Traditional Chinese medicine polygonatum sibiricum composition for treating diabetes mellitus with syndrome of dampness-heat obstructing spleen

Abstract

The invention discloses a traditional Chinese medicine polygonatum sibiricum composition for treating diabetes mellitus with syndrome of dampness-heat obstructing spleen. The traditional Chinese medicine decoction piece is prepared by extracting the following traditional Chinese medicine decoction pieces in parts by weight: 20-30 parts of herba eupatorii, 10-20 parts of fructus amomi, 30-50 parts of rhizoma polygonati, 15-25 parts of radix fici simplicissimae, 10-20 parts of rhodiola rosea, 20-30 parts of codonopsis pilosula, 10-20 parts of radix isatidis, 12-18 parts of dandelion, 10-20 parts of lophatherum gracile, 20-30 parts of fructus broussonetiae, 8-12 parts of flatstem milkvetch seed, 15-25 parts of eclipta, 10-20 parts of dogwood, 20-30 parts of salvia miltiorrhiza, 8-12 parts of campsis grandiflora and 10-20 parts of radix aucklandiae. The invention also discloses a preparation method and application thereof.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a traditional Chinese medicine Huangjing composition for treating diabetes mellitus with damp-heat syndrome and its preparation method. Background Technology

[0002] Diabetes mellitus is a chronic disease characterized by hyperglycemia, caused by absolute or relative insulin deficiency and impaired insulin utilization. It is mainly classified into three types: type 1, type 2, and gestational diabetes. The etiology is primarily attributed to the combined effects of genetic and environmental factors, including decreased insulin secretion due to pancreatic islet cell dysfunction, or insensitivity to insulin, or both, resulting in the ineffective utilization and storage of glucose in the blood. Some diabetic patients and their families exhibit disease clustering. Furthermore, the incidence and prevalence of diabetes are on the rise globally. The main symptoms of diabetes are the "three highs and one low": polydipsia (excessive thirst), polyuria (excessive urination), polyphagia (excessive hunger), and weight loss. In addition, long-term patients may experience chronic progressive lesions, functional decline, or even failure of organs such as the eyes, kidneys, nerves, heart, and blood vessels, and may develop acute severe metabolic disorders. The main treatment for diabetes is to maintain blood glucose levels within the normal range through scientific and rational treatment methods, prevent the occurrence of acute metabolic disorders, prevent or delay the occurrence and development of complications, and improve quality of life. The prognosis depends on disease control and the presence or absence of complications. Prevention of diabetes mainly relies on a healthy lifestyle, including a balanced diet, moderate exercise, maintaining a normal weight, and regular check-ups. In traditional Chinese medicine, diabetes falls under the category of "Xiao Ke Zheng" (wasting and thirsting syndrome), which is believed to be related to Yin deficiency and dryness-heat, as well as dysfunction of the internal organs. Treatment emphasizes holistic conditioning and syndrome differentiation. Summary of the Invention

[0003] This invention aims to provide a traditional Chinese medicine composition of Polygonatum sibiricum for treating diabetes mellitus caused by damp-heat in the spleen, and its preparation method.

[0004] A traditional Chinese medicine composition for treating diabetes mellitus due to damp-heat in the spleen is prepared by extracting the following parts by weight of traditional Chinese medicine decoction pieces: 20-30 parts of Eupatorium fortunei, 10-20 parts of Amomum villosum, 30-50 parts of Polygonatum sibiricum, 15-25 parts of Ficus hirta, 10-20 parts of Rhodiola rosea, 20-30 parts of Codonopsis pilosula, 10-20 parts of Isatis indigotica, 12-18 parts of Taraxacum mongolicum, 10-20 parts of Lophatherum gracile, 20-30 parts of Broussonetia papyrifera, 8-12 parts of Astragalus complanatus, 15-25 parts of Eclipta prostrata, 10-20 parts of Cornus officinalis, 20-30 parts of Salvia miltiorrhiza, 8-12 parts of Campsis grandiflora, and 10-20 parts of Aucklandia lappa.

