Information

on the Russian-Kazakhstan workshop

"Pharmacological and clinical trials of the anthelmintic

drug Sausalin"

On May 20, 2016 in the International Research and Production Holding "Phytochemistry" (Karaganda, the Republic of Kazakhstan) the Russian-Kazakhstan scientific workshop dedicated to the Pharmacological and clinical trials of the anthelmintic drug Sausalin took place. 

 

Opening speech of the academician S.M. Adekenov, Karaganda, the Republic of Kazakhstan

The Russian and Kazakhstan researchers-infectious disease specialists with research results of the anthelmintic drug Sausalin, doctors of regional clinics, heads of research institutes, universities, leading scientists and representatives of the Russian and Kazakhstan research centers, over 30 participants in all took part in the workshop session.

 Academician S.M. Adekenov officially opened the workshop session with his speech.

Participants listened to and discussed the reports of Professor V.A. Mordvinov "Search for the new highly effective and safe anthelmintic drugs for treatment of opisthorchiasis", Doctor of Medical Science, honored worker of science and technology of the Russian Federation, Professor V.G. Bychkov "Anthelminticefficiency of Sausalin and cinaropicrin at various opisthorchiasis forms (preclinical research)",  

 

 

Speech of Professor V.A. Mordvinov Novosibirsk, the Russian Federation

Speech of Professor V.G. Bychkov Tyumen, the Russian Federation

Doctor of Medical Science, Professor D.A. Bayesheva "New methods of antiparasitic therapy of the biliary excretion pathways of liver",

 

Speech of Professor D.A. Bayesheva, Astana, the Republic of Kazakhstan

Doctor of Medical Science, Professor, Academician of the Russian Academy of Natural Sciences R.H. Begaidarova "Development of the advanced treatment methods of children and adults suffering from the chronic lambliasis at molecular and cellular levels".

 

Speech of Professor R.H. Begaidarova, Karaganda, the Republic of Kazakhstan

In the International Research and Production Holding "Phytochemistry" (Karaganda) the original drug Sausalin with anti-lambliasis and anti-opisthorchiasis effects has been developed based on the biologically active terpenoids from Saussurea salsa DC.

The main components of extract from the aerial parts of Saussurea salsa DC. are sesquiterpene lactones, flavonoids, polysaccharides, essential oils, and tannins. The active ingredient of Sausalin drug is a sesquiterpene lactone cinaropicrin which causes proteins denaturation in protozoa (gardias and opisthorchis) resulting in their immobilization and death.

 The conducted preclinical research proved the development of medicinal substance based on the extract from Saussurea salsa DC. prospective for treatment of parasitic diseases of the hepatobiliary system (lambliasis, opisthorchiasis), specific (trichomoniasis) and non-specific (bacterial) infections of urogenital system.

The I phase of clinical trials of Sausalin drug was carried out on 30 healthy volunteers in Astana according to the Order of Committee of Pharmacy of Ministry of Health of Kazakhstan No. 140 as of 08.08.2007. During the I phase of clinical trials at the moment and in three months after the administration of the medicine, the general condition of volunteers was good, no signs of deterioration were shown, no complaints were reported. No pathological changes in body and systems were observed at the objective inspection. Clinical blood and urine tests did not reveal any changes in these values.

The II phase of clinical trials of Sausalin was carried out on 90 patients with acute and chronic lambliasis at the Regional Infectious Diseases Hospital in Karaganda according to the approved Order of Committee of Pharmacy of Ministry of Health of Kazakhstan No. 29 of 21.02.2008. During the treatment by Sausalin drug a full sanitation of the small intestine from lamblias was observed in patients which was confirmed by the duodenal sounding data. Whereas, in the group of patients taking the comparator product Metronidazole, the sanitation of a small intestine was observed in 28% of patients only.

Sausalin does not affect the excretory function of kidneys and liver, the composition of normal microflora of a large intestine, vagina and uterus, and does not show a local irritant action.

As a result of clinical trials of the drug Sausalin as an anti-lambliasis agent during the III phase of clinical trials, which was carried out according to the Order of Control Committee of Medical and Pharmaceutical Activity No. 68 of 15.02.2011, its high giardicidal efficiency and safety was confirmed on 250 patients diagnosed with chronic lambliasis.

Sausalin can be viewed as a drug with anthelmintic, choleretic, and anti-inflammatory activities. Three phases of clinical trials did not reveal the deterioration of general state and health in patients associated with Sausalin side effects.

Based on the results of preclinical and clinical trials of Sausalin drug, its efficiency for treatment of a chronic opisthorchiasis was determined. The anti-opisthorchiasis activity of Sausalin is comparable to a comparative drug Ornisid.

