Application of achyranthes bidentata polysaccharide and pharmaceutical composition of achyranthes bidentata polysaccharide in resisting diabetic secondary influenza
The pharmaceutical composition prepared using Achyranthes bidentata polysaccharide achieves synergistic intervention of hypoglycemia, immune regulation, and antiviral action in patients with diabetes mellitus secondary to seasonal influenza, thus addressing the issue of influenza susceptibility in diabetic patients and providing a safe and effective treatment option.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- THE FIFTH PEOPLES HOSPITAL OF SHANGHAI
- Filing Date
- 2026-04-08
- Publication Date
- 2026-05-19
AI Technical Summary
Current technologies have not effectively addressed the fundamental pathological mechanisms underlying the increased susceptibility of diabetic patients to influenza and its complications, and there is a lack of effective drugs to combat influenza and its complications in diabetic patients.
A pharmaceutical composition containing pharmaceutically acceptable excipients was prepared using Achyranthes bidentata polysaccharide. Various dosage forms were designed for the treatment of diabetes mellitus secondary to seasonal influenza, achieving synergistic intervention through hypoglycemic, immunomodulatory, and antiviral activities.
Achyranthes bidentata polysaccharide showed significant reduction in post-infection mortality, relief of weight loss, and promotion of weight recovery during the recovery period in diabetic model mice. It has both safety and therapeutic effects, providing a novel treatment option using a single Chinese medicine.
Smart Images
Figure CN122056914A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to the pharmaceutical use of Achyranthes bidentata polysaccharide and its pharmaceutical compositions in the treatment of diabetic secondary influenza. Background Technology
[0002] Diabetes mellitus is a globally prevalent metabolic disease characterized by chronic hyperglycemia caused by insulin secretion defects or dysfunction. Its prevalence is rising rapidly, and the various chronic complications it causes have placed a heavy disease burden on society and families, making it a serious public health problem.
[0003] Diabetic patients, due to their chronic metabolic disorders, generally suffer from impaired immune defense systems, resulting in significantly increased susceptibility to various pathogens. Influenza viruses, in particular, pose a serious health threat to diabetic patients due to their high variability, rapid spread, and seasonal epidemic pattern. Clinical influenza infection often leads to uncontrolled hyperglycemia, which in turn exacerbates influenza infection. Therefore, a thorough understanding of the immunological and metabolic mechanisms underlying this interaction is of crucial theoretical and practical significance for developing new intervention targets and optimizing existing clinical management pathways.
[0004] The fundamental pathological mechanisms underlying the increased susceptibility of diabetic patients to influenza and its complications are not yet fully understood, but impaired immune responses may increase the risk of infection in diabetic patients. On the one hand, chronic hyperglycemia can inhibit the chemotaxis, phagocytosis, and oxidative functions of neutrophils and weaken the activation of T and B lymphocytes, leading to a weakening of both innate and adaptive immune responses, creating favorable conditions for the initial replication and spread of the virus in the body. On the other hand, diabetic patients are often in a state of chronic low-grade inflammation, making them more susceptible to cytokine storms when exposed to viral infection stress, thereby exacerbating the risk of lung tissue damage and multiple organ failure. Acute influenza infection often leads to a sharp deterioration in blood glucose control. The stress response triggered by infection activates the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, prompting the release of large amounts of insulin-antagonistic hormones such as glucocorticoids and catecholamines, exacerbating insulin resistance and causing a significant stress-induced hyperglycemia. During the course of diabetes, symptoms such as loss of appetite and dehydration, along with the use of glucocorticoids, disrupt the stability of routine blood glucose control regimens, significantly increasing the risk of acute metabolic complications such as diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). Long-term use of blood glucose-lowering drugs may lead to weight gain, gastrointestinal inflammation, hypoglycemia, and even drug resistance.
