A complex for inhibiting α-glucosidase and its application

Through the complex of luteolin and quercetin or 3-O-methylquercetin, a synergistic complex is formed, which solves the problem of major side effects of existing α-glucosidase inhibitors, and effectively inhibits and reduces side effects of α-glucosidase.

CN118615276BActive Publication Date: 2025-06-20GUANGZHOU INST OF GEOGRAPHY GUANGDONG ACAD OF SCI
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Patent Information

Application Number
CN202410801340.8
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2024-06-20
Publication Date
2025-06-20
Estimated Expiration
2044-06-20

AI Technical Summary

Technical Problem

Existing α-glucosidase inhibitors have side effects such as causing digestive system disorders in clinical applications, and it is difficult to effectively control blood sugar levels.

Method used

Through the reasonable complexation of luteolin with quercetin or 3-O-methylquercetin, a complex inhibiting α-glucosidase is formed, and its synergistic effect is used to enhance the inhibition of α-glucosidase activity and reduce the dosage of drugs to reduce side effects.

Benefits of technology

Effective inhibition of α-glucosidase is achieved, reducing the burden on the human body by drugs, reducing side effects, and improving the effect of lowering blood sugar.

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Abstract

The present invention provides a complex for inhibiting α-glucosidase and its application. The complex for inhibiting α-glucosidase comprises a first component and a second component; the first component is luteolin; the second component is quercetin or 3-O-methylquercetin. By reasonably compounding luteolin with quercetin or 3-O-methylquercetin, the present invention enhances the inhibitory effect on the activity of α-glucosidase and avoids the antagonistic effect caused by the reaction of two components with similar effects.
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Description

Technical Field

[0001] The present invention belongs to the field of pharmaceutical technology, and particularly relates to a complex for inhibiting α-glucosidase and its application. Background Art

[0002] At present, diabetes has become one of the well-recognized stubborn diseases endangering people's health. Excessively high blood glucose level is the main factor causing diabetes. Therefore, the most effective way to prevent diabetes is to control the blood glucose level. The main physiological function of α-glucosidase is to hydrolyze polysaccharides. Controlling the activity of α-glucosidase is an effective method for treating pre-diabetic patients and alleviating diabetic symptoms. At present, some synthetic α-glucosidase inhibitors have been used in clinical treatment, but there are side effects such as causing digestive system disorders. Therefore, it is particularly important to develop a drug with inhibitory effect on α-glucosidase and low side effects. At present, flavonoids have attracted more and more attention due to their good free radical scavenging and antioxidant functions.

[0003] In the process of ingesting food or health products, it is very common for two or more drug components to have similar effects. The main goal of combination drug therapy is to improve the efficacy when different drugs are used in combination, while reducing the side effects of the drugs and avoiding unnecessary burden on the human body. Summary of the Invention

[0004] The purpose of the present invention is to overcome the defects and deficiencies in the prior art, and provide a complex for inhibiting α-glucosidase, which realizes synergistic effect through the compounding of different components, has simple ingredients and reduced dosage, so as to reduce side effects and thus reduce the burden on the human body.

[0005] The present invention is realized through the following technical solutions:

[0006] A complex for inhibiting α-glucosidase, comprising a first component and a second component; the first component is luteolin; the second component is quercetin or 3-O-methylquercetin.

[0007] In the complex for inhibiting α-glucosidase provided by the present invention, through the reasonable compounding of luteolin and quercetin or 3-O-methylquercetin, the inhibitory effect on the activity of α-glucosidase is enhanced, and the antagonistic effect caused by the reaction of two components with similar effects is avoided.

[0008] Further, the mass ratio of luteolin to quercetin is 5:5 to 6:4. Limiting the mass ratio of luteolin to quercetin to achieve the synergistic effect.

[0009] Further, the mass ratio of luteolin to 3-O-methylquercetin is 4:6 to 6:4. Limiting the mass ratio of luteolin to 3-O-methylquercetin to achieve the synergistic effect.

