A compound, a composition and its use in preparing medicine for treating heart disease

Abstract

The present invention relates to the field of medicinal chemistry and specifically discloses a compound, a composition, and their use in preparing a medicament for treating heart disease. The compound is dihydroanemulyl acetate, isosaxifen, or lindera lactone. The composition comprises dihydroanemulyl acetate, isosaxifen, and lindera lactone. Studies have shown that compounds such as dihydroanemulyl acetate, isosaxifen, and lindera lactone have therapeutic effects on ischemic heart disease. Therefore, using dihydroanemulyl acetate, isosaxifen, or lindera lactone, or a combination thereof, as an active ingredient in preparing a medicament for treating heart disease has important application value.

Description

Technical Field

[0001] The present invention relates to the field of medicinal chemistry, and in particular to a compound, a composition and application thereof in preparing medicine for treating heart disease. Background Art

[0002] The circulatory system is composed of the heart, blood vessels, and neurohumoral tissues that regulate blood circulation. Circulatory system diseases are also called cardiovascular diseases, and heart disease is a relatively common type of circulatory system disease. It can significantly affect the patient's work capacity.

[0003] Ischemic heart disease is a type of heart disease. It includes coronary artery obstruction or stenosis caused by atherosclerotic lesions, left ventricular aneurysm caused by myocardial ischemia, ventricular septal defect after myocardial embolism, and mitral regurgitation caused by papillary muscle ischemia. It is a common acquired heart disease in middle-aged and elderly individuals. Therefore, developing a compound or composition for the treatment of ischemic heart disease has important application value. Summary of the Invention

[0004] In order to overcome at least one of the technical problems existing in the prior art, the present invention provides a compound, a composition and use thereof in preparing a medicament for treating heart disease.

[0005] The present invention aims to solve the above technical problems by implementing the following technical solutions:

[0006] The invention discloses an application of a compound in preparing a medicine for treating heart disease. The compound is dihydroanemyl acetate, isosaxifen or lindera lactone.

[0007] The inventors surprisingly discovered during their research that compounds such as dihydroanthellol acetate, isosaxifen and lindera lactone have the effect of treating ischemic heart disease; therefore, using dihydroanthellol acetate, isosaxifen or lindera lactone as active ingredients for the preparation of drugs for treating heart disease has important application value.

[0008] Preferably, the heart disease is ischemic heart disease.

[0009] The present invention also provides a composition, which is composed of dihydroanemyl acetate and any one or two of the following compounds:

[0010] The compounds are isosaxifen and lindera lactone.

[0011] Since compounds such as dihydroanthellol acetate, isosaxifen and lindera lactone all have the effect of treating ischemic heart disease, the composition obtained by combining any two or three of dihydroanthellol acetate, isosaxifen and lindera lactone also has the effect of treating ischemic heart disease.

[0012] Preferably, the composition consists of dihydroanemyl acetate, isosaxifen and lindera lactone.

[0013] The inventors also surprisingly discovered during their research that a combination of dihydroanthellol acetate, isosaxifen, and lindera lactone is significantly more effective in treating ischemic heart disease than either dihydroanthellol acetate, isosaxifen, or lindera lactone alone. Furthermore, the combination of dihydroanthellol acetate, isosaxifen, and lindera lactone can synergistically treat ischemic heart disease.

[0014] In addition, the inventors also found in the study that the effect of the composition obtained by combining dihydroanemulyl acetate with any two of the three compounds, namely, isosaxifen and lindera lactone, in treating ischemic heart disease was not improved or significantly improved compared with that of dihydroanemulyl acetate, isosaxifen or lindera lactone alone; this shows that the combination of dihydroanemulyl acetate with any two of the three compounds, namely, isosaxifen and lindera lactone, cannot produce a synergistic effect in treating ischemic heart disease; only when dihydroanemulyl acetate, isosaxifen and lindera lactone are combined at the same time can a synergistic effect in treating ischemic heart disease be achieved.

