A compound or composition and its application in the preparation of anesthetic drugs

Abstract

The present invention relates to the technical field of medicinal chemistry, and specifically discloses a compound or composition and its application in the preparation of anesthetic drugs. The compound selected is solamargine or andrographolide. The composition contains solamargine and andrographolide. Since solamargine or andrographolide has a certain anesthetic effect; therefore, using solamargine or andrographolide as an active ingredient in the preparation of anesthetic drugs has important application value; in addition, when the weight ratio of solamargine and andrographolide is controlled within the range of 1-5:1-5, the anesthetic effect of the obtained composition is significantly higher than that of single solamargine or andrographolide, and a synergistic effect can be produced, having a more excellent anesthetic effect; therefore, compared with using single solamargine or andrographolide, using the composition of the present invention is beneficial to reducing the dosage of anesthetic drugs.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical chemistry, and particularly relates to a compound or composition and its application in the preparation of anesthetic drugs. Background Art

[0002] Anesthesia is the reversible functional inhibition of the central nervous system and / or peripheral nervous system by drugs or other methods, so as to cause the loss of sensation, especially pain sensation, to achieve the purpose of painlessness, and to provide convenient conditions for surgical treatment or other medical examinations and treatments.

[0003] "Mafeisan" invented by Hua Tuo, an outstanding medical scientist in the late Eastern Han Dynasty and the Three Kingdoms period, is the first anesthetic drug used in the world; as early as the 2nd century AD, laparotomy under general anesthesia with "Mafeisan" has been carried out in China. With the development of medical technology, there are now a variety of anesthetic drugs applied in clinical practice. Such as commonly used anesthetic drugs include acetorphine, acetylalphamethylfentanyl, and acetylmethadol, etc. However, continuous use of certain anesthetic drugs is prone to physical dependence and psychological dependence; in addition, some anesthetic drugs also have the problem of high cost. Therefore, developing more drugs with anesthetic effects and providing patients with different choices of anesthetic drugs has important application value.

[0004] Solasonine is a steroidal glycoalkaloid. Modern pharmacology shows that it has anti-tumor, anti-inflammatory, anticoagulant and other effects; the prior art has not reported that solasonine has anesthetic effects. Amsonia alkaloid was initially isolated from the leaves of Amsonia tabernaemontana. Modern pharmacology shows that it has antihypertensive effects; the prior art has also not reported that amsonia alkaloid has anesthetic effects. Summary of the Invention

[0005] In order to overcome at least one of the technical problems existing in the prior art, the present invention provides a compound or composition and its application in the preparation of anesthetic drugs.

[0006] The technical solution of the present invention to solve the above technical problems is as follows:

[0007] The present invention first provides a compound, and the compound is selected from solasonine or amsonia alkaloid.

[0008] The inventors surprisingly found in the research that solasonine or amsonia alkaloid has certain anesthetic effects; therefore, using solasonine or amsonia alkaloid as an active ingredient for the preparation of anesthetic drugs has important application value.

[0009] The present invention also provides a composition, which comprises solasonine and amsonia alkaloid.

[0010] Since solanine or andrographolide has a certain anesthetic effect; therefore, the composition obtained by combining the two also has an anesthetic effect.

[0011] Preferably, the weight ratio of solanine to andrographolide in the composition is 1-100:1-100.

[0012] More preferably, the weight ratio of solanine to andrographolide in the composition is 1-50:1-50.

[0013] Even more preferably, the weight ratio of solanine to andrographolide in the composition is 1-5:1-5.

[0014] Most preferably, the weight ratio of solanine to andrographolide in the composition is 2:1.

[0015] The inventors further surprisingly found in the research that the anesthetic effect of the composition obtained by combining solanine and andrographolide is significantly higher than that of solanine or andrographolide alone. Combining solanine and andrographolide can produce a synergistic anesthetic effect.

[0016] However, the inventors need to emphasize that to obtain a composition with better anesthetic effect; the dosage of solanine and andrographolide in the composition is very crucial; research shows that when the weight ratio of solanine to andrographolide is controlled within the range of 1-5:1-5, the anesthetic effect of the obtained composition is significantly higher than that of solanine or andrographolide alone, and a synergistic effect can be produced; in particular, when the weight ratio of solanine to andrographolide is controlled at 2:1, the anesthetic effect of the obtained composition is much higher than that of solanine or andrographolide alone, and it has an excellent anesthetic effect. However, when the weight ratio of solanine to andrographolide is not within the scope of the present invention, the anesthetic effect of the obtained composition is not higher than or significantly higher than that of solanine or andrographolide alone. When the weight ratio of solanine to andrographolide is not within the scope of the present invention, the obtained composition cannot produce a synergistic anesthetic effect.

