Subject and tasks of pharmaceutical chemistry.
Pharmaceutical chemistry (PC) is a science that studies methods of obtaining,
buildings, physical and chemical properties medicinal substances; the relationship between their chemical structure and effect on the body; methods of quality control of drugs and changes that occur during their storage. The problems facing it are solved with the help of physical, chemical and physicochemical research methods, used both for the synthesis and analysis of medicinal substances. Physics is based on the theory and laws of related chemical sciences: inorganic, organic, analytical, physical and biological chemistry. It is closely related to pharmacology, biomedical and clinical disciplines.
Terminology in FX
The object of study of PCs are pharmacological and medicinal products. The first of these is a substance or mixture of substances with an established pharmacological activity, which are the object clinical trials. After conducting clinical trials and obtaining positive results, the drug is approved for use by the Pharmacological and Pharmacopoeial Committees and is given the name of the drug. A drug substance is a substance that is an individual chemical compound or biological substance. A dosage form is a state convenient for use given to a medicinal product, in which the required healing effect. It includes powders, tablets, solutions, ointments, suppositories. A dosage form manufactured by a specific company and given a brand name is called a drug.
Sources medicines
Medicinal substances by their nature are divided into inorganic and organic. They can be obtained from natural sources and synthetically. Raw materials for obtaining inorganic substances may be rocks, gases, sea water, industrial waste, etc. Organic medicinal substances are obtained from oil, coal, oil shale, gases, plant tissues, animals, microorganisms and other sources. In recent decades, the number of drugs obtained synthetically has increased sharply.
Often, the complete chemical synthesis of many compounds (alkaloids, antibiotics, glycosides, etc.) is technically complex and new methods of obtaining drugs are used: semi-synthesis, biosynthesis, genetic engineering, tissue culture, etc. Using semi-synthesis, drugs are obtained from intermediate products of natural origin, for example semisynthetic penicillins, cephalosporins, etc. Biosynthesis is the natural synthesis of the final product by living organisms based on natural intermediates.
The essence genetic engineering consists of changing the genetic programs of microorganisms by introducing into their DNA genes encoding the biosynthesis of certain drugs, such as insulin. Tissue culture is the reproduction in artificial conditions of animal or plant cells, which become raw materials for the production of drugs. To produce the latter, hydrobionts, plant and animal organisms of the seas and oceans are also used.
Classification of medicinal substances.
There are two types of classification of a large number of used medicinal substances: pharmacological and chemical. The first of them divides medicinal substances into groups depending on the mechanism of action on individual organs and systems of the body (central nervous, cardiovascular, digestive, etc.). This classification is convenient for use in medical practice. Its disadvantage is that substances with different chemical structures may appear in the same group, which complicates the unification of methods for their analysis.
According to chemical classification medicinal substances are divided into groups based on the commonality of their chemical structure and chemical properties, regardless of their pharmacological action. For example, pyridine derivatives have different action on the body: nicotinamide is vitamin PP, nicotinic acid diethylamide (cordiamin) stimulates the central nervous system, etc. Chemical classification is convenient because it allows us to identify the relationship between the structure and mechanism of action of medicinal substances, and also allows us to unify methods for their analysis. In some cases, a mixed classification is used to take advantage of the pharmacological and chemical classification of drugs.
Requirements for medicines.
The quality of a medicinal product is determined by appearance, solubility, identification of its authenticity, degree of purity and quantitative determination of the content of pure substance in the drug. The complex of these indicators constitutes the essence of pharmaceutical analysis, the results of which must comply with the requirements of the State Pharmacopoeia (SP).
The authenticity of a medicinal substance (confirmation of its identity) is established using chemical, physical and physicochemical research methods. Chemical methods include reactions to functional groups included in the structure of the drug that are characteristic of a given substance: These, according to the Global Fund, are reactions to aromatic primary amines, ammonium, acetates, benzoates, bromide, bismuth, ferrous and oxide iron, iodides, potassium, calcium, carbonates (bicarbonates), magnesium, arsenic, sodium, nitrates, nitrites, mercury oxide, salicylates, sulfates, sulfites, tartrates, phosphates, chlorides, zinc and citrates.
Physical methods for establishing the authenticity of a drug include determining its: 1) physical properties: state of aggregation, color, smell, taste, crystal shape or type of amorphous substance, hygroscopicity or degree of weathering in air, volatility, mobility and flammability and 2) physical constants: temperatures melting (decomposition) and solidification, density, viscosity, solubility in water and other solvents, transparency and degree of turbidity, color, ash, insoluble in hydrochloric acid and sulfate and volatile substances and water.
Physico-chemical methods for studying authenticity involve the use of instruments for chemical analysis: spectrophotometers, fluorometers, flame photometers, chromatography equipment, etc.
Impurities in medicines and their sources.
Many medicines contain certain impurities of foreign substances. Exceeding their level may cause undesirable effects. The reasons for the ingress of impurities into medicinal substances may be insufficient purification of the starting materials, synthesis by-products, mechanical impurities, impurities in the materials from which the equipment is made, and violation of storage conditions.
GF requires either complete absence impurities, or allows a maximum permissible limit determined for a given drug, which does not affect the quality and therapeutic effect of the drug. To determine permissible limit standard solutions are provided for GF impurities. The result of the reaction to a particular impurity is compared with the result of the reaction carried out with the same reagents and in the same volume with the reference one, standard solution containing an acceptable amount of impurity. Determining the degree of purity of a medicinal product includes testing for: chlorides, sulfates, ammonium salts, calcium, iron, zinc, heavy metals and arsenic.
region. State Pharmacopoeia of the USSR (SF USSR)
State Fund of the USSR - a collection of mandatory national standards and regulations regulating the quality of medicinal substances. It is based on the principles of Soviet healthcare and reflects modern achievements in the field of pharmacy, medicine, chemistry and other related sciences. The Soviet Pharmacopoeia is a national document; it reflects the social essence of Soviet healthcare, the level of science and culture of the population of our country. The State Pharmacopoeia of the USSR is of a legislative nature. Its requirements for medicines are mandatory for all enterprises and institutions of the Soviet Union that manufacture, store, control the quality and use medicines.
