A type of diarylheptane and its preparation method and application

Abstract

This invention provides a class of diarylheptanes, their preparation methods, and applications, belonging to the field of pharmaceutical technology. This invention isolates five novel diarylheptanes (kaemgalangins) A-E (1-5) from kaempferia galanga using activity-directed immunosorbent assay (LC-MS) and LC-MS analysis. These kaemgalangins can promote GLP-1 secretion and inhibit GPa and α-glucosidase activity, which is of great significance for the application of kaempferia galanga and the development of new hypoglycemic drugs, functional foods, and health foods.

Description

Technical Field

[0001] The present invention belongs to the field of pharmaceutical technology, and specifically relates to a class of diarylheptanes and a preparation method and application thereof, and more specifically, relates to five diarylheptane kaemgalangins AE (1-5), and a pharmaceutical composition containing compounds 1-5 as active ingredients, their preparation methods, and applications thereof in preparing GLP-1 secretagogue drugs, in preparing GPa and α-glucosidase inhibitor drugs, and in preparing blood sugar-lowering drugs. Background Art

[0002] Diabetes is a serious chronic metabolic disease that can be divided into type 1 diabetes (T1DM), type 2 diabetes (T2DM) and gestational diabetes (GDM), of which type 2 diabetes accounts for more than 90% of the total number of diabetic patients. At present, the main drugs for the treatment of diabetes in clinical practice include insulin sensitizers, drugs that promote insulin secretion, drugs that inhibit carbohydrate absorption, insulin, enzyme target regulators, and other drugs such as sodium / glucose transporter 2 (SGLT2) inhibitors. However, various side effects (such as acute hypoglycemia, weight gain, adverse skin reactions, ketoacidosis, peripheral neuropathy and infection) limit the application of the above-mentioned diabetes drugs. Therefore, it is necessary to find new drugs for the treatment of diabetes.

[0003] Currently, finding drug targets that can regulate blood sugar levels is a hot topic in diabetes treatment. These targets include receptors and enzymes. Among them, glucagon-like peptide 1 (GLP-1) can stimulate insulin secretion in a glucose-dependent manner, inhibit gastric emptying, food intake and glucagon secretion, and reduce fasting and postprandial blood sugar in diabetic patients. Increased hepatic glucose production is one of the main causes of T2DM. Hepatic glucose production is closely related to the balance between gluconeogenesis, glycogenolysis, glycolysis, and glycogenogenesis. Glycogen phosphorylase GP is composed of two subunits GPa (catalytically active form) and GPb (catalytically inactive form), which is a key enzyme controlling glycogenolysis. Therefore, inhibiting GPa can inhibit glycogenolysis, which is beneficial to controlling hepatic glucose production and maintaining glucose homeostasis. α-glucosidase inhibitors are key enzymes that hydrolyze carbohydrates in food. Inhibiting α-glucosidase can inhibit the body's absorption of glucose to reduce patients' postprandial blood sugar. Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin signaling and can also inhibit the conduction of leptin signals. Experiments have shown that mice with PTP1B knockout not only have enhanced insulin sensitivity, but also do not develop obesity and insulin resistance under a high-fat diet. Currently, most GLP-1 receptor agonists have disadvantages such as high cost, injection, and gastrointestinal and pancreatic side effects. Therefore, it is of great significance to find more GLP-1 receptor agonists from natural medicines.

[0004] my country has a rich variety of medicinal plants, and their safety and effectiveness have been verified through long-term practical use, which provides an important basis for finding hypoglycemic enzyme inhibitors in medicinal plants. Kaempferia galanga is the dried rhizome of Kaempferia galanga L., a plant of the ginger family. It can regulate qi, promote diuresis, stimulate the appetite, kill insects, relieve anxiety, etc. It is used to treat hypertension, chest and abdominal pain, headache, rheumatism, indigestion, etc. Kaempferia galanga has a variety of chemical components, including volatile oils, terpenes, diarylheptanes, flavonoids, cyclic peptides and other chemical components. It has a wide range of pharmacological effects, including antioxidant, anti-inflammatory, analgesic, anthelmintic, anti-cancer, anti-thrombotic, anti-tuberculosis, anti-angiogenesis, sedative, etc. Mahmud ZA et al. first reported the potential hypoglycemic activity of Kaempferia galanga extract in mice. The results of the oral glucose tolerance test showed that the methanol extract and chloroform extract of Kaempferia galanga could effectively inhibit the increase of blood glucose in mice after giving mice excessive glucose for 30 minutes, with inhibition rates of 61.2% and 89.6%, respectively, showing a more significant inhibitory effect than the positive drug glibenclamide (34.8%). However, the anti-diabetic components in Kaempferia galanga have not yet been fully understood.

