Composition for treating increased blood sugar caused by SARS-CoV-2 infection, preparation method, application and medicine

Abstract

The present invention provides a composition for treating hyperglycemia caused by SARS-CoV-2 infection, a preparation method, an application and a medicine, and relates to the field of pharmaceutical compositions. The composition comprises, by weight, 10-40 parts of rhein, 15-60 parts of magnolol, 2.5-10 parts of quercetin, 10-40 parts of licorice chalcone and 10-20 parts of formononetin. The composition of the present invention has the effect of treating hyperglycemia caused by SARS-CoV-2 infection. OGTT and ITT experimental results show that the composition can significantly improve fasting blood sugar and glucose tolerance in mice, effectively reduce the adverse effects of SARS-CoV-2 infection on the endocrine system, and improve the quality of life of patients.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical compositions, and in particular to a composition for treating increased blood sugar caused by SARS-CoV-2 infection, as well as a preparation method, application and medicine. Background Art

[0002] After the acute infection period of SARS-CoV-2 virus infection, patients will experience long-term persistent symptoms involving multiple systems throughout the body. Studies have found that SARS-CoV-2 infection and inflammation are important triggers of diabetes, which can induce type 1 diabetes (T1DM) or aggravate clinical type 2 diabetes (T2DM), and diabetic patients are more likely to experience long-term persistent symptoms of multiple systems throughout the body caused by SARS-CoV-2 infection.

[0003] At present, Chinese medicine formulas have been widely used as the prevention and treatment of COVID-19. Among them, Huashi Baidu Fang is a formula clinically approved for the treatment of COVID-19, which has antiviral and anti-inflammatory effects. Huashi Baidu Fang contains 14 Chinese medicines, including raw ephedra, Patchouli, gypsum, apricot kernel, French pinellia, Magnolia officinalis, Atractylodes macrocephala, Amomum villosum, Poria, Astragalus, Red Peony Root, Lemongrass Seed, Rhubarb and Licorice. Its main effects are detoxification and dampness removal, clearing away heat and relieving asthma. This formula can play a multi-link comprehensive treatment role and is suitable for the treatment of mild, ordinary and severe patients.

[0004] Chinese patent CN113274470A specifically discloses the formula, preparation method and application of Huashibaidu Fang, wherein the formula is specifically composed of the following components by weight: 5-9 parts of raw ephedra, 6-10 parts of almonds, 12-20 parts of gypsum, 3-8 parts of licorice, 6-12 parts of patchouli, 8-15 parts of magnolia bark, 10-18 parts of atractylodes, 5-12 parts of tsaoko, 8-12 parts of pinellia tuber, 10-20 parts of tuckahoe, 7-12 parts of rhubarb, 8-15 parts of astragalus, 8-16 parts of scutellariae, and 7-14 parts of red peony root. Chinese patent CN112043804A discloses Huashibaidu granules, and specifically optimizes the processing methods of raw materials such as almonds and tsaoko. Chinese patent CN111729055A optimizes the preparation method of the decoction for dehumidification and decoction, which specifically includes: (1) stir-frying bitter almonds, atractylodes and / or tsaoko kernels; (2) taking raw gypsum and decocting with water; (3) adding ephedra, stir-fried bitter almonds, liquorice, Magnolia officinalis, stir-fried atractylodes with bran, stir-fried tsaoko kernels, Pinellia ternata, Poria, Astragalus, Lepidium and Paeonia lactiflora, and decocting with water; (4) adding patchouli and rhubarb, decocting with water, filtering, and obtaining a first decoction and a medicinal residue; (5) decocting the medicinal residue with water again, filtering, and obtaining a second decoction; (6) concentrating the first decoction and the second decoction to obtain a clear paste; (7) processing the clear paste to obtain a dehumidification and decoction Chinese medicine composition; (8) determining the effective ingredients of the dehumidification and decoction Chinese medicine composition. However, the dehumidification and decoction of the dehumidification and decoction in the above inventions are all prepared by directly decocting and mixing Chinese medicines, and the accuracy of the medication is not high, and there is still room for improvement in safety.

