64 results about "Tiamulin" patented technology

The invention relates to a preparation method of tiamulin base. The preparation method includes: filtering pleuromulin fermentation broth, drying mycelium, performing leaching by using methanol as solvent, using acetone to extract leach liquor after vacuum concentration, concentrating extract, transferring concentrate into a synthetic reactor, adding paratoluensulfonyl chloride, allowing for synthetic reaction at pH of 11-12 and reaction temperature of 20-30 DEG C, allowing for standing and layering after complete reaction, adding tetrabutylammonium bromide and diethylaminoethyl mercaptide into ketone phase respectively , allowing for full reaction at pH of 9-10 and the reaction temperature of 50-60 DEG C, adding water for extraction, discarding aqueous phase, filtering the ketone phase, and reducing the original volume to 60-70% by vacuum concentration to obtain tiamulin base. The original process is improved, the salifying and crystallization process is omitted, the tiamulin base is used to produce preparations directly, and accordingly equipment investment cost and production cost are lowered, product quality is improved, and the content of tiamulin base reaches 80-90%. Organic solvents used in the preparation method are recyclable, environmental pollution is reduced, and the preparation method has promising development prospect.

The invention relates to Mulin acetate containing substituted squaric acid and an application thereof which belong to the technical field of medicines, specifically to substituted squaric acid containing Mulin acetate as shown in a general formula (I), pharmaceutically acceptable salt, a hydrate and an isomer thereof, wherein R1, R2, R3, R4, R5 and B are defined in the specification. The invention also relates to a preparation method of these compounds, a pharmaceutical composition containing these compounds and an application of these compounds in the preparation of drugs for treating or preventing bacteria and virus. As for staphylococcus aureus and Streptococcus equin MIC value, the compounds have an antibacterial effect 15-20 times higher than a control commercially-available antibiotic tiamulin in the test. And the compounds provided by the invention are effective antimicrobial agents. And the compounds provided by the invention are effective antimicrobial agents.

The invention discloses a pleuromutilin derivative with a pyrimidine side chain. The structural formula of the derivative is shown in the specification, wherein R1 is C1-C4 alkoxy groups or hydroxyl groups; R2 is an amino group or an amide group; R3 is hydrogen or C1-C4 alkyl groups. The compound can be applied to preparation of antibacterial drugs, particularly to preparation of MRSA (methicillin-resistant staphylococcus aureus), MRSE (methicillin-resistant staphycoccus epidermidis) and / or antagonistic bacillus subtilis drugs, and the antibacterial effect is superior to that of tiamulin.

The invention discloses a method for recovering 4-methyl-2-pentanone from tiamulin wastewater by acidification. The method comprises the following steps: inorganic salt is added to the tiamulin wastewater for carrying out salting out, part of organic substance sediment is dissolved out, the sediment is removed by filtering, and then inorganic strong acid is added to the wastewater for adjusting the pH value of the wastewater, the wastewater is enabled to be layered, and the separated organic phase is 4-methyl-2-pentanone. The invention also provides the treatment method for the tiamulin wastewater. According to the method, 4-methyl-2-pentanone is recovered from the tiamulin wastewater through salting-out and acidification, the recycle of waste is realized, the COD (Chemical Oxygen Demand)of the wastewater in which the 4-methyl-2-pentanone is recovered is greatly lowered, and the emission requirements can be achieved through common wastewater treatment procedures. Compared with the current treatment of tiamulin wastewater, the difficulty of the wastewater treatment method is low, the cost is low, the cyclic utilization of raw materials is realized, and the requirements on circulareconomy and clean production are met.

