Topic Occupational health in pharmacies. Measures to improve working conditions Occupational health in the pharmaceutical industry

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1. Occupational health in the chemical industry pharmaceutical industry

4. Occupational health in the production of antibiotics

6. Occupational health in the production of herbal preparations and finished dosage forms

9. Hygienic characteristic working conditions in the manufacture of tablets

10. Genetic characteristics of working conditions in the production of pills

Conclusion

Bibliography

1. OCCUPATIONAL HEALTH IN THE CHEMICAL AND PHARMACEUTICAL INDUSTRY

labor security medicine production

The chemical and pharmaceutical industry is one of the leading branches of the national economy. It includes a complex of productions, in which, along with by chemical means materials processing is widely used biological synthesis of drugs.

The modern chemical and pharmaceutical industry has a number of features that determine the specifics of its development, for example, high requirements for the chemical purity of products. In addition, for drugs intended for subcutaneous, intramuscular injections and intravenous infusions, they ensure complete sterility. Their quality must strictly comply with the requirements of the State Pharmacopoeia of Russia.

The next feature of the chemical-pharmaceutical industry is the small volume of production of most drugs.

This industry is also characterized by a large consumption of raw materials, which is due to the multi-stage and complexity of the synthesis of drugs.

Finally, the chemical-pharmaceutical industry is characterized by a relatively rapid renewal of the range of drugs. This feature, as well as a small volume of production of medicines, led to the widespread use of combined technological schemes that allow the production of 2-3 types of medicines or more during the year. In addition, all substances produced by this industry must be processed into finished dosage forms. These features of the chemical and pharmaceutical industry pose a number of new and complex tasks for hygienic science and practice in the field of organizing and conducting recreational activities.

2. Hygienic characteristics of the main technological processes

There are several groups of enterprises in the chemical-pharmaceutical industry. Leading among them are factories for the manufacture of synthetic drugs, factories for the production of antibiotics and enterprises for the production of drugs and finished dosage forms.

The industrial production of synthetic medicines is based on the widespread use of organic synthesis, which brings these enterprises closer to the industry of basic chemistry.

Antibiotic enterprises are united in a special group. This is due to the fact that the basis of the technological process for obtaining these drugs is biological synthesis.

A characteristic feature of factories for the production of galenic pharmaceuticals and finished dosage forms is the production of a large number of various medicines in the form of liquid extracts and tinctures, injection solutions in ampoules, tablets, dragees, patches, etc.

AT industrial production Chemical-pharmaceutical preparations widely use a variety of raw materials obtained both from plant and animal products, and by chemical synthesis. The most common is chemical raw materials. Mineral raw materials are used for the production of inorganic salts, as well as ingredients for various synthesis of organic compounds. A large number of mineral acids and alkalis are used. The initial organic raw materials are supplied by the coke-chemical, petrochemical, aniline-dye industries and enterprises of the main organic synthesis.

In the production of medicines, animal raw materials are also widely used, in particular, histidine is obtained from the blood of animals, adrenaline from the adrenal glands, insulin from the pancreas, thyroidin from the thyroid gland, etc.

All types of technological operations in the preparation of medicinal products can be divided into preparatory, actual processes for obtaining a medicinal product, final and additional operations.

Preparatory operations - storage, movement of solid, liquid and gaseous materials, their transformation: grinding and crushing of solid raw materials, separation solids, removal of liquids and gases from them using the methods of sedimentation, filtration, centrifugation, cooling, crystallization, evacuation, etc.

The actual processes for obtaining drugs are based on exchange, thermal, electrochemical, biological processes, electrolysis, etc. At this stage of the technological process, the reactions of sulfonation, nitration and halogenation, amination and oxidation, reduction and oxidation, etc. are widely used.

At the final stage, drugs are dried, crushed, tableted, ampouled, packaged and packaged.

preparatory operations. A significant part of the feedstock for the production of galenic and synthetic drugs is in the solid state and is subjected to crushing and grinding. The need for this operation often arises when receiving dosage forms (tablets, dragees, etc.). Crushing is carried out on jaw, roller, cone, hammer and other crushers. Grinding is carried out using ball and porcelain mills, disintegrators. Small amounts of the medicinal product are crushed in mechanically driven mortars, Islamgulov, Excelsior, etc.

Occupational hazards in crushing, grinding and separating drug precursors are dust, intense noise and general vibration. Dust is released at the point of entry of medicinal raw materials or the finished product into crushers and mills and at the point of exit of the crushed substance.

A hygienically unfavorable operation is the separation of materials into fractions. The air separators and mechanical sieves used in this process are significant sources of dust emission. In the production of small-tonnage drugs (for example, hormonal drugs), rubbing by hand on sieves is often used, which is associated with the release of dust and contamination of the skin and overalls of workers.

To combat dust emissions, proper organization technological process and equipment, shelter of places of dust release with aspiration of dusty air. Since noise and vibration in crushing and grinding plants can exceed the permissible values, this equipment must be placed in separate industrial premises, and the foundations under them should not be connected with the building structures. In the fight against noise and vibration, it is necessary to use anti-noise and vibration-damping devices and materials. It is advisable to control the grinding and crushing processes remotely.

Transportation of the initial components has a significant impact on the level of air pollution of the working area with harmful substances at the preparatory stage. This is due to the heavy load on communication facilities, the presence of mechanisms and devices designed to move substances that do not have effective exhaust devices and the necessary tightness.

During transportation, workers can come into contact not only with vapors and gases, but also with liquid and bulk harmful substances. In some cases, manual transportation, loading and unloading of medicinal raw materials (for example, of plant origin) is still used.

The movement of liquid substances is carried out through pipelines using pumps, air or steam pressure, gravity and vacuum. Gaseous substances are transported by compression and vacuum. The supply of raw products with compressed air is associated with an increase in pressure in communication networks, which can lead to the release of harmful vapors and gases through leaks in pipelines, apparatus and containers. It should be noted as hygienically imperfect transportation of liquid products using pumps, which are an additional factor contributing to air pollution with chemicals. From this point of view, the most favorable transportation of liquid products by gravity or with the help of vacuum. Main hygiene requirements to the equipment are the resistance of pipelines, gasket and stuffing material to the action of liquids, the replacement of stuffing box pumps with glandless and submersible ones.

The supply of solid medicinal raw materials (products of plant origin, organic and mineral substances) from raw material warehouses to preparatory workshops, from one equipment to another, is carried out using belt conveyors, elevators, screws, as well as pneumatic and hydraulic systems. The method of transportation is determined by the aggregate state of substances, their toxicity, the nature of production, etc.

Giving a hygienic assessment of these processes, it should be noted that transportation using belt conveyors, screws, etc. is associated with a significant release of dust. The most perfect in hygienic terms is the supply of dry raw materials using pneumatic transport.