[0005] To address this issue, it is necessary to further study the active ingredients in the Hua Shi Baidu prescription and screen out safer and more effective ingredients for treating increased blood sugar caused by SARS-CoV-2 infection. Summary of the invention

[0006] In view of the problems existing in the prior art, the present invention provides a composition for treating increased blood sugar caused by SARS-CoV-2 infection, and a preparation method, application and medicine thereof. The composition has the effect of treating increased blood sugar caused by SARS-CoV-2 infection.

[0007] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0008] The invention provides a composition, which comprises, by weight, 10-40 parts of rhein, 15-60 parts of magnolol, 2.5-10 parts of quercetin, 10-40 parts of licorice chalcone and 10-20 parts of formononetin.

[0009] Furthermore, the composition comprises, by weight, 10-20 parts of rhein, 15-30 parts of magnolol, 2.5-5 parts of quercetin, 10-20 parts of licorice chalcone and 10-20 parts of formononetin.

[0010] Preferably, the composition comprises, by weight, 20 parts of rhein, 30 parts of magnolol, 5 parts of quercetin, 20 parts of licorice chalcone and 20 parts of formononetin.

[0011] In some specific embodiments, the composition comprises, by weight, 10-40 mg / kg of rhein, 15-60 mg / kg of magnolol, 2.5-10 mg / kg of quercetin, 10-40 mg / kg of licorice chalcone and 10-20 mg / kg of formononetin.

[0012] In some specific embodiments, the composition comprises, by weight, 10-20 mg / kg rhein, 15-30 mg / kg magnolol, 2.5-5 mg / kg quercetin, 10-20 mg / kg licorice chalcone, 10-20 mg / kg formononetin, and the remainder carrier and / or excipient.

[0013] In some specific embodiments, the composition comprises, by weight, 20 mg / kg rhein, 30 mg / kg magnolol, 5 mg / kg quercetin, 20 mg / kg licorice chalcone and 20 mg / kg formononetin.

[0014] In some specific embodiments, the composition comprises, by weight, 20 mg / kg rhein, 30 mg / kg magnolol, 5 mg / kg quercetin, 20 mg / kg licorice chalcone, 20 mg / kg formononetin, and the remainder of carriers and / or excipients.

[0015] Furthermore, the weight ratio of magnolol, licorice chalcone and formononetin is (15-60): (10-40): (10-20).

[0016] Preferably, the weight ratio of magnolol, licorice chalcone and formononetin is 3:2:2.

[0017] Furthermore, the present invention also provides a method for preparing the above-mentioned composition, comprising the following steps: mixing rhein, magnolol, quercetin, licorice chalcone and formononetin to obtain the composition.

[0018] Furthermore, the use of the above-mentioned composition of the present invention or the composition prepared by the above-mentioned preparation method in the preparation of a drug for treating increased blood sugar caused by SARS-CoV-2 infection.

[0019] Furthermore, the present invention also provides a medicine, comprising the above-mentioned composition or the composition prepared by the above-mentioned preparation method.

[0020] Furthermore, the drug also includes at least one of a carrier and an excipient.

[0021] Preferably, the carrier is physiological saline; in some specific embodiments, the carrier is 20% SBE-β-CD physiological saline.

[0022] Furthermore, the preparation method of the drug comprises the following steps: mixing rhein, magnolol, quercetin, licorice chalcone and formononetin, and adding at least one of a pharmaceutically acceptable carrier and excipient to obtain the composition.

[0023] Furthermore, the dosage form of the drug is selected from granules, tablets, capsules, oral solutions or injections.

[0024] Furthermore, the emodin, magnolol, quercetin, licorice chalcone or formononetin can be prepared by extracting from traditional Chinese medicine using conventional extraction methods in the art, or can be directly purchased from commercial products.