The invention relates to a method for extracting sodium p-toluenesulfonate from tiamulin synthesis wastewater, which comprises the following steps: regulating the pH value of tiamulin ammonification production wastewater to 7-8, and concentrating to 75-80% of the original volume under reduced pressure; cooling to 0-4 DEG C, stirring for 1-2 hours while keeping the temperature, and filtering; mixing the filter cake with purified water, adding activated carbon, heating to 80 DEG C, stirring for 30-60 minutes while keeping the temperature, and carrying out hot filtration; and cooling the mother solution to 2-4 DEG C to recrystallize, and filtering to obtain the sodium p-toluenesulfonate. A simple method is utilized to extract and recover the sodium p-toluenesulfonate, thereby changing wastes into valuable substances, increasing the available resources, lowering the wastewater COD (chemical oxygen demand), reducing the wastewater treatment pressure and lowering the wastewater treatment cost; and the method is green and environment-friendly, and has sustainable development meanings for production. The COD of the ammonification wastewater treated by the method is lowered by 50-60%, and the concentration of the sodium p-toluenesulfonate is 310 kg / m<3>.

The invention discloses a method for reclaiming diethylaminoethanethiol from tiamulin production wastewater, which belongs to the technical field of medical and chemical industries. The method comprises the following steps: the tiamulin production wastewater is subjected to pressure reduction concentration and the pH value of the wastewater is adjusted; then the extraction is performed; then the heating concentration is performed; and finally the rectification is performed, and fractions obtained at a temperature of between 70 and 100 DEG C are taken. The method ensures that the diethylaminoethanethiol in wastewater is dissociated out from the wastewater by adjusting the pH value, then uses an organic solvent with good intermiscibility for extraction and layering, and then performs heating concentration and rectification to obtain the diethylaminoethanethiol with higher purity. The reclaiming method has reasonable design and simple operation; and the obtained product has higher purity and good reclaiming effect.

The invention discloses a synthesis method of tiamulin. According to the method, firstly, p-toluene sulfonic acid pleuromutilin ester prepared by pleuromutilin is converted into sulpho-pleuromutilin. After that, sulpho-pleuromutilin reacts with the salt of an ethyl amino ethane derivative to generate tiamulin. The method is simple to operate, low in cost, and environment-friendly. The total recovery of tiamulin is over 80%. Therefore, the method is applied to the industrial production of tiamulin.

The invention discloses a method for preparing Pleuromutilin raw material used in the course of synthesizing Thiamutin, comprising the steps: drying the wet thalli containing the Pleuromutilin to obtain dry thalli, then making extraction at normal temperature by using methyl ethyl butyl ketone as menstruum, filtering the extracted liquid, discarding filter residues, concentrating the filtrate and obtaining Pleuromutilin concentrate. The invention has high Thiamutin yield, is easy to operate and only uses a kind of menstruum.

The invention belongs to the technical field of industrial sewage treatment, in particular to a method for recovering fumaric acid from liquid wastes containing the fumaric acid or fumarates, which are generated in tiamulin production mother solution. The method comprises the following steps: (1) carrying out decompression desolvation on the mother solution to remove an organic solvent to obtain a desolvation solution; (2) adding water the volume of which is 0.5-2.0 times of the desolvation solution and an organic extracting agent the volume of which is 0.3-1.0 time of the desolvation solution to the desolvation solution, and sufficiently stirring; (3) regulating the pH value of the mixed solution obtained in the step 2 to be greater than 10, evenly stirring and then standing for layering, removing an oil layer and preserving a water layer; and (4) adding acid to the water layer so as to regulate the pH value of the water layer to be 1-2 to separate out the fumaric acid and filtering to obtain the fumaric acid. The fumaric acid has high yield and low cost.

The invention discloses a method for preparing tiamulin. The method comprises the following synthesis routes: by taking a compound of formula 1, namely pleuromutilin, as a raw material, performing p-tosylation; synthesizing an intermittent, namely tosylate; performing a direct nucleophilic substitution reaction with beta-mercaptoethanol without separation so as to obtain an intermittent of formula2, namely 14-O-[(1-hydroxyl propane-2-yl) sulfur acetyl] tiamulin; activating the intermittent of the formula 2 by using a halogenation reagent or a sulfonylation reagent so as to form an intermittent of formula 3; enabling the intermittent to react with diethylamine directly without separation, thereby synthesizing a compound of formula 4, namely tiamulin. By adopting the method, 2-lignocaine ethanethiol which is supervised is not used, current main adverse factors which restrict the yield of tiamulin are solved, and tiamulin is prepared through synthesis routes which are low in cost, gentlein condition, environmental-friendly and applicable to industrial production.