The actual processes for obtaining drugs.

The technological stage The production of medicines is characterized by a wide variety of technological processes and operations, equipment and chemicals used. Significant specific gravity in the industrial synthesis of intermediates and medicinal substances, processes associated with the reactions of substitution of hydrogen atoms in the nucleus of aromatic compounds by one or another group of atoms, the transformation of substituents already existing in the molecule of an organic compound into others in order to give it new properties, and, finally, a change in the carbon structure of the molecule . These are the reactions of nitration, sulfonation, halogenation, reduction, alkylation, etc. These processes are carried out in reactors of various types, which got their name depending on the chemical reactions carried out in them (chlorinator, nitrator, sulfator, etc.).

Reactors can operate under conditions of high and normal atmospheric pressure or under vacuum. They can be intermittent or continuous. These are steel, lead or cast iron tanks with or without agitators, heated or cooled. Depending on the processes occurring in the reactors, various types of mixers are used: paddle, screw, frame, anchor, etc.

The main harmful factor in the reactor compartment is chemically th. Places for release of toxic substances from reactors can be agitator stuffing boxes, hatches through which products are loaded and unloaded, measuring glasses, viewing windows, flange connections. At the same time, the composition and level of harmful substances in the air of the working area depend on the perfection of the equipment used, the type of medicinal intermediate or finished drug obtained, the mode of operation and other factors. Unfavorable hygienic conditions may be due to manual operations, for example, when measuring the level of liquids, sampling. Transfer of equipment to a vacuum process, the use of closed reactors with shielded stirrer motors, as well as automatic control, significantly reduce the release of harmful substances into the air of working rooms.

A large proportion at this stage is occupied by the processes of separation of chemical components. The main equipment for carrying out such operations is a distillation apparatus and distillation units. The maintenance of this equipment is associated with the possibility of contact of workers with harmful substances that can enter the air through communication systems, hatches, taps, sampling points, etc.

Filtration and centrifugation processes are widely used to separate suspensions into solid and liquid phases. Filtration is carried out on filters of periodic and continuous action. The former include suction filters, filter presses, leaf filters, and the latter include drum, disc and belt filters. The operation of suction filters and filter presses is often accompanied by the release of toxic substances into the air of the working area, associated with the use manual labor and the possibility of intense contamination of the skin and overalls. From a hygienic point of view, drum filters are more favorable, which are sealed and equipped with exhaust ventilation.

Batch and continuous centrifuges are used to quickly separate the medicinal intermediate. Batch centrifuges are less perfect and have a number of disadvantages, the main of which are the inconvenience of removing the pressed material, the use of manual labor, and the lack of reliable tightness. These shortcomings cause the release of harmful substances into the air of the working area and contamination of the skin.

Hygienically reliable are mechanized and closed filters, self-emptying bottom discharge centrifuges, drum vacuum filters and automatic filter presses.

A significant part of semi-finished products and finished medicines is subjected to drying. This process is necessary for the production of herbal, synthetic drugs, antibiotics, vitamins, etc. Moisture is removed by mechanical (filtration, pressing, centrifugation), physico-chemical (absorption by hygroscopic materials) and thermal (evaporation, evaporation and condensation) methods.

In the production of medicines, chamber, drum, spray, shaft and other dryers are most widely used. Maintenance work on most dryers is accompanied by increased heat generation directly at the workplace and the release of toxic substances.

A significant disadvantage of dryers is insufficient mechanization and sealing of the processes of loading and unloading substances that are subjected to drying, which causes air pollution of the working area with the dust of the finished product. Significantly less harmful substances are emitted when using continuous dryers (raking, spraying, drying drums, etc.), provided with complete sealing and mechanization of loading and unloading processes.

Evaporation and crystallization processes are widely used in the production of medicines. The former are used to obtain more concentrated solutions from less concentrated ones (synthetic and herbal preparations, antibiotics, vitamins, etc.). For this purpose, in most cases, multi-effect evaporators are used. Hygienically unfavorable operations when working with them are the supply of solutions and the unloading of the finished product, since they are accompanied by the release of harmful compounds into the air of the working area.

Crystallization processes are used in the purification of medicinal substances from impurities or separation from a liquid. These processes are carried out in open and closed crystallizers. The main disadvantage of this equipment is insufficient sealing and mechanization of the processes of loading and unloading medicinal substances.

More favorable sanitary conditions at workplaces are created during the maintenance of vacuum crystallizers.

Obtaining finished dosage forms in the form of tablets, dragees, ampoules consists of many preparatory and basic processes and operations carried out in a certain sequence on the appropriate equipment.

final operations. In the final stage of the technological process, medicinal substances are labeled, packaged and packaged. Dosage forms are packaged in plastic, paper and glass containers. Most operations on this stage mechanized.

Dust is the main hygienically unfavorable factor in this stage of drug production. Workers, as a rule, are exposed to dust of a complex composition, since several types of medicines can be packed and packaged at the same time.

Work with a semi-mechanized and especially manual method of packaging and packaging of tablets, ampoules, dragees, as well as gluing boxes and convales with strips of cellophane and a number of other operations are associated with a forced position of the body.

3. general characteristics industrial factors that determine working conditions in the production of medicines

1. Chemical factor. Studies show that the main unfavorable operating factor of the production environment at the enterprises of the chemical and pharmaceutical industry is the pollution of the air of the working area, clothing and skin with harmful organic and inorganic substances.

Air pollution with toxic substances is possible at all stages of the technological process: during preparatory, main and final operations. The main reasons for the content of harmful substances in the air of industrial premises are the imperfection of equipment, violation of technological regimes, the absence or insufficient mechanization of many operations associated with the transportation, loading and unloading of materials from apparatuses, the use of leaky equipment, overflows chemical products when filling devices, etc.

The composition of workspace air pollutants in most drug manufacturing plants is complex, due to the simultaneous presence of many chemical ingredients in the form of aerosols, vapors or gases. Depending on the stage of the technological process, the type of the resulting medicinal product, the air of industrial premises may be polluted by the initial, intermediate and finished products of chemical synthesis. At the same time, the entry of harmful substances into the body is carried out mainly through the respiratory tract and, to a lesser extent, through the skin and the gastrointestinal tract.

The impact of a harmful substance on the body is possible at various stages of the technological process: during the preparation of raw materials, the implementation of the actual processes for obtaining a medicinal product, and final operations. At the same time, the severity and nature of the impact of the chemical factor on the body of workers are determined by the perfection of technology and equipment, the formulation of the medicinal substance, as well as the construction and planning decisions of the premises and the organization of air exchange in them.