[0005] Therefore, further analysis and development of anti-diabetic components in kaempferia galanga is of great significance for the application of kaempferia galanga and the development of new hypoglycemic drugs. Summary of the invention

[0006] In view of the above shortcomings, the present invention provides a class of diarylheptanes and their preparation method and application. The present invention separated 5 diarylheptane kaemgalangins AE (1-5) with novel structures and capable of promoting GLP-1 secretion and inhibiting GPa and α-glucosidase activity from kaempferia galanga through activity-guided and LC-MS analysis, which is of great significance for the application of kaempferia galanga and the development of new hypoglycemic drugs.

[0007] In order to achieve the above-mentioned object of the invention, the technical solution of the present invention is as follows:

[0008] In one aspect, the present invention provides a class of diarylheptanes, wherein the diarylheptanes are compounds 1-5 represented by the following structural formulas, namely kaemgalangins AE (1-5),

[0009] .

[0010] On the other hand, the present invention provides a method for preparing the above-mentioned diarylheptane, the preparation method comprising the following steps:

[0011] (1) The dried rhizomes of Kaempferia galanga were crushed and then extracted by soaking in ethanol at room temperature to obtain a crude extract;

[0012] (2) extracting the crude extract obtained in step (1) with ethyl acetate, concentrating, subjecting to silica gel column chromatography, gradient elution with acetone-petroleum ether as eluent, silica gel column chromatography, gradient elution with methanol-chloroform mixed solvent, silica gel column chromatography, gradient elution with acetone-chloroform mixed solvent and methanol-chloroform mixed solvent, to obtain fractions;

[0013] (3) The fraction prepared in step (2) was subjected to reverse phase RP C 18 The diarylheptane is prepared by column chromatography, Sephadex LH-20 separation, high performance liquid chromatography, gel column chromatography, silica gel column chromatography or HPLC.

[0014] Specifically, the concentration of ethanol in step (1) is 75-95%, preferably 90%.

[0015] Specifically, the gradient of the eluent acetone-petroleum ether in step (2) is 5:95-100:0.

[0016] Specifically, the gradient of the eluent methanol-chloroform in step (2) is 2:98 to 100:0.

[0017] Specifically, the gradient of the eluent acetone-chloroform in step (2) is 10:90 to 40:60, and the gradient of methanol-chloroform is 10:90 to 100:0.

[0018] In certain embodiments, the preparation method of diarylheptanes of the present invention comprises the following steps: crushing the dried rhizome of Kaempferia galanga, soaking and extracting it in 90% ethanol at room temperature for 3 times, each time for 48 hours, combining the ethanol extracts, recovering the ethanol under reduced pressure to obtain a crude extract, dispersing the crude extract in water and extracting it with ethyl acetate, and then concentrating it to obtain an ethyl acetate extract, subjecting the ethyl acetate extract to silica gel column chromatography, and gradient eluting with acetone-petroleum ether (5:95~100:0, v / v) as an eluent to obtain fractions Fr. 1~Fr. 10; Fr.8 was subjected to silica gel column chromatography and gradient eluted with a methanol-chloroform mixed solvent (2:98-100:0) to obtain 9 fractions: Fr.8-1-Fr.8-9; Fr.8-7 was subjected to silica gel column chromatography and gradient eluted with an acetone-chloroform mixed solvent (10:90-40:60) and a methanol-chloroform mixed solvent (10:90-100:0) to obtain 3 fractions: Fr.8-7-1-Fr.8-7-3; Fr.8-7-1 was subjected to reverse phase RP C 18 Column chromatography (MeOH-H2O, 30:70-90:10) and Sephadex LH-20 (MeOH-CHCl3, 50:50) were used for separation, followed by semi-preparative HPLC (MeOH-H2O, 37:67), (MeCN-H2O, 20:80) and (MeOH-H2O, 47:53) to obtain compounds 1, 4 and 5. Fr.8-7-2 was purified by multiple reverse phase C 18 Column chromatography, gel column chromatography and silica gel column chromatography, and finally semi-preparative HPLC (MeOH-H2O, 45:65) purification to obtain compound 3; Fr.8-7-3 was purified by multiple reverse phase C 18 Compound 2 was purified by column chromatography, silica gel column chromatography, and semi-preparative HPLC (MeOH-H2O, 28:72).

