogens are often infected at the same time, so that the compound preparation can play a good role in preventing and treating diseases. Lincomycin is a lincomycin amine antibiotic, mainly acts on bacterial ribosome 50s subunit, inhibits the synthesis of bacterial protein by inhibiting the extension of peptide chain, and is sensitive to gram-positive bacteria, mycoplasma and anaerobic bacteria. Spectinomycin is an aminoglycoside antibiotic, has a bactericidal effect by interfering with the synthesis of bacterial proteins, destroying membrane structures and the like, and is highly sensitive to gram-negative bacteria and mycoplasma. The lincomycin and the spectinomycin are prepared into a compound preparation, so that the antibacterial spectrum is further expanded, and the antibacterial effect is enhanced.
In livestock and poultry breeding, the number of bred animals is very large, and the animals are mostly infected by groups due to infectious diseases, so that vaccines and medicaments are required to be used for prevention and early treatment in advance in seasons with high disease incidence in breeding clinics. Injection is one mode of administration that provides the fastest absorption and distribution of drugs, and is the best mode for systemic infections. However, lincomycin and spectinomycin are not completely absorbed after oral administration, and are quickly and completely absorbed after injection administration, so that the lincomycin and spectinomycin compound preparation is more suitable for injection from the perspective of guaranteeing the drug effect. In the face of a large administration group, the work load is huge because vaccines and medicines are required to be injected, and the stress reaction of animals can be caused by repeated injection. Therefore, the injection of a drug and a vaccine after mixing is a novel administration method which has been proposed in recent years.
Vaccines for livestock and poultry include aqueous vaccines and oily vaccines, while most veterinary drugs are water-soluble and almost insoluble in oil. The addition of the medicament into the aqueous vaccine is relatively simple, and the medicament is directly dissolved into the aqueous vaccine or is dissolved by water and then is uniformly mixed with the vaccine. However, the addition of drugs into oily vaccines has more problems, and because the drugs cannot be directly dissolved into oily matrixes, some people can directly add the drugs into the vaccines in clinical use, and drug particles are dispersed in the vaccines for a short time by shaking, but the use mode has the defects of needle blockage, high irritation, inaccurate administration dosage and the like. At present, in order to better solve the problem of difficult dosing of oily vaccines, the mixing uniformity of medicines and oily vaccines is mainly increased by adding an auxiliary agent, for example, patent document CN112043720A discloses an spectinomycin lincomycin soluble powder which can be completely dissolved in various solvents and a preparation method thereof, the soluble powder is prepared by crushing and mixing raw materials and auxiliary materials into a product with a particle size of 80 meshes (about 180 μm) through simple processes, medicine particles cannot be completely dissolved in oil seedlings, although taurine is used as a solubilizer, medicines are partially settled, the dissolving time of the soluble powder prepared in the patent in water and oil seedlings needs 5min to reach a relatively completely dissolved level, and meanwhile, the dissolving amount in the oil seedlings is only 10g/250mL, and the solubility is small; patent document CN101829082A discloses a preparation method of veterinary spectinomycin hydrochloride and lincomycin hydrochloride injection, which mainly adopts cyclodextrin to perform inclusion to prepare a spectinomycin hydrochloride inclusion compound, and then the spectinomycin hydrochloride inclusion compound and the lincomycin hydrochloride are prepared into a compound preparation, so that the stability of spectinomycin in an aqueous solution is significantly improved, the cyclodextrin inclusion effect is only to improve the stability of spectinomycin in an aqueous solution, and the solubility problem of spectinomycin cannot be solved, and the method does not relate to the stability and the solubility of the compound preparation in an oily solution, and the compound preparation prepared by the patent is only suitable for an aqueous injection; patent document CN111297808A discloses a soluble powder of spectinomycin hydrochloride which is soluble in water and then miscible with oil vaccine and a preparation method thereof, the product is prepared by adding an oil/water type emulsifier, a water/oil type emulsifier and immune polysaccharide, and through the processes of crushing, sieving and