A hypoglycemic composition, its preparation method and use

Abstract

The application belongs to the technical field of traditional Chinese medicine compositions, and particularly relates to a blood glucose-lowering composition and a preparation method and application thereof. The traditional Chinese medicine composition comprises the following raw materials in parts by weight: clove 5-10 parts, cassia 10-20 parts, dandelion 20-30 parts, jujube 20-30 parts and small Chinese eupatorium 25-35 parts. The application controls the specific types and proportions of drugs, improves the mutual synergistic effect among components, and improves the blood glucose-lowering effect.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a hypoglycemic composition, its preparation method, and its application. Background Technology

[0002] Hyperglycemia is a major characteristic of diabetes mellitus, and its pathogenesis is complex and not yet fully understood. Numerous studies have shown that hyperglycemia is closely related to insulin resistance and pancreatic β-cell dysfunction, with these two factors interacting and forming a vicious cycle, forming the core pathological basis for the development of type 2 diabetes. In addition, various factors such as inflammation, oxidative stress, endoplasmic reticulum stress, and ectopic lipid deposition also participate in the development of hyperglycemia, jointly promoting disease progression by interfering with insulin signaling pathways and β-cell function. Sustained hyperglycemia can lead to disordered glucose metabolism, thereby promoting insulin resistance and hyperinsulinemia, and may ultimately develop into metabolic diseases such as diabetes mellitus. As a chronic metabolic disease accompanied by hyperglycemia, diabetes mellitus can cause serious complications such as cardiovascular disease, neuropathy, and kidney damage due to long-term hyperglycemia, significantly impairing patients' health and quality of life. Therefore, the development of safe, effective, and well-defined hypoglycemic drugs is of significant clinical importance.

[0003] Traditional Chinese medicine (TCM) has accumulated a relatively systematic theoretical foundation and rich clinical experience in the diagnosis and treatment of diabetes, and has achieved relatively ideal therapeutic effects in long-term practice. The earliest records of diabetes mellitus are found in the *Huangdi Neijing* (Yellow Emperor's Inner Classic), where it is discussed extensively. The *Suwen* (Plain Questions) chapter on "Strange Diseases" classifies it as a "strange disease," stating: "Spleen deficiency. When the five flavors enter the mouth, they are stored in the stomach, and the spleen distributes their essence and qi. The body fluids reside in the spleen, hence the sweet taste in the mouth. This is caused by excessive consumption of rich and fatty foods. Such a person must frequently eat sweet and fatty foods. Fat causes internal heat, and sweetness causes fullness in the middle, so the qi overflows upwards, turning into diabetes mellitus." It is believed that the occurrence of this disease is mostly related to excessive consumption of rich and fatty foods. Improper diet leads to the internal generation of phlegm and dampness, which, over time, transforms into heat, further depleting body fluids and causing diabetes mellitus. Zhang Zhongjing's *Shanghan Lun* (Treatise on Cold Damage) records, "If the pulse is floating, urination is difficult, and there is slight fever and diabetes mellitus, Wuling San (Five-Ingredient Powder with Poria) is the main treatment." Here, diabetes mellitus only represents one symptom. "Xiao" means to dry up or dissipate, referring to emaciation and loss; "ke" means thirsting or wanting to drink. Traditional Chinese medicine believes that the basic pathogenesis of diabetes is deficiency of yin fluids and excessive dryness and heat, with yin deficiency as the root cause and dryness and heat as the manifestation. Therefore, the treatment of diabetes often focuses on resolving yin deficiency and dryness and heat.

[0004] Some traditional Chinese medicine formulas are used to treat diabetes (Xiao Ke) and regulate glucose metabolism disorders, thereby lowering blood sugar. For example, the Cui's Eight-Ingredient Pill recorded in *Synopsis of Prescriptions of the Golden Chamber* is composed of Rehmannia glutinosa, Cornus officinalis, Dioscorea opposita, Alisma plantago-aquatica, Poria cocos, Paeonia suffruticosa, Cinnamomum cassia (bark cinnamon), and Aconitum carmichaelii. It is mainly used to treat kidney deficiency, cold limbs, lower abdominal distension, difficulty or frequent urination, pale and swollen tongue, edema, beriberi, Xiao Ke, and chronic diarrhea. It is now used for diabetes, hypothyroidism, chronic nephritis, adrenal insufficiency, and bronchial asthma, all of which are attributed to kidney deficiency. The Jiaotai Pill recorded in *Han's Medical Treatise* is composed of Cinnamomum cassia and Coptis chinensis, and has the function of harmonizing the heart and kidneys and balancing Yin and Yang. The Six-Ingredient Clove Powder recorded in *Tibetan Medicine Formulae* is composed of clove, Piper longum, dried ginger, Terminalia chebula, Phyllanthus emblica, and Glycyrrhiza uralensis, and has the effects of warming the middle jiao, promoting qi circulation, and resolving dampness and turbidity. The Zhijuzi Pill, recorded in Shiyi Dexiaofang, is mainly used to treat excessive drinking, combined with extreme heat, resulting in dryness of body fluids and blood, frequent urination, muscle wasting, and a craving for cold foods and drinks.

[0005] Chinese invention patent application CN121648215A discloses a traditional Chinese medicine composition for assisting in lowering blood sugar and its preparation method. The composition comprises Anemarrhena asphodeloides, Cornus officinalis, Pueraria lobata, Panax quinquefolius, Morus alba leaves, and Cinnamomum cassia. This traditional Chinese medicine composition effectively assists in lowering blood sugar and improving related symptoms, and has good safety profile. It can be prepared as a traditional Chinese medicine or health food for assisting in lowering blood sugar. Patent CN119523028A discloses a method for preparing a fast-acting hangover-relieving and liver-protecting beverage. This beverage is composed of chamomile extract and various plant ingredients (dandelion, bergamot, and Hovenia dulcis, etc.). The chamomile extract is extracted using a special process, making it an effective hangover-relieving and liver-protecting beverage that is beneficial for preventing and treating disorders of glucose and lipid metabolism. Patent CN118853331A discloses an invention that discloses a fermented broth of noni fruit that lowers uric acid and blood sugar. It is composed of fermented noni fruit, dried hawthorn, kudzu root, poria cocos, corn silk, cloves, and sweeteners. It can be developed as a food, health product, and drug for the treatment of gout, hyperuricemia, and type II diabetes.