A significant role in air pollution in industrial premises is played by the nature of the technological process and, above all, its discontinuity. The implementation of processes according to a periodic scheme is associated with repeated loading and unloading of liquids or bulk materials, the use of various ways transportation of the processed material. This greatly complicates the organization of effective measures to prevent air pollution. At the same time, the organization of the technological process according to a continuous scheme makes it possible to exclude a number of processes and operations (unloading, transportation, loading of semi-finished products, etc.), which are a source of air pollution in the working area. In addition, favorable conditions are created for the elimination of time-consuming and dangerous manual operations.

The level of air pollution with vapors and gases of harmful substances is greatly influenced by the pressure in devices and communication networks. From a hygienic point of view, the most favorable conditions are created during the synthesis of drugs carried out under vacuum, since in this case toxic substances cannot be released from the equipment. Vacuum processes take place in the reactor compartment and are widely used in drying and drug isolation.

However, many chemical processes synthesis of intermediates and finished drugs proceed at elevated and high pressure, for example, the formation of aniline from chlorobenzene proceeds at a temperature of about 200 "C and a pressure of 5.9--9.8 MPa (60--100 atm), the hydrolysis of an amine to phenol occurs at temperature 350 "C and pressure 19.6 MPa (200 atm).

In such processes, the tightness of the equipment is achieved by using flanged joints of pipes and devices of a special design using fluoroplastic, asbestos-lead and other gasket materials.

As shown by special chronometric observations, the operator in the production of sulfanilamide preparations, on average 10--12% of the working time, is in conditions of high levels of harmful substances in the air. The highest levels of chemical pollution are observed at the time of leakage of technological equipment, for example, in the stage of hydrolysis of phenylhydrazine sulfate in the production of amidopyrine during sampling through the open hatch of the apparatus, the concentration of sulfur dioxide can be 4 times higher than the MPC.

2.Dust. Air pollution of working premises with dust is observed mainly at the preparatory and final stages of obtaining medicinal substances. The main sources of dust emission at the preparatory stage are the delivery of feedstock from storage facilities to production shops, as well as operations related to crushing, grinding, screening, transportation, loading, etc.

Thus, a significant amount of dust is observed at workplaces when grinding vegetable raw materials, crushing the initial components of synthetic agents. At the same time, the level of dust can be 3-5 times higher than the permissible one.

In the final stage of obtaining drugs, the most often high levels of air pollution with dust of the finished drug, several times higher than the permissible ones, are observed in the process of tableting, drageeing, drying, grinding, sifting mixtures, filling and packaging finished drugs. Under these conditions, medicinal dust should be considered as industrial and industrial poison. The dust content in the air of the working area when working on vibrating sieves and especially when manually sieving can

5 times or more exceed the allowable values. Yes, during
manual packaging dust concentration in the breathing zone of workers
can reach 100 mg/m3 and more.

It is known that the nature of the impact of dust on the body and the severity of biological changes is largely determined by its dispersion. The dust of some drugs is 85--98% composed of particles smaller than 5 microns. This contributes to the penetration of a large amount of drugs into the body through the respiratory tract and digestive organs (with saliva).

3.Microclimate. At the enterprises of the chemical and pharmaceutical industry, the microclimate of industrial premises must comply with the requirements established by SanPiN 2.2.4.548--96. However, studies show that with insufficient thermal insulation of the heated surfaces of apparatuses and communication heating networks, it is possible to influence the microclimate on those working simultaneously with the chemical factor. Elevated air temperature is found mainly in drying compartments and in apparatuses in which the reaction proceeds with the release of heat or at high temperature (crystallizers, solvents, hydrolyzers, etc.). So, in the warm season, the air temperature in these areas can reach 34–38 ° C with a relative humidity of 40–60%.

Thus, the thermal microclimate at individual workplaces of chemical and pharmaceutical industry enterprises is an additional factor that aggravates the effect of the chemical factor.

4. Noise. The source of industrial noise in the workplace in the manufacture of drugs are many technological devices. These include compressors, vacuum filters, drum dryers, centrifuges, crushers, vibrating screens, vacuum pumps, etc. In some cases, the noise level may exceed the permissible level. So, at workplaces at centrifuges, noise parameters can exceed the permissible values by 5 dB, at a vacuum pump - by 5-6 dB, at a compressor - by 14-17 dB.

The most unfavorable areas are engine rooms, where the total level of high-frequency noise often exceeds the permissible values by 20-25 dB. It should be noted that industrial noise, even at an acceptable level, can exacerbate the adverse effects of chemicals.

4. OCCUPATIONAL HEALTH IN THE ANTIBIOTIC PRODUCTION

Antibiotics are substances produced by microorganisms, higher plants and animal tissues in the process of life and have a bactericidal or bacteriostatic effect. Now there are about 400 antibiotics belonging to various classes of chemical compounds. The antibacterial properties of antibiotics served as the basis for their widespread use in medicine, in particular in the treatment and prevention of infectious diseases and inflammatory processes.

In addition to being used in medicine, antibiotics have found application in the food and meat and dairy industry for canning products.

The technological process for obtaining antibiotics consists of several stages carried out in a certain sequence and on the appropriate equipment:

a) cultivation of inoculum and biosynthesis of antibiotics (fermentation);

b) pre-treatment of the culture fluid;

c) filtration;

d) isolation and chemical purification (extraction method, ion exchange method, precipitation method);

e) production of finished dosage forms;

e) packing and packaging

The basis of the initial technological processes is the cultivation of seed (producer) in flasks and fermenters. The grown production strain of the producer for the purpose of its further enrichment is transferred to special devices - inoculators. The process of growing fungi and bacteria in inoculators is carried out under strictly defined conditions, which are provided by heating and cooling systems, air supply, devices for mixing the production mass. Then the producer goes to fermentation. By fermentation is understood the cultivation (growing) of the producer and the formation of the maximum amount of the antibiotic. Antibiotics are synthesized in the cells of microorganisms or released during biosynthesis into the culture fluid.

Pure antibiotic The main technological scheme for the recovery and purification of antibiotics.

The main equipment for the fermentation process are fermenters, which are huge containers up to 100,000 liters. They are equipped with heating and cooling systems, supply of a sterile air mixture, agitators, as well as devices for loading and unloading the nutrient medium, culture fluid. This stage of the technological process is characterized by the tightness of the equipment used, in connection with which the possibility of air pollution by substances used for the biosynthesis of antibiotics, as well as by the biomass itself, which is formed at the end of the fermentation process, is practically excluded.