[0005] The traditional Chinese medicine Huangjing composition for treating diabetes mellitus due to damp-heat in the spleen is prepared by extracting the following parts by weight of traditional Chinese medicine decoction pieces: 25 parts of Peilan, 15 parts of Amomum villosum, 40 parts of Huangjing, 20 parts of Ficus hirta, 15 parts of Rhodiola rosea, 25 parts of Codonopsis pilosula, 15 parts of Isatis indigotica, 15 parts of Taraxacum mongolicum, 15 parts of Lophatherum gracile, 25 parts of Broussonetia papyrifera, 10 parts of Astragalus complanatus, 20 parts of Eclipta prostrata, 15 parts of Cornus officinalis, 25 parts of Salvia miltiorrhiza, 10 parts of Campsis grandiflora, and 15 parts of Aucklandia lappa.

[0006] The traditional Chinese medicine Huangjing composition for treating diabetes mellitus due to damp-heat in the spleen is prepared by extracting the following parts by weight of traditional Chinese medicine decoction pieces: 20 parts of Peilan, 20 parts of Amomum villosum, 30 parts of Huangjing, 25 parts of Maotao, 10 parts of Rhodiola rosea, 30 parts of Codonopsis pilosula, 10 parts of Isatis indigotica, 18 parts of Taraxacum mongolicum, 10 parts of Lophatherum gracile, 30 parts of Broussonetia papyrifera, 8 parts of Astragalus complanatus, 25 parts of Eclipta prostrata, 10 parts of Cornus officinalis, 30 parts of Salvia miltiorrhiza, 8 parts of Campsis grandiflora, and 20 parts of Aucklandia lappa.

[0007] The traditional Chinese medicine Huangjing composition for treating diabetes mellitus due to damp-heat in the spleen is prepared by extracting the following parts by weight of traditional Chinese medicine decoction pieces: 30 parts of Peilan, 10 parts of Amomum villosum, 50 parts of Huangjing, 15 parts of Maotao, 20 parts of Rhodiola rosea, 20 parts of Codonopsis pilosula, 20 parts of Isatis indigotica, 12 parts of Taraxacum mongolicum, 20 parts of Lophatherum gracile, 20 parts of Broussonetia papyrifera, 12 parts of Astragalus complanatus, 15 parts of Eclipta prostrata, 20 parts of Cornus officinalis, 20 parts of Salvia miltiorrhiza, 12 parts of Campsis grandiflora, and 10 parts of Aucklandia lappa.

[0008] The preparation method of the Polygonatum sibiricum composition for treating diabetes mellitus due to damp-heat in the spleen includes the following steps:

[0009] S1. Supercritical fluid extraction of Eupatorium fortunei, Amomum villosum, and Salvia miltiorrhiza: Eupatorium fortunei, Amomum villosum, and Salvia miltiorrhiza were washed, dried, and pulverized to obtain powders of Eupatorium fortunei, Amomum villosum, and Salvia miltiorrhiza. These powders were mixed and subjected to supercritical fluid extraction, using ethanol as an entrainer. The ethanol was recovered to obtain oils of Eupatorium fortunei, Amomum villosum, and Salvia miltiorrhiza. The solid residue was dried and retained. The supercritical fluid extraction conditions were: extraction pressure: 25-30 MPa, extraction temperature: 32-40℃, CO2 flow rate: 7-12 L / h, extraction time: 2-3 h, and the amount of entrainer added was 2.5-4 wt%.

[0010] S2. Water extraction: Wash, dry, and pulverize the remaining Chinese herbal medicine pieces, mix them evenly with the solid residue from step S1 to obtain Chinese herbal medicine powder, add water and heat to boiling to extract for 2-4 hours. The solid-liquid ratio of the Chinese herbal medicine powder to water is 1:7-10 g / mL. Filter, dry the filter residue and keep it for use, and dry the filtrate to obtain the water extract.

