Thiazole alkaloid compound or pharmaceutically acceptable salt thereof as well as preparation method and application thereof

Abstract

The invention provides a thiazole alkaloid compound or a pharmaceutically acceptable salt thereof as well as a preparation method and application thereof, and belongs to the field of medicines. The thiazole alkaloid compound or the pharmaceutically acceptable salt thereof has a remarkable inhibition effect on the activity of alpha-glucosidase, and can be used for preventing or treating diabetes mellitus or complications thereof.

Description

Technical Field

[0001] The invention belongs to the field of medicine, and specifically relates to a thiazole alkaloid compound or a pharmaceutically acceptable salt thereof, and a preparation method and application thereof. Background Art

[0002] Diabetes is a common metabolic disease with high blood sugar as the main feature caused by genetic and environmental factors. The basic pathological characteristics are absolute (type I diabetes) or relative insufficiency of insulin secretion (type II diabetes). Diabetes can cause endocrine metabolic disorders of sugar, protein, secondary water and electrolyte metabolism disorders and acid-base imbalance. In the long term, it can also cause complications such as blindness, renal failure, heart attack, stroke, vascular disease, and even lead to foot nerve degeneration and central nervous system dysfunction. Among them, type II diabetes mellitus (T2DM) is the main form of diabetes, accounting for 90% of the incidence of diabetes, and insulin resistance is common in type II diabetes. At present, Western medicine for the treatment of diabetes in clinical practice is mainly divided into six categories: biguanides, sulfonylureas, α-glucosidase inhibitors, insulin sensitizers, meglitinide insulin secretagogues, dipeptidyl peptidase 4 (DPP-4) inhibitors, etc.

[0003] α-glucosidase inhibitors are one of the first-line drugs for the clinical treatment of type II diabetes. Their main mechanism of action is to inhibit the conversion of carbohydrates by α-glucosidase at the brush border of small intestinal mucosal cells, thereby reducing postprandial blood sugar. Clinical studies have shown that α-glucosidase inhibitors can control the increase in postprandial blood sugar in diabetic patients, reduce the stimulation of high-sugar environment on body tissues and organs, and delay the process of transformation of patients with impaired glucose tolerance to type II diabetes. In addition, this type of drug can also overcome some shortcomings of traditional hypoglycemic drugs and has broad application prospects in regulating glucose and lipid metabolism, improving insulin sensitivity, protecting pancreatic islet cell function, and improving various diabetic complications.

[0004] Cordyceps sinensis is a dried complex of the fruiting bodies of the larvae of the ergot family fungus Cordyceps sinensis (BerK.) Sacc. parasitizing on the larvae of the bat moth family insects and the larvae. It has multiple pharmacological effects such as regulating immunity, anti-tumor, anti-oxidation, and anti-diabetes. Literature reports that the chemical components of Cordyceps sinensis mainly include polysaccharides, proteins, sugar alcohols, nucleosides, amino acids, sterols, and organic acids. It is of great significance to discover new active ingredients from Cordyceps sinensis. Summary of the invention

[0005] The object of the present invention is to provide a thiazole alkaloid compound or a pharmaceutically acceptable salt thereof, a preparation method and application thereof, and a pharmaceutical composition or pharmaceutical preparation containing the thiazole alkaloid compound or a pharmaceutically acceptable salt thereof.

[0006] In a first aspect, the present invention provides a class of compounds represented by formula (I) or pharmaceutically acceptable salts thereof.

[0007] A compound represented by formula (I) or a pharmaceutically acceptable salt thereof,

[0008]

[0009] In some embodiments, the pharmaceutically acceptable salt is a salt formed by the compound represented by formula (I) and an inorganic base, an inorganic acid or an organic acid.

[0010] In some embodiments, the pharmaceutically acceptable salt is a sodium salt or a potassium salt of the compound represented by formula (I).

[0011] In some embodiments, the pharmaceutically acceptable salt is a hydrochloride, hydrobromide, sulfate, nitrate, acetate, propionate, malonate, butyrate, lactate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, maleate, benzoate, succinate, picrate, tartrate, citrate or fumarate of the compound of formula (I).

[0012] In some embodiments, the inorganic base is sodium hydroxide or potassium hydroxide.

[0013] In some embodiments, the inorganic acid is hydrochloric acid, hydrobromic acid, sulfuric acid or nitric acid.

[0014] In some embodiments, the organic acid is acetic acid, propionic acid, malonic acid, butyric acid, lactic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, maleic acid, benzoic acid, succinic acid, picric acid, tartaric acid, citric acid, or fumaric acid.

[0015] In a second aspect, the present invention provides a pharmaceutical composition.

[0016] A pharmaceutical composition comprising the compound represented by formula (I) or a pharmaceutically acceptable salt thereof according to the first aspect and a pharmaceutically acceptable excipient.

[0017] In some embodiments, the pharmaceutical composition is in the form of an oral preparation or an injection.

[0018] In some embodiments, the pharmaceutical composition is in the form of tablets, granules, capsules, pills, oral liquids, oral emulsions, aqueous injections, infusions or lyophilized powder injections.

[0019] In some embodiments, the tablet is a conventional tablet, a sustained-release tablet, a controlled-release tablet, a rapid-release tablet, a lozenge, a sublingual tablet, an oral patch, a chewable tablet, an effervescent tablet, a dispersible tablet or an enteric-coated tablet.

[0020] In some embodiments, the content of the compound shown in formula (I) or its pharmaceutically acceptable salt in the pharmaceutical composition is 0.01%-99.99% by weight of the pharmaceutical composition. In some embodiments, the content of the compound shown in formula (I) or its pharmaceutically acceptable salt in the pharmaceutical composition is 0.1%-99.9% by weight of the pharmaceutical composition. In some embodiments, the content of the compound shown in formula (I) or its pharmaceutically acceptable salt in the pharmaceutical composition is 1%-99% by weight of the pharmaceutical composition. In some embodiments, the content of the compound shown in formula (I) or its pharmaceutically acceptable salt in the pharmaceutical composition is 0.01%, 0.1%, 1%, 2%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99% or 99.99% by weight of the pharmaceutical composition.

[0021] In some embodiments, the pharmaceutically acceptable excipients include at least one of a diluent, a lubricant, a binder, a disintegrant, a stabilizer, a solvent, and the like.

[0022] In some embodiments, the diluent includes but is not limited to at least one of starch, microcrystalline cellulose, sucrose, dextrin, lactose, powdered sugar, glucose, and the like.

[0023] In some embodiments, the lubricant includes but is not limited to at least one of magnesium stearate, stearic acid, sodium chloride, sodium oleate, sodium lauryl sulfate, poloxamer, and the like.

[0024] In some embodiments, the binder includes but is not limited to at least one of water, ethanol, starch slurry, syrup, hydroxypropyl methylcellulose, sodium carboxymethyl cellulose, sodium alginate, polyvinyl pyrrolidone, and the like.

[0025] In some embodiments, the disintegrant includes but is not limited to a starch effervescent mixture, namely sodium bicarbonate and at least one of citric acid, tartaric acid, low-substituted hydroxypropyl cellulose, and the like.

[0027] In some embodiments, the stabilizer includes but is not limited to polysaccharides such as acacia gum, agar, alginic acid, cellulose ether and carboxymethyl chitosan, etc.; the solvent includes but is not limited to at least one of water, a balanced salt solution, etc.

[0028] In some embodiments, the pharmaceutical composition is used to inhibit α-glucosidase activity.

[0029] In some embodiments, the pharmaceutical composition is used to prevent and / or treat diabetes or its complications.

[0030] In some embodiments, the complications include at least one of diabetic nephropathy, diabetic retinopathy, uveitis, diabetic cataracts, diabetic foot, diabetic cardiovascular complications, diabetic cerebrovascular disease, and diabetic neuropathy.

[0031] In a third aspect, the present invention provides a pharmaceutical preparation.

[0032] A pharmaceutical preparation comprising the compound represented by formula (I) or a pharmaceutically acceptable salt thereof according to the first aspect and a pharmaceutically acceptable excipient.

[0033] In some embodiments, the pharmaceutical preparation is an oral preparation or an injection.