[0025] The technical effects achieved by the present invention are:

[0026] Based on the Huashi Baidu prescription, the present invention studies the active ingredients of related traditional Chinese medicines and obtains a more accurate and safe active ingredient composition. The composition of the present invention and the medicine prepared therefrom have the effect of treating SARS-CoV-2 infection-induced hyperglycemia. The results of OGTT and ITT experiments show that the glucose tolerance and insulin tolerance of mice can be significantly improved, and the adverse effects of SARS-CoV-2 infection on the endocrine system can be effectively reduced, thereby improving the quality of life of patients. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 This is a significant difference analysis of the effects of the compositions in Comparative Examples 1 to Comparative Examples 4 and Example 1 on blood glucose in mice (*p<0.05);

[0028] Figure 2 This is the significant difference analysis of the effects of the compositions in Examples 1 to 3 on blood glucose in mice (*p<0.05);

[0029] Figure 3 Blood glucose status of mice in the blank group, model group, and Example 1 to Example 3 groups;

[0030] Figure 4 is the blood glucose status of mice in the blank group and the model group; a is the fasting blood glucose at 60 dpi in the blank group and the model group, b is the OGTT curve of the blank group and the model group, and c is the area under the blood glucose curve AUC of the blank group and the model group;

[0031] Figure 5The results of pancreatic tissue pathology HE staining of the blank group and the model group show that the pancreatic cell damage of the mice in the model group is more serious;

[0032] Figure 6 Fasting blood glucose at 60 dpi of Example 1 group (i.e., TCM group) and model group;

[0033] Figure 7 are the OGTT curves and AUCs of the Example 1 group (i.e., the TCM group) and the model group, wherein a is the OGTT curves of the Example 1 group (i.e., the TCM group) and the model group, and b is the area under the OGTT curve AUC of the Example 1 group (i.e., the TCM group) and the model group;

[0034] Figure 8 are the ITT curves and AUCs of the Example 1 group (i.e., the TCM group) and the model group, wherein a is the ITT curves of the Example 1 group (i.e., the TCM group) and the model group, and b is the area under the ITT curve AUC of the Example 1 group (i.e., the TCM group) and the model group;

[0035] Fig. 9 The results of HE staining of pancreatic tissue pathology of the model group and Example 1 group (ie, TCM group) were observed under a transmission electron microscope, showing that the pancreatic islets of mice in the model group had hemorrhage, vacuoles, and necrosis. DETAILED DESCRIPTION

[0036] The following describes the embodiments of the present invention through specific examples, and those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and the details in this specification can also be modified or changed in various ways based on different viewpoints and applications without departing from the spirit of the present invention.

[0037] Before further describing the specific embodiments of the present invention, it should be understood that the scope of protection of the present invention is not limited to the specific embodiments described below; it should also be understood that the terms used in the examples of the present invention are for describing specific embodiments rather than for limiting the scope of protection of the present invention.

[0038] When the embodiment gives a numerical range, it should be understood that, unless otherwise specified in the present invention, the two endpoints of each numerical range and any numerical value between the two endpoints can be selected. Unless otherwise defined, all technical and scientific terms used herein have the same meanings as those of ordinary skill in the art to which the present invention belongs.

[0039] It is worth noting that the emodin, magnolol, quercetin, licorice chalcone or formononetin used in the present invention are purchased from Baoji Yirui Biotechnology Co., Ltd. magnolol CAS: 528-43-8; formononetin CAS: 485-72-3; emodin CAS: 518-82-1; licorice chalcone CAS: 34221-41-5; quercetin CAS: 117-39-5, and the remaining raw materials are all common commercial products, so their sources are not specifically limited.

[0040] Example 1

[0041] A composition, the raw materials are: 20 mg / kg rhein, 30 mg / kg magnolol, 5 mg / kg quercetin, 20 mg / kg licorice chalcone and 20 mg / kg formononetin. The above active ingredients are weighed in sequence, fully mixed, and 20% SBE-β-CD physiological saline is added to prepare a solvent.

[0042] Example 2

[0043] A composition, wherein the raw materials are: 10 mg / kg rhein, 15 mg / kg magnolol, 2.5 mg / kg quercetin, 10 mg / kg licorice chalcone and 10 mg / kg formononetin. The above active ingredients are weighed in sequence, mixed thoroughly, and 20% SBE-β-CD saline is added to prepare a solvent.

[0044] Example 3

[0045] A composition, the raw materials are: 40 mg / kg rhein, 60 mg / kg magnolol, 10 mg / kg quercetin, 40 mg / kg licorice chalcone and 40 mg / kg formononetin. The above active ingredients are weighed in sequence, fully mixed, and 20% SBE-β-CD saline is added to prepare a solvent.