[0006] Another Chinese invention patent application, CN202510095755.2, discloses a traditional Chinese medicine composition for treating non-alcoholic steatohepatitis (NAHPC) and its application. The technical problem this invention aims to solve is to provide a new treatment option for patients with NHAPC. The technical solution of this invention is a traditional Chinese medicine composition for treating NHAPC, comprising the following ingredients: clove, thistle, gardenia, peach kernel, Japanese raisin tree fruit, saffron, tangerine peel, kudzu root, and dandelion. The main purpose of this invention is to provide a traditional Chinese medicine composition for treating NHAPC.

[0007] Another Chinese invention patent application, CN202110454789.8, discloses a traditional health-preserving tea formula, comprising the following components by weight: 1-5 parts Polygonatum sibiricum, 1-5 parts Taraxacum mongolicum, 1-5 parts Glycyrrhiza uralensis, 1-5 parts Hawthorn, 1-5 parts Raisinia serratifolia, 0-5 parts Malt, 0-5 parts Tangerine peel, 0-5 parts Lily bulb, 0-5 parts Poria cocos, 0-5 parts Cassia tora, 0-5 parts Lycium barbarum, and 0-5 parts Ginseng. This formula is said to detoxify the internal organs, eliminate excess fat and food waste, nourish the five internal organs, calm the mind and aid sleep, strengthen the spleen and stomach, promote urination and defecation, regulate blood pressure, blood sugar, and cholesterol, treat menstrual irregularities, prostate diseases, acne, allergies, improve immunity, promote blood circulation, dissipate stagnation, eliminate tumors, and has a good anti-inflammatory effect on hepatitis and gastritis. It also possesses antiviral and cancer-preventive properties. It has the effects of strengthening the body's foundation, regulating yin and yang, beautifying the skin, fading spots and delaying aging.

[0008] The prior art represented by the aforementioned documents has at least the following unresolved technical problems or defects: The existing technologies mentioned above have all made some progress in exploring traditional Chinese medicine treatments for lowering blood sugar. However, some of these technologies involve numerous medicinal materials, making decoction difficult, and the mechanisms of action remain unclear in later research on the pharmacodynamic material basis. Some of these technologies have fewer components but less prominent effects, and the preparation methods have not been thoroughly studied, making it difficult to maximize the effects of the drugs.

[0009] In solving the above problems or overcoming the above defects, the present invention encountered the following difficulties and obstacles: To address the core shortcomings of existing technologies, this invention faces several key bottlenecks during its development. First, the pathogenesis of hyperglycemia is complex, involving multiple pathways such as glucose metabolism disorders, insulin resistance, and pancreatic islet damage, making it difficult for single-effect medicinal materials to achieve synergistic regulation of multiple targets. Second, the efficacy of traditional Chinese medicine compound prescriptions is highly dependent on precise formulation; even slight fluctuations in the proportion of core medicinal materials can significantly affect the hypoglycemic effect. Balancing the ratio of cold and warm medicinal materials is difficult, and the synergistic effect range is narrow, making precise selection of the optimal ratio extremely challenging. Third, the dissolution efficiency of active ingredients is strongly correlated with the preparation process; conventional extraction methods easily lead to the loss of effective components and low bioavailability. Optimizing process parameters requires balancing activity retention and maximizing efficacy, presenting significant technical challenges. Fourth, while simplifying medicinal materials and processes, it is necessary to consider multiple effects such as hypoglycemic control, liver protection, and pancreatic protection, avoiding the contradiction of "simplification equals reduced efficacy," resulting in a low tolerance for error and a long validation cycle. Summary of the Invention

[0010] To address the shortcomings of existing technologies, this invention provides a hypoglycemic composition, its preparation method, and its application.

[0011] Terminology Explanation: Unless otherwise defined, all technical terms in this document have the same meanings as commonly understood by one of ordinary skill in the art to which the subject matter of the claims pertains. Unless otherwise stated, all patents, patent inventions, and publications cited in this document are incorporated herein by reference in their entirety. If multiple definitions exist for terms in this document, the definitions in this chapter shall prevail.

[0012] It should be understood that the above brief description and the following detailed description are exemplary and for illustrative purposes only, and do not limit the subject matter of the invention in any way. In this invention, the singular is used in conjunction with the plural unless otherwise specifically stated. It should also be noted that, unless otherwise stated, the use of “or” or “or” means “and / or”. Furthermore, the use of the term “comprising” and other forms such as “including,” “containing,” and “contains” are not limiting.

[0013] The definitions of standard chemical terms can be found in the reference "Pharmacopoeia of the People's Republic of China (2025 Edition)".

[0014] Unless otherwise stated, conventional methods within the scope of the art, such as centrifugation, reflux, concentration, resuspension, etc., shall be used.

[0015] Unless specifically defined herein, the use of all commercially available products herein employs standard techniques. For example, it may be carried out using the manufacturer's instructions for use with the kit, or in accordance with methods known in the art or the description of this invention. The techniques and methods described herein can generally be implemented according to conventional methods well known in the art, based on the descriptions in the various summary and more specific documents cited and discussed in this specification.