[0034] In some embodiments, the dosage form of the pharmaceutical preparation is tablets, granules, capsules, pills, oral liquids, oral emulsions, water injections, infusions or lyophilized powder injections.

[0035] In some embodiments, the dosage form of the pharmaceutical preparation is tablets, granules, capsules, pills, oral liquids, oral emulsions, aqueous injections, infusions or lyophilized powder injections.

[0036] In some embodiments, the tablet is a conventional tablet, a sustained-release tablet, a controlled-release tablet, a rapid-release tablet, a lozenge, a sublingual tablet, an oral patch, a chewable tablet, an effervescent tablet, a dispersible tablet or an enteric-coated tablet.

[0037] In some embodiments, the pharmaceutical formulation is used to inhibit α-glucosidase activity.

[0038] In some embodiments, the pharmaceutical formulation is used to prevent and / or treat diabetes or its complications.

[0039] In some embodiments, the complications include at least one of diabetic nephropathy, diabetic retinopathy, uveitis, diabetic cataracts, diabetic foot, diabetic cardiovascular complications, diabetic cerebrovascular disease, and diabetic neuropathy.

[0040] In a fourth aspect, the present invention provides a Cordyceps sinensis extract.

[0041] A cordyceps sinensis extract contains a compound represented by formula (I) or a pharmaceutically acceptable salt thereof.

[0042] In a fifth aspect, the present invention provides a Cordyceps sinensis extract.

[0043] A cordyceps sinensis extract, the cordyceps sinensis extract is named cordyceps sinensis extract F3, the cordyceps sinensis extract F3 contains the compound represented by formula (I) or a pharmaceutically acceptable salt thereof, and the preparation method of the cordyceps sinensis extract F3 comprises: taking cordyceps sinensis, extracting, extracting, separating by a first chromatography, concentrating or drying to obtain the cordyceps sinensis extract F3.

[0044] In some embodiments, the extraction includes: mixing the crude extract with water to obtain a suspension, extracting the suspension with an alkane solvent and an ester solvent in sequence to obtain an alkane solvent extract and an ester solvent extract, respectively, and concentrating the ester solvent extract to obtain an extract.

[0045] In some embodiments, the extracting is selected from the following operations:

[0046] (S1) the extraction comprises extracting with an alcohol solution A, separating the solid from the liquid to obtain an alcohol extract, and concentrating the extract to obtain a crude extract, wherein the alcohol in the alcohol solution A comprises at least one of methanol or ethanol; or

[0047] (S2) the extraction comprises extraction with water, solid-liquid separation, obtaining a water extract, adsorbing the water extract with a macroporous resin, eluting with an alcohol solution B, obtaining an alcohol eluate, and concentrating to obtain a crude extract, wherein the alcohol in the alcohol solution B comprises at least one of methanol or ethanol; or

[0048] (S3) The extraction includes extraction with water, solid-liquid separation, and obtaining a water extract and a solid residue, and the solid residue is then extracted with an alcohol solution A, and solid-liquid separation is performed to obtain an alcohol extract; the water extract is adsorbed with a macroporous resin and eluted with an alcohol solution B to obtain an alcohol eluent; the alcohol eluent and the alcohol extract are combined and concentrated to obtain a crude extract, wherein the alcohol in the alcohol solution A includes at least one of methanol or ethanol, and the alcohol in the alcohol solution B includes at least one of methanol or ethanol.

[0049] The first chromatographic separation is selected from the following operations:

[0050] (i) the first chromatographic separation comprises: subjecting the extract to a first chromatographic separation using an ODS chromatographic column, using methanol-water mixed solvents in different proportions as eluents to sequentially perform gradient elution, collecting the eluates eluted with the methanol-water mixed solvents in different proportions, confirming that the eluate contains the compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof, and taking the eluate containing the compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof for subsequent concentration or drying operations;

[0051] or

[0052] (ii) the first chromatographic separation comprises: performing a first chromatographic separation on the extract using an ODS chromatographic column, sequentially using methanol-water mixed solvents in different ratios of 3:97-7:93, 8:92-12:88 and 28:72-32:68 as eluents for gradient elution; collecting the methanol-water mixed solvent in a volume ratio of 28:72-32:68 after elution for subsequent concentration or drying operations;

[0053] or

[0054] (iii) the first chromatographic separation comprises: performing a first chromatographic separation on the extract using an ODS chromatographic column, sequentially using a methanol-water mixed solvent having a volume ratio of methanol to water of 5:95, 10:90 and 30:70 as an eluent for gradient elution; collecting the methanol-water mixed solvent having a volume ratio of methanol to water of 30:70 after the elution for subsequent concentration or drying;

[0055] or

[0056] (iv) the first chromatographic separation comprises using an ODS chromatographic column as a chromatographic column for the first chromatographic separation; the filler particle size of the chromatographic column of the first chromatographic separation is 25 μm-75 μm; the weight ratio of the filler to the extract of the chromatographic column of the first chromatographic separation is 1:1-20:1; the first chromatographic separation sequentially uses a methanol-water mixed solvent with a volume ratio of methanol to water of 3:97-7:93, 8:92-12:88, and 28:72-32:68 for elution; the elution volume of the methanol-water mixed solvent with different volume ratios in the first chromatographic separation is independently 3-10 times the column volume of the chromatographic column of the first chromatographic separation; the methanol-water mixed solvent with a volume ratio of methanol to water of 28:72-32:68 after elution is collected for subsequent concentration or drying operations;

[0057] or

[0058] (v) The first chromatographic separation includes using an ODS chromatographic column as a chromatographic column for chromatographic separation; the filler particle size of the chromatographic column of the first chromatographic separation is 50 μm; the weight ratio of the filler to the extract of the chromatographic column of the first chromatographic separation is 10:1; the first chromatographic separation uses a methanol-water mixed solvent with a volume ratio of methanol to water of 5:95, 10:90, and 30:70 for elution; the elution volume of the methanol-water mixed solvent with different volume ratios in the first chromatographic separation is 5 times the column volume of the chromatographic column of the first chromatographic separation; the methanol-water mixed solvent with a volume ratio of methanol to water of 30:70 after elution is collected for subsequent concentration or drying operations.

[0059] In some embodiments, the alcohol solution A in the extraction operation (S1) or (S3) is a mixed solution or a pure alcohol solution in which the volume ratio of alcohol to water is greater than or equal to 90:10 and less than 100:0; or the alcohol solution A in the extraction operation (S1) or (S3) is a 95% vol alcohol aqueous solution.

[0060] In some embodiments, the alcohol solution B in the extraction operation (S2) or (S3) is a mixed solution or a pure alcohol solution in which the volume ratio of alcohol to water is greater than or equal to 90:10 and less than 100:0; or the alcohol solution B in the extraction operation (S2) or (S3) is a 95% vol alcohol aqueous solution.

[0061] In some embodiments, the alcohol in the alcohol solution A in the extraction operation (S1) or (S3) or the alcohol in the alcohol solution B in the extraction operation (S2) or (S3) is independently selected from at least one of methanol or ethanol.

[0062] In some embodiments, the alcohol solution A in the extraction operation (S1) or (S3) is the same as the alcohol solution B in the extraction operation (S2) or (S3).

[0063] In some embodiments, the alcohol solution A in the extraction operation (S1) or (S3) is the same as the alcohol solution B in the extraction operation (S2) or (S3), which is a 95% vol ethanol aqueous solution.

[0064] In some embodiments, the Cordyceps sinensis is crushed before extraction.

[0065] In some embodiments, in the water extraction step described in the extraction operation (S2) or (S3), 1 mL-100 mL of water is used for every 1 g of Cordyceps sinensis. In some embodiments, in the water extraction step described in the extraction operation (S2) or (S3), 1 mL, 5 mL, 8 mL, 10 mL, 15 mL, 20 mL, 25 mL, 30 mL, 40 mL, 50 mL, 60 mL, 70 mL, 80 mL, 90 mL or 100 mL of water is used for every 1 g of Cordyceps sinensis. In some embodiments, in the water extraction step described in the extraction operation (S2) or (S3), 8 mL of water is used for every 1 g of Cordyceps sinensis.