[0019] In another aspect, the present invention provides the use of the above-mentioned diarylheptane in the preparation of GLP-1 secretagogue drugs.

[0020] In yet another aspect, the present invention provides a GLP-1 secretagogue drug, wherein the drug comprises the above-mentioned diarylheptane.

[0021] In another aspect, the present invention provides the use of the above diarylheptane in the preparation of GPa and α-glucosidase inhibitor drugs.

[0022] In another aspect, the present invention provides a GPa and α-glucosidase inhibitor drug, wherein the drug comprises the above-mentioned diarylheptane.

[0023] In another aspect, the present invention provides use of the above diarylheptane in the preparation of hypoglycemic drugs.

[0024] In another aspect, the present invention provides a hypoglycemic drug, wherein the hypoglycemic drug comprises the above-mentioned diarylheptane.

[0025] In yet another aspect, the present invention provides a pharmaceutical composition comprising the above-mentioned diarylheptane and a pharmaceutically acceptable carrier or excipient.

[0026] Specifically, the pharmaceutically acceptable carrier or excipient includes, but is not limited to, a diluent, an excipient, a filler, a wetting agent, a disintegrant, a flavoring agent, and a binder.

[0027] Specifically, the pharmaceutical composition includes, but is not limited to, capsules, tablets, lozenges, pills, pellets, suppositories, sprays, creams, patches and the like.

[0028] In another aspect, the present invention provides use of the above pharmaceutical composition in the preparation of a GLP-1 secretagogue drug.

[0029] In another aspect, the present invention provides use of the above pharmaceutical composition in the preparation of GPa and α-glucosidase inhibitor drugs.

[0030] In another aspect, the present invention provides use of the above-mentioned pharmaceutical composition in the preparation of hypoglycemic drugs.

[0031] In another aspect, the present invention provides a method for preparing the above-mentioned pharmaceutical composition, the method comprising the following steps: using the above-mentioned diarylheptane as a raw material, adding a pharmaceutically acceptable carrier or excipient. The pharmaceutically acceptable carrier or excipient is one or more solid, semi-solid and liquid diluents, fillers and pharmaceutical product adjuvants.

[0032] In certain embodiments, the diarylheptanes of the present invention can be used directly or in the form of a pharmaceutical composition when used as a GLP-1 secretagogue and a GPa and α-glucosidase inhibitor or drug. The pharmaceutical composition contains 0.1-99%, preferably 0.5-90% of compound 1-5, and the rest is a pharmaceutically acceptable, non-toxic and inert pharmaceutical carrier and / or excipient to humans and animals. The pharmaceutical composition of the present invention is used in the form of a dosage per unit body weight. The drug of the present invention can be administered in two forms: injection (intravenous injection, intramuscular injection) and oral administration.

[0033] Compared with the prior art, the present invention has the following positive and beneficial effects:

[0034] 1. The present invention provides a new class of diarylheptanes, which are new compounds reported for the first time.

[0035] 2. The present invention isolates 5 new diarylheptanes from Kaempferia galanga. At a concentration of 50.0 μM, compounds 1-5 can significantly stimulate the secretion of GLP-1 in NCI-H716 cells; compound 1 has moderate GPa inhibitory activity, with an inhibition rate of 63.6% at 200 μM; compounds 1 and 5 have significant α-glucosidase inhibitory activity, with IC 50 The values ​​were 45.3 and 116.0 μM, respectively. The present invention shows that the monomeric diarylheptane in Kaempferia galanga has a potential hypoglycemic effect.