[0046] Comparative Example 1

[0047] A composition, which is different from Example 1 only in that the licorice chalcone and formononetin are replaced by an equal amount of magnolol.

[0048] That is, the raw materials are: 20 mg / kg rhein, 70 mg / kg magnolol and 5 mg / kg quercetin. The above active ingredients are weighed in sequence, mixed thoroughly, and 20% SBE-β-CD saline is added to prepare a solvent.

[0049] Comparative Example 2

[0050] A composition, which is different from Example 1 only in that the licorice chalcone and magnolol are replaced by an equal amount of formononetin.

[0051] That is, the raw materials are: 20 mg / kg rhein, 5 mg / kg quercetin and 70 mg / kg formononetin. The above active ingredients are weighed in sequence, mixed thoroughly, and 20% SBE-β-CD saline is added to prepare a solvent.

[0052] Comparative Example 3

[0053] A composition, which is different from Example 1 only in that honokiol and formononetin are replaced by an equal amount of licorice chalcone.

[0054] That is, the raw materials are specifically: 20 mg / kg of rhein, 5 mg / kg of quercetin and 70 mg / kg of licorice chalcone. The above active ingredients are weighed in sequence, fully mixed, and 20% SBE-β-CD saline is added to prepare a solvent.

[0055] Comparative Example 4

[0056] A composition, which is different from Example 1 only in that the raw material ratio is different.

[0057] That is, the raw materials are: 10 mg / kg rhein, 50 mg / kg magnolol, 2 mg / kg quercetin, 40 mg / kg licorice chalcone and 10 mg / kg formononetin. The above active ingredients are weighed in sequence, mixed thoroughly, and 20% SBE-β-CD saline is added to prepare a solvent.

[0058] All infectious operations on mice were performed in a biosafety level 3 laboratory, and all experimental procedures were approved by the Animal Care and Use Committee of the Institute of Medical Laboratory Animals, Chinese Academy of Medical Sciences and the Center for Comparative Medicine, Peking Union Medical College Hospital (QC23007).

[0059] Experiment 1:

[0060] 1.1 Experimental Materials

[0061] Experimental samples: the compositions in Comparative Examples 1 to 4.

[0062] 1.2 Animal experiments

[0063] 6-8 weeks old SPF ob / ob mice were provided by the Institute of Medical Laboratory Animal Science, Chinese Academy of Medical Sciences. After the mice were adaptively raised, they were randomly divided into a blank group, comparative example 1-comparison example 4 groups, a total of 5 groups, each with 4 mice (Note: one mouse in comparative example 1 group died during the experiment, so relevant data could not be counted). Each group was given normal feeding and uninterrupted drinking water during the period; the blank group was given a buffer solvent, and the Example 1-Example 3 groups were continuously gavaged with the composition of each example for three weeks, and the dosage was 0.4 mL / mouse / day. The infected mice were observed every day, and the body weight, blood sugar, and response to external stimuli were recorded. The fasting blood sugar of the mice was analyzed at the beginning of the experiment (recorded as the first week), one week later (recorded as the second week), two weeks later (recorded as the third week), and three weeks later (recorded as the fourth week).

[0064] 1.3 Detection

[0065] Fasting blood glucose test: Each group of mice were fasted but not watered, and blood was collected from the tip of the tail to test fasting blood glucose (FBG): a blood glucose test strip was placed in the detection area of ​​the blood glucose tester, and a drop of blood was squeezed out from the tail of the mouse and placed in the blood glucose test area. The first drop of blood was poured out, and then the second drop of blood was tested with a blood glucose meter, and the blood glucose concentration value displayed by the blood glucose tester was recorded.

