The topic of occupational hygiene in pharmacies. Measures to improve working conditions Labor hygiene at pharmaceutical industry enterprises

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1. Occupational health in the chemical and pharmaceutical industry

4. Occupational health in the production of antibiotics

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

9. Hygienic characteristics of working conditions in the manufacture of tablets

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

Conclusion

List of references

1. LABOR HYGIENE IN THE CHEMICAL AND PHARMACEUTICAL INDUSTRY

labor protection medicine production

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

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 preparations intended for subcutaneous, intramuscular injections and intravenous infusions, they provide complete sterility. Their quality must strictly comply with the requirements of the State Pharmacopoeia of Russia.

Another feature of the chemical and pharmaceutical industry is the small volume of production of most drugs.

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

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

2. Hygienic characteristics of the main technological processes

There are several groups of enterprises in the chemical and pharmaceutical industry. The leading ones are factories for the production 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 drugs is based on the widespread use of organic synthesis, which brings these enterprises closer to the basic chemistry industry.

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 pharmaceutical 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, plasters, etc.

In the industrial production of chemical and pharmaceutical preparations, a variety of raw materials are widely used, obtained both from plant and animal products, and by chemical synthesis. The most common are 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 lot of mineral acids and alkalis are used. The initial organic raw materials are supplied by the by-product coke, petrochemical, aniline-paint industry and enterprises of basic organic synthesis.

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

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

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

The processes of 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, filled and packaged.

Preparatory operations. A significant part of the feedstock for the production of galenic and synthetic drugs is in a solid state and is subjected to crushing and grinding. The need for this operation often arises when receiving dosage forms (tablets, pills, 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 a medicinal product are ground in mortars on a mechanical drive, in Islamgulov, Excelsior and others mills.

Dust, intense noise and general vibration are occupational hazards in crushing, grinding and separating the starting drug products. Dust is emitted at the place where the medicinal raw material or finished product enters the crushers and mills and at the place where the crushed substance exits.

A hygienically unfavorable operation is the separation of materials into fractions. Air separators and mechanical screens used here are significant sources of dust emission. In the production of low-tonnage drugs (for example, hormonal drugs), manual wiping on sieves is often used, which is associated with the emission of dust and contamination of the skin and overalls of workers.

To combat the emission of dust, the correct organization of the technological process and equipment, the shelter of places where dust is generated with aspiration of dusty air are required. Since noise and vibration at crushing and grinding plants can exceed the permissible values, this equipment must be placed in separate production rooms, and the foundations under them should not be associated 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 crushing and crushing processes remotely.

Transportation of the initial components has a significant impact on the level of air pollution in 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 intended for the movement of 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 hazardous substances. In some cases, manual transportation, loading and unloading of medicinal raw materials (for example, of plant origin) are still used.

The movement of liquid substances is carried out through pipelines using pumps, air or steam pressure, gravity and due to vacuum. Gaseous substances are transported using compression and vacuum. The supply of initial 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 using a vacuum. The main hygienic requirements for equipment are the resistance of pipelines, cushioning and packing material to the action of liquids, replacement of stuffing box pumps with non-gland and submersible pumps.

The supply of solid medicinal raw materials (products of plant origin, organic and mineral substances) from raw materials warehouses to preparatory shops, from one equipment to another is carried out using belt conveyors, elevators, augers, as well as pneumatic and hydraulic systems. The method of transportation is determined by the state of aggregation 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, augers, etc. is associated with significant dust emission. The most perfect in terms of hygiene is the supply of dry raw materials using pneumatic transport.

The actual processes of obtaining medicinal substances.

This technological stage of drug production is characterized by a wide variety of technological processes and operations, equipment and chemicals used. A significant proportion in the industrial synthesis of intermediates and medicinal substances is occupied by processes associated with the reactions of substitution of hydrogen atoms in the nucleus of aromatic compounds with certain groups of atoms, the transformation of substituents already present in the molecule of an organic compound into others in order to impart new properties to it and, finally, a change carbon structure of the molecule. These are 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 elevated and normal atmospheric pressure or under vacuum. They can be of periodic or continuous action. These are steel, lead or cast iron containers 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 chemicallyth. Places of release of toxic substances from reactors can be glands of mixers, hatches through which loading and unloading of products, measuring glasses, viewing windows, flange connections are made. 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 the obtained medicinal intermediate or finished drug, the operating mode and other factors. Unfavorable hygienic conditions can be caused by manual operations, for example, when measuring the level of liquids, taking samples. The transfer of equipment to the 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 specific weight at this stage is occupied by the processes of separation of chemical components. The main equipment for carrying out such operations is the distillation apparatus and rectification plants. 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 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, and leaf filters, and the latter include drum, disc and belt filters. The operation of nutch filters and filter presses is often accompanied by the release of toxic substances into the air of the working area, is associated with the use of manual labor and the possibility of intensive contamination of the skin and workwear. From a hygienic point of view, drum filters are more favorable, which are hermetically sealed and equipped with exhaust ventilation.