[0016] The terms “optional / arbitrary” or “optionally / arbitrarily” mean that the event or situation described below may or may not occur, including both the occurrence and non-occurrence of the event or situation.

[0017] "Effective dose" refers to a dose that can achieve treatment, prevention, reduction and / or relief of the disease or condition described in this invention in a subject.

[0018] In this invention, unless otherwise specified, the medicinal materials refer to materials that meet relevant standards, can be purchased from the market, or can achieve the purpose of this invention.

[0019] Clove is the dried flower bud (male clove) or mature fruit (female clove) of the clove plant (Syzygium aromaticum), belonging to the Myrtaceae family. Clinically, male clove is more commonly used. It has a pungent and warm flavor; it enters the spleen, stomach, and kidney meridians, and has the effects of warming the middle jiao and relieving nausea, dispelling cold and relieving pain, and warming the kidneys and assisting yang. Clinically, it is used for stomach cold with vomiting, diabetic nephropathy, toothache / hastelessness, etc.

[0020] Cinnamon is the dried bark of the cinnamon tree (Cinnamomum cassia Presl), a plant in the Lauraceae family. It is classified into "official cinnamon" (bark of young trees) and "ban cinnamon" (thick bark of older trees) based on the part harvested and processed. It is pungent, sweet, and very hot in nature; it enters the kidney, spleen, heart, and liver meridians. It has the effects of tonifying fire and assisting yang, guiding fire back to its source, dispelling cold and relieving pain, and warming and unblocking the meridians. It is used to improve abdominal pain due to cold hernia and yin-type carbuncles (combined with ephedra and deer antler glue); to treat kidney yang deficiency (impotence, cold uterus, and cold pain in the lower back and knees, such as the Shenqi Wan in *Jinkui Yaolue*); to relieve sore throat and oral ulcers caused by upward floating of deficient yang (combined with coptis); and to treat dysmenorrhea and chest pain caused by cold stagnation and blood stasis (such as Guixin San in *Heji Jufang*). Its active ingredients, cinnamaldehyde and polyphenols (such as proanthocyanidins), have the effect of regulating glucose and lipid metabolism.

[0021] Dandelion is the dried whole herb of plants such as *Taraxacum mongolicum* Hand.-Mazz. and *Taraxacum borealisinense* Kitam., belonging to the Asteraceae family. It has the effects of clearing heat and detoxifying, promoting diuresis and relieving strangury, and clearing the liver and improving eyesight; it belongs to the category of heat-clearing and detoxifying medicines.

[0022] The seeds of Hovenia dulcis Thunnb., Hovenia acerba Lindl., and Hovenia trichocarpa Chun et Tsiang, both belonging to the genus Hovenia in the family Rhamnaceae, are mature. They are used to detoxify alcohol, quench thirst, relieve irritability, stop vomiting, and promote urination and defecation. They are primarily used to treat drunkenness, thirst, vomiting, and difficulty in urination and defecation.

[0023] Small thistle is the dried aerial parts (whole plant with flowers) of *Cephalanoplos segetum* (Bunge) Kitam. [Cirsium segetum Bunge], a plant belonging to the genus *Cephalanoplos* of the Asteraceae family. The rhizome is also used medicinally. The whole plant with flowers is harvested in summer, impurities are removed, and it is used fresh or dried. Whole plant: Cools the blood and stops bleeding, removes blood stasis and reduces swelling. Used for epistaxis, hematemesis, hematuria, hematochezia, metrorrhagia, traumatic bleeding, carbuncles and boils. Rhizome: Hepatitis.

[0024] The objective of this invention is achieved through the following technical solution: On one hand, the present invention provides a hypoglycemic composition comprising the following ingredients: clove, cinnamon, dandelion, Japanese raisin tree seed, and thistle.

[0025] As some specific embodiments of the present invention, the ingredients include the following by weight: 5-10 parts cloves, 10-20 parts cinnamon, 20-30 parts dandelion, 20-30 parts Japanese raisin tree fruit, and 25-35 parts small thistle.

[0026] As some specific embodiments of the present invention, the ingredients include the following by weight: 5-6 parts cloves, 15-20 parts cinnamon, 20-25 parts dandelion, 18-22 parts Japanese raisin tree fruit, and 25-30 parts small thistle.

[0027] As some specific embodiments of the present invention, the mass ratio of cinnamon to thistle is 1:1-4.

[0028] As some specific embodiments of the present invention, the mass ratio of dandelion to Japanese raisin tree seeds is 1-1.5:1 by weight.

[0029] As some specific embodiments of the present invention, the raw materials are as follows by weight: 6 parts cloves, 15 parts cinnamon, 25 parts dandelion, 20 parts Japanese raisin tree fruit, and 30 parts small thistle. Alternatively, 5 parts cloves, 20 parts cinnamon, 20 parts dandelion, 20 parts Japanese raisin tree fruit, and 25 parts thistle; Alternatively, use 10 parts cloves, 10 parts cinnamon, 30 parts dandelion, 30 parts Japanese raisin tree fruit, and 35 parts thistle.

[0030] Secondly, the present invention provides a method for preparing the aforementioned hypoglycemic composition, comprising the following steps: Mix cloves, cinnamon, dandelion, Japanese raisin tree seeds, and thistle, extract with water, filter, and concentrate to obtain the final product.

[0031] As some specific embodiments of the present invention, the extraction is carried out by solvent extraction, filtration, and concentration to obtain the product.

[0032] Preferably, the extraction is by decoction or reflux extraction, and / or the solvent is water, methanol, ethanol, or a mixture of water and methanol or ethanol, and / or the amount of solvent used is 5-15 times the total mass of clove, cinnamon, dandelion, Japanese raisin tree seed, and thistle, and / or the number of extractions is 1-3, and / or the extraction time for each extraction is 0.5-2 hours; and / or the product is dried after concentration.

