JPH02131422A - Medicine for diabetes mellitus - Google Patents

Abstract

PURPOSE:To provide the subject medicine containing one or more of D- phenylalanine, L-phenylalanine and DL-phenylalanine, capable of efficient control of diabetes mellitus and efficient protection of complication thereof, free from side effects and having high safety. CONSTITUTION:The subject medicine containing one or more of D-phenylalanine, L-phenylalanine and DL-phenylalanine as an amino acid is administrated by itself or together with insulin for effective action thereof to a diabetic to inhibit diabetes mellitus and complication thereof and to effectively control diabetes mellitus. Additional oral administration of either of the above-mentioned medicines in an amount of 100-250mg per day to a serious diabetic taking insulin and an oral hypoglycemic agent enable disappearance of subjective symptom and can return blood-sugar levels, blood-urea nitrogen levels, total cholesterol levels, triglyceride levels, etc., to the normal levels.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention provides drugs useful for the treatment of diabetes and diabetic complications;
Specifically, the present invention relates to a drug useful for treating diabetes and diabetic complications, containing at least one of D-phenylalanine, L-phenylalanine, and DL-phenylalanine.

[Conventional technology]

Diabetes is a disease that occurs as a result of disorders in carbohydrate metabolism, protein metabolism, lipid metabolism, etc. due to absolute or relative insulin deficiency.The true cause of its onset is still unclear, but genetics, glucose or eating too many calories,
It is thought that various infectious diseases, endocrine disorders, trauma, mental disorders, drug-induced disorders, etc. are triggers. This treatment uses dietary and exercise therapy, as well as insulin and hypoglycemic drugs. Insulin is a hormone secreted from the β-cells of Langerhaus's island in the Swiss viscera, and has the effect of lowering blood sugar levels, accumulating glycogen in the liver and muscles, and promoting the burning of sugar. It reduces the insulin secretion ability and eventually stops the insulin secretion function of the sui viscera. On the other hand, hypoglycemic drugs include sulfonylureas and biguanides, but their mechanisms of action are believed to include suppression of α cells in the islets of Langerhaus, promotion of β cell function, and inhibition of insulinase. However, it is not clear and its hypoglycemic effect is weak.
Strong side effects. Therefore, it is absolutely necessary to follow a doctor's instructions when using these drugs for diabetes. Since the discovery of insulin, deaths due to diabetes have sharply decreased, and current diabetes treatment focuses on controlling diabetes and preventing diabetic complications. However, there are no drugs that can appropriately control diabetes and prevent its complications.

[Problem to be solved by the invention]

The present invention provides a safe drug that efficiently controls diabetes and prevents diabetic complications and exhibits no side effects.

[Means to solve the problem]

As a result of various studies, the present inventor found that D-phenylalanine (hereinafter referred to as D-PA), L-phenylalanine (hereinafter referred to as L-PA), and DL-phenylalanine (hereinafter referred to as DL-PA) are effective for diabetic patients. I learned that it works effectively, suppresses diabetes and its complications, and efficiently controls diabetes. D-PA and L-PA are amino acids that can be easily obtained by optical resolution of synthetically prepared DL-PA. L-PA is known as an essential amino acid and a substance indispensable to living organisms, and DPA also has various It is recognized that it has physiological effects. In general, diabetic patients often suffer from increased blood sugar levels as well as renal damage and hyperlipidemia, and increased blood urea nitrogen (abbreviated as BUN), total cholesterol levels, and triglyceride levels. It has been found that such abnormalities can be restored to normal values by administering any one of D-PA, L-PA, and DL-PA alone or together with insulin.

In addition, D-PA, L-PA and DL-P are used in severely diabetic patients receiving insulin and oral hypoglycemic agents.
By orally administering 100 to 250 μ/day of any one of Type A, subjective symptoms such as fatigue, loss of appetite, stiff shoulders, heavy head, and abdominal bloating disappear from about 3 weeks after administration of phenylalanine (PA). , clinical test results also indicate blood sugar level, BU
The N value, total cholesterol level, triglyceride level, etc. returned to normal values, indicating that the comorbidities were cured, and the amount of exercise and dietary calories increased, and the weight returned to normal. More oral blood I1! There was no change in subjective symptoms or clinical test results even after the administration of the anti-depressant drug was discontinued, indicating that the administration of PA efficiently controlled diabetes and was effective in suppressing diabetic complications. These results can be confirmed by administering PA in conjunction with diet and exercise therapy in the case of mild diabetes, and in patients with a relatively long and severe medical history who are using insulin or oral hypoglycemic agents. This can be said to indicate that diabetes can be efficiently controlled and complications can be improved by administering PA in combination with this drug, that is, administration of PA is suitable for preventing complications. D-P
A is a white powder that is obtained by optical resolution of DL-PA together with L-PA and is sparingly soluble in water.
D.

