DE2244909A1 - MEDICINAL PREPARATIONS FOR THE TREATMENT OF DIABETES MELLITUS - Google Patents

Description

DIPL.-CHEM., Dr. RER. Nat. D-8012 OTTOBRUNN, September 12th.

GERHARDVONDERBEY AUENSTRASSE 31a

PATENT ADVERTISER FERNRUF (0811) 6013189

224A909

SN 179.870.

Ivlagnor, Inc.,

Chicago, Illinois 60603 (V.St.A.).

"Medicinal preparations for the treatment of diabetes mellitus" Priority: September 13, 1971, V.St.A., No. 179 870.

The invention relates to medicinal preparations for the treatment of diabetes mellitus, the biotin either alone or in combination with insulin or with sulfonylureas, such as tolbutamide, if appropriate together with the usual pharmacologically compatible Contain carriers and / or diluents.

In short, according to the prevailing opinion, diabetes is a metabolic disease, where the pancreas does not make enough active insulin to raise the glucose or blood sugar up to keep the normal height. When the blood sugar level rises in healthy people, the insulin secretion slows down the pancreas increases, and vice versa, if the blood sugar level is decreased, the insulin secretion is decreased.

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set. Occasionally the ability goes down with individuals lost to maintain this homeostatic mechanism, so that functionally the disease diabetes mellitus results.

Diabetes is usually determined by controlling the patient's diet and / or by the administration of insulin or some other known agent such as tolbutamide, for example the one under the trademark "Orinase" from Upjohn Go. known preparation, or other orally administered antidiabetic agents. ·

While these known agents have generally been recognized, it has been found that the administration of biotin, in Combination with insulin, the administration of biotin in combination with tolbutamide and the administration of biotin alone. in the treatment of diabetes it is considerably more effective to lower the blood sugar content than it is with the known means is attainable. The aforementioned features and advantages of the invention are explained in more detail below. The attached Drawings serve to explain the invention.

Fig. 1 is a bar graph showing the disappearance of free biotin with various additives;

2 shows the structural similarities on the basis of the formula images between biotin and oral sulfonylureas;

Figure 3 is a bar graph showing the results with the addition of Biotin as a treatment diet illustrated} and the

Figures 4, 5 and 6 are graphs showing the results of Show test examples.

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It is assumed that the vitamin biotin is physiological Role in relation to insulin and diabetes mellitus. It is also assumed that one of the possible explanations for the observed effect is a chemical or physical reaction between biotin and insulin. About the; correctness

- I.

To attempt to establish these assumptions are in vitro studies carried out, the disappearance of the free, that is, the biotin not bound to protein from a mixture to measure biotin, insulin and serum under different conditions. A health recovery investigation by means of biotin concentrations is from the in Pig. 1 can be seen. In this investigation are the following additions were made to each bottle differently than indicated in Fig. 1:

15 mug / ml biotin, 100 u units / ml insulin, 1.0 ml normal serum and 0.5 ml phosphate buffer with a pH value of 7 »0 are added to a total volume of 5.0 ml. Using a microbiological test method, the free biotin is measured ^{after incubation at 37 ° C. for one hour.}

Following these in vitro investigations, additional Investigations and studies carried out on a number of patients. The results obtained underline the effectiveness treatment with biotin.

In terms of the structural similarity between biotin and orally administered sulfonylureas according to Pig. 2 will furthermore provided that one of the possible explanations for the effect of the orally administered sulfonylureas in

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an effect in the normal biotin metabolism. That is why biotin is combined with "Orinase" in one Series of examinations and exams has been tested. One Summary of results is in Pig. 3 indicated the blood sugar levels before and after administration of biotin shows in fasted patients and after eating.

The results of the examples are given in Figs. The data given for each example shows the dose given to the patient on a milligram per kilogram basis Body weight and per day have been given. Particular care is taken to maintain or increase the caloric value of the diet during the duration of the biotin administration, so that the results obtained can be viewed as the effect of the biotin and not as a result of a decrease in the caloric value of the diet. It is still established that an increased caloric value of the diet most likely underscores a previously indicated hyperglycemiaI would. · I

The data are also used to determine whether biotin is associated with a possible Blood sugar increase. The patients included in this study showed prior to administration biotin almost normal blood sugar levels. No hyperglycemia is noticed during the biotin test.

The tests are also used to examine the effects of biotin in detail performed on hyperglycemia in untreated diabetics. The tests show that during treatment with biotin, the blood sugar levels do not deviate from the normal level.

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soft and not lowered to the normal level, even when the caloric value of the diet during the administration of the biotin is increased.