[0066] In some embodiments, in the extraction step of using alcohol solution A in the extraction operation (S1) or (S3), 1 mL-100 mL of alcohol solution A is used for extraction per 1 g of Cordyceps sinensis. In some embodiments, in the extraction step of using alcohol solution A in the extraction operation (S1) or (S3), 1 mL, 5 mL, 8 mL, 10 mL, 15 mL, 20 mL, 25 mL, 30 mL, 40 mL, 50 mL, 60 mL, 70 mL, 80 mL, 90 mL or 100 mL of alcohol solution A is used for extraction per 1 g of Cordyceps sinensis. In some embodiments, in the extraction step of using alcohol solution A in the extraction operation (S1) or (S3), 8 mL of alcohol solution A is used for extraction per 1 g of Cordyceps sinensis.

[0067] In some embodiments, the number of extractions using water in the extraction operation (S2) or (S3) is independently 1-5 times, 2-4 times, or 3 times. In some embodiments, the number of extractions using water in the extraction operation (S2) or (S3) is independently 1 time, 2 times, 3 times, 4 times, or 5 times.

[0068] In some embodiments, the number of extractions performed with the alcohol solution A in the extraction operation (S1) or (S3) is independently 1-5 times, 2-4 times, or 3 times. In some embodiments, the number of extractions performed with the alcohol solution A in the extraction operation (S1) or (S3) is independently 1 time, 2 times, 3 times, 4 times, or 5 times.

[0069] In some embodiments, the extraction time of each extraction with water in the extraction operation (S2) or (S3) is independently 1 hour to 5 hours, 2 hours to 4 hours, 2.5 hours to 3.5 hours or 3 hours. In some embodiments, the extraction time of each extraction with water in the extraction operation (S2) or (S3) is independently 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours or 5 hours.

[0070] In some embodiments, the extraction time of each extraction with alcohol solution A in the extraction operation (S1) or (S3) is independently 1 hour to 5 hours, 2 hours to 4 hours, 2.5 hours to 3.5 hours or 3 hours. In some embodiments, the extraction time of each extraction with alcohol solution A in the extraction operation (S1) or (S3) is independently 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours or 5 hours.

[0071] In some embodiments, the extraction temperature of the water extraction in the extraction operation (S2) or (S3) is independently 80°C-100°C. In some embodiments, the water extraction in the extraction operation (S2) or (S3) is reflux extraction with water. In some embodiments, the extraction temperature of the water extraction in the extraction operation (S2) or (S3) is independently 80°C, 85°C, 90°C, 95°C or 100°C.

[0072] In some embodiments, the extraction temperature of the extraction with alcohol solution A in the extraction operation (S1) or (S3) is independently 40° C.-80° C. In some embodiments, the extraction with alcohol solution A in the extraction operation (S1) or (S3) is reflux extraction with alcohol solution A. In some embodiments, the extraction temperature of the extraction with alcohol solution A in the extraction operation (S1) or (S3) is independently 40° C., 45° C., 50° C., 55° C., 60° C., 65° C., 70° C., 75° C. or 80° C.

[0073] In some embodiments, the macroporous resin in the extraction operation (S2) or (S3) is independently selected from AB-8, D101 or HP-20. In some embodiments, the macroporous resin in the extraction operation (S2) or (S3) is HP-20.

[0074] In some embodiments, when the water extract is adsorbed by a macroporous resin in the extraction operation (S2) or (S3), the weight ratio of the macroporous resin to Cordyceps sinensis is 0.1:1-10:1. In some embodiments, when the water extract is adsorbed by a macroporous resin in the extraction operation (S2) or (S3), the weight ratio of the macroporous resin to Cordyceps sinensis is 1:1. In some embodiments, when the water extract is adsorbed by a macroporous resin in the extraction operation (S2) or (S3), the weight ratio of the macroporous resin to Cordyceps sinensis is 0.1:1, 0.5:1, 1:1, 1.5:1, 2:1, 2.5:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1 or 10:1.

[0075] In some embodiments, in the extraction operation (S2) or (S3) in which the alcohol solution B is eluted, the volume ratio of the alcohol solution B to the macroporous resin is 1: 1-10: 1. In some embodiments, in the extraction operation (S2) or (S3) in which the alcohol solution B is eluted, the volume ratio of the alcohol solution B to the macroporous resin is 1: 1, 2: 1, 3: 1, 4: 1, 5: 1, 6: 1, 7: 1, 8: 1, 9: 1 or 10: 1. In some embodiments, in the extraction operation (S2) or (S3) in which the alcohol solution B is eluted, the volume ratio of the alcohol solution B to the macroporous resin is 1: 1.

[0076] In some embodiments, the alkane solvent is cyclohexane.

[0077] In some embodiments, the ester solvent is ethyl acetate.

[0078] In some embodiments, in the extraction step, the volume ratio of the alkane solvent to the suspension is 1:1 to 5:1. In some embodiments, in the extraction step, the volume ratio of the alkane solvent to the suspension is 1:1, 2:1, 3:1, 4:1 or 5:1. In some embodiments, in the extraction step, the volume ratio of the alkane solvent to the suspension is 1:1.

[0079] In some embodiments, in the extraction step, the volume ratio of the ester solvent to the suspension is 1:1 to 5:1. In some embodiments, in the extraction step, the volume ratio of the ester solvent to the suspension is 1:1, 2:1, 3:1, 4:1 or 5:1. In some embodiments, in the extraction step, the volume ratio of the ester solvent to the suspension is 1:1.

[0080] In some embodiments, in the extraction step, the number of extractions with an alkane solvent is 1-5 times. In some embodiments, in the extraction step, the number of extractions with an alkane solvent is 1, 2, 3, 4 or 5 times. In some embodiments, in the extraction step, the number of extractions with an alkane solvent is 3 times.

[0081] In some embodiments, in the extraction step, the number of extractions with the ester solvent is 1-5 times. In some embodiments, in the extraction step, the number of extractions with the ester solvent is 1 time, 2 times, 3 times, 4 times or 5 times. In some embodiments, in the extraction step, the number of extractions with the ester solvent is 3 times.

[0082] In some embodiments, the filler particle size of the chromatographic column of the first chromatographic separation is 25 μm-75 μm. In some embodiments, the filler particle size of the chromatographic column of the first chromatographic separation is 25 μm, 30 μm, 35 μm, 40 μm, 45 μm, 50 μm, 55 μm, 60 μm, 65 μm, 70 μm or 75 μm. In some embodiments, the filler particle size of the chromatographic column of the first chromatographic separation is 50 μm.

[0083] In some embodiments, the weight ratio of the filler of the chromatographic column of the first chromatographic separation to the extract is 1: 1 to 20: 1. In some embodiments, the weight ratio of the filler of the chromatographic column of the first chromatographic separation to the extract is 1: 1, 2: 1, 3: 1, 4: 1, 5: 1, 6, 7: 1, 8: 1, 9: 1, 10: 1, 11: 1, 12: 1, 13: 1, 14: 1, 15: 1, 16: 1, 17: 1, 18: 1, 19: 1 or 20: 1. In some embodiments, the weight ratio of the filler of the chromatographic column of the first chromatographic separation to the extract is 10: 1.

[0084] In certain embodiments, the elution volumes of the methanol-water mixed solvents of different volume ratios in the first chromatographic separation are each independently 3-10 times of the total volume of the filler of the chromatographic column of the first chromatographic separation. In certain embodiments, the elution volumes of the methanol-water mixed solvents of different volume ratios in the first chromatographic separation are each independently 3 times, 4 times, 5 times, 6 times, 7 times, 8 times, 9 times or 10 times of the total volume of the filler of the chromatographic column of the first chromatographic separation. In certain embodiments, the elution volumes of the methanol-water mixed solvents of different volume ratios in the first chromatographic separation are each independently 5 times of the total volume of the filler of the chromatographic column of the first chromatographic separation.

[0085] In a sixth aspect, the present invention provides another Cordyceps sinensis extract.

[0086] In some embodiments, the present invention provides another Cordyceps sinensis extract, which is named Cordyceps sinensis extract F3.8. The Cordyceps sinensis extract F3.8 contains the compound represented by formula (I) or a pharmaceutically acceptable salt thereof. The preparation method of the Cordyceps sinensis extract F3.8 comprises: taking the Cordyceps sinensis extract F3 described in the fifth aspect, subjecting it to a second chromatographic separation, concentrating or drying, to obtain Cordyceps sinensis extract F3.8.

