A mucolytic agent bromhexine-verein

 

The invention relates to the field of medicine and is about creating funds on the basis of Bromhexine hydrochloride. The invention lies in the fact that the tool Bromhexine-Verein made in the form of a syrup contains Bromhexine hydrochloride and excipients propylene glycol, sorbitol food, the essence of aromatic food and purified water at a specific ratio of ingredients. The invention provides for obtaining Bromhexine syrup-therein that the ingestion does not intrude on the wall of the stomach, non-toxic. 1 table, 4 Il.

The invention relates to the field of medicine and is about creating funds on the basis of Bromhexine hydrochloride.

Known drug Bromhexine with mucolytic and expectorant action. The tool is made in pill form. As an expectorant it is used in acute and chronic bronchitis, infectious-allergic form of asthma, pulmonary tuberculosis, acute and chronic pneumonia (M. D. Mashkovsky, Medicines, Moscow, "Medicine", 1993, T. 1, page 442).

Famous syrup of Bromhexine with multicolor as sugar (patent , what there might be in the form of syrup.

The present invention is the creation of a domestic preparation on the basis of Bromhexine in syrup, not having irritating to the stomach wall.

To solve this problem is proposed syrup called Bromhexine-Verein containing the active substance of Bromhexine hydrochloride and excipients propylene glycol, sorbitol, nutritive essence of aromatic and purified water. These components the product contains the following ratios, wt.%: Bromhexine hydrochloride - 0,06-0,16 Propylene glycol - 18-26 Sorbitol food - 25-45 Food essence aromatic - 0,005-0,05 purified Water - the Rest is a Specific example embodiment of the invention.

Bromhexine hydrochloride (in terms of 100% substance), 0.07 g of Propylene glycol - 21,74 g of Sorbitol food - 34,28 g Food essences of aromatic - 0,013 g
0.1 M solution of hydrochloric acid Up to pH 4.0
Purified water - 100 g
To obtain Bromhexine syrup-Verein in the reactor 1 pour the purified water in the amount of 250 l and boil for 5 minutes. In the reactor with the help of vacuum in boiling water load sorbitol (200,0 kg). After downloading the vacuum off. The mass in the reactor boiled tenny syrup should be transparent. The presence of opalescence is unacceptable. Transparent syrup is cooled to a temperature of 65oC.

In the reactor 2 manually load a portion of the propylene glycol (125,0 kg) and Bromhexine hydrochloride (0.4 kg). Close the lid of the reactor including a stirrer and a homogenizer. Turn up the heat reactor steam setting temperature 65oC. Stirring is continued until complete dissolution of Bromhexine. The resulting solution should be clear and colorless.

Cooled to a temperature of 65oWith the syrup in the reactor 1 add a solution of Bromhexine from the reactor 2 with the help of vacuum and mix thoroughly. The resulting syrup should be transparent.

Thoroughly mixed the syrup is cooled to a temperature of 25oC.

A portion of 0.1 M solution of hydrochloric acid contribute to the cooled syrup and stirred for 30 minutes. Then contribute a portion of food essences of aromatic and mix thoroughly. The density of the obtained syrup from 1.10 to 1.20 g/cm3and a pH of from 3.5 to 5.0.

The finished syrup is filtered and poured into bottles.

The drug Bromhexine-Verein passed preclinical trials. The study was conducted in comparison with the drug, produced by German company "Berlin Chemie", dosage form "p(Case of medicines 1993).

The active ingredient of the drug is Bromhexine hydrochloride.

The drug has a mucolytic, secretomotor and weak spasmolytic effect. The effect of Bromhexine due to its ability to stimulate the production of endogenous surfactant - surfactant-lipid-protein-mukopolisaharidnyh nature, synthesized in the alveolar cells. Pulmonary surfactant or antecedently factor is lined in a thin film inner surface of the lungs, ensuring the stability of the alveolar cells in the breathing process and protecting them from adverse factors that helps to regulate the rheological properties of bronchopulmonary secretions, improving its slipping through the epithelium and the relief of mucus from the respiratory tract.

The drug has a mucolytic (secretolytic) and mild expectorant action. Bromhexine causes activation of ciliated epithelium, and liquefies phlegm, increases its volume, which increases the serous component of bronchial secretions, which, ultimately, promotes the discharge of mucus.

The drug has been used in diseases of the respiratory tract, accompanied by the formation of TradeAbility, complicated by bronchiectasis;
- infectious-allergic bronchial asthma;
- pulmonary tuberculosis;
- pneumonia;
- preoperative and preventive rehabilitation of the bronchi.