[0036] 3. The compounds of the present invention have both GLP-1 secretion promoting activity and GPa and α-glucosidase inhibitory activity, and are a novel class of multi-target hypoglycemic active molecules.

[0037] 4. The preparation method of the present invention is simple and easy to operate, has a high yield, is environmentally friendly and safe, and has high feasibility. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 The promoting effect of compounds 1-5 of the present invention on GLP-1 secretion in NCI-H716 cells, cholic acid was used as a positive control, and the values ​​are expressed as mean ± standard deviation (n=3). DETAILED DESCRIPTION

[0039] The present invention will be further described in detail below in conjunction with specific examples. The following examples are not intended to limit the present invention, but are only intended to illustrate the present invention. The experimental methods used in the following examples are generally conventional, unless otherwise specified, and the materials, reagents, etc. used in the following examples are commercially available, unless otherwise specified.

[0040] Example 1. Preparation of Compound 1-5

[0041] The dried rhizome of Kaempferia galanga was crushed, and extracted with 90% ethanol at room temperature for 3 times, each time for 48 hours. The ethanol extracts were combined, and the ethanol was recovered under reduced pressure to obtain a crude extract. The crude extract was dispersed in water and extracted with ethyl acetate, which was then concentrated to obtain an ethyl acetate extract. The ethyl acetate extract was subjected to silica gel column chromatography and chromatographed with acetone-petroleum ether (5:95-100:0, v / v) as the eluent for gradient elution to obtain fractions Fr.1~Fr.10; Fr.8 (52 g) was subjected to silica gel column chromatography and gradient eluted with a methanol-chloroform mixed solvent (2:98-100:0) to obtain 9 fractions: Fr.8-1~Fr.8-9; Fr.8-7 was subjected to silica gel column chromatography and gradient eluted with an acetone-chloroform mixed solvent (10:90-40:60) and a methanol-chloroform mixed solvent (10:90-100:0) to obtain 3 fractions: Fr.8-7-1~Fr.8-7-3; Fr.8-7-1 was subjected to reverse phase RP C 18 Column chromatography (MeOH-H2O, 30:70-90:10) and Sephadex LH-20 (MeOH-CHCl3, 50:50) were used for separation, followed by semi-preparative HPLC (MeOH-H2O, 37:67), (MeCN-H2O, 20:80) and (MeOH-H2O, 47:53) to obtain compounds 1, 4 and 5. Fr.8-7-2 was purified by multiple reverse phase C 18 Column chromatography, gel column chromatography and silica gel column chromatography, and finally semi-preparative HPLC (MeOH-H2O, 45:65) purification to obtain compound 3; Fr. 8-7-3 was subjected to multiple reverse phase C 18 Compound 2 was purified by column chromatography, silica gel column chromatography, and semi-preparative HPLC (MeOH-H2O, 28:72).

[0042] Structural data of compounds 1-5:

[0043] Optical rotation was measured by a Jasco model 1020 polarimeter (Horiba, Tokyo, Japan). Infrared spectra (IR) were measured by a Bio-Rad FTS-135 infrared spectrometer (Hercules, California, USA) using the KBr pellet method. UV spectra were measured by a UV-2401PC UV spectrometer (Shimadzu, Kyoto, Japan). ECD spectra were measured by an Applied Photophysics circular dichroism spectrometer (Agilent, Santa Clara, United States). Nuclear magnetic resonance spectra (1D and 2D NMR) were measured by an Avance III-600 superconducting nuclear magnetic resonance spectrometer (Bruker, Bremerhaven, Germany) using deuterated methanol as the solvent. High-resolution mass spectra (HRMS) were measured by an LCMS-IT-TOF mass spectrometer (Shimadzu, Kyoto, Japan; thin layer chromatography silica gel and column chromatography silica gel (200-300 mesh) were purchased from Linyi Haixiang Chemical Co., Ltd. (Linyi, China) and Yantai Xinnuo New Materials Technology Co., Ltd. (Yantai, China).