[0087] In some embodiments, the second chromatographic separation includes: using an ODS chromatographic column as a chromatographic column for chromatographic separation; using a methanol solution containing formic acid as an elution solvent for gradient elution, and collecting the elution solvent containing the compound represented by formula (I) or a pharmaceutically acceptable salt thereof described in the first aspect for subsequent concentration or drying operations.

[0088] In some embodiments, the gradient elution is performed using an aqueous solution containing 0.05% vol-0.20% vol or 0.10% vol formic acid and 10.00% vol-15.00% vol methanol as the initial elution solvent and methanol containing 0.05% vol-0.20% vol or 0.10% vol formic acid as the termination elution solvent for continuous gradient elution.

[0089] In some embodiments, the filler particle size of the chromatographic column of the second chromatographic separation is 25 μm-75 μm. In some embodiments, the filler particle size of the chromatographic column of the second chromatographic separation is 25 μm, 30 μm, 35 μm, 40 μm, 45 μm, 50 μm, 55 μm, 60 μm, 65 μm, 70 μm or 75 μm. In some embodiments, the filler particle size of the chromatographic column of the second chromatographic separation is 50 μm.

[0090] In some embodiments, the weight ratio of the filler of the chromatographic column of the second chromatographic separation to the Cordyceps extract F3 is 1: 1 to 20: 1. In some embodiments, the weight ratio of the filler of the chromatographic column of the second chromatographic separation to the Cordyceps extract F3 is 1: 1, 2: 1, 3: 1, 4: 1, 5: 1, 6, 7: 1, 8: 1, 9: 1, 10: 1, 11: 1, 12: 1, 13: 1, 14: 1, 15: 1, 16: 1, 17: 1, 18: 1, 19: 1 or 20: 1. In some embodiments, the weight ratio of the filler of the chromatographic column of the second chromatographic separation to the Cordyceps extract F3 is 10: 1.

[0091] In some embodiments, the elution flow rate of the gradient elution is 5 mL / min-15 mL / min. In some embodiments, the elution flow rate of the gradient elution is 5 mL / min, 6 mL / min, 7 mL / min, 8 mL / min, 9 mL / min, 10 mL / min, 11 mL / min, 12 mL / min, 13 mL / min, 14 mL / min or 15 mL / min. In some embodiments, the elution flow rate of the gradient elution is 10 mL / min.

[0092] In some embodiments, the gradient elution comprises using the following elution program:

[0093]

[0094] In some embodiments, the gradient elution comprises using the following elution program:

[0095]

[0096] In some embodiments, the gradient elution comprises using the following elution program:

[0097]

[0098] In some embodiments, the gradient elution comprises using the following elution program:

[0099]

[0100] In some embodiments, the elution solvent containing the compound represented by formula (I) or a pharmaceutically acceptable salt thereof in the first aspect in the second chromatographic separation is the elution solvent after elution for 80min-150min in the second chromatographic separation. In some embodiments, the second chromatographic separation includes using an ODS chromatographic column for chromatographic separation; the filler particle size of the chromatographic column of the second chromatographic separation is 25μm-75μm; the weight ratio of the filler of the chromatographic column of the second chromatographic separation to the Cordyceps sinensis extract F3 is 1:1 to 20:1; the elution solvent of the second chromatographic separation is an aqueous solution containing 0.05%vol-0.20%vol or 0.10%vol formic acid and 10.00%vol methanol and methanol containing 0.05%vol-0.20%vol or 0.10%vol formic acid; the elution mode of the second chromatographic separation is gradient elution; the elution flow rate of the gradient elution is 5mL / min-15mL / min; the gradient elution includes the following elution procedure:

[0101]

[0102] ;

[0103] The elution solvent containing the compound represented by formula (I) or a pharmaceutically acceptable salt thereof after elution in the first aspect is collected for subsequent concentration or drying operation, or the elution solvent after elution for 80min-150min in the second chromatographic separation is collected for subsequent concentration or drying operation.

[0104] In some embodiments, the second chromatographic separation includes chromatographic separation using an ODS chromatographic column; the filler particle size of the chromatographic column of the second chromatographic separation is 50 μm; the weight ratio of the filler of the chromatographic column of the second chromatographic separation to the Cordyceps sinensis extract F3 is 10:1; the elution solvent of the second chromatographic separation is an aqueous solution containing 0.05% vol-0.20% vol or 0.10% vol formic acid and 10.00% vol methanol and methanol containing 0.05% vol-0.20% vol or 0.10% vol formic acid; the elution mode of the second chromatographic separation is gradient elution; the elution flow rate of the gradient elution is 10 mL / min; the gradient elution includes the following elution program:

[0105] ;

[0106] The elution solvent containing the compound represented by formula (I) or a pharmaceutically acceptable salt thereof according to the first aspect is collected for subsequent concentration or drying operation, or the elution solvent after 80min-150min of elution in the second chromatographic separation is collected for subsequent concentration or drying operation.

[0107] In a seventh aspect, the present invention provides another Cordyceps sinensis extract.

[0108] In some embodiments, the present invention provides another Cordyceps sinensis extract, which is named Cordyceps sinensis extract F3.8.1, and the Cordyceps sinensis extract F3.8.1 contains the compound represented by formula (I) or a pharmaceutically acceptable salt thereof. The preparation method of the Cordyceps sinensis extract F3.8.1 comprises: taking the Cordyceps sinensis extract F3.8 described in the sixth aspect, subjecting it to third chromatographic separation, taking the mobile phase containing the compound represented by formula (I) or a pharmaceutically acceptable salt thereof described in the first aspect, concentrating or drying, and obtaining the Cordyceps sinensis extract F3.8.1.

[0109] In some embodiments, the third chromatographic separation comprises using a Phenomex Gemini C 18 Chromatographic separation is performed on a chromatographic column.

[0110] In some embodiments, the inner diameter of the chromatographic column of the third chromatographic separation is 5.0 mm-20.0 mm. In some embodiments, the inner diameter of the chromatographic column of the third chromatographic separation is 5.0 mm, 10.0 mm, 15.0 mm or 20.0 mm. In some embodiments, the inner diameter of the chromatographic column of the third chromatographic separation is 10.0 mm.

[0111] In some embodiments, the length of the chromatographic column of the third chromatographic separation is 100 mm-300 mm. In some embodiments, the length of the chromatographic column of the third chromatographic separation is 100 mm, 150 mm, 200 mm, 250 mm or 300 mm. In some embodiments, the length of the chromatographic column of the third chromatographic separation is 200 mm-250 mm.

[0112] In some embodiments, the filler particle size of the chromatographic column of the third chromatographic separation is 2 μm-10 μm. In some embodiments, the filler particle size of the chromatographic column of the third chromatographic separation is 2 μm, 3 μm, 4 μm, 5 μm, 6 μm, 7 μm, 8 μm, 9 μm or 10 μm. In some embodiments, the filler particle size of the chromatographic column of the third chromatographic separation is 5 μm.

[0113] In some embodiments, the flow rate of the third chromatographic separation is 1 mL / min-5 mL / min. In some embodiments, the flow rate of the third chromatographic separation is 1 mL / min, 2 mL / min, 3 mL / min, 4 mL / min or 5 mL / min. In some embodiments, the flow rate of the third chromatographic separation is 3 mL / min.

[0114] In some embodiments, the mobile phase of the third chromatographic separation is a mixed solvent of acetonitrile, water and formic acid in a volume ratio of (15.00-25.00):(75.00-85.00):(0.05-0.20). In some embodiments, the mobile phase of the third chromatographic separation is a mixed solvent of acetonitrile, water and formic acid in a volume ratio of 20.0:80.0:0.10.

[0115] In some embodiments, the third chromatographic separation comprises using a Phenomex Gemini C 18 The method comprises the following steps of: using a chromatographic column for chromatographic separation; the inner diameter of the chromatographic column for the third chromatographic separation is 5.0 mm-20.0 mm; the length of the chromatographic column for the third chromatographic separation is 100 mm-300 mm; the filler particle size of the chromatographic column for the third chromatographic separation is 2 μm-10 μm; the flow rate of the third chromatographic separation is 1 mL / min-5 mL / min; the mobile phase for the third chromatographic separation is a mixed solvent of acetonitrile, water and formic acid in a volume ratio of (15.00-25.00):(75.00-85.00):(0.05-0.20), and collecting the mobile phase containing the compound represented by formula (I) or a pharmaceutically acceptable salt thereof according to the first aspect for subsequent concentration or drying operations.