[0011] S3. Alcohol extraction: Add the filter residue from step S2 to a 60-70 wt% ethanol aqueous solution, wherein the solid-liquid ratio of the filter residue to the ethanol aqueous solution is 1:3-5 g / mL, heat to 50-70℃, extract for 1-3 h, filter, dry and retain the filter residue, recover the ethanol from the filtrate, dry, and obtain the alcohol extract.

[0012] S4. Add excipients to the water extract obtained in S2 and the alcohol extract obtained in S3, and spray in the oils of Eupatorium fortunei, Amomum villosum and Salvia miltiorrhiza obtained in S1 to prepare an oral solid dosage form.

[0013] The preparation method of the traditional Chinese medicine Huangjing composition for treating diabetes mellitus due to damp-heat in the spleen includes step S4, in which the oral solid dosage form is one of granules, tablets, or syrup.

[0014] The application of the Chinese herbal medicine Huangjing composition for treating diabetes mellitus due to damp-heat in the preparation of a drug for treating diabetes mellitus due to damp-heat in the spleen.

[0015] According to the guiding principles for clinical research of new traditional Chinese medicine drugs, diabetes is a multifactorial metabolic disease characterized by chronic hyperglycemia, accompanied by disorders of glucose, fat, and protein metabolism caused by defects in insulin secretion and / or action. This disease falls under the category of "Xiao Ke Bing" (wasting and thirsting disease) in traditional Chinese medicine. It is divided into:

[0016] I. Yin Deficiency with Excessive Heat Syndrome: Main symptoms: Dry throat and mouth, irritability and aversion to heat. Secondary symptoms: Thirst with preference for cold drinks, increased appetite and easy hunger, dark urine and constipation. Tongue and pulse: Red tongue with yellow coating, thready, slippery and rapid pulse, or thready, wiry and rapid pulse.

[0017] II. Damp-Heat Trapping the Spleen Syndrome: Main symptoms: Distension in the chest, epigastrium, and abdomen, or fullness after meals, and heaviness in the head and body. Secondary symptoms: Obesity, chest tightness and irritability, fatigue in the limbs, dark yellow urine, and incomplete bowel movements. Tongue and pulse: Red tongue with a yellow and greasy coating, and a slippery and rapid pulse.

[0018] III. Qi and Yin Deficiency Syndrome: Main symptoms: Dry throat and mouth, fatigue and weakness. Secondary symptoms: Increased appetite and hunger, thirst and preference for drinking, shortness of breath and reluctance to speak, hot flashes in the palms, soles, and chest, palpitations, insomnia, dark urine, and constipation. Tongue and pulse: Red tongue with little saliva, thin or patchy coating, thready, rapid, and weak pulse, or thready and wiry pulse.

[0019] IV. Yin-Yang Deficiency, Blood Stasis and Water Retention Syndrome: Main symptoms: fatigue, dry throat and mouth, soreness and coldness in the lower back and knees, or cold hands and feet, frequent urination at night. Secondary symptoms: dizziness, palpitations, insomnia, spontaneous sweating, susceptibility to illness, shortness of breath, reluctance to speak, facial and limb edema, frequent urination with cloudy urine or scanty urine, impotence in men, decreased libido in women, and irregular bowel movements (dry or loose). Tongue and pulse: enlarged tongue with teeth marks, deep, thready, and weak pulse.

[0020] V. Blood Stasis in the Meridians Syndrome: Main symptoms: Chest pain, rib pain, lower back pain, back pain, fixed location, or stabbing pain; numbness of limbs; pain worsens at night. Secondary symptoms: Rough and scaly skin; dark purple lips; facial ecchymosis; forgetfulness; palpitations; irritability; insomnia. Tongue and pulse: Dark tongue with ecchymosis; bluish-purple and tortuous sublingual veins; wiry pulse, or deep and hesitant pulse.

