16 results about "Bromhexine hydrochloride" patented technology

The application discloses a modified bromhexine hydrochloride inhalation solution with enhanced stability and a preparation method thereof, and belongs to the technical field of medical preparations. The inhalation solution is mainly prepared from a targeting impurity control modified bromhexine hydrochloride inclusion compound, a special composite buffer mother liquor for inhibiting impurity B, inhalation grade sodium chloride, pharmaceutical grade sodium hydroxide and water for injection, and the pH value of the finished product is 4.5-5.5. The application constructs a three-stage progressive modification system, covalently grafts a mercapto-activated L-cysteine derivative onto hydroxypropyl-gamma-cyclodextrin to prepare a functional carrier, and realizes molecular-level isolation of bromhexine hydrochloride through host-guest inclusion, thereby blocking the generation of impurity B of bromhexine hydrochloride from the whole path, and solving the core pain points of easy impurity exceeding, short effective period and airway irritation of the existing product. The application can realize long-acting stable storage for 36 months, is suitable for the existing industrial production line, and has high clinical application and industrialization values.

The present invention discloses a method for preparing a stable solution of 2-amino-3,5-dibromobenzylamine derivative for inhalation. The stable solution of 2-amino-3,5-dibromobenzylamine derivative for inhalation has a pH value of 3.0 and its composition is as follows: 2 g of bromhexine hydrochloride, 1 g of DL-tartaric acid, 0.1-0.5 g of L-serine, and the injection water is added to 1000 mL. The method comprises: 1) mixing bromhexine hydrochloride and L-serine and grinding them to obtain a mixture of bromhexine hydrochloride and L-serine; 2) taking 90% of the injection water, adding DL-tartaric acid under stirring, after dissolution, adding the mixture of bromhexine hydrochloride and L-serine and stirring until completely dissolved, adjusting the pH to 3 with sodium hydroxide, and making up the injection water to the full volume; 3) filtering and filling. The present invention does not need to add a large amount of stabilizers. Using a trace amount of L-serine as an auxiliary agent can improve the stability of the bromhexine hydrochloride solution. L-serine is an amino acid beneficial to the human body and will not bring risks, ensuring the safety of drug use.

The invention discloses bromhexine hydrochloride oral liquid and a preparation method thereof.The oral liquid is prepared from, by 5 ml of solution, 8 mg to 12 mg of bromhexine hydrochloride, 45 mg to 55 mg of liquorice root extract, 130 mg to 150 mg of glycerinum, 0.2 mg to 0.5 mg of fruit essence, 0.3 mg to 0.5 mg of sodium chloride, 0.2 mg to 0.4 mg of pH regulator, 0.1 mg to 0.3 mg of disodium hydrogen phosphate and purified water. The relative humidity is 60% + / -10%, and the total impurity amount can still be ignored after the oral liquid is placed for 12 months, which indicates that the bromhexine hydrochloride oral liquid in the scheme has better long-term stability and can be stored for a long time. According to the scheme, the licorice extract is heated to enhance the cough relieving effect, relieve throat discomfort and improve the taste, the glycerol is added, the taste can be improved, the viscosity and lubricity of the liquid medicine can be improved, and meanwhile the fruit essence is added to improve the taste, increase the acceptability and cover the bitter taste of the medicine.

The invention belongs to the technical field of medicine quality detection, and particularly relates to a method for detecting bacterial endotoxin of a raw material medicine in bromhexine hydrochloride injection. According to the method, a mode of heating and dissolving the hydrochloric acid solution with the pH value of 4.0 is adopted, and the 001 * 7 type cation exchange resin microcolumn purification is combined, so that the inhibition effect of cation impurities in the raw material medicine on agglutination reaction of the tachypleus amebocyte lysate can be effectively eliminated, and a stable and uniform test solution is prepared. According to the process, the minimum non-interference dilution multiple is obviously reduced to 160 times, and the operation error and the detection sensitivity loss caused by high-multiple dilution are reduced. As the dilution ratio is greatly reduced, a tachypleus amebocyte lysate with the sensitivity of 0.25 EU.mL <-1 > can be selected in the method. Compared with a high-sensitivity reagent needed in the prior art, the reagent of the specification is easier to purchase and lower in cost, solves the problems that the high-sensitivity reagent is large in daily purchase difficulty and high in price, and is more suitable for conventional application in industrial quality control.

The application discloses a compound enrofloxacin injection, which contains 10-25g of enrofloxacin, 2-10g of sulfadimoxine sodium, 5-12g of florfenicol, 0.5-2.5g of bromhexine hydrochloride, 1-20g of glacial acetic acid, 2-5g of Tween 80, 5-15g of alpha-pyrrolidone and 5-20g of N, N-dimethylformamide per 100ml of the injection, and the rest is water for injection. The compound enrofloxacin injection has advanced and reasonable prescription design, stable and reliable preparation process, good preparation stability and small irritation, and can achieve the effect of treating all samples for respiratory system diseases of livestock and poultry.

