KR790000961B1 - Process for preparing haptaminol adenosin-5'-monophosphate - Google Patents

Abstract

5'-AMP heptaminol salt (I) was useful for treatment of circulatory disturbances. The effects of I (5mg/kg) on cardiac function in dogs (increased coronary sinus flow and pvO2 decreased systemic arterial pressure and heart rate, and increased left ventricular contraction amplitude) were unequal to the sum of those of AMP and heptaminol sep., I(4-6 × 300mg/day orally) relieved pain, cramps, and edema in patients with peripheral vein disturbances.

Description

Method for preparing heptaminol adenosine-5'-monophosphate

The present invention relates to a method for preparing heptaminol adenosine-5'-monophosphate having an effect on the cardiovascular system. This compound can be used in particular as a medicine for the treatment of venous insufficiency.

Heptaminol adenosine-5'-monophosphate is represented by the following structural formula.

Compounds of the present invention are prepared by isotropic reaction of heptaminol with adenosine-5'-monophosphonic acid (AMP). The following example shows a method for preparing heptaminol adenosine-5'-monophosphate.

EXAMPLE

145.24 g (1 mol) of heptaminol is dissolved in 1,000 ml of cold distilled water, and 347.23 g (1 mol) of anhydrous AMP is slowly added. After a few minutes, the solution is evenly frozen and frozen in a vacuum at 40 ° C for 12 hours to dissolve the ice.

The product is obtained as a white powder, soluble in water and insoluble in organic solvents. This compound has a melting point of 118 ± 1 ° C. measured by capillary measurement. The UV spectrum of the 1% solution is 300 ± 15 at 261 mm. This compound has the following analytical values.

Calculated Value: C 43.89%: H 6.75%: N 17.06%

Found: C 43.59%: H 7.33%: N 17.53%

It should be noted that the combination of two compounds, starting materials, is completely different from the simple mixture of the two compounds.

Therefore, first of all, the investigation of physical and chemical properties confirmed the existence of a new substance. Second, the action of the new compound on the cardiovascular system is significantly different from the simple mixing of the two starting materials.

This compound and two starting materials were tested in dogs to investigate:

Blood flow rate such as coronary vein,

P _V O ₂ , such as coronary vein,

Right ventricular amplitude,

Blood pressure,

Pulse rate.

The results are shown in Table 1 below.

TABLE 1

As a result, the following comment can be made.

First of all, in the above investigation, the activity of the compounds of the present invention is not only due to the effects of AMP and heptaminol. On the contrary, for example, heptaminol has no effect on the change in blood flow rate of the coronary vein, whereas the compound of the present invention has less effect than AMP. Furthermore, AMP shows a positive effect on the present factor in ventricular contractility, whereas the compound of the present invention has a significantly less effect than heptaminol. This unexplained difference clearly indicates that a compound is not a simple mixture.

Secondly, it should be noted that while heptaminol has no effect, AMP increases only slightly, but the compound of the present invention greatly increases P _V 0 ₂ such as coronary veins. Since the compound raises blood pressure and stimulates the amplitude and heart rate of heart contraction, improving oxygen balance in the blood flow from the myocardium is not a bad effect on the heart.

The present compounds can be used in the field of venous medicine for the treatment of cerebrovascular insufficiency such as neuro-circulatory dysfunction, fatigue, dizziness, headache, tinnitus, etc. as such effects.

Therefore, a pharmaceutical is prepared by combining the present compound with a carrier or a diluent. Carriers and diluents are liquids and solids, and liquids include liquids, suspensions, syrups, and oils. Solids include pills, tablets, and dragees.

Of the applied layer of the compound, of particular interest in venipology, a capsule containing 300 mg of the active ingredient is prepared and prepared by mixing the following ingredients.

Compound of the Invention: 300 mg

Corn starch: 190 mg

Magnesium Stearate: 5mg

Talc: 10 mg

The compound of the present invention is mixed completely uniformly in a mixer, and magnesium stearate and talc are then added to fill the capsule of No. 0. This product was clinically tested by administering 4-6 capsules per day to patients with multiple venous Maltz vascular disorders.

This compound produced the results shown in Table 2.

TABLE 2

Claims (1)

A process for preparing adenosine-5'-monophosphonic acid by reacting heptaminol and adenosine-5'-monophosphonic acid.