59 results about "Valnemulin Hydrochloride" patented technology

The invention mainly discloses a crystallization method of valnemulin hydrochloride. The method comprises the following steps: dissolving valnemulin in an organic solvent; adding a certain amount of dried hydrogen chloride gas or hydrogen chloride organic solution; separating out crystals; and collecting the obtained crystals, and drying so as to obtain valnemulin hydrochloride. The method is convenient for operation, is suitable for industrial production on large scale, has low cost and can be used for purifying the product. The chromatograph content of the valnemulin hydrochloride obtained by the method in the invention is improved by 1-5% as compared with the chromatograph content of the corresponding valnemulin.

The invention discloses valnemulin hydrochloride emulsion for animals. Each 100ml of emulsion mainly comprises the following components by weight: 5 to 10g of valnemulin hydrochloride, 1 to 5g of emulsifier, 20 to 40g of oil for injection, 5 to 15g of ethanol and the balance of water for injection. The valnemulin hydrochloride emulsion for animals has the advantages of quick in vivo distribution and good target, can reduce the medicament residue in vivo and the toxic or side effect on the animals, and also can mask the unpleasant odor of the medicament, and improve the stability of the medicament. The valnemulin hydrochloride emulsion for animals can effectively treat gram-positive bacteria and mycoplasma infection, particularly swine dysentery and porcine enzootic pneumonia, and can reduce the using amount of the medicament and avoid medicament tolerance.

The invention discloses a chemical synthesis method of valnemulin hydrochloride, which comprises the following steps of: taking refined pleuromutilin as raw material, carrying out sulfonation by paratoluensulfonyl chloride, and reacting with dimethyl cysteamine hcl, to obtain the pleuromutilin dimethyl cysteamine substitute; reacting D-valine, methyl acetoacetate and potassium hydroxide to obtain (R)-2-(1-methoxycarbonyl group-2-allyl) amino-3-methyl potassium butyrate, activating by ethyl chloroformate and reacting with the pleuromutilin dimethyl cysteamine substitute, adjusting PH value, carrying out reverse phase extraction, and carrying out freeze-drying to obtain the valnemulin hydrochloride. The method has the advantages that due to the refining of the raw material pleuromutilin, the impurities in the product can be effectively removed, and the purifying process can be simplified from the source; the carboxyl of D-valine can be activated by the ethyl chloroformate, so that the reaction is easier to carry out; and due to the pH adjustment, the reverse phase extraction, and the freeze-drying, the product can be obtained, so that the product is stable in quality, and high in purity.

The invention belongs to preparation of antibiotic, in particular to preparation method of Valnemulin and hydrochloride thereof.D-hydroxy valine Dane salt is added into more than ten weight of tetrahydrofuran and is suspended by stirring at 0-20 DEG C, and triethylamine, N, N-dimethyl formamide (acetamide) and N-methyl morpholine are added until reaction liquid is clear; methyl (ethyl) chloroformate molar weight of which is not more than that of D-hydroxy valine Dane salt is added; (2-amino-1, 1-dimethyl ethyl) mercaptoacetic acid, (3aS, 4R, 5S, 6S, 8R, 9R, 9aR, 10R)-octohydrogen-5, 8-dyhydroxy-4, 6, 9,10-tetramethyl-6-ethenyl-3a, 9-propane-3aH-cyclopentene (cyclooctene)-1(4H)-keto-8-ester the molar weight of which is not more than that of D-hydroxy valine Dane salt is dissolved in equal mass of tetrahydrofuran, the reaction liquid is dripped in and stirred at 0-10 DEG C, and reaction is carried out for 2-5h at 0-20 DEG C; the organic solvent is removed, the residue is added with water and hydrochloric acid is used for adjusting pH value, heating up, stirring and decontaminating are carried out, and the filtration is freeze dried to obtain Valnemulin hydrochloride. The invention solves the problems of low purity and high reaction condition of the existing product and has the advantages of simple technology and high product purity.