[0044]

[0045] Kaemgalangin A (1)

[0046] Molecular formula: C 19 H 22 O5

[0047] Molecular weight: 330

[0048] Appearance: Colorless colloidal solid

[0049] HRESIMS m / z :331.1557 [M + H] + (calcd. for C 19 H 23 O5, m / z 331.1540);

[0050] UV (MeOH) l max (log e ):195 (3.80), 223 (3.07), 280 (2.62) nm;

[0051] IR (KBr) v max : 3247, 2937, 1601, 1516, 1459, 1380, 1245, 1027, 824 cm –1 ;

[0052] ECD ( c 0.05, MeOH) l max (∆ e ): 202 (−7.48), 216 (+1.53), 228 (−0.03), 243 (+2.16) nm;

[0053] [ α ]20D–100.2 ( c 0.1, MeOH);

[0054] 1 HNMR and 13 CNMR (DEPT) data are shown in Table 1.

[0055]

[0056] Kaemgalangin B (2)

[0057] Molecular formula: C 20 H 24 O7

[0058] Molecular weight: 376

[0059] Appearance: Colorless colloidal solid

[0060] HRESIMS m / z : 399.1399 [M + Na] + (calcd. for C 20 H 24 O7Na, m / z 399.1414);

[0061] UV (MeOH) l max (log e ): 196 (3.96), 224 (3.23), 278 (2.74) nm;

[0062] IR (KBr) n max : 3435, 1614, 1518, 1451, 1382, 1274, 1237, 1051, 821 cm –1 ;

[0063] ECD ( c 0.04, MeOH) l max (∆ e ): 201 (−18.67), 215 (2.51), 230 (−3.50), 247 (3.16) nm;

[0064] [ α ]20D –70.1 ( c 0.09, MeOH);

[0065] 1 H-NMR and 13 C-NMR (DEPT) data are shown in Table 2.

[0066]

[0067] Kaemgalangin C (3)

[0068] Molecular formula: C 29 H 32 O 10

[0069] Molecular weight: 540

[0070] Appearance: Colorless colloidal solid

[0071] HRESIMS m / z 563.1906 [M + Na] + (calcd. for C 29 H 32 O 10 Na, m / z 563.1888);

[0072] UV (MeOH) l max (log e ): 200 (4.06), 218 (3.41), 229 (3.48), 250 (2.70), 279 (3.27), 312 (3.05) nm;

[0073] IR (KBr) n max : 3431, 2925, 2853, 1681, 1595, 1516, 1464, 1428, 1385,1272, 1128, 1031, 816 cm –1 ;

[0074] ECD ( c 0.04, MeOH) l max (∆ e ): 196 (+18.93), 236 (−2.20), 247 (+1.86), 265 (+0.93), 312 (+3.25) nm;

[0075] [ α ]20D–4.6 ( c 0.08, MeOH);

[0076] 1 H-NMR and 13 C-NMR (DEPT) data are shown in Table 2.

[0077]

[0078] Kaemgalangin D (4)

[0079] Molecular formula: C 20 H 26 O6

[0080] Molecular weight: 362

[0081] Appearance: Colorless colloidal solid

[0082] HRESIMS m / z 385.1644 [M + Na] + (calcd. for C 20 H 26 O6Na, m / z 385.1622);

[0083] UV (MeOH) l max (log e ): 214 (3.17), 224 (3.25), 249 (2.41), 282 (2.84)nm;

[0084] [ α ]20D+15.7 ( c 0.06, MeOH);

[0085] 1 H-NMR and 13 C-NMR (DEPT) data are shown in Table 3.

[0086]

[0087] Kaemgalangin E (5)

[0088] Molecular formula: C 19 H 24 O5

[0089] Molecular weight: 332

[0090] Appearance: Colorless colloidal solid

[0091] HRESIMS m / z 331.1541 [M – H] – (calcd for C 19 H 23 O5, m / z 331.1551);

[0092] UV (MeOH) l max (log e ): 218 (3.15), 223 (3.16), 252 (2.28), 282 (2.72)nm;

[0093] [ α ]20D–11.5 ( c 0.08, MeOH);

[0094] 1 H-NMR and 13 C-NMR (DEPT) data are shown in Table 3.

