Personnel: Principal scientific researcher E. Kemertelidze, Senior scientific researcher M. Benidze; Senior scientific researcher V. Nebieridze; Scientific researcher N. Sakvarelidze; Scientific researcher N. Buliskeria
History: Information about the direction of steroidal (and some other) compounds of TSMU Iovel Kutateladze Institute of Pharmacochemistry Varied flora and rich resources of Georgia can be regarded as inexhaustible source of biologically active compounds and give the great opportunity for receiving medical remedies. Pharmaceutical science and chemical-pharmaceutical industry were developed on the basis of study and usage and was conceived as one of the important fields of the Republic.
Pharmaceutical science has an ancient tradition in Georgia and is an inseparable part of the original cultural heritage of Georgian nation. But the foundation for Georgian scientific pharmacy and pharmacochemistry was laid only after the opening of Tbilisi State University when great Ivane Javakhishvili invited Professor Iovel Kutateladze, already a well-known
scientist, to be a Head of the Department of Pharmacy and Pharmacognosy.
Alongside with the pedagogical work, Professor Iovel Kutateladze together with his group carried out scientific research and achieved such results that laid the foundation for establishing an independent scientific establishment.
In 1932, Tbilisi Chemical-pharmaceutical Research Institute was established. From 1961, the Institute was placed under the authority of the Georgian Academy of Sciences. After Academician Iovel Kutateladze’s death, the Institute was named after its founder. In 1964-1972, the worldwide scientist, Academician Vladimer Asatiani was the director of the Institute.
After the establishment of the Institute of Pharmacochemistry, the purposeful research of natural resources started to obtain medicinal and other kinds of remedies. Creation of medicinal products is quite difficult. It requires involvement of adjacent fields. For this purpose, a complex system was established at the institute where biologically active compounds were sought for and produced. The flora of Georgia as well as the chemical composition of the exposed interesting plants was studies; the methods of analysis and technologies were developed; their pharmacological efficiency and safety were determined and they were prepared for the clinical approval.
In order to provide medications with the base of raw materials, experimental stations of medical plants were established in different regions where biological peculiarities of growth and development of those species, whose natural resources are limited, were studied and the agrorecommendations for their cultivation were worked out. In particular, the experimental stations were established in Kobuleti, Tbilisi, Shiraki; also, Tsebelda station in the Kodori Valley which was wasted by the valley occupation. The experimental production base was launched for the development of substance technologies, also for clinical trials of medications, their production and realization.
Researches were carried out using classical biological, physicochemical and modern spectral analyses.
The Department of Phytochemistry was established in 1960 and investigations of substances of the following classes began: alkaloids, steroidal and triterpene saponins, cardiac glycosides, lipids, cycloartans, flavonoids, tannides, lignanes, coumarins, antraquinones, polysaccharids, proteolotoc ferments, etc. Later, these groups began functioning as independent laboratories.
70 medicinal preparations created at the Institute were used in medical practice at different times. The earlier work carried out at the Institute provided the basis for the establishment of Tbilisi and Batumi Chemical Pharmaceutical Plants. They took the leading position in the Soviet Union in the field of manufacturing phytochemical medications.
The presented work briefly discusses the recently achieved results in the production of steroidal compounds. The preparations made after studying other chemical classes are also discussed.
Preparations of the species of Digitalis – cardenolids and bufadienolids are irreplaceable in treatment of cardiovascular diseases for nearly three centuries. Among 40 species of Digitalis, Digitalis ciliata Twautv. is strongly endemic species of the Caucasus. Compared to others, it is distinguished for high content of cardenolides. Among 60 cardenolides, 35 were characterized. The plant is used as the raw material for cardical cardioglycosides – acetyldigitoxin and digitoxin. From the plant were prepared galenic preparations – “Digicilen” in ampules and “Digicil” in tablets which were successfully used in cardiology. Seeds of Digitalis ciliate contains significant amount of irreplaceable reagent “Digitonin”. Digitonin is being produced nowadays and the technology of its production is patented in England, Germany and Switzerland.
Methoxylated flavonoids, antraquenones are isolated from Digitalis ciliate; fatty oil of the seeds is the remedy against flu virus. The putative drug “Digipurol” is prepared. About 100 compounds are found in plant roots. Digitalis ciliata produces clean sprouts in a large area and gives a large mass of raw materials.
Endemic species of Georgia and the Caucasus – Helleborus abchasicus A.Br. and Helleborus caucasicus A.Br. are rich in the second group of cardiac glycosides – bufadienolids. Some of them are characterized. Neutral lipids biosynthesized in large amount (15-18%) are characterized by specific chemical composition and have antimalignant properties. The drug “Helipol” is prepared for the treatment of surface localization cancer (in combination with radiotherapy).
Tigogenin isolated from the leaves of perennial, evergreen tree-shrub plant – Yucca gloriosa L. is recognized as the initial raw material for the synthesis of steroidal hormonal preparations and the synthesis of some medicines has already been carried out. To provide the base of tigogenin raw material, Yucca gloriosa was cultivated on 180 ha on Shiraki Valley and in this desert a certain oasis was created with white flowering plants. After flowering of Yucca gloriosa is over (15-20 days), flowers wither and fall down as useless parts. Alexin – an effective plant growth stimulant was prepared from the steroidal glycosides of Yucca gloriosa. By the pre-sowing treatment of the seeds with low concentration of water solutions (2-5 mg%) or spraying of seedings, the yield increases by 30-50 % and ecologically pure, high quality product is produced. Roots, barks of rhizomes and stems contain new stilbenes with rare spirostructure (gloriosaols A, B, C, D, E) which are characterized with high antioxidant, pro-apoptotic and antiproliferative actions.