The invention relates to a preparation method of valnemulin hydrochloride. The preparation method comprises the following steps: reacting pleuromutilin with p-toluenesulfonyl chloride, substituting with 1-amino-2-methyl propyl-2-mercaptan hydrochloride so as to obtain [(2-amino-1,1-dimethyl S, 6S, 8R,9R, 9aR, 10R)-6-vinyl decahydro-5-hydroxyl-4,6,9,10-tertamethyl-1-oxo-3a, 9-propanol-3aH-cyclopentacyclooctene-8-yl ester for later use; reacting D-valine with methyl acetoacetate; synthesizing the product with isobutyl chloroacetate so as to generate anhydride; and reacting anhydride with [(2-amino-1,1-dimethyl ethyl) sulfenyl] acetic acid (3aS, 4R, 5, 6S, 8R,9R, 9aR, 10R)-6-vinyl decahydro-5-hydroxyl-4,6,9,10-tertamethyl-1-oxo-3a, 9-propanol-3aH-cyclopentacyclooctene-8-yl ester so as to generate amide, and then carrying out deprotection with hydrochloric acid so as to prepare valnemulin hydrochloride. The method has the advantages that (1) reaction temperature is mild, thereby being applicable to large-scale production; (2) post-treatment is simple, thereby directly obtaining the product; (3) used solvents are less, thereby reducing environmental pollution; and (4) the valnemulin hydrochloride content and yield of the obtained product are high.

The invention belongs to a process for preparing a valnemulin hydrochloride premix of pleuromutilin antibiotics specially used for animals, and in particular relates to a method for preparing a valnemulin hydrochloride coating granule. The method comprises the following process steps of pre-granulation of the valnemulin hydrochloride, preparation of coating solution, coating of the valnemulin hydrochloride and the like. The method has the advantages of solving the problems existing in the prior art that the valnemulin hydrochloride materials are hygroscopic, sensitive to light and strong in powder irritation, and are easily decomposed when being mixed with feed and the like, effectively achieving the aim of odor masking and the like; moreover, after coating, the coating granule is stable under conditions of a light accelerating experiment.

The invention provides a method for purifying valnemulin hydrochloride. The method comprises the following steps of: directly alkalizing crude valnemulin in an aqueous solution thereof; and directly preparing into phosphate in an alcohol solution and curing. In the method, multiple times of extraction of valnemulin hydrochloride and introduction of other salts are not required, the treating process is easy and convenient, the loss of the product is small, waste water is easy to treat, and the problem of difficulty in purifying the valnemulin hydrochloride is solved.

The invention discloses a veterinary-use intestinal targeted antibacterial pellet. The veterinary-use intestinal targeted antibacterial pellet comprises a main drug and auxiliary drugs, wherein the main drug is composed of valnemulin hydrochloride and chlortetracycline hydrochloride; the mass of the valnemulin hydrochloride is 1-5% of that of the pellet; the mass of the chlortetracycline hydrochloride is 5-16 times of that of the valnemulin hydrochloride; the pellet sequentially comprises a valnemulin hydrochloride core, an intestinal targeted coating layer, a chlortetracycline hydrochloride drug layer and an outer coating layer from inside to outside. The invention further discloses a preparation method of the veterinary-use intestinal targeted antibacterial pellet. Through the combination of the method and the formula, the valnemulin hydrochloride and the chlortetracycline hydrochloride are adopted for preparing the pellet; the pellet is released in a gradient form in an animal digestion system; the chlortetracycline hydrochloride is firstly released and absorbed by the stomach and the intestine; the valnemulin hydrochloride is rapidly released and absorbed by the intestinal tract with the pH value larger than or equal to 6.8, so that an excellent intestinal tract sterilization effect is achieved, the drug absorbed by the colon can be prevented from suffering from the first-pass effect of the liver and the intestine, the haemoconcentration and bioavailability of the valnemulin hydrochloride can be improved, and an excellent treatment effect for systemic diseases is obtained.