For the rapid separation of the medicinal intermediate, centrifuges of periodic and continuous action are used. Batch centrifuges are less perfect and have a number of disadvantages, the main ones being the inconvenience of removing the squeezed material, the use of manual labor, and the lack of reliable tightness. These disadvantages are the reason for the release of harmful substances into the air of the working area and contamination of the skin.

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

A significant part of intermediates and finished pharmaceuticals is dried. This process is necessary for the production of galenic, synthetic drugs, antibiotics, vitamins, etc. Moisture is removed by mechanical (filtration, pressing, centrifugation), physicochemical (absorption of hygroscopic materials) and thermal (evaporation, evaporation and condensation) methods.

In the production of pharmaceuticals, chamber, drum, spray, shaft and other dryers are most widely used. Maintenance work for 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 loading and unloading processes of substances being dried, which causes air pollution in the working area with the dust of the finished product. Significantly less harmful substances are emitted when using continuous dryers (rake, spray, drying drums, etc.), provided with complete sealing and mechanization of loading and unloading processes.

Evaporation and crystallization processes are widespread in the production of pharmaceuticals. The former are used to obtain more concentrated solutions from less concentrated ones (synthetic and galenic preparations, antibiotics, vitamins, etc.). For this purpose, in most cases, multi-shell evaporators are used. Unfavorable hygienic 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 loading and unloading of medicinal substances.

More favorable sanitary conditions in the workplace are created when servicing 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. At the final stage of the technological process, medicinal substances undergo labeling, packaging and packaging. Packaging of dosage forms is made in plastic, paper and glass containers. Most of the operations at this stage are mechanized.

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

Work with a semi-mechanized and especially manual method of filling and packaging tablets, ampoules, dragees, as well as sealing boxes and convalues \u200b\u200bwith cellophane strips and a number of other operations are associated with a forced position of the body.

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

1. The chemical factor. Studies show that the main unfavorable operating factor of the working 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 the preparatory, main and final operations. The main reasons for the content of harmful substances in the air of industrial premises are imperfection of equipment, violation of technological regimes, absence or insufficient mechanization of many operations associated with the transportation, loading and unloading of materials from the apparatus, the use of leaky equipment, overflow of chemical products when filling the apparatus, etc.

The composition of air pollutants in the working area in most drug manufacturing facilities 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 obtained medicinal product, the air of the production premises can be polluted with the initial, intermediate and finished products of chemical synthesis. In this case, 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 of obtaining a medicinal product, and final operations. At the same time, the severity and nature of the effect of the chemical factor on the organism of workers are determined by the perfection of technology and equipment, the formulation of the medicinal substance, as well as the construction and planning solutions 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 methods of transporting 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 to eliminate labor-intensive and dangerous manual operations.

The level of air pollution with vapors and gases of harmful substances is greatly influenced by the magnitude of pressure in devices and communication networks. From a hygienic point of view, the most favorable conditions are created during the synthesis of medicinal products 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 recovery.

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

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

As shown by special time-keeping observations, the operator during the production of sulfanilamide preparations on average 10-12% of the working time is in conditions of an increased content of harmful substances in the air. The highest levels of contamination by chemical substances are noted at the time of the breach of the tightness of the technological equipment, for example, at the stage of hydrolysis of phenylhydrazine sulfate in the production of amidopyrine during the selection through the open hatch of the apparatus, the concentration of sulfur dioxide can be 4 times higher than the MPC.

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

Thus, a significant amount of dust is observed at workplaces when grinding plant materials, crushing the initial components of synthetic products. In this case, the dust level can be 3-5 times higher than the permissible one.

