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III-Intellectual Resource of the Preparation Fitesten1. The trademark Fitesten® is registered in 32 countries including:
BG – Bulgaria BX – BeNeLux BY – Belarus CH - Switzerland CN – China DK –Denmark EE – Estonia ES – Spain FI – Finland FR – France GB – United Kingdom GR – Greece HU – Hungary JP – Japan LI – Liechtenstein LT – Lithuania NO – Norway PL – Poland PT – Portugal RO – Romania RU – Russian Federation SE – Sweden SG – Singapore SL – Slovenia SK – Slovakia SZ – Swaziland KZ – Kazakhstan UZ – Uzbekistan
The rights to the trademark Fitesten® belong to „BF-esse” LLC (2 Juglas street, Riga, LV-1024, phone+371 67 323499, e-mail: sekretare@bfesse.lv; fitesten@bfesse.lv, Website: www.fitesten.lv).
2. Own research Unique biological properties of the dense conifer needle extract (DCNE) and its components have been proved in the following patents and developed products.
2.1. Patent LV 10915 В. Date: 03.12.93
The owner of the patent: “BF-esse”LLC The title: A Means of Antibacterial Action on Gram-positive Bacteria and Fungicidal Action on Fungi Annotation: Diterpene alcohol of plant origin – izoabienol (a mixture of diterpene alcohols - Silbiol®) – has a combined antibacterial and fungicidal activity; it inhibits the development of Gram-positive microflora and fungi Candida. It has been experimentally proved that diterpene alcohol- izoabienol (a mixture of diterpene alcohols) which is a component of chlorophyll-carotene paste (dense conifer needle extract of the preparation Fitesten®) inhibits the growth of the test-cultures Staphilococcus aureus, Bacillus subtilis and Candida albicans. 2.2. Patent LV 10925 В. Date 03.12.93
The owner of the patent: “BF-esse”, LLC The title: The Preparation with Immunomodelatory Properties. Annotation: immunomodulator and adapter of plant origin- polyprenols. It protects the immune system against chronic emotional stress and depressive immune response. In cases of weak immunity the increasing of immune response (~ 2 times) and humoral activity (~ 2 times) are observed, it stimulates macrophagocytal activity (~ 2 times). At the increased activity of the immunity (autoimmune diseases) it normalizes the immune response and reduces the humoral activity tenfold. The action of polyprenols of plant origin (a component of chlorophyll-carotene paste of dense conifer needle extract of the preparation Fitesten®) has been investigated in the experimental conditions on the models with genetically determined impaired and strengthened immunity. It has been experimentally proved that a mixture of plant isoprenoids (polyprenols) is a new immunomodulatory substance; it protects the immune system against chronic emotional stress, it stimulates the humoral link of immune reaction and non-specific activity of phagocytes; and at the increased activity of the immunity it normalizes the immune response and reduces humoral activity tenfold.
2.3. Patent LV 10926 В. Date: 03.12.93
The owner of the patent: “BF-esse”,LLC. The title: The Preparation with Immunomodulatory Properties Annotation: the immunomodulator of plant origin diterpene alcohol – izoabienol – enhances the humoral immune response, increases (~ 2-3 times) the number of cells that produce antibodies, increases hemagglutinine titer (~ 4-32 times) stimulates macrophagocytal activity, decreases delayed reaction in immunocompetent cells and the reaction of “graft versus host disease”. It has been experimentally proved that diterpene alcohol – izoabienol ( a component of chlorophyll-carotene paste (dense conifer needle extract -Fitesten®)) extracted from green needle biomass has immunomodelatory properties, stimulates humoral immunity, the clearance of phagocytes, and weakened immune response.
The owner of the patent: „BF-esse”,LLC under contract with a group of the authors and Riga Medical Institute and scientific – industrial cooperative „Biofitecs” The title: The Substance Having Germicidal and Reparative Action Annotation: the invention relates to the chemistry of bioactive compounds and is connected with the creation of medicinal preparations possessing complex effect on various links of the pathological process. It has been experimentally proved that dense conifer needle extract has reparative effect on the gastric ulcer and antibacterial activity.