The invention relates to a bromhexine hydrochloride oral solution. Specifically, the invention provides the bromhexine hydrochloride oral solution, and the bromhexine hydrochloride oral solution comprises bromhexine hydrochloride, sucralose, glycerol, propylene glycol, polysorbate-80, fructose, sorbitol, citric acid, disodium hydrogen phosphate and water. The bromhexine hydrochloride oral solution disclosed by the invention has excellent illumination and high-temperature stability, the storage and transportation stability of the bromhexine hydrochloride oral solution is improved, the storage and transportation cost is reduced, and the quality safety of the bromhexine hydrochloride oral solution is ensured.

The present invention provides a solid composition that contains: (a) bromhexine or a salt thereof; (b) a nonionic surfactant; and (c) a compound selected from the group consisting of a vitamin-based antioxidant, a phenolic antioxidant, meloxicam and acetaminophen (solid compositions containing ibuprofen, clemastine fumarate, dihydrocodeine phosphate, noscapin, dl-methylephedrine hydrochloride, anhydrous caffeine, bromhexine hydrochloride, tranexamic acid, riboflavin, benfotiamine, ascorbic acid, hesperidin, D-mannitol, low-substituted hydroxypropyl cellulose, crystalline cellulose, hydroxypropyl cellulose, polyoxyethylene hardened castor oil 60, hypromellose, talc, hydroxypropyl cellulose, and light anhydrous silicic acid are excluded).

The application relates to a preparation method of bromhexine hydrochloride, which comprises the following steps: adding 3,5-dibromo-o-amino benzaldehyde, N-methyl cyclohexylamine and a water absorbent into a reaction solvent, stirring under a protective atmosphere, adding a reducing agent in batches at low temperature, continuing to stir under the condition of rising to room temperature, adding a quenching solvent after the reaction is completed, performing suction filtration, rotating and drying the filtrate, adding purified water and an organic solvent, adding concentrated hydrochloric acid under the condition of room temperature to adjust the pH to 0.5-4.0, stirring, performing suction filtration, washing, drying and obtaining bromhexine hydrochloride. The preparation method provided by the application is high in yield and purity, mild in conditions, simple in operation and suitable for industrialized production.

The present invention provides a solid composition comprising the following components: (a) bromhexine or a salt thereof; (b) a nonionic surfactant; and (c) a compound selected from the group consisting of vitamin antioxidants, phenolic antioxidants, meloxicam, and acetaminophen (wherein R1 represents a hydrogen atom or a hydrogen atom). The pharmaceutical composition does not contain ibuprofen, clemastine fumarate, dihydrocodeine phosphate, noscapine, racemic methyephedrine hydrochloride, anhydrous caffeine, bromhexine hydrochloride, tranexamic acid, riboflavin, benfotiamine, ascorbic acid, hesperidin, D-mannitol, low-substitution-degree hydroxy propyl cellulose, crystalline cellulose, hydroxy propyl cellulose and polyoxyethylene hydrogenated castor oil 60, and the pharmaceutical composition can be used for preparing the pharmaceutical composition. The invention relates to a solid composition of hydroxypropyl methylcellulose, talc, hydroxy propyl cellulose and light anhydrous silicic acid.

This invention relates to the field of pharmaceutical analysis technology, and provides a method for detecting N-methylcyclohexylamine hydrochloride in bromhexine hydrochloride. The method involves dissolving N-methylcyclohexylamine in an organic solvent as a reference solution, and dissolving bromhexine hydrochloride in an organic solvent containing an acid-binding agent as the test solvent, followed by headspace gas chromatography for detection. This method is simple, efficient, specific, sensitive, repeatable, and stable, and can be used for the quality control of bromhexine hydrochloride raw material, providing technical support for its production.

This invention discloses a method for synthesizing bromhexine hydrochloride, with the following specific steps: Step (1), using 2-amino-3,5-dibromobenzoic acid as a raw material, reacting it with trimethylacetyl chloride via an anhydride method under the action of an acid-binding agent to obtain compound 2-amino-3,5-dibromobenzoic acid anhydride; Step (2), the 2-amino-3,5-dibromobenzoic acid anhydride obtained in Step 1 undergoes nucleophilic addition with N-methylcyclohexylamine to obtain compound 5, bromhexine hydrochloride intermediate; Step (3), the above compound 5, bromhexine hydrochloride intermediate undergoes amide reduction and salt formation reaction to obtain bromhexine hydrochloride. This process provides a new route for preparing bromhexine hydrochloride, avoiding the heavily regulated chlorination process, reducing the release of toxic gases from strong halogen reagents such as thionyl chloride, significantly reducing safety risks and environmental protection investment, and the reaction itself is safe and fast, which is conducive to industrial production.