[0005] Traditional Chinese medicine has accumulated rich practical experience in the prevention and treatment of diabetes. Exploring novel hypoglycemic active ingredients with multiple targets and low toxicity from natural products has become an important direction in diabetes drug research and development. Achyranthes bidentata, a traditional Chinese medicine, has the effects of tonifying the liver and kidneys, strengthening tendons and bones, removing blood stasis and promoting blood circulation, and guiding blood downwards. It is often used in traditional Chinese medicine prescriptions to treat arthralgia and traumatic injuries. Modern pharmacological studies have shown that Achyranthes bidentata polysaccharides (ABPS), abundant in Achyranthes bidentata, are the main material basis for its immunomodulatory, anti-tumor, anti-osteoporosis, and antioxidant activities. At the same time, ABPS shows great potential in improving glucose and lipid metabolism disorders, providing a solid theoretical basis for exploring its effects on diabetes. Preliminary in vitro and in vivo experiments reveal that ABPS may exert its hypoglycemic effect through multiple pathways and multiple targets. First, it may improve insulin secretion defects by protecting pancreatic β cells, reducing cell apoptosis, and promoting glucose-stimulated insulin secretion. Secondly, Achyranthes bidentata polysaccharide can significantly enhance insulin sensitivity, and its mechanism may be related to the activation of the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway in skeletal muscle and liver, the promotion of glucose transporter 4 (GLUT4) translocation, and the inhibition of hepatic gluconeogenesis. Furthermore, diabetes is often accompanied by chronic low-grade inflammation, and Achyranthes bidentata polysaccharide has significant anti-inflammatory and antioxidant properties, which help reduce inflammatory responses in adipose tissue and liver, and improve insulin resistance. In recent years, the "gut microbiota-host metabolic axis" theory has opened up new perspectives for understanding the mechanisms of action of natural products. As a dietary fiber that is not easily digested directly, Achyranthes bidentata polysaccharide may indirectly regulate glycemic homeostasis by regulating the gut microbiota structure, promoting the proliferation of beneficial bacteria, and thereby increasing the levels of hormones such as gut-derived GLP-1.
[0006] However, the fundamental pathological mechanism by which diabetic patients are more susceptible to influenza and its complications is not yet fully understood in the current technology, and there are no effective drugs to combat influenza and its complications in diabetic patients. Therefore, how to obtain an effective drug to combat influenza and its complications in diabetic patients is a technical problem that urgently needs to be solved in this field. Summary of the Invention
[0007] The use of Achyranthes bidentata polysaccharide in the preparation of drugs for treating seasonal influenza secondary to diabetes.
[0008] The purpose of this invention is to overcome the shortcomings of the prior art and to provide the following technical solution: The first aspect of the present invention provides a pharmaceutical composition for treating seasonal influenza secondary to diabetes, the pharmaceutical composition comprising Achyranthes bidentata polysaccharide; Furthermore, the pharmaceutical composition also includes pharmaceutically acceptable excipients; Furthermore, the pharmaceutically acceptable excipients are selected from any one or more of fillers, binders, lubricants, flavoring agents, solubilizers, preservatives, and pH adjusters; Furthermore, the filler is selected from any one or more of lactose, microcrystalline cellulose, starch, sucrose, and glucose; Furthermore, the adhesive is selected from any one or more of polyvinylpyrrolidone, hydroxypropyl methylcellulose, and starch; Furthermore, the lubricant is selected from any one or more of magnesium stearate, micronized silica gel, and talc. Furthermore, the flavoring agent is selected from any one or more of sucrose, glucose, maltose, and aspartame; Furthermore, the co-solvent is selected from any one or more of water, ethanol, and glycerol; Furthermore, the preservative is selected from any one or more of benzoic acid, sodium benzoate, and ethanol; Furthermore, the pH adjuster is formic acid; Furthermore, the pharmaceutical composition is any pharmaceutically acceptable dosage form; Furthermore, the dosage form is selected from oral preparations, injections, transdermal preparations, mucosal preparations, or topical liquid preparations; Furthermore, the oral dosage form is an oral solid dosage form or an oral liquid dosage form; further still, the oral solid dosage form is a tablet, capsule, or granule. Furthermore, the topical preparation is a transdermal drug delivery preparation. Furthermore, the transdermal drug delivery formulation is a patch; Furthermore, the mucosal delivery formulation is a suppository or an inhalation formulation; Furthermore, the topical liquid preparation is a tincture; A second aspect of the invention provides the use of Achyranthes bidentata polysaccharide or any of the above-mentioned pharmaceutical compositions containing Achyranthes bidentata polysaccharide in the preparation of a medicament for treating seasonal influenza secondary to diabetes. Furthermore, the intended use is for the inhibition of influenza virus and / or for immunomodulatory effects; Compared with the prior art, the advantages of this invention are as follows: Achyranthes bidentata polysaccharide, derived from the traditional Chinese medicine Achyranthes bidentata, is natural and low in toxicity. Clinical application studies have shown that it has substantial benefits in areas such as immune regulation, anti-inflammation, bone health, and metabolic regulation. In this invention, high-dose Achyranthes bidentata polysaccharide was used in diabetic mouse models, and no significant toxic side effects were observed, demonstrating good safety. Simultaneously, Achyranthes bidentata polysaccharide significantly reduced the mortality rate of mice after infection (survival rate reached 60% in the high-dose group), effectively alleviated the trend of weight loss, and promoted rapid weight recovery during the recovery period, exhibiting a clear therapeutic effect. This invention, through the construction of a stable diabetic-influenza co-infection animal model, has for the first time confirmed the therapeutic value of Achyranthes bidentata polysaccharide for diabetic secondary seasonal influenza. It reveals a new use of Achyranthes bidentata polysaccharide in the preparation of drugs for treating diabetic secondary seasonal influenza, providing a novel single-component traditional Chinese medicine treatment for this complex co-infection condition and expanding the application scope of Achyranthes bidentata polysaccharide.