[0010] Furthermore, the complex for inhibiting α-glucosidase further includes at least one of a carrier, a solvent, a diluent, and an excipient, and is used to carry the first component and the second component.

[0011] The present invention also provides a pharmaceutical dosage form of the complex for inhibiting α-glucosidase, including any one of powder, granule, capsule, injection, oral liquid, tablet, or dropping pill.

[0012] The present invention also provides the application of the complex for inhibiting α-glucosidase in the field of inhibiting α-glucosidase.

[0013] The present invention also provides an α-glucosidase inhibitor, including the above-mentioned complex for inhibiting α-glucosidase.

[0014] For better understanding and implementation, the present invention will be described in detail below with reference to the accompanying drawings. Description of the Drawings

[0015] Figure 1 It is the inhibition curve of luteolin on α-glucosidase.

[0016] Figure 2 It is the inhibition curve of quercetin on α-glucosidase.

[0017] Figure 3 It is the isobolographic analysis of the interaction between luteolin and quercetin in different ratios with α-glucosidase.

[0018] Figure 4 It is the inhibition curve of 3-O-methylquercetin on α-glucosidase.

[0019] Figure 5 It is the isobolographic analysis of the interaction between luteolin and 3-O-methylquercetin in different ratios with α-glucosidase. Detailed Embodiments

[0020] The following further describes the embodiments of the present invention in detail with reference to the drawings and examples. It can be understood that the specific embodiments described herein are only used to explain the embodiments of the present invention, rather than limiting the embodiments of the present invention. Additionally, it should be noted that for the sake of description, only parts related to the embodiments of the present invention are shown in the drawings, rather than all structures.

[0021] In addition, the terms first, second, third, etc. in the description and claims are only used for the purpose of differentiating the description of the same technical features, and should not be construed as indicating or implying relative importance or implicitly specifying the quantity of the indicated technical features, nor necessarily describing the order or time sequence. The terms can be interchanged under appropriate circumstances. Thus, the features defined with "first" and "second" may explicitly or implicitly include at least one such feature.

[0022] Similarly, the terms "fixed" and "connected" are also used in the description and claims and should not be construed as being limited to direct connection. Therefore, the expression "device A is connected to device B" should not be limited to device A being directly connected to device B in the device or system, but means that there is a path between device A and device B, which can be a path including other devices or tools.

[0023] Example 1

[0024] This embodiment provides a complex for inhibiting α-glucosidase, which comprises a first component and a second component; the first component is luteolin; the second component is quercetin or 3-O-methylquercetin; the mass ratio of the first component to the second component is 2:8 to 8:2.

[0025] In the complex for inhibiting α-glucosidase provided by this embodiment, through the reasonable compounding of luteolin and quercetin or 3-O-methylquercetin, the inhibitory effect on the activity of α-glucosidase is enhanced, and synergistic effect is achieved, avoiding the antagonistic effect caused by the reaction of two components with similar effects.

[0026] Compared with the prior art, the complex for inhibiting α-glucosidase provided by this embodiment has simple components, and due to the synergistic effect, while reducing the dosage, it achieves the inhibition rate of the existing combined treatment of multiple drugs, reduces the side effects, and reduces the burden on the human body caused by the drugs.

[0027] In this embodiment, the mass ratio of luteolin to quercetin is 5:5 to 6:4. The mass ratio of luteolin to quercetin is defined to achieve the synergistic effect.

[0028] In this embodiment, the complex for inhibiting α-glucosidase further comprises at least one of a carrier, a solvent, a diluent, and an excipient, which is used to carry the first component and the second component.

[0029] The molecular formula of luteolin is C 15 H 10 O6; molecular weight: 286.23; CAS registry number: 491-70-3, and the structural formula is as follows:

[0030]

[0031] The molecular formula of Quercetin is C 15 H 10 O7; molecular weight: 302.23; CAS registry number: 117 - 39 - 5, and the structural formula is as follows:

[0032]

[0033] The amino acid residues of luteolin, quercetin combined with α - glucosidase are different, and their inhibitory activities on α - glucosidase are also different. Therefore, through reasonable compounding, the inhibitory activities on different amino acid residues of α - glucosidase can be controlled, acting on multiple targets to achieve synergistic enhancement, improving the inhibition rate while reducing the dosage.

