Insulin Pills

The issue of insulin-dependent diabetes has long been discussed. No wonder, as the problem concerns more than 5% of the world population. However, despite the enormous efforts and funds spent on its solution, the scientists so far have failed to replace the injections with pills. The difficulty is that insulin (like any other polypeptide) gets easily destroyed under the influence of proteolytic enzymes in the stomach and small intestines. The scientists have tried a variety of means: insulin plasters, inhalations, capsules covered with a special protective coating, but none of the above has ensured the required effect. The amount of insulin thus getting into the blood is insufficient for normal functioning of the organism.

Chemists from the the Topichev Institute for Petrochemical Synthesis have suggested a unique and efficient solution to the problem having split it into two parts. To ensure that the remedy gets into the blood out of the pill, it is required that the remedy slipped `safely` through the stomach – this is stage one. Then it is necessary to make sure that the remedy gets into the blood in the small intestines quicker than the enzymes would destroy it – this is stage two.

The first part of the problem can be solved easily. It is sufficient to cover the pill with a layer that is resistant to the stomach ferments action and dissolves once the pill gets into the intestine. Quite harmless polyacrylic or polymethacrylic acid suits this purpose, therefore the researchers have proposed to use it as a coating. However, in such case insulin will not `live` long enough – it will be destroyed by the enzymes earlier than it gets through the intestine walls. At this stage works the major specificity that differs the pills from all the previous remedy forms applied.

The researchers have suggested that the pills should be made of the pressed little grains of hydrogel, where three substances are introduced. The first substance is insulin per sei. It is not chemically bound with the hydrogel and therefore can be easily released. The second substance is an inhibitor which protect insulin against the enzymes. To ensure that the inhibitor does no harm to the organism, it is made chemically bound with the hydrogel. Thus it will react only with those enzyme molecules which try to penetrate into the hydrogel grain and to `eat up` the insulin from its surface. The hydrogel is indigestible by a human organism, so the bound inhibitor will not get into the blood and leave the organism in a natural way with the hydrogel grains.

And finally, it is necessary to retain the hydrogel grains near the intestine wall so that the insulin protected by the inhibitor against the enzyme attack could stick to the mucous membrane of the intestines and successfully get into the blood. Some `anchor` is required to achieve this. The scientists have proposed to use some polysaccharide as an anchor, the polysaccharide also being chemically bound with the hydrogel. The point is that the intestine wall contains the so-called lectins – the substances which interact with sugars. The lectins are quite capable of binding with polysaccharides on the surface of the hydrogel grains and holding them attached to the mucous membrane.

The last thing to do was to introduce three types of compounds into the hydrogel, namely insulin, enzyme inhibitor and polysaccharide serving as an anchor. However, the developers and patent holders have come to the conclusion that the process can be simplified – it is required to find a substance which could fulfil two functions simultaneously – of an `anchor` and of an inhibitor.

The scientists suggested that the ovomucoid glycoprotein could play this role. This compound seems to be deliberately created for this purpose by nature. The ovomucoid happens to consist of two parts. The protein part is responsible for the enzyme binding, and the carbohydrate part reacts with lectins of the mucuous membrane. The scientists have assumed that the ovomucoid should be added to the hydrogel containing insulin.

As a result the researches have produced the insulin pills based on the hydrogel containing the chemically immobilized ovomucoid. The pills were initially tried on animals – rabbits, mice and rats. Since the results were rather promising, it was decided to proceed with clinical trials of the pills – the pills could not do any harm, but their efficiency should be proved.

The pills are currently undergoing the second stage of the clinical trial and the results are very convincing. Judging by the glucose and insulin concentration in the blood, the perroral intake ensures the same effect as the insulin injection directly into the blood.

“Our drug produces the same effect as traditional injections. The pill should also be taken four times a day, about half an hour before the meal. Of course, the drug does not eliminate the problem completely, it does not cure the patient, what it does – it relieves the patient 4 injections a day. No other remedy has succeeded to achieve that so far,” says Professor L. I. Valuyev, one of the drug developers. The scientists called the drug `RANSULIN`, the name originates from the Russian abbreviation for the Russian Academy of Sciences and insulin.

Apparently the way from the clinical trials to the pharmacies can take several years. However, this is only a matter of time, since the efficiency of perroral insulin developed by the Russian scientists gives rise to no doubts.