Bromhexine promotes the penetration of antibiotics (erythromycin, cephalexin) in the lung tissue, but its joint application with salicylates, phenylbutazone and oxyphenbutazone may cause severe irritation of the gastric mucosa.

The drug is not used in conjunction with antitussive drugs that reduce the excitability of the cough center (e.g., codeine), especially before bedtime. The drug is also not prescribed for ulcers of the gastrointestinal tract. Bromhexine is not compatible with alkaline solutions.

Carried out a determination of the absorption spectrum of drugs.

For registration UV spectrum was used spectrophotometer "U1-trospec-II" produced by LKB Biochrom. To register absorption spectra of aliquots of the test and control syrups prepared solution in a dilution of 1: 100, the solvent used distilled water, after which the solution was filtered through misiorowski filter with pore size 0.45 Ám.

In Fig. 1 and 2 presents an overview of absorption spectra of the solutions of apparatov the same as the position of the peak optical density, and their values. Optical activity is observed in the interval of wavelengths from 200 nm to 380 nm, and at wavelengths from 380 nm to 700 nm and no peak optical density not observed in both of the investigated drugs.

In Fig. 3 and 4 presents the absorption spectra of the solutions of an experienced drug - Fig.3 and the comparison drug - Fig. 4 in the most interesting range of wavelengths from 200 nm to 380 nm. Optimal absorption optical density sufficiently symmetric, resulting in pronounced and minima of the absorption. The absolute value of the optical density on the characteristic values of the wavelengths of the provisions of the minimum and maximum optical absorption are presented in the table. From the presented results, it follows that there are three peaks of absorption corresponding to 210 nm and 246 nm and 310 nm, and three wavelength corresponding to the minimum optical absorption - 206 nm 236 nm and 277 nm. Moreover, the difference in the values of optical density in the control and experimental drugs not exceed 6%, indicating almost the same concentration of the active substance.

Acute toxicity was studied on white outbred mice weighing 18-20, the Drug was administered intragastrically through a tube. Maksimalnogo introduction and drug concentrations in finished dosage form (0.8 mg/ml). The maximum single dose for mice was 40 mg/kg

Introduction the maximum achievable doses in laboratory animals as study drug and the comparator drug did not lead to the appearance of visible signs of intoxication, but in some cases it was noted the occurrence of dyspeptic disorders, which was reflected in the appearance of vomiting, increasing the number of bowel movements, loose stools. However, within 14 days after a single injection of drugs there are no reported fatal case.

Subacute toxicity of the drug was studied on white outbred rats weighing 180-220, the Drugs were injected intragastrically. Based on the fact that therapeutic dose of 0.4 mg/kg, and ten times therapeutic dose of 4.0 mg/kg (in terms of Bromhexine), laboratory animals were divided into five groups.

Group 1 - 10 times therapeutic dose of 4 mg/kg Bromhexine-Verein syrup.

Group 2 - therapeutic dose of 0.4 mg/kg Bromhexine-Verein syrup.

Group 3 - 10 times therapeutic dose of 4 mg/kg Bromhexine syrup manufactured by Berlin-Chemie, Germany.

Group 4 - therapeutic dose of 0.4 mg/kg Bromhexine syrup manufactured by Berlin-Chemie, Germany.

Group 5 - in the texts of the experiment, the degree of intoxication was assessed according to the General condition of the animals, condition of coat, the change in the number of uriasi, defecation, salivation, the onset of tremor, seizures, changes in frequency and rhythm of the breath.

After the injection was performed pathologic-anatomic dissection of animals. For optical analysis of selected samples of kidney, liver, spleen, thymus and brain. In addition, in the blood of animals was determined such biochemical and hematological parameters like total protein, glucose, urea, activity of ALT, AST, alkaline phosphatase, hemoglobin concentration, platelets and leukocytes.

Deaths for the whole time of the experiment was not observed. No marked change in the condition of coat, was not observed onset of tremor, changes of rhythm and breathing rate, although in some cases it was noted the appearance of dyspeptic disorders. And dyspepsia observed in the group of animals treated with the experimental drug, and in the group of animals treated with the drug comparisons. In General, both of the drug in therapeutic and 10 times therapeutic dose) did not cause significant signs of intoxication.

On the 15th day of the injection, animals were scored by decapitation. Blood for the formation of a clot and centrifuged for 10 min in a centrifuge cum-1. Selected serum was stored at minus 20oWith prior research.

