40 results about "Terbutaline Sulfate" patented technology

The invention provides a synthetic method for terbutaline sulfate. The method comprises the following specific synthetic route: using 3,5-dihydroxyacetophenone as a raw material, performing benzyl protection, performing oxidization, performing esterification, performing reductive amination, performing debenzylation, and finally performing salt formation with sulfuric acid to obtain the terbutalinesulfate. The preparation method for the terbutaline sulfate provided by the invention has the following beneficial effects: 1, dimethyl sulfoxide (DMSO) is adopted to replace highly-toxic product selenium dioxide, a highly-dangerous reagent is avoided from being used, and the method is safe and high-efficiency; 2, the method does not have a bromination process, and has less pollution to the environment; and 3, the method is easy to operate, has mild reaction conditions, short steps and low costs, and is more suitable for industrialized production.

The invention discloses a preparation method of terbutaline sulfate. The method comprises the steps: taking 3,5-dihydroxyacetophenone as an initial raw material, firstly, carrying out benzyl protection to obtain 3,4-dibenzyloxyacetophenone, carrying out copper bromide bromination and DMSO oxidation on 3,5-dibenzyloxyacetophenone to obtain 3,5-dibenzyloxyacetophenone aldehyde, carrying out reductive amination on 3,5-dibenzyloxyacetophenone aldehyde and tert-butylamine to generate 1-[3,5-di(benzyloxy)phenyl]-2-(tert-butylamino)ethanol, and finally carrying out hydrogenation debenzylation and sulfuric acid salification, to obtain terbutaline sulfate. Compared with the prior art, the method has the advantages that the used raw materials and auxiliary materials are cheap and easily available, the use of high-risk and highly-toxic reagents is avoided, high-temperature and high-pressure reaction is avoided, the operation is simple and convenient, the reaction conditions are mild, and the defects of long steps, low yield, potential safety hazards and the like in the prior art are overcome.

The invention relates to the technical field of pharmaceutical preparations, and particularly discloses a terbutaline sulfate injection and a preparation method thereof. The preparation tank is subjected to complexing treatment by using a sodium ethylene diamine tetracetate solution, and after complexing is completed, the preparation tank is flushed by using water for injection until the pH value is 5.0-7.0 and the electrical resistivity is less than 0.5, so that the preparation tank can be used for preparing the injection; and in the preparation process, the water for injection is filled with nitrogen, the terbutaline sulfate is added after dissolved oxygen in the water is controlled to be lower than 100 ppb, and the headspace residual oxygen content in an ampoule bottle is controlled to be smaller than 2% in cooperation with nitrogen introduction in the filling process, so that the influence of oxygen and metal ions on the terbutaline sulfate is effectively avoided. The terbutaline sulfate injection provided by the invention is simple in prescription, and the stability of terbutaline sulfate is remarkably improved on the premise of not introducing other auxiliary materials such as an antioxidant or a complexing agent, a stabilizer and the like, so that the clinical application safety is improved.

The invention discloses a stable terbutaline sulfate injection, wherein 1 ml of the stable terbutaline sulfate injection comprises 0.1-0.4mg of terbutaline sulfate, 8.0-10mg of sodium chloride and the balance of water for injection. In the preparation process of the stable terbutaline sulfate injection, nitrogen is used for protection so that the using of antioxidant can be decreased; low-temperature preparation is adopted to control the stability of the product so that the impurity stability after steam sterilization is ensured and the metal ion complexing agent can be decreased. According to the stable terbutaline sulfate injection and the preparation process thereof, the problem of adding other auxiliary materials to maintain the stability of the preparation in a clinic intravenous fluid is solved and the clinic safe medication is ensured.

The invention provides a method for analyzing related substances of terbutaline sulfate via high performance liquid chromatography. A C18 reversed chromatographic column is used, a mobile phase is a mixture of a 0.05 M ammonium acetate buffer solution with pH 4.0 and methanol, gradient elution is carried out, and qualitative and quantitative detection of terbutaline and 9 impurities is achieved byonce sample injection. Compared with the prior art, the method provided by the invention has the advantages of being able to not only detect more impurities, but also having good sensitivity to various impurities. In the specific application, according to the detection result of each batch of samples, the limit of the key impurity formulated, and the economic applicability in the actual production process is greatly improved.

The method of a high-precision method for EDTA-2Na content in an terbutaline sulfate atomized solution. The method comprises: (1) using sample reference; (2) using sample performance; (3) using high performance liquid chromatography to determine the Different Concentration of the standard reference solutions and the sample solutions, to be more specific, a mobile phase comprises acetonitrile and a0.006 M tetrabutyl ammonium hydroxide aqueous solution in the ratio of 1:4, then isocratic elution is carried out, a column temperature is 30 Degree Celsius, a flow rate is 1.0 mL / min, a detectionwavelength is 254 nm, injection amount is 25 MuL, and a chromatographic column is a C18 column with the inner diameter of 4.6 mm, column height of 150 mm and packing pore diameter of And um recordingthe concentrations and corresponding peak areas of the standard reference o Lutions and peak area of the sample solutions; (4) using the external standard method to determine The corresponding EDTA-2Na content according to the peak area of the sample solutions.