[0021] Among these, damp-heat trapping the spleen syndrome is the most common. The causes include: 1. Dietary factors: Long-term overconsumption of rich, fatty, spicy, and greasy foods damages the spleen and stomach, leading to water retention, which over time transforms into heat, resulting in internal damp-heat. 2. Constitutional factors: Individuals with a weak spleen constitution have poor water metabolism, making them prone to dampness accumulation. If they are exposed to external heat or experience emotional distress that transforms into fire, damp-heat is easily formed. 3. Environmental factors: Long-term exposure to a humid and hot environment allows external dampness to invade and combine with internal dampness, exacerbating damp-heat symptoms. Main symptoms: Chest and abdominal distension, or fullness after meals, and heaviness in the head and body. Secondary symptoms: Obesity, chest tightness and irritability, fatigue in the limbs, dark yellow urine, and incomplete bowel movements. Tongue and pulse: Red tongue with a yellow, greasy coating, and a slippery and rapid pulse.

[0022] The *Neijing* (Inner Canon of Medicine) refers to diabetes as "xiaodan," believing that factors such as excessive consumption of rich and sweet foods, emotional imbalance, and weakness of the five internal organs are closely related to the occurrence of diabetes. For example, the *Suwen* (Plain Questions) chapter on "Strange Diseases" states: "This person must frequently eat sweet and fatty foods. Fat causes internal heat, and sweet foods cause fullness in the middle, so the qi overflows upwards, turning into diabetes." The *Lingshu* (Spiritual Pivot) chapter on "Five Changes" states: "Anger causes qi to rise upwards, accumulating in the chest, blood and qi stagnate, the skin of the hips becomes swollen, blood vessels do not circulate, turning into heat. Heat then consumes the skin, hence xiaodan." The *Suwen* chapter on "Strange Diseases" proposes the treatment of "spleen xiaodan" as "treating it with orchids to remove stagnant qi." Therefore, this invention adopts the treatment principle of drying dampness and invigorating the spleen. This invention uses *Eupatorium fortunei* (peppermint) combined with *Amomum villosum* (amomum fruit) as the principal herbs: *Eupatorium fortunei* has a fragrant aroma, clears the lungs, invigorates the stomach, and resolves dampness and soothes the spleen; *Amomum villosum* has a strong, turbid aroma, regulates qi, relieves chest congestion, resolves dampness, and stops vomiting. The combination of these two herbs has the effects of aromatically resolving dampness, invigorating the spleen, invigorating the stomach, and relieving nausea and vomiting. It is suitable for symptoms such as dampness obstructing qi, nausea and loss of appetite, abdominal distension, and greasy tongue coating.

[0023] The pathogenesis of diabetes mellitus (Xiao Ke) primarily lies in the deficiency of Yin fluids and the predominance of dryness and heat. Yin deficiency is the root cause, while dryness and heat are the manifestation; the more deficient the Yin, the more intense the dryness and heat, and vice versa. Further development of diabetes mellitus can deplete the Qi of the spleen and kidneys, leading to both Qi and Yin deficiency. Over time, it can also damage the Yang of the spleen and kidneys, resulting in both Yin and Yang deficiency. The lungs govern Qi and are the upper source of water, distributing body fluids. When the lungs are damaged by dryness and heat, they cannot distribute body fluids and instead allow them to flow downwards, being excreted through urination, hence frequent and copious urination. The inability of the lungs to distribute fluids also leads to thirst and excessive drinking. The *Compendium of Medicine* states, "The lungs govern Qi. When the lungs are healthy, Qi can control and retain the essence of body fluids, nourishing the muscles, bones, and blood vessels; the remainder is urination. When the lungs are diseased, body fluids are not controlled by the Qi, and the essence is also excreted through urination, hence the excessive drinking." This illustrates the connection between the lungs and the pathogenesis of diabetes mellitus.