2.5. Patent LV 11276 В. Date: 14.11.94
The owner of the patent: “BF-esse”,LLC The title: A Means with a Reparative Action on Gastric ulcer and Anti-bacterial Action on Gram-positive Microflora and Pseudomonas aeruginosa. Annotation: the action of chlorophyll-carotene paste (dense conifer needle extract of the preparation Fitesten®) on the chronic gastric ulcer was investigated during the experiment (the model of the pathology was caused by the introduction of 0,05 ml of 10% acetic acid submucously - „acetate”gastric ulcer); the action of chlorophyll-carotene paste (dense conifer needle extract of the preparation Fitesten®) on different microflora (Staphylacoccus aureus, E.coli, Bacillus subtilis, Candida albicans, Pseudomonas aeruginosa) was investigated as well. Conclusion: it has been experimentally proved that chlorophyll-carotene paste (dense conifer needle extract of the preparation Fitesten®) really stimulates the healing of the experimental gastric ulcer and inhibits the growth of Gram-positive bacteria Pseudomonas aeruginosa.
2.6. Patent LV 11277 В. Date: 14.11.94
The owner of the patent: “BF-esse”LLC The title: A Means with Hepatoprotective Property Annotation: hepatoprotector – polyprenols of plant origin improves liver function test and it is much more (ten times) efficient than other preparations. The comparative action of polyprenols ( a component of chlorophyll-carotene paste – dense conifer needle extract of the preparation Fitesten®) of plant origin has been investigated experimentally on the model of hepatoso-hepatitis caused by the administration of carbon tetrachloride (CCl4). Conclusion: It has been experimentally proved that a mixture of plant polyisoprenol alcohols (polyprenols) has evident hepatoprotective properties. They are ten times more efficient than traditional hepatoprotectors, such as Essenciale Forte ™)
2.7. Patent UK Patent Application GB 2 310 138 A Date 28.08.1997.
The owner of the patent: „BF-esse”,LLC, under contract with the group of the authors. The title: Polyprenols are Plant Immunomodulators. Annotation: It has been experimentally proved that the mixture of acyclic isoprenoids – polyprenols,( a part of dense conifer needle extract of the preparation Fitesten®), obtained from woody greenery has immunomodelatory properties and protects the organism from chronic emotional stress.
2.8. Patent US 5, 731, 357. Date: March 24.1998.
The owner of the patent: „BF-esse” LLC, under contract with the group of the authors. The title: The Substance Possessing Immunomodulatory Properties Annotation: It has been experimentally proved that the mixture of acyclic isoprenoids – polyprenols, (a part of dense conifer needle extract of the preparation Fitesten®) obtained from woody greenery has immunomodulatory properties and protects the organism from chronic emotional stress.
2.9. Patent Euroasian 001115. Date 07.07.2000.
The owner of the patent: “BF-esse”, LLC The title: A Diagnostic Method of Exacerbation or Remission of Acquired Immunodeficiency and Autoimmune Diseases Annotation: the invention relates to the field of medicine, it relates to the diagnosis of exacerbation or remission of acquired immunodeficiency and autoimmune diseases
2.10. Patent LV 13067 В. Date: 16.04.2002
The owner of the patent: “BF-esse”, LLC The title: A Way to Obtain Long-Term Storage Premix Annotation: original premix - bioactive food supplement used in animal husbandry - has been worked out. Chlorophyll-carotene paste (dense conifer needle extract) is used in the premix. The paste has the properties of phytoantibiotics, biostimulator, and antioxidant. In a natural way it can increase daily gain in body weight by 6%, the level of carotene by 10%, strengthen immunity to 18%. It has been experimentally proved that the premix containing chlorophyll—carotene paste (dense conifer needle extract) has evident bioactive properties and can lengthen the shelf-life.
2.11. Patent LV 13434 В. Date: 23.01.2006
The owner of the patent: “BF-esse”, LLC The title: Sugar Candy Caramel with Bioactive Supplements Annotation: Caramel contains a bioactive supplement obtained from woody greenery – a mixture of acyclic isoprenoids – polyprenols, (a component of dense conifer needle extract of the preparation Fitesten®), it has immunomodelatory and hepatoprotective properties. Caramel can be used as therapeutic and prophylactic means at immune disorders and liver diseases
2.12. Patent LV 13433 В. Date: 20.08.2006
The owner of the patent: “BF-esse”, LLC The title: Sugar Candy Caramel with Bioactive Supplements Annotation: the invention relates to the food industry, namely, confectionery and can be used in the production of caramel. The caramel contains a bioactive supplement obtained from woody greenery – diterpene alcohol – izoabienol, (a component of dense conifer needle extract of the preparation Fitesten®), which has immunomodulatory, phytoantibacterial , and original organoleptic (taste) properties – fresh taste, aroma, a long fresh aftertaste. Caramel can be used as therapeutic and preventive agent for diseases of the throat and upper respiratory tract.