At the final stage of drug production, the most often high levels of air pollution by the dust of the finished drug, several times higher than the permissible ones, are observed in the process of tableting, panning, drying, grinding, sifting mixtures, filling and packaging finished drugs. Under these conditions, medicinal dust should be considered as industrial and considered an 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 permissible values. So, during
manual filling 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 are largely determined by its dispersion. The dust of some drugs consists of 85-98% particles less than 5 microns in size, which facilitates the penetration of a large amount of drugs into the body through the respiratory tract and digestive organs (with saliva).

3. Microclimate. At 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 in case of insufficient thermal insulation of the heated surfaces of devices and communication heating networks, it is possible to influence those working simultaneously with a chemical factor and a microclimate. Elevated air temperatures are found mainly in drying rooms and apparatus in which the reaction proceeds with the release of heat or at high temperatures (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 certain workplaces of the chemical and pharmaceutical industry is an additional factor that aggravates the effect of the chemical factor.

4. Noise. Many technological devices are the source of industrial noise in the workplace during the manufacture of medicines. These include compressors, vacuum filters, drum dryers, centrifuges, crushers, vibrating screens, vacuum pumps, etc. The noise level in some cases may exceed the permissible level. So, at workstations near centrifuges, noise parameters can exceed the permissible values \u200b\u200bby 5 dB, for 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 \u200b\u200bby 20-25 dB. It should be noted that industrial noise, even at an acceptable level, can aggravate the adverse effect of chemicals.

4. LABOR HYGIENE IN THE PRODUCTION OF ANTIBIOTICS

Antibiotics are substances produced by microorganisms, higher plants and animal tissues in the process of vital activity and possessing 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 industries for preserving food.

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) pretreatment of the culture fluid;

c) filtration;

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

e) manufacturing of finished dosage forms;

f) packing and packaging

At the heart of the initial technological processes is the cultivation of seed material (producer) in flasks and fermenters. The grown production strain of the producer for the purpose of its further enrichment is transferred into special apparatus - 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, and devices for mixing the production mass. Then the producer goes to fermentation. Fermentation is understood to mean the cultivation (cultivation) 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 basic technological scheme of antibiotic extraction and purification.

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 sterile air mixture, stirrers, as well as devices for loading and unloading the culture medium and culture liquid. 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 liquid, to increase the concentration, as well as more complete precipitation of impurities, the culture liquid is acidified to pH 1.5-2.0 with oxalic acid or a mixture of oxalic and hydrochloric acids ... The treated culture fluid is filtered from mycelium and precipitated ballast substances to obtain a clear filtrate, called the native solution. Filtration of the treated culture fluid is carried out on open frame filter presses, as a result of which the native solution can be sprayed. Manual unloading of filter presses brings workers into contact with the culture liquid containing the antibiotic.

The next stage of antibiotic production is isolation and chemical purification. At this stage, the antibiotic solution is concentrated and purified to such a purity that a finished medicinal product can be obtained from it. The content of the antibiotic in the native solution is very low; therefore, its isolation in pure form, purification and bringing to the finished dosage form is a very complex and laborious process: for example, to obtain 1 kg of an antibiotic, about 600 liters of culture liquid must be processed.

For the isolation and chemical purification of antibiotics, one of the following methods is used: extraction method using various solvents; deposition 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 the isolation and purification of antibiotics has also been used in the production 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.

Extraction of antibiotics from the native solution is carried out in extractors-separators, the main disadvantage of which is the need for manual unloading, as a result of which the air in the shops may be polluted with solvents, for example, isooctanol during the production of tetracycline and oxytetracycline.

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

The method of ionic sorption consists in the fact that the native solution is fed by means of centrifugal pumps into a 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 ammonia-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 excludes contact of workers with concentrated solutions and antibiotic sediments. This method does not use toxic organic solvents.

The pasty products obtained in the process of chemical cleaning are further dried and sieved. 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 drying ovens. Antibiotics obtained after chemical treatment in the form of aqueous concentrates are dried in evaporation-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 implementation of these operations, as well as the need for mixing the powdery mass and monitoring 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, 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 hydroxy-tetracycline hydrochlorides - n-butanol and hydrochloric acid.