The exams are also performed on patients who are using "Orinase" and on which this preparation shows no significant effects. When in treatment If biotin is administered, there is a decrease in blood sugar

hold both when sober and after eating

remarkable. ;

Tests are also carried out on patients who have previously been administered have been treated with both "Orinase" and insulin. Treatment with "Orinase" and insulin is discontinued and treatment with biotin alone is started. The blood sugar levels, which are recorded while the patient is fasting, begin immediately after the use of biotin instead to drop high doses of "Orinase". The measurements after eating show a similar -. Effect to a slightly lesser extent.

Tests are also done on patients who are using insulin have been treated without significant effects, «The Treatment with insulin is modified by the inclusion of biotin, that is, giving the patient a combination of biotin and insulin is administered. The measurements made in the fasting state of the patient show that the blood sugar levels immediately fall to the almost normal height »The one after the Measurements made at Essen show a steady decrease

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the blood sugar levels.

In summary, it has been found that the addition of biotin A previously practiced treatment is beneficial by lowering the measurements of blood sugar levels when the patient is fasted and after eating. It has also been found that the administration biotin does not show any signs of hyperglycaemia.

As mentioned earlier, the exemplary results are given below and shown in Figs.

Example 1 (Fig. 4).

An initial or control phase I on the basis of three days given a general diet of 1,800 calories without any anti-diabetic supplements. Phase II (same diet) consists of a four-day treatment with "Orinase" in one dose from 500 mg four times a day (reduced to 500 mg twice a day on the last day). During phase III (same diet) during five days is "Orinase" on an amount of three times a day 500 mg on the first day and 500 mg twice daily for the remaining days. Twice a day, 10 mg of biotin are used in a Do = at a rate of 0.32 mg / kg / day. As can be seen from Fig. 4, during phase I blood sugar levels are fasting Patients increased (the patients' blood sugar levels after a meal are also increased). During phase II the blood sugar levels remain elevated in the fasted patients, and the levels in the patients after eating show obvious a moderate drop from the value of $ 164 mg. Immediately

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" ⁷ " 22A4909

after the start of the biotin treatment, the blood sugar levels are both in the fasted patient and in the post-meal patient within normal limits.

Example 2 (Pig, 5).

For five days during phase I, a diet of 1,800 calories is used Maintained daily and 40 units of NPH insulin administered. Like from Pig. 5 can be seen is the Insulin treatment not effective. In phase II it will be the same Maintain diet and administer biotin at a dosage of 0.44 mg / kg / day. The blood sugar levels in an empty person Patients immediately drop almost completely to normal, and so does patients' blood sugar levels after eating v / earth gradually lowered.

Example 3 (Pig. 6).

During phase I, a diet of 1,800 per day is used for nine days Preserve calories. "Orinase" is administered in large, varying doses, that is, two or three times a day 1000 mg on five of the nine days, and insulin is also given in varying doses of approximately 30 units per day administered on six of the nine days. The same diet is maintained during phase II of these nine days. "Orinase" won't work administered, but approximately 30 units of insulin per day and 10 mg biotin four times a day (10 mg biotin three times a day for the first two days). The biotin dosage is about 0.39 mg / kg / day. The use of biotin instead of "Orinase" is associated with a decrease in blood sugar levels when the

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ternal patients and connected to patients after eating. During phase III of six days, the same diet is maintained, but neither "Orinase" nor insulin is administered with the exception of the first and third days, on which 20 and 15 units are administered, respectively, but 10 mg biotin four times a day given. During this phase, the blood sugar levels in fasting patients reach a low and relatively constant level, and in patients after eating, the blood sugar levels drop evenly. Thereafter, neither ^M Orinase nor insulin nor biotin is administered for four days. It has been found that during this phase the blood sugar levels in fasting patients and in patients after eating remain relatively constant.

From the above it can be seen that the addition or use of biotin in the earlier practice Treatment is associated with a remarkable decrease in blood sugar levels.

Although in the above description certain typical products and compositions are described, however, it is clear that modifications and changes can be made therein without departing from the spirit and scope of the invention.

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Claims (5)

PATENT CLAIMS 1) Medicinal products for the treatment of diabetes mellitus,
characterized by a content of biotin and
if necessary, customary pharmacologically acceptable carriers and / or diluents » 2) Medicinal preparations according to claim 1, characterized by an additional content of insulin. ■ · 3) Medicinal preparations according to claim 2, characterized by a content of biotin of 0.25 to 0.75 mg per kilogram of body weight and a Göhalt of insulin of 15 to 4-0 units for the
Daily requirement. 4) Medicinal preparations according to claim 1, characterized by a additional content of an orally administered sulfonyl urea. 5) Medicinal preparations according to claim 4 _? characterized by a biotin content of 0.25 to 0.75 mg per kilogram of body weight and a tolbutamide content of 1000 to 2000 mg for the
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