2.13. Patent LV 13566 В. Date: 22.02.2007
The owner of the patent: “BF-esse”, LLC, under contract with the group of the authors. The title: The Composition Containing Dense Conifer Needle Extract and the Method of Its Application. Annotation: as a result of experimental and clinical investigations it has been proved that the composition containing dense conifer needle extract normalizes the activity of the stomach and gastro-intestinal tract, stimulates the immunity. Found ratios of dense conifer needle extract and the components of the composition allow to incapsulate it into soft gelatine capsules
2.14. Patent LV 13888 B. Date: 04.12.2008
The owner of the patent: „BF-esse”, LLC, under contract with Riga Stradins University. The title: The Composition Containing Dense Conifer Needle Extract for the Incapsulation Annotation: the invention relates to the pharmaceutical, para-pharmaceutical and food industry, it relates to the developing of compositions that improve technological properties and the stability of dense conifer needle extract, increase shelf-life of ready-made capsule forms. It has been experimentally proved that the ratio of dense conifer needle extract and the components – emulsifiers, stabilizers reduces surface tension at the interface of the dispersed system, promotes the mixing of the hydrophilic ( dense conifer needle extract) and hydrophobic (vegetable oil, vitamin E, etc.) components.
2.15. The Results of preclinical investigations ( with a list of all stages)
Preclinical investigations were conducted in 1986-1990. by Riga Medical Institute within the framework of the Republican interbranch scientific-technical complex on the complex use of wood of the Latvian SSR (RISTC “Forest”), the project “Forest”. The members of the project: * Riga Medical Institute ( further: Medical Academy of Latvia), Riga Stradins University (RSU) Riga, Latvia is a coordinator of the project. the investigation of general biological and specific activity of chlorophyll-carotene paste (dense conifer needle extract of the preparation Fitesten®).
* Scientific-industrial association “Silava”, Salaspils, Latvia The improving of the production technology of chlorophyll-carotene paste (dense conifer needle extract of the preparation Fitesten® and its components).
* Leningrad Forest-Technical Academy named after Kirov. Leningrad (Saint Petersburg) Russian Federation. The improving of the production technology of chlorophyll-carotene paste – dense conifer needle extract of the preparation Fitesten® and its components.
* The Institute of Organic Synthesis named after Zelinskij. Moscow, Russian Federation. Prospective synthesis of water-soluble compounds of acyclic isoprenoids (vegetable polyprenols) - a component of chlorophyll-carotene paste. Preclinical investigations of dense conifer needle extract (of the preparation Fitesten®) were conducted according to the requirements of the Pharmacological Committee of the Ministry of Health of the USSR. The materials on the experimental investigation of dense conifer needle extract ( the preparation Fitesten®) were prepared in accordance with the order of the Ministry of Health of the USSR dated 30.12.83 ”On further measures for improvement of procedures for obtaining permits to medical application and transfer for industrial production of new remedies”. The Head and responsible executor of the project “Forest” is a senior research man of Riga Medical Institute, candidate of med. science Juris Rubens. According to the contract on the use of the materials, patents and certificates of authorship on the use of dense conifer needle extract (the preparation Fitesten®), all the rights on the use of intellectual ownership belong to the company “BF-esse”. The contract was signed on 17 February 1992 between Medical Academy of Latvia and the scientific industrial company “BF-esse”.
The Parts of the Work
2.15.2. The application of the Vice-Chancellor of Medical Academy of Latvia on the scrutiny of the materials of the experimental investigation of dense conifer needle extract.