[0066] 1.4 Results

[0067] Table 1. Blood glucose status of mice in the blank group, Example 1 and Comparative Examples 1-4

[0068]

[0069] When actually analyzing the results, Example 1 in Experiment 2 was compared with Comparative Examples 1 to Comparative Examples 4 in Experiment 1. The significant difference analysis of the effects of the compositions of Comparative Examples 1 to Comparative Examples 4 and Example 1 on the blood glucose of mice is shown in detail. Figure 1 The experimental results show that in the fourth week, Example 1 has the best blood sugar lowering effect, and the compositions in Comparative Examples 1 to 4 have no obvious blood sugar lowering effect. Therefore, the compositions corresponding to Comparative Examples 1 to 4 will not be further experimentally explored.

[0070] Experiment 2:

[0071] 2.1 Experimental Materials

[0072] Virus: SARS-CoV-2 / human / CHN / Delta-2 / 2021 (Genbank: OM061695) was provided by the Institute of Laboratory Animals, Chinese Academy of Medical Sciences.

[0073] Experimental samples: compositions of Examples 1 to 4.

[0074] 2.2 Animal experiments

[0075] 6-8 week old SPF ob / ob mice were provided by the Institute of Medical Laboratory Animal Science, Chinese Academy of Medical Sciences. After the mice were adaptively raised, they were randomly divided into a blank group (i.e., the blank group in Experiment 1), a control group, and Example 1-Example 3 groups, a total of 5 groups, with 4 mice in each group. Each group was fed normally and had uninterrupted drinking water; the blank group was given a buffer solvent, and the Example 1-Example 3 groups were continuously gavaged with the composition of each example for three weeks, with a dosage of 0.4 mL / mouse / day. The mice in the model group and the treatment group were anesthetized and nasally instilled with 1×10 SARS-CoV-2 virus 5 TCID50 / mL, observe the infected mice every day, record the body weight, blood sugar, and response to external stimuli. Observe the infected mice every day, record the body weight, blood sugar, and response to external stimuli, and analyze the fasting blood sugar of mice at the beginning of the experiment (recorded as the first week), one week after infection (recorded as the second week), two weeks after infection (recorded as the third week), and three weeks after infection (recorded as the fourth week).

[0076] 2.3 Detection

[0077] Fasting blood glucose test: On the 60th day, mice in each group were fasted but not watered, and blood was collected from the tail tip to test fasting blood glucose (FBG): a blood glucose test strip was placed in the detection area of ​​the blood glucose tester, and a drop of blood was squeezed out from the mouse's tail and placed in the blood glucose test area. The first drop of blood was poured out, and then the second drop of blood was tested with a blood glucose meter, and the blood glucose concentration value displayed by the blood glucose tester was recorded.

[0078] 2.4 Results

[0079] Table 2. Blood glucose status of mice in the blank group, model group, and each group of Examples 1 to 4

[0080]

[0081] The significant difference analysis of the composition in Examples 1 to 3 on the blood glucose of mice infected with SARS-CoV-2 virus is detailed in Figure 2 The effects of the blank group, model group, and Example 1 to Example 3 groups on blood glucose in mice infected with SARS-CoV-2 virus are detailed in Figure 3, combined with the experimental results, it can be seen that in Example 2, when the initial (unchallenged) blood sugar is the highest, the blood sugar does not increase after one week of the attack, and continues to decrease subsequently, while in Example 1 and Example 3, the blood sugar still increases after one week of the attack. And in the third week of the attack, it can be seen that the three examples have a significant hypoglycemic effect compared with the model group, among which Example 1 has the best effect. In addition, although there is no significant difference in the p value calculation between the blank group and the model group, this experiment is in the scope of the pre-experiment, and it can be seen that the blood sugar of the model group tends to increase compared with the blank group, which has reference value.

[0082] Experiment 3:

[0083] 3.1 Experimental Materials

[0084] Virus: SARS-CoV-2 / human / CHN / Delta-2 / 2021 (Genbank: OM061695) was provided by the Institute of Laboratory Animals, Chinese Academy of Medical Sciences.

[0085] Experimental sample: the composition in Example 1.