[0033] Water is the preferred solvent.

[0034] Thirdly, the present invention provides a pharmaceutical preparation comprising the aforementioned hypoglycemic composition or the hypoglycemic composition prepared by the aforementioned preparation method, and pharmaceutically acceptable excipients.

[0035] Fourthly, the present invention provides the use of the hypoglycemic composition or the hypoglycemic composition or the pharmaceutical preparation prepared by the aforementioned method in the preparation of a drug for treating, preventing or adjuvantly treating hyperglycemia, regulating glucose metabolism or lowering blood sugar while protecting the liver and reducing pancreatic tissue damage.

[0036] The technical feature of this invention, "a hypoglycemic composition, characterized in that it comprises the following raw materials: clove, cinnamon, dandelion, Japanese raisin tree seed, and small thistle," is derived from the common features summarized in the foregoing explanation and / or Examples 1-3. Therefore, those skilled in the art can reasonably infer that the subordinate concepts of the technical features clove, cinnamon, dandelion, Japanese raisin tree seed, and small thistle, substantially equivalent technical means, and technical means that can be replaced within the scope of conventional technical means and common knowledge based on the existing technical level, should all fall within the protection scope of this invention. For example, replacing clove with purple clove while keeping other technical features unchanged still falls within the protection scope of this invention.

[0037] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) Relationship between principal, assistant, and adjuvant herbs: Dandelion and small thistle are the principal herbs: Dandelion clears heat and detoxifies, promotes diuresis and relieves strangury, clears internal heat and harmonizes the Qi of the internal organs, and helps improve glucose metabolism disorder; Small thistle cools blood and removes blood stasis, reduces swelling and dissipates nodules, and can clear blood stasis and relieve visceral obstruction caused by abnormal blood sugar. The two herbs work together to lay the core foundation for lowering blood sugar. Cinnamon and Japanese raisin tree fruit are the assistant herbs: Cinnamon tonifies fire and assists Yang, warms and unblocks the meridians. Its active ingredients, cinnamaldehyde and polyphenols, can directly regulate glucose and lipid metabolism, while also warming Yang and dispelling cold, avoiding the coldness of the principal herb from harming the body; Japanese raisin tree fruit quenches thirst and relieves irritability, promotes urination and defecation, and can relieve common symptoms of diabetes such as thirst and poor metabolism, assisting the principal herb in enhancing the hypoglycemic effect, while also taking into account the regulation of the internal organs. Clove as an adjuvant: Clove warms the middle jiao and relieves nausea, dispels cold and relieves pain, warms the kidneys and assists yang. It can restrain the cold nature of the principal herbs, dandelion and thistle, and prevent cold damage to the spleen and stomach. It can also warm the kidneys and assist yang, regulate qi and blood, assist cinnamon in guiding fire back to its source, improve the slow metabolism caused by insufficient kidney yang and spleen and stomach deficiency, and help regulate blood sugar.

[0038] (2) Combining cold and warm herbs: Dandelion and small thistle clear heat and cool blood, promote diuresis and remove blood stasis; cinnamon and clove warm yang and dispel cold, warm and unblock the meridians. The cold and warm herbs restrain and cooperate with each other, avoiding the cold from damaging the stomach and the warm from drying and consuming yin. They take into account both clearing heat and protecting the body's resistance, which is in line with the "mixed cold and heat" constitution that is common in diabetic patients. Taking into account both symptoms and root cause: Dandelion, small thistle, and jujube fruit clear heat and promote diuresis, quench thirst and dissipate nodules, treating the symptoms to relieve the thirst and blood stasis caused by elevated blood sugar; cinnamon and clove warm the kidneys and assist yang, warm the middle and strengthen the spleen, treating the root cause to improve the metabolic function of the internal organs, enhance the body's ability to transport sugar, and regulate blood sugar from the root. Multi-target effects: This formula encompasses multiple effects such as clearing heat, warming yang, cooling blood, removing blood stasis, and promoting body fluid production. It can regulate the functions of multiple organs such as the spleen, kidney, and liver. At the same time, it directly regulates glucose and lipid metabolism through the active ingredients of cinnamon. It exerts its hypoglycemic effect through multiple pathways, such as improving insulin resistance, promoting the excretion of metabolic waste, and harmonizing the qi and blood of the internal organs. It reflects the advantages of traditional Chinese medicine in "holistic regulation" and "treatment based on syndrome differentiation", achieving both hypoglycemic effect and protection of the body's resistance, and simultaneous improvement of symptoms and conditioning of the body's constitution.

[0039] (3) By controlling the specific types (clarifying the medicinal materials) and specific weight ratios of cloves, cinnamon, dandelion, Japanese raisin tree fruit and small thistle, this invention strengthens the synergistic effect between the components, effectively improves the effect of lowering blood sugar and regulating sugar metabolism, and at the same time takes into account the care of the internal organs, avoiding the limitation of the effect of a single component.

[0040] (4) The five medicinal materials of clove, cinnamon, dandelion, Japanese raisin tree and small thistle interact with each other to integrate the regulatory pathways related to glucose and lipid metabolism and form a multi-target synergistic regulatory network. It can directly regulate glucose and lipid metabolism through the active ingredients of cinnamon, and improve insulin resistance and help stabilize blood sugar by taking advantage of the heat-clearing, warming, blood-cooling and fluid-generating effects of each medicinal material.

[0041] (5) The present invention further studies the preparation method and finds that by using a specific reflux extraction method (reflux extraction twice with different solid-liquid ratios and concentration of combined filtrates), the active ingredients of each medicinal material in the composition are fully dissolved, the combination is reasonable and the activity is high, the drug utilization rate and stability are improved, and the hypoglycemic effect is effectively exerted.