2.15.3. The programme on clinical trial
2.15.4. The report of the experimental testing of specific and general pharmacological activity
2.15.4.1. Experimental study of dense conifer needle extract as an antiulcer agent
2.15.4.2. The study of the influence of dense conifer needle extract on the central nervous system
2.15.4.3. The study of bactericidal properties
2.15.4.4. The report of the investigation of the influence of dense conifer needle extract on the cardiovascular system 2.15.4.5. The study of antioxidant activity Conclusion Experimental study of the specific and general pharmacological activity of dense conifer needle extract shows that it has evident positive biological activity. Thus, as a result of experimental study of reparative activity (section 4.1) of dense conifer needle extract on the models of erosive-ulcerative damages of upper part of gastro-intestinal tract caused by different reasons a number of fundamentally new properties compared with other remedies of plant origin have been revealed, they are the following: - dense conifer needle extract (the preparation Fitesten®) has evident protective-preventive influence on the mucous membrane of gastro-intestinal tract - dense conifer needle extract (the preparation Fitesten®) eliminates the complications of ulcerative process (reduction of inflammation, adhesions, etc) - dense conifer needle extract (the preparation Fitesten®) possessing antibacterial properties (section 4.3) influences one of the main pathological mechanisms of the beginning of peptic ulcer- kampilloz of upper parts of gastro-intestinal tract. The study of the influence on the central nervous system led to the conclusion that dense conifer needle extract (the preparation Fitesten®) can depress the central nervous system at the same time it does not have anticonvulsant activity (section 4.2), it does not influence the motor function of the gastro-intestinal tract. When evaluating the action on the cardiovascular system negative influence has not been found (section 4.4) The investigation of antioxidant activity has shown that dense conifer needle extract (the preparation Fitesten®) has evident antioxidant activity (section 4.5)
2.15.5. The justification of the impossibility to study pharmacokinetics of dense conifer needle extract (DCNE) experimentally Conclusion Dense conifer needle extract is a pasty polycomponent substance obtained by processing coniferous woody greenery. It is water-alkaline solution, its group composition is in table No.1 and table No.2.
2. Neutral substances including:
Table 2. The group composition of neutral substances of dense conifer needle extract
According to the study of the group composition of dense conifer needle extract ( the preparation Fitesten®) the experimental investigation of pharmacokinetics is impossible because of its multi component structure.
2.15.6. The report of the experimental test of DCNE toxicity
The experimental test of DCNE toxicity was conducted according to “The requirements to the preclinical investigation of general toxic action of new pharmacological substances” (Methodological recommendations . The Ministry of Health of the USSR. Pharm. Committee. – M.,1984 – p. 19)
2.15.6.1. Acute toxicity
2.15.6.2. Chronical toxicity Conclusion As the result of the experimental investigation of acute and chronical toxicity of dense conifer needle extract and its components (of the preparation Fitesten®) it has been found that dense conifer needle extract (the preparation Fitesten®) can be considered as non-toxic multicomponent composition.
2.15.7. Data on local irritating action of DCNE
Local irritating action of dense conifer needle extract ( the preparation Fitesten®) was investigated on the mucous membranes of the gastro-intestinal tract when it was administrated during a chronic toxicological experiment and the study of the cumulation of the preparation. As a result of the experiments it has been stated that dense conifer needle extract (the preparation Fitesten®) does not change the histological structure of the mucous membrane of the gastric-intestinal tract when it was administrated. Consequently, it does not have local irritating action.
2.15.8. Data of the allergenic properties of DCNE
Conclusion As a result of experimental investigation of allergenic properties of dense conifer needle extract of the preparation Fitesten® it has been proved that dense conifer needle extract (Fitesten®) does not have allergenic properties.
2.15.9. Data of the influence of DCNE on the immune system Conclusion As a result of the experimental investigation on the influence of dense conifer needle extract of the preparation Fitesten® it has been proved that dense conifer needle extract (Fitesten®) has immunomodulatory activity.
2.15.10. Data of the experimental investigation of poisoning connected with the overdose of dense conifer needle extract ((Fitesten®) Conclusion The experimental investigation of dense conifer needle extract (of the preparation Fitesten®) as well as the experience of folk medicine, literature data and information accumulated during a lot of years of the use of so called chlorophyll -carotene paste in the perfume industry demonstrate the complete safety of dense conifer needle extract (Fitesten®) in its use in medicine and the absence of toxic properties of this preparation. LD50 mg/kg was not detected. Clinical-biochemical and pathomorphological investigations of acute and chronic toxicity on experimental animals (rats, dogs) have shown the absence of toxic properties of dense conifer needle extract. Thus, this preparation has broad therapeutic action and the possibility of its overdose is hardly probable; it is possible to speak about excessive unjustified use of the preparation by some patients, which in its turn will not result in the manifestations of intoxication. Consequently, there will not be necessary specific methods of detoxification. If patients abuse this preparation and have adverse dyspeptic reactions, it is necessary to stop the administration of dense conifer needle extract for some time , if it is necessary, to conduct standard detoxification activities (gastric lavage, the use of laxatives, symptomatic therapy). In some days it is possible to continue the use of the preparation in adequate doses taking into consideration the recommendations of attending doctor. Thus, taking into consideration the absence of toxic properties of dense conifer needle extract it is not necessary to use specific activities of the first aid in case of overdose; it will be enough to remove excessive amounts of the preparation from the gastro-intestinal tract.