The first edition of the Soviet Pharmacopoeia, called the VII edition of the State Pharmacopoeia of the USSR (GF VII), was put into effect in July 1926. To create it, in 1923, a special pharmacopoeial commission was formed at the People's Commissariat of Health of the RSFSR, chaired by prof. A. E. Chichibabina. The first Soviet Pharmacopoeia differed from previous editions by its increased scientific level and the desire for the possible replacement of medicines made from imported raw materials with domestically produced medicines. In Global Fund VII, higher requirements were imposed not only on medicinal products, but also on the products used for their manufacture.
Based on these principles, GF VII included 116 articles on new drugs and excluded 112 articles. Significant changes have been made to the requirements for drug quality control. A number of new methods for chemical and biological standardization of drugs were provided, 30 general articles were included in the form of appendices, descriptions of some common reactions used to determine quality were given medicines, etc. Organoleptic control of many drugs was for the first time replaced by more objective physicochemical methods, and biological control methods were introduced.
Thus, in GF VII, priority was given to improving the quality control of medicines. This principle has found its way further development in subsequent editions of pharmacopoeias.
In 1949, the VIII edition was published, and in October 1961, the IX edition of the State Pharmacopoeia of the USSR was published. By this time, new groups of highly effective drugs (sulfonamides, antibiotics, psychotropic, hormonal and other drugs) had been created, which required the development of new methods of pharmaceutical analysis.
The X edition of the State Pharmacopoeia (SP X) came into force on July 1, 1969. It reflected the new successes of domestic pharmaceutical and medical science and industry.
The fundamental difference between GF IX and GF X is the transition to new international terminology for drugs, as well as a significant update of both the nomenclature and methods of drug quality control.
In GF X, the requirements for the quality of medicinal products have been significantly increased, methods of pharmacopoeial analysis have been improved, and the scope of application of physicochemical methods has been expanded. Numerous general articles, reference tables and other materials included in GF X reflected the requirements necessary to assess the quality and quantitative characteristics medicines.
The State Pharmacopoeia of the USSR X edition includes 4 parts: “Introductory part”; “Medicines” (private and group articles); " General methods physico-chemical, chemical and biological research"; "Applications".
The “Introductory Part” outlines the general principles of construction and the procedure for using GF X, indicates the compilers, changes that distinguish GF X from GF IX, list A and list B of medicinal substances.
GF X contains 707 articles on medicinal substances (in GF IX there were 754) and 31 group articles (in GF IX there were 27). The nomenclature was updated by 30% due to the exclusion of discontinued drugs and those with limited use. The quality of the latter is established in accordance with the requirements of Global Fund IX.
Compared to GF IX, the number of individual (synthetic and natural) drugs increased from 273 to 303, from 10 to 22 antibiotic drugs, and for the first time radioactive drugs were included in GF X. Among the drugs included in the Global Fund X are new cardiovascular, psychotropic, ganglion-blocking, antimalarial, anti-tuberculosis drugs, drugs for the treatment of malignant neoplasms, fungal diseases, new anesthesia drugs, hormonal drugs, and vitamins. Most of them were obtained for the first time in our country.
“Drugs” is the main part of GF X (p. 39-740). 707 articles set out the requirements for the quality of medicines (quality standards). Each drug, in accordance with the requirements of the pharmacopoeia, is subjected to physical properties testing, authenticity testing, purity testing and determination of the quantitative content of the drug. Global Fund X details the structure of articles reflecting the sequence of control. The "Properties" section has been replaced by two sections: "Description" and "Solubility". Descriptions of authenticity reactions for 25 ions and functional groups are summarized in one general article, and links are provided in specific articles.
The order of the articles has been changed. For the first time in Global Fund X, articles on finished dosage forms are located after articles on the corresponding medicinal product. Most articles of the Global Fund X contain a section indicating the pharmacological action of the drug. Information on higher doses of drugs for in various ways introduction.
The third part of the State Fund X “General methods of physicochemical, chemical and biological research” provides a brief description of the methods used for pharmacopoeial analysis and provides information on reagents, titrated solutions and indicators.
“Appendices” to Global Fund X contain reference tables atomic masses, densities, constants (solvents, acids, bases) and other quality indicators of drugs. It also includes tables of the highest single and daily doses of poisonous and potent drugs for adults, children, and also for animals.
After the publication of the X edition of the State Pharmacopoeia, the Ministry of Health of the USSR approved for use in medical practice a number of new highly effective medicines. Many of them were first developed by scientists in our country. At the same time, ineffective drugs were excluded, which were replaced by more modern means. Therefore, there is a need to create a new XI edition of the State Pharmacopoeia of the USSR, which is currently being prepared. Involved in this work are: scientific institutions and enterprises of the USSR Ministry of Health, the Ministry of Medical Industry and other departments. The new State Pharmacopoeia will reflect modern achievements in the field of pharmaceutical analysis and improving the quality of medicines.
National and regional pharmacopoeias
Such large capitalist states as the USA, Great Britain, France, Germany, Japan, Italy, Switzerland and some others systematically release national pharmacopoeias every 5-8 years. Published in 1924-1946. the pharmacopoeias of Greece, Chile, Paraguay, Portugal, and Venezuela have already lost their significance.