[0009] This invention utilizes the hypoglycemic, immunomodulatory, and antiviral activities of Achyranthes bidentata polysaccharide to achieve synergistic intervention in the complex pathology of diabetic secondary influenza, where metabolic disorders and immune dysregulation coexist. This approach offers potential advantages over single antiviral or hypoglycemic drugs. It boasts the advantages of definite efficacy and multi-target synergy, and its water solubility and bioavailability can be addressed through chemical or physical modifications to design and develop various dosage forms, demonstrating promising clinical application prospects. Attached Figure Description
[0010] Figure 1 The results of median lethal dose determination in a mouse model of influenza virus-mediated lung injury are shown in the figure; (a) shows the weight monitoring results of the mice; (b) shows the survival curve of the mice. Figure 2 The figure shows the effect of Achyranthes bidentata polysaccharide of the present invention on a mouse model of influenza virus infection-mediated lung injury; where (a) is the mouse weight monitoring results; and (b) is the mouse survival curve. Figure 3 The figure shows the effect of different dosages of Achyranthes bidentata polysaccharide of the present invention on the body weight of DM mice; Figure 4 The figure shows the therapeutic effect of Achyranthes bidentata polysaccharide on DM mice of the present invention; where (a) is the weight monitoring result of mice; and (b) is the survival curve of mice. Detailed Implementation
[0011] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments and accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.
[0012] Example 1. Main experimental reagents Achyranthes bidentata polysaccharide: The Achyranthes bidentata polysaccharide in this embodiment of the invention is an analytical standard, purchased from Shanghai Yuanye Biotechnology Co., Ltd., product number: B25872; website: https: / / www.shyuanye.com / goods-B25872.html?u_atoken=69a2e524- ae6f-15fd-c35b-2e6cb27764a8&u_asig=79593aac17722831729675741e.
[0013] 2. Influenza virus: The mouse-adapted strain of influenza A virus (A / Puerto Rico / 8 / 1934 (H1N1)) in this embodiment of the invention was preserved at the Animal Vaccine Innovation Center of China Agricultural University.
[0014] 2. Establishment of an influenza virus model The mouse-adapted strain of influenza A virus (A / Puerto Rico / 8 / 1934 (H1N1)) was used to inoculate susceptible chicken embryos aged 9-11 days, and the allantoic fluid of the infected chicken embryos (i.e., PR8 virus fluid) was harvested.
[0015] C57 mice around 16 weeks old were randomly divided into 6 groups of 10 mice each. Except for the blank control group (16-week-old mice), the other 5 groups of mice were lightly anesthetized and inoculated with 50 μL of appropriate dose of PR8 virus solution via intranasal drip in 5 different doses. They were observed for 14 days, and changes in body weight, mortality rate and lung pathological changes were observed.
[0016] pass Figure 1 It can be seen that the influenza virus caused death in all mice at high doses, and the survival rate increased as the concentration decreased, indicating that the influenza virus infection-mediated mouse lung injury model was successfully established. Furthermore, its LD50 was calculated. 50 The value is 3.3 / 0.05 mL.