[0042] (6) This invention combines single Chinese medicines such as cloves and cinnamon into a specific composition, clearly defining the functional division and synergistic relationship of each medicinal material. The bioavailability of the drug is high and the components are clearly defined. It not only retains the advantages of the overall regulation of traditional Chinese medicine, but also improves the stability and repeatability of the hypoglycemic treatment effect.

[0043] Furthermore, based on the present invention: Based on the comparison of Examples 1-3 and Comparative Examples 1-5, the present invention uses a combination of raw materials such as cloves (5-10 parts), cinnamon (10-20 parts), dandelion (20-30 parts), Japanese raisin tree fruit (20-30 parts), and small thistle (25-35 parts) in specific proportions to achieve a better new technical effect in lowering blood sugar. The combined technical effect is superior to the sum of the effects of each individual technical method. Attached Figure Description

[0044] Figure 1 The results of HE staining of mouse livers in each group in Example 1 are shown (Note: H&E, 40x, scale bar is 100 μm, n = 3). Figure 2 The results of H&E staining of the pancreas of mice in each group in Example 1 are shown (Note: H&E, 40x, scale bar is 100 μm, n = 3).

[0045] Among them, CON is the normal control group, MOD is the model group, MET is the positive group (metformin group), JTF-L is the low-dose group of Example 1, JTF-M is the medium-dose group of Example 1, and JTF-H is the high-dose group of Example 1. Detailed Implementation

[0046] The technical solution of the present invention will be further described below with reference to specific embodiments. All materials used in the following experiments are commercially available conventional raw materials.

[0047] Example 1 This embodiment provides a blood glucose-lowering composition and its preparation method.

[0048] The composition, by weight, comprises the following components: 6 parts cloves, 15 parts cinnamon, 25 parts dandelion, 20 parts Japanese raisin tree fruit, and 30 parts thistle.

[0049] The preparation method and steps are as follows: Weigh out cloves, cinnamon, dandelion, Japanese raisin tree seeds, and thistle, add water at a ratio of 1:10, soak for 45 minutes, heat under reflux for 1 hour, and filter while hot using gauze. Then add water again at a ratio of 1:8, heat under reflux for 1 hour, and filter while hot using gauze. Combine the two filtrates, concentrate, and obtain the medicinal liquid.

[0050] Example 2 This embodiment provides a blood glucose-lowering composition and its preparation method.

[0051] The composition, by weight, comprises the following components: 5 parts cloves, 20 parts cinnamon, 20 parts dandelion, 20 parts Japanese raisin tree fruit, and 25 parts thistle.

[0052] The preparation method and steps are as follows: Weigh out cloves, cinnamon, dandelion, Japanese raisin tree seeds, and thistle, add water at a ratio of 1:15, soak for 45 minutes, heat under reflux for 1.5 hours, and filter while hot using gauze. Then add water again at a ratio of 1:5, heat under reflux for 0.5 hours, and filter while hot using gauze. Combine the two filtrates, concentrate, and obtain the medicinal liquid.

[0053] Example 3 This embodiment provides a blood glucose-lowering composition and its preparation method.

[0054] The composition, by weight, comprises the following components: 10 parts cloves, 10 parts cinnamon, 30 parts dandelion, 30 parts Japanese raisin tree fruit, and 35 parts thistle.

[0055] The preparation method and steps are as follows: Weigh out cloves, cinnamon, dandelion, Japanese raisin tree seeds, and thistle, add water at a ratio of 1:10, soak for 45 minutes, heat under reflux for 1 hour, and filter while hot using gauze. Then add water again at a ratio of 1:8, heat under reflux for 1 hour, and filter while hot using gauze. Combine the two filtrates, concentrate, and obtain the medicinal liquid.

[0056] Comparative Example 1 The traditional Chinese medicine comprises the following components by weight: The difference between this comparative example and Example 1 is that the amount of the composition is different. Specifically, the mass ratio of cinnamon to thistle is 5:4, that is: 6 parts cloves, 25 parts cinnamon, 25 parts dandelion, 20 parts Japanese raisin tree fruit, and 20 parts thistle.

[0057] The preparation method is the same as in Example 1.

[0058] Comparative Example 2 The difference between this comparative example and Example 1 is that the amount of the composition is different. Specifically, the mass ratio of dandelion and Japanese raisin tree fruit is 7:3, that is: 6 parts clove, 15 parts cinnamon, 31.5 parts dandelion, 13.5 parts Japanese raisin tree fruit, and 30 parts thistle.

[0059] The preparation method is the same as in Example 1.

[0060] Comparative Example 3 The difference between this comparative example and Example 1 is that dandelion is replaced with honeysuckle and forsythia in a 1:1 mass ratio; otherwise, the preparation method is the same as in Example 1. Weigh out cloves, cinnamon, forsythia, honeysuckle, Japanese raisin tree fruit, and small thistle according to the formula, mix with water at a solid-liquid ratio of 1g:10mL, soak for 45 minutes, decoct, reflux for 1 hour, and filter while hot using gauze to obtain filtrate and residue; add water to the residue again at a solid-liquid ratio of 1g:8mL, reflux for 1 hour, and filter while hot using gauze; combine the two filtrates, concentrate, and obtain the traditional Chinese medicine composition. The preparation method is the same as in Example 1.

[0061] Comparative Example 4 The composition provided in this comparative example is the preferred embodiment of CN119633067A, and the components are as follows by weight: 3 parts cloves, 12 parts thistle, 10 parts gardenia, 10 parts peach kernel, 10 parts Japanese raisin tree fruit, 3 parts saffron, 10 parts dried tangerine peel, 15 parts kudzu root, and 10 parts dandelion.