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

Working conditions in the production of antibiotics are characterized by the possible intake of highly dispersed dust of antibiotics, vapors and gases, chemicals used in the technological process, and the release of excess heat into the air. 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 pretreatment 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 the methods of extraction and precipitation, are associated with the possibility of exposure to the body of 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 concentration of these substances in the air in some cases may exceed the maximum permissible. The main reasons for air pollution in the working area with harmful substances are insufficient tightness of equipment, the presence of manual operations, low efficiency of ventilation devices, etc.

At the final stages, as studies show, the processes of drying, sieving, tableting, filling and packaging of antibiotics can be accompanied by significant environmental pollution with fine dust of finished products. In addition, workers in the preparatory shops, 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, increased fatigue, pain and dry throat. In some cases (for example, when exposed to streptomycin), workers also note hearing loss and pain in the heart.

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 renal function, cardiovascular and nervous systems.

Currently, 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 lesions of the skin and respiratory organs. Allergy occurs both by inhalation and by contact with the skin. The development of skin sensitization is facilitated by the violation of the integrity of the skin. Positive allergenic tests, for example, for penicillin, were detected in 18% of those working with the antibiotic, for streptomycin - in 18.5%, for both antibiotics with combined action - in 47%. People who are in constant contact with antibiotics most often (50%) develop dermatitis, eczema, urticaria, localized mainly on the hands, forearms, and face. These changes are most often registered in workers with over 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, it is possible to develop acute or subacute recurrent dermatitis, 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. With the progression of the disease, asthmoid bronchitis and bronchial asthma can be complicated. One of the manifestations of the side effects of antibiotics is dysbiosis - a violation of the normal microflora of the body. Those working in the production of antibiotics have secondary mycoses (often candidiasis), changes in the gastrointestinal tract and upper respiratory tract, which developed against the background of dysbiosis of the mucous membranes, as well as inhibition of natural immunity factors. The workers observed 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, acute respiratory viral infections 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. For this purpose, 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 makes it possible to eliminate the effect on the working of the emitted harmful substances, but also to exclude the unfavorable influence of meteorological factors.

Particular attention in the fight against air pollution with harmful substances should be paid to the sealing of 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 taken 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 / m, 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 (by the content of chlortetracycline in the air) - 0.1 mg / m3, oleandomycin - 0.4 mg / m3, phytobacterin - 0.1 mg / m3.

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

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

The organization of a proper diet and rest is of great importance in preventing diseases and strengthening the state of health. It is recommended to issue lactic acid colibacterin for the prevention of 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 your 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, linen, footwear, gloves and mittens, anti-dust respirators such as "Petal-5", "Petal-40", and goggles.

6. LABOR HYGIENE IN THE PRODUCTION OF GALENIC PREPARATIONS AND FINISHED MEDICINAL FORMS

The pharmaceutical industry unites enterprises for the production of galenic, novogalenic drugs, as well as finished dosage forms (pelleting, ampouling, tableting, etc.). The enterprises of this industry produce galenic and novogalenic preparations, such dosage forms as tinctures, liquid and dry extracts, syrups, solutions, drops, tablets, plasters. A large amount of work falls on the weighing, mixing, crushing and packaging of pharmaceuticals, completing first-aid kits, etc. The technological process is built according to the shop principle and includes such main shops as galenic, ampoule, tablet, filling, dragee, etc.

A variety of substances of plant, animal and mineral origin are used as the initial medicinal raw material 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 basic technological and auxiliary operations. These industries often operate according to a combined technological scheme, that is, the equipment is arranged and placed in such a way that it would be possible to obtain various medicinal products, similar in terms of the technological manufacturing regulations.

7. Hygienic characteristics of working conditions in the manufacture of phytopreparations

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 leakage of the equipment and low ventilation efficiency, the workers may be exposed to vapors of extractants (dichloroethane, ethers, alcohols, etc.). Operations to grind fresh medicinal herbs should be considered as unfavorable in hygienic terms, since at this moment droplets of their juice and small particles can enter the respiratory system, on the skin from the covered parts of the body (hands, face), while providing skin-irritating and a sensitizing effect.

Dried herbal preparations include tinctures and extracts.

Tinctures are alcohol or alcohol ester 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 extracts.

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

a) extraction of dry plant materials;

b) separation of the liquid phase from the solid by settling, filtration, centrifugation and pressing;

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

There are many ways to extract. In general, they can be classified into static and dynamic.

From a hygienic point of view, the most progressive methods are dynamic extraction, which is based on a constant change of the 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 drying the dry extract in a spray dryer.

