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Bioactive Preparations Production by Lasers

#1706


Creation of Biologically Active Preparations by Laser Technologies

Tech Area / Field

  • PHY-OPL/Optics and Lasers/Physics
  • BIO-CHM/Biochemistry/Biotechnology
  • MED-DRG/Drug Discovery/Medicine

Status
3 Approved without Funding

Registration date
08.12.1999

Leading Institute
NIIEFA Efremov, Russia, St Petersburg

Supporting institutes

  • Institute of Highly Pure Biopreparations, Russia, St Petersburg\nMilitary Medical Academy named after S.M.Kirov, Russia, St Petersburg

Collaborators

  • Procter & Gamble Company / Procter & Gamble European Service GmbH, Germany, Schwalbach am Taunus\nUniversity of Food Technologies, Bulgaria, Plovdiv\nUniversität Ulm, Germany, Ulm

Project summary

Introduction and review. Preservation of organism internal medium constancy in particular the antigenic homeostasis - is a key problem of the adaptation to various endogenic and exogenic effects.

Now there are literary data, confirming these negative endogenic and exogenic effects result in infringement of one of the most important process of cell normal functioning - the process of glycosylation. Under the influence of xenobiotics the change of glycoconjugate content in various tissues takes place. Under malignization the protein glycosylation processes disturb, for example, such proteins, as a-fetoprotein, cholinesterase, g-glutamyl-transpeptidase and others. Tumor metastatic potential correlates with the increaseof galactoside-binding protein expression. The disturbance in a-1-acidic-protein glycosylation results in appearance of immunosuppressive properties. The disturbance of mannose receptors functioning on dendrite cells results in suppression of mannosilated antigens capture and their subsequent presentation, followed by suppressing of cytokine secretion by monocytes.

It is also known, that the disturbance in proteins glycosylation process plays an essential role in regulation of cell functional state, intercellular interactions, cell adhesion and cell enzymes activation. Directly proteins glycosylation process is related with certain compounds, called lectins which bound specifically the end residues of polysaccharides, glycoproteins and glycolipides. Now it has been already proved, that in organism they and their ligands play one of the important roles in maintenance of functioning of immunobiological supervision system. Lectins are proteins, agglutinating the cells and possessing the high specificity to sugars. Natural sources of lectins are seeds of plants, and also invertebrates and lowest vertebrates. The binding of lectins with cell plasmatic membrane surface results in various consequences for a structural and functional state of membranes, for example, it causes changes in the arrangement of superficial proteins and glycoproteins, changes membrane permeability for various substances and influences activity of enzymes. Infringement in lectins synthesis results in fixing of blocking antibodies on tumor antigens, immune receptors on T-lymphocytes (NK-cells) and monocytes.

The application of lectins and their ligands (carbohydrates) is possible to find in the fields of immunocorrection and achievement of antitumor effect. On the data of some authors, the usage of such oligosaccharides as oligogalacturones, lectins from agrape snail (Helix Pomatia) and Misletoe lectins, phytohemagglutinin prevents from metastasis, results in NK-cells activation and decreases the level of the blocking factors. Taking of pectin oligosaccharides increases the elimination of blocking antibodies and immune complexes: for example, low-molecular polysaccharide from ginseng Ginzan reduces the contents of antibody blocking Ig-G1, keeping cytotoxic Ig-G2a level, activates the cytokines secretion by macrophages and stimulates cell immunity. Low-molecular polysaccharides from Rehmania geltinosa strengthen expression of p53 protein, which causes tumor cells death. There are the data polysaccharides from cedar nut, brown alga, Spirulline, Chlorella, Laminaria, brewers yeast, bifidobacteria, mushrooms Phellinus Eruteus and Agaricus blazei possess the immunistimulating activity.

Sulfatated malto- and cyclomaltosaccharides and sialic acid derivatives show antitumor- and antimetastatic effects also. Sialooligosaccharides suppress viral and bacterial infection, fructooligosaccharides promote intestinal flora normalization (increase the contents of bifidobacteria). Also oligosaccharides activate NK- and cytotoxic lymphocytes, influence the pharmacokinetic and activate such enzymes as cholinesterase, various hydrolases. Chitoolygosaccharides, obtained from crab’s chitin possess anti-inflammatory action.

By means of chemical or physical modification of natural polysaccharides and lectins it is possible to amplificate their adaptogenic properties and to increase their specific biological activity. It is known, that the chemical modification of citrus pectin results in appearance of antitumor activity` that may to reduce mammary and prostate glands tumors metastasis. The ultrasonic processing of chitosan results in appearance of low-molecular chitooligosaccharides with antimutagenic and immunostimulating properties. Low-molecular hepariniods, obtained from chitin under ultrasonic processing, have antimetastatic and immunostimulating activities.

Also it is known, that laser processing of polysaccharides of sea alga Zostera and Iceland moss (Cetraria Islandica) results in their low-molecular fractions possessing increased desired biological activity in comparison with starting compounds.

Preliminary experiments fulfilled in NIIEFA and VMA, disclosed the most advantage of laser modification of natural compounds, owing to the most energy concentration at treating object, the high selectivity of the exposure and the optimal degree of the process control.

Taking into account stated above, the subject matter submitted for ISTC consideration concerns to the development of the methods for design of new biologically active preparations by means of laser technologies. The experimental basis of this project is the complex of laser sets, operating in NIIEFA laser center. They function in contiguous and pulse-periodic modes and have the radiation power in interval 10 wt-20 kwt in visible and IR light. The essence of this work consists in usage of laser radiation for physical and chemical modification of natural compounds exactly polysaccharides and lectins in order to receipt the appropriate glycosilated derivatives, possessingincreased biological and adaptogenic activity.