[0116] In some embodiments, the chromatographic column for the third chromatographic separation is a Phenomex Gemini C 18 A chromatographic column, wherein the inner diameter of the chromatographic column is 10.0 mm, the length of the chromatographic column is 250 mm, the filler particle size of the chromatographic column is 5 μm, and a mixed solvent of acetonitrile-water-formic acid with a volume ratio of 20.00:80.00:0.10 is used as the mobile phase for elution at a flow rate of 3 ml / min; the mobile phase for the third chromatographic separation is a mixed solvent of acetonitrile, water and formic acid with a volume ratio of 20:80:0.1, and the mobile phase containing the compound represented by formula (I) or a pharmaceutically acceptable salt thereof according to the first aspect is collected for subsequent concentration or drying operations.

[0117] In some embodiments, the elution time of the third chromatographic separation is 30 min-60 min. In some embodiments, the elution time of the third chromatographic separation is 35 min-40 min.

[0118] In an eighth aspect, the present invention provides a use of the compound represented by formula (I) or a pharmaceutically acceptable salt thereof according to the first aspect, the pharmaceutical composition according to the second aspect, the Cordyceps sinensis extract according to the fourth aspect, the Cordyceps sinensis extract according to the fifth aspect, the Cordyceps sinensis extract according to the sixth aspect, or the Cordyceps sinensis extract according to the seventh aspect in the preparation of a pharmaceutical product.

[0119] In some embodiments, the pharmaceutical product is used to inhibit alpha-glucosidase.

[0120] In some embodiments, the pharmaceutical product is used to prevent and / or treat diabetes or its complications.

[0121] In some embodiments, the complications include at least one of diabetic nephropathy, diabetic retinopathy, uveitis, diabetic cataracts, diabetic foot, diabetic cardiovascular complications, diabetic cerebrovascular disease, and diabetic neuropathy.

[0122] Beneficial Effects

[0123] Compared with the prior art, the present invention has the following beneficial effects:

[0124] The present invention provides a new class of compounds represented by formula (I) or pharmaceutically acceptable salts thereof, which have a significant inhibitory effect on α-glucosidase activity and can be used to prevent or treat diabetes or its complications.

[0125] Terminology

[0126] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification and the features of the different embodiments or examples, without contradiction.

[0127] The term "% vol" means volume percentage.

[0128] The term "M" means molar concentration, mol / L.

[0129] In the following, whether or not the word "about" or "approximately" is used, it means within 1%, within 2%, within 5%, within 7%, within 8%, within 10%, within 15%, within 20%, etc. of a given value or range. Alternatively, for those of ordinary skill in the art, the term "about" or "approximately" means within the acceptable standard error range of the mean. Whenever a number with a value of N is disclosed, any number with a value of N+ / -1%, N+ / -2%, N+ / -3%, N+ / -5%, N+ / -7%, N+ / -8%, N+ / -10%, N+ / -15% or N+ / -20% will be explicitly disclosed, where "+ / -" means plus or minus. BRIEF DESCRIPTION OF THE DRAWINGS

[0130] Figure 1 This is a statistical graph of the α-glucosidase inhibition effect of cordyceps thiazole A and acarbose in Example 3. DETAILED DESCRIPTION

[0131] In order to enable those skilled in the art to better understand the technical solution of the present invention, some non-limiting embodiments are further disclosed below to further describe the present invention in detail.

[0132] The reagents used in the present invention can be purchased from the market or prepared by the method described in the present invention.

[0133] In the following examples, the mass spectrometer is a Synapt G2 TOF mass spectrometer produced by Waters Corporation of the United States. The superconducting nuclear magnetic resonance instrument is a Bruker AV-600. The macroporous resin is HP-20. The particle size of the ODS filler is 50 μm, which is a product of Japan YMC Company. The liquid chromatograph is a product of Shanghai Lisui Electronic Technology Co., Ltd. The chromatographic column used for liquid phase separation is a Phenomenex Gemini C18 column (10.0 mm × 250 mm, 5 μm). Acetonitrile and methanol used in liquid chromatography are chromatographically pure, water is double distilled water, and other reagents are analytically pure.

[0134] Example 1: Cordyceps sinensis sample pretreatment method

[0135] (1) 15 kg of Cordyceps sinensis was crushed, and then extracted with water and 95% vol ethanol solution for 3 times, respectively. The volume of water for each extraction was 120 L, the volume of 95% vol ethanol solution for each extraction was 120 L, the extraction time for each extraction was 2 hours, and the extraction time for each extraction was 2 hours. Filter to obtain a water extract and a 95% vol ethanol extract, respectively. The water extract was adsorbed with 15 kg of macroporous resin, and eluted with 95% vol ethanol in a volume of 5 times the total volume of the macroporous resin to obtain a 95% vol ethanol eluate. The 95% vol ethanol eluate and the 95% vol ethanol extract were combined, and the combined solution was concentrated under reduced pressure to obtain 3130.0 g of crude extract.

[0136] (2) The crude extract obtained in step (1) was suspended in 50 L of water, first extracted three times with cyclohexane, each time with a volume of 50 L of cyclohexane, and the aqueous layer was then extracted three times with ethyl acetate, each time with a volume of 50 L of ethyl acetate. The three ethyl acetate extracts were combined and concentrated under reduced pressure to obtain 36.1 g of ethyl acetate extract.

[0137] Example 2: Preparation of the compound represented by formula (I)

[0138]

[0139] The ethyl acetate extract (36.1 g) obtained in Example 1 was separated using an ODS (361 g) chromatographic column, and gradient elution was performed using methanol-water solvents with a methanol-water volume ratio of 5:95, 10:90, and 30:70, respectively; the elution volume of the methanol-water solvent in each volume ratio was 5 times the total volume of the ODS filler, and the eluates after elution with the methanol-water solvent with the same methanol-water volume ratio of 30:70 were combined and then concentrated to obtain Cordyceps sinensis extract F3.

[0140] Cordyceps sinensis extract F3 (3.7 g) was chromatographically separated using an ODS (37 g) column at an elution flow rate of 10 mL / min. The elution gradient was eluted from 0 min with a 10% vol methanol aqueous solution containing 0.1% vol formic acid, then gradient eluted to 180 min with methanol containing 0.1% vol formic acid, and then eluted with methanol containing 0.1% vol formic acid for 60 min. The eluate from 80 min to 150 min was collected and concentrated to obtain Cordyceps sinensis extract F3.8 (yield: 43.8 mg).

[0141] Cordyceps sinensis extract F3.8 (43.8 mg) was prepared by HPLC and analyzed by Phenomex Gemini C 18 The chromatographic column was used as a separation column. The specification of the chromatographic column was 10.0 mm × 250 mm, the filler particle size was 5 μm, and a mixed solution of acetonitrile-water-formic acid with a volume ratio of 20:80:0.1 was used for elution. The flow rate was 3 mL / min, and the compound represented by formula (I) (or referred to as Cordyceps sinensis extract F3.8.1, the compound represented by formula (I) is referred to as Cordyceps thiazole A) (retention time = 28.7 min, 7.3 mg, purity 99%, yellow needle-shaped crystals) was obtained. The obtained compound represented by formula (I) was subjected to ultraviolet-visible absorption spectrum, infrared spectrum, carbon spectrum, hydrogen spectrum and mass spectrum, and the results were as follows:

[0142] UV(MeOH)λ max (logε)207(8.93),355(8.37)nm;

[0143] IR(KBr)v max 3423,3120,3015,2941,2842,1704,1687,1605,1586,1517,1466,1424,1339,1206,1118,1033,980,875,757cm -1 .

[0144] HRESIMS m / z 310.0373[M+H] + (calcd.for C 13 H 12 NO 6 S, 310.0380);

[0145] 13 C NMR and 1 H NMR see Table 1.