[0062] The preparation method is as follows: Weigh out cloves, thistle, gardenia, peach kernel, Japanese raisin tree fruit, saffron, dried tangerine peel, kudzu root, and dandelion according to the formula. Mix with water at a solid-liquid ratio of 1g:10mL, soak for 45 minutes, decoct, reflux for 1 hour, and filter while hot using gauze to obtain filtrate and residue. Add water to the residue again at a solid-liquid ratio of 1g:8mL, reflux for 1 hour, and filter while hot using gauze. Combine the two filtrates, concentrate, and obtain the traditional Chinese medicine composition. The preparation method is the same as in Example 1.

[0063] Comparative Example 5 The only difference between this comparative example and Example 1 is that the jujube seed is replaced with kudzu root and poria cocos in a 1:1 mass ratio, and the small thistle is replaced with angelica root and peach kernel in a 1:1 mass ratio.

[0064] Study on the Hypoglycemic Effect in Animal Experiments Basic Pharmacodynamic Study on Hypoglycemic Effect of Drug Combination: Wherein, the dose setting: according to the latest conversion method of drug dose between humans and animals and the results of pre-experiment, the equivalent dose of the traditional Chinese medicine composition in mice corresponding to the daily dose of normal adults is taken as the medium dose, the low dose is designed by reducing the medium dose by 1 time, and the high dose is designed by increasing the medium dose by 1 time. Calculated by crude drug amount, the high, medium and low doses are 3.049 g / kg, 6.097 g / kg and 12.194 g / kg respectively; metformin suspension is 100 mg / kg. The administration volume for mice is 10 mL / kg.

[0065] Wherein, CON is the normal control group, MOD is the model group, MET is the positive control group (metformin group), JTF-L is the low-dose group of Example 1, JTF-M is the medium-dose group of Example 1, and JTF-H is the high-dose group of Example 1.

[0066] 1. Experimental Materials 1.1 Experimental Animals Adult C57 mice, male, SPF grade, weighing 22 g, were purchased from Zhuhai Baishitong Biological Technology Co., Ltd., with the experimental animal production license number SYXK (Guangdong) 2020-0125. After 7 days of adaptive feeding, they entered the experimental period.

[0067] 1.2 Experimental Drugs Blank control: normal saline Positive control: Metformin Hydrochloride Tablets, provided by Merck KGaA, batch number 1423108A2.

[0068] 1.3 Experimental Reagents

[0069] 1.4 Experimental Instruments

[0070] 2. Experimental Methods 2.1 Animal grouping: after 7 days of adaptive feeding, SPF adult male C57 mice were randomly divided into 2 groups: the normal control group (12 mice), which was given conventional maintenance diet during the experiment, and the experimental group (96 mice), which was given high-fat (60%) diet.

[0071] 2.2 Modeling Method After feeding the experimental group a high-fat diet for 6 weeks, the mice were brought to a weight of approximately 30 g. For 5 consecutive days, the mice were intraperitoneally injected with STZ (50 mg / kg) to mildly damage pancreatic β-cells, causing insufficient insulin secretion and elevated blood glucose levels, thus inducing hyperglycemia. 72 hours after STZ injection, fasting blood glucose (FBG) was measured at a level ≥ 11.1 mmol / L and < 20.0 mmol / L, indicating successful model establishment.

[0072] Animal grouping and administration: Rats with successful model establishment were divided into 12 groups: model group, positive group, low-dose group of Example 1, high-dose group of Example 1, medium-dose group of Example 1, group 2, group 3, and comparative examples 1-5, with 8 rats in each group. Administration began the day after successful model establishment. The normal control group and model group were given distilled water. Based on the amount of raw drug, the low, medium, and high-dose groups of Example 1 were given 3.049 g / kg, 6.097 g / kg, and 12.194 g / kg of the traditional Chinese medicine composition prepared in Example 1, respectively. Examples 2-3 and comparative examples 1-5 were given 6.097 g of raw drug / kg of the corresponding traditional Chinese medicine composition. The positive group was given metformin suspension 100 mg / kg. The dosage for mice was 10 mL / kg. Administration continued for 6 weeks.

[0073] 2.3 Measurement of glucose metabolism indicators All mice were fasted for 12 hours prior to sampling, but allowed free access to water. Blood was then collected from the orbital cavity after anesthesia. After standing for 30 minutes, the blood was centrifuged at 3500 rpm, 4°C, for 15 minutes. The supernatant was used to detect glucose metabolism parameters. Fasting serum glucose (GLU) was detected using the glucose oxidase method. Fasting serum insulin (INS) was measured using a mouse insulin ELISA kit. The HOMA-IR index was calculated using the formula HOMA-IR = GLU (mmol / L) × INS (μIU / mL) / 22.5. Glycated serum protein (GSP) was measured using a (NBT colorimetric method) kit. All assays were performed strictly according to the manufacturer's instructions, and absorbance readings were used to calculate concentrations based on the standard curve.

[0074] 2.4 Oral glucose tolerance test The mice to be tested were fasted (for 12 hours) overnight at 8 PM the night before sampling. Drinking water was ensured for all mice. The weight of all mice was measured by 8 AM the following day, and the weight of each mouse was recorded to within 0.1 g. An oral glucose tolerance test (OGTT) intervention was performed at an oral dose of 10 μL / g body weight, prepared according to the animal's body weight at a standard dose of 2 g glucose / kg. Sampling time points included the baseline time point (0 min) before glucose solution injection and six time points at 15, 30, 60, 90, and 120 min after injection. Blood was collected by cutting the tail with sterilized scissors, and the first drop of blood was wiped away with clean absorbent paper. Blood glucose levels were measured using a blood glucose meter and blood glucose test strips, and the blood glucose concentration value of each mouse at each time point was systematically recorded. A time-blood glucose curve was plotted, and the area under the curve (AUC) of the OGTT was calculated.