[0017] 3. Pharmacological experiments 3.1 In vivo virus inhibition experiment Male C57BL / 6 mice aged 15 weeks were randomly divided into four groups of 10 mice each: a normal control group, a low-dose Achyranthes bidentata polysaccharide group (ABP-L) (100 mg / kg / d), a medium-dose Achyranthes bidentata polysaccharide group (ABP-M) (400 mg / kg / d), and a high-dose Achyranthes bidentata polysaccharide group (ABP-H) (800 mg / kg / d). Mice in the low-dose, medium-dose, and high-dose Achyranthes bidentata polysaccharide groups were administered Achyranthes bidentata polysaccharide via gavage at a fixed time each day for three consecutive days. During this period, mice in the normal control group and the three Achyranthes bidentata polysaccharide groups had free access to food and water, and their body weight was measured daily. Eight hours after the initial administration, mice in each group were lightly anesthetized and inoculated with 50 mg / kg of Achyranthes bidentata polysaccharide via intranasal drip. μ Mice were given L doses of PR8 virus solution and their mental state, coat color, water intake, food intake, urine output, and activity were observed daily to evaluate the inhibitory effect of Achyranthes bidentata polysaccharide on PR8.
[0018] pass Figure 2 It can be seen that the three doses of Achyranthes bidentata polysaccharide can significantly inhibit PR8-induced mouse mortality, with a survival rate of 20% in the low-dose group, 30% in the medium-dose group, and 60% in the high-dose group. This indicates that Achyranthes bidentata polysaccharide has significant antiviral or immunomodulatory effects in vivo.
[0019] 3.2 Treatment of PR8 influenza virus infection with Achyranthes bidentata polysaccharide via gavage in C57 mice (a diabetic model) This invention establishes and characterizes a stable diabetic-influenza co-infection mouse model to simulate the pathological process of worsening symptoms in diabetic patients after influenza infection in clinical settings. Compared with healthy mice, diabetic mice infected with PR8 influenza virus exhibit higher mortality, more significant weight loss, more severe lung pathological damage, higher viral load, and more severe cytokine storm.
[0020] 3.2.1 Constructing a diabetic-influenza co-infection mouse model Six-week-old male C57BL / 6J mice were selected, as males exhibit relatively small individual differences, thus avoiding interference from the estrogen cycle on metabolism. The selected mice were housed in a barrier system animal laboratory, with the room temperature maintained at 18–24°C, humidity at 50%–70%, and pressure at -10 Pa. Disinfection methods included spraying and wiping, using 75% alcohol and 1000 mg / L 84 disinfectant. Bedding was changed every four days, and the animal room was equipped with an automated day-night cycle. After purchase, the mice were acclimatized to a standard diet for 1–2 weeks to allow them to adapt to the new environment and stabilize their basal metabolic indicators. After acclimatization, the standard diet was replaced with a high-fat diet for 5–8 weeks. Weight was measured weekly during the experiment until the mice showed significant weight gain. After the feeding program was completed, hyperglycemia was monitored.
[0021] Mice with a successfully established diabetes model will exhibit typical symptoms such as polydipsia, polyphagia, polyuria, and weight loss. Fasting blood glucose tests will be performed on the mice. The mice will be fasted for 4-6 hours before the test, and blood will be collected from the tail vein. The blood glucose level will be measured using a portable blood glucose meter. If the blood glucose level is ≥11.1 mmol / L (200 mg / dL) for two consecutive measurements, the mouse diabetes model is considered to be successfully established.
[0022] Male C57BL / 6 mice with successfully established diabetic models were randomly divided into three groups of 10 mice each: a diabetic model group (DM), a low-dose Achyranthes bidentata polysaccharide group (ABP-L), and a high-dose Achyranthes bidentata polysaccharide group (ABP-H). Healthy male C57BL / 6 mice were used as the normal control group (MOCK group). The mice in each group were fed as follows: Normal control group (MOCK group): fed with normal feed and administered an equal volume of physiological saline by gavage; Diabetes model group (DM): After successful modeling, the same volume of physiological saline was administered by gavage; Low-dose Achyranthes bidentata polysaccharide group (ABP-L): After successful modeling, low-dose ABP (100 mg / kg / d) was administered by gavage. High-dose Achyranthes bidentata polysaccharide group (ABP-H): After successful modeling, high-dose ABP (800 mg / kg / d) was administered by gavage.