[0086] 3.2 Animal experiments

[0087] 6-8 week old SPF ob / ob mice were provided by the Institute of Medical Laboratory Animal Science, Chinese Academy of Medical Sciences. After the mice were adaptively raised, they were divided into two groups of experiments. The first group of experiments was divided into two groups, with n=13 mice in the model group and n=8 mice in the blank group; the second group of experiments was divided into n=16 mice in the model group and n=18 mice in the treatment group. The treatment group was the combination group (i.e., the solvent prepared in Example 1 of the invention, named TCM group). Each group was fed normally and had uninterrupted drinking water during the period; the blank group was given a buffer solvent, and the combination group was given continuous oral administration for 60 days, with a dosage of 0.4 mL / mouse / day. The mice in the model group and the treatment group were anesthetized and nasally instilled with 1×10 SARS-CoV-2 virus. 5 TCID50 / mL, observe the infected mice every day, record the body weight, blood sugar, and response to external stimuli. 60 days after infection, fasting blood sugar, ITT, OGTT analysis, HE staining and transmission electron microscopy were performed on the mice to observe the pathological and ultrastructural changes of pancreatic tissue.

[0088] 3.3 Detection

[0089] Fasting blood glucose test: On the 60th day, mice in each group were fasted but not watered, and blood was collected from the tail tip to test fasting blood glucose (FBG): a blood glucose test strip was placed in the detection area of ​​the blood glucose tester, and a drop of blood was squeezed out from the mouse's tail and placed in the blood glucose test area. The first drop of blood was poured out, and then the second drop of blood was tested with a blood glucose meter, and the blood glucose concentration value displayed by the blood glucose tester was recorded.

[0090] OGTT test: Oral glucose tolerance test (OGTT) was performed 60 days after administration. Mice were fasted for 12 hours but not water. -1 The mice were gavaged with 20% glucose and blood was collected from the tail. The blood glucose levels of the mice were measured and recorded with a blood glucose meter before gavage (0 min) and 30 min, 60 min, 90 min, and 120 min after gavage. The oral glucose tolerance test curve was drawn and the area under the blood glucose curve (AUC) was calculated to reflect glucose tolerance and insulin resistance.

[0091] ITT test: Insulin tolerance test (ITT) was performed 60 days after administration. The mice were fasted but not watered for 6 h, and insulin was injected intraperitoneally at 0.75 U kg. Blood glucose concentrations were measured and recorded at 0 min, 30 min, 60 min, 90 min, and 120 min using the tail blood sampling method. Blood glucose curves were drawn and AUC was calculated.

[0092] HE staining was used to detect the pathological morphology of mouse pancreatic tissue: mice were killed by cervical dislocation and pancreatic tissue was removed. Part of the pancreatic tissue was cut with ophthalmic scissors and immersed in 4% paraformaldehyde solution for 24 hours, gradient dehydration, paraffin embedding, and prepared into 5 μm thick sections for HE staining. After dewaxing the paraffin sections of mouse pancreatic tissue to water, they were stained with hematoxylin for 10-20 minutes, differentiated with 1% hydrochloric acid alcohol for a few seconds, and returned to blue with 50°C warm water; stained with eosin for 3-5 minutes, washed with water for 3s-5s; dehydrated in gradient alcohol and xylene in turn to make it transparent, and sealed with neutral gum; examined under a microscope, and image acquisition and analysis were performed.

[0093] 3.4 Statistical analysis

[0094] All data were analyzed using GraphPad Prism 8.0 software (GraphPad software, Inc). Two-tailed unpaired t-test was used for comparison between groups. The AUC method was used with *p<0.05, **p<0.01 to determine the difference was statistically significant.

[0095] 3.5 Results:

[0096] The average fasting blood glucose levels of the blank group and the model group 60 days after infection (days post infection, dpi) were as follows: the fasting blood glucose level of the model group was significantly higher than that of the blank group (p<0.001). Figure 4a. OGTT experiment showed that the blood glucose levels of the model group were higher than those of the blank group at each time point; at 30 minutes after administration, the blood glucose levels of the blank group and the model group increased significantly; at 60 minutes after administration, the blood glucose levels of the blank group and the model group decreased significantly; at 90 minutes and 120 minutes after administration, the blood glucose level curves of the blank group and the model group tended to be flat, as shown in Figure 2. Figure 4 The area under the blood glucose-time curve (AUC) in the model group was significantly greater than that in the blank group (P<0.01), indicating that the glucose tolerance of mice in the model group was significantly decreased, showing obvious insulin resistance. Figure 4 In terms of the detection of pancreatic tissue pathological morphology in mice, the pancreatic cell structure of the blank group mice was normal, the pancreatic tissue was relatively complete, the islets and exocrine glands were clearly demarcated, and the arrangement was orderly; the pancreatic cells of the model group mice were severely damaged, the overall shape was atrophic, the shape was irregular, and the arrangement was disordered. Figure 5 .