[0075] 2.5 Insulin Tolerance Testing Insulin tolerance test (ITT) determination: One week prior to sampling, all mice were fasted overnight for 12 hours (with unlimited water). Blood was then collected from the tail of each mouse to measure basal blood glucose levels. First, sterilized scissors were used, then approximately 1 mm of the tail was gently cut off. The first drop of blood was wiped away with a clean cotton ball, and blood glucose was measured using a glucometer; this was the 0-minute blood glucose level. Subsequently, mice were intraperitoneally injected with an insulin solution of 0.75 IU / kg body weight. Following the same procedure, blood glucose levels were measured at 15 min, 30 min, 60 min, 90 min, and 120 min. AUC was calculated based on the measurement results.

[0076] 2.7 Organ Coefficient All mice were fasted but allowed free access to water the night before weekly sampling at 9 PM. After 12 hours of fasting, blood samples were collected, and the liver and pancreas were weighed and recorded. The surface blood was quickly rinsed off with PBS, and the surface liquid was gently blotted dry with absorbent paper. The wet weight of the organs was then measured using an electronic balance. The organ coefficient was calculated using the formula: Organ coefficient (%) = Wet weight of organ (g) / Body weight at sacrifice (g) × 100.

[0077] 2.8 HE staining of liver and pancreas A. Fixation: Place the sample in 5–10 times its volume of fixative and fix at room temperature for ≥ 24 h, gently shaking to prevent adhesion to the walls. B. Dehydration: Treat sequentially with 75%→85%→90%→95%→100% alcohol, benzene, xylene, and paraffin (adjusting time according to tissue condition).

[0078] C. Embedding and trimming: Embed the wax block according to the cut surface or requirements, and trim away any excess parts of the wax block at the edges.

[0079] D. Dewaxing: After treatment with xylene I and II, the sections are rehydrated with anhydrous ethanol I and II in sequence, and then rinsed with running water. E. Staining and dehydration: After HE staining, the sections are treated with a gradient of different concentrations of ethanol, n-butanol and xylene.

[0080] F. Sealing: After drying, seal the film with neutral resin.

[0081] G. Radiography: Bright-field observation was performed under an Olympus microscope.

[0082] 3. Experimental Results 3.1 Glucose metabolism indicators Table 1. Effects of this invention on glucose metabolism parameters in HF-STZ-induced hyperglycemic mice.

[0083] Note: Compared with the CON group, ****P<0.0001, ***P<0.001, **P<0.01, *P<0.05; compared with the MOD group, ###P<0.001, ##P<0.01, #P<0.05; compared with Example 1 group, &&P<0.01, &P<0.05.

[0084] As shown in Table 1, after high-fat combined with STZ induction, the levels of GLU, INS, and GSP in the model group mice were significantly increased, indicating a successful hyperglycemia model. Compared with the MOD group, the GLU level in groups 1-3 was significantly reduced after JTF intervention. Except for the Example 1-JTF-L group, the levels of INS and GSP in the positive control group and other groups in Examples 1-3 were significantly reduced. These results suggest that the example groups can effectively reduce serum blood glucose, glycated serum protein, and insulin levels, thereby achieving hypoglycemia and demonstrating a good effect in improving glucose disorders.

[0085] 3.2 Oral glucose tolerance and insulin tolerance, insulin resistance index Table 2. Effects of each group on OGTT, ITT, and HOMA-IR in HF-STZ-induced hyperglycemic mice.

[0086] Note: Compared with the CON group, the model group showed ***P<0.001; compared with the MOD group, each example group showed ###P<0.001, ##P<0.01, #P<0.05; compared with Example 1 group, each comparative example group showed &&P<0.01, &P<0.05.

[0087] As shown in Table 2, after high-fat combined with STZ induction, the AUT-OGTT, AUC-ITT, and HOMA-IR levels in the MOD group mice were significantly higher than those in the CON group, indicating abnormal glucose tolerance, insulin tolerance, and insulin resistance. Compared with the MOD group, the AUT-OGTT level was significantly reduced in the positive drug group, the JTF-M group in Example 1, and Example 2. The AUC-ITT and HOMA-IR coefficients of the positive drug group and the Example 1-3 groups were significantly decreased. These results indicate that JTF can reduce glucose tolerance and insulin tolerance levels and alleviate insulin resistance, thereby promoting normal insulin secretion and achieving blood glucose reduction. The above results, combined with the results in Table 1, indicate that the example groups can effectively regulate glucose metabolism disorders and correct hyperglycemia.

[0088] 3.3 Liver and pancreas organ coefficients Table 3 Effects of each group on organ coefficients in HF-STZ-induced hyperglycemic mice

[0089] Note: Compared with the CON group, ***P<0.001, **P<0.01, *P<0.05; compared with the MOD group, #P<0.05; compared with the Example 1 group, &P<0.05.

[0090] As shown in Table 3, after high-fat combined with STZ induction, the liver weight and coefficient of the MOD group mice in the model group increased significantly, possibly indicating liver damage, while the pancreas weight and pancreatic organ coefficient decreased significantly, indicating that STZ induced pancreatic islet tissue damage. After JTF intervention, the liver coefficients of the positive drug, Example 1 JTF-M, and Example 2 JTF-M groups decreased significantly. The pancreatic weight of the positive drug and Example 1 JTF-M groups recovered, and the pancreatic coefficients of Example 1 JTF-L, Example 1 JTF-M, and Example 2 JTF-M also recovered, with an increase in pancreatic weight. The Example 1-2 groups effectively inhibited the trend of pancreatic weight reduction, indicating that the Example groups have a protective effect on the liver, can reduce pancreatic tissue damage, and protect pancreatic islet function.