As natural objects for modification it is offered to use sea alga Zostera, wine-materials, Iceland moss (Cetraria Islandica) and compounds producing by Aacilla Thuringiesis, which possess antitumor activity and are used now as pesticides.

In the project the experience of NIIEFA in elaborating of laser equipment and usage of laser radiation for treatment of various materials in order to impart them new properties, NIIOCHB achievement in development of highly pure biopreparations, and the experience of physicians from the Naval Medical Academy will be used.

Expected results. The following results will be obtained during the progress of the project:

­ laser equipment for treatment of biological objects;

­ the technology for treatment of natural products of vegetable and animal origin with laser radiation;

­ technology of attachment peptides, aminoacids and their derivatives to compound obtained in a result of the treatment of the origin products with laser radiation with the aim to increase their biological activity;

­ samples of the preparation and food additives with high biological activity including the preparations obtained in a result of attachment of peptides, aminoacids and their derivatives to origin products processed with laser radiation;

­ the data on their biological testing;

­ the pilot batches of perspective preparations for medicinal and prophylactic aims;

­ the results of the investigation of the peculiarities of diagnostic and medicinal application of the preparations developed on the experimental models of pathological states;

­ the results of the clinical evaluation of the efficiency of the preparations and food additives developed for treatment and prophylaxis of chronic alimentary canal disorders, onco- and broncho-pulmonal pathologies;

­ the data on the usage of the preparations obtained in preventive and clinical medicine.

As a whole the main result of this work consists in the development of new laser technologies for design of biologically activepreparations and food additives, the development of the technology for attachment peptides, aminoacids and their derivatives to compound obtained in a result of the treatment of the origin products with laser radiation with the aim to increase their biological activity and the development of the procedures of their application in preventive, sanitation and clinical medicine.

The following goals and objectives of the ISTC will be realized as the result of Project accomplishment:

­ opportunity will be provided for employees of NIIEFA and NIIOCHB with previous weapons expertise to engage in output of production for peaceful purposes;

­ applied investigations will be supported, the final goal of which is to adopt into pharmacological basis of practical and preventive medicine of new biologically active preparations and food additives. It is of prime importance in ecologically unfavorable regions;

­ assistance will be rendered in solving of the problems associated with general deterioration of the health of population;

­ transition to civil market economy will be supported.

Scope of activities. The work comprises three large directions, each of which provides the scientific and engineering basis for the following. They are:

­ The development and design of laser installation for processing of the biological objects and the development of the technology for treatment of natural product of vegetative and animal origin by laser radiation.

­ Processing of natural raw material by laser radiation in order to receiptthe preparations and food additives with specific biological activity; development of the technology for attachment peptides, aminoacids and their derivatives to compound obtained in a result of radiation of origin products with laser and the productionof the samples and pilot batches of the preparations.

­ Evaluation of the biological activity of the preparations and food additives obtained, investigation of peculiarities of diagnostic and medicinal application of the preparations developed on experimental models of pathological states; clinical evaluation of the efficiency of preparations and food additives developed for treatment and prophylaxis of chronic alimentary canal disorders, onco- and broncho-pulmonal pathologies.

On the basis of the results received the selection of the perspective preparations will be carried out and pilot batches of the preparations selected for medical and preventive aims will be obtained.

The following works will be undertaken for successful realization of the project:


­ laser installation for treatment of biological objects with laser radiation will be designed and produced;
­ the technology for treatment of natural products of vegetable and animal origin with laser radiation will be developed;
­ the technology for attachment of peptides, aminoacids and their derivatives to origin products processed with laser radiation in order to increase their biological activity will be developed and the samples of the preparations will be obtained;
­ the data on their biological testing will be obtained;
­ the pilot batches of the perspective preparations for medicinal and prophylactic aims will be synthesized;
­ the investigation of the peculiarities of diagnostic and medicinal application of preparations developed on the experimental models of pathological states will be narried out;
­ clinical evaluation of the efficiency of preparations and food additives developed for treatment and prophylaxis of chronic alimentary canal disorders, onco- and broncho-pulmonal pathologies will be carried out;
­ the procedures for rational usage of the preparations developed in preventive and clinical medicine will be developed.

Cooperation with foreign collaborators is perceived to be in the form of:


­ exchange of information in the course of the project realization;
­ preparation of comments for the technical reports submitted to ISTC;
­ cross examinations of the results obtained in the project progress;
­ participation in technical inspection of the activities under the Project undertaken by the ISTC employees;
­ organization of joint symposia and seminars.

Technical approach and methodology by virtue of the persification of the work are multiform.

The methods characteristic for physical and physicochemical experiments will be mainly applied at the stage relating to the treatment of origin products with laser radiation.

At the stage of the chemical modification of the mixtures radiated a set of procedures and the methods characteristic for peptide and carbohydrate chemistry, concerning to selective blocking and activation of corresponding functional groups and synthesis of aminoacid derivatives, peptides, peptidoglycans will be applied.

In consequence it will be created a set of new preparations and food additives the estimation of biological activity of which will be spent at the third stage of the work using the methods, applied in experimental medicine and biology. The result of this stage will be the selection of the preparations, perspective for use in practical, preventive and clinical medicine, in particular for preventive maintenance and treatment of chronic alimentary canal disorders, onco- and broncho-pulmonal pathologies.

In the investigation various measuring techniques from electrotechnical and optical to gas and liquid chromatography, NMR-spectroscopy and aminoacid analysis will be used. By and large, the work will be of complex character and for its accomplishment various procedures and methods applied in physics, chemistry, biology and medicine will be used.


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