It was concluded that administration of Sausalin helps "washing away" lamblias from the upper part of small intestine which is a favourable sign in therapy of this parasitosis. Moreover, it was more effective than a comparative drug Metronidazole.

Production of pilot batches of Sausalin drug is carried out at the bese of Karaganda Pharmaceutical Plant LLP.

 Within the III phase of clinical research Protocols of clinical trials "Study of the clinical efficiency and safety of Sausalin drug as anti-lambliasis agent" and "Study of the clinical efficiency of Sausalin drug as anti-opisthorchiasis agent" were prepared and discussed.

The production method of antitrichomonad, giardicidal and anti-inflammatory drug Sausalin is protected by the Euroasian Patent No. 201100065 and Innovative Patent of the Republic of Kazakhstan No. 23374, Patent of RK No. 17518. As a result of conducted research 20 papers were published.

After the discussion and exchange of opinions at the Russian-Kazakhstan scientific workshop "Pharmacological and clinical trials of the anthelmintic drug Sausalin" a number of decisions were made. They are as follows:

- to recommend Sausalin as anti-lambliasis and anti-opisthorchiasis agent for clinical trials (III phase) at the base of Karaganda State Medical University and Astana Medical University;

- to study pharmacokinetics of cinaropicrin as Sausalin active ingredient at the base of Research Institute of Molecular Biology and Biophysics of SB RAS (Novosibirsk) with the purpose to identify a median effective dose of the drug;

- introduce PCR-analysis to diagnose opisthorchiasis by a know-how method of Research Institute of Molecular Biology and Biophysics for a more precise diagnostics and a broader coverage of patients with this nosology;

- study in detail the mechanism of anti-opisthorchiasis action of Sausalin drug and cinaropicrin at the base of Research Institute of Molecular Biology and Biophysics (in Novosibirsk under the supervision of Professor V.A. Mordvinov);

- to provide for review the Program of clinical trials of original drug Sausalin for treatment of opisthorchiasis and lambliasis to the National Center for Expertise of Drugs, Medical Devices and Equipment of the Ministry of Health and Social Development of Kazakhstan;

- considering the high level of infectious diseases and meeting the demands in antiparasitic drugs, to prepare a joint international Project "Scientific approaches in the development and application of new domestic antiparasitic drugs" with a Business Plan which will also cover the development, clinical trials, marketing of new medicines and commercialization of the research results.

 

 Information on the workshop

 "Bases of technologies commercialization "

 On February 20, 2016 in the International Research and Production Holding "Phytochemistry" the workshop on the topic "Bases of technologies commercialization" took place. It was organized by GS "Alliance of Professionals on Commercialization of Technologies" (Astana) and JSC "IRPH "Phytochemistry".

Over 70 participants including leading scientists, researchers, PhD and master students of holding "Phytochemistry", E.A. Buketov Karaganda State University, Karaganda State Medical University, Karaganda State Technical University, Karaganda Economic University of Kazpotrebsoyuz, Karaganda State Industrial University, Zh. Abishev Chemical-Metallurgical Institute, Institute for issues in complex soil development, Scientific Research Institute of Regional Development took part in the workshop session.

The above-mentioned workshop was dedicated to the issues of science and business integration, technology commercializations of results of research works which had been reviewed by the MES Board on February 5, 2016. The Board of MES RK discussed the new principle and approaches to financing of Research Projects, Scientific and Technical Programs; one of positions to which the Ministry of Education and Science and Committee of Science adhere is to involve business structures in Research Projects, and Scientific and Technical Programs. The deployment of business structures in production is done to make the results of our research works and developments in demand.

At the educational workshop "Bases of technologies commercialization" experts of GS "Alliance of Professionals on Commercialization of Technologies" considered issues of development of system of technologies commercialization in Kazakhstan and clarified the Law of the Republic of Kazakhstan “On commercialization of the results of scientific and research activity”; management of the projects on technologies commercialization: from an idea to the market using pharmaceutical technologies as an example. Special attention was paid to the transfer of technologies, reference standards, conclusion of license agreements on the use of intellectual property items, development of the system of technologies commercialization in pharmaceutical production; defining the pharmaceutical market, marketing of original Kazakhstan drugs.

President of GS "Alliance of Professionals on Commercialization of Technologies", Abdilda Shamenov, familiarized the audience with the organization’s activity.

 

Speech of the President of GS "Alliance of Professionals on Commercialization of Technologies" A. Shamenov

He noted that the Alliance of Professionals on Commercialization of Technologies, as a competent organization, is the platform for technological brokers and those who are professionally engaged in the support of projects for technologies commercialization. The Alliance of Professionals on Commercialization of Technologies was established within the frames of Commercialization of Technologies Project of MES RK and the World Bank and aimed at bringing knowledge and experience gained in the course of work with a portfolio of various technologies. The Alliance of Professionals on Commercialization of Technologies serves as a bridge between business and science representatives.