The invention discloses a Tiamulin monoclonal antibody hybridoma cell line and application thereof, belonging to the field of food security immunity detection. The complete antigen of Tiamulin and equivalent Freund's adjuvant are mixed and emulsified completely, and then are injected into a BALB / c mice through back subcutaneous tissues so as to immunize the BALB / c mice; the first time of immunizing (100 mug / one mice) uses the complete Freund's adjuvant, immunity enhancement (50 mug / one mice) for multiple times uses the incomplete Freund's adjuvant, and finally, the complete antigen of the Tiamulin (20 mug / one mice, not containing adjuvant) is used for impacting immunity. Efficient but low-cost spleen cells of IC50 mice are fused with mice myeloma cells through a PEG method, and the hybridoma cell line is obtained through screening through an indirect cELISA and three times of subcloning. The monoclonal antibody secreted by the cell line has high specificity and detection flexibility (the value for IC50 is 0.73ng / mL) for the Tiamulin, and provides a raw material for immunity detection of residual Tiamulin in food, thereby having practical application value.

The invention relates to mulin acetate comprising substituted squaric acid, and an application thereof. The invention belongs to the field of chemical medicine. A mulin acetate compound comprising substituted squaric acid, a pharmaceutically acceptable salt thereof, a solvate thereof, an isomer thereof, a prodrug thereof, or a prodrug of salt thereof have a structural general formula represented by the formula (I). The MIC values of the compound against staphylococcus aureus and strepococcus equi are higher by 20-30 times than the antibacterial effect of a reference product of tiamulin in market. The mulin acetate comprising substituted squaric acid is a high-efficiency antibacterial medicine.

The invention provides antibacterial medical hemostasis absorbent cotton gauze, which consists of medicine dressing and a tissue material carrying the medicine dressing, wherein the medicine dressingis prepared from traditional Chinese medicine and western medicine; the tissue material carrying the medicine dressing is blended by scleroprotein fiber and cotton fiber. The hemostasis and the antibacterial effects are integrated; the obvious effects are achieved on abnormal bleeding in operations of lung, liver, pancreas, adrenal gland and the like, the bleeding except for obstetrics departmentand postpartum hemorrhage, urinary tract bleeding and the like; in addition, the antibacterial medical hemostasis absorbent cotton gauze can be used under the conditions of great and deep wound and great bleeding quantity; the hemostasis is fast; the wound surface wound recovery is facilitated; meanwhile, the antibacterial spectrum is wide; the sterilization power is strong; the action is fast; the effectiveness can also be achieved on pseudomonas aeruginosa, klebsiella, escherichia coli, enterobacter, staphylococcus, mycoplasma and chlamydia; in addition, good effects are achieved on trimethoprim drug resistant bacteria, penicillin drug resistant staphylococcus aureus andtylosin or tiamulin drug resistant mycoplasma.

The invention discloses tiamulin famarate soluble powder which is prepared by the following raw materials in parts by weight: 50-60 parts of tiamulin famarate, 20-30 parts of a pullulan polysaccharide-polyglutamic acid cross-linked polymer, 10-15 parts of garlic polysaccharide solid dispersion, 5-9 parts of soluble starch, 4-6 parts of sodium alginate, 2-3 parts of sodium tripolyphosphate, 1-1.6 parts of disodium ethylenediaminetetraacetate and 0.3-0.5 part of citric acid. The tiamulin famarate soluble powder disclosed by the invention is uniform in particle size distribution, stronger in high temperature and high humidity resistance and good in stability. The tiamulin famarate soluble powder is simple and efficient in preparation process, recyclable in used ethanol solvent, mature in recycling process, energy-saving, environment-friendly, suitable for industrial production and wide in application prospect.