Due to the fact that antibiotics form insoluble compounds with many substances present in the culture fluid, to increase the concentration, as well as to more completely precipitate impurities, the culture fluid is acidified to pH 1.5–2.0 with oxalic or a mixture of oxalic and hydrochloric acids. . The treated culture liquid is filtered from mycelium and precipitated ballast substances to obtain a clear filtrate, called native solution. Filtration of the treated culture liquid is carried out on open-type frame filter presses, as a result of which splashing of the native solution may occur. Manual unloading of filter presses exposes workers to culture fluid containing antibiotics.

The next step in obtaining an antibiotic is isolation and chemical purification. At this stage, the antibiotic solution is concentrated and purified to such a purity that it can be used to obtain a finished drug product. The content of the antibiotic in the native solution is very low, so its isolation in its pure form, purification and bringing to the finished dosage form is very complex and complex. laborious process: for example, to obtain 1 kg of antibiotic, you need to process about 600 liters of culture fluid.

For the isolation and chemical purification of antibiotics, one of the following methods is used: extraction method using various solvents; precipitation method; ion exchange method. Extraction and ion-exchange methods have found the widest application in the biosynthesis of antibiotics, and in recent years, the ion-exchange method for isolating and purifying antibiotics has also been used in the preparation of other drugs. Its main advantage is that it eliminates the need to use toxic and explosive solvents. The method is economically beneficial, since its technology is simple and does not require expensive equipment and raw materials.

The extraction of antibiotics from the native solution is carried out in extractor-separators, the main disadvantage of which is the need for manual unloading, as a result of which the air of workshops can be contaminated with solvents, for example, isooctanol in the production of tetracycline and oxytetracycline.

Along with solvents, oleic acid, sodium hydroxide, oxalic acid, butyl and ethyl alcohols, butyl acetate, etc. can enter the air at the stage of isolation and chemical purification of antibiotics due to the imperfection of the equipment used.

The method of ion sorption consists in the fact that the native solution is fed with the help of centrifugal pumps into the battery of ion-exchange columns loaded with SBS-3 sulfonic cation exchanger. As a result of ion exchange, the antibiotic is sorbed on the ion exchanger, after which it is desorbed (eluted) with an ammonium borate buffer solution.

This method has certain hygienic advantages over precipitation and extraction methods. It does not require manual labor when working with sediments, which eliminates the contact of antibiotics working with concentrated solutions and sediments. This method does not use toxic organic solvents.

Pasty products obtained in the process of chemical cleaning are further dried and screened. The drying process in the production of antibiotics plays exclusively important role, since the quality of products depends on its organization. Thermostable antibiotics, obtained in crystalline form with a low moisture content, are usually dried in vacuum ovens. Antibiotics obtained after chemical purification in the form of aqueous concentrates are dried in evaporative drying units and vacuum freeze dryers. These processes must be carried out under sterile conditions.

The main disadvantage of working in drying departments is the use of manual labor when loading and unloading products. The performance of these operations, as well as the need to mix the powdered mass and control the technological mode of operation of the drying units, are associated with the possibility of contact of antibiotics working with dust. Insufficient sealing of drying units contributes to the release of some toxic substances into the air of industrial premises, the residual amounts of which may be contained in antibiotics. For example, finished chlortetracycline may contain an admixture of methanol, tetracycline - isooctyl alcohol, tetracycline and oxy-tetracycline hydrochlorides - n-butanol and hydrochloric acid.

5. Hygienic characteristics of working conditions and the state of health of workers in the production of antibiotics

Working conditions in the production of antibiotics are characterized by the possible entry into the air of highly dispersed dust of antibiotics, vapors and gases, chemicals used in the technological process and the release of excess heat. During the fermentation stages, workers may be exposed to phenol and formaldehyde vapors used to sterilize premises and equipment, as well as producer dust.

At the stages of pre-treatment and filtration, workers come into contact with oxalic and acetic acid. Manual operations often lead to contamination of the skin and overalls with culture fluid and native antibiotic solution.

The processes of isolation and chemical purification of the antibiotic, carried out by extraction and precipitation methods, are associated with the possibility of exposure to the working vapors and gases of butyl, isopropyl and methyl alcohols, butyl acetate, oxalic, acetic, sulfuric and hydrochloric acids and other substances used in this stage. The concentrations of these substances in the air in some cases may exceed the maximum allowable. The main causes of air pollution of the working area with harmful substances are insufficient tightness of the equipment, the presence of manual operations, low efficiency of ventilation devices, etc.

On the final stages studies show that drying, screening, tableting, filling and packaging of antibiotics can be accompanied by significant contamination environment fine dust finished products. In addition, the workers of the preparatory workshops, drying department, fermentation, in addition to the chemical factor, can simultaneously be exposed to excess heat, the main source of which is inoculators, fermenters, drying units, as well as the surfaces of communication networks in case of insufficient thermal insulation.

The study of the state of health of workers in the production of antibiotics shows that under the influence of occupational hazards, violations of the functional state of the body are possible, and in some cases the development of occupational diseases.

One of the characteristic manifestations of the toxic effect of antibiotics are complaints of persistent itching of the skin, frequent headaches, pain in the eyes, fatigue, pain and dryness in the throat. In some cases (for example, when exposed to streptomycin), workers also note hearing loss and pain in the region of the heart.

The most common and characteristic symptoms when exposed to antibiotics are complications from gastrointestinal tract: lack of appetite, nausea, flatulence, abdominal pain. A significant group of complications are liver damage, impaired function of the kidneys, cardiovascular and nervous systems.

At present, significant material has been accumulated on the effect of antibiotics on the blood system: the development of anemia, agranulocytosis, leukopenia, and impaired vitamin metabolism.

Antibiotics should be attributed to the group of so-called allergens, the sensitizing effect of which is manifested mainly in the defeat of the skin and respiratory organs. Allergies occur both through inhalation and through contact with the skin. The development of skin sensitization contributes to the violation of the integrity of the skin. Positive allergenic tests, for example, for penicillin, were detected in 18% of those working with an antibiotic, for streptomycin - in 18.5%, for both antibiotics with combined action - in 47%. In persons constantly in contact with antibiotics, most often (50%) develop dermatitis, eczema, urticaria, localized mainly on the hands, forearms, face. These changes are most often recorded in workers with more than 5 years of experience in the production of biomycin, chloramphenicol, tetracycline, penicillin. In this case, skin lesions begin with diffuse hyperemia and swelling of the face (especially in the eyelids), hands and forearms. With further contact with antibiotics, acute or subacute recurrent dermatitis may develop, turning into eczema.

Changes in the upper respiratory tract are expressed in the development of hyperemia and atrophy of the mucous membranes, mainly of the nose and larynx. As the disease progresses, it can be complicated by asthmatic bronchitis and bronchial asthma. One of the manifestations of the side effects of antibiotics is dysbacteriosis - a violation of the normal microflora of the body. Secondary mycoses (more often candidiasis), changes in the gastrointestinal tract and upper respiratory tract, which developed against the background of mucosal dysbacteriosis, as well as suppression of natural immunity factors, are detected in those working in the production of antibiotics. The workers had constipation, diarrhea, flatulence, erosion and ulcers of the rectal mucosa. The detected changes in the state of health to a certain extent resemble the manifestations of the side effects of antibiotics in the conditions of their clinical use.

