36 results about "Milbemycin oxime" patented technology

The invention relates to the technical field of gene recombination, and particularly relates to streptomycete generating 5-keto-milbemycins and a method for producing 5-keto-milbemycins. The invention provides a recombinant vector for knocking out the milF gene of streptomycete, including the homologous fragment of the milF gene, wherein the sequence of the fragment is obtained by losing 105-767 nucleotides from the nucleotides from the sites 158-924 in the nucleotide sequence shown by SEQ ID No.2. The invention also provides an establishment method of the recombinant vector, a method for knocking out the milF gene in streptomycete by use of the recombinant vector and streptomycete without milF gene. The streptomycete can be directly fermented to generate 5-keto-milbemycins, so that the synthesis process of milbemycin oxime is simplified, and the pollution caused by the traditional chemical synthesis method is avoided.

A method of preparing high-purity milbemycin oxime is disclosed. The method includes extracting milbemycin A3 and milbemycin A4 from a fermentation liquor, performing preliminary purification, oxidizing with an oxidant low in oxidizing activity, performing silica gel chromatography to increase the content of milbemycin A3 ketone and milbemycin A4 ketone to a value higher than 75% from a value lower than 25%, naturally crystallizing during concentration to increase the content of the milbemycin A3 ketone and the milbemycin A4 ketone to a value higher than 95%, performing oximation, and performing resin chromatography to adjust the ratio of the content of milbemycin A3 oxime to the content of milbemycin A4 oxime to be 1:4 and to increase the product purity to be higher than 98%. The method is simple in process, low in equipment requirement, good in universality and suitable for large-scale production.

The invention relates to a phage antibody library which assembles an ScFv gene fragment between Restriction Enzyme cutting sites of SfiI and NotI of a pCANTAB5E carrier. The phage antibody library is characterized in that the ScFv gene fragment can be affinitive and enriched with antigens of 16-membered macrolide agricultural chemicals to form a soluble single-chain antibody and the phage antibody library is applied to immunoassay of pesticide residue. The phage antibody library has the advantages that the antibody with high affinity can be obtained without animal immunization, the test period is short, the antibody library is the phage antibody library which takes small molecular milbemycin oxime of a 16-membered macrolide generic structure as immunogen to construct, the antibody library theoretically can directly obtain a specific antibody library of 16-membered macrolide compound through screening, the screening flux is high, the efficiency is high, the specificity is strong, and the affinity selecting range is wide, so that the phage antibody library has wide application prospect in the aspects such as agricultural chemical antibody preparation, testing technique development and the like.

The invention provides a preparation method of milbemycin oxime. The preparation method of milbemycin oxime comprises the following steps: extracting milbemycins, namely taking milbe mycelia obtained through fermentation as a raw material, extracting, concentrating, extracting, concentrating, extracting again and concentrating again, so as to obtain milbemycin; preparing milbemycin ketone, namely taking the milbemycin as a raw material, establishing an oxidation reaction system, after reaction is finished, filtering, concentrating, extracting and concentrating the reaction system, so as to obtain an intermediate product milbemycin ketone; synthesizing milbemycin oxime, namely dissolving milbemycin ketone with methanol and dioxane, dropwise adding hydroxylamine hydrochloride solution and reacting, concentrating the reaction system, extracting, drying and concentrating, so as to obtain a milbemycin oxime crude product; and purifying milbemycin oxime, namely crystallizing the milbemycin oxime crude product with a mixed solvent of trichloromethane and normal heptane, dissolving a crystalline product with ethanol, dropwise adding into water while stirring for carrying out crystallization, filtering, and drying, so that the milbemycin oxime finished product is obtained. The preparation method of the milbemycin oxime has the advantages that productivity is greatly improved, and cost is obviously reduced, so that the preparation method provided by the invention is obviously better than an existing preparation method.