mixing, the effect that the medicine can be directly added into an oil vaccine is realized, the embodiment describes that 10g of a sample is added into 500ml of the oil vaccine, the dissolution time is long, the oil vaccine contains 20-50% of a water phase, and the 500ml of vaccine contains 100-250 ml of water, the solubility requirements of the spectinomycin and the lincomycin can be met under general conditions, but the emulsion breaking of the vaccine can be caused after the common medicine is dissolved, and the product in the invention is added with the oil/water type emulsifier and the water/oil type emulsifier, so as to have good emulsification effect, the medicine can be kept stable for 24 hours in the vaccine, but the amount of the dissolved medicine in the oil vaccine prepared by the patent is only 2 percent, which is difficult to meet the requirement of injection dosage; CN111388498A discloses a soluble powder of spectinolincomycin hydrochloride which is soluble in water and then mutually soluble with oil seedlings and a preparation method thereof, the emulsifier is added in the patent to enable the medicinal solution dissolved in water to be emulsified with the oil seedlings to achieve the effect of uniform mixing, the maximum solubility of the spectinolincomycin hydrochloride in water contained in the soluble powder prepared by the patent is 10g/30mL according to the pure dosage, the dissolution time is 1min, the time required for the solubility in water to be reduced to 10g/50mL is 0.5min, even if the dissolution time is shortened by half, the dissolution amount is reduced by more than half, in addition, the soluble powder prepared by the patent needs to be mixed with water before being mixed with the oil seedlings, the operation steps are added, and the dissolution time can reach 1min after being further mixed with the oil seedlings, but the dissolution amount is very low.
Based on the fact that great difficulty still exists in the research of complete dissolution of the medicine in the oil vaccine in the prior art, in order to better reduce the risk of infectious diseases of cultured animals, the compound preparation with high dosage of lincomycin and spectinomycin which can be rapidly and completely dissolved in aqueous vaccines and oily vaccines is prepared, and the compound preparation has better prevention and treatment effects in the season with high incidence of diseases.
Disclosure of Invention
Aiming at the problems in the prior art, the invention provides an oil-water double-soluble veterinary linke grand compound preparation as well as a preparation method and application thereof.
In a first aspect, the invention provides an oil-water-soluble veterinary linke grand scale compound preparation, which comprises the following materials in parts by weight: 5-10 parts of polyethylene glycol, 6-12 parts of cyclodextrin derivative, 2-4 parts of poloxamer, 2-7 parts of anhydrous sodium sulfite, 60-100 parts of spectinomycin and/or salifying form, 20-40 parts of lincomycin and/or salifying form and 10-20 parts of lactose.
Preferably, the lincomycin salt-forming form and the spectinomycin salt-forming form are selected from the forms of the hydrochloride or sulfate thereof, i.e. the salts
Respectively spectinomycin hydrochloride, spectinomycin sulfate, lincomycin hydrochloride and lincomycin sulfate;
More preferably, the mass content of the spectinomycin in the hydrochloric acid/sulfuric acid is 74% +/-0.5%, and the mass content of the lincomycin in the hydrochloric acid/sulfuric acid is 95% +/-0.5%;
furthermore, the polyethylene glycols are polyethylene glycols with Mw of 3000-10000.
Further, the cyclodextrin derivative is selected from one or a combination of (2-hydroxypropyl) -alpha-cyclodextrin, (2-hydroxypropyl) -beta-cyclodextrin, (2-hydroxyethyl) -beta-cyclodextrin, carboxymethyl-beta-cyclodextrin or sodium salt, (2-hydroxypropyl) -gamma-cyclodextrin, methyl-beta-cyclodextrin, triacetyl-beta-cyclodextrin and beta-cyclodextrin sulfobutyl ether or sodium salt.
In a second aspect, the invention provides a preparation method of an oil-water double-soluble veterinary linke grand compound preparation, which comprises the following specific preparation steps:
s1, adding polyethylene glycol into a proper amount of water, stirring, adding cyclodextrin derivatives, stirring, adding anhydrous sodium sulfite, stirring, adding spectinomycin in a salt form, stirring, adding lincomycin in a salt form, stirring, adding poloxamer, and stirring to prepare a solution;
s2, spray drying the solution prepared in the S1 by a spray drying device to prepare powder;
S3, carrying out superfine grinding on lactose in the formula amount, adding the lactose into the powder prepared in the S2, and mixing for 20-40 min to obtain the veterinary ciconi grand compound preparation dissolved in oil and water.