Along with this, workers have an increased incidence of influenza, SARS and diseases of the female genital area.

Preventive measures in the production of antibiotics should be aimed primarily at combating the release of harmful substances into the air of the working area. To this end, in the complex of recreational activities, it is necessary to provide for the automation and mechanization of technological processes, efficient work general and local ventilation, compliance with the technological regime. This not only eliminates the effect on workers of released harmful substances, but also eliminates the adverse effects of meteorological factors.

Special attention in the fight against air pollution by harmful substances, attention should be paid to sealing technological equipment and communications, mechanization of processes and operations for loading, unloading and transporting raw materials, semi-finished products and finished products.

An important place in the prevention of the harmful effects of chemical factors should be occupied by laboratory control over the content of harmful substances in the air of the working area, the amount of which should not exceed the established norms. Currently, MPCs have been established for the following antibiotics: streptomycin - 0.1 mg/m3, oxacillin - 0.05 mg/m3, florimycin - 0.1 mg/m3, hygromycin B - 0.001 mg/m3, oxytetracycline - 0 .1 mg/m3, ampicillin - 0.1 mg/m3, biovit (according to the content of chlortetracycline in the air) - 0.1 mg/m3, oleandomycin - 0.4 mg/m, phytobacterin - 0.1 mg /m3.

To a large extent, the improvement of the air environment in the production of antibiotics will be facilitated by the replacement of harmful ingredients in the technological formulation with new, less toxic compounds.

In order to prevent allergization of the body and the skin-irritating effect of chemicals, it is recommended to carry out preventive desensitization, the use of protective ointments (for example, 2% salicylic), detergents, etc.

The organization of a proper diet and rest is important in preventing diseases and strengthening the state of health. It is recommended to issue lactic acid colibacterin to prevent dyspeptic disorders among workers, as well as enrichment of food rations with vitamins A, B, PP, C. It is necessary to strictly observe the rules of personal hygiene - wash hands after each manipulation with antibiotics, wash in the shower and change clothes after work. In addition, workers in the production of antibiotics should be provided with rational work clothes, underwear, footwear, gloves and mittens, anti-dust respirators such as "Petal-5", "Petal-40", goggles.

6. OCCUPATIONAL HEALTH IN THE MANUFACTURE OF HALENIC MEDICINES AND FINAL DOSAGE FORMS

The pharmaceutical industry unites enterprises for the production of galenic, new galenic preparations, as well as finished dosage forms (coated, ampoule, tableting, etc.). At the enterprises of this industry, galenic and novogalenic preparations are produced, such dosage forms as tinctures, liquid and dry extracts, syrups, solutions, drops, tablets, patches. A large amount of work falls on the weighing, mixing, grinding and packaging of pharmaceuticals, completing first-aid kits, etc. The technological process is built according to the workshop principle and includes such main workshops as galenic, ampoule, tablet, packaging, coating, etc.

Various substances of plant, animal and mineral origin are used as initial medicinal raw materials for the production of galenic and novogalenic preparations. The features of this production are a wide range of products, a variety of raw materials, the production of numerous drugs in small quantities (low-tonnage), a variety of equipment used for the main technological and auxiliary operations. These industries often operate on a combined basis. technological scheme, i.e., the equipment is designed and placed in such a way that it can be used to obtain various drugs that are similar in terms of the manufacturing procedure.

7. Hygienic characteristics of working conditions in the manufacture of herbal medicines

Phytopreparations are obtained from medicinal plant materials. They are divided into two groups: preparations from fresh plants and preparations from dried plant materials. During their manufacture, in the event of a violation of the tightness of the equipment and low ventilation efficiency, workers can be exposed to vapors of extractants (dichloroethane, ethers, alcohols, etc.). Unfavorable in hygienic terms should be considered operations for grinding fresh medicinal herbs, since at this moment droplets of their juice and small particles can enter the respiratory organs, on the skin from open parts of the body (hands, face), while providing a skin-irritating and sensitizing effect.

Dried herbal preparations include tinctures and extracts.

Tinctures are alcohol or alcohol-ether extracts from dry plant materials, obtained without heating and removing the extractant. Tinctures are obtained by infusion, percolation (continuous filtration through a filter) and dissolution of the extracts.

Extracts - herbal preparations, concentrated extracts from dry plant materials, purified from ballast substances. By concentration, liquid, thick and dry extracts are distinguished. The main operations in the technological scheme for obtaining extracts are:

a) extraction of dry plant materials;

b) separating the liquid phase from the solid by settling, filtering, centrifuging and pressing;

c) distillation of extractants - water, ether, alcohol, chloroform, etc. by evaporation (thick extracts) or drying under vacuum (dry extracts).

There are many extraction methods. In general, they can be classified into static and dynamic.

In hygienic terms, the most progressive methods are dynamic extraction, which is based on a constant change of extractant or extractant and raw materials.

Thick extracts are obtained by evaporation (thickening) of liquid extracts in vacuum evaporators at a temperature of 50-60 °C.

Dry extracts are extracts from dry plant materials. They are obtained by further drying the thick extract in a vacuum roller dryer or by drying the non-thickened extract in a spray dryer.

The working conditions in the manufacture of galenic and novogalenic preparations are characterized by the possibility of exposure to working dust of medicinal plants released during crushing of plant materials, sifting, transportation, loading, unloading, etc. herbs. Its concentration depends on the type of plant material, the degree of its grinding, mass, etc.: for example, the concentration of Eleutherococcus dust when loaded into percolators was 2-4 times higher than the pollution levels when loaded with valerian root.

Medicinal dust, depending on the physical properties, chemical structure, can have a wide variety of effects on the body: general toxic, skin-irritating, allergenic, etc. For example, when loading, belladonna herb containing alkaloids of the atropine group, getting on the skin, causes irritation. With prolonged exposure, especially when the dust of this herb enters through the respiratory tract, the toxic effect manifests itself in the form of dizziness, general arousal, increased heart rate and respiration. The dust of red pepper, sage, wormwood, etc. has a skin-irritating effect. Cases of allergic lesions in contact with the dust of lemongrass, lycopodium and other herbs are described.

The preparation of galenic and novogalenic preparations is associated with air pollution of the working area with vapors of extractants and solvents (alcohol, ether, chloroform, dichloroethane, etc.). For example, high concentrations ethyl alcohol vapors were found at a number of enterprises in the premises for the production of alcohol solutions, where in 20--30% of the samples taken, the content of vapors in the air of the working area exceeded the MPC.