The invention relates to a compound preparation for expelling in-vivo and in-vitro parasites from dogs and cats and a preparation method thereof. The compound preparation mainly comprises milbemycin oxime and praziquantel, wherein the milbemycin oxime is a novel and specific 16-membered ring macrolide medicament for preventing and controlling the in-vivo and in-vitro parasites of the dogs and the cats, which can specially prevent and control heartworms and efficiently prevent and control in-vivo parasites such as hookworms, roundworms, whipworms, belly worms and the like and in-vitro parasites such as hair follicle mites, scabies, louses, fleas and the like; and the praziquantel is effective to nematodes, trematodes and tapeworms in animal bodies. The milbemycin oxime and the praziquantel expel the parasites complementarily. The two medicaments are combined, so that a parasite expelling range is expanded and one-step parasite expelling effect is improved. The invention also provides a method for preparing compound tablets. The tablets prepared by the method can be released rapidly and dispersed fully.

The invention provides a milbemycin oxime separation and purification method. The milbemycin oxime separation and purification method comprises the following steps: carrying out crude separation on a sample to be separated through silicagel column chromatography, wherein the silicagel column chromatography adopts wet-process column packing and dry-method sample loading; purifying the product after crude separation by high performance liquid chromatography; concentrating the purified sample by a nanofiltration membrane to obtain concentrated solution; performing reduced-pressure vaporization to the concentrated solution, filtering and drying to obtain a refined product; dissolving the refined product, heating up, dropwise adding isooctyl alcohol, normal heptane or petroleum ether, cooling to be crystallized, and filtering to obtain a crystallized product; dissolving the crystallized product, filtering, dropwise adding filtrate into purified water stirred constantly, after dropwise adding, carrying out suction filtration to obtain a crystal transformation product; drying the crystal transformation product, crushing, and drying again to obtain milbemycin oxime finished product. The method can realize industrial production of milbemycin oxime in China firstly, and the product has high purity and high yield which are higher than those of the similar products at home and abroad.

The invention relates to a preparation method of a milbemycin oxime intermediate II. The preparation method comprises the step of reacting milbemycins (I) with pypocholoride as an oxidant in the presence of a catalyst and bromide to generate the milbemycin oxime intermediate II. The preparation method provided by the invention is simple in process operation, high in yield, low in cost, and is very suitable for industrial production. The formula I and the formula II are shown in the description, wherein R is equal to CH3 or C2H5.

The invention discloses an LC-MS/MS method for determining the milbemycin oxime content in animal plasma and belongs to the fields of veterinary drug content determination, pharmacokinetics and residue law. The method comprises the following steps of: adding 4mL of acetonitrile and 0.3g of sodium chloride into 1mL of plasma sample, mixing and then centrifuging the mixture, drying the supernatant by blowing nitrogen gas, adding 3mL of methanol and 5mmol/L of ammonium acetate into the residue in a ratio of 1:9, purifying the mixture by a C18 solid extraction column; and using a liquid chromatography-mass spectrometry instrument for analysis under the following conditions: electrospray ionization, nitrogen gas spray pressure of 49psi, spray voltage of 4800V, nitrogen gas pressure of 20psi, temperature of 300 DEG C, Source CID of 12V; m/z of 536, detection of fragment ions of which m/z is 536 by the full scan, composition of mobile phase by acetonitrile and 0.5mmol/L of ammonium acetate in a ratio of 85:15, flow speed of 0.25mL/min, and column temperature of 20 DEG C. The method has the characteristics of fastness, sensitivity and low detection limit.