[0091] 3.4 Liver and pancreas - HE staining Figure 1The results of liver H&E staining in Example 1 were presented. In the CON group, the liver tissue structure was clear and normal, hepatocytes were neatly arranged, hepatocyte cytoplasm was abundant, and there were no obvious lesions. In the MOD group, hepatocytes showed diffuse swelling, accompanied by typical hydropic degeneration, pale cytoplasm, and loose structure. Some hepatocytes underwent nuclear dissolution and disappearance, forming scattered punctate and patchy necrotic foci. Scattered inflammatory cell infiltration was visible around the necrotic foci, indicating pathological changes in the liver. In the MET group, the liver lobule structure was restored to some extent, hepatocytes were relatively neatly arranged, cell nuclei were normal and neatly arranged, hepatocyte morphology was regular, cytoplasm was abundant, and the sinusoidal structure was intact. In the JTF-M group, the overall liver lobule structure was not significantly disordered, only slight hepatocyte swelling was observed, accompanied by loose and pale cytoplasm, cell boundaries were still clear, there were no typical hydropic degeneration, several necrotic areas with nucleus disappearance were visible, there was no obvious inflammatory cell infiltration, effectively improved liver damage, and had a protective effect on hepatocytes. Figure 1 .

[0092] Figure 2 The H&E staining results of the pancreas in each group of Example 1 were presented. The CON group showed a compact pancreatic tissue structure, normal islet morphology, abundant cytoplasm, and neatly arranged, evenly distributed cells within the islets. The MOD group showed destruction and disorder of the exocrine acinar structure, swollen acinar cells, and damage to the endocrine islet structure. Islet cells exhibited necrotic changes such as nuclear pyknosis and karyolysis, accompanied by inflammatory cell infiltration. The pancreatic tissue showed typical pathological changes of inflammation-mediated damage. The MET group showed a dense and regular pancreatic tissue structure, neatly arranged and structurally intact acinar cells, normal islet morphology, abundant cytoplasm, and evenly arranged, moderately sized, and evenly distributed cells within the islets. There was no acinar destruction, fibrosis, or inflammatory cell infiltration. In the JTF-M group, the morphology of acinar cells in the exocrine part of the pancreas was basically normal, and the integrity of the acinar structure was still acceptable. Damage to the islet tissue in the endocrine part was significantly improved compared to the model group, with marked improvement in islet cell lesions. Cell morphology became more regular, cell volume increased, and the number of cells within the islets increased, although swelling still existed. This approach can effectively partially repair pancreatic tissue damage, promote the recovery of islet cell morphology and number, and is beneficial for improving islet function. Figure 2 .

[0093] In summary, the interaction of the traditional Chinese medicine composition provided by this invention has a positive effect on lowering blood sugar levels.

[0094] This article uses specific examples to illustrate the inventive concept in detail. The description of the above embodiments is only for the purpose of helping to understand the core idea of ​​the present invention. It should be noted that any obvious modifications, equivalent substitutions or other improvements made by those skilled in the art without departing from the inventive concept should be included within the protection scope of the present invention.

Claims

1. A hypoglycemic composition, characterized in that, The ingredients include cloves, cinnamon, dandelion, Japanese raisin tree seeds, and thistle.

2. The hypoglycemic composition according to claim 1, characterized in that, By weight, it includes the following ingredients: 5-10 parts cloves, 10-20 parts cinnamon, 20-30 parts dandelion, 20-30 parts Japanese raisin tree fruit, and 25-35 parts thistle.

3. The hypoglycemic composition according to claim 1, characterized in that, By weight, it includes the following ingredients: 5-6 parts cloves, 15-20 parts cinnamon, 20-25 parts dandelion, 18-22 parts Japanese raisin tree fruit, and 25-30 parts thistle.

4. The hypoglycemic composition according to any one of claims 1-3, characterized in that, The mass ratio of cinnamon to thistle is 1:1-4.

5. The hypoglycemic composition according to any one of claims 1-3, characterized in that, The mass ratio of dandelion to Japanese raisin tree seeds is 1-1.5:1 by weight.

6. The hypoglycemic composition according to claim 1, characterized in that, The ingredients, by weight, are as follows: 6 parts cloves, 15 parts cinnamon, 25 parts dandelion, 20 parts Japanese raisin tree seeds, and 30 parts thistle. Alternatively, 5 parts cloves, 20 parts cinnamon, 20 parts dandelion, 20 parts Japanese raisin tree fruit, and 25 parts thistle; Alternatively, use 10 parts cloves, 10 parts cinnamon, 30 parts dandelion, 30 parts Japanese raisin tree fruit, and 35 parts thistle.

7. A method for preparing the hypoglycemic composition according to any one of claims 1-6, characterized in that, Includes the following steps: Mix cloves, cinnamon, dandelion, Japanese raisin tree fruit, and thistle, extract with solvent, filter, and concentrate to obtain the final product.

8. The preparation method according to claim 7, characterized in that, The extraction is performed by decoction or reflux extraction, and / or the solvent is water, methanol or ethanol, and / or the amount of solvent used is 5-15 times the total mass of clove, cinnamon, dandelion, Japanese raisin tree seed and thistle, and / or the number of extractions is 1-3, and / or the extraction time for each extraction is 0.5-2 hours; and / or the product is dried after concentration.

9. A pharmaceutical preparation, characterized in that, The composition comprises the hypoglycemic composition according to any one of claims 1-6 or the hypoglycemic composition prepared by the preparation method according to any one of claims 7-9, and pharmaceutically acceptable excipients.

10. The use of a hypoglycemic composition according to any one of claims 1-6, or a hypoglycemic composition prepared by any one of claims 7-9, or a pharmaceutical preparation according to claim 9, in the preparation of a medicament for treating, preventing or adjuvantly treating hyperglycemia, regulating glucose metabolism or lowering blood sugar while protecting the liver and reducing pancreatic tissue damage.

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