From different vegetal organs of Yucca glorisa 81 individual substances were identified, 32 new organic compounds among them.
- In the widespread weed plant – tribulus terrestris L. content of steroidal glycosides was discovered by us for the first time. “Tribusponin” substance was produced at Chimkent Chemical-Pharmaceutical Plant and its finished form – tablets was produced at first at Tbilisi Chemical-Pharmaceutical Plant and then at the experimental-production base of the Institute. Tribusponin is an effective remedy for treatment and prevention of atherosclerosis.
It is distinguished by the anabolic and generative function stimulating action. Nucleosides, megastigmanes, phenolcarbonic acids, rare flavonoids – apiosides were isolated from Tribulus terrestris L. which can somehow contribute to the mechanism of the action of this many-sided preparation.
- On the basis of the steroidal glycosides (product of neoruscogenin) of relict plant – Ruscus ponticus Wor. Ex Grossh. “Ruscoponin”, the proposed preparation with anti-inflammatory and phlebodynamic action, was developed for clinical approbation.
- The over ground parts of another species Ruscus colchicus P. F. Yeo are rich in steroidal glycosides a part of which is sulfurized. Their chemical structures are identified, among them are 20 new compounds.
Lactogenic activity of Ruscus colchicus is established. It causes increase of milk and improves its quality. Prospect for creating herbal lactonic drug is set. Ruscus colchicus is the best food for cattle. The plant develops strong roots over ground and prevents soil erosion.
- Caucasian endemic relict plant Rhododendron Trautv. highly effective medication “Rodopes” produced from phenolic compounds is the preparation treatment for herpes virus infections. It completely destroys virus and is successfully used in medical practice.
- Astragalus falcatus Lam. – Phenolic glycoside Robinin has antiureamic properties and the preparation “Flaronin” is produced which is used while renal failure. The question of obtaining “Flaronin” from the leaves of widespread plant in Georgia – Pueraria hirsute Matsum is settled.
- Decorative plant – Fatsia japonica (Trumb) Dacne et Planch is rich in triterpene saponins. The first antirheumatic, analgetic and anti-inflammatory plant medication “Fatsiflogin” is produced from it.
- The hepatoprotective and bile expelling preparation “Tsarubol” is produced from soluble in lipids phenol compounds of fruits – Paliurus spina-christi Mill.
- The preparation “Saturin” is produced from flavonoids – a product of Luteolin of the leaves and flowers of Saturena hortensis. It is produced for the treatment and prophylaxis of 2nd type diabetes. In Shiraki experimental station, agronomist Badri Grigolava studied the conditions of growth, development and cultivation of the plant. From 1 ha plot, 600-700 kg a/d high condition raw material can be produced.
- The ancient plant Gingko biloba L. is rare species. It tolerated ice period and is considered as the most ancient plant grown on the earth. Its lifetime reaches 2000 years. Biological properties of the plant have been studied. It is included in the culture at the experimental station of medicinal plants of the Institute. Chemical composition of the leaves of the cultivated plant complies with the international standard. The preparation “Gingko-Bath” is produced from it in the form of fluid 1 ml of which corresponds to the extract produced from 120 mg leaves. Gingko-Bath is the preparation for treatment of vascular system, improves functioning of capillary, venous, arterial vessels and cerebral systems. It is used in cases of mental weakness and work decrement.
- The only remedy “Colchicin” is produced from alkaloids of tuber-bulbs Colchicum speciosum Stev. for treatment of periodic disease and amyloidosis. The preparation is created in collaboration with Professor Pavle Iavich.
- “Extralax” – the single use micro-enema is intended for diagnosing gastrointestinal diseases of patients.
- In collaboration with the direction of lipids and anthraquinones, “Psorantron” and “Psorantron C” are provided in the form of ointment for treatment of psoriasis.
- Priority of cultivation of Cotinus coggygria Scop. over the wild growing plant is established. High-quality medical tannin is produced. The plant is cultivated in Sharaki experimental station of medicinal plants on 3 ha plot. The economic priority of cultivation is confirmed by full mechanization of labor-intensive processes.
- Unused wastes of Thea sinensis L. plantation – tea seeds are rich in triterpene saponins. The preparation “Theasaponin” produced from them was found as effective adjuvant veterinary vaccines. It is used in production of medical photographs. Its inclusion in perfume-cosmetic compositions significantly improves their quality. Thea seed oil is a substitute of olive oil and is an excellent food product; it also lowers the level of cholesterol in blood and has medicinal purpose.
Chemical composition of all preparations, raw materials and basic processes related to their production are studied. Practical usage of all medicines are allowed by the Ministry of Public Health of the USSR, Russian Federation, Georgia and relevant State Agencies. The preparations are provided with stable raw material base necessary for manufacturing; the required scientific-technical documentation is compiled and added; the scales of their realization are determined.