Further, stirring the polyethylene glycol in water for 5-10 min;
further, the stirring time of the cyclodextrin derivative is 10-20 min;
further, the stirring time of the anhydrous sodium sulfite is 2-10 min;
further, the stirring time of the salified spectinomycin is 10-20 min;
further, the stirring time of the salified lincomycin is 10-20 min;
further, the stirring time of the poloxamer is 10-20 min;
further, the temperature of the spray drying process is 140-170 ℃, and the temperature of a nozzle is 50-70 ℃;
further, the particle size of the powder in the step S2 is 10-15 μm.
Further, the lactose in the step S3 is pulverized to a particle size of 10-20 μm;
further, the particle size of the oil-water double-soluble veterinary ciconia compound preparation obtained in the step S3 is 10-20 μm.
In a third aspect, the invention provides an application of an oil-water double-soluble veterinary linke macro-scale compound preparation in medicines or vaccines for resisting bacteria, fungi and pathogenic bacteria infection, but not limited to the medicines;
Further, the oil-water-soluble veterinary ciconia grandma compound preparation is dissolved in the water-based vaccine in an amount of 370-390 g/L and in the oil-based vaccine in an amount of 80-120 g/L.
Furthermore, the vaccine can be inactivated avian influenza vaccine, newcastle disease inactivated vaccine, newcastle disease virus and avian influenza virus bigeminy inactivated vaccine, but is not limited to the oily vaccine.
The oily vaccine contains 20-50% of water phase, 500ml of vaccine contains 100-250 ml of water, the solubility requirements of lincomycin and spectinomycin can be met under common conditions, but the demulsification of the vaccine can be caused after the dissolution of common drugs, so that the dissolution difficulty of the drugs in the oily vaccine is high, and the solid compound preparation containing the lincomycin breaks through the outer oil phase of water-in-oil through oscillation, and the drugs can permeate into the water phase of the oily vaccine instantly, so that the technical effect that the high-dose lincomycin and spectinomycin drugs are dissolved in the oily vaccine quickly is realized; on the other hand, the preparation process of the solid compound preparation for the spectinomycin comprises the steps of sequentially dissolving and clathrating materials, and then carrying out spray drying, wherein the particle size is controlled to be 10-20 microns, and the crystal state of the spectinomycin for the linke can be changed into the amorphous state, so that the solubility is improved.
Compared with the prior art, the invention has the following beneficial effects:
1. the solid compound preparation can be instantly and directly dissolved in oily and aqueous vaccines, a cosolvent is not required to be added, the dissolving amount is large, the speed is high, the solubility of the solid compound preparation in the aqueous vaccine can reach 370-390 g/L, and the solubility of the solid compound preparation in the oily vaccine can reach 80-120 g/L.
2. The oil-water-soluble compound preparation can be directly dissolved in water, can keep no precipitation, has stable content within 24 hours and no degradation, is completely dissolved in an oily vaccine, has no drug particles on the bottle wall and the bottle bottom, is still uniformly distributed in the vaccine after standing for 8 hours, and has high stability, no precipitation and other phenomena.
3. The oil-water-soluble veterinary compound preparation for animals with grand appearance can expand the antibacterial spectrum, prevent and treat various diseases, particularly effectively prevent and control mycoplasma synoviae infection, and has a direct toxicity attack protection rate of 7 weeks.
Detailed Description
Experimental procedures for the invention not specifically indicated in the following examples are generally carried out under conventional conditions, or as recommended by the manufacturer. The various chemicals used in the examples are commercially available.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the description is intended to be exemplary only, and is not intended to limit the scope of the present invention. Moreover, in the following description, descriptions of well-known structures and techniques are omitted so as to not unnecessarily obscure the concepts of the present invention.