The invention discloses a compound milbemycin oxime nanoemulsion anti-parasite medicine and a preparation method thereof. The diameter of a liquid drop of the nanoemulsion medicine ranges from 1nm to 100nm, the medicine is composed of the following raw materials by mass: milbemycin oxime 0.5%-3.5%, levamisole 0.1%-0.5%, a surface active agent 23.5%-38.5%, oil 3.0%-17.0%, the remaining part is distilled water, and the sum of the mass percentage of the raw materials is 100%. The nanoemulsion preparation is clear and transparent liquid, has good stability and fast absorption, is released to targets, has the advantages of high efficiency, broad spectrum, low toxicity and the like, is a medicine for preventing and treating internal and external parasites of pets, and is mainly used for preventing and treating dirofilariasis and removing internal parasites of nematodes, hookworms, roundworms, whipworms and the like and external parasites of itch mites, nasal mites, hair follicle mites, louses, fleas and the like. The compound milbemycin oxime nanoemulsion anti-parasite medicine solves the problem of water insolubility of milbemycin oxime, is simple in preparation process, high in safety and convenient to popularize.

The invention relates to an insect-repellent hairball remedy and a preparation method of the insect-repellent hairball remedy. The insect-repellent hairball remedy is prepared from the following raw materials in parts by weight: 10-15 parts of salmon bones, 5-10 parts of salmon scales, 5-10 parts of pteridium aquilinum, 5-10 parts of black fungus, 5-10 parts of psyllium seed husks powder, 20-30 parts of sickle alfalfa, 10-15 parts of olive oil, 10-15 parts of duck fat, 3-6 parts of bacillus subtilis, 1-1.5 parts of calcium lactate, 2-5 parts of malt polysaccharide, 2-5 parts of taurine, 5-8 parts of hickory epicarp, 2-2.5 parts of mirabilite, 2-2.5 parts of carrot, 0.5-1 part of milbemycin oxime and 0.3-0.5 part of praziquantel.

The invention relates to a long-acting compound anthelmintic liquid preparation as well as a preparation method and application thereof, and belongs to the field of veterinary drug preparations. The compound preparation is mainlycomposed of anti-parasitic active ingredients, namely milbemycin oxime, benzimidazoles and juvenile hormone ingredients, and comprises, in percent by mass, 0.5%-1% of milbemycin oxime, 5%-10% of benzimidazoles, 3%-5% of juvenile hormone, 0.1%-5% of macromolecule suspending agent, 0.1%-5% of wetting agent, 0.01%-1% of antioxidant and the balance of a dispersion medium.According to the invention, anti-parasitic drugs are combined for use, the insect-resistant spectrum is expanded, and a comprehensive and efficient in-vivo and in-vitro simultaneous-expelling effect is achieved.

The invention discloses a milbemycin oxime nano suspension for treating dog parasitic diseases and a preparation method thereof. Each 100 mL of suspension contains 2 to 5 grams of milbemycin oxime, 0.1 to 0.4 mL of wetting agent, 3.0 to 5.5 grams of suspending agent, 1.0 to 2.0 grams of flocculating agent, and the balance being purified water or injection water. The provided milbemycin oxime nano suspension is mainly made of milbemycin oxime, and at the same time, a wetting agent, a suspending agent, and a flocculating agent are added, so the milbemycin oxime nano suspension has a stable property and can be used to prepare oral or injection drugs. The detention time of the drugs in human body is prolonged, thus the drugs can be fully absorbed by human body, and the biological utilization degree is improved. The milbemycin oxime nano suspension is used to treat dog in-vitro/in-vivo parasitic diseases in clinic and has the advantages of safety, good curative effect, little side effect, and user-friendliness.

The invention relates to the technical field of pharmaceutical compositions, in particular to a pharmaceutical composition for treating ear mites. The pharmaceutical composition is transparent milbemycin oxime ear drops, and comprises the following raw material medicines in percentages by weight: 0.1-1.0% of milbemycin oxime, 19.0-92.5% of a solvent, 2.0-50.0% of a solubilizer and 2.0-30.0% of a stabilizer. The ear drops provided by the invention are an innovative preparation for treating ear mites, can be dropped into ear canals of cats and dogs for use, directly act on ear mites, have an extremely strong curative effect on medium and severe ear mite infection, and are high in safety. The composition prepared by the invention has the characteristics of being convenient to administrate, accurate in dosage, lasting in effect and strong in curative effect, is non-irritant due to ear drop use, and has higher animal medicine taking compliance compared with oral medicines.