[0034] Figure 1 is the inhibition curve of luteolin on α - glucosidase, Figure 2 is the inhibition curve of quercetin on α - glucosidase. Please refer to Figure 1-2 , luteolin has a good inhibitory effect on α - glucosidase, and its inhibitory effect is better than that of the commonly used acarbose inhibitor; quercetin has a good inhibitory effect on α - glucosidase, and its inhibitory effect is better than that of the commonly used acarbose inhibitor.

[0035] Figure 3 is the isobologram analysis of the interaction between luteolin and quercetin with α - glucosidase at different ratios. Please refer to Figure 3 , when luteolin and quercetin are used in combination, and the ratios are 5:5 and 6:4, the Interaction index (mutual interaction index γ) is less than 1, showing a synergistic effect rather than a simple additive effect, and can achieve the same or better blood - glucose - lowering effect as using luteolin or quercetin alone, and the dosages of luteolin and quercetin in the blood - glucose - lowering compounds are both reduced compared with the dosages used alone.

[0036] Example 2

[0037] This embodiment provides a complex for inhibiting α - glucosidase, including a first component and a second component; the first component is luteolin; the second component is 3 - O - methylquercetin; the mass ratio of the first component to the second component is 2:8 to 8:2.

[0038] In this embodiment, the mass ratio of luteolin to 3 - O - methylquercetin is 4:6 to 6:4. Limiting the mass ratio of luteolin to 3 - O - methylquercetin to achieve the effect of synergistic enhancement.

[0039] In this embodiment, the complex for inhibiting α-glucosidase further comprises at least one of a carrier, a solvent, a diluent, and an excipient, and is used to carry the first component and the second component.

[0040] Compared with the prior art, the complex for inhibiting α-glucosidase provided in this embodiment has a simple composition. Moreover, due to the synergistic effect, while reducing the dosage, it can achieve the inhibition rate of the existing combined treatment with multiple drugs, reduce side effects, and reduce the burden on the human body caused by drugs.

[0041] The molecular formula of 3-O-Methylquercetin is C 16 H 12 O7; molecular weight: 316.26; CAS registration number: 1486-70-0, and the structural formula is as follows:

[0042]

[0043] The amino acid residues of luteolin, 3-O-methylquercetin binding to α-glucosidase are different, and their inhibitory activities on α-glucosidase are also different. Therefore, through reasonable compounding, the inhibitory activities on different amino acid residues of α-glucosidase can be controlled, and multiple targets can play a role to achieve synergistic effect, while reducing the dosage and increasing the inhibition rate.

[0044] Figure 4 is the inhibition curve graph of 3-O-methylquercetin on α-glucosidase. Please refer to Figure 1 and Figure 4 , luteolin has a good inhibitory effect on α-glucosidase, and its inhibitory effect is better than that of the commonly used acarbose inhibitor; 3-O-methylquercetin has a good inhibitory effect on α-glucosidase, and its inhibitory effect is better than that of the commonly used acarbose inhibitor.

[0045] Figure 5 is the isobolographic analysis of the interaction of luteolin and 3-O-methylquercetin with α-glucosidase in different ratios. Please refer to Figure 5 , when luteolin and 3-O-methylquercetin are used in combination, and the ratios are 4:6, 5:5, and 6:4, the Interaction index (mutual interaction index γ) is less than 1, showing a synergistic effect rather than a simple additive effect. It can achieve the same or better blood glucose lowering effect as that of using luteolin or methylquercetin alone, and the dosages of luteolin and 3-O-methylquercetin in the blood glucose lowering compounds are both reduced compared with the dosages used alone.