The invention relates to a preparation method of terbutaline sulfate, which comprises the following steps: dissolving a compound of formula I or formula II into a solvent A, adding a metal catalyst for catalytic hydrogenation, so as to obtain 5-[2-[(1,1-dimethylethyl)amido]-1-ethoxyl]-1,3-resorcinol; after the reaction is finished, filtering, collecting filter liquor, adding a certain amount of concentrated sulfuric acid in the filter liquor, after stirring is stopped, recycling the solvent A, adding a solvent B into a residue, stirring to separate out a white crystal substance, performing suction filtration, thus obtaining the terbutaline sulfate. According to the method provided by the invention, the treating difficulty after the reaction is greatly reduced, the introduction of water and inorganic salt is avoided, and the product content is high; furthermore, the stability of the terbutaline sulfate is obviously improved by distilling the product under acidic conditions, the catalyst and the reaction solvents are recyclable, so that the environmental protection pressure is greatly reduced.

The invention relates to a preparation method of a terbutaline sulfate solution for inhalation. The terbutaline sulfate solution contains a main ingredient, a stabilizer, an iso-osmolar agent, a pH regulator and injection water, and pH value of the terbutaline sulfate solution is 3.0-5.0. The terbutaline sulfate solution has good effect on improving lung functions.

The invention provides a solution preparation for terbutaline sulphate aerosol inhalation and a preparation method of the solution preparation. The solution preparation for terbutaline sulphate aerosol inhalation comprises terbutaline sulphate and/or a hydrate thereof, an osmotic pressure regulator, a pH regulator and a solvent. The solution preparation for terbutaline sulphate aerosol inhalationdisclosed by the invention has the characteristics of being efficient, low in toxicity, good in stability and high in safety degree.

The invention provides a method for preparing terbutaline sulfate crystal form B, which comprises the steps: a solvent is selected and 1-(3, 5 dibenzyloxyphenyl)-2-t-butylamido ethanol is dissolved in the solvent, the phenmethyl is removed by hydrogenolysis of a universal method to obtain terbutaline free alkali, and then sulphuric acid is added to form the terbutaline sulfate of crystal form B; or the terbutaline sulfate of non-crystal form B is dissolved in the solvent and stirred at certain temperature until the terbutaline sulfate of the non-crystal form B is converted to form the terbutaline sulfate crystal form B by the dissolution and precipitation process, then the precipitated terbutaline sulfate crystal form B is recycled. The invention has the advantages that the terbutaline sulfate crystal form B which has stable chemical and physical appearances and meets the requirements of pharmaceutical preparations is obtained by the simple method.

The present invention discloses a medicine terbutaline sulfate dripping pills preparation with the action of relieving asthma and its preparation process. It is made up by using terbutaline sulfate and matrix for making dripping pills.

The invention discloses a terbutaline sulfate intermediate, a preparation method thereof, and a method for preparing terbutaline sulfate from the terbutaline sulfate intermediate, and belongs to the technical field of medical chemistry. The novel method for preparing terbutaline sulfate is mild in reaction condition, high in yield and environment-friendly, and comprises the following steps: firstly, providing the terbutaline sulfate intermediate represented by formula I; and then carrying out hydrogenation reduction by taking 10% Pd/C as a catalyst and an alcohol-water solution as a solvent toobtain the terbutaline sulfate represented by formula II. The free alkali hydrochloride or hydrobromide in a formula I is converted into the compound of the formula I before hydrogenation reduction,and the terbutaline sulfate is directly obtained after hydrogenation reduction, so extremely unstable terbutaline free alkali is prevented from appearing independently, and the method has the advantages of mild reaction conditions, high product yield, high purity, low production cost and the like, and is beneficial to industrial production of the terbutaline sulfate.

The invention discloses a preparation method of a pharmaceutical terbutaline sulfate crystal form B. The preparation method comprises the following steps: S1, dissolving terbutaline sulfate of an amorphous form B in pure water, and conducting stirring and dissolving to obtain a terbutaline sulfate aqueous solution; S2, dropwise adding the amorphous form B terbutaline sulfate aqueous solution obtained in the step S1 into an alcohol or ketone solvent, conducting stirring for dissolving, adding a crystal seed of the terbutaline sulfate crystal form B, and conducting stirring for crystallizing toobtain a terbutaline sulfate crystal solution of the crystal form B; and S3, filtering the terbutaline sulfate crystal liquid with the crystal form B obtained in the step S2 and conducting drying to obtain a terbutaline sulfate crystal form B, wherein the ratio of the mass (unit: g) of the amorphous form B terbutaline sulfate to the mass (unit: g) of pure water to the mass (unit: g) of the crystalseed of the terbutaline crystal form B to the volume (unit: mL) of the alcohol or ketone solvent is 1:(4-5):(0.01-0.1):(50-60). The method has the advantages of simple operation, high repeatability,environment-friendly raw materials, and easy realization of industrial production application.

