Description

This invention relates to polymer containing guanidino groups who are capable of specifically binding phosphate. Kidney disorders are very common and can, if treatment is delayed or inadequate, progress through renal conditions in the terminal phase, the patient subsequently requiring dialysis treatment. Renal Dialysis patients suffer from high levels of serum phosphate. In addition, patients who have often ineffective Reins develop "kidney" composed of two extremely insoluble salts, calcium phosphate and calcium oxalate. Both anions cause toxic effects in these patients. The development of high levels of phosphate is minimized in these patients by the addition of aluminum hydroxide, magnesium hydroxide or calcium hydroxide or mixtures of any of these compounds in the diet. However the use of magnesium hydroxide or calcium can lead to serious side effects, which is aluminum hydroxide compound, which is the most commonly used. The presence of aluminum ions in the intestine patient reduces the absorption of phosphate from the diet, thereby reducing the concentration of phosphate in the cavity. The result is a concentration gradient of phosphate from a high level in the blood at a low level in the cavity. Phosphate moves therefore blood on the concentration gradient and into the light. Continuation of treatment with aluminum hydroxide or related preparations led to the gradual accumulation of aluminum ions in the tissues of the body, which must then be disposed of by the administration of the compound desferrioxamine. Desferrioxamine, an iron chelator, is known to have side effects, especially in people who are not "heavy iron" (eg as a result of a blood transfusion). Sick kidneys are not overloaded with iron, hence the constant use of the concession desferrioxamine to reduce levels of aluminum may cause undesirable side effects. Description of Invention It is therefore an object of the present invention to provide a practical way to reduce the absorption of phosphate from the diet in the kidneys of patients and reduce levels of phosphate in the blood of kidney patients. It was noted that this goal can be achieved through the incorporation into the composition pharmaceutical or food for a polymer composed of a backbone and guanidino groups said attached to the spine. Phosphate ions are known to bind to guanidino groups. This attraction is so strong connections involving two electrostatic and two stereochemically favorable hydrogen bonds. However, the incorporation of guanidino groups in a polymer structure and the therapeutic application of guanidino groups and structures of polymers containing guanidino groups has not been previously suggested. Accordingly, the present invention provides a physiologically acceptable polymer composed of a backbone that are directly or indirectly tied guanidino groups, the polymer having a minimum molecular weight of 10,000. The present invention extends to the use of polymer compounds of the invention in therapy, for example, in pharmaceutical compositions and foodstuffs as described below. The invention is of particular interest for the treatment of kidney patients for the control of phosphate from the diet and the elimination of excess phosphate in the blood of these individuals. The polymeric material on which the guanidino groups are attached can be essentially a polymer structure, because the nature of the polymer backbone is not of primary importance in phosphate binding, this effect is rather due to the presence in the polymer of the guanidino groups. However, preferably, the polymer is pharmaceutically acceptable and appropriate molecular weight of these not to be absorbed by patients when taken orally, but to stay in the intestine. The molecular weight of the guanidino group polymer containing at least 10,000. The guanidino group containing polymers of the invention must be physiologically acceptable. As is known to those skilled in the art, polymers are large molecules consisting of small units chemical simple. In some cases, the repetition is linear, and a chain is built up of these units. In other cases, or branched chains are interconnected to form 3-dimensional networks. These 3-dimensional networks can also be formed by cross-linking polymer chains. Types of polymer that can be used, including those with a skeleton staff, in particular the polymers in which the spine is made of carbon atoms, such as polyvinyl alcohol polymer derivatives, and polymethacrylic polyacrylic acid polymer derivatives, and other polvinyl, and polyisobutylene polyisoprene polymers, but also organic polymers in which the backbone includes hetero such as oxygen or nitrogen and the carbon atoms. Polymers of particular interest in the present context of the invention include polymers forming a 3-dimensional network structure, for example because of a new cross-linking of the polymer. The degree of crosslinking control of the porosity of the polymer matrix, which in turn can influence both the capacity and selectivity of the molecular weight of the matrix. Preferred polymers of this type include polymers having a backbone Crosslinked polyethylene with divinyl benzene. Also of interest are some of polymers with inorganic base, eg polyphosphazene polymers. The polymers can be sequenced from two or more different types of monomer. Since the preferred route of administration is oral, and they remain in the intestine