[0046] For the complexes for inhibiting α-glucosidase in Example 1 and Example 2, an in vitro inhibition test of α-glucosidase activity was carried out, and the steps are as follows:

[0047] The experimental instruments and reagents include: α-glucosidase (α-glucosidase, Sigma, 750 U), 4-nitrophenyl-α-D-glucopyranoside (pNPG, TOKYO Chemica Industry Co., LTD), acarbose (Acarbose, TOKYO Chemica Industry Co., LTD), luteolin, quercetin, 3-O-methylquercetin (Beijing Solarbio), Millipore Simplicity water purification system (Millipore, France), sodium phosphate buffer solution (pH 6.8, 0.1 molL -1 ), and the microplate reader TECAN infinite M200 PRO (Teacan Group Ltd., Switzerland).

[0048] Taking luteolin, quercetin, 3-O-methylquercetin, the complex composed of luteolin and quercetin in different mass ratios, and the complex composed of luteolin and 3-O-methylquercetin in different mass ratios as the test objects, and using acarbose as the control group, the inhibitory activity of each test object on α-glucosidase was tested by the above method, and the half-inhibitory concentration IC 50 value was used to represent. The specific operation is as follows:

[0049] In a 96-well plate, 100 μL of the test solution to be measured was added successively, 40 μL of α-glucosidase (0.25 U / mL) was added, and it was incubated in a constant temperature water bath at 37 °C for 10 min. Then, 60 μL of 5 mmol / mL substrate p-nitrophenyl-α-D-glucopyranoside (pNPG) was added, and it was shaken with a micro vortex oscillator to mix evenly. The reaction was carried out in a constant temperature water bath at 37 °C for 15 min. After the reaction ended, the 96-well plate was taken out, and 100 μL of 0.1 mol / L Na2CO3 solution was added to each well to terminate the reaction; after the reaction was terminated, the 96-well plate was immediately placed in a microplate reader, and the absorbance (OD) value of each well was read at 405 nm. According to the OD value, the inhibition rate of α-glucosidase activity at each gradient was calculated. The inhibition rate = [1 - (OD 样品 - OD 样品空白 ) / (OD 阴性对照 - OD 空白 )] × 100%. According to the inhibition rate of α-glucosidase activity at each gradient, the half-inhibitory concentration (IC 50 ) of the experimental object was calculated, and the calculation and statistical processes were carried out using SPSS 20.0.

[0050] The test solution experimental groups were set as follows:

[0051] Sample group: 100 μL of the sample to be tested + 40 μL of enzyme + 60 μL of pNPG;

[0052] Sample blank group: 100 μL of the sample to be tested + 40 μL of PBS + 60 μL of pNPG;

[0053] Positive control group: 100 μL of acarbose + 40 μL of enzyme + 60 μL of pNPG;

[0054] Negative control group: 2 μL of DMSO + 98 μL of PBS + 40 μL of enzyme + 60 μL of pNPG;

[0055] Blank group: 2 μL of DMSO + 98 μL of PBS + 40 μL of PBS + 60 μL of pNPG.

[0056] Principle for setting concentration gradients: Taking luteolin and quercetin (8:2) as an example, the initial concentration of the complex inhibiting α-glucosidase is set to 10 μg / mL, where the initial concentration of luteolin is 8 μg / mL and the initial concentration of quercetin is 2 μg / mL. Based on the initial concentration of 10 μg / mL, serial two-fold dilutions are carried out successively to 10 μg / mL, 5 μg / mL, 2.5 μg / mL, and 1.25 μg / mL. Similarly, in the complex formed by luteolin and quercetin, the initial concentration of the complex inhibiting α-glucosidase is set to 10 μg / mL, and serial two-fold dilutions are carried out based on the initial concentration of 10 μg / mL to form a concentration gradient. Other compositions also follow this principle.