[0015] More preferably, the weight ratio of dihydroanemyl acetate to isosaxifen and lindera lactone in the composition is 2-4:1:1.

[0016] Most preferably, the weight ratio of dihydroanemyl acetate to isosaxifen and lindera lactone in the composition is 3:1:1.

[0017] The present invention also provides an application of the composition in preparing medicine for treating heart disease.

[0018] Preferably, the heart disease is ischemic heart disease.

[0019] Preferably, the drug is in the form of granules, tablets, capsules, oral solutions or injections.

[0020] Beneficial Effects: The present invention provides a novel use of the known compounds dihydroanthellol acetate, isosaxifen, and lindera lactone. Studies have shown that compounds such as dihydroanthellol acetate, isosaxifen, and lindera lactone have therapeutic effects on ischemic heart disease. Therefore, using dihydroanthellol acetate, isosaxifen, or lindera lactone, or combinations thereof, as active ingredients in the preparation of drugs for treating heart disease has significant application value. DETAILED DESCRIPTION

[0021] The present invention is further explained below with reference to specific examples, but the examples do not limit the present invention in any form.

[0022] Example 1 Ischemic heart disease experiment

[0023] Method for establishing an ischemic heart model mouse: a male ICR mouse weighing 24-26 g was anesthetized with sodium pentobarbital and then fixed; the mouse hair on the chest was then removed and the animal was connected to a ventilator with a respiratory ratio of 1:1, a tidal volume of 2 mL / kg, and a respiratory rate of 100 times / min; the thoracotomy was then performed between the third and fourth intercostal spaces in the left chest cavity of the mouse to expose the heart; the left coronary artery under the left atrial appendage was ligated with a sterile suture; after ligation, the chest cavity was sutured to obtain an ischemic heart model mouse.

[0024] Mice with ischemic heart models obtained according to the above-mentioned modeling method were randomly divided into a model group and experimental groups 1 to 7, with 12 mice in each group. The experimental groups were gavaged daily with the test compound or composition at a dose of 10 mg / kg / d; the model group was gavaged with an equal amount of 0.5% CMC-Na aqueous solution. At the same time, normal male ICR mice weighing 24 to 26 g were gavaged daily as a normal control group with an equal amount of 0.5% CMC-Na aqueous solution. After 7 consecutive days of gavage, left ventricular ejection fraction (EF) and fractional shortening (FS) were measured by ultrasound. The test results are shown in Table 1.

[0025] The compound administered orally to experimental group 1 was dihydroanemyl acetate; the compound administered orally to experimental group 2 was isosaxifen; the compound administered orally to experimental group 3 was linderalide; the compound administered orally to experimental group 4 was a combination of dihydroanemyl acetate and isosaxifen at a weight ratio of 3:1; the compound administered orally to experimental group 5 was a combination of dihydroanemyl acetate and linderalide at a weight ratio of 3:1; the compound administered orally to experimental group 6 was a combination of isosaxifen and linderalide at a weight ratio of 1:1; and the compound administered orally to experimental group 7 was a combination of dihydroanemyl acetate, isosaxifen and linderalide at a weight ratio of 3:1:1.

[0026] Table 1. Experimental results of the compounds or compositions of the present invention in treating ischemic heart disease

[0027]

[0028]

[0029] From the experimental data in Table 1, it can be seen that the left ventricular ejection fraction (EF) and fractional shortening (FS) of the model group were significantly lower than those of the normal control group; this indicates that the ischemic heart model mice were successfully established.

[0030] From the experimental data in Table 1, it can be seen that the left ventricular ejection fraction (EF) and fractional shortening (FS) of experimental groups 1 to 3 were significantly higher than those of the model group; this indicates that compounds such as dihydrocarbamidoacetic acid ester, isosaxifragine and lindera lactone have certain effects in treating ischemic heart disease.

[0031] As can be seen from the experimental data in Table 1, the left ventricular ejection fraction (EF) and fractional shortening (FS) of experimental groups 4 to 6 were also significantly higher than those of the model group; this indicates that the composition composed of any two of the three compounds, dihydrocarbendazim acetate, isosaxifragine and lindera lactone, also has a certain effect in treating ischemic heart disease.