[0023] Mice in the low-dose group (ABP-L) and high-dose group (ABP-H) of Achyranthes bidentata polysaccharide were administered Achyranthes bidentata polysaccharide by gavage once daily for 3 consecutive days. During the experiment, all mice in all groups had free access to food and water, and their body weight was measured daily. Eight hours after the first administration, mice in each group were lightly anesthetized and inoculated with 50 μL of 5LD50 dose of PR8 virus solution via intranasal drops. The mice's mental state, coat color, water intake, food intake, urine output, and activity were observed daily to evaluate the therapeutic effect of Achyranthes bidentata polysaccharide on diabetes mellitus complicated with PR8 infection.
[0024] pass Figure 3 Experimental results showed that although high and low doses of Achyranthes bidentata polysaccharide led to a weight loss of less than 10% in diabetic model mice, the overall condition of the mice remained good. Figure 4 It can be seen that comparing the weight changes and mortality rates of mice in the normal control group and the diabetes mellitus (DM) model group, the DM group experienced a more significant weight loss and a higher mortality rate. Comparing the dosage administered to C57 DM mice, it was found that after 3 days of continuous treatment with Achyranthes bidentata polysaccharide, the higher dose reduced the trend of weight loss and resulted in faster weight gain during the recovery period. The survival rate of mice treated with the high dose of Achyranthes bidentata polysaccharide was 60%, while the survival rate of mice treated with the low dose was 30%. This indicates that Achyranthes bidentata polysaccharide has a certain therapeutic effect, and that high-dose treatment can exert a certain protective effect.
[0025] Although embodiments of the invention have been shown and described, those skilled in the art will understand that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the claims and their equivalents.
Claims
1. A pharmaceutical composition for treating seasonal influenza secondary to diabetes, characterized in that, The drug contains Achyranthes bidentata polysaccharide.
2. The pharmaceutical composition for treating diabetic secondary seasonal influenza according to claim 1, characterized in that, The pharmaceutical composition further includes pharmaceutically acceptable excipients; further, the pharmaceutically acceptable excipients are selected from any one or more of fillers, binders, lubricants, flavoring agents, solubilizers, preservatives, and pH adjusters.
3. The pharmaceutical composition for treating diabetic secondary seasonal influenza according to claim 2, characterized in that, The filler is selected from any one or more of lactose, microcrystalline cellulose, starch, sucrose, and glucose.
4. The pharmaceutical composition for treating diabetic secondary seasonal influenza according to claim 2, characterized in that, The adhesive is selected from any one or more of polyvinylpyrrolidone, hydroxypropyl methylcellulose, and starch.
5. The pharmaceutical composition for treating diabetic secondary seasonal influenza according to claim 2, characterized in that, The lubricant is selected from any one or more of magnesium stearate, micronized silica gel, and talc.
6. The pharmaceutical composition for treating diabetic secondary seasonal influenza according to claim 2, characterized in that, The flavoring agent is selected from any one or more of sucrose, glucose, maltose, and aspartame.
7. The pharmaceutical composition for treating diabetic secondary seasonal influenza according to claim 2, characterized in that, The cosolvent is selected from any one or more of water, ethanol, and glycerol.
8. The pharmaceutical composition for treating diabetic secondary seasonal influenza according to claim 2, characterized in that, The preservative is selected from any one or more of benzoic acid, sodium benzoate, and ethanol.
9. The pharmaceutical composition for treating diabetic secondary seasonal influenza according to claim 2, characterized in that, The pH adjuster is formic acid.
10. The pharmaceutical composition for treating diabetic secondary seasonal influenza according to claim 2, characterized in that, The pharmaceutical composition is any pharmaceutically acceptable dosage form; Furthermore, the dosage form is selected from oral preparations, injections, transdermal preparations, mucosal preparations, or topical liquid preparations; Furthermore, the oral dosage form is an oral solid dosage form or an oral liquid dosage form; further still, the oral solid dosage form is a tablet, capsule, or granule. Furthermore, the transdermal drug delivery formulation is a patch; Furthermore, the mucosal delivery formulation is a suppository or an inhalation formulation; Furthermore, the topical liquid preparation is a tincture.
11. Use of Achyranthes bidentata polysaccharide or a pharmaceutical composition containing Achyranthes bidentata polysaccharide according to any one of claims 1 to 10 in the preparation of a drug for treating seasonal influenza secondary to diabetes; further, the use is for the inhibitory effect on influenza virus and / or the immunomodulatory effect.