A method for extracting pleuromutilin from tiamulin fermentation liquor is characterized by including: firstly, filtering the tiamulin fermentation liquor, leading obtained wet fungus dregs to undergo flash vaporization, then extracting by utilizing methyl alcohol as solvent, and concentrating extraction liquid to obtain pleuromutilin concentrated liquor. The pleuromutilin is extracted from the tiamulin fermentation liquor by utilizing the methyl alcohol as the solvent, and the method has the advantages of small use amount of organic solvent, high extraction yield, low production cost and the like.

The invention provides an electrochemical immunosensor for detecting tiamulin antigen and a preparation method thereof. According to the invention, AgNPs is reduced to GO in situ to obtain the Ag-GO nano composite material, and the Ag-GO nano composite material shows good conductivity and oxidation-reduction activity. Perfluorosulfonic acid has excellent film-forming ability and high chemical stability and is used as a dispersing agent to obtain an Ag-GO-Nf composite solution, and the composite solution is used for modifying the surface of a basic electrode. Then, gold nanoparticles are electrodeposited on the surface of Ag-GO-Nf, and the effects of fixing an antibody and amplifying an electrochemical signal are achieved. The electrochemical immunosensor constructed by applying the method is simple, convenient, efficient and sensitive, has a wide detection range and a low detection limit when being used for detecting tiamulin antigens, and has good accuracy when being applied to detection of tiamulin residues in samples of animal-derived foods such as eggs, pork and pork livers.

The invention relates to a refining method of tiamulin hydrogen fumarate. The method is characterized by comprising the following steps: taking crude tiamulin hydrogen fumarate, adding crude tiamulin hydrogen fumarate in acetone in a weight ratio of 1:3-4; stirring at 35-45rpm while heating to 55-57 DEG C, refluxing for 3-5h while keeping the temperature; reducing the temperature at 8-10 DEG C / h, reducing the stirring speed to 18-22rpm, refluxing for crystallization; adding a defined amount of tiamulin hydrogen fumarate seed crystals when the temperature is reduced to 48 DEG C, keeping the temperature for 2-3h when the temperature is reduced to 1 DEG C to perform complete crystallization; performing suction filtering with a suction filtering machine to ensure that no filtrate drops, adding a defined amount of cold acetone to wash twice, removing impurities to draw off water and generate the refined tiamulin hydrogen fumarate powder; and placing the refined powder in a vacuum drying oven, heating at 6 DEG C / h to 55-65 DEG C, and drying for 2-4h under the vacuum degree of -(0.07-0.09)MPa to obtain the refined tiamulin hydrogen fumarate raw powder. The invention utilizes the property of tiamulin hydrogen fumarate that tiamulin hydrogen fumarate is slightly soluble in acetone, thus the dosage of the refined solvent can be reduced, the consumption of solvent can be lowered, the production cost can be reduced, the impurities of the product can be reduced and the product quality can be greatly increased.

The invention provides a pharmaceutical composition for treating livestock respiratory diseases and a method for preparing the pharmaceutical composition for treating livestock respiratory diseases. The pharmaceutical composition consists of exocarpium citri grandis extract, poria extract, radix glycyrrhizae extract and fumaric acid tiamulin, wherein the exocarpium citri grandis extract accounts for 8-15 parts by weight, the poria extract accounts for 2-10 parts by weight, the radix glycyrrhizae extract accounts for 1-5 parts by weight, the fumaric acid tiamulin accounts for 5-20 parts by weight, and the pharmaceutical composition is prepared through a mixing mode. According to the pharmaceutical composition for treating livestock respiratory diseases, traditional Chinese medicine and western medicine are reasonably compounded, so that the effective treatment drug for preventing livestock respiratory diseases is provided for the breeding industry; the pharmaceutical composition has the functions of relieving coughs and asthma, resisting bacteria and virus, improving the immunity of the organism and the like and treats both the manifestation and root causes, the curative process is shortened, and the occurrence probability of drug resistance is greatly reduced; and the method for preparing the pharmaceutical composition is simple, is convenient to use and meets the requirements of mass industrial production.