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

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

The production 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 of 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 vapor content in the air of the working area exceeded the MPC.

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

The nature and severity of the effect of the chemical factor on the workers in the galenic shops is determined by the perfection of the technological equipment used, the composition of the medicinal raw materials, as well as the construction 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 galenic and novogalenic preparations, and the processes of loading, unloading and transportation of 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, violation of the tightness of equipment and communications, the use of manual labor, the presence of open surfaces, intermittent technological processes, imperfection of ventilation devices are one of the reasons for the high content of harmful substances in the air of the working area, 2-5 times or more exceeding the MPC.

The most important health-improving event 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 is essential in improving working conditions. First of all, it is necessary to equip local exhaust devices near crushers, vibrating screens, places of loading and unloading raw materials, auxiliary ingredients, etc.

Planning solutions for galenic shops, taking into account the emission of harmful substances and sources of noise, play an exceptionally important role in ensuring normal working conditions. Personal protective equipment is of great importance in preventing the harmful effects of production factors. Workers serving crushers, mills, sieves, auger and belt conveyors and other technological equipment must be provided with overalls, goggles of type 03-N, 03-K, gloves, respirators of the type ShB-1. In addition, apparatchiks in contact with organic extractants must have gas masks with a filter box of grade A.

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

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

Manufacturing of ampoules. It is produced in the department of the ampoule shop using special devices (automatic or semi-automatic). Ampoules are made of long, chemically resistant glass tubes - drots. First, the dart is washed, and then reinforced on carousel semiautomatic devices or automatic machines, where ampoules are obtained from it using gas burners. At the subsequent stages, ampoules with open capillaries are washed in vacuum semiautomatic devices. Ultrasonic treatment of ampoules has been widely used in recent years for more efficient cleaning. The washed ampoules are dried with hot air in drying ovens and then transported to the ampoule filling sections.

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

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

Solution preparation and ampulation. 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. The treatment of water for injection is carried out on high-performance distillers that ensure its appropriate quality, including pyrogen-freeness.

Ampulation is performed using a syringe or vacuum method: at the first, 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 of it.

Filling ampoules with a medicinal substance requires perfect cleanliness, therefore, especially strict sanitary and hygienic requirements are imposed on technological operations, layout, 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. To a greater extent, these requirements are met by coating it with a polymeric material (PVC tiles, relin, etc.). An important point is air purification (filtration) and its disinfection using germicidal lamps. It is necessary to systematically wet cleaning the room.

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In our country, in a short time, a new branch of the chemical and 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 the overall structure of the medical industry is 18%.

In addition to being used in medicine, antibiotics have found application in the food and meat and dairy industries for preserving food. They are added to animal and bird feed to increase the rate of weight gain.,

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

b) preliminary treatment of the culture fluid; c) filtration; d) isolation and chemical purification (extraction method, ion exchange method, precipitation method); e) manufacturing of finished dosage forms; f) packing and packaging (Figure 11.1).

At the heart of the initial technological processes is the cultivation of seed material (producer) in flasks and fermenters. The grown production strain of the producer for the purpose of its further enrichment is transferred to special apparatus - 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, and devices for mixing the production mass. Then the producer goes to fermentation. Fermentation is understood to mean the cultivation (cultivation) 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 liquid, in order to increase the concentration, as well as more complete precipitation of impurities, the culture liquid is acidified to pH 1.5-2.0 with oxalic or a mixture of oxalic and hydrochloric acids. The treated culture fluid is filtered from mycelium and precipitated ballast substances to obtain a clear filtrate, called the native solution. Filtration of the treated culture fluid is carried out on open frame filter presses, as a result of which the native solution can be sprayed. Manual unloading of filter presses brings workers into contact with the culture liquid containing the antibiotic.

The next stage of antibiotic production is isolation and chemical purification. At this stage, the antibiotic solution is concentrated and purified to such a purity that a finished medicinal product can be obtained from it. The content of the antibiotic in the native solution is very low; therefore, its isolation in pure form, purification and bringing to the finished dosage form is a very complex and laborious process: for example, to obtain 1 kg of antibiotic, about 600 liters of culture liquid must be processed.