The utility model relates to the technical field of bromhexine hydrochloride raw material processing, and discloses a bromhexine hydrochloride raw material stirring device which comprises a tank body, the top of the tank body is fixedly connected with a first servo motor, an output shaft of the first servo motor is fixedly connected with a first rotating shaft, and the bottom end of the first rotating shaft is fixedly connected with a rotating column. The bottom of the rotating column is fixedly connected with a first square frame, the outer surface of the rotating column is fixedly connected with a connecting disc in a sleeving mode, and through starting of a first servo motor and the connecting disc, the two first rotating shafts are used for conducting circumferential rotation, and meanwhile the second square frame is used for ascending and descending; the two rotating columns are driven to move towards each other or away from each other at the bottom of the first square frame, so that a plurality of stirring columns on the two rotating columns can be used for increasing the stirring action through reciprocating horizontal movement under the rotating stirring condition, and the stirring efficiency of a mixture is improved.

The invention provides a method for separating and / or detecting bromhexine hydrochloride and related substances thereof. A chromatographic column stationary phase of the high performance liquid chromatography is octadecylsilane chemically bonded silica, a mobile phase is composed of a phase A and a phase B, the phase A is ammonium acetate, the phase B is methanol-acetonitrile, the mobile phase is gradient elution, and the detection wavelength is 250nm. The related substance is selected from any one or a combination of a related substance 1, a related substance 2, a related substance 3, a related substance 4, a related substance 5, a related substance 6, a related substance 7, a related substance 8 and a related substance 9. According to the method disclosed by the invention, efficient separation and detection of bromhexine hydrochloride and related substances thereof can be realized, and the drug quality of bromhexine hydrochloride can be effectively controlled.

The invention provides a bromhexine hydrochloride composition and a preparation method thereof, and particularly relates to the field of medicines. The bromhexine hydrochloride injection comprises 3-5 mg of bromhexine hydrochloride, 4-6 g of glucose, 0.8-1 g of sodium chloride, a proper amount of a pH regulator and water for injection, the volume is fixed to 100 ml, and the pH is 4-5. Adding 70% of water for injection into the mixing tank, wherein the temperature of the water for injection is less than 40 DEG C; the preparation method comprises the following steps: weighing bromhexine hydrochloride according to a prescription amount, adding the bromhexine hydrochloride into a mixing tank, controlling the temperature at 30-40 DEG C, and mixing and stirring for 20-30 minutes to obtain a mixed solution; weighing the glucose and the sodium chloride according to the prescription amount, sequentially adding the glucose and the sodium chloride into the mixed solution, controlling the temperature to be 30-40 DEG C, and mixing and stirring for 20-30 minutes; adding a pH regulator to regulate the pH value to a target value; fixing the total volume to 100% by using water for injection, and then mixing and stirring for 20-30 minutes; and sterilizing and filtering to obtain a target product. The bromhexine hydrochloride for oral administration or injection is prepared by reducing auxiliary materials, and the composition is good in stability.

The invention relates to the field of pharmaceutical preparations, in particular to a bromhexine hydrochloride oral solution and a preparation method thereof. The chitosan quaternary ammonium salt and the polyoxyethylene 60 hydrogenated castor oil are added into the bromhexine hydrochloride oral solution, the chitosan quaternary ammonium salt and the polyoxyethylene 60 hydrogenated castor oil are matched to obtain the oral solution with excellent stability, and the oral solution shows better product stability in an acceleration test and a long-term test; the method for preparing the bromhexine hydrochloride oral solution is simple and easy to implement, low in cost and more suitable for industrial production.

The invention discloses bromhexine hydrochloride sustained-release micro-tablets and a preparation process thereof. The bromhexine hydrochloride sustained-release micro-tablets are prepared from the following raw materials through direct powder compression: 5-20 parts of bromhexine hydrochloride, 15-35 parts of hydroxypropyl methylcellulose, 5-15 parts of carbomer, 5-15 parts of ethyl cellulose, 10-40 parts of microcrystalline cellulose, 2-8 parts of povidone and 0.5-5 parts of a lubricant. The preparation method comprises the following steps: sieving and mixing the raw materials except the lubricant for 20-40 minutes, adding the lubricant, continuously mixing for 3-8 minutes, and pressing into micro-tablets with the diameter of 2-4mm. Wherein the povidone is added in the form of dry powder, is used as a dry powder adhesive, and forms a composite sustained-release skeleton together with the hydroxypropyl methylcellulose, the carbomer and the ethyl cellulose to cooperatively control drug release. Through the synergistic effect of the ternary composite skeleton and the dry povidone powder, 24-hour stable release of bromhexine hydrochloride is realized, and the release behavior is not influenced by pH; the process avoids the influence of damp and hot factors on the drug stability; the dosage form of the micro-tablet obviously improves the medication compliance of children, old people and patients with dysphagia.