[0146] Table 1: Compounds represented by formula (I) 13 C NMR and 1 H NMR results (600 MHz, CD 3 OD is the test solvent)

[0147]

[0148] The identification structure is:

[0149]

[0150] Example 3: Test of the inhibitory effect of the compound represented by formula (I) on α-glucosidase activity

[0151] The compound represented by formula (I) of the present invention is called cordyceps thiazole A.

[0152] 3.1 Principle of α-glucosidase inhibition activity test

[0153] α-Glucosidase catalyzes the hydrolysis of p-nitrophenyl-α-D-pyranoglucoside (p-NPG) to generate glucose and p-nitrophenol (p-NP). p-NP (yellow) has a maximum absorption at 405nm. The maximum amount of p-NP generated per unit time can reflect the activity of α-glucosidase.

[0154] 3.2 Reagent and solution preparation

[0155] 0.1 mol / L phosphate buffer (PBS): weigh 2.622 g NaH 2 PO 4 ·H 2 O, 21.714 g Na 2 HPO 4 7H 2 O, mix, add water to 1000 mL, and adjust the pH to 6.9 with 1 M HCl.

[0156] 5 mM p-NPG: Weigh 45.2 mg p-NPG and dissolve it in 30 mL PBS and store at -20°C.

[0157] 0.1M Na2 CO 3 : Take 1.06g Na 2 CO 3 , add water to 100mL.

[0158] 0.2U / mL α-glucosidase solution: 100U of α-glucosidase is dissolved in 1mL of the above PBS to prepare a mother solution with a concentration of 100U / mL, and stored at -70℃ for later use. Dilute 500 times before use to prepare a 0.2U / mL enzyme solution for later use.

[0159] Positive drug solution: weigh 32.3 mg of acarbose and add DMSO to make the concentration of acarbose 1×10 -1 M of acarbose stock solution. Take 1×10 -1 16 μL of acarbose stock solution of 10 M was added to 384 μL of PBS to obtain 400 μL of acarbose with a concentration of 4×10 -3 M acarbose solution. Take 4×10 -3 200 μL of 10 M acarbose solution was added to 200 μL of PBS containing 4% DMSO to obtain a concentration of 2 × 10 -3 M acarbose solution. Take 2×10 -3 200 μL of 10 M acarbose solution was added to 200 μL of PBS containing 4% DMSO to obtain a concentration of 1 × 10 -3 M acarbose solution. Take 1×10 -3 200 μL of 10 M acarbose solution was added to 200 μL of PBS containing 4% DMSO to obtain a concentration of 5 × 10 -4 M of acarbose solution.

[0160] Cordyceps thiazole A solution: Take 1 mg of cordyceps thiazole A (i.e., the compound represented by formula (I)) and prepare 1×10 -1 M mother solution. Take 1×10 -1 M stock solution 16 μL, add 384 μL PBS to obtain 400 μL with a concentration of 4×10 -3 M cordyceptazolidinone A solution. Take 4×10 -3 200 μL of 10 M cordyceptazolidinone A solution was added to 200 μL of PBS containing 4% DMSO to obtain a concentration of 2 × 10 -3 M cordyceps thiazole A solution. Take 2×10 -3 200 μL of 10 M cordyceptazolidinone A solution was added to 200 μL of PBS containing 4% DMSO to obtain a concentration of 1×10 -3 M Cordyceps thiazole A solution. Take 1×10 -3 200 μL of 10 M cordyceptazolidinone A solution was added to 200 μL of PBS containing 4% DMSO to obtain a concentration of 5 × 10-4 M test compound cordyceps triazole A solution.

[0161] 3.3 Experimental steps 25 μL of the test sample (positive drug solution, test compound cordyceps thiazole A solution or solvent DMSO) and 50 μL of 0.2U / mL α-glucosidase solution were incubated in a 96-well plate at 37°C for 10 min. 25 μL of 5mM p-NPG was added to each well, and after incubation for 5 min, 100 μL of 0.1M Na 2 CO 3 The reaction was terminated by adding the solution. Within 5 minutes, the OD was measured on an enzyme reader. 405nm The tested sample was the positive drug solution, which was the positive drug group; the tested sample was the test compound cordyceps thiazole A solution, which was the cordyceps thiazole A group; the positive drug group and the cordyceps thiazole A group were the tested drug groups; the tested sample was the solvent DMSO, which was the solvent control group.

[0162] 3.4 Data Processing

[0163] Enzyme activity inhibition rate (%) = (solvent control group OD 405nm Value-test drug group OD 405nm value) / solvent control group OD 405nm Value × 100%

[0164] 3.5 Experimental results: α-glucosidase inhibitory activity Figure 1 shown.

[0165] Conclusion: The experimental results show that cordyceps thiazole A can inhibit the activity of α-glucosidase in a concentration-dependent manner.

[0166] The method of the present invention has been described through preferred embodiments, and relevant personnel can obviously modify or appropriately change and combine the methods and applications described herein within the content, spirit and scope of the present invention to implement and apply the technology of the present invention. Those skilled in the art can refer to the content of this article and appropriately improve the process parameters. It is particularly important to point out that all similar replacements and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention.

Claims

1. A compound represented by formula (I) or a pharmaceutically acceptable salt thereof, 2. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 1, wherein: The pharmaceutically acceptable salt is a salt formed by the compound represented by formula (I) and an inorganic base, an inorganic acid or an organic acid; or The pharmaceutically acceptable salt is a sodium salt or a potassium salt of the compound represented by formula (I); or The pharmaceutically acceptable salt is a hydrochloride, hydrobromide, sulfate, nitrate, acetate, propionate, malonate, butyrate, lactate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, maleate, benzoate, succinate, picrate, tartrate, citrate or fumarate of the compound represented by formula (I).

3. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 2, wherein: The inorganic base is sodium hydroxide or potassium hydroxide; and / or The inorganic acid is hydrochloric acid, hydrobromic acid, sulfuric acid or nitric acid; and / or The organic acid is acetic acid, propionic acid, malonic acid, butyric acid, lactic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, maleic acid, benzoic acid, succinic acid, picric acid, tartaric acid, citric acid or fumaric acid.

4. A pharmaceutical composition, characterized in that Comprising the compound represented by formula (I) according to any one of claims 1 to 3 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient; Optionally, the pharmaceutical composition is in the form of an oral preparation or an injection; Optionally, the dosage form of the pharmaceutical composition is tablets, granules, capsules, pills, oral liquids, oral emulsions, water injections, infusions or lyophilized powder injections; Optionally, the tablet is a common tablet, sustained-release tablet, controlled-release tablet, immediate-release tablet, lozenge, sublingual tablet, buccal patch, chewable tablet, effervescent tablet, dispersible tablet or enteric-coated tablet; Optionally, the pharmaceutical composition is used to inhibit α-glucosidase activity; Optionally, the pharmaceutical composition is used for preventing and / or treating diabetes or its complications; and / or The complications include at least one of diabetic nephropathy, diabetic retinopathy, uveitis, diabetic cataracts, diabetic foot, diabetic cardiovascular complications, diabetic cerebrovascular disease, and diabetic neuropathy.

5. A pharmaceutical preparation, characterized in that Comprising the compound represented by formula (I) according to any one of claims 1 to 3 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient; Optionally, the pharmaceutical preparation is an oral preparation or an injection; Optionally, the dosage form of the pharmaceutical preparation is tablets, granules, capsules, pills, oral liquids, oral emulsions, water injections, infusions or lyophilized powder injections; Optionally, the dosage form of the pharmaceutical preparation is tablets, granules, capsules, pills, oral liquids, oral emulsions, water injections, infusions or lyophilized powder injections; Optionally, the tablet is a common tablet, sustained-release tablet, controlled-release tablet, immediate-release tablet, lozenge, sublingual tablet, buccal patch, chewable tablet, effervescent tablet, dispersible tablet or enteric-coated tablet; Optionally, the pharmaceutical preparation is used to inhibit α-glucosidase activity; Optionally, the pharmaceutical preparation is used for preventing and / or treating diabetes or its complications; and / or The complications include at least one of diabetic nephropathy, diabetic retinopathy, uveitis, diabetic cataracts, diabetic foot, diabetic cardiovascular complications, diabetic cerebrovascular disease, and diabetic neuropathy.

6. A Cordyceps sinensis extract, characterized in that: Contains a compound represented by formula (I) or a pharmaceutically acceptable salt thereof.

