Composition containing clausenamide and application of composition in preparation of medicine with effect of treating liver injury

Abstract

The invention relates to the technical field of biological medicines, and particularly discloses a composition containing clausenamide and application of the composition in preparation of a medicine with a liver injury treatment effect. The composition containing the clausenamide is prepared from the clausenamide and an active compound, the active compound is selected from ergolactone and / or isosaxifolin. Researches show that the composition has the effect of resisting alcoholic liver injury; in addition, the compound also has an anti-hepatitis B virus effect. Therefore, the composition has important application value when being used as an effective component for preparing the medicine with the effect of treating the liver injury and the medicine with the effect of resisting the hepatitis B virus.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedicine, and in particular to a composition containing clavamide and application of the composition in preparing a medicine for treating liver damage. Background Art

[0002] The liver is the largest solid organ in the abdominal cavity and is responsible for important physiological functions of the human body. Liver injury refers to damage to the liver by various factors, resulting in abnormalities in its structure and function. Common liver injuries include drug-induced liver injury and alcoholic liver injury. The liver is the main metabolic organ of alcohol. It first metabolizes alcohol into acetaldehyde, then further metabolizes it into acetic acid, and finally metabolizes it into carbon dioxide and water, thus completing the metabolism of alcohol. However, excessive drinking or long-term alcoholism will increase the metabolic burden of the liver, thereby causing liver damage. If alcoholic liver injury cannot be treated, it will be accompanied by cirrhosis, liver cancer and viral hepatitis over time. Therefore, providing a drug for the treatment of alcoholic liver injury has important application value.

[0003] Clausinamide is a known compound isolated from the leaves of the plant of the genus Clausin of the Rutaceae family, and its CAS number is 103541-15-7. Although the prior art reports that it has the effect of treating drug-induced liver injury, there is no report on the treatment of alcoholic liver injury, which needs further research and exploration. 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 composition containing clavamide and use thereof in preparing a medicament for treating liver damage.

[0005] The technical solution of the present invention is as follows:

[0006] The present invention first provides a composition containing clausenamide, which comprises clausenamide and an active compound; the active compound is selected from ergolactone and / or isosaxifen.

[0007] The inventors found in the study that the composition obtained by combining clavamide with ergolide has a significantly improved anti-liver injury effect compared with clavamide alone. The composition obtained by combining clavamide with isosaxifragin has an improved anti-liver injury effect compared with clavamide alone; however, the degree of improvement is not as good as the composition obtained by combining clavamide with ergolide.

[0008] The inventors also found in further research that the composition obtained by combining clavamide with ergolide or isosaxifen also has an anti-HBV effect. The anti-HBV effect of the composition obtained by combining clavamide with isosaxifen is significantly higher than that of the composition obtained by combining clavamide with ergolide.

[0009] Preferably, the mass ratio of clausenamide to the active compound is 1-5:1-5.

[0010] More preferably, the mass ratio of clausenamide to the active compound is 1-3:1-3.

[0011] Most preferably, the mass ratio of clausenamide to the active compound is 2:3.

[0012] Preferably, the composition comprises clausenil as well as ergolide and isosaxifen.

[0013] The inventors found in further research that the anti-liver injury effect of the composition consisting of clavamide, ergolide and isosaxifen is much higher than that of clavamide alone; it is also significantly higher than the composition obtained by combining clavamide with ergolide and the composition obtained by combining clavamide with isosaxifen; this may be the result that the combination of clavamide, ergolide and isosaxifen can produce a synergistic anti-liver injury effect.

[0014] In addition, the inventors also found that the anti-hepatitis B virus effect of the composition consisting of chrysinamide, ergolide and isosaxifen is much higher than that of the composition obtained by combining chrysinamide and ergolide and the composition obtained by combining chrysinamide and isosaxifen; this may be the result that the combination of chrysinamide, ergolide and isosaxifen can produce a synergistic anti-hepatitis B virus effect.

[0015] More preferably, the mass ratio of clavanamide to ergolactone and isosaxifen is 1-5:1-3:1-2.

[0016] Most preferably, the mass ratio of clafamide to ergolactone and isosaxifen is 2:2:1.

[0017] The present invention also provides an application of the above-mentioned composition containing clasylamide in preparing a medicine for treating liver damage.

[0018] Preferably, the liver damage is alcoholic liver damage.

[0019] The present invention also provides an application of the above-mentioned clausenamide-containing composition in the preparation of a medicine having an anti-hepatitis B virus effect.

[0020] The present invention also provides an application of the above-mentioned clavamide-containing composition in the preparation of a medicine having both the effects of resisting hepatitis B virus and treating liver damage.

[0021] Preferably, the liver damage is alcoholic liver damage.

[0022] Beneficial effects: The present invention provides a new composition, and studies have shown that the composition has an effect of resisting alcoholic liver damage; in addition, it also has an effect of resisting hepatitis B virus. Therefore, the composition of the present invention has important application value when used as an effective ingredient to prepare a drug having an effect of treating liver damage and a drug having an effect of resisting hepatitis B virus; in particular, it has more important application value to prepare a drug having both an effect of resisting hepatitis B virus and a effect of treating liver damage. DETAILED DESCRIPTION

[0023] The present invention is further explained below in conjunction with specific examples, but the examples do not limit the present invention in any form.