In combination with the chemical factor in some areas, workers are exposed to the simultaneous effects of the microclimate, determined by excess heat, and noise.

The nature and severity of the impact of the chemical factor on those working in galenic shops is determined by the perfection of the technological equipment used, the composition of medicinal raw materials, as well as the building and planning solutions of the premises and the organization of air exchange in them.

Studies show that at those enterprises where sealed equipment is widely used in the production of herbal and novogalenic preparations, and the processes of loading, unloading and transporting semi-finished products and finished dosage forms are mechanized, the concentration of vapors and aerosols of extractants and medicines in the air does not exceed permissible levels. At the same time, the violation of the tightness of equipment and communications, the use of manual labor, the presence of open surfaces, the discontinuity of technological processes, the imperfection of ventilation devices are one of the reasons for the high content of harmful substances in the air of the working area, which is 2–5 times or more higher than the MPC.

The most important health improvement measure in the shops for the production of herbal preparations is the rationalization of technological processes with the widespread introduction of automation and mechanization. Sealing of equipment, communications, conveyors, etc. is an important condition in the system of preventive measures. Supply and exhaust ventilation plays an important role in the improvement of working conditions. First of all, it is necessary to equip local exhaust devices at crushers, vibrating screens, places for loading and unloading raw materials, auxiliary ingredients, etc.

An exceptionally large role in ensuring normal working conditions is played by the planning decisions of galenical shops, taking into account the emission of harmful substances and noise sources. Great importance in the prevention of harmful effects production factors have personal protective equipment. Workers servicing crushers, mills, sieves, screw and belt conveyors and other technological equipment must be provided with overalls, goggles of type 03-N, 03-K, gloves, respirators of type ShB-1. In addition, apparatchiks in contact with organic extractants must have gas masks with a Grade A filter box.

8. Hygienic characteristics of working conditions in the production of medicines in ampoules

The technological process for the production of medicines in ampoules is carried out in the ampoule workshop pharmaceutical plant. The production cycle production of ampoules consists of the following main operations: production of ampoules, preparation of injection solution and filling of ampoules (ampouling), sealing of ampoules, sterilization, control, labeling and packaging.

Production of ampoules. It is produced in the department of the ampoule workshop using special devices (automatic or semi-automatic). Ampoules are made from long chemically resistant glass tubes - drots. First, the dart is washed, and then it is fixed on carousel semi-automatic machines or automatic machines, where ampoules are obtained from it with the help of gas burners. At subsequent stages, the ampoules with open capillaries are washed in vacuum semi-automatic machines. For more efficient washing, ultrasonic treatment of ampoules has been widely used in recent years. The washed ampoules are dried with hot air in ovens and then transported to the ampoule filling departments.

Studies have shown that workers in this area are exposed to carbon monoxide and high temperatures (up to 28 °C). The main source of emitted hazards is the combustion process. natural gas in gas burners ampoule machines.

In case of violation of the rules for cleaning premises, in particular when removing dust mechanically and by blowing off the surface of ampoule machines, the concentration of glass dust during this period may exceed the MPC by 2 times or more. Along with the specified industrial hazards, workers are exposed to noise, the source of which is ampoule machines. In addition, it must be borne in mind that when washing darts and ampoules, as well as when servicing ampoule machines, there is a risk of injury from glass fragments.

Solution preparation and ampouling. The preparation of the injection solution begins with the treatment of the solvent, which is used as water, various oils (peach, almond, peanut, etc.), synthetic and semi-synthetic compounds. Treatment of water for injection is carried out on high-performance distillers that ensure its appropriate quality, including non-pyrogenicity.

Ampoules are performed using a syringe or vacuum method: at the first time, the ampoules are filled with a solution automatically using a syringe, at the second, a vacuum is created in them of a certain depth, after which the ampoule, immersed in the injection solution, is filled with a certain volume.

Filling ampoules with a medicinal substance requires perfect cleanliness, therefore, especially strict sanitary and hygienic requirements are imposed on technological operations, planning, decoration and maintenance of premises. Walls should be tiled or covered with oil paint. The floor material must be resistant to water, disinfectants, organic solvents and other chemicals. These requirements are more consistent with the coverage of its polymeric material(PVC tiles, relin, etc.). An important point is air purification (filtration) and its disinfection with the help of bactericidal lamps. Indoors, it is necessary to systematically carry out wet cleaning.

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In our country for short term A new branch of the chemical-pharmaceutical industry for the production of antibiotics was created. Currently, the domestic medical industry produces more than 30 types of antibiotics and more than 75 dosage forms. Their share in overall structure medical industry is 18%.

Antibiotics - substances produced by microorganisms, higher plants and animal tissues in the process of life and have a bactericidal or bacteriostatic effect. Now there are about 400 antibiotics belonging to various classes of chemical compounds. The antibacterial properties of antibiotics served as the basis for their widespread use in medicine, in particular in the treatment and prevention of infectious diseases and inflammatory processes.

In addition to their use in medicine, antibiotics have found application in the food and meat and dairy industries for food preservation. They are added to the feed of animals and birds in order to increase the rate of weight gain.,

The technological process for obtaining antibiotics consists of several stages carried out in a certain sequence and on the appropriate equipment: a) cultivation of seed and biosynthesis of antibiotics (fermentation);

b) pre-treatment of the culture liquid; c) filtration; d) isolation and chemical purification (extraction method, ion exchange method, precipitation method); e) production of finished dosage forms; e) packing and packaging (Fig. 11.1).

The basis of the initial technological processes is the cultivation of seed (producer) in flasks and fermenters. The grown production strain of the producer is transferred to special devices - inoculators for the purpose of its further enrichment. The process of growing fungi and bacteria in inoculators is carried out under strictly defined conditions, which are provided by heating and cooling systems, air supply, devices for mixing the production mass. Then the producer goes to fermentation. By fermentation is understood the cultivation (growing) of the producer and the formation of the maximum amount of the antibiotic. Antibiotics are synthesized in the cells of microorganisms or released during biosynthesis into the culture fluid.

Pure Antibiotic

Due to the fact that antibiotics form insoluble compounds with many substances present in the culture fluid, to increase the concentration, as well as to more completely precipitate impurities, the culture fluid is acidified to pH 1.5-2.0 with oxalic or a mixture of oxalic and hydrochloric acids. The treated culture liquid is filtered from mycelium and precipitated ballast substances to obtain a clear filtrate, called native solution. Filtration of the treated culture liquid is carried out on open-type frame filter presses, as a result of which splashing of the native solution may occur. Manual unloading of filter presses exposes workers to culture fluid containing antibiotics.

