ISSC of RAS(UB) / Developments / Novel materials for medicine
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Novel materials for medicine

 
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Novel materials for medicine

A new generation of radiopaque substances 



Radiopaque substances are indispensable for the majority of radiologic investigations. Without them, nothing except skeleton images can be obtained, because only bones entrap X-rays. In order to examine cavitary organs (gastrointestinal tract, bile-excreting tracts, urinary tracts, kidneys, uterine tubes) with X-rays, compositions are required which would absorb a substantial percentage of X-ray radiation while depositing on the surface of tissues. This leads to better image contrast and visualization of a tissue or an organ cavity on the image. Here, it is important that the radiation dose be minimal.


Nowadays iodine- and barium-containing radiopaque substances (RS) are used in X-ray diagnostics most frequently. Although they are being constantly improved, they still have many drawbacks. Iodine-containing RS have a toxic effect on blood, kidneys, liver, and especially on thyroid gland, and cause allergic reactions. Iodized RS irritate mucous tunic, easily penetrate alveoles during bronchography, and stay too long in lungs provoking inflammation. For example, an oil suspension of RS containing barium sulfate gives rise to lipogranulomas, oil pneumonias, sclerotic degeneration of lung tissues and is removed from lungs for almost a year.


Iodine- and barium-containing RS fail to meet modern requirements also because they show no promise for computer tomography when thousands of X-ray images are obtained simultaneously at different angles around a patient’s body and then are computer processed. This technique employs a higher radiation dose rate than in usual radiography and calls for radiopaque substances, which absorb X-ray radiation much more intensively than barium or iodine.


That is why chemists in cooperation with physicians have been looking for new promising agents, which may serve as a basis for synthesis of safer and more efficient RS. Such studies have been carried out for several years by a research team headed by Dr. M. G. Zuev at the Institute of Solid State Chemistry UB RAS. As a result, a new generation of tantalate-based RS has been created.


These substances are complex tantalum oxides, namely, yttrium and lanthanum orthotantalates. Tantalum, named after Tantalus – a hero of ancient Greek mythology for the torments experienced by scientists trying for a hundred of years to obtain it in a pure form, possesses some remarkable properties. It is not rejected in living tissues and therefore is widely used in surgery; it absorbs well X-ray radiation and is only slightly toxic. At the same time, pure tantalum powder has a number of drawbacks, because of which its oxides are used.


The studies into physicochemical properties of tantalates were performed in close cooperation with the Department of pharmacology at the Ural State Medical Academy. Preclinical trials of the new RS were carried out under the supervision of the Head of the Department Dr. L. P. Larionov. Experiments on animals showed that tantalates have no local irritant, skin-resorptive, sensibilizing or mutagenic action; they do not exert any harmful effect on the general habitus and the mass of animals, on the functional parameters of the organism’s most important systems, peripheral blood or biochemical parameters of blood plasma. The new RS cause no allergic reaction or side effects typical of iodine-containing RS and are quickly excreted from the organism. They absorb X-rays much better than iodine- or barium-containing RS and therefore can be used in computer tomography. Much promise hold gel-like tantalates: the gel uniformly covers the walls of examined organs and keeps there longer than a liquid or a powder.


Tantalum RS are universal – they can be used to examine different organs including lungs and tracheobronchial tree, ENT organs, digestive and bile-excreting tract organs, pancreas, as well as in gynaecology and stomatology.


Tantalates can be easily synthesized; sufficient sources of raw materials are available for their production. To produce tantalates even for the requirements of the whole country there is no need to build a plant. They can be produced in an institute laboratory, in those high-temperature ovens where they are synthesized. It is true that tantalates are more expensive than the conventional substances, for example, barium sulfate, but we do try to reduce their cost.


The introduction of drugs takes a lot of time everywhere in the world. Even in the USA, usually 11 years elapse from the moment a promising substance has been synthesized till it is used in medical practice. We have gone through all the stages except the last one – trials on patients. Clinical trials must be carried out in two local clinics and one metropolitan clinic with participation of several tens of patients. This requires a considerable amount of money, among other things for the work of medical staff and for the insurance of patients in case of complications. Several years ago we received a permission to carry out clinical trials, but they have not been initiated as yet for lack of financing.


 


Bone grafting


The search for materials which are biologically compatible with living organisms is a topical problem of modern medicine. Several millions operations for implantation of bone grafts and tens of millions of operations for bone restoration are performed annually in the world. Today, a large number of different materials suitable for reconstruction and replacement of bone tissue, such as ceramics, glassceramics, polymers, some metals, have been created. However, most of them are biologically inert or biologically tolerant materials. This means that they are neither rejected by the organism nor engrafted completely being separated from natural tissue by a layer of connective fibrous tissue. That is why of particular interest are biologically active materials which could be naturally compatible with living tissues and which could participate in biochemical reactions in the organism in full measure. Among such bioactive materials there are calcium-phosphorous compounds (tricalcium phosphate and hydroxyapatite) synthesized in the Laboratory of chemical compounds of dispersed elements at the ISSCh under the leadership of Prof. S. P. Yatsenko.


Tricalcium phosphate and hydroxyapatite have the structure and chemical composition, which are almost identical with those of the natural osseous tissue, and exhibit pronounced osteogenetic behavior in biological media. They can be used with success in reparative (restorative) osteoplasty, especially in osteoplasty of spongy bones, small unloaded bones of jaws, face and teeth.


In the gel-like form, the biologically active calcium-phosphorous compounds can be also used to treat soft tissues and mucous tunic lesions thanks to their epithelium-forming, wound-healing, and antimicrobial properties. The compositions developed at the ISSCh on the basis of gel-like hydroxyapatite with hetero-organic substances have been tested in the laboratories and training clinics of the Ural State Medical Academy. One of the experimental compositions was tested at the Department of stomatology to treat parodentium for a group of patients. The superiority of this preparation as compared to its conventional counterparts allows us to patent this novel therapeutic and prophylactic drug for oral cavity care.


Besides, interesting results have been obtained on anti-inflammatory and anti-burn action of the compositions. The experiments with animals showed that the hydroxyapatite-based ointment not only noticeably decreases edema and hyperemia on an inflamed area, but also prevents the development of inflammation if used for prophylaxis. When the new compositions are used to treat burns, the period of cicatrisation decreases approximately by three days, the burn scar being much thinner and softer than as a result of conventional treatment. However, wide application of these preparations is still far away ... for the reasons, which do not depend on the scientists.   



E. Ponizovkina


(Abbreviated)

Design and programming N-Studio 
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