Along with pharmacopoeias, some countries periodically publish collections of official requirements for drugs such as the US National Formulary and the British Pharmaceutical Code. They standardize the quality of new drugs that are not included in pharmacopoeias or were included in earlier editions of pharmacopoeias.
The first experience in creating a regional pharmacopoeia was carried out by the Scandinavian countries (Norway, Finland, Denmark and Sweden). The published Scandinavian Pharmacopoeia since 1965 has acquired a legislative character for these countries.
Eight Western European countries (Great Britain, Germany, France, Italy, Belgium, Luxembourg, the Netherlands and Switzerland), members of the EEC (European Economic Community), created a pharmacopoeial commission in 1964. She prepared and published in 1969 the first and in 1971 the second volume of the EEC Pharmacopoeia (a supplement to these publications was published in 1973). In 1976, the EEC Pharmacopoeia was recognized by the Scandinavian countries, Iceland and Ireland. The EEC Pharmacopoeia has a legislative nature, but does not replace the national pharmacopoeias of these countries.
Regional pharmacopoeias contribute to the unification of nomenclature and quality requirements for medicines obtained in different countries
Quality control of drugs in pharmacies
In-pharmacy drug quality control includes not only analytical control, but also a system of measures that ensure proper storage, preparation and dispensing of drugs. It is based on strict adherence to the pharmaceutical and sanitary regime in the pharmacy. Particular care must be taken to follow the rules for storing medications and the technology for preparing injection solutions, concentrates and eye drops.
For in-pharmacy quality control of drugs, pharmacies must have analytical rooms or analytical tables equipped with the necessary instruments, reagents, reference and special literature. In-pharmacy control is carried out by pharmacist-analysts who are part of the staff of large pharmacies, as well as pharmacist-technologists, whose responsibilities include checking the quality of drugs. They have an equipped workstation on or next to the assistant's desk. The head of the pharmacy and his deputies manage the quality control of medicines. They must master all types of intra-pharmacy control, and in small pharmacies they themselves must perform the functions of a pharmacist-analyst or pharmacist-technologist.
Direct analytical control in a pharmacy includes three main areas: quality control of medicinal substances coming from industry, quality control of distilled water and various types of quality control dosage forms, manufactured in a pharmacy.
Medicinal substances supplied to pharmacies from industry, regardless of the presence of a Quality Control Department stamp, are controlled for identity. Drugs that change rapidly during storage are sent for testing to control and analytical laboratories at least once a quarter.
Systematic control over the quality of distilled water in a pharmacy ensures the quality of preparation of all liquid dosage forms. Therefore, distilled water in each cylinder is monitored for the absence of chlorides, sulfates and calcium salts. Even higher demands are placed on water used for the preparation of injection solutions. It is checked for the absence of reducing substances, ammonia, and carbon dioxide. At least once a quarter, the pharmacy sends distilled water for complete analysis to a control and analytical laboratory, and twice a year to a sanitary and bacteriological laboratory to check the absence of microflora contamination.
All dosage forms manufactured in pharmacies are subject to internal pharmacy control. There are several types of control: written, organoleptic, questionnaire, physical and chemical. Written, organoleptic, survey and physical control is carried out, as a rule, by a pharmacist-technologist after the pharmacist has prepared at least 5 drugs, and chemical control is carried out by a pharmacist-analyst.
All medications manufactured in any pharmacy are subject to written control. The essence of written control is that after preparing the medicine, the pharmacist writes down from memory on a special form the name and total weight of each ingredient or indicates the content of each concentrate taken. Then the form along with the recipe is handed over to the pharmacist-technologist for verification. Completed forms are stored in the pharmacy for 12 days.
Organoleptic control includes checking the appearance (color, uniformity of mixing), smell and taste of drugs, and the absence of mechanical impurities. All medicines prepared for children are tested for taste. internal use, and selectively formulated for adults (excluding medications containing Schedule A ingredients).
Survey control is carried out by a pharmacist-technologist. He names the ingredient, and in complex medicines the content of the first ingredient. After this, the pharmacist names all other ingredients and their quantities. If concentrates were used to make the medicine, the pharmacist lists them indicating the percentage. Questionnaire control is carried out immediately after the manufacture of medicines, if they are intended for injection or if they contain drugs from list A. If there is doubt about the quality of the manufactured medicine, survey control is an additional type of control.
Physical control consists of checking the total volume (mass) of the prepared drug or the mass of its individual doses. 5-10% of the number of doses prescribed in the prescription is controlled, but not less than three doses. Physical control is carried out selectively, periodically throughout the working day. Along with physical control, accuracy checks are carried out to check the correctness of the formulation of the medicines and the compliance of the packaging with the physicochemical properties of the ingredients included in the dosage form.
Chemical control includes qualitative and quantitative chemical analysis of drugs prepared in a pharmacy. All injection solutions are subjected to qualitative chemical analysis (before they are sterilized); eye drops; each series of concentrates, semi-finished products and in-pharmacy preparations; medicines coming from the supplies department to the assistant's departments; children's dosage forms; medicines containing drugs of list A. Medicines manufactured according to individual impurities are selectively monitored.
To perform qualitative analysis, the drop method is mainly used, using tables of the most characteristic reactions.
This practical work requires studying the fundamentals of general pharmaceutical chemistry and methods for studying qualitative and quantitative research substances most commonly encountered in veterinary practice.