2.15.11. Data of the absence of possible carcinogenic activity of DCNE The Scotch pine - Pinus silvestris – can be on the first place among the trees that have medicinal substances. Not only bracing air of a pine forest has medicinal importance but all parts of the tree. Buds and needles of the Scotch pine are widely used in folk medicine. The buds of the pine contain ethereal oil (up to 0.36%), mainly, pinenes, limonene, borneol, camphene, mucous substances, flavonoids, carotenoids, trace elements – magnesium, copper, aluminium, etc. Pine buds are used as an expectorant and disinfectant. Ethereal oil from pine buds is used to treat gout and rheumatism. It is a part of the preparation “PINABIN”. Heavy fraction of ethereal oils of coniferous trees is used as the basis of this preparation. Pharmacopeia Committee of the Ministry of Health of the USSR confirmed Temporary Inter-Republic Technical Requirements (МРТУ 42 № 3781-69 instead of ВТУ-Ф № 1319-51) on the chlorophyll-carotene paste. Starting from 1968 dense conifer needle extract or so called coniferous chlorophyll-carotene paste (State Standard 21802-84 instead of State Standard 21802-76) was produced in Strench forestry industrial enterprise of the Latvian SSR till 90 tons per year. There were no cases of cancer among workers who had a direct contact with conifer-carotene paste throughout the period of their work. Dense conifer needle extract, the preparation Fitesten®,or so-called chlorophyll-carotene paste of Strench forestry industrial enterprise was used in perfumery and cosmetics industry of the USSR: * toilet soap “Forest” (manufacturer – Nevsky plant of cosmetics of Leningrad group of enterprises SMS named after Kirov, Standard 13-326-78); * toilet soap “Forest Fairy Tale”(manufacturer-factory “Freedom”, Moscow, Standard 18-326-78) * toothpaste “Forest” (manufacturer-factory “Freedom”, Moscow, Standard 7983-82) * toothpaste “Forest” (manufacturer –industrial association “Dzintars”, Riga, State Standard 7983-82); * “Soap shaving cream” with coniferous chlorophyll-carotene paste (manufacturer- Nevsky Plant named after Kirov, Leningrad); * conifer needle extract natural (for bathes) (manufacturer-the Ministry of Forestry of the Estonian SSR). Pine needles contain ascorbic acid (0.1-0.3%), carotene, tannin (5%), a small amount of alkaloids as well as ethereal oil (0.13-1.3%) that contains pinene, limonene, borneol, bornilacetate, cadinene,etc. It has been found out that dense conifer needle extract contains free acids and neutral substances. The bulk of free acids are dibasic, oxo-and hydroxy acids. Neutral substances include hydrocarbons consisting of alkanes and terpenes that have Тº of boiling within 156º - 183ºС. From literature it is known that highest hydrocarbons having a boiling point above 500ºС-600ºС possess carcinogenic properties. When the boiling point lowers (300ºС - 400ºС) carcinogenic properties decrease, they disappear at the boiling point till 200ºС. Decoctions and infusions that are rich in vitamin C are prepared from pine needles. It was pine needles as a vitamin concentrate that helped people of Leningrad during the siege. /15/. Coniferous- carotene paste was prepared from pine needles for medicinal purposes. It was approved by Academic Medical Council at the Chief of the Medical Directorate of the Red Army in July 23,1943 with the subsequent approval by the Pharmacological Committee of the Academic Medical Council of People’s Commissariat of the USSR in April 15, 1944. This paste was prepared for external use. One of the indicators of carcinogenic activity of a substance can be mutagenesis which correlates well with the ability of substances to cause tumors The investigations conducted in Riga Medical Institute (there is a report among the materials submitted to the Pharmcommittee of the Ministry of Health of the USSR) have not found mutagenic properties of dense conifer needle extract. Thus, the material that is at our disposal allows to make the following conclusions: 1. There are no substances that are similar to known carcinogens in the composition of dense conifer needle extract – the preparation Fitesten® (so-called chlorophyll-carotene paste). 2. Dense conifer needle extract – the preparation Fitesten® -in the form of coniferous chlorophyll-carotene paste does not cause tumors among people who produce it 3. The widespread use of dense conifer needle extract –the preparation Fitesten® - in the form of chlorophyll-carotene paste in the perfume industry have not revealed the tumors among people who use corresponding perfume preparations. 4. Dense conifer needle extract –the preparation Fitesten® does not have mutagenic properties. Taking into consideration all above-written it is possible to state that dense conifer needle extract does not seem to have carcinogenic properties. .