In the serum was determined by the concentration of total protein, glucose concentration; the concentration of urea; the activity of aspartate aminotransferase (ACT); the activity of alanine aminotransferase (ALT), alkaline phosphatase activity, hemoglobin concentration, platelet count, and leukocyte count.

A comparative study of subacute toxicity of the drug Bromhexine-Verein syrup (experimental drug) and Bromhexine syrup manufactured by Berlin-Chemie" (drug comparison) shows that such biochemical and hematological blood parameters, as the content of total protein, glucose, urea, activity of alanine(ALT) and aspartate(ACT)-transaminase, alkaline phosphatase activity, haemoglobin concentration, platelet count and leukocyte statistically not different in the group of animals treated with the experimental drug from the group of animals treated with the comparator drug in therapeutic dose, and a 10-fold therapeutic dose in both species of experimental animals. In addition, the experiment shows that both drugs do not lead to significant changes of these parameters and compared to the introduction of the drugs was performed pathologic-anatomic dissection. The slaughter of animals was performed by perturbational pairs of chloroform.

At postmortem autopsy laboratory animals is not detected the development of pathological changes in the liver, kidney, spleen, thymus, brain in response to the introduction of both experienced and control of drugs.

Histological analysis also showed that the experimental drug and the comparator drug when administered to laboratory animals in therapeutic and 10-fold therapeutic doses does not cause cytomorphological changes in the tissues of the kidneys, thymus, spleen and brain.

Experienced drug Bromhexine and drug comparisons when intragastric administration does not cause local irritation of the gastric wall.


Claims

A mucolytic agent, characterized in that it is made in the form of a syrup contains Bromhexine hydrochloride and excipients propylene glycol, sorbitol food, the essence of aromatic food and purified water in the following ratio, wt. %:
Bromhexine hydrochloride - 0,06-0,16
Propylene glycol - 18-26
Sorbitol food - 25-45
Food essences of aromatic - 0,005-0,05
The water cleaned up the

 

Same patents:

The invention relates to new derivatives of Proline, and more specifically to individual forms new derivative of 1-substituted N-[2-methyl-1-(TRIFLUOROACETYL)- propyl]pyrrolidin-2-carboxamide, which are inhibitors of elastase of human leukocytes (ALC), also known as elastase human neutrophils (ANC), which are important, for example, as a means of research work in pharmacological, diagnostic and related studies and in the treatment of diseases of mammals, which also involved ALC

The invention relates to medicine, namely to the chemical-pharmaceutical industry and relates to a composition for injection on the basis of mannitol
The invention relates to medicine

The invention relates to the field of pharmacy and relates to pharmaceutical compositions cyclosporine

The invention relates to the preparation on the basis oxaliplatin in the form of a pharmaceutically stable aqueous solution, the method of its production and use
The invention relates to chemical-pharmaceutical industry, in particular for medical preparations, has analgesic and antipyretic action and is used to treat pain syndromes medium and low intensity: pain headache, toothache, trauma, burns, migraine, neuralgia, myalgia and fever

The invention relates to the field of medicine and refers to drugs with antiemetic effect and the ability to regulate the function of the gastrointestinal tract
The invention relates to medicine, and is intended for the treatment of inflammatory lung diseases, including asthma

-modification of the hydrochloride of 2 - dimethylaminoethanol ether p-butylaminoethyl acid as a local anesthetic means and how you can get" target="_blank">

The invention relates to a new crystalline-modification of the hydrochloride of 2 - dimethylaminoethanol ether p-butylaminoethyl acid as a local anesthetic remedies, the way it is received, namely, that the solution of the hydrochloride of 2 - dimethylaminoethanol ether p-butylaminoethyl acid in water, in an organic solvent or their mixture is heated to boiling, it is dispersed in the refrigerant and subjected to freeze-drying

The invention relates to medicine and pharmaceutical technology and relates to a bronchodilator, and method of its production

The invention relates to the field of pharmaceutical industry and relates to a method of obtaining a pharmaceutical composition

The invention relates to medicine and can be used as a neuroprotective funds, anticonvulsants, tranquilizers
The invention relates to the field of pharmaceutical industry and relates to a method of obtaining a solution of dopamine for parenteral introduction
The invention relates to medicine, Mycology and dermatology, to methods of treatment of onychomycosis

The invention relates to medicine

The invention relates to medicine and veterinary medicine and relates to pharmacological agents that have antimicrobial, wound healing and anti-inflammatory action
Up!