Examples 1 to 4 preparation of oil-water-soluble veterinary linke grand scale compound preparation
The formula composition of the oil-water double-soluble veterinary linke grand compound preparation is shown in table 1:
table 1:
The preparation method of the oil-water double-soluble veterinary linke grand compound preparation comprises the following steps:
s1, adding polyethylene glycol into a proper amount of water, stirring for 5min, adding cyclodextrin derivatives, stirring for 10min, adding anhydrous sodium sulfite, stirring for 2min, adding salified spectinomycin (mass content of spectinomycin in hydrochloric acid/sulfuric acid is 74% +/-0.5%) and stirring for 10min, adding salified lincomycin (mass content of lincomycin in hydrochloric acid/sulfuric acid is 95% +/-0.5%) and stirring for 10min, and finally adding poloxamer and stirring for 10min to prepare a solution;
s2, spray drying the solution prepared in the S1 by a spray drying device, wherein the temperature in the spray drying process is 155 +/-2 ℃, the temperature of a nozzle is 62 +/-2 ℃, and the solution is prepared into 14 +/-1 mu m powder;
s3, carrying out superfine grinding on lactose with the formula amount to obtain the powder with the particle size of 15 +/-1 mu m, adding the powder prepared in the S2, and mixing for 20min to obtain the veterinary civet and grand scale compound preparation with the particle size of 15 +/-1 mu m and oil-water double-dissolved.
Test example I, determination of solubility and solution stability of oil-water-soluble veterinary linke grand scale compound preparation in water
Putting 1000ml of tap water into a clean beaker, adding 100g of the oil-water-double-soluble veterinary lincomycin macroscope compound preparation, stirring for 5min at 200rpm, observing whether the preparation is dissolved, if the preparation is dissolved, continuously adding the medicine according to the dose of 10g until the eye can not be dissolved, recording the solubility of the medicine in the water, referring to table 2, taking the solution with the maximum solubility, adding a mobile phase for ultrasonic extraction, filtering, detecting the lincomycin content in the solution by a high performance liquid chromatograph (the calculation method is that the lincomycin content in the solution is = the peak area of a sample and the concentration of a lincomycin reference substance/the peak area of a lincomycin reference substance), detecting the content of the spectinomycin by an antibiotic microbiological detection method, sampling after placing the solution for 2h, 4h, 6h, 8h, 12h and 24h at room temperature respectively, determining the content of the lincomycin and the spectinomycin, observing the change condition of the medicine content in the water, the results are shown in Table 3;
Table 2: the oil-water double-soluble veterinary civic grandma compound preparation of the embodiments 1 to 4 has the maximum solubility in water
Table 3: the change of the drug content of the oil-water-soluble veterinary civic grand scale compound preparation in water along with time in the embodiments 1 to 4
The results in table 2 show that the oil-water-soluble veterinary ciconian spectacular compound preparation has high solubility in water, the maximum solubility of the solid compound preparation can reach 370-390 g/L, and the compound preparation can respectively improve the solubilities of the ciconian spectacular mycin and the lincomycin to 155.0-166.8 g/L and 68.4-74.3 g/L by combining the contents of the ciconian spectinomycin and the lincomycin in table 1.
On the other hand, as can be seen from the results in table 3, the oil-water-soluble veterinary ciconia spectabilis compound preparation of the present invention has no decrease in the drug content (spectinomycin and lincomycin) in the aqueous solution within 24 hours, good stability, no precipitation, and the like, with the increase of time.
Test example II, mixing test of the oil-water-soluble veterinary linke grand scale compound preparation and the oily vaccine
Respectively and accurately weighing 20g of samples prepared in the embodiments 1-4, adding the samples into 250ml of the newcastle disease virus (La Sota strain) and avian influenza virus (H9 subtype, ss/94 strain) bigeminy inactivated vaccine, shaking for 2 minutes, observing the dissolution condition of the drugs, standing for 8 hours, respectively sampling from the upper layer, the middle layer and the lower layer of the mixed solution at 0H, 1H, 2H, 4H, 6H and 8H, adding a mobile phase for ultrasonic extraction, filtering, and detecting the lincomycin content by high performance liquid chromatography, wherein the results are shown in a table 4.
Table 4: the oil-water-soluble veterinary lincomycin macroscopical compound preparation of the embodiments 1 to 4 is dissolved in the time-dependent change situation of the lincomycin content (mg/ml) in the combined inactivated vaccine of newcastle disease virus and avian influenza virus
In the same way as the test method, the oil-water double-soluble veterinary forest macroscopical compound preparation prepared in the embodiment 1 to 4 is dissolved in the triple inactivated vaccine (La Sota strain, M41 strain and K-11 strain) for Newcastle disease, infectious bronchitis and egg drop syndrome; the time-dependent change of lincomycin content in avian influenza (H9 subtype) inactivated vaccine (SS strain) (purchased from Zhaoqing Dahua agricultural chemicals Co., Ltd.) was determined, and it was found that the lincomycin content in different vaccines was not significantly different from the lincomycin content in Table 4.