[0095]

[0096]

[0097]

[0098] Example 2. Compounds promote GLP-1 secretion and GPa, PTP1B and α-glucosidase inhibitory activities

[0099] 1. Materials and Methods

[0100] 1.1. Materials

[0101] NCI-H716 cells were purchased from the Cell Bank of the Chinese Academy of Sciences (Shanghai); human GLP-1 ELISA kit was purchased from Signalway Antibody (Maryland, USA); α-glucosidase (G5003-100UN) and GPa (P1261-10MG) were purchased from Sigma Aldrich (St. Louis, MO, USA); PTP1B (10304-H07E) was purchased from Sino Biological (Wayne, PA, USA); acarbose was purchased from Beijing Bailingwei Technology Co., Ltd.; sodium orthovanadate was purchased from Sane Chemical Technology Co., Ltd.

[0102] 1.2. Instruments

[0103] Flex Station 3 desktop multifunctional microplate reader was purchased from Bio-Rad Laboratories; FlexA-200 full-wavelength microplate analyzer was purchased from Hangzhou Aosheng Instrument Co., Ltd.; analytical balance ME104E was purchased from Mettler-Toledo Instrument (Shanghai) Co., Ltd.; electric constant temperature incubator (DHP-9082) was purchased from Shanghai Yiheng Technology Co., Ltd.

[0104] 1.3 Experimental procedures

[0105] GLP-1 secretion experiment: The experiment was carried out according to the literature report (Biochem. Biophys. Res. Commun. 2013,435, 165-170) and adjusted. NCl-H716 cells were cultured in RPMI-1640 medium containing 10% FBS and 1% PS at 37°C and 5% CO2 saturated humidity incubator; when the cells grew to 80-90%, the diluted cell suspension was inoculated in a 24-well plate (5×10 5 Each well was starved for 1 hour after adding KRBH working solution III; each well was starved for 2 hours after adding KRBH working solution IV containing the compound, and the supernatant was collected; the GLP-1 content in the supernatant was detected using a human GLP-1 ELISA kit.

[0106] GPa, α-glucosidase, and PTP1B inhibition experiments were performed according to the methods reported in the literature (Ind. Crop. Prod. 2020, 144, 112028) and (Chin. J. Chem. 2021, 39, 3051-3063).

[0107] 2. Results:

[0108] Compounds 1-5 were evaluated for their ability to stimulate GLP-1 secretion in NCl-H716 cells at a concentration of 50 μM. Figure 1 As shown, at a concentration of 50 μM, the compounds all showed a significant effect of promoting GLP-1 secretion, with the secretion promotion rate ranging from 826.9% to 1738.3%.

[0109] The inhibitory activity of compounds 1-5 on GPa was tested at concentrations of 200 μM and 100 μM. As shown in Table 4, compound 1 had a moderate inhibitory effect on GPa, with an inhibition rate of 63.6% at a concentration of 200 μM.

[0110] As shown in Table 4, compounds 1 and 5 have significant inhibitory activity against α-glucosidase, and their inhibitory activity is better than that of positive acarbose (IC50: 392.0 μM), and their IC50 are 45.3 μM and 116.0 μM, respectively.

[0111] At 200 μM, all compounds showed weak inhibitory activity against PTP1B.

[0112]

[0113] a Values ​​are expressed as mean ± SD (n = 3); b CP-91149 is the positive control for the GPa inhibition assay; cAcarbose was the positive control for the α-glucosidase inhibition assay; d Sodium orthovanadate was used as a positive control for the PTP1B inhibition assay.

[0114] 3. Conclusion:

[0115] The present invention separates 5 new diarylheptanes from Kaempferia galanga. At a concentration of 50 μM, the compounds all show obvious GLP-1 secretion-promoting effects, with secretion-promoting rates ranging from 826.9% to 1738.3%. Compound 1 has a moderate inhibitory effect on GPa, with an inhibition rate of 63.6% at a concentration of 200 μM. Compounds 1 and 5 have obvious α-glucosidase inhibitory activity, with IC 50 The results show that the diarylheptanes in Kaempferia galanga have the effect of reducing blood sugar.