It has been shown that there is no risk of acute toxicity even when administered to humans at 4 g/day, making it a safe substance like L-PA.

[For production]

It is not yet clear exactly how D-PA, L-PA, and DL-PA effectively control diabetes and effectively treat its complications. However, it has been revealed that D-PA and L-PA have the effect of activating the humoral and cellular immune capacities of rats and mice. This activation effect is due to the fact that these drugs inhibit the activity of carpoxypebutidase A and increase the concentration of morphine-like substances such as β-endorphin in the blood, and this increase in concentration activates immune function. It has been demonstrated that this is possible. That is, an increase in the concentration of β-endorphin increases host resistance.

It is presumed that the administration of D-PA and L-PA increases the resistance of the body and efficiently controls diabetes and suppresses complications.

The present invention will be specifically explained by giving examples (including clinical examples and animal experiment examples) below.

A. Comparison of the effects of D-PA, L-PA, and β-endorphin with those of insulin in animal experiments.

Experiment-1 Diabetic rats induced by intraperitoneal administration of alloxan 180/kg were treated with the treatment plan shown in Table ■.
D-PA2 50 μ/kg was administered intraperitoneally (ip), insulin 10 units/day subcutaneously (sc), and β-endorphin 10 −8 mol Zrr & intravenously (iv).

The therapeutic effect after administration of each drug was evaluated by measuring the serum glucose level. The results are shown in Table 2. It is clear that D-PA and β-endorphin, like insulin, effectively lower serum glucose levels in alloxan diabetic rats. Body weight recovery was observed with β-endorphin and insulin, but not with D-PA alone.

Experimental Example 2 Streptozotocin
n) D-PA and L-P were administered to diabetic rats induced by administration of 60 μ/kg (intravenous injection) according to the treatment plan shown in Table 3.
A, 250 μ/kg was administered intraperitoneally; 10 units of insulin was administered subcutaneously for 7 days.

The results after treatment are shown in Table-3. Similar to experiment-1,
In streptozotocin-induced diabetic rats, D
-PA and L-PA, similar to insulin, significantly improved serum glucose levels. However, the effect is D-
PAO was superior to L-PA. The combination of D-PA and insulin significantly improved body weight.

Method B of administering D-phenylalanine (D-PA) Noenyl I727 (L-PA) and inshelin to 1 runt
．． Clinical Case: A patient diagnosed with intractable diabetes and having a blood sugar level of 580 µ/dI was started on 10 units of insulin and 1 tablet of the oral hypoglycemic drug cymetrine. After 10 months of continuous administration, the blood sugar level decreased to 335■/d1, but after that, the blood sugar level decreased to 1
For three months, there was no improvement in his blood sugar level or subjective symptoms, and he was in poor physical condition. Therefore, when we started oral administration of D-PA250■/day, improvement was seen in the patient's subjective symptoms from 3 weeks after starting administration of D-PA, and after 1 month, the patient's visual acuity due to diabetic cataracts improved. Subjective symptoms other than the disorder, such as fatigue, loss of appetite, stiff shoulders, heavy head, abdominal bloating, and bleeding gums, disappeared. Six months after starting D-PA administration, simetrine was discontinued, but there was no change in subjective symptoms. Regarding exercise therapy, 2000 to 2
Physical activity of 500 steps/day decreased to 2 on average 6 months after D-PA
500-5, O O O steps/day, average 5.5 after 12 months. I was able to increase it to 0 0 0 steps/day.

Regarding dietary therapy, before administration of D-PA, 1,000
Ocal/day, but 6 months after administration, it decreased to 1, 2
0 0cal/day, 1,200 to 1 after 12 months
．． The patient's weight was 40 kg before administration of D-PA, but the patient's weight was 40 kg before administration of D-PA.
Six months after administering PA, the patient's weight was 48 kg, and 12 months later, it was 55 kg, which is almost normal weight. These changes are also noticeable in the clinical test results, and as shown in Table 5, D-P
The results indicate that various test results returned to normal values after administration of A. That is, diabetes was effectively controlled and complications were suppressed by administration of D-PA.

When L-PA and DL-PA were administered, results similar to those of D-PA were obtained, indicating that the combination of these drugs effectively controls diabetes and suppresses complications. However, the effects of L-PA and DL-PA are
- It was observed that the temperature was somewhat lower than that of PA.

〔Effect of the invention〕

By using D-PA, L-PA, and DL-PA alone or in combination with insulin, diabetes can be efficiently controlled and its complications suppressed. D-PA, L-P
Since A and DL-PA are amino acids and are harmless to living bodies, their use has the advantage of not causing any side effects to living bodies, and provides an appropriate treatment for controlling diabetes and preventing complications that did not previously exist. This is what we provide.

Agent: Patent Attorney Hideaki Kuwahara

Claims (1)

[Claims] D-phenylalanine, L-phenylalanine and DL
- A drug for diabetes characterized by containing at least one type of phenylalanine.