2.15.12. Test data of possible teratogenic properties of dense conifer needle extract. Conclusion As a result of experimental investigations on possible teratogenic influence of dense conifer needle extract – of the preparation Fitesten® it has been stated that dense conifer needle extract of the preparation Fitesten®does not have teratogenic properties.
2.15.13. Test data of possible mutagenic properties of DCNE Conclusion As a result of the investigation of mutagenic properties of dense conifer needle extract of the preparation Fitesten® it does not have he ability to induce gene mutation, dominant lethal mutations in germ cells of mice, it did not cause chromosomal mutations in bone marrow cells of mice and human peripheral blood lymphocytes.
2.15.14. The literature data of pharmacological properties of DCNE and its prototype Conclusion At present pharmacological treatment of diseases of the digestive tract is becoming increasingly important. It is connected with the identification of etiological factors and better understanding of the pathogenesis of a disease. However, the choice of drugs for certain nosological forms presents specific difficulties. The possibilities of unwanted side effects especially of synthetic preparations are taken into consideration. The factor of duration of treatment is of vital importance, this is actual for such common diseases as stomach and duodenal ulcer. A number of new methods of medical treatment of gastrointestinal diseases have been worked out in recent years. There are about 200 preparations for the treatment of the diseases of digestive tract. Most of them are the products of chemical synthesis The actuality of finding new remedies of plant origin for the treatment of stomach ulcer is evident as the arsenal of them is too small. Rhythm disturbance and especially in the diet, the depletion of natural compounds, the rapid narrowing of the range of food and edible plants consumed by man are specific socially determined factors, the background of the emergence and growth of stomach diseases. The use of complex phytopreparations can neutralize these factors to some extent, mitigate the effects of the departure from the normal human habitat. It is well known that preparations based on natural resources have the most effective action aimed at improving the processes of healing and trophism of tissues. They do not cause side effects and addiction, they have minerals and vitamins necessary for the organism, they have restorative action on organs and systems. Prophylactic trend in the development of health system of the USSR, the possibility of pharmacosanation of people allow to rely on the revival of phytotherapeutic methods of preventing and treatment stomach diseases. Thousand year positive experience guarantees the success in searching phytopreparations for the treatment of stomach diseases Among the medicines that are allowed to be used in Latvian Republic the above-mentioned group of substances of plant origin has a special place because of the complexity of collecting and processing of raw materials and, consequently, a high cost of ready medicinal forms, which leads to a limitation of widespread use of such effective preparations as sea buckthorn oil and allantoin and others. However, at present there are objective and real prerequisites and conditions for the development and clinical application of plant extracts of coniferous woody greenery. Evolutionary history of conifers has accumulated a rich spectrum of biologically active compounds that are used now in small amounts in national health service. Modern technological support of the processes of secondary forest resources processing allowed to single out a large group of new extra-active complexes and separate substances that are conventionally called the products of forest-bio-chemistry. The products of the processing of woody greenery are complex, multicomponent preparations. Their spectral chemical composition is known. Thus, dense conifer needle extract includes bioactive carotenoinds, chlorophyll, vitamin E, phytosterols, terpenes, and other substances. The analogue of dense conifer needle extract is chlorophyll-carotene paste that was classified as a means of influencing the processes of tissue metabolism. Key indicators for external application of the paste were burns (after subsided exudative process), sluggish healing wounds and ulcers. Carotene and sea buckthorn oil are very close to dense conifer needle extract by their character of biological action, they have the same properties and promote the epithelialization of ulcers. Sea buckthorn oil can be effectively used in the treatment of stomach ulcer. Judging by the composition of the preparation: a mixture of carotene, carotenoids and tocophenol, the mechanism of antiulcer effect of sea