Afterwards, Abilda Shamenov presented the report "Development of the system of technologies commercialization in Kazakhstan" dedicated to the Law of the Republic of Kazakhstan “On commercialization of the results of research and(or) scientific-technical activity”, cooperation of business and science with the purpose of introduction of competitive developments, increase in the competence of employees working in technologies commercialization offices, higher institutions, technological parks, business incubators, and technological enterprises; improvement of regulatory base in the sphere of technologies commercialization, international experience, in particular the USA offices of technologies commercialization, issues of grant funding and investors funds, practical aspects of promotion of the commercialized projects starting from an idea to the market. Expert in the field of technologies commercialization, Adina Mamrayeva, presented the report on setting up and functioning of the startup companies. She acquainted workshop participants with the creation and startup of these companies, market research, marketing and sales in startup companies on the example of pharmaceutical market, the team building principle, the role of research supervisor and businessman in a team, business models, stages of companies funding, venture funds.

 

Presentation of expert in the field of technologies commercialization A. Mamrayeva

In her report she pointed out that there are over 80 enterprises, both foreign and local manufacturers of medical products in Kazakhstan. Domestic enterprises: Karaganda Pharmaceutical Plant, Chimpharm, Global Pharm, Nobel AFF, pharmaceutical companies Romat and Dospharm represent the full cycle enterprises including development and introduction of technological processes, production of ready dosage forms, selling them to medical institutions and consumers through the distribution and pharmaceutical networks. The following companies form the ten largest distributors of pharmaceutical drugs in the territory of Kazakhstan: Medservice Plus, Zerde, EMITI International, Inkar, Medikus, Interfarm, Akniet, Stofarm and Romat.

According to the Law, the main form of state support is the implementation of Support Programs for commercialization of results of research and (or) scientific-technical activity. These programs will be prepared at all levels starting from higher institutions and research organizations. The Republican Program will be developed under the supervision of Committee of Science of MES RK taking into account suggestions of branch authorities, local executive bodies, higher institutions and the research organizations. 

In this Program the main types of commercialization will be supported within grant and program-targeted funding with active attraction of private investments and capital. The lecture of an expert in the field of technologies commercialization Abylay Akhymbekov "Preparation of grant applications for the technologies commercialization" touched upon there issues.

 

Speech of the expert in the field of technologies commercialization A. Akhymbekov

The speaker gave concrete recommendations about drawing up applications for grant funding, making project presentations, supporting the application, focus areas and most common mistakes during applications preparation, what experts review most thoroughly while evaluating the applications; he also provided information on the applications review process, deployment of the Kazakhstan and foreign experts.

Then A. Akhymbekov clarified a new funding scheme of grant projects and scientific-technical programs aimed at the commercialization of results of research activities with attraction of business-partner funds.

The final report of the expert in the field of technologies commercialization in intellectual property and licensing was presented by Abay Zhangabylov and dedicated to the issues of  intellectual property rights protection and technologies licensing.

Legal protection of intellectual property is a necessary prerequisite during  the commercialization of technologies.

The speaker made an overview of practical aspects of patenting the objects of industrial property in Kazakhstan and abroad, showed the stages of intellectual property protection, technologies licensing, forms of rights transfer for the intellectual property items and types of license agreements; he also consulted workshop participants on signing agreements for licensing the technologies and copyright royalties in Kazakhstan and abroad.

 

Speech of the expert in the field of technologies commercialization in

the intellectual property and licensing A. Zhangabylov

The president of Alliance of Professionals on Commercialization of Technologies, Abdilda Shamenov, noted that researchers of “Phytochemistry” holding are working effeciently to commercialize the scientific developments and introduce them into production.

In holding “Phytochemistry” the principle of continuous research and technical developments is used from basic research including the applied developments up to the introduction of high technologies into production. Thus, considerable success of both fundamental and applied character has been made which allowed the creation of a basis for introduction of the knowledge-intensive developments of competitive pharmaceutical products with a high Kazakhstan content in the manufacture. Production sites with the unique and expensive equipment were set up which can also be used for the contract manufacturing.

Holding employees investigated over 500 plant species of Kazakhstan, of which over 1000 natural compounds were isolated and identified, based on them over 2000 new derivatives were synthesized, 72 new original drugs were developed and deployed in production. Among them an anti-tumor drug Arglabin, a hepatoprotector Salsocollin included in the National medicinal form of Kazakhstan (Order of MHSD RK No. 593 of September 09, 2011), as well as the antiparasitic drug Sausalin, lipid-lowering agent Aterolid, and adaptogenic drug Ecdyphyt, etc.

On the basis of the International Research and Production Holding "Phytochemistry", the Republican Bank of Biologically Active Compounds and Reference Standards of Medicinal Substances operates which contains reference standards and the information database on 3600 natural compounds and their derivatives.