The results show that the oil-water-soluble veterinary forest compound preparation prepared in the embodiments 1 to 4 can be completely dissolved in different oily vaccines, no drug particles are found on the bottle wall and the bottle bottom, and the drug is still uniformly distributed in the vaccines after standing for 8 hours, so that the stability is high, and the phenomena such as precipitation are avoided.
Comparative examples 1 to 6
The formula composition of the linke grand compound preparation prepared in comparative examples 1-6 is shown in table 5:
table 5:
the preparation method is the same as in examples 1 to 4.
Comparative examples 7 to 8
The difference between the comparative example 7 and the example 2 is that the granularity of the powder prepared in the step S2 in the preparation process of the compound preparation is 6 +/-1 mu m, the granularity of the lactose subjected to superfine grinding in the step S3 is 8 +/-1 mu m, the granularity of the prepared compound preparation is 8 +/-1 mu m, and the other steps are consistent with the example 2;
the difference between comparative example 8 and example 2 is that the particle size of the powder prepared in step S2 is 22 + -1 μm, the particle size of the lactose pulverization in step S3 is 25 + -1 μm, the particle size of the compound preparation is 25 + -1 μm, and the other steps are the same as example 2.
Third test example and third test example 1-8 determination of solubility and solution stability of oil-water double-soluble veterinary linke grand compound preparation in water and oily vaccine
The test example determines the solubility and the solution stability of the oil-water-soluble veterinary forest macroscopic compound preparation sample prepared in the proportion of 1-8 in water and an oily vaccine newcastle disease virus (La Sota strain) and avian influenza virus (H9 subtype, ss/94 strain) bivalent inactivated vaccine, the determination method is the same as that of the first test example and the second test example, and the determination results are shown in a table 6;
table 6:
from the results in table 6, compared with the solubility of the veterinary civic complex formulation with both oil and water in water and an oily vaccine prepared in example 2, the solubility of the compound formulation prepared in comparative examples 1 to 6 in water and an oily vaccine is significantly reduced, the combination of the molecular weight of polyethylene glycol, the cyclodextrin and the poloxamer in the compound formulation can effectively promote the dissolution of the compound formulation, the solubility of the civic and the spectinomycin in the compound formulation is improved, and the stability of the compound formulation in the oily vaccine is significantly improved, the content of the lincomycin in the upper layer, the middle layer and the lower layer of the oily vaccine in the 0h and the 8h in table 6 shows that the compound formulation/the lincomycin dissolved in the oily vaccine has an obvious sedimentation phenomenon, so that the combination components and the proportions of the molecular weight of polyethylene glycol, the cyclodextrin and the poloxamer are changed, precipitation of the preparation in the oily vaccine is caused to generate sedimentation, and the stability may be insufficient, so that the concentration of the medicine in the solution is not uniform any more; on the other hand, the test results of the comparative example 7 and the comparative example 8 show that the particle size of the compound preparation is less than 10 mu m, the solubility in water and oil seedlings is obviously lower, certain sedimentation problems exist, the stability is poor, and the particle size of the compound preparation exceeds 20 mu m, more sedimentation particles exist in water and oil seedlings, and the vaccine is fast in demulsification and unstable.
Fourth test example, clinical test of the oil-water-soluble veterinary linke grand scale compound preparation for preventing and controlling mycoplasma synoviae
300 local yellow chickens divided into 6 groups (Shi)Group of example 1, group of example 2, group of example 3, group of example 4, positive control group, and healthy control group), 0.5ml of a mixture of the avian influenza vaccine and each of the drugs of examples was co-injected on day 10 (20 g of each of the drugs of examples (the oil-water-soluble veterinary cicerone grand compound preparation prepared in each example) was directly added to 250ml of a bivalent inactivated vaccine against newcastle disease virus (LaSota strain) and avian influenza virus (subtype H9, ss/94 strain) (manufactured by Zhaoqing Dahua biopharmaceutical Co., Ltd.), respectively), and the mixture was shaken and dissolved by subcutaneous injection at the neck of each feather, 0.5ml was injected at the neck of each feather, and all chickens other than the healthy control group were injected with 0.4ml of 10-day-10 air-bag for three consecutive days 1 week after the administration8~109ccu/ml of Mycoplasma Synoviae (MS), continuously observing for 49 days, and recording the morbidity and mortality of all groups of chickens, wherein the results are shown in a table 7;
table 7: the oil-water-soluble veterinary linkeda macroscopical compound preparation and oily vaccine mixture of the invention have the clinical test result of preventing and controlling mycoplasma synoviae
The results in the table 7 show that the oil-water-soluble veterinary forest spectacular compound preparation prepared by the invention can be directly added into an oily vaccine for use, so that the morbidity of mycoplasma synoviae can be effectively reduced, the death of chickens is reduced, and the effect of a healthy control group can be achieved.