List of medicines subject to quantitative analysis, depends on the availability of a pharmacist-analyst in the pharmacy. If the pharmacy has one on staff, then all injection medications are subjected to quantitative analysis (before sterilization); eye drops (containing silver nitrate, atropine sulfate, dicaine, ethylmorphine pilocarpine hydrochloride); atropine sulfate solutions for internal use; all concentrates, semi-finished products and in-pharmacy preparations. The remaining drugs are analyzed selectively, but daily by each pharmacist. First of all, drugs used in pediatric and ophthalmic practice are monitored, as well as those containing drugs from List A. Perishable drugs (solutions of hydrogen peroxide, ammonia and formaldehyde, lime water, ammonia-anise drops) are analyzed at least once a quarter.
If there is no pharmacist-analyst, but the pharmacy staff has two or more pharmacists, then injection solutions (before sterilization) containing novocaine, atropine sulfate, calcium chloride, sodium chloride, glucose are subjected to quantitative analysis; eye drops containing silver nitrate, atropine sulfate, pilocarpine hydrochloride; all concentrates; hydrochloric acid solutions. Perishable medicines from these pharmacies are sent for testing to control and analytical laboratories.
Injection solutions containing novocaine and sodium chloride are subject to qualitative and quantitative analysis in pharmacies of category VI with one pharmacist on staff and in pharmacies of the first group; eye drops containing atropine sulfate and silver nitrate.
The procedure for assessing the quality of drugs manufactured in pharmacies and the norms of permissible deviations in the manufacture of drugs are established by order of the USSR Ministry of Health No. 382 dated September 2, 1961. To assess the quality of manufactured drugs, the terms are used: “satisfies” or “does not satisfy” the requirements of the State Fund of the USSR, FS , VFS or instructions of the USSR Ministry of Health.
Features of pharmaceutical analysis.
Pharmaceutical analysis is one of the main branches of pharmaceutical chemistry. It has its own specific features that distinguish it from other types of analysis. They consist in the fact that substances of various chemical natures are subjected to research: inorganic, organic, radioactive, organic compounds from simple aliphatic to complex natural biologically active substances. The range of concentrations of the analyzed substances is extremely wide. The objects of pharmaceutical research are not only individual medicinal substances, but also mixtures containing different numbers of components. The number of drugs used is increasing every year. This leads to the need to both develop new methods of analysis and unify already known ones.
Continuously increasing requirements for the quality of medicines dictate the need for continuous improvement of pharmaceutical analysis. Moreover, the requirements for both the good quality of medicinal substances and the quantitative content are growing. This necessitates the widespread use of not only chemical, but also more sensitive physicochemical methods to assess the quality of drugs.
There are high demands on pharmaceutical analysis. It must be quite specific and sensitive, accurate in relation to the standards stipulated by the USSR State Fund, VFS, FS and other scientific and technical documentation, and carried out in short periods of time using minimal quantities of tested drugs and reagents.
Pharmaceutical analysis, depending on the objectives, includes various shapes drug quality control: pharmacopoeial analysis, step-by-step control of drug production, analysis of individually manufactured dosage forms, express analysis in a pharmacy and biopharmaceutical analysis.
An integral part Pharmaceutical analysis is pharmacopoeial analysis. It is a set of methods for studying drugs and dosage forms set out in the State Pharmacopoeia or other regulatory and technical documentation (VFS, FS). Based on the results obtained during the pharmacopoeial analysis, a conclusion is made about the compliance of the medicinal product with the requirements of the USSR State Fund or other regulatory and technical documentation. If you deviate from these requirements, the medicine is not allowed for use.
Performing a pharmacopoeial analysis makes it possible to establish the authenticity of the drug, its good quality, and determine the quantitative content of the pharmacologically active substance or ingredients included in the dosage form. Although each of these stages has its own specific goal, they cannot be considered in isolation. They are interconnected and mutually complement each other. For example, melting point, solubility, pH of the medium aqueous solution etc. are criteria for both the authenticity and good quality of a medicinal substance.
The State Pharmacopoeia X describes the methods of relevant tests in relation to a particular pharmacopoeial drug. Many of these techniques are identical. To summarize a large amount of private information on pharmacopoeial analysis, the main criteria for pharmaceutical analysis and the general principles of testing for authenticity, goodness and quantitative determination of medicinal substances will be considered. The state and prospects for the use of physicochemical and biological methods in the analysis of drugs are discussed in separate sections.
Phys. and chem. Saints, as well as methods of qualities and quantities, analysis. Basic pharmaceutical problems: obtaining biologically active ingredients and their research; identifying patterns between structure and. chem. conn.; improvement of medical quality assessment. Wed to ensure their max, therapeutic. efficiency and safety; research and development analysis methods lek. in-in in. objects for toxicological and eco-pharmaceutical. monitoring.
F pharmaceutical is closely related to specialties. disciplines such as lek technology. forms, pharmacognosy (studies of medicinal raw materials of plant and animal origin), organization and economics of pharmacy, and is included in the complex of disciplines that form basic pharmaceutical science. education.
Application of chemical B-B as a lec. sr-v was carried out already in ancient and medieval medicine (Hippocrates, Galen, Avicenna). The emergence of pharmaceuticals is usually associated with the name of Paracelsus (who contributed to the introduction of chemical drugs into medicine) and the subsequent discoveries of the therapeutic effect of MH. chem. conn. and elements (K. Scheele, L. Vauquelin, B. Courtois), as well as with the works of M. V. Lomonosov and his school on methods of obtaining and methods for studying the quality of drugs. Wed. The formation of pharmaceutical science is attributed to the 2nd half. 19th century The 90s should be considered milestone periods in the development of pharmaceuticals. 19th century (preparation, ), 1935-37 (use of sulfonamides), 1940-42 (discovery), 1950 (psychotropic drugs of the phenothiazine group), 1955-60 (semi-synthetic and later cephalosporins), 1958 (b-blockers) and 80s ( antibacterial drugs group of fluoroquinolones).