The invention belongs to the technical field of medicine, and provides an aerosol inhalation medicine composition for treating cough and asthma. The aerosol inhalation medicine composition for treating cough and asthma is prepared from 300 to 600ug of budesonide, 600 to 1200ug of terbutaline sulfate, 10 to 15mg of ambroxol hydrochloride, 0.5 to 1mL of radix astragali extracts, 0.5ml of propanedioland 10ml of normal saline. The invention also provides a preparation method of the aerosol inhalation medicine composition.

The invention relates to a preparation method of terbutaline sulfate and a B crystal form thereof, which comprises the following steps: sequentially carrying out bromination, reduction reaction and substitution reaction to obtain 1-[3, 5-bis (benzyloxy) phenyl]-2-(tert-butylamino) ethanol; reacting 1-[3, 5-di (benzyloxy) phenyl]-2-(tert-butylamino) ethanol with a reducing agent and a catalyst, performing salifying with sulfuric acid to obtain a terbutaline sulfate crude product, and crystallizing the terbutaline sulfate crude product under a heating reflux condition to obtain the terbutaline sulfate medicinal B crystal form. Raw materials and auxiliary materials used in the method are cheap and easy to obtain, highly toxic and explosive reagents are avoided in the reaction process, the whole reaction route is short, operation is easy and convenient, reaction conditions are mild and safe, the yield of the obtained finished product terbutaline sulfate and the medicinal B crystal form thereof is high, the yield of terbutaline sulfate is 83% or above, and the yield of the medicinal B crystal form is 70% or above, and industrialized production can be achieved easily.

The invention relates to the technical field of drug detection methods, in particular to a detection method for determining terbutaline sulfate injection and related substances, the detection method adopts high performance liquid chromatography for detection, and the detection conditions are as follows: a mobile phase is composed of a mobile phase A and a mobile phase B, wherein the mobile phase A is an ammonium formate-formic acid buffer solution containing 3.75-4.31 g/L of sodium hexanesulfonate and 1.25-1.57 g/L of sodium sulfate, and the pH value is 3.0 +/-0.1; the mobile phase B is methanol; the mixing volume ratio of the mobile phase A to the mobile phase B is 80: 20; the detection method can realize simultaneous detection of degradation impurities of raw material medicines and preparations, and has the advantages of high separation degree, good durability and the like.

The invention provides a preparation method of terbutaline sulfate. The preparation method comprises the following steps: with 3,5-dihydroxyacetophenone as a raw material, directly carrying out an oxidation reaction on 3,5-dihydroxyacetophenone without protecting a phenolic hydroxyl group so as to obtain aromatic glyoxal, and then carrying out a condensation reaction, a reduction reaction and sulfuric acid salification on the aromatic glyoxal and tert-butylamine to obtain terbutaline sulfate. According to the method, a high-risk operation unit for hydrogenation debenzylation in an existing terbutaline sulfate preparation process is eliminated; and meanwhile, bromination reaction with relatively large pollution to the environment is avoided, and the whole process is more suitable for industrial production.

The invention discloses a synthesis method of terbutaline, which is characterized by comprising the following steps: (1) reacting 3, 5-dimethoxyacetophenone with tetrabutylammonium tribromide to obtain 2-bromo-1-(3, 5-dimethoxyphenyl)ethanone; (2) reacting the 2-bromo-1-(3, 5-dimethoxyphenyl)ethanol with a reducing agent in methanol to obtain 2-bromo-1-(3, 5-dimethoxyphenyl)ethanol; (3) carrying out cyclization reaction on the 2-bromo-1-(3, 5-dimethoxyphenyl)ethanol under an alkaline condition to generate 2-(3, 5-dimethyloxy) ethylene oxide; (4) carrying out a reaction on the 2-(3, 5-dimethyloxy) ethylene oxide and tert-butylamine to generate 1-(3, 5-dimethoxyphenyl)-2-tert-butylamino-ethanol; and (5) hydrolyzing under an acidic condition to obtain a salt of 1-(3, 5-dihydroxyphenyl)-2-tert-butylamino-ethanol, namely terbutaline. The total molar yield is about 60% and is far higher than the yield in the prior art, and the synthesis method of terbutaline and the application of terbutaline in the preparation of terbutaline sulfate are suitable for industrial production.