The invention relates to an extraction method of methyl isobutyl ketone and sodium p-toluenesulfonate. The extraction method comprises the following steps: carrying out atmospheric distillation on high-concentration tiamulin wastewater to distill out a mixed solution of an organic phase and water; cooling, carrying out liquid separation on the mixed solution, removing the water layer to obtain anorganic phase, adding calcium oxide into the organic phase, removing water and carrying out reduced pressure distillation to obtain high-purity methyl isobutyl ketone; carrying out vacuum concentration, cooling, separating out crystals and filtering on the residual wastewater mother liquor after distilling and separating out the organic phase and water mixed liquor; adding a solvent into the filter cake, heating and carrying out reflux water diversion; and after water separation, cooling, filtering and drying the filter cake to obtain high-purity sodium p-toluenesulfonate. The extraction method is simple, the extracted methyl isobutyl ketone and sodium p-toluenesulfonate are high in purity and the COD value of wastewater is greatly reduced.

The present invention discloses a reagent, a kit and a treatment method for treating mycoplasma contamination. The reagent is a solution containing antibiotic tiamulin, minocycline and antibiotic ciprofloxacin, wherein a concentration ratio of the antibiotic tiamulin to the minocycline to the antibiotic ciprofloxacin is 4:1:3. According to the present invention, with the reagent, the kit and the treatment method, the combination comprising the antibiotic tiamulin, the minocycline and the antibiotic ciprofloxacin according to the specific ratio is used, such that the mycoplasma contamination treatment effect can be significantly increased; and the mycoplasma contamination problem can be simply, safely, rapidly and effectively treated.

The invention provides a preparation method of a tiamulin / tiamulin salt micro-capsule. The preparation method is characterized by comprising the following steps: adding corn protein aqueous solution or glutin aqueous solution in tiamulin / tiamulin salt, completely stirring to obtain uniform mixed solution; slowly heating to 50-60 DEG C, preserving the heat for 0.5-1h, and then crosslinking and curing with formaldehyde serving as a crosslinking agent; washing with isopropanol, carrying out suction filtering, washing a filter cake with isopropanol-petroleum ether till formaldehyde is completely washed away; drying till the drying loss is less than 1%, thus obtaining the tiamulin / tiamulin salt micro-capsule. The preparation method can be used for preparing the tiamulin / tiamulin salt micro-capsule which can be directly applied to animal feed; and the prepared tiamulin / tiamulin salt micro-capsule has the advantages that irritation to respiratory tracts of people and animals can be reduced and the stability and the medicinal bioavailability of medicinal preparations can be improved. The preparation method is simple.

The invention discloses a poultry and waterfowl one-day-age hatching device purifying spray. The poultry and waterfowl one-day-age hatching device purifying spray is composed of tiamulin, neomycin sulfate, nuramyl dipeptide and taurine. The poultry and waterfowl one-day-age hatching device purifying spray has the advantage that the poultry and waterfowl one-day-age hatching device purifying sprayis applied in a sprayed mode inside a hatching device, and after being fully atomized, achieves drug delivery via lung absorption to purify one day old baby chicks or ducklings, thereby combining breeding environment, chicken purifying situation and the like in China, taking into full consideration of pharmacokinetic factors of drugs as well as nutrition demands of the baby chicks, achieving comprehensive purifying effects on both bacteria prone to vertical propagation among chicks such as mycoplasmas and salmonellas, and bacteria prone to infection during hatching such as staphylococcus aureus, pseudomonas aeruginosa and Escherichia coli, taking into account lack of energy of chicks during transportation as well as injuries of respiratory tract villi and the like caused by stress of transportation, comprehensively improving the health of chicks, reducing incidence of diseases and enhancing food safety.