Prerequisites for searching for lek. Weds usually serve as data about . in-va, the similarity of its structure with biogenic physiologically active substances (for example, diff.,). Sometimes lek. Wed can be obtained by modifying biogenic compounds. (eg animals) or due to the study of substances foreign to humans (eg derivatives and benzodiazepines).
Synthetic substances are obtained through org. synthesis or apply methods using achievements.
Methods for studying the content of lek are important in the pharmaceutical industry. substances in the preparation, its purity and other factors that form the basis for quality indicators. Analysis of lec. Wed, or pharmaceutical. analysis aims to identify and quantify the basic. component (or components) in a medicine. Pharmaceutical analysis depending on pharmacological action of the drug (purpose, dosage, route of administration) · provides for the determination of impurities, auxiliary. and accompanying medications. forms. Lek. Weds are assessed comprehensively, according to all indicators. Therefore, the expression “pharmacopoeial quality” means the suitability of the drug for use in medicine.
Compliance with lek. Wed-in the required level of quality is established using standard methods analysis, usually specified in the pharmacopoeia. For lek. along with with group chem. r-tions use and. For the analysis of multicomponent lek. formsusually used. Purity tests are designed to confirm the absence (within the limits of the method used) of individual impurities, and in some cases to assess their content. For this purpose, chromatography is used. methods, often in combination with optical ones.
Pharmacokinetic characteristics of lek. Wed (the effect of the drug and its distribution in time) represent extremely important and mandatory information that ensures rational and effective application drugs, allow you to expand knowledge regarding
Pharmaceutical chemistry as a science. History of development. Modern scientific problems
Modern scientific problems of pharmaceutical chemistry is an elective discipline and belongs to the variable part of the professional cycle of the Federal State Educational Standard.
The study of the discipline ends with current control in the 9th semester - undifferentiated credit.
The goal of mastering an elective discipline is for students to acquire in-depth knowledge on the main research problems of pharmaceutical chemistry:
creation of new medicines;
development of new and improvement existing methods quality control of medicines.
Pharmaceutical chemistry is an applied science that, based on the general laws of chemical sciences, studies:
chemical nature of the drug;
methods of obtaining drugs;
drug structure;
physical and chemical properties of drugs;
methods of drug analysis;
the connection between the chemical structure of a drug and its effect on the body;
changes that occur during drug storage;
application and forms of release of drugs.
History of the development of pharmaceutical chemistry
I. Period of iatrochemistry (XVI-XVII centuries)
Iatrochemistry, outdated. iatrochemistry (from ancient Greek ἰ ατρός - doctor) is a rational direction of alchemy of the 16th–17th centuries, which sought to put chemistry at the service of medicine and set as its main goal the preparation of medicines.
Explained the origin of diseases chemical processes in the human body.
The origin and development of iatrochemistry, which is most widespread in Germany and the Netherlands, is associated with the activities of a number of researchers.
Jan Baptist van Helmont(1580-1644) – Dutch naturalist, physician. Van Helmont was one of the first to use silver nitrate (lapis) to cauterize wounds, inflammations and warts. Believed that acid plays a decisive role in digestion gastric juice, and therefore proposed to treat diseases caused by excess acids in the stomach with alkalis. He introduced the term “gas” into chemistry.
Francis Silvius, aka Francois Dubois, France de la Boe
(1614-1672) - Dutch physician, physiologist, anatomist and chemist. counted
“caustics” of an acidic or alkaline nature and prescribed alkalis for one type of disease, and acids for another. I learned to obtain silver nitrate (lapis) and use it to cauterize wounds, inflammations and warts. Opened the first chemical laboratory for analysis at Leiden University.
(real name Philip Aureolus Theophrastus Bombast von Hohenheim, 1493-1541) - famous alchemist and physician of Swiss-German origin, one of the founders of iatrochemistry. He believed that “chemistry should serve not the extraction of gold, but the protection of health.”
The essence of Paracelsus' teaching was based on the fact that the human body represents a totality chemicals and a deficiency of any of them can cause disease. Therefore, for healing, Paracelsus used chemical compounds of various metals (mercury, lead, copper, iron, antimony, arsenic, etc.), as well as extracts from plants. Paracelsus conducted a study of the effect on the body of many mineral and plant origin. He improved a number of instruments and apparatus for performing analysis. That is why Paracelsus is rightfully considered one of the founders of pharmaceutical analysis, and iatrochemistry – the period of the birth of pharmaceutical chemistry.
Pharmacies in the XVI-XVII centuries. were original centers for the study of chemical substances. In them, substances of mineral, plant and animal origin were obtained and studied. A number of new compounds were discovered here, and the properties and transformations of various metals were studied. This allowed us to accumulate valuable chemical knowledge and improve chemical experiments.
II. The period of origin of the first chemical theories (XVII-XIX centuries)
To develop industrial production during this period, it was necessary to expand the scope of chemical research beyond iatrochemistry. This led to the creation of the first chemical industries and the formation of chemical science. Second half of the 17th century. – the period of the birth of the first chemical theory – the theory of phlogiston. With its help, they tried to prove that the processes of combustion and oxidation are accompanied by the release of a special substance - “phlogiston” - I. Becher (1635-1682) and G. Stahl (1660-1734). Despite some erroneous provisions, it was undoubtedly progressive and contributed to the development of chemical science.
In the struggle with supporters of the phlogiston theory, the oxygen theory arose, which was a powerful impetus in the development of chemical thought.