[0032] As can be seen from the experimental data in Table 1, the left ventricular ejection fraction (EF) and fractional shortening (FS) of experimental group 7 were significantly higher than those of the model group, and also significantly higher than those of experimental groups 1 to 3. This indicates that the composition obtained by combining dihydroanemulyl acetate, isosaxifen and lindera lactone has a significantly higher effect on treating ischemic heart disease than dihydroanemulyl acetate, isosaxifen or lindera lactone alone; at the same time, the combination of dihydroanemulyl acetate, isosaxifen and lindera lactone can play a synergistic role in treating ischemic heart disease.

[0033] In addition, although the left ventricular ejection fraction (EF) and fractional shortening (FS) of experimental groups 4 to 6 were significantly higher than those of the model group, they were not improved or significantly improved compared with experimental groups 1 to 3; this shows that the effect of the composition obtained by combining any two of the three compounds, dihydroanthell acetate, isosaxifen and lindera lactone, on treating ischemic heart disease was not improved or significantly improved compared with dihydroanthell acetate, isosaxifen or lindera lactone alone; the effect of combining dihydroanthell acetate with any two of the three compounds, isosaxifen and lindera lactone, on treating ischemic heart disease was not improved or significantly improved; The combination of dihydroanemyl acetate, isosaxifen and lindera lactone did not produce a synergistic effect in treating ischemic heart disease; only when dihydroanemyl acetate, isosaxifen and lindera lactone were combined at the same time could they produce a synergistic effect in treating ischemic heart disease; only when the combination of dihydroanemyl acetate, isosaxifen and lindera lactone resulted in a composition with a significantly higher effect in treating ischemic heart disease than that of dihydroanemyl acetate, isosaxifen or lindera lactone alone.

[0034] Example 2 Preparation of granules

[0035] The granules are prepared with dihydroanemyl acetate as an active ingredient according to conventional preparation technology in the art.

[0036] Example 3 Preparation of granules

[0037] The granules are prepared with isosaxifenesin as the active ingredient according to conventional preparation technology in the art.

[0038] Example 4 Preparation of granules

[0039] The granules are prepared with lindera lactone as the active ingredient according to conventional preparation technology in the art.

[0040] Example 5 Preparation of granules

[0041] A composition consisting of dihydroanemyl acetate, isosaxifen and lindera lactone in a weight ratio of 3:1:1 is used as an active ingredient and is prepared into granules according to conventional preparation technology in the art.

[0042] Example 6 Preparation of Tablets

[0043] The tablets are prepared with dihydroanemyl acetate as an active ingredient according to conventional preparation technology in the art.

[0044] Example 7 Preparation of Capsules

[0045] The capsule is prepared with isosaxifenesin as an effective ingredient according to conventional preparation technology in the art.

[0046] Example 8 Preparation of Oral Liquid

[0047] The oral liquid is prepared with lindera lactone as the active ingredient according to conventional preparation technology in the art.

[0048] Example 9 Preparation of Injection

[0049] The injection is prepared by using a composition consisting of dihydroanemyl acetate, isosaxifen and lindera lactone in a weight ratio of 3:1:1 as an active ingredient according to conventional preparation technology in the art.

Claims

1. A composition, characterized in that The composition consists of dihydrocarbendazole acetate, isosaxifen and lindera lactone; The weight ratio of dihydrocarbendazole acetate to isosaxifen and lindera lactone in the composition is 2-4:1:

1.

2. The composition according to claim 1, characterized in that The weight ratio of dihydrocarbendazole acetate to isosaxifen and lindera lactone in the composition is 3:1:

1.

3. Use of the composition according to claim 1 or 2 in the preparation of a medicament for treating heart disease.

4. The use according to claim 3, characterized in that The heart disease is ischemic heart disease.

5. The use according to claim 3, characterized in that The medicine is in the form of granules, tablets, capsules, oral liquid or injection.

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