7. A Cordyceps sinensis extract, characterized in that: The Cordyceps sinensis extract is named Cordyceps sinensis extract F3, and the Cordyceps sinensis extract F3 contains the compound represented by formula (I) or a pharmaceutically acceptable salt thereof. The preparation method of the Cordyceps sinensis extract F3 comprises: taking Cordyceps sinensis, extracting, extracting, separating by first chromatography, concentrating or drying to obtain the Cordyceps sinensis extract F3; The extraction is selected from the following operations: (S1) the extraction comprises extracting with an alcohol solution A, separating the solid from the liquid to obtain an alcohol extract, and concentrating the extract to obtain a crude extract, wherein the alcohol in the alcohol solution A comprises at least one of methanol or ethanol; or (S2) the extraction comprises extraction with water, solid-liquid separation, obtaining a water extract, adsorbing the water extract with a macroporous resin, eluting with an alcohol solution B, obtaining an alcohol eluate, and concentrating to obtain a crude extract, wherein the alcohol in the alcohol solution B comprises at least one of methanol or ethanol; or (S3) the extraction includes extraction with water, solid-liquid separation, obtaining a water extract and a solid residue, the solid residue is then extracted with an alcohol solution A, solid-liquid separation, and an alcohol extract is obtained; the water extract is adsorbed with a macroporous resin and eluted with an alcohol solution B to obtain an alcohol eluent; the alcohol eluent and the alcohol extract are combined and concentrated to obtain a crude extract, the alcohol in the alcohol solution A includes at least one of methanol or ethanol, and the alcohol in the alcohol solution B includes at least one of methanol or ethanol; The extraction comprises: mixing the crude extract with water to obtain a suspension, first extracting the suspension with an alkane solvent to obtain a water layer, then extracting the water layer with an ester solvent to obtain an ester solvent extract, and concentrating the ester solvent extract to obtain an extract; The first chromatographic separation is selected from the following operations: (i) the first chromatographic separation comprises: subjecting the extract to a first chromatographic separation using an ODS chromatographic column, using methanol-water mixed solvents in different proportions as eluents to sequentially perform gradient elution, collecting the eluates eluted with the methanol-water mixed solvents in different proportions, confirming that the eluate contains the compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof, and taking the eluate containing the compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof for subsequent concentration or drying operations; or (ii) the first chromatographic separation comprises: performing a first chromatographic separation on the extract using an ODS chromatographic column, sequentially using methanol-water mixed solvents in different ratios of 3:97-7:93, 8:92-12:88 and 28:72-32:68 as eluents for gradient elution; collecting the methanol-water mixed solvent in a volume ratio of 28:72-32:68 after elution for subsequent concentration or drying operations; or (iii) the first chromatographic separation comprises: performing a first chromatographic separation on the extract using an ODS chromatographic column, sequentially using a methanol-water mixed solvent having a volume ratio of methanol to water of 5:95, 10:90 and 30:70 as an eluent for gradient elution; collecting the methanol-water mixed solvent having a volume ratio of methanol to water of 30:70 after the elution for subsequent concentration or drying; or (iv) the first chromatographic separation comprises using an ODS chromatographic column as a chromatographic column for the first chromatographic separation; the filler particle size of the chromatographic column of the first chromatographic separation is 25 μm-75 μm; the weight ratio of the filler to the extract of the chromatographic column of the first chromatographic separation is 1:1-20:1; the first chromatographic separation sequentially uses a methanol-water mixed solvent with a volume ratio of methanol to water of 3:97-7:93, 8:92-12:88, and 28:72-32:68 for elution; the elution volume of the methanol-water mixed solvent with different volume ratios in the first chromatographic separation is independently 3-10 times the column volume of the chromatographic column of the first chromatographic separation; the methanol-water mixed solvent with a volume ratio of methanol to water of 28:72-32:68 after elution is collected for subsequent concentration or drying operations; or (v) The first chromatographic separation includes using an ODS chromatographic column as a chromatographic column for chromatographic separation; the filler particle size of the chromatographic column of the first chromatographic separation is 50 μm; the weight ratio of the filler to the extract of the chromatographic column of the first chromatographic separation is 10:1; the first chromatographic separation uses a methanol-water mixed solvent with a volume ratio of methanol to water of 5:95, 10:90, and 30:70 for elution; the elution volume of the methanol-water mixed solvent with different volume ratios in the first chromatographic separation is 5 times the column volume of the chromatographic column of the first chromatographic separation; the methanol-water mixed solvent with a volume ratio of methanol to water of 30:70 after elution is collected for subsequent concentration or drying operations.

8. The Cordyceps sinensis extract according to claim 7, The alcohol solution A in the extraction operation (S1) or (S3) is a mixed solution or a pure alcohol solution having a volume ratio of alcohol to water of greater than or equal to 90:10 and less than 100:0; or the alcohol solution A in the extraction operation (S1) or (S3) is a 95% vol alcohol aqueous solution; and / or The alcohol solution B in the extraction operation (S2) or (S3) is a mixed solution or a pure alcohol solution having a volume ratio of alcohol to water of greater than or equal to 90:10 and less than 100:0; or the alcohol solution B in the extraction operation (S2) or (S3) is a 95% vol alcohol aqueous solution; and / or The alcohol in the alcohol solution A in the extraction operation (S1) or (S3) or the alcohol in the alcohol solution B in the extraction operation (S2) or (S3) is independently selected from at least one of methanol and ethanol; and / or The alcohol solution A in the extraction operation (S1) or (S3) is the same as the alcohol solution B in the extraction operation (S2) or (S3); and / or The alcohol solution A in the extraction operation (S1) or (S3) is the same as the alcohol solution B in the extraction operation (S2) or (S3), which is a 95% vol ethanol aqueous solution; and / or The cordyceps is crushed before extraction; and / or In the extraction step (S2) or (S3), 1 mL to 100 mL of water is used for every 1 g of Cordyceps sinensis; and / or In the extraction operation (S2) or the water extraction step in (S3), 8 mL of water is used for every 1 g of Cordyceps sinensis; and / or In the extraction step (S1) or (S3), 1 mL to 100 mL of alcohol solution A is used for extraction of 1 g of Cordyceps sinensis; and / or In the extraction step (S1) or (S3) described in the step of extracting with alcohol solution A, 8 mL of alcohol solution A is used for every 1 g of Cordyceps sinensis; and / or The number of extractions with water in the extraction operation (S2) or (S3) is independently 1-5 times, 2-4 times or 3 times; and / or The number of extractions performed with the alcohol solution A in the extraction operation (S1) or (S3) is independently 1-5 times, 2-4 times or 3 times; and / or The extraction time of each extraction with water in the extraction operation (S2) or (S3) is independently 1 hour to 5 hours, 2 hours to 4 hours, 2.5 hours to 3.5 hours or 3 hours; and / or The extraction time of each extraction with the alcohol solution A in the extraction operation (S1) or (S3) is independently 1 hour to 5 hours, 2 hours to 4 hours, 2.5 hours to 3.5 hours or 3 hours; and / or The extraction temperature of the water extraction in the extraction operation (S2) or (S3) is independently 80°C-100°C; or the water extraction in the extraction operation (S2) and (S3) is water reflux extraction; and / or The extraction temperature of the alcohol solution A in the extraction operation (S1) or (S3) is independently 40°C-80°C; the extraction with the alcohol solution A in the extraction operation (S1) or (S3) is reflux extraction with the alcohol solution A; and / or The macroporous resins in the extraction operation (S2) or (S3) are independently selected from AB-8, D101 or HP-20; and / or When the water extract is adsorbed by a macroporous resin in the extraction operation (S2) or (S3), the weight ratio of the macroporous resin to Cordyceps sinensis is 0.1:1-10:1 or 1:1; and / or In the extraction operation (S2) or (S3) of eluting with alcohol solution B, the volume ratio of the alcohol solution B to the macroporous resin is 1:1-10:1 or 1:1; and / or The alkane solvent is cyclohexane; and / or The ester solvent is ethyl acetate; and / or In the extraction step, the volume ratio of the alkane solvent to the suspension is 1:1 to 5:1 or 1:1; and / or In the extraction step, the volume ratio of the ester solvent to the suspension is 1:1 to 5:1 or 1:1; and / or In the extraction step, the number of extractions with the alkane solvent is 1-5 times or 3 times; and / or In the extraction step, the number of extractions with the ester solvent is 1-5 times or 3 times; and / or The filler particle size of the chromatographic column for the first chromatographic separation is 25 μm-75 μm or 50 μm; and / or The weight ratio of the filler to the extract in the chromatographic column of the first chromatographic separation is 1:1 to 20:1 or 10:1; and / or The elution volumes of the methanol-water mixed solvents in different volume ratios in the first chromatographic separation are each independently 3-10 times or 5 times the total volume of the filler material of the chromatographic column of the first chromatographic separation.