M.V. Lomonosov (1711-1765) was one of the first scientists in the world to prove the inconsistency of the phlogiston theory. Despite the fact that oxygen was not yet known, M.V. Lomonosov experimentally showed in 1756 that in the process of combustion and oxidation, it is not decomposition, but addition
(1742-1786), whose merit was also the discovery of chlorine, glycerin, a number of organic acids and other substances.
Second half of the 18th century. was a period of rapid development of chemistry. Pharmacists made a great contribution to the progress of chemical science, who made a number of remarkable discoveries that are important for both pharmacy and chemistry.
The French pharmacist L. Vauquelin (1763-1829) discovered new elements - chromium, beryllium.
The French chemist B. Courtois (1777-1836) discovered iodine in seaweed.
In 1807, the French pharmacist Seguin isolated morphine from opium, and his compatriots Peltier and Caventou were the first to obtain quinine, strychnine, brucine and other alkaloids from plant materials.
The pharmacist Karl Friedrich Mohr (1806-1879), a German chemist and pharmacist, did a lot for the development of pharmaceutical analysis. He was the first to use burettes, pipettes, and pharmaceutical scales, which bear his name.
Development of pharmaceutical chemistry in Russia
The emergence of pharmacy in Russia is associated with the widespread development traditional medicine and witchcraft. The first cells of the pharmacy business in Rus' were herbal shops (XIII-XV centuries), in which “herbalists” sold various herbs and medicines prepared from them.
The emergence of pharmaceutical analysis should be attributed to the same period (XIII-XV centuries), as there was a need to check the quality of drugs. Russian pharmacies in the XVI-XVII centuries. were unique laboratories for the production of not only drugs, but also acids (sulfuric and nitric), alum, vitriol, sulfur purification, etc. Consequently, pharmacies were the birthplace of pharmaceutical chemistry. The training of pharmacists was carried out by the first medical school opened in Moscow in 1706. One of the special disciplines in it was pharmaceutical chemistry. Many Russian chemists were educated at this school.
The true development of chemical and pharmaceutical science in Russia is associated with the name of Mikhail Vasilyevich Lomonosov (1711–1765). On the initiative of M.V. Lomonosov in 1748, the first scientific chemical laboratory was created, and in 1755 the first Russian university was opened. Together with the Academy of Sciences, these were centers of Russian science, including chemical and pharmaceutical science.
One of the many successors of M.V. Lomonosov was a pharmacy student, and then a major Russian scientist, Toviy Yegorovich Lovitz (1757-1804). He first discovered the adsorption capacity of coal and
used it to purify water, alcohol, tartaric acid; developed methods for producing absolute alcohol, acetic acid, and grape sugar. Among the numerous works of T.E. Lowitz's development of a microcrystalscopic method of analysis (1798) is directly related to pharmaceutical chemistry.
A worthy successor to M.V. Lomonosov was the largest Russian chemist Vasily Mikhailovich Severgin (1765-1826). Highest value For pharmacy, two of his books, published in 1800, are available: “A Method for Testing the Purity and Innocence of Medicinal Chemical Products” and “A Method for Testing Mineral Waters.” V.M. Severgin created the scientific basis of not only pharmaceutical, but also chemical analysis in our country.
The “Encyclopedia of Pharmaceutical Knowledge” refers to the works of the Russian scientist Alexander Petrovich Nelyubin (1785-1858). He was the first to formulate the scientific foundations of pharmacy and carried out a number of applied research in the field of pharmaceutical chemistry; improved methods for obtaining quinine salts, created instruments for obtaining ether and for testing arsenic. A.P. Nelyubin conducted extensive chemical studies of Caucasian mineral waters.
The founders of the first Russian chemical schools in Russia were
A.A. Voskresensky (1809-1880) and H.H. Zinin (1812-1880).
A.A. Voskresensky and H.H. Zinin played an important role in personnel training,
V creation of laboratories, provided great influence for the development of chemical sciences, including pharmaceutical chemistry. A.A. Voskresensky carried out a number of studies with his students that were directly related to pharmacy. They isolated the alkaloid theobromine and conducted studies of the chemical structure of quinine. The outstanding discovery of H.H. Zinina was a classic reaction for the conversion of aromatic nitro compounds into amino compounds.
DI. Mendeleev (1834-1907) is the creator of the Periodic Law and the Periodic Table of Elements. DI. Mendeleev also paid attention to pharmacy. Back in 1892, he wrote about the need for “a device
V Russia of factories and laboratories for the production of pharmaceutical and hygienic preparations” in order to be exempt from imports.
hexamethylenetetramine, discovered quinoline, studying the structure of quinine, synthesized sugary substances from formaldehyde. A.M. brought world fame. Butlerov created (1861) the theory of the structure of organic compounds.
Periodic table of elements D.I. Mendeleev and the theory of the structure of organic compounds A.M. Butlerov had a decisive influence on the development of chemical science and its connection with production.
At the end of the 19th century. In Russia, extensive research has been carried out on natural substances. Back in 1880, long before the work of the Polish scientist Funk
Russian doctor N.I. Lunin suggested that in addition to protein, fat, and sugar, food contains “substances essential for nutrition.” He experimentally proved the existence of these substances, which were later called vitamins.
In 1890, E. Shatsky’s book “The Doctrine of Plant Alkaloids, Glucosides and Ptomaines” was published in Kazan. It examines the alkaloids known at that time, according to their classification according to their producing plants. Methods for extracting alkaloids from plant materials are described, including the apparatus proposed by E. Shatsky.
