Insulin solution for peroral intake

FIELD: medicine, pharmaceutics.

SUBSTANCE: the present insulin solution for peroral intake should be applied for treating patients with diabetes mellitus. The suggested insulin solution consists of water and insulin, additionally, it contains sodium chloride at the following ratio of components, weight%: insulin 0.005-0.02, sodium chloride 0.5-1.0, water - up to 100.0. The innovation provides decreased glucose level in blood of animals in case of peroral intake of the solution up to 40% at insulin dosages being about 10 U/kg animal body weight.

EFFECT: higher efficiency.

12 ex, 1 tbl

 

The invention relates to medicine, namely to a solution of insulin for oral administration, which is used for the treatment of patients with diabetes mellitus.

Diabetes mellitus is one of the most common serious diseases, based on an absolute or relative lack of the pancreatic hormone insulin.

Insulin (insulin from the outside) and is the only traditional method of treatment of disease (especially for patients with insulin-dependent diabetes mellitus - IDDM), allowing to compensate for the deficiency of insulin in the body. The most common method of insulin administration is subcutaneous injection. This method is inconvenient, injure the psyche of patients (especially children), causes physical and mental suffering, but most importantly, can itself exacerbate the pathology of the disease. The latter is due to the fact that after subcutaneous injection of insulin normal concentration of glucose in the blood is achieved through systematic hyperinsulinemia peripheral tissues, while the liver (the main place of activity of endogenously produced in the body, insulin) lack of insulin.

The only way to prevent complications is inevitable concomitant injection of insulin therapy is to achieve a complete simulation of the natural markrecapture hormone in vivo and to simulate the physiological difference in the level of insulin in the portal and peripheral blood circulation systems. And from this point of view, oral (through the mouth) route of insulin delivery, at which it is absorbed through the intestinal-hepatic path, the most favorable.

The main obstacle to the oral route of administration of insulin is the low stability of the hormone to the action of proteolytic enzymes of the gastrointestinal tract that leads to the destruction of insulin during its passage from the mouth to the small intestine.

In recent decades there have been many attempts to create an oral form of insulin, however, still failed to develop an effective drug that can compete on its therapeutic effect with insulin, administered by injection.

A known solution of insulin for oral administration, consisting of insulin and water [WO 96/36352, PCT/CA/00305, AND 61 R 38/28, 1996]. The solution additionally contains a substance that accelerates the absorption of insulin in the small intestine, as well as inhibitors of proteolytic enzymes of the small intestine, preventing the destruction of the insulin.

The disadvantage of this solution is the impossibility of direct use for oral administration of insulin. Since the solution does not contain compounds that prevent hydrolysis of insulin in the stomach, before orally administered solution animate CC is completed with a sodium bicarbonate solution, which neutralizes the acidic environment of the stomach. Although the physiological action of the solution is rather high (oral rat 10 units of insulin in the composition of the solution containing 0.02 wt.% insulin causes a decrease in the concentration of glucose in the blood of animals 70-80%), the need to fully neutralize the acidic environment of the stomach sodium bicarbonate before the introduction of the solution makes it completely unsuitable for practical application.

The closest in technical essence and the achieved results to the claimed solution is a solution of insulin for oral administration, consisting of insulin and water in the following ratio of components: water to 99.6 wt.%, insulin 0.4 wt.% [M.Saffran, B.Pansky, G.C.Budd, F.E.Williams, Insulin and the gastrointestinal tract, Journal of Controlled Release, 1997, V.46, p.89-98].

The disadvantage of this method is the low efficiency of insulin. When using this solution instead of drinking water, that is, when a rat hundred mg of insulin, the glucose concentration in the blood of rats is reduced by 40-60%, but a large number of concentrated solution of insulin has a negative effect on the digestive process. After introduction of the solution animals lose weight, and in their digestive tract find a large amount of undigested food.

The aim of the invention is to increase the effektivnosti of insulin action.

The solution of the set goal is achieved by the fact that the solution of insulin for oral administration, consisting of water and insulin further comprises sodium chloride is in the following ratio of components:

insulin - 0,005-0,02 wt.%,

sodium chloride is 0.5 to 1.0 wt.%,

water up to 100 wt.%.

Example 1. In the water dissolve the sodium chloride to achieve a concentration of 0.9 wt.% and insulin to achieve a concentration of 0.01 wt.%. 10 ml of the obtained solution containing 1 mg (25 units) of insulin orally administered to the rabbit. Insulin dose of 9.7 units/kg of body weight of the rabbit. Then after 30, 60, 90 and 120 minutes measure the concentration of glucose in the blood, which is taken from the ear of the rat. The results are shown in the table.

Examples 2-8. The solutions prepared in example 1. The composition of the solutions and the results of their tests are given in the table.

Examples 9-11 (control). The solutions prepared in example 1. The composition of the solutions and the results of their tests are given in the table.

Example 12 (control). Rabbit injected subcutaneously with 3 ml of insulin with a concentration of 0.02 wt.%. The insulin dose is 5 units/kg weight of the animal. The results are given in the table.

It is seen that the use of dilute solutions of insulin claimed composition reduces the level of glucose in the blood of animals by oral administration of the solution to 40% at doses of insulin 10 units/to the weight of the animal. A similar decrease in the level of glucose in the blood after subcutaneous injection of a solution of insulin is achieved at a dose of only 2 times lower (example 12K). Increasing the concentration of a solution of insulin by oral administration leads to less efficient use of insulin (examples 9K and 10K). The decrease in the concentration of a solution of insulin while maintaining the dose of insulin is impractical, as it requires the introduction of large quantities, but does not improve the efficiency of insulin. Dose reduction of insulin (example 11K) does not provide sufficient reduction of glucose by oral administration of a solution. In the prototype, the reduction of the glucose level of 40% is achieved by oral administration to animals of a solution of insulin in doses of more than 1000, which in principle is dangerous and never, apparently, will not be approved for use.

Table.
# exampleCon-tion of NaCl, wt.%Con-tion of insulin, wt.%The insulin dose, units/kgThe concentration of glucose in the blood of rabbits, mg/100 ml
Exodus306090120*
10,90.01the 9.77580525459
21,00,01a 12.79088605158
30,50,0114,010068705957
40,70,0077,810069596268
51,00,00510,710887728184
60,90,0210,59782676772
70,80,029,310391708088
80,90,00711,4106111648676
9K0,90,0310,48889818792
10K1,10,0311,210291968594
11K0,90,0013,010197104100108
12K, subcutaneous injection0,90,025,19758515360
*the time after injection, min

A solution of insulin for oral administration, consisting of insulin, and water, characterized in that it further contains sodium chloride is in the following ratio, wt.%:

Insulin0,005-0,02
Sodium chloride0,5-1,0
Water100



 

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