[0097] The average fasting blood glucose values ​​of the model group and the treatment group 60 days after infection (days post infection, dpi) were as follows: the fasting blood glucose values ​​of the model group were significantly higher than those of the blank group (p<0.001). Figure 6 The OGTT experiment showed that the blood glucose levels of the model group were higher than those of the treatment group at each time point. The blood glucose increase in the model group was significantly greater than that in the treatment group at 30 minutes after administration. At 60 minutes, 90 minutes, and 120 minutes after administration, the blood glucose levels of the model group were significantly reduced, while the blood glucose increase and decrease levels of the treatment group fluctuated smoothly at each time period. Figure 7 The area under the blood glucose-time curve (AUC) in the model group was significantly greater than that in the treatment group (P<0.001), indicating that the glucose tolerance of mice in the model group was significantly reduced, showing obvious insulin resistance. Figure 7 b. The ITT experiment showed that after the ob / ob mice were intraperitoneally injected with insulin, the blood glucose levels of the model group were higher than those of the treatment group at each time point; compared with the 0th minute (when no insulin was injected), the blood glucose levels of the model group and the treatment group showed a downward trend at the 30th minute, and the blood glucose level of the model group decreased slowly at the 60th and 90th minutes; while the blood glucose level of the treatment group increased slightly at the 30th to 60th minute, and then decreased slowly at the 90th minute. Figure 8 The area under the blood glucose-time curve (AUC) in the model group was significantly greater than that in the treatment group (P<0.01). Figure 8 In terms of the detection of pancreatic tissue pathology in mice, the pancreatic tissue structure of mice in the model group was incomplete, with blurred and uneven boundaries, vacuolar infiltration, necrosis, and hemorrhage; compared with the model group, the pancreatic tissue pathology of mice in the treatment group was improved, and the structure was relatively complete. Fig. 9 .

[0098] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A composition for treating elevated blood sugar caused by SARS-CoV-2 infection, characterized in that: The invention is composed of the following ingredients by weight: 10-40 parts of rhein, 15-60 parts of magnolol, 2.5-10 parts of quercetin, 10-40 parts of licorice chalcone and 10-20 parts of formononetin.

2. The composition according to claim 1, characterized in that: The invention is composed of the following ingredients by weight: 10-20 parts of rhein, 15-30 parts of magnolol, 2.5-5 parts of quercetin, 10-20 parts of licorice chalcone and 10-20 parts of formononetin.

3. The composition according to claim 2, characterized in that: The invention is composed of the following ingredients by weight: 20 parts of rhein, 30 parts of magnolol, 5 parts of quercetin, 20 parts of licorice chalcone and 20 parts of formononetin.

4. The composition according to claim 1, characterized in that: The weight ratio of magnolol, licorice chalcone and formononetin is 3:2:

2.

5. The method for preparing the composition according to any one of claims 1 to 4, characterized in that: The following steps are involved: The composition is obtained by mixing rhein, magnolol, quercetin, licorice chalcone and formononetin.

6. Use of the composition according to any one of claims 1 to 4 or the composition prepared by the preparation method according to claim 5 in the preparation of a medicament for treating increased blood sugar caused by SARS-CoV-2 infection.

7. A drug for treating elevated blood sugar caused by SARS-CoV-2 infection, characterized in that: The invention comprises the composition according to any one of claims 1 to 4 or the composition prepared by the preparation method according to claim 5.

8. The drug according to claim 7, characterized in that: The medicine further comprises at least one of a carrier and an excipient.

9. The drug according to claim 8, characterized in that: The carrier is physiological saline.

10. The drug according to claim 8, characterized in that: The dosage form of the drug is selected from granules, tablets, capsules or oral liquids.

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