[0057] Specifically, the concentration gradients for each experimental subject are set as follows;

[0058] Luteolin and quercetin (8:2): (8 + 2) μg / mL, (4 + 1) μg / mL, (2 + 0.5) μg / mL, (1 + 0.25) μg / mL;

[0059] Luteolin and quercetin (6:4): (6 + 4) μg / mL, (3 + 2) μg / mL, (1.5 + 1) μg / mL, (0.75 + 0.5) μg / mL;

[0060] Luteolin and quercetin (5:5): (5 + 5) μg / mL, (2.5 + 2.5) μg / mL, (1.25 + 1.25) μg / mL, (0.625 + 0.625) μg / mL;

[0061] Luteolin and quercetin (4:6): (4 + 6) μg / mL, (2 + 3) μg / mL, (1 + 1.5) μg / mL, (0.5 + 0.75) μg / mL;

[0062] Luteolin and quercetin (2:8): (2 + 8) μg / mL, (1 + 4) μg / mL, (0.5 + 2) μg / mL, (0.25 + 1) μg / mL.

[0063] Luteolin and 3-O-methylquercetin (8:2): (8 + 2) μg / mL, (4 + 1) μg / mL, (2 + 0.5) μg / mL, (1 + 0.25) μg / mL;

[0064] Luteolin and 3-O-methylquercetin (6:4): (6 + 4) μg / mL, (3 + 2) μg / mL, (1.5 + 1) μg / mL, (0.75 + 0.5) μg / mL;

[0065] Luteolin and 3-O-methylquercetin (5:5): (5 + 5) μg / mL, (2.5 + 2.5) μg / mL, (1.25 + 1.25) μg / mL, (0.625 + 0.625) μg / mL;

[0066] Luteolin and 3-O-methylquercetin (4:6): (4 + 6) μg / mL, (2 + 3) μg / mL, (1 + 1.5) μg / mL, (0.5 + 0.75) μg / mL;

[0067] Luteolin and 3-O-methylquercetin (2:8): (2 + 8) μg / mL, (1 + 4) μg / mL, (0.5 + 2) μg / mL, (0.25 + 1) μg / mL.

[0068] The combined drug interaction of the complex inhibiting α-glucosidase was determined by the isobologram method, the Interaction index was calculated, and the interaction between drugs was evaluated.

[0069] IC 50 The calculation formula for the theoretical value is: IC 50add = IC 50A / (P1 + R * P2), where R is the potency ratio of two compounds A and B acting alone, that is, R = IC 50A / IC 50B ; P1 is the proportion of compound A in the complex, and P2 is the proportion of compound B in the complex.

[0070] Synergy rate (%) = (IC 50add - IC 50mix ) / IC 50add * 100.

[0071] Interaction index (γ) interaction index value = IC 50Amix / IC50A +IC 50Bmix / IC 50B , where IC 50Amix is the concentration of compound A in the coordinate system corresponding to the complex reaching the corresponding inhibition rate, and IC 50Bmix is the concentration of compound B in the coordinate system corresponding to the complex reaching the corresponding inhibition rate. When γ > 1, the two compounds exhibit an antagonistic effect; when γ = 1, the two compounds exhibit an additive effect; when γ = 1, the two compounds exhibit a synergistic effect.

[0072] Table 1 is the interaction table of combined drugs. Table 2 is the inhibition rate of the complex of luteolin and quercetin on α-glucosidase. Table 3 is the inhibition rate of the complex of luteolin and 3-O-methylquercetin on α-glucosidase. Please refer to Table 1. The IC 50 value of luteolin is 4.84 ± 0.32 μg / mL, the IC 50 value of quercetin is 2.28 ± 0.29 μg / mL, and the IC 50 value of 3-O-methylquercetin is 4.22 ± 0.84 μg / mL.

[0073] The total concentration of the complex formed by luteolin and quercetin is 10 μg / mL. The IC 50 values of the complexes formed by luteolin and quercetin with different mass ratios (8:2, 6:4, 5:5, 4:6, 2:8) are 4.34 ± 0.40 μg / mL, 2.84 ± 0.34 μg / mL, 2.74 ± 0.24 μg / mL, 3.68 ± 0.76 μg / mL, and 4.90 ± 0.69 μg / mL respectively. When luteolin and quercetin are used in combination, at mass ratios of 6:4 and 5:5, the IC 50 values are significantly lower than the IC 50 values of luteolin or quercetin used alone. The Interaction index (mutual interaction index γ) is 0.85 and 0.88 respectively, and the synergy rates are 14.96% and 11.77% respectively, indicating a strong synergistic effect, which can significantly reduce the dosage of each component and improve the inhibitory activity on α-glucosidase; at mass ratios of 8:2, 4:6, and 2:8, the IC 50 values that can significantly reduce the inhibitory activity of α-glucosidase are not present. γ > 1, and the synergy rate is negative, showing an antagonistic effect.