buckthorn oil has a reparative action on the defects of epithelium of skin and mucous sheets. This statement is a key one for the planning of the experimental investigations to study a specific action of anti-ulcer means. Comprehensive study of anti-ulcer activity includes the evaluation of the influence on secretion, motility, and the protective properties of the mucous membrane of the gastro-intestinal tract. According to the basic methodological requirements of the experimental investigation of anti-ulcer means the study of potential reparants begins with the evaluation of healing effect on ulcers. Pharmacotherapeutic investigation of anti-ulcer means is conducted on several models of pathology with different mechanisms of their beginning. Due to the investigation it was found out that the reparant action of dense conifer needle extract is connected with the acceleration of the process of epithelialization of the mucous membrane of the stomach and the differentiation of proliferating epithelium with the formation in early stages mucous glands in the area of defects. As to the antiulcerogene effect of the fruits of the sea buckthorn it is shown that alongside the main reparative action therapeutic and preventive action is connected with the decreased activity of acid proteases of the gastric mucosa./6/. When РрН is 4.5-5, complete inhibition of proteolitic activity takes place. The reducing of aggressive action in the beginning plays a very important role in the acceleration of healing ulcers and the effectiveness of experimental therapy. Knowing clinical-morphological character of dense conifer needle extract that has therapeutic and preventing action it is possible to assume that it has the phytohormone stimulating effect and antimicrobial action due to which positive effect is achieved in spite of possible complications and reducing microbial contamination of necrotic tissues. A good combination for strengthening preventive properties is the resistance of stomach tissues to the alteration. This effect is inherent to a large group of phytopharmacological preparations that have the influence on the process of regeneration. An example of clinical experience of the use of chlorophyllin sodium in gastroenterological practice can be an argument of the connection of antioxidant, antiblastic and regenerative action of such phytopharmacological means. On the basis of the investigations it has been stated that dense conifer needle extract has not only antiulcerogene but also antimicrobial and antioxidant action influencing on the main elements of the complex pathogenetic mechanism of the beginning of the diseases of upper parts of gastrointestinal tract, which is relatively rare for the antiulcer preparations in traditional medicine..
2.15.15. The project of the name of the preparation Fitesten®
Clinical testing was carried out in three medical centres from 1992 till 1994. 2.16. The results of clinical investigations. 2.16.1. The Department of Health of the the Ministry of Welfare of the Republic of Latvia. Medical Academy of Latvia.The clinical approbation of the preparation Fitesten. 2.16.2. The Department of Health of the Ministry of Welfare of the Republic of Latvia. Stradins Republican Clinical Hospital. The clinical approbation of the preparation Fitesten. 2.16.3. The Department of Health of the the Ministry of Welfare of the Republic of Latvia. Republican Diagnostic Centre. The clinical approbation of the preparation Fitesten.
Generalized Results Fitesten is obtained from pine needles and sprigs of the Scotch pine (Pinus silvestris). This is a dense dark green mass of bitter taste with the smell of pine needles that contains biologically active substances [1,2]: • chlorophyll - 1300-1500 mgг%*, • carotenoids (provit.. А) not < 43mg%*, • polyprenols - 1 %*, • izoabienol - 3-4%* • vit.. С - 2000 mg%*, • vit.. Е - 200 mg%*, • В1, В2, В6, D and other substances in a little dose __________________ * - from dry mass
The analog- chlorophyll-carotene paste – that refers to substances which influence the metabolism is well known in medicine. It was used externally at trophic, radiation, chemical ulcers, burns as well as locally in treatment of gynecological diseases (colpitis, vulvovaginitis, cervical erosion ) [3]. The preparation was tested and perorally administrated for the prevention of septic complications before and after operations on the lungs, the gastrointestinal tract [4]. Fitesten® is a cleaner preparation in comparison with the chlorophyll-carotene paste [1-5]. Preclinical trials have shown that что Fitesten® has the following properties: 1) restorative effect on the experimental gastric ulcer [6]; 2) bactericidal activity on gram-positive microflora and Рseidomonas аеruginosа [6] 3) antioxidant action [7]; 4) weak immunomodulatory effect [7].