At the turn of the 20th century. Chemotherapy arose in connection with the rapid development of medicine, biology and chemistry. Both domestic and foreign scientists contributed to its development. One of the creators of chemotherapy is the Russian doctor D.L. Romanovsky. He formulated in 1891 and confirmed experimentally the foundations of this science, indicating that it is necessary to look for a “substance” that, when introduced into a diseased organism, will cause the least harm to the latter and cause the greatest destructive effect in the pathogenic agent. This definition has retained its meaning to this day.
Based on the one developed at the end of the 19th century. German scientist P. Ehrlich theory, called the principle of chemical variation, many, including Russian scientists (O.Yu. Magidson, M.Ya. Kraft, M.V. Rubtsov, A.M. Grigorovsky) created a large number of chemotherapeutic agents with antimalarial effects .
The creation of sulfonamide drugs, which marked the beginning new era in the development of chemotherapy, is associated with the study of the azo dye prontosil, discovered in the search for drugs for treatment bacterial infections(G. Domagk, 1930). The discovery of Prontosil was a confirmation of the continuity of scientific research - from dyes to sulfonamides.
The antibiotic penicillin, first discovered in 1928 by the Englishman A. Fleming, was the ancestor of new chemotherapeutic agents effective against pathogens of many diseases. A. Fleming's work was preceded by research by Russian scientists.
In 1872 V.A. Manassein established the absence of bacteria in the cultural liquid when growing green mold (Pénicillium glaucum). The antibiotic effect of mold was confirmed in 1904 by veterinarian M.G. Tartakovsky in experiments with the causative agent of chicken plague. The research and production of antibiotics led to the creation of an entire branch of science and industry, revolutionizing the field drug therapy many diseases.
Thus, carried out by Russian scientists at the end of the 19th century. Research in the field of chemotherapy and the chemistry of natural substances laid the foundation for the production of new effective drugs in subsequent years.
Development of pharmaceutical chemistry in the USSR
Formation and development of pharmaceutical chemistry in the USSR
happened in the first years of Soviet power in close connection with chemical science and production. The domestic schools of chemists created in Russia, which had a huge influence on the development of pharmaceutical chemistry, have been preserved.
Large schools:
organic chemists A.E. Favorsky and N.D. Zelinsky;
terpene chemistry researcher S.S. Nametkina;
creator of synthetic rubber C.B. Lebedeva;
researcher in the field physical and chemical research methods N.S. Kurnakova and others.
The center of science in the country is the USSR Academy of Sciences (now the Russian Academy of Sciences - RAS).
Pharmaceutical chemistry developed on the basis of fundamental theoretical research, which were carried out at research institutes of chemical and medical-biological profiles of the USSR Academy of Sciences (RAN) and the USSR Academy of Medical Sciences (now RAMS). Scientists from academic institutes were directly involved in the creation of new medicines.
A.E. Chichibabin (1871-1945) – the first research in the field of chemistry of natural biologically active substances (BAS).
I.L. Knunyants (1906-1990), O.Yu. Magidson (1890-1971) – development of technology for the production of the domestic antimalarial drug akriquin.
H.A. Preobrazhensky (1896-1968) - new methods for obtaining vitamins A, E, PP were developed and introduced into production, the synthesis of pilocarpine was carried out, studies of coenzymes, lipids and other biologically active substances were carried out.
V.M. Rodionov (1878-1954) - contributed to the development of research in the field of chemistry of heterocyclic compounds and amino acids, one of the founders of the domestic fine organic synthesis industry
And chemical-pharmaceutical industry.
A.P. Orekhov (1881-1939) - development of methods for isolating, purifying and determining the chemical structure of many alkaloids, which were then used as drugs.
MM. Shemyakin (1908-1970) - the Institute of Chemistry of Natural Compounds was created. Conducted basic research in the field of chemistry of antibiotics, peptides, proteins, nucleotides, lipids, enzymes, carbohydrates, steroid hormones. New drugs have been created on this basis. The institute laid the theoretical foundations of a new science – bioorganic chemistry.
A.N. Nesmeyanov, A.E. Arbuzov, B.A. Arbuzov, M.I. Kabachnik, I.L. Knunyants – research in the field of organoelement compounds.
Development theoretical basis creation of new drugs that are organic element compounds.
Synthetic chemists (N.V. Khromov-Borisov, N.K. Kochetkov), microbiologists (Z.V. Ermolyeva, G.F. Gause, etc.), pharmacologists (S.V. Anichkov, V.V. Zakusov , M.D. Mashkovsky, G.N. Pershin, etc.) - created original domestic drugs.
Creation of pharmaceutical research institutes in the USSR
1920 - Research Chemical and Pharmaceutical Institute (NIHFI), in 1937 - renamed VNIHFI named after. S. Ordzhonikidze.
1920 – NIHFI in Kharkov.
1930 – NIHFI in Leningrad.
1932 – NIHFI in Tbilisi.
70s - NIHFI in Novokuznetsk to provide scientific and technical assistance to chemical and pharmaceutical enterprises in Siberia.
VNIHFI research
The iodine problem in our country was solved (O.Yu. Magidson, A.G. Baychikov, etc.). Methods have been developed for the production of original antimalarial drugs, sulfonamides (O.Yu. Magidson, M.V. Rubtsov, etc.), antituberculosis drugs (S.I. Sergievskaya), organoarsenic drugs (G.A. Kirchhoff, M.Ya. Kraft and etc.), steroid hormonal drugs(V.I. Maksimov, N.N. Suvorov, etc.), major research was carried out in the field of alkaloid chemistry (A.P. Orekhov). Now this institute is called the Center for the Chemistry of Medicines (CHLS). The center carries out research work and produces pharmaceutical substances.