[0017] The present invention also provides an application of the above compound or composition in the preparation of anesthetic drugs.

[0018] Preferably, the dosage form of the anesthetic drug is an injection.

[0019] Beneficial effects: Since solanine or andrographolide has a certain anesthetic effect; therefore, using solanine or andrographolide as an active ingredient in the preparation of anesthetic drugs has important application value; the present invention also provides a new application of solanine or andrographolide in the preparation of anesthetic drugs for the first time.

[0020] In addition, when the weight ratio of solasonine and andrographolide is controlled within the range of 1-5:1-5, the obtained composition has a significantly higher anesthetic effect than single solasonine or andrographolide, and can produce a synergistic effect; since the composition obtained by combining solasonine and andrographolide within the dosage range of the present invention has a more excellent anesthetic effect; therefore, compared with using single solasonine or andrographolide, using the composition of the present invention is beneficial to reducing the dosage of anesthetic drugs. Detailed implementation manners

[0021] The following specific examples are used to further explain the present invention, but the examples do not limit the present invention in any form.

[0022] Experimental example 1

[0023] The sequential method was used to test the anesthetic effect of the compound or composition of the present invention: male SD rats with a body weight of 250±20 g were selected; they were randomly divided into 8 experimental groups, with 12 rats in each group; during the experiment, the compound or composition of the present invention was administered via the tail vein of the rats, and the administration volume for each rat was 0.5 ml and the administration speed was 0.1 ml / s. The disappearance of the righting reflex of the front paw of the rat for 30 seconds was used as an index for the generation of general anesthesia effect; the median effective dose (ED50) of the compound or composition of the present invention to produce general anesthesia was tested; the test results are shown in Table 1.

[0024] Among them, the compound tested in experimental group 1 was solasonine alone; the compound tested in experimental group 2 was andrographolide alone; the composition tested in experimental group 3 was composed of solasonine and andrographolide with a weight ratio of 2:1; the composition tested in experimental group 4 was composed of solasonine and andrographolide with a weight ratio of 1:2; the composition tested in experimental group 5 was composed of solasonine and andrographolide with a weight ratio of 5:1; the composition tested in experimental group 6 was composed of solasonine and andrographolide with a weight ratio of 1:5; the composition tested in experimental group 7 was composed of solasonine and andrographolide with a weight ratio of 1:8; the composition tested in experimental group 8 was composed of solasonine and andrographolide with a weight ratio of 8:1.

[0025] Table 1. Experimental results of the anesthetic effect of the compound or composition of the present invention

[0026]

[0027]

[0028] It can be seen from the experimental data of experimental groups 1 and 2 in Table 1 that solamargine or amabiline has a certain anesthetic effect; therefore, using solamargine or amabiline as an active ingredient in the preparation of anesthetic drugs has important application value.

[0029] It can be seen from the experimental data in Table 1 that the ED50 values of experimental groups 3-6 are significantly smaller than those of experimental groups 1 and 2; this indicates that: for the composition obtained by combining solamargine and amabiline, its anesthetic effect is significantly higher than that of solamargine or amabiline alone. Combining solamargine and amabiline can produce a synergistic anesthetic effect.

[0030] It can be seen from the experimental data in Table 1 that the ED50 values of experimental groups 7 and 8 are not less than or significantly less than those of experimental groups 1 and 2, and their ED50 values are significantly higher than those of experimental groups 3-6. This indicates that: the dosage of solamargine and amabiline in the composition is very crucial; only when the weight ratio of solamargine to amabiline is controlled within the range of 1-5:1-5 can the obtained composition have an anesthetic effect significantly higher than that of solamargine or amabiline alone and can produce a synergistic effect; when the weight ratio of solamargine to amabiline is not within the scope of the present invention, the obtained composition does not have an anesthetic effect higher than or significantly higher than that of solamargine or amabiline alone; when the weight ratio of solamargine to amabiline is not within the scope of the present invention, the obtained composition cannot produce a synergistic anesthetic effect.

[0031] It can be seen from the experimental data in Table 1 that the ED50 value of experimental group 3 is much smaller than those of experimental groups 1 and 2; it is also significantly smaller than those of experimental groups 4-6; this indicates that: for the composition obtained by controlling the weight ratio of solamargine to amabiline at 2:1, its anesthetic effect is much higher than that of solamargine or amabiline alone, and is also significantly higher than the compositions obtained with other weight ratios of solamargine and amabiline, and has an extremely excellent anesthetic effect.

Claims

1. A composition, characterized in that, It contains solanine and amabiline; the weight ratio of solanine to amabiline in the composition is 2:

1.

2. Use of the composition according to claim 1 in the preparation of an anesthetic drug.

3. The application according to claim 2, wherein The dosage form of the anesthetic drug is an injection.

Images