It has been proved that Fitesten® does not have irritant action, allergic, carcinogenic, teratogenic and mutagenic properties; it is non-toxic for warm-blooded animals. [7]. Methods Clinical trial of Fitesten® was conducted in Medical Academy of Latvia (Rector - J. Vetra) on the clinical base of the third Department of inner diseases in the Republican Stradins Clinical hospital (RCH, head doctor H. Rund ), Republican Gastroenterological Centre (RGC, prof. N. Skuja) and in Republican Diagnostic Centre (RDC, head doctor J. Ducmanis). Two-week course of Fitesten® was taken for the trial. It was given to patients per 1,5 g three times a day thirty minutes before meal (taking warm water or tea without sugar). Before the trial the patients received the instruction of the use of Fitesten®, they were introduced with the preparation, its action, the order of the trial and possible unconveniences. The selection of patients and tactic trial were conducted according to the principles of Helsinki Declaration. [9]. The selection of patients Planning the selection of patients we tried to use the recommendations on classification and the choice of patients that had already been used in the same conditions. [10]. Eighty patients (one of them refused) participated in the trial. Their age was from twenty till sixty (they did not have severe complications). All of them had ulcer dyspepsia after preliminary esophagogastroduodenoscopic verification. The control group consisted from the patients with ulcer disease who were treated in above mentioned institutions. They were divided according to the principle paired and unpaired. Clinical observations The trial chart of each patient was filled in during the trial. In it such clinical symptoms as nausea, vomiting, burning sensation behind the sternum, etc. were recorded according to the clinical definitions [11]. In the chart standard laboratory data were recorded as well.
Immunological tests 1. lymphocyte subpopulation by the method of indirect immunofluorescence using monoclonal antibodies [12]; . 2. the level of immunoglobulins by the method of radial immunodiffuzia. [13-15]; 3. circulating immunocomplexes using deposition with polyethylene glycol. [16]. Lymphocyte subpopulation, the level of immunoglobulins and circulating immunocomplexes were determined in the samples of peripheral venous blood.. Secretory immunoglobulin was determined in saliva and in gastric juice. Saliva was collected before endoscopy , and gastric juice under the control was sucked at least two-three ml from gastric lake with a help of gastric probe introduced through the biopsy channel of the endoscope.. Intragastric рН-metry Intragastric рН-metry was conducted in the Department of Functional Diagnostics (the Head- G. Grinberge). Traditional two-olive intragastric pH-metry in modification of prof. J. Leja was used..! The evaluation was made using the recommendations of J. Leja at al.[19] The investigation had two tasks: 1) to determine the influence of Fitesten® on decreased and low gastric secretion; 2) to find out the influence of Fitesten® on the normal gastric secretion. 3) basal pH of the stomach of twenty patients from SCH was measured. If the index was higher 5.0 ( i.e. anacidity), then 1,5 g of Fitesten® dissolved in 200 ml of warm water was introduced by the probe. Stomach pH was registered during 60 minutes. If the index of pH was lower 2.0, secretory stimulant (200 mg of the broth) was introduced , and pH kept on registering during 60 minutes. If in this case the index of pH was less 2.0, hymoral irritant was introduced (Sо1. Penagastrini 0,025% 0,1 ml on 10 kg of the body mass or 0,006 mg/kg) , and during 60 minutes stomach pH was registered. If there was a normal secretion, i.e. the index of pH was less 2.0, 200 mg of aqueous solution of Fitesten® (1.5 g) was introduced through the probe, then 200 ml of aqueous solution was introduced through the probe, and then the index of pH was registered during 60 minutes. In some cases the endoscopic determination of pH was conducted during esophagogastroduodenoscopy. [21]. The evaluation of the function of the gall-bladder. The evaluation of the function of the gall-bladder was carried out by the ultrasonography Sonо1ауеr SAL-77А (Japan). Patients whose pathology of the gall-bladder and biliary tract were not stated in their history and recorded during the survey took 1.5 g Fitesten® dissolved in 200ml of warm water. The size of the gall-bladder was determined again in 15 minutes. Esophagogastroduodenoscopy Esophagogastroduodenoscopy was carried out according to the traditional method in the morning with the help of gastrointestinoscopies О1уmpus Орt. Со., Gif-Q, Gif | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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2.15.1.
Conducted