[0074] Please refer to Table 1-2. When luteolin and quercetin are selected for compound use, the ratio of the two needs to be restricted to achieve synergistic effects, so as to reduce the dosage of luteolin and quercetin respectively to reduce side effects while increasing the inhibition rate of α-glucosidase. The complex of luteolin and quercetin can achieve the effect of inhibiting α-glucosidase by using luteolin or quercetin alone through synergistic effects while reducing the dosage of luteolin and quercetin respectively, and has an excellent inhibition rate.

[0075] The IC 50 values of the complexes formed by luteolin and 3-O-methylquercetin with different mass ratios (8:2, 6:4, 5:5, 4:6, 2:8) are 5.66±1.05 μg / mL, 3.58±0.37 μg / mL, 4.33±0.19 μg / mL, 3.81±0.51 μg / mL and 5.66±0.17 μg / mL respectively. When luteolin and 3-O-methylquercetin are used in combination, at mass ratios of 6:4, 5:5 and 4:6, the IC 50 values are significantly lower than the IC 50 values of using luteolin or 3-O-methylquercetin alone. The Interaction index (mutual interaction index γ) are 0.78, 0.98 and 0.86 respectively, and the synergy rates are 21.75%, 1.75% and 14.25% respectively, indicating that there is a strong synergistic effect, which can significantly reduce the dosage of each component while increasing the inhibitory activity of α-glucosidase; at mass ratios of 8:2 and 2:8, the IC 50 values for inhibiting α-glucosidase activity are not significantly reduced, and the mutual interaction index > 1, showing an antagonistic effect.

[0076] Please refer to Table 1 and Table 3. When luteolin and 3-O-methylquercetin are selected for compound use, the ratio of the two needs to be restricted to achieve synergistic effects, so as to reduce the dosage of luteolin and 3-O-methylquercetin respectively to reduce side effects while increasing the inhibition rate of α-glucosidase. The complex of luteolin and 3-O-methylquercetin can achieve the existing effect of inhibiting α-glucosidase by using luteolin or quercetin alone through synergistic effects while reducing the dosage of luteolin and quercetin respectively, and has an excellent inhibition rate.

[0077] Table 1 Table of interaction of combined drugs

[0078]

[0079]

[0080] Table 2 Inhibition rate of the complex of luteolin and quercetin on α-glucosidase

[0081]

[0082]

[0083] Table 3 Inhibition rate of the complex of luteolin and 3-O-methylquercetin on α-glucosidase

[0084]

[0085] Example 3

[0086] This example provides an application of a complex for inhibiting α-glucosidase in the field of inhibiting α-glucosidase. The complex for inhibiting α-glucosidase includes a first component and a second component; the first component is luteolin; the second component is quercetin or 3-O-methylquercetin, and the mass ratio of the first component to the second component is 2:8 to 8:2. It can be prepared into corresponding powder, granule, capsule, injection, oral liquid or tablet by adding pharmaceutically or food-acceptable carriers, solvents, diluents, excipients or other media, drugs or health products as required, and prepared into hypoglycemic drugs or health products.

[0087] Comparative Example 1

[0088] This comparative example provides a composition of luteolin and formononetin, and the mass concentration ratio of luteolin to formononetin is 8:2, 6:4, 5:5, 4:6, 2:8.

[0089] Comparative Example 2

[0090] This comparative example provides a composition of luteolin and kaempferol, and the mass concentration ratio of luteolin to kaempferol is 8:2, 6:4, 5:5, 4:6, 2:8.