[0024] The clavamide, ergolactone and isosaxifen in the following examples are all known compounds in the art and are purchased through conventional purchasing channels. Among them, the CAS number of clavamide is 103541-15-7; the CAS number of ergolactone is 54999-07-4; and the CAS number of isosaxifen is 482-27-9.

[0025] Example 1 Preparation of a Composition Containing Clausinamide

[0026] Preparation method: Take clafamide and ergolactone, mix them evenly in a mass ratio of 2:3 to obtain the clafamide-containing composition.

[0027] Example 2 Preparation of a Composition Containing Clausinamide

[0028] Preparation method: Take clafianide and isosaxifen in a mass ratio of 2:3 and mix them evenly to obtain the clafianide-containing composition.

[0029] Example 3 Preparation of a Composition Containing Clausinamide

[0030] Preparation method: Take clafianide, ergolide and isosaxifen in a mass ratio of 2:2:1 and mix them evenly to obtain the clafianide-containing composition.

[0031] Example 4 Preparation of a Composition Containing Clausinamide

[0032] Preparation method: Take clafamide and ergolactone, mix them evenly in a mass ratio of 5:1 to obtain the clafamide-containing composition.

[0033] Example 5 Preparation of a Composition Containing Clausinamide

[0034] Preparation method: Take clafamide and ergolactone, mix them evenly in a mass ratio of 1:5 to obtain the clafamide-containing composition.

[0035] Example 6 Preparation of a Composition Containing Clausinamide

[0036] Preparation method: Take clasifamide and isosaxifen in a mass ratio of 1:3 and mix them evenly to obtain the clasifamide-containing composition.

[0037] Example 7 Preparation of a Composition Containing Clausinamide

[0038] Preparation method: Take clasifamide and isosaxifen in a mass ratio of 3:1 and mix them evenly to obtain the clasifamide-containing composition.

[0039] Example 8 Preparation of a Composition Containing Clausinamide

[0040] Preparation method: Take clafianide, ergolide and isosaxifen in a mass ratio of 5:1:1 and mix them evenly to obtain the clafianide-containing composition.

[0041] Example 9 Preparation of a Composition Containing Clausinamide

[0042] Preparation method: Take clafianide, ergolide and isosaxifen in a mass ratio of 3:1:2 and mix them evenly to obtain the clafianide-containing composition.

[0043] Example 10 Preparation of a composition containing chrysinamide

[0044] Preparation method: Take clafianide, ergolide and isosaxifen in a mass ratio of 1:3:1 and mix them evenly to obtain the clafianide-containing composition.

[0045] Example 1 Anti-liver damage experiment

[0046] KM male mice weighing 20±2g were divided into 6 groups, with 12 mice in each group; they were normal group, alcohol model group and drug groups 1 to 4. Except for the normal group, the alcohol model group and the drug group were gavaged with a 53% alcohol aqueous solution once a day, and the gavage dose was 15mL / kg / d. The drug group was gavaged with the drug to be tested suspended in distilled water 2h before alcohol gavage every day, and the gavage dose was 15mg / kg / d; the normal group and the alcohol model group were gavaged with an equal amount of distilled water 2h before alcohol gavage every day; the gavage lasted for 14 days, and the eyeballs were removed 6h after the last alcohol gavage to collect blood. The ALT and AST levels in the serum of mice in each group were detected by an automatic biochemical analyzer. The test results are shown in Table 1.

[0047] Among them, the drug to be tested in experimental group 1 is the composition prepared in Example 1; the drug to be tested in experimental group 2 is the composition prepared in Example 2; the drug to be tested in experimental group 3 is the composition prepared in Example 3; and the drug to be tested in experimental group 4 is chrysinamide.

[0048] Table 1. Results of the anti-liver injury experiment

[0049]

[0050]

[0051] It can be seen from the experimental results in Table 1 that the levels of ALT and AST in the serum of mice in experimental groups 1 to 3 are significantly or even substantially lower than those in the alcohol model group; this indicates that the compositions containing clavamide described in the present invention have the effect of treating alcoholic liver injury.

[0052] It can be seen from the experimental results in Table 1 that the levels of ALT and AST in the serum of mice in Experimental Group 1 that were gavaged with the composition prepared in Example 1 were significantly lower than those in Experimental Group 4 that were gavaged with chrysogenum; this indicates that the composition obtained by combining chrysogenum and ergolactone has a significantly improved anti-alcoholic liver injury effect compared to chrysogenum alone.

[0053] It can be seen from the experimental results in Table 1 that the levels of ALT and AST in the serum of mice in Experimental Group 2 that were gavaged with the composition prepared in Example 2 were also lower than those in Experimental Group 4 that were gavaged with clafamide; this indicates that the composition obtained by combining clafamide with isosaxifen has an improved anti-alcoholic liver injury effect compared to clafamide alone.