[0116] Example 3. Formulation Example

[0117] 1. Take any one of compounds 1-5 or any combination thereof, dissolve it with a small amount of DMSO, add water for injection according to the routine method, filter it, and sterilize it by filling to prepare an injection solution.

[0118] 2. Take any one of compounds 1-5 or any combination thereof, dissolve it with a small amount of DMSO, dissolve it in sterile water for injection, stir to dissolve, filter with a sterile suction funnel, filter aseptically, dispense into ampoules, freeze-dry at low temperature, and aseptically seal to obtain powder injection.

[0119] 3. Take any one of compounds 1-5 or any combination thereof, add excipients at a weight ratio of 9:1 to the excipients to prepare powders.

[0120] 4. Take any one of compounds 1-5 or any combination thereof, add excipients at a weight ratio of 5:1 to the excipients, and granulate and tablet.

[0121] 5. Take any one of compounds 1-5 or any combination thereof and prepare an oral liquid according to a conventional oral liquid preparation method.

[0122] 6. Take any one of compounds 1-5 or any combination thereof, add excipients at a weight ratio of 5:1 to the excipients, and prepare capsules.

[0123] 7. Take any one of compounds 1-5 or any combination thereof, add excipients at a weight ratio of 3:1 to the excipients, and prepare capsules.

[0124] 8. Take any one of compounds 1-5 or any combination thereof, add excipients at a weight ratio of 5:1 to the excipients to prepare granules.

[0125] The above-mentioned embodiments only express several implementation methods of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the scope of the patent of the present invention. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, which all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A diarylheptane, characterized in that: The diarylheptane is a compound shown in the following structural formula: 。 2. A method for preparing the diarylheptane according to claim 1, characterized in that: The preparation method comprises the following steps: (1) The dried rhizomes of Kaempferia galanga were crushed, and then soaked and extracted with 90% ethanol at room temperature for 3 times, each time for 48 h. The ethanol extracts were combined, and the ethanol was recovered under reduced pressure to obtain a crude extract; (2) The crude extract prepared in the above step (1) is dispersed in water and extracted with ethyl acetate, which is then concentrated to obtain an ethyl acetate extract. The ethyl acetate extract is subjected to silica gel column chromatography and gradient eluted with acetone-petroleum ether in a volume percentage of 5:95-100:0 as an eluent to obtain fractions Fr.1-Fr.10; Fr.8 is subjected to silica gel column chromatography and gradient eluted with a mixed solvent of methanol-chloroform in a volume percentage of 2:98-100:0 to obtain 9 fractions: Fr.8-1-Fr.8-9; Fr.8-7 is subjected to silica gel column chromatography and gradient eluted with a mixed solvent of acetone-chloroform in a volume percentage of 10:90-40:60 and a mixed solvent of methanol-chloroform in a volume percentage of 10:90-100:0 to obtain 3 fractions: Fr.8-7-1-Fr.8-7-3; (3) The fraction Fr.8-7-2 prepared in step (2) above was subjected to multiple reverse phase C 18 Column chromatography, gel column chromatography and silica gel column chromatography, and finally semi-preparative HPLC purification, with the eluent being MeOH-H2O 45:65, to obtain the diarylheptane according to claim 1.

3. Use of the diarylheptane according to claim 1 in the preparation of GLP-1 secretagogue drugs.

4. Use of the diarylheptane according to claim 1 in the preparation of α-glucosidase inhibitor drugs.

5. Use of the diarylheptane according to claim 1 in the preparation of hypoglycemic drugs.

6. A pharmaceutical composition, characterized in that: The pharmaceutical composition comprises the diarylheptane according to claim 1 and a pharmaceutically acceptable carrier.

7. Use of the pharmaceutical composition according to claim 6 in the preparation of a GLP-1 secretagogue drug.

8. Use of the pharmaceutical composition according to claim 6 in the preparation of α-glucosidase inhibitor drugs.

9. Use of the pharmaceutical composition according to claim 6 in the preparation of hypoglycemic drugs.

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