The next step in obtaining an antibiotic is isolation and chemical purification. At this stage, the antibiotic solution is concentrated and purified to such a purity that it can be used to obtain a finished drug product. The content of the antibiotic in the native solution is very low, so its isolation in its pure form, purification and bringing to the finished dosage form is a very complex and time-consuming process: for example, to obtain 1 kg of an antibiotic, about 600 liters of culture fluid must be processed.

For the isolation and chemical purification of antibiotics, one of the following methods is used: 1) extraction method using various solvents; 2) deposition method; 3) ion exchange method. Extraction and ion-exchange methods have found the widest application in the biosynthesis of antibiotics, and in recent years, the ion-exchange method for isolating and purifying antibiotics has also been used in the preparation of other drugs. Its main advantage is that it eliminates the need to use toxic and explosive solvents. The method is economically beneficial, since its technology is simple and does not require expensive equipment and raw materials.

Pasty products obtained in the process of chemical cleaning are further dried and screened. The drying process in the production of antibiotics plays an extremely important role, since the quality of the products depends on its organization. Thermostable antibiotics, obtained in crystalline form with a low moisture content, are usually dried in vacuum ovens. Antibiotics obtained after chemical purification in the form of aqueous concentrates are dried in evaporative-drying units and vacuum-freeze dryers (Fig. 11.2). These processes must be carried out under sterile conditions.

The main disadvantage of working in drying departments is the use of manual labor when loading and unloading products. The performance of these operations, as well as the need to mix the powdered mass and control the technological mode of operation of the drying units, are associated with the possibility of contact of antibiotics working with dust. Insufficient sealing of drying units contributes to the release of some toxic substances into the air of industrial premises, the residual amounts of which may be contained in antibiotics. For example, the finished chlortetracycline may contain an admixture of methanol, tetracycline - isooctyl alcohol, tetracycline and oxy-tetracycline hydrochloride - p-butanol and hydrochloric acid.

Sterile dried antibiotics are packaged in sterile glass vials. Dosing of dry antibiotic into vials, capping, capping and running-in are performed on automatic machines. In some cases, semiautomatic devices "Technologist" are used for this, in which only the process of filling vials is automated. The rest of the operations are carried out manually, and therefore the air of industrial premises may be contaminated with antibiotic dust, and with the simultaneous packaging of two or more of their types, workers may be exposed to the combined effects of these products.

For oral administration, antibiotics are available in the form of tablets and dragees. The tableting process is as follows: all components included in the mixture - antibiotics, fillers (powdered sugar, calcium stearate, talc, etc.) are loaded into the mixer, mixed and moistened with a mixture of sugar syrup, gelatin solution, hydrochloric acid and ethyl alcohol. Then the mass is granulated and sent for drying, which is usually carried out in calorific dryers. After drying, the granulate is powdered with a mixture of talc, calcium stearate and starch to increase flowability, and then pressed on rotary tablet machines and packed into convales.

From a hygienic point of view, the tableting process is characterized by intermittency, lack of tightness and a large number of manual operations. Due to these reasons, the antibiotic can be released into the air during almost all tableting operations.

At the stages of pre-treatment and filtration, workers come into contact with vapors of oxalic and acetic acids. Manual operations often lead to contamination of the skin and overalls with culture fluid and native antibiotic solution.

The processes of isolation and chemical purification of the antibiotic, carried out by extraction and precipitation methods, are associated with the possibility of exposure to the body of working vapors and gases of butyl, isopropyl and methyl alcohols, butylacetate, oxalic, acetic, sulfuric and hydrochloric acids and other substances used in this stage . The concentrations of these substances in the air in some cases may exceed the maximum allowable. The main causes of air pollution of the working area with harmful substances are insufficient tightness of the equipment, the presence of manual operations, low efficiency of ventilation devices, etc.

At the final stages, as studies show, the processes of drying, screening, tableting, packaging and packaging of antibiotics can be accompanied by significant environmental pollution with fine dust of finished products. In addition, workers in the preparatory workshops, drying department, fermentation, in addition to the chemical factor, can simultaneously be exposed to excess heat, the main source of which is inoculators, fermenters, drying units, as well as the surfaces of communication networks in case of their insufficient thermal insulation.

The most common and characteristic symptoms when exposed to antibiotics are complications from the gastrointestinal tract: lack of appetite, nausea, flatulence, and abdominal pain. A significant group of complications are liver damage, impaired function of the kidneys, cardiovascular and nervous systems.

At present, significant material has been accumulated on the effect of antibiotics on the blood system: the development of anemia, agranulocytosis, leukopenia, and impaired vitamin metabolism.

Changes in the upper respiratory tract are expressed in the development of hyperemia and atrophy of the mucous membranes, mainly of the nose and larynx. As the disease progresses, it can be complicated by asthmatic bronchitis and bronchial asthma. One of the manifestations of the side effects of antibiotics is dysbacteriosis - a violation of the normal microflora of the body. Workers in the production of antibiotics have secondary mycoses (more often candida - goats), changes in the gastrointestinal tract and upper respiratory tract, which developed against the background of dysbacteriosis of the mucous membranes, as well as suppression of natural immunity factors. The workers had constipation, diarrhea, flatulence, erosion and ulcers of the rectal mucosa. The detected changes in the state of health to a certain extent resemble the manifestations of the side effects of antibiotics in the conditions of their clinical use.

Along with this, workers have an increased incidence of influenza, SARS and diseases of the female genital area.

Preventive measures in the production of antibiotics should be aimed primarily at combating the release of harmful substances into the air of the working area. To this end, in the complex of recreational activities, it is necessary to provide for the automation and mechanization of technological processes, the effective operation of general and local ventilation, and compliance with the technological regime. This not only eliminates the effect on workers of released harmful substances, but also eliminates the adverse effects of meteorological factors.

Particular attention in the fight against air pollution by harmful substances should be given to sealing technological equipment and communications, mechanization of processes and operations for loading, unloading and transporting raw materials, semi-finished products and finished products.

In the production of antibiotics, therapeutic and preventive measures are also important. These primarily include the organization and conduct of preliminary and periodic medical examinations. Employment in the preparatory, reactor, drying and other departments should be carried out taking into account the contraindications provided for work in contact with the hazards present in these departments. Conducting periodic medical examinations is aimed at timely detection of possible occupational diseases. In order to prevent allergization of the body and the skin-irritating effect of chemicals, it is recommended to carry out preventive desensitization, the use of protective ointments (for example, 2% salicylic), detergents, etc.