The invention provides application of pithecellobium cypearia or extract to preparation of a medicine for treating and / or adjunctively treating bronchopneumonia of livestock and poultry. The inventionalso provides a medicinal composition for treating bronchopneumonia of livestock and poultry. The invention also provides a preparation method and application of the medicinal composition. The pithecellobium cypearia can be used for treating and / or adjunctively treating bronchopneumonia of livestock and poultry, has a clear medicinal effect, has a more excellent treatment effect on bronchopneumonia when being used together with tiamulin, and has a good clinical application prospect.

The invention discloses a one-pot method for synthesizing tiamulin. According to the method, methylbenzenesulfonate pleuromutilin, diethylamine and ethylene sulfide is subject to an one-pot reaction in a ratio of 1: (1.0 to 1.5) :( 1.0 to 2.0) at room temperature of 50 DEG C to obtain the tiamulin. The method is convenient to operate, low in cost and environment-friendly, and is suitable for industrial production of the tiamulin.

The invention relates to a chemical synthesis method of a veterinary bulk drug tiamulin, in particular to a method for preparing tiamulin from isothiourea salt and p-toluenesulfonic acid pleuromutilinester. The method comprises the following steps: reacting aminochloroethane prepared from bromochloroethane and diethylamine with thiourea to prepare isothiourea salt; reacting pleuromutilin with p-toluenesulfonyl chloride to prepare p-toluenesulfonic acid pleuromutilin ester, adding isothiourea salt into the p-toluenesulfonic acid pleuromutilin ester, and carrying out alkaline washing, neutral washing, phase inversion and other extraction steps on the reaction solution to obtain the high-purity tiamulin. According to the invention, the supervised dangerous intermediate diethylaminoethanethiol is completely avoided, the tiamulin is prepared by adopting a mild route, the product management and control cost is greatly reduced, and the raw materials are easy to obtain, so that the method isvery suitable for industrial large-scale production.

The invention discloses a preparation method for a tiamulin micro-capsule preparation, which belongs to the field of veterinary medicine preparations. The tiamulin micro-capsule preparation is obtained by adding tiamulin raw powder medicine in hydrogenated vegetable oil containing magnesium stearate and tripolyglycerol monostearate, and adequately and uniformly stirring, then adding the materials above in an aqueous solution containing chitosan, pectin and tween-80, and carrying out cooling treatment. The preparation method is scientific, simple and practicable, high in medicine encapsulation rate and recovery rate, adjustable in particle size according to the particle size of the raw material medicine and the dosage of a coating wall material. Clinical tests prove that the preparation method disclosed by the invention is capable of improving palatability and good in slow-release action, and provides an efficient tiamulin micro-capsule preparation for veterinary clinically.

The invention provides a tiamulin hydrogen famarate premixing agent. The tiamulin hydrogen famarate premixing agent is prepared from, by mass, 75-85% of tiamulin hydrogen famarate and 15-25% of lacticacid. The invention further provides a preparing method of the tiamulin hydrogen famarate premixing agent. The tiamulin hydrogen famarate premixing agent can treat pig bacillary enteritis, bacterialpneumonia and treponema swine dysentery and has obvious therapy effects on mycoplasmal pneumonia and pneumonia which is caused by mixed infection of bordetella bronchiseptica and pasteurella multocida, during preparation, conventional equipment is adopted, the preparing method is simple, the substance cost is low, and the preparing method is suitable for industrial large-batch production of the livestock antibiotic premixing agent.

The invention relates to a purification method for a tiamulin reaction solution in industrial production. Specifically, the method includes: in a purification process of a tiamulin reaction solution, firstly using water to wash off water soluble impurities, i.e. p-toluene sulfonic acid and an alkaline catalyst from the tiamulin reaction solution, then adjusting the pH value of the tiamulin reaction solution to 6.7-7.0 with phosphoric acid, selectively making the organic impurity 2-diethylaminoethanethiol therein acidified into a salt, then using water to wash 2-diethylaminoethanethiol phosphate away from the tiamulin reaction solution, thus obtaining a tiamulin-ethyl acetate solution with chromatographic purity of 98-98.5% of. The method has the advantages of simple purification process and low cost.