At present, there is no common center for the development of reference standards of medicinal substances in Kazakhstan. In the near abroad countries, Institute of Standardization of Medicines of MH of the Russian Federation (Moscow), All-Russian Research Institute of Medicinal and Aromatic Plants (VILAR, Moscow) and others  are engaged in the development of the national reference standards. In the far abroad countries, such companies as LGC Standards (Poland), Chroma Dex (USA), Phyto Lab (Germany), and others, which have over 50000 samples of medicinal compounds in their catalogues, supply reference standards.

It should be noted that the cost of reference standards of medicinal substances with a high purity provided by the above-mentioned companies is very expensive. For instance, 1 gram of tricine costs 23100 Euros, 1 gram of isoalantalactone - 19200 Euros, 1 gram of artemisinin – 3300 Euros, 1 gram of ecdysterone - 4440 Euros, 1 gram of luteolin - 6000 Euros.

In this regard, the Republican Bank of Biologically Active Compounds and Reference Standards of Medicinal Substances of holding “Phytochemistry” has great prospects in attraction of the foreign companies’ investments.

To attract investments by means of the intellectual property, holding “Phytochemistry” patent reference standards of a number of biologically active compounds. After the evaluation of received patents, holding will include them as shares in the registered capital of the created innovative joint ventures which will promote new developments and stimulate their authors to put forward and introduce the created technologies in production.

Thus, to implement the Project "Construction of the 2nd stage of the Pharmaceutical Plant in Karaganda", the investments of JSC National Innovation Fund of Kazakhstan in the amount of 338000000 tenge were attracted by means of intellectual property of holding “Phytochemistry”, namely Patents of RK No.13247 and No.10913 for the production method of Arglabin drug.

There are some evaluated patents for the organization of production of original drugs, they are as follows: the Euroasian Patent No. 011072 “Production method for cytoprotective drug Salsocollin” in the amount of 351929000 tenge; Innovative Patents of RK No. 23473 for harmine hydrochloride having a pharmacological activity in the amount of 109528958 tenge, No. 23374 for “Production method of Sausalin” in the amount of 206785000 tenge, and the RK Patent No. 28028 “Production method of the antitubercular, antimicrobial and anti-inflammatory medicine Eferol based on the essential oil from Artemisia glabella Kar. et Kir.” in the amount of 253142 960 tenge which can be used to attract business investors.

Holding “Phytochemistry” and Karaganda Pharmaceutical Plant have unique process equipment for the supercritical fluid extraction by means of the liquefied carbon dioxide (CO2). It makes it possible to use supercritical CO2-extraction of medicinal plant raw materials for the contract manufacturing and obtain extracts for the pharmaceutical and cosmetology companies such as LLC Biolit (Tomsk, the Russian Federation), LLC Neva Cosmetics (St. Petersburg, the Russian Federation), PC Kyzyl May. Requests were received from the Hungarian company Pannon Pharma LTD for the production of CO2-extracts by LLP Karaganda Pharmaceutical Plant.

Biological activity assays are an integral part of all pharmacological research. At present, there is no common center to carry out the enhanced screening for biological and pharmacological activities in Kazakhstan. In many research centers and institutes of Kazakhstan, screening for only certain types of biological activity are conducted.

Prospects for the creation of system of effective biological and pharmacological screening of new natural compounds and their derivatives are justified by Kazakhstan need in qualitative medicinal raw materials and highly efficinet drugs generally affordable for the population and capable to compete with the imported drugs.

This is the reason why holding “Phytochemistry” incorporates a Laboratory of Experimental and Clinical Pharmacology where screening of natural compounds and their derivatives is performed. The techniques developed by this Laboratory can be used to study natural compounds and their derivatives samples for the antimicrobial, cytotoxic, anti-inflammatory, antispasmodic, analgetic and anti-pyretic activities by the request of research centers, higher education institutions, etc.

On completion of the reports’ presentation by GS "Alliance of Professionals on Commercialization of Technologies", the discussion took place. The most active participants of the discussion included Director of Karaganda Pharmaceutical Plant, Doctor of Pharmaceutical Sciences E.G. Tolokonnikov, Chief Technologist of the International Research and Production Holding "Phytochemistry", corresponding member of NAS RK, Doctor of Pharmaceutical Sciences H.I. Itzhanova, Director of Research Institute of Economic and Legal Studies of Karaganda Economic University of Kazpotrebsoyuz, Doctor of Jurisprudence, Assistant Professor T.A. Hanov, Head of the Center on Technologies Commercialization of Academician E.A. Buketov KarSU A.S. Baltabekov.

The workshop was very thought-provoking and conducted in the form of a discussion. Workshop participants received the certificates.