[0091] An in vitro inhibition test of α-glucosidase activity was carried out on Comparative Example 1 and Comparative Example 2, and the steps are as follows:

[0092] Add 100 μL of the solution to be tested into each well of a 96-well plate, then add 40 μL of α-glucosidase (0.25 U / mL), incubate in a constant temperature water bath at 37 °C for 10 min, add 60 μL of 5 mmol / mL substrate p-nitrophenyl-α-D-glucopyranoside (pNPG), shake with a micro vortex oscillator to mix evenly, react in a constant temperature water bath at 37 °C for 15 min. After the reaction, take out the 96-well plate, add 100 μL of 0.1 mol / L Na2CO3 solution to each well to terminate the reaction; after terminating the reaction, immediately put the 96-well plate into a microplate reader and read the absorbance (OD) value of each well at 405 nm.

[0093] Among them, the solution to be tested is the composition of luteolin and formononetin in Comparative Example 1 and the composition of luteolin and kaempferol in Comparative Example 2. First, use dimethyl sulfoxide (DMSO) to prepare stock solutions of luteolin, formononetin, and kaempferol at 10 mg / mL respectively, and then dilute and prepare sample solutions of luteolin, formononetin, and kaempferol at specific concentrations with PBS buffer.

[0094] The positive control group is 100 μL of acarbose (30 μL / mL) + 40 μL of enzyme + 60 μL of pNPG; the blank group is 2 μL of DMSO + 98 μL of PBS + 40 μL of PBS + 60 μL of pNPG.

[0095] Table 4 is the combined drug interaction table of the compositions in the comparative examples. Refer to Table 4, the IC 50 value of luteolin is 4.84 ± 0.32 μg / mL, and the IC 50 value of formononetin is 18.56 ± 1.29 μg / mL, and the IC 50 value of kaempferol is 2.72 ± 0.84 μg / mL. The IC 50 values of luteolin and formononetin in Comparative Example 1 at different mass ratio concentrations are all greater than the IC 50 values of the corresponding monomers, and their Interaction index (interaction index γ) are all greater than 1, and the synergy rates are all negative, showing an antagonistic effect. The IC 50 values of luteolin and kaempferol in Comparative Example 2 at different mass ratio concentrations are all greater than the IC 50 values of the corresponding monomers, and their Interaction index (interaction index γ) are all greater than 1, and the synergy rates are all negative, showing an antagonistic effect. That is, in order to achieve the inhibition rate of single drug use, the combined use of luteolin and formononetin and the combined use of luteolin and kaempferol need to increase the dosage and cannot achieve the effect of reducing the dosage to reduce side effects.

[0096] Table 4 Combined drug interaction table of the compositions in the comparative examples

[0097]

[0098]

[0099] The present invention is not limited to the above embodiments. If various modifications or variations of the present invention do not depart from the spirit and scope of the present invention, and provided that these modifications and variations are within the scope of the claims of the present invention and equivalent technical scope, then the present invention also intends to include these modifications and variations.

Claims

1. A complex for inhibiting α-glucosidase, characterized in that: It comprises a first component and a second component; the first component is luteolin; the second component is 3-O-methylquercetin; The mass ratio of luteolin to 3-O-methylquercetin is 4:6 to 6:

4.

2. The α-glucosidase inhibiting complex according to claim 1, characterized in that: It also includes at least one of a carrier, a solvent, a diluent and an excipient for carrying the first component and the second component.

3. A pharmaceutical dosage form comprising the complex for inhibiting α-glucosidase according to any one of claims 1 to 2, characterized in that: It includes any one of powder, granules, capsules, injections, oral solutions, tablets or pills.

4. An α-glucosidase inhibitor, characterized in that: A compound for inhibiting α-glucosidase comprising the compound according to any one of claims 1 to 3.

Citation Information

Patent Citations

  • Application of 3-O-methyl quercetin to resisting oxidation or reducing blood sugar

    CN111166740A

  • Process to obtain a standardized extract of quercetin and 3-o-methylquercetin from inflorescences of macela-do-campo, a cosmetic, pharmaceutical and veterinary composition containing extract of macela-do-campo, the use of this extract and the method of application of the aforesaid extract

    US20130012577A1