9. A Cordyceps sinensis extract, characterized in that: The Cordyceps sinensis extract is named Cordyceps sinensis extract F3.8, and the Cordyceps sinensis extract F3.8 contains the compound represented by formula (I) or a pharmaceutically acceptable salt thereof. The preparation method of the Cordyceps sinensis extract F3.8 comprises: taking the Cordyceps sinensis extract F3 according to any one of claims 7 to 8, subjecting the extract to second chromatographic separation, concentrating or drying, to obtain the Cordyceps sinensis extract F3.8; The second chromatographic separation comprises: using an ODS chromatographic column as a chromatographic column for chromatographic separation; using a methanol solution containing formic acid as an elution solvent for gradient elution, collecting the elution solvent containing the compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof for subsequent concentration or drying operations; Optionally, the gradient elution is performed by using an aqueous solution containing 0.05% vol-0.20% vol or 0.10% vol formic acid and 10.00% vol-15.00% vol methanol as the initial elution solvent and using methanol containing 0.05% vol-0.20% vol or 0.10% vol formic acid as the final elution solvent for continuous gradient elution; Optionally, the filler particle size of the chromatographic column of the second chromatographic separation is 25 μm-75 μm or 50 μm; Optionally, the weight ratio of the filler of the chromatographic column of the second chromatographic separation to the Cordyceps sinensis extract F3 is 1:1 to 20:1 or 10:1; Optionally, the elution flow rate of the gradient elution is 5 mL / min-15 mL / min or 10 mL / min; and / or The gradient elution includes the following elution procedure: ； or The gradient elution includes the following elution procedure: ； or The gradient elution includes the following elution procedure: ； or The gradient elution includes the following elution procedure: Optionally, the elution solvent containing the compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof in the second chromatographic separation is the elution solvent after elution for 80 min to 150 min in the second chromatographic separation; Optionally, the second chromatographic separation includes chromatographic separation using an ODS chromatographic column; the filler particle size of the chromatographic column of the second chromatographic separation is 25 μm-75 μm; the weight ratio of the filler of the chromatographic column of the second chromatographic separation to the Cordyceps sinensis extract F3 is 1:1 to 20:1; the elution solvent of the second chromatographic separation is an aqueous solution containing 0.05% vol-0.20% vol or 0.10% vol formic acid and 10.00% vol methanol and methanol containing 0.05% vol-0.20% vol or 0.10% vol formic acid; the elution mode of the second chromatographic separation is gradient elution; the elution flow rate of the gradient elution is 5 mL / min-15 mL / min; the gradient elution includes the following elution program: ； Collecting the elution solvent containing the compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 1 for subsequent concentration or drying operation, or collecting the elution solvent after 80 min to 150 min of elution in the second chromatographic separation for subsequent concentration or drying operation; Optionally, the second chromatographic separation includes chromatographic separation using an ODS chromatographic column; the filler particle size of the chromatographic column of the second chromatographic separation is 50 μm; the weight ratio of the filler of the chromatographic column of the second chromatographic separation to the Cordyceps sinensis extract F3 is 10:1; the elution solvent of the second chromatographic separation is an aqueous solution containing 0.05% vol-0.20% vol or 0.10% vol formic acid and 10.00% vol methanol and methanol containing 0.05% vol-0.20% vol or 0.10% vol formic acid; the elution mode of the second chromatographic separation is gradient elution; the elution flow rate of the gradient elution is 10 mL / min; the gradient elution includes the following elution program: ； The elution solvent containing the compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 1 is collected for subsequent concentration or drying operations, or the elution solvent after 80 min-150 min of elution in the second chromatographic separation is collected for subsequent concentration or drying operations.

10. A Cordyceps sinensis extract, characterized in that: The Cordyceps sinensis extract is named Cordyceps sinensis extract F3.8.1, and the Cordyceps sinensis extract F3.8.1 contains the compound represented by formula (I) or a pharmaceutically acceptable salt thereof. The preparation method of 8.1 comprises: taking the Cordyceps sinensis extract F3.8 as claimed in claim 9, subjecting it to a third chromatographic separation, taking a mobile phase containing the compound represented by formula (I) as claimed in claim 1 or a pharmaceutically acceptable salt thereof, concentrating or drying, and obtaining the Cordyceps sinensis extract F3.8.1; Optionally, the third chromatographic separation comprises using a Phenomex Gemini C 18 chromatographic columns for chromatographic separation; and / or The inner diameter of the chromatographic column for the third chromatographic separation is 5.0 mm-20.0 mm or 10.0 mm; and / or The length of the chromatographic column for the third chromatographic separation is 100 mm-300 mm or 200 mm-250 mm; and / or The filler particle size of the chromatographic column for the third chromatographic separation is 2 μm-10 μm or 5 μm; and / or The flow rate of the third chromatographic separation is 1 mL / min-5 mL / min or 3 mL / min; and / or The mobile phase for the third chromatographic separation is a mixed solvent of acetonitrile, water and formic acid in a volume ratio of (15.00-25.00):(75.00-85.00):(0.05-0.20) or a mixed solvent of acetonitrile, water and formic acid in a volume ratio of 20.0:80.0:0.10; Optionally, the third chromatographic separation comprises using a Phenomex Gemini C 18 The method comprises the following steps of: performing chromatographic separation on a chromatographic column; the inner diameter of the chromatographic column for the third chromatographic separation is 5.0 mm-20.0 mm; the length of the chromatographic column for the third chromatographic separation is 100 mm-300 mm; the particle size of the filler of the chromatographic column for the third chromatographic separation is 2 μm-10 μm; the flow rate of the third chromatographic separation is 1 mL / min-5 mL / min; the mobile phase for the third chromatographic separation is a mixed solvent of acetonitrile, water and formic acid in a volume ratio of (15.00-25.00):(75.00-85.00):(0.05-0.20), and collecting the mobile phase containing the compound represented by formula (I) or a pharmaceutically acceptable salt thereof according to claim 1 for subsequent concentration or drying operation; Optionally, the chromatographic column for the third chromatographic separation is Phenomex Gemini C 18 A chromatographic column, wherein the inner diameter of the chromatographic column is 10.0 mm, the length of the chromatographic column is 250 mm, the filler particle size of the chromatographic column is 5 μm, and a mixed solvent of acetonitrile-water-formic acid with a volume ratio of 20.00:80.00:0.10 is used as the mobile phase for elution at a flow rate of 3 ml / min; the mobile phase for the third chromatographic separation is a mixed solvent of acetonitrile, water and formic acid with a volume ratio of 20:80:0.1, and the mobile phase containing the compound represented by formula (I) or a pharmaceutically acceptable salt thereof according to claim 1 is collected for subsequent concentration or drying operations; Optionally, the elution time of the third chromatographic separation is 30 min-60 min.

11. Use of the compound of formula (I) or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, the pharmaceutical composition according to claim 4, the pharmaceutical preparation according to claim 5, the Cordyceps sinensis extract according to claim 6, the Cordyceps sinensis extract according to any one of claims 7 to 8, the Cordyceps sinensis extract according to claim 9 or the Cordyceps sinensis extract according to claim 10 in the preparation of a pharmaceutical product, Optionally, the drug product is used to inhibit α-glucosidase activity; Optionally, the pharmaceutical product is for use in preventing and / or treating diabetes or its complications; and / or The complications include at least one of diabetic nephropathy, diabetic retinopathy, uveitis, diabetic cataracts, diabetic foot, diabetic cardiovascular complications, diabetic cerebrovascular disease, and diabetic neuropathy.

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