For the isolation and chemical purification of antibiotics, one of the following methods is used: 1) the method of extraction 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 the isolation and purification of antibiotics has also been used in the production 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 extractors-separators, the main disadvantage of which is the need for manual unloading, as a result of which the air in the shops can be polluted with solvents, for example, isooctanol in the production of tetracycline and oxy-tetracycline.

The pasty products obtained in the process of chemical cleaning are further dried and sieved. 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 drying ovens. Antibiotics obtained after chemical purification in the form of aqueous concentrates are dried in evaporation-drying units and vacuum-freeze dryers (Figure 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 implementation of these operations, as well as the need for mixing the powdery mass and monitoring 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, 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 hydroxy - tetracycline hydrochlorides - 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 machines. In some cases, for this purpose, semi-automatic machines "Technologist" are used, in which only the process of filling the bottles is automated. The rest of the operations are carried out manually, in connection with which the air pollution of industrial premises with antibiotic dust is possible, and with the simultaneous packing of two types of them or more, workers may be exposed to the combined effect of these products.

For oral administration, antibiotics are available in the form of tablets and pills. The tableting process is as follows: all the components included in the mixture - antibiotics, fillers (powdered sugar, calcium stearate, talc, etc.) are loaded into a mixer, mixed and moistened with a mixture of sugar syrup, a solution of gelatin, hydrochloric acid and ethyl alcohol. Then the mass is granulated and sent to drying, which is usually carried out in hot-air 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 in concurrency.

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

The processes of isolation and chemical purification of the antibiotic, carried out by the methods of extraction and precipitation, are associated with the possibility of exposure of the body to 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 concentration of these substances in the air in some cases may exceed the maximum permissible. The main reasons for air pollution in the working area with harmful substances are insufficient tightness of equipment, the presence of manual operations, low efficiency of ventilation devices, etc.

At the final stages, as studies show, the processes of drying, sieving, tableting, filling and packaging of antibiotics can be accompanied by significant environmental pollution with fine dust of finished products. In addition, workers in 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.

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

Antibiotics should be attributed to the group of so-called allergens, the sensitizing effect of which is manifested mainly in the lesions of the skin and respiratory organs. Allergy occurs both by inhalation and by contact with the skin. The development of skin sensitization is facilitated by 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 a combined effect - in 47%. People who are in constant contact with antibiotics most often (50%) develop dermatitis, eczema, urticaria, localized mainly on the hands, forearms, and face. These changes are most often registered in workers with over 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, it is possible to develop acute or subacute recurrent dermatitis, 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. With the progression of the disease, asthmoid bronchitis and bronchial asthma can be complicated. One of the manifestations of the side effects of antibiotics is dysbiosis - a violation of the normal microflora of the body. Those working in the production of antibiotics are found to have secondary mycoses (more often candidiasis - goats), changes in the gastrointestinal tract and upper respiratory tract, which developed against the background of dysbiosis of the mucous membranes, as well as inhibition of natural immunity factors. The workers observed 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, acute respiratory viral infections and diseases of the female genital area.

An important place in the prevention of the harmful effects of chemical factors should be taken 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. At present, MPCs have been established for the following antibiotics: streptomycin - 0.1 mg / m, 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 (by the content of chlortetracycline in the air) - 0.1 mg / m3, oleandomycin - 0.4 mg / m3, phytobacterin - 0.1 mg / m3 ...

In the production of antibiotics, therapeutic and prophylactic 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 working in contact with the hazards present in these departments. Periodic medical examinations are aimed at timely detection of possible occupational diseases. In order to prevent allergization of the body and skin irritating effect of chemicals, it is recommended to carry out prophylactic desensitization, use of protective ointments (for example, 2% salicylic ointment), detergents, etc.

The organization of a proper diet and rest is of great importance in preventing diseases and strengthening the state of health. It is recommended that lactic acid colibacterin be dispensed for the prevention of dyspeptic disorders in workers, as well as enrichment of food rations with vitamins A, B, PP, C. Personal hygiene rules must be strictly observed - wash hands after each antibiotic manipulation, shower and change clothes after work. In addition, those working in the production of antibiotics should be provided with rational work clothes, linen, footwear, gloves and mittens, anti-dust respirators such as "Petal-5", "Petal-40", and goggles.

The production of synthetic chemical pharmaceuticals is usually located in 1-2-3-storey production buildings with side lights. Cases with top or combined side and top lights are very rare.