The organization of a proper diet and rest is important in preventing diseases and strengthening the state of health. It is recommended to issue lactic acid colibacterin to prevent dyspeptic disorders in workers, as well as enrichment of food rations with vitamins A, B, PP, C. It is necessary to strictly observe the rules of personal hygiene - wash hands after each manipulation with antibiotics, wash in the shower and change clothes after work. In addition, those working in the production of antibiotics should be provided with rational work clothes, underwear, shoes, gloves and mittens, anti-dust respirators such as "Petal-5", "Petal-40", goggles.

The production of synthetic chemical-pharmaceutical preparations is usually located in 1-2-3-storey industrial buildings with side lighting. Cases with top or combined side and top light are very rare.

The organic synthesis of drugs in terms of the accuracy of the operations performed is mainly rough work (the size of the object of distinction is more than 10 mm) or, less often, work of low accuracy (the size of the object is from 1 to 10 mm), and therefore the KEO values for them are relatively small and should be 0.5% or, more rarely, 1% (only laboratory premises KEO should be equal to 1.5%). However, in these workshops, both on the floor and on the working platforms, there is always a significant amount of equipment installed, which, due to its large size, prevents access to daylight into the working rooms. Therefore, in such industries, natural light alone can be limited only on bright days.

Artificial lighting of the main working premises of the chemical-pharmaceutical industry should be carried out mainly by incandescent lamps, and the most appropriate lighting system should be considered a general one. Fluorescent light lighting systems can also be used, which are most appropriate for use in chemical laboratories, as well as in packaging shops. When choosing the type of luminaire, consider the conditions external environment in industrial premises: in case of high humidity and dustiness in the premises, the use of moisture-proof and dust-proof lamps is mandatory. Local lamps in the combined light system are used relatively rarely, mainly for lighting instrumentation. At repair work inside the apparatus, hand-held portable lamps should be used.

In accordance with the requirements of sanitary regulations, the minimum illumination should be 30 lux in chemical workshops (at a level of 0.8 m from the floor), 150 lux on control and measuring devices, 50 lux in packing shops (when packing in large containers), and in chemical laboratories on tables at least 150 lux.

Along with general measures, all workers involved in the organic synthesis of drugs must be provided with personal protective equipment. The issued overalls must correspond to the nature of the influencing harmful factors and the production environment. To protect the respiratory organs from harmful vapors and gases, each worker is given an individual filtering gas mask with a mask corresponding to the size of the face. The type of gas mask must correspond to the nature of toxic impurities that can be released into the air of working premises (from organic vapors, acid gases, etc.). In addition, the workshop should have a sufficient supply of hose gas masks, which should be used in the elimination of accidents accompanied by high gas contamination of the premises. Hose gas masks are also necessary when working inside devices in which reactions with highly toxic substances occur (for example, when cleaning them internally). To protect against splashes of acids, alkalis and other caustic products, it is necessary to provide workers with safety goggles, and to protect against inhalation of medicinal and other dust - anti-dust respirators.

At enterprises producing synthetic medicines, a complex of sanitary facilities (showers, changing rooms, toilets, as well as rooms for repair, decontamination, drying and dedusting of overalls) is provided. If work is being done with highly toxic substances, then this complex of sanitary facilities should include a sanitary inspection room.

An important preventive measure is the removal of contaminants from the skin. In some cases, when the usual method of handwashing fails to remove contamination, special detergents should be used. These include a mixture of soda and calcium hypochlorite, 30 parts each in 940 parts of water; a mixture of 3% potassium permanganate solution with 10% calcium hypochlorite solution and a number of others.

Finally, it should be pointed out that all entering the enterprises for the production of synthetic chemical-pharmaceutical preparations must pass a preliminary medical checkup and for workers dealing with harmful substances, periodic medical examinations are also mandatory.

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Another reason for unfavorable working conditions may be violations of the tightness of operating devices and communications, insufficient availability of hermetic equipment and closed equipment. The use in the synthesis of various complex chemical reactions occurring with the release of toxic vapors and gases requires good tightness of reactors and other equipment. Particularly vulnerable areas are stuffing box seals on apparatus with agitators, butt joints and couplings on communications. It is in these places, especially when working on devices operating under pressure, that emergency breakthroughs of gases and liquids can occur. With open drains of products during reloading from apparatus to apparatus, as well as into containers, onto filters, etc., evaporation surfaces increase sharply, which is especially unfavorable when working with volatile products that easily emit vapors and gases.

The reasons for the occurrence of harmful factors also include cases of violation of the technological mode of operation of the apparatus (failure to comply with the required temperature and pressure, untimely release of vapors and gases formed through the air valves, overheating of the reaction mass, etc.), which most often occur due to insufficient use of automatic control over the course of the technological process.

Finally, disruptions in operation and insufficient efficiency of ventilation systems can play a significant role in creating an unfavorable sanitary working environment at chemical-pharmaceutical plants. Insufficient supervision of ventilation units leads to a significant reduction in their performance, and therefore they can no longer perform their task.

The decrease in the efficiency of ventilation is most often manifested with an increase in production capacity. In this case, there is both an increase in the amount of processed substances per apparatus, and an increase in the number of apparatuses in the same production areas. As a result, there is an additional to the usual entry into the air harmful impurities, for the removal of which ventilation unit did not count.

The general basis for the improvement of working conditions at all enterprises for the production and production of chemical-pharmaceuticals and antibiotics is the elimination of the above causes of unfavorable working conditions. However, any plant from all the indicated groups of enterprises of the chemical-pharmaceutical industry has its own characteristics that require a number of other measures of a more private nature.

The synthetic drug industry produces several hundred different drugs, which can be grouped into six groups:

1. Inorganic medicinal substances (preparations of bromine, iodine, potassium permanganate).

2. Medicinal compounds of the aliphatic series (alcohols, ethers, aldehydes, aldehyde acids, carboxylic acids, aliphatic amines, amino acids, etc.).

3. Medicinal compounds of the alicyclic series (terpenoids, vitamins A, K, P, E, D, hormones, blood plasma substitutes).

4. Aromatic medicinal compounds (phenols and their derivatives, aromatic carboxylic acids and their derivatives, sulfanilamide preparations, derivatives of aromatic sulfonic acids).

5. Organoelement medicinal substances (organic compounds of arsenic, antimony, bismuth, mercury, phosphorus, radiopaque agents).

6. Medicinal compounds of the heterocyclic series (derivatives of five- and six-membered heterocycles with one or two heteroatoms).

Distillation products are used as raw materials for synthetic medicines. hard coal, oil and other substances, the number of which is many hundreds of items. These are a variety of organic and inorganic chemicals that are in liquid, solid and gaseous states. From them, through complex technological processing, organic semi-products are obtained, which are predominantly aromatic, less often heterocyclic and aliphatic compounds, mainly various aromatic amines and nitro compounds, phenols and naphthols, their sulfonic acids and halogenated.

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