[0054] It can be seen from the experimental results in Table 1 that the levels of ALT and AST in the serum of mice in Experimental Group 2 that were gavaged with the composition prepared in Example 2 were lower than those in Experimental Group 4 that were gavaged with clafamide, but the reduction was not significant, and the reduction was significantly lower than that in Experimental Group 1 that were gavaged with the composition prepared in Example 1; this shows that the anti-alcoholic liver injury effects of clafamide and different active ingredient compositions are different; the anti-alcoholic liver injury effect of the composition obtained by combining clafamide with ergolactone is significantly improved compared with that of clafamide alone, which is higher than that of the composition obtained by combining clafamide with isosaxifragine.

[0055] It can be seen from the experimental results in Table 1 that the levels of ALT and AST in the serum of mice in the experimental group 3 that were gavaged with the composition prepared in Example 3 were close to those in the normal group, and were significantly lower than those in the mice in the experimental group 4 that were gavaged with clafamide, and were also significantly lower than those in the mice in the experimental groups 1 and 2; this shows that the composition consisting of clafamide, ergolide and isosaxifen has a very excellent anti-alcoholic liver injury effect; its anti-alcoholic liver injury effect is further significantly higher than that of clafamide alone; and it is also further significantly higher than that of the composition obtained by combining clafamide with ergolide and the composition obtained by combining clafamide with isosaxifen; this may be the result that the combination of clafamide, ergolide and isosaxifen can produce a synergistic anti-alcoholic liver injury effect.

[0056] Experimental Example 2 Anti-HBV Effect

[0057] Human hepatoma cells Hep G2.2.15 expressing HBV were inoculated in a 96-well plate (containing DMEM medium), with a cell content of 1×10 6 The cells were then placed in an incubator (5% CO2, 37°C) for 24 h. After the culture, the experimental group replaced the culture medium with DMEM culture medium containing 300 μg / mL of the drug to be tested, and the culture medium was replaced every 2 days. The control group replaced the culture medium with DMEM culture medium without the drug to be tested, and the culture medium was replaced every 2 days. After 10 days of continuous culture, the supernatant was taken and the HBsAg and HBeAg contents were detected using an ELISA kit. The inhibition rates of HBsAg and HBeAg in each group were calculated, and 5 parallel wells were set for each group. The test results are shown in Table 1.

[0058] Among them, the drug to be tested in experimental group 1 is the composition prepared in Example 1; the drug to be tested in experimental group 2 is the composition prepared in Example 2; and the drug to be tested in experimental group 3 is the composition prepared in Example 3.

[0059] Table 2. Results of anti-HBV experiments

[0060]

[0061] It can be seen from the experimental results in Table 2 that experimental groups 1 to 3 all showed inhibitory effects on HBsAg and HBeAg; this indicates that the compositions containing clavamide described in the present invention all have anti-hepatitis B virus effects.

[0062] From the experimental results in Table 2, it can be seen that the inhibition rate of HBsAg and HBeAg in experimental group 2 is significantly higher than that in experimental group 1; this shows that the anti-hepatitis B virus effect of the composition obtained by combining chrysinamide and isosaxifen is significantly higher than that of the composition obtained by combining chrysinamide and ergolactone.

[0063] From the experimental results in Table 2, it can be seen that the inhibition rate of HBsAg and HBeAg in experimental group 3 is much higher than that in experimental groups 1 and 2; this shows that the anti-hepatitis B virus effect of the composition composed of chrysinamide, ergolide and isosaxifen is much higher than that of the composition obtained by combining chrysinamide with ergolide and the composition obtained by combining chrysinamide with isosaxifen; it has excellent anti-hepatitis B virus effect; this may be the result that the combination of chrysinamide, ergolide and isosaxifen can produce synergistic anti-hepatitis B virus.

Claims

1. A composition containing chrysinamide, characterized in that The invention comprises clausenil and an active compound; the active compound is selected from ergolactone and / or isosaxifen.

2. The composition containing chrysinamide according to claim 1, characterized in that The mass ratio of clafamide to the active compound is 1-5:1-5.

3. The composition containing clasylamide according to claim 1, characterized in that The mass ratio of clafamide to the active compound is 1-3:1-3.

4. The composition containing chrysinamide according to claim 1, characterized in that The mass ratio of clafamide to active compound is 2:

3.

5. The composition containing chrysinamide according to claim 1, characterized in that The composition comprises clavanamide, ergolide and isosaxifen.

6. The composition containing chrysinamide according to claim 5, characterized in that The mass ratio of clavanamide, ergolide and isosaxifen is 1-5:1-3:1-2.

7. The composition containing clafamide according to claim 5, characterized in that The mass ratio of clafianamide, ergolide and isosaxifen is 2:2:

1.

8. Use of the composition containing clasylamide according to any one of claims 1 to 7 in the preparation of a medicament for treating liver damage.

9. Use of the composition containing clasylamide according to any one of claims 1 to 7 in the preparation of a drug having an anti-hepatitis B virus effect.

10. Use of the composition containing clavamide according to any one of claims 1 to 7 in the preparation of a drug having both anti-hepatitis B virus and liver damage treatment effects.

Images