In terms of the accuracy of the operations performed, the organic synthesis of drugs is mainly rough work (the size of the object of discrimination 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 values \u200b\u200bof KEO for them are relatively small and should be 0.5% or, less often, 1% (only in laboratory premises, KEO should be equal to 1.5%). However, in these workshops, both on the floor and on the work sites, a significant amount of equipment is always installed, which, due to its large size, prevents access to daylight in the work areas. Therefore, in such industries, natural light can be limited only on bright days.

Artificial lighting of the main working rooms of the chemical and pharmaceutical industry should be carried out mainly with incandescent lamps, and the general lighting system should be considered the most appropriate. Also, fluorescent lighting installations can be used, which are most expedient to use in chemical laboratories, as well as in filling shops. When choosing the type of luminaire, one should take into account the environmental conditions in industrial premises: in the case of high humidity and dustiness in the premises, it is necessary to use moisture-proof and dust-proof lamps. Local luminaires in a combined lighting system are used relatively rarely, mainly for lighting control and measuring devices. Hand-held portable lamps should be used for repair work inside the apparatus.

In accordance with the requirements of sanitary rules, the minimum illumination should be 30 lux in chemical shops (at the level of 0.8 m from the floor), on measuring instruments 150 lux, in filling shops (when filling in large containers) 50 lux, in chemical laboratories on tables not less than 150 lux.

Along with the 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 working environment. To protect the respiratory system from harmful vapors and gases, each worker is given an individual filtering gas mask with a mask that matches the size of the face. The type of gas mask must correspond to the nature of the poisonous impurities that can be released into the air of working rooms (from organic vapors, acid gases, etc.). In addition, the shop must have a sufficient supply of hose gas masks, which should be used in the elimination of accidents accompanied by high gas content in the premises. Hose gas masks are also required 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 corrosive products, it is necessary to provide workers with protective goggles, and to protect against inhalation of medicinal and other dust - dust masks.

At the enterprises producing synthetic drugs, a complex of sanitary facilities is provided (showers, dressing rooms, toilets, as well as premises for repair, degassing, drying and dust removal of workwear). If work is carried out with highly toxic substances, then this complex of sanitary facilities should include a sanitary inspection.

An important preventive measure is the removal of impurities from the skin. In some cases, when the usual method of hand washing cannot remove dirt, you should use special detergents. These include a mixture of soda and calcium hypochlorite, 30 parts each for 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 persons entering enterprises for the production of synthetic chemical-pharmaceutical preparations must undergo a preliminary medical examination, and periodic medical examinations are also mandatory for workers dealing with hazardous substances.

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Another reason for unfavorable working conditions can be violations of the tightness of operating devices and communications, insufficient availability of hermetic equipment and closed equipment. The use of various complex chemical reactions in the synthesis, proceeding with the release of poisonous vapors and gases, requires good tightness of reactors and other equipment. Particularly vulnerable areas are stuffing box seals on machines 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. When the product is openly discharged when reloading from the apparatus to the apparatus, as well as into containers, filters, etc., the evaporation surfaces sharply increase, 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 (non-observance of the required temperature and pressure, untimely release of the formed vapors and gases 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, operational irregularities 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 productivity, and therefore they can no longer fulfill their task.

A 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 apparatus at the same production areas. As a result, additional to the usual intake of harmful impurities into the air occurs, which the ventilation unit was not designed to remove.

The general basis for improving working conditions at all enterprises for the production and production of chemical-pharmaceutical preparations and antibiotics is the elimination of the above reasons for unfavorable working conditions. However, any plant from all the indicated groups of enterprises of the chemical and 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 products that can be combined into six groups:

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

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. Medicinal compounds of the aromatic series (phenols and their derivatives, aromatic carboxylic acids and their derivatives, sulfa drugs, derivatives of aromatic sulfonic acids).

5. Organoelement medicinal substances (organic compounds of arsenic, antimony, bismuth, mercury, phosphorus, X-ray contrast agents).

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

The starting raw material for synthetic drugs is the distillation products of coal, oil and other substances, the number of which is many hundreds of names. These are a variety of organic and inorganic chemical substances in liquid, solid and gaseous states. From them, through complex technological processing, organic semi-products are obtained, which are mainly aromatic, less often heterocyclic and aliphatic compounds, mainly various aromatic amines and nitro compounds, phenols and naphthols, their sulfonic acids and halogenated ones.

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