The invention provides a recipe of a valnemulin hydrochloride enteric-coated pellet and a preparation method thereof, wherein, acrylic resin water dispersion is taken as coating liquid, and water is taken as a solvent, thus changing the method that the existing resin coating liquid selects high concentration alcohol as the solvent, lowering cost and overcoming the defect of environmental influence due to evaporation of a large amount of alcohol during the coating process. The preparation method of the valnemulin hydrochloride enteric-coated pellet comprises the steps of preparation of the valnemulin hydrochloride medicine carrying pellet, preparation of the coating liquid and preparation of valnemulin hydrochloride coating. By adopting an extrusion-spheronization process procedure, the preparation method solves the defects of a one-step fluidized bed granulating method such as coarse and loose particles, large particle size range, a large amount of dust; and the pellet prepared by the method has even particle size and narrower distribution range, thus being beneficial to uniform saturation of the coating liquid on the particles, and improving the taste masking effect.

The invention provides an application of valnemulin hydrochloride which is utilized to prepare a medicine for treating and preventing chicken mycoplasma infection and bacterial infection diseases. The medicine prepared by the valnemulin hydrochloride is a premix, soluble powder and a solution. Compared with traditional technology, the valnemulin hydrochloride provided by the invention is applied to chicken respiratory disease and chicken bacterial infection disease, so that the treatment effect of the valnemulin hydrochloride is more significant and the two diseases can be completely healed under the reasonable dose; and the residual quantity of the medicine in the chicken bodies is very low after the chicken is healed, the healed chicken is free from drug resistance of the medicine, so that the medicine can be repeatedly utilized but the curative effect of the medicine is not influenced.

The invention relates to a refining method of valnemulin hydrochloride. The refining method comprises the following steps: adding purified water or distilled water into an ether solution of valnemulin alkali; mixing; heating the solution until the temperature of the solution reaches 40-50 DEG C; stirring for 0.5-1h; standing for layering; taking the supernatant; adding an ethanol solution into the supernatant; stirring for 0.5-1h; standing for layering; taking the supernatant organic liquid; leading dry hydrogen chloride gas into the supernatant organic liquid; slowly stirring for 2-3h at the room temperature; separating out a large number of crystals; slowly reducing the temperature of the solution to 0 DEG C; filtering after completely crystallizing; drying the crystals. According to the refining method, the characteristics that the valnemulin alkali can be dissolved in the ether solution and the valnemulin hydrochloride cannot be dissolved in the ether solution are utilized, the valnemulin is become into a salt and then separated out through crystallization; the water and the ethanol solution are used for washing the valnemulin alkali so as to remove inorganic salt impurities and organic impurities from the valnemulin alkali, thus achieving a purifying purpose. The refining method has the characteristics of simple process, easy implementation in production, low cost, no pollution, relatively-high yield and high product purity.

The invention relates to the technical field of veterinary antibiotic preparations, and particularly discloses a veterinary valnemulin hydrochloride premix and a preparation method thereof. The premix comprises a valnemulin hydrochloride clathrate and a matrix diluent, wherein the coating carrier of the clathrate is any one of or a mixture of two of beta-cyclodextrin, hydroxypropyl beta-cyclodextrin, polyethylene glycol 4000, polyethylene glycol 6000, and ethyl cellulose; and the matrix diluent is any one of or a mixture of two or three of starch, maltodextrin, miropowder silica gel and talcum powder. Anhydrous ethanol and liquid state polyethylene glycol are added in the clathrate to promote the bonding of the clathrate, and wetting agent sorbitol is added to form a semi-solid state, so as to increase the molecular acting force between the entire medicine and a polymer carrier and increase the encapsulation rate of the clathrate. The prepared veterinary valnemulin hydrochloride premix has the advantages of stable properties, good uniformity, high fluidity, and no pungent odor.