[0024] Traditional Chinese medicine theory also points out that heat accumulation in the stomach and intestines, and depletion of body fluids, are the main mechanisms of diabetes mellitus. For example, the *Suwen* (Plain Questions) chapter "On the Differentiation of Yin and Yang" states, "The accumulation of two yang energies is called diabetes mellitus." The book clearly records the main symptoms of diabetes mellitus, such as excessive drinking, excessive eating, excessive urination, and emaciation. The *Suwen* chapter "On Qi Collapse" states, "Those with lung diabetes mellitus drink one sip and urinate two sips," and "The large intestine transfers heat to the stomach, causing a good appetite but a thin physique." The *Lingshu* (Spiritual Pivot) chapter "On the Transmission of the Master" states, "When there is stagnation in the stomach, food is consumed, causing anxiety and hunger." In terms of treatment, it is emphasized that patients with diabetes mellitus should avoid rich, greasy foods and hot, drying, and heat-depleting substances such as herbs and mineral medicines. Therefore, this invention heavily utilizes Polygonatum sibiricum, adopting the treatment principle of strengthening the spleen and replenishing qi, clearing heat and generating body fluids to quench thirst, and selecting Polygonatum sibiricum, Ficus hirta, Rhodiola rosea, Codonopsis pilosula, Isatis indigotica, Taraxacum mongolicum, and Lophatherum gracile as assistant herbs.

[0025] Although the pathogenesis of diabetes is related to all five internal organs, it is mainly affected by the lungs, spleen (stomach), and kidneys, with the kidneys being the most severely affected. The *Ling Shu* (Spiritual Pivot) states, "Those whose five internal organs are all weak are prone to diabetes." Insufficient congenital endowment and weakness of the five internal organs, especially a deficiency in the kidneys, are related to the occurrence of this disease. This is because the five internal organs are responsible for storing essence, which is the foundation of life. The kidneys receive and store the essence from the five internal organs and six bowels. If the five internal organs are weak, there will be insufficient essence and qi, and weakness of qi and blood. The kidneys will also have no essence to store. Furthermore, due to improper regulation, the essence and fluids will eventually be depleted, leading to diabetes. The *Ling Shu* (Spiritual Pivot), in its chapter "Ben Zang" (Original Organs), states: "A weak heart is prone to wasting diseases and internal heat," "A weak lung is prone to wasting diseases and easily injured," "A weak liver is prone to wasting diseases and easily injured," "A weak spleen is prone to wasting diseases and easily injured," and "A weak kidney is prone to wasting diseases and easily injured." The *Yi Guan* (Medical Compendium), in its chapter "Xiao Ke Lun" (Treatise on Diabetes), states: "When a person's water and fire are in balance, and their qi and blood are nourished, what wasting disease could there be?" This invention adopts the treatment principle of nourishing the liver and kidneys, replenishing essence and blood, and selects *Broussonetia papyrifera* fruit, *Astragalus complanatus* seed, *Eclipta prostrata*, and *Cornus officinalis* fruit as adjuvant herbs.

[0026] Blood stasis is a common pathological factor in the development of diabetes mellitus. Prolonged diabetes mellitus can affect the five internal organs, leading to various diseases. Therefore, Danshen (Salvia miltiorrhiza) and Lingxiaohua (Campsis grandiflora) are used as guiding herbs to invigorate blood circulation and remove blood stasis, while Muxiang (Saussurea costus) promotes qi circulation and relieves stagnation.

[0027] The entire formula consists of Eupatorium fortunei, Amomum villosum, Polygonatum sibiricum, Ficus hirta, Rhodiola rosea, Codonopsis pilosula, Isatis indigotica, Taraxacum mongolicum, Lophatherum gracile, Broussonetia papyrifera, Astragalus complanatus, Eclipta prostrata, Cornus officinalis, Salvia miltiorrhiza, Campsis grandiflora, and Aucklandia lappa. It can dry dampness and invigorate the spleen, strengthen the spleen and replenish qi, clear heat and promote body fluid production and quench thirst, nourish the liver and kidneys