TsHLS-VNIHFI today
Main Mission:
development, preclinical research and introduction into industrial production of original medicines for the prevention and treatment of widespread diseases;
reproduction of expensive synthetic drugs used in world medical practice in order to make them available to patients in Russia;
development of original and reproduced medicines (antihistamines, hormonal, ophthalmic, anti-inflammatory, antiviral, antimicrobial, psychotropic, cardiovascular, antispasmodic, cytostatic and other drugs);
preclinical research of synthetic drugs (clause
28 Roszdravnadzor letter dated July 14, 2009 No. 04I-389/09);
leading organization implementing scientific and technical examination of draft regulatory and technological documentation for the production of synthetic medicines, single- and multi-component finished dosage forms in accordance with paragraph
4.9 and Appendix A to OST 64-02-003-2002;
manufacturer of pharmaceutical substances, intermediates and placebos (Roszdravnadzor license No. FS-99-04-000667 dated 02/06/2009);
more than 170 generics have been reproduced, widely used in world medical practice: Akrikhin, Aminazin, Diphenhydramine, Ibuprofen, Imipramine, Clonidine, Lidocaine, Nitrazepam, Ortofen, Piracetam, Sinaflan, Tropindol, Cyclodol, Cisplatin, etc.;
about 80 original domestic medicines have been developed, including such well-known ones as Azafen (Pipofezin), Arbidol, Galantamine, Dioxidine, Metacin, Metronidazole hemisuccinate, Pyrazidol (Pirlindol), Platiphylline, Proxodolol, Promedol, Riodoxol, Salazopyridazine (Mesalazine), Tetraxoline (Oxolin) , Fenkarol (Hifenadine), Ftivazid, Emoxipine;
Preclinical studies of drugs are being carried out:
pharmacological studies, including studying the mechanism of action of drugs and studying the effectiveness of the drug in comparison with analogues;
biological studies, including primary studies of in vitro and in vivo activity of compounds;
toxicological studies;
analysis of acute, chronic toxicity and pyrogenicity of drugs;
pharmacokinetic studies.
The Industrial Technology Department of the Center for the Chemistry of Medicines produces the following pharmaceutical substances:
Benzethonium chloride is an antimicrobial agent;
Collargol is an antiseptic;
Methylethylpyridinol hydrochloride (emoxipine) is an antioxidant;
Mycosidine is an antifungal agent;
Proxodolol - alpha and beta blocker;
Protargol (silver proteinate) is an anti-inflammatory agent for topical use;
Tropindole (tropisetron) is an antiemetic.
VILAR - All-Russian Research Institute of Medicinal and Aromatic Plants (established in 1931)
Based on the study of plant raw materials, more than 100 drugs were developed at the institute: individual drugs or a sum of substances,
medicinal preparations, individual plants with various types actions:
cardiovascular;
neurotropic;
antiviral;
anti-inflammatory;
antibacterial;
wound healing;
bronchodilator;
regulating the functions of the gastrointestinal tract and genitourinary tract;
immunomodulatory.
Dietary supplements have been created based on plant raw materials (general strengthening and mild tonic effect).
VILAR structure
Plant Science Center;
Center for Chemistry and Pharmaceutical Technology;
Medicine Center;
Research and educational and methodological center of biomedical technologies;
Center for the Development and Support of Scientific Research, etc. Main Goals of the Institute:
fundamental and priority applied scientific research in life sciences on molecular, cellular, tissue
And organismal levels;
development and creation of promising technologies for living systems and medications aimed at improving the quality and life expectancy of the population;
introduction of scientific achievements and best practices in the field of agro-industrial complex, ensuring its innovative technological, economic and social development;
development and modernization of our own research and production
GNIISKLS
The State Research Institute for Standardization and Control of Medicines (GNIISKLS) was created in 1976 to improve quality control of medicines. The Institute carried out fundamental and applied research on the issue of “Standardization of Medicines”, including the development of reference materials (RM) and regulatory documentation (ND) for drugs, the development of quality control methods and the study of physicochemical and biological properties of drugs.
In 1999, GNIISKLS was reorganized into two research institutes: the Institute for Quality Control of Medicines and the Institute for Standardization
medicines. Both of them became part of the State Scientific Center for Expertise and Control of Medicines.
History of the Department of Pharmaceutical Chemistry of the OOO
In 1918, the Soviet government issued a decree on the opening of a pharmaceutical department at Perm State University. Classes in the pharmaceutical chemistry course were held at the university. The founder of the Department of Pharmaceutical Chemistry is Professor Nikolai Ivanovich Kromer.
1931 - the beginning of the formation of the department. The department operated in the building of the Medical Institute (K. Marx Street) from 1931 to 1937.
The Department of Pharmaceutical Chemistry was established as an independent structural unit in 1937 after a series of transformations and the separation of the pharmaceutical department into the Perm Pharmaceutical Institute. In a building on the street. Lenin, 48, the department operated from 1941 to 1965.
Main problems of pharmaceutical chemistry
I. Creation of new medicines.
II. Development of new and improvement of existing methods for quality control of medicines.
The problem of creating and researching new drugs in Russia is being addressed by:
universities;
chemical-technological institutions;
research institutions;
educational institutions;
research institutions of the Russian Academy of Medical Sciences, etc.
I. Creation of new medicines
Empirical search is a method of random discoveries. Variety – general screening (screening). A large number of obtained substances are subjected to pharmacological tests on animals and substances with biological activity are identified.
Directed synthesis – involves the production of drugs with expected biological activity.
Main types of directed synthesis
1. Reproduction of biogenic physiologically active substances (vitamins, hormones, enzymes, biogenic amines, etc.).
2. Identification of physiologically active metabolites and creation of new drugs based on metabolites and antimetabolites.