and is not absorbed into the bloodstream of the patient, polymers of the invention are preferably more acceptable to consumers. Examples of such polymers include cellulose polymers in carbohydrates and agarose. The carbohydrate polymers are particularly advantageous since many kidney patients to take carbohydrates bulk up their food. Based on this way we are providing food in bulk and at the same time prevent the absorption of phosphate from the diet and make its excretion in feces and not via the bloodstream and kidneys, and thus reducing toxic side effects . The guanidino groups are attached to the polymer backbone through chemical bonding through the terminal NH group of the guanidino group (NH2 -- C (. Dbd.NH) -- NH --). The chemical bonding of the guanidino groups at the base of polymers may be either directly or through some form of association acting as a "space" through which it is attached to the base polymer. Various forms of attachment can be used, the forms vary depending on the type of base polymer. For example, alkylene groups of 1-4 carbon atoms, amide groups, groups ether or a combination thereof, may be used. The method of fixing guanidino groups at the base polymer will obviously depend on the nature of the backbone, but for the simplicity of direct liaison between the atoms of the backbone and the NH group of guanidino group is preferable to the extent possible. The amount of polymer to be administered to the patient is an important consideration bearing on the number of guanidino groups in the polymer. Preferably, the proportion of guanidino groups for the remainder of the polymer is in the range of 1 part by weight of guanidino groups at 1 part by the weight of the rest of the polymer and 1 part by weight of guanidino groups at 100 parts by weight Rest of the polymer. Preferably the range is between 1 part by weight of guanidino groups at 1 part by the weight of the rest of the polymer and 1 part by weight of guanidino groups of 10 parts by weight of the end of the polymer, such as 1 part to 10 parts . Methods of preparing the guanidino containing polymers will be apparent to a person skilled in the art, but for example, they may be prepared following the teachings of Schnaar, L. And R. Lee, Y. C., 1975, Biochemistry 14, 1535 -1.541 Who describes a method for linking biologicaly active ligands in a polymer matrix, polymers or can alternatively be determined by the reaction with a polymer containing amino groups attached the spine polymer (a) 3.5-dimethylpyrazole-1-Carboxamidine nitrate (b) S-methylthiouronium sulfate or (c) O-methylpseudourea hydrogen sulphate. It was found that the polymers of the invention are able to specifically bind phosphate anions in vitro and in vivo. The polymers of the invention have a particular use for the prevention of phosphate from the diet and also the removal of excess phosphate in the blood of these patients with a deficit since the kidneys of phosphate binding in the intestine the diet disrupts the balance of the body and the effects of the movement of phosphate blood flow in the intestine. The polymers of the invention can be administered to patients orally as food or as a complement to a food, pharmaceutical or a song. According to a second aspect of the invention, there is provided a food or a supplement to a foodstuff physiologically acceptable composed of a polymer of the invention. These foods can take various forms, for example by taking the conventional form of the human diet. According to a third aspect of the invention, it is anticipated pharmaceutical composition suitable for oral administration physiologically acceptable composed of a polymer of the invention in combination with a diluent or pharmaceutically acceptable carrier. The guanidino group containing polymer can be made in a pharmaceutical composition by a variety of methods. The pharmaceutical composition normally be administered orally, as it should be present in the patient's intestine rather than in the blood. Although the compositions incorporating a liquid solvent can be used for oral administration, it is preferable to use compositions comprising a solid carrier such as starch, lactose, dextrin or magnesium stearate. Such compositions sound should be composed of a kind, for example in the form of tablets, capsules, etc. The compositions of pharmaceuticals, food products or more for food can be made in unit dose, ie in the form of discrete parts containing a unit dose, or a multiple or sub-unit of a unit of dose. The mix of guanidino group containing polymer will of course depend on the circumstances and severity of kidney disease in the patient, as well as the chemical structure of the guanidino group containing polymer. As an orientation daily dose in terms of guanidine be in the range of 1 g to 10 g and therefore the amount of polymer can be calculated accordingly. According to another aspect of the invention is a method for treating a patient who understands the administration said the patient a guanidino group containing polymer described above to control phosphate from the diet and to eliminate excess phosphate in the bloodstream. According to another aspect of the invention, it is planned to use a guanidino containing polymer described above for the manufacture of a drug for the treatment of a patient with the aim of controlling phosphate from the diet and to remove excess phosphate in the bloodstream.