It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. This need not be, nor should it be exhaustive of all embodiments. And obvious variations or modifications derived therefrom are intended to be within the scope of the invention.
Claims (10)
1. An oil-water-soluble veterinary linke grand scale compound preparation is characterized by comprising the following materials in parts by weight: 5-10 parts of polyethylene glycol, 5-12 parts of cyclodextrin derivative, 2-4 parts of poloxamer, 2-7 parts of anhydrous sodium sulfite, 60-100 parts of spectinomycin and/or salifying form, 20-40 parts of lincomycin and/or salifying form and 10-20 parts of lactose.
2. The veterinary lincomycin macranthus compound preparation capable of dissolving in both water and oil according to claim 1, wherein the salt-forming form of lincomycin and the salt-forming form of spectinomycin in the material are selected from the hydrochloride or sulfate forms thereof.
3. The veterinary civic but macroscopical compound preparation according to claim 1, wherein the polyethylene glycol is polyethylene glycol 3000-10000.
4. The veterinarian lincomanium compound formulation with oil-water double solubility according to claim 1, characterized in that said cyclodextrin derivatives are selected from one or a combination of (2-hydroxypropyl) - α -cyclodextrin, (2-hydroxypropyl) - β -cyclodextrin, (2-hydroxyethyl) - β -cyclodextrin, carboxymethyl- β -cyclodextrin or sodium salt, (2-hydroxypropyl) - γ -cyclodextrin, methyl- β -cyclodextrin, triacetyl- β -cyclodextrin and β -cyclodextrin sulfobutyl ether or sodium salt.
5. The method for preparing the oil-water-soluble veterinary civic lincomania grandma compound preparation according to any one of claims 1 to 4, comprising the following steps:
s1, adding polyethylene glycol into a proper amount of water, stirring, adding cyclodextrin derivatives, stirring, adding anhydrous sodium sulfite, stirring, adding spectinomycin in a salt form, stirring, adding lincomycin in a salt form, stirring, adding poloxamer, and stirring to prepare a solution;
s2, spray drying the solution prepared in the S1 by a spray drying device to prepare powder;
s3, carrying out superfine grinding on lactose in the formula amount, adding the lactose into the powder prepared in the S2, and mixing for 20-40 min to obtain the veterinary ciconi grand compound preparation dissolved in oil and water.
6. The preparation method according to claim 5, wherein the polyethylene glycols are stirred in water for 5-10 min; the added cyclodextrin derivative is stirred for 10-20 min; the stirring time for adding the anhydrous sodium sulfite is 2-10 min; the stirring time for adding the salified spectinomycin is 10-20 min; the stirring time for adding the salified lincomycin is 10-20 min; and the stirring time for adding the poloxamer is 10-30 min.
7. The method according to claim 5, wherein the spray drying temperature of step S2 is 140-170 ℃ and the nozzle temperature is 50-70 ℃.
8. The method according to claim 5, wherein the powder of step S2 has a particle size of 10 to 15 μm; the step S3, crushing lactose to the granularity of 10-20 μm; the particle size of the oil-water-soluble veterinary ciconia compound preparation obtained in the step S3 is 10-20 microns.
9. The use of the oil-water-soluble veterinary civic but macroscopical compound preparation according to any one of claims 1 to 4 in drugs or vaccines against bacteria, fungi and pathogenic infections.
10. The use of claim 9, wherein the compound preparation is dissolved in the aqueous vaccine in an amount of 370-390 g/L and in the oily vaccine in an amount of 80-120 g/L.
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