The invention discloses a valnemulin hydrochloride freeze-dried powder injection and a preparation method thereof. The preparation method comprises the following steps: dissolving the proportioned valnemulin raw powder and excipient by adopting injection water, removing the heat source, obtaining the valnemulin hydrochloride freeze-dried stock solution, pre-freezing, subliming drying, parsing drying, obtaining the freeze-dried powder, plugging, rolling a cover, inspecting, and obtaining a valnemulin hydrochloride freeze-dried powder injection finished product. The finished product appearance is in a white loose block shape, can be rapidly dissolved into clear liquid after the injection water is added, and is good in re-solubility. When the valnemulin hydrochloride freeze-dried powder injection is stored for six months under the condition of 40 plus or minus 2 DEG C and RH75 percent plus or minus 5 percent, the quality is stable. The valnemulin hydrochloride freeze-dried powder injection is simple, easy, stable and reliable in process, accurate in administration dosage of a dosage form, and suitable for the industrialized production.

The present invention provides uses of valnemulin hydrogen tartrate in veterinary drugs, and mainly relates to uses of the valnemulin hydrogen tartrate in preparations of drugs for treatments and preventions of veterinary diseases related to swine mycoplasma infection and bacterial infection. Compared to the prior art, the following characteristics in the present invention are provided: valnemulin hydrogen tartrate is made into a premix or a granule or powder, a mixing feeding way is adopted to achieve prevention and treatment of swine mycoplasma infection and bacterial infection, an anti-mycoplasma effect of the drug of the present invention is better than anti-mycoplasma effects of other similar products, and no drug resistance is generated. According to the present invention, the uses of the valnemulin hydrogen tartrate in veterinary diseases in the present invention are not presented in the prior art; compared with valnemulin hydrochloride, preparations prepared by the valnemulin hydrogen tartrate provide better effects for treatments of veterinary diseases, and especially for swine diseases; hygroscopicity of the valnemulin hydrogen tartrate is low, and is easily stored for a long time, wherein effects of the drug can not be affected; and palatability of the preparations prepared by the valnemulin hydrogen tartrate is stronger than palatability of valnemulin hydrochloride preparations in the prior art.

The invention discloses a valnemulin hydrochloride granule which comprises the following raw materials by weight: 10% of valnemulin hydrochloride, 89% of fillers, and 1% of wetting agents. The invention also discloses a preparation method of the valnemulin hydrochloride granule. Since valnemulin hydrochloride itself has heavy peculiar smell and is unstable, the invention prepares granules to overcome the peculiar smell of valnemulin hydrochloride, and improves the stability; no dosage form administrated in a granule form is on the market; the invention introduces a dosage form of a same medicament, makes the administration become more diverse, and meets the deficiency in the market. The valnemulin hydrochloride granule of the invention has the advantages of fast absorption, quick effect, capability of overcoming the deficiencies of former dosage forms, convenience, stability, and good taste.

The invention discloses valnemulin hydrochloride sustained-release granules and a preparation method and application thereof.The valnemulin hydrochloride sustained-release granules are prepared from, by mass, 5-50% of valnemulin hydrochloride and the balance carrier auxiliary materials through the fluidized spraying technology.The carrier auxiliary materials are one or more of animal fat, beewax, carnauba wax, hydrogenated vegetable oil, stearyl alcohol, fatty acid monoglyceride, fatty acid di-glyceride and paraffin.The valnemulin hydrochloride sustained-release granules solve the problem that medicine stability is poor, improve product quality and stability, and prolong service life.The problems that medicine powder is high in irritation and poor in palatability are solved.The granules and feed are mixed to be supplied, the medicine is released slowly, effective blood concentration maintenance time is longer, the administration frequency is reduced, the bioavailability of valnemulin hydrochloride is improved, and the clinical use effect is remarkable.