The invention discloses a method for recovering manganese dioxide from milbemycin oxime filter residues, which belongs to the technical field of manganese dioxide recovery and sequentially uses ethanol and deionized water to perform top washing on the manganese dioxide filter residues. According to the method, manganese dioxide can be effectively recycled from the filter residues generated in milbemycin oxime production through a manganese dioxide oxidation method, acetone and residual products in the filter residues can be effectively removed, the manganese dioxide is stopped from continuingto react with the products, combustible gas in the filter residues is removed, and potential safety hazards caused by reaction heat release are thoroughly avoided; meanwhile, the obtained manganese dioxide still has certain oxidation activity and can be reutilized after being recycled and treated, the production cost of enterprises is effectively reduced, the used ethyl alcohol and deionized waterare used for top washing, the raw materials are easy to obtain and low in price, the ethyl alcohol and the deionized water are non-toxic, and secondary pollution cannot be caused.

The invention discloses a preparation method of milbemycin oxime. The preparation method comprises the following steps: taking an ethyl acetate-ethanol solution as a reaction solvent to dissolve milbemycin ketone, and adding and a water solution of hydroxylamine hydrochloride for carrying out a reaction for 4-6 hours to prepare the milbemycin oxime. The preparation method also comprises the stepsof purifying the prepared milbemycin oxime, and the specific purifying steps are as the follows: washing the prepared milbemycin oxime with water, dissolving the washed milbemycin oxime with ethanol,dropwise adding the obtained solution into water for crystallization under stirring, and carrying out filtering and drying to obtain the pure product of milbemycin oxime. Compared with the prior art,the preparation method can be used to greatly reduce the occupational health hazard of employees by using the low-toxicity solvent instead of a high-toxicity solvent. The reaction time is greatly shortened, and the production efficiency is improved.

The invention provides a method for simultaneously detecting contents of praziquantel, clofenoxine and milbemycin oxime, which comprises the following steps: firstly preparing a blank solution, then preparing a test solution containing praziquantel, clofenoxine and milbemycin oxime, finally preparing a system applicability test solution, respectively injecting into a liquid chromatograph, and recording chromatograms under ultraviolet wavelength; according to the method, acetonitrile is taken as a diluent, octadecylsilane chemically bonded silica is taken as a chromatographic column in a liquid chromatograph, gradient elution is carried out, the flow rate is 1.0 mL/min, the column temperature is 30 DEG C, the ultraviolet detection wavelength is 230 nm, and the sample size is 20 mu L; the mobile phase A is a phosphoric acid solution with the content of 10-30 wt%, and the mobile phase B is acetonitrile with the content of 70-90 wt%; the detection method provided by the invention is simple and convenient, saves time, reduces cost, has good specificity, accuracy, linearity, durability and precision, and is suitable and accurate for detecting the content of the three components, so that the detection method can be used for daily detection of the pet medicine.

The invention discloses a panda epidermis insect repellent spray and a preparation method thereof. The spray is prepared from the following components in parts by weight: 18 to 25 parts of minoxidil,10 to 20 parts of stearic acid, 8 to 13 parts of polyethylene glycol, 22 to 34 parts of milbemycin oxime, 8 to 15 parts of tea leaves, 7 to 18 parts of ivory crumbs, 11 to 21 parts of bead tree bark,10 to 16 parts of cotex dictamni, 3 to 6 parts of seaweed, 3 to 5 parts of fructus xanthii, 2 to 6 parts of folium artemisiae argyi, 4 to 7 parts of honeycomb, 8 to 16 parts of galla chinensis, 2 to 3parts of dioctyl sulfosuccinate sodium salt, and 1 to 2 parts of fatty alcohol-polyoxyethylene ether. The spray can be used for quickly expelling insects and relieving itching, is durable in effect and not easy to recur, and has no toxic and side effects on pandas at the same time.