The invention discloses valnemulin hydrochloride self-emulsified oral nano emulsion for veterinary use and a preparation method thereof. The valnemulin hydrochloride self-emulsified oral nano emulsion for veterinary use comprises the following components: valnemulin hydrochloride, oil, surfactant, preservative, antioxygen and auxiliary surfactant. After disintegrating in water and being stirred slightly or being taken orally and moving with intestine movement, the self-emulsified emulsion can spontaneously form emulsion with emulsion droplet size of 10 to 100 nanometers; the drawbacks of decomposition of valnemulin during long standing and content reduction of the valnemulin or valnemulin hydrochloride nano emulsion prepared in the prior art are overcome and the content stability of the product is increased; the palatability of the valnemulin product is improved; and the preparation process is simple, and the valnemulin hydrochloride self-emulsified oral nano emulsion is suitable to be produced in large scale by veterinary medicine enterprises.

The invention provides a valnemulin-O-benzoyl sulfonimide compound. The compound is prepared by adopting a method comprising the following steps: firstly dissolving O-benzoyl sulfonamide in water, regulating a pH value to 4-5, adding an organic solvent for extraction, collecting an organic layer, then adding valnemulin into the organic layer for reaction, reducing the temperature to 0-5 DEG C after the end of reaction, performing suction filtration and collection on a solid precipitate and then drying to obtain the valnemulin-O-benzoyl sulfonimide compound. The valnemulin-O-benzoyl sulfonimidecompound provided by the invention solves the problem in the prior art, can improve the palatability of existing valnemulin hydrochloride, improve the bioavailability of the valnemulin and achieve the purpose of ensuring a clinical treatment effect.

The invention relates to a valnemulin hydrochloride hydrate crystal form and a preparation method thereof and a pharmaceutical composition containing the crystal form. Specifically, the valnemulin hydrochloride hydrate crystal form shows characteristic peaks 2 Theta at 9.2+/-0.2 degrees, 9.5+/-0.2 degrees, 10.3+/-0.2 degrees, 11.8+/-0.2 degrees, 12.3+/-0.2 degrees, 12.8+/-0.2 degrees, 15.1+/-0.2 degrees, 17.5+/-0.2 degrees and 18.2+/-0.2 degrees in an X-ray powder diffraction pattern. The valnemulin hydrochloride hydrate crystal form has high bulk density, no hygroscopicity and good stability.The invention also provides the preparation method of the valnemulin hydrochloride hydrate crystal form and the pharmaceutical composition containing the crystal form. The composition can be used forpreparing various preparations, such as dosage forms of soluble powder, oral liquids, sustained-release particles, injections and the like, and has wide clinical application prospect.

The invention discloses soluble powder of crystalline valnemulin hydrochloride and application thereof. The soluble powder consists of valnemulin hydrochloride hydrate crystal, a flavoring agent and auxiliary materials. The soluble powder made of the crystalline valnemulin hydrochloride does not induce dampness, has good thermal stability and low production cost, has no pungent smell, does not need to be coated, has better water solubility, and is beneficial to take by drinking water for livestock and poultry groups. Meanwhile, the soluble powder medicine has good palatability, improves the compliance of livestock and poultry medicines, increases the water drinking amount and the feed intake of animals, ensures the medicine dosage of livestock and poultry, and further improves the curativeeffect of valnemulin hydrochloride in prevention and treatment of mycoplasma infection and sensitive bacterial infection diseases of livestock and poultry.

The invention discloses a valnemulin hydrochloride solution. The valnemulin hydrochloride solution consists of the following raw materials in percentage by weight: 5% of valnemulin hydrochloride and 95% of polyglycol. The invention also discloses a preparation method of the valnemulin hydrochloride solution. In the invention, an organic solvent is adopted to dissolve the valnemulin hydrochloride, so that the valnemulin hydrochloride exists in a manner of solution, and is administered in the form of oral liquid. The valnemulin hydrochloride has the characteristics of high liposolubility, difficulty in dissolving in water and general organic solvents, low premix dissolution rate and low bioavailability, but solvent of the valnemulin hydrochloride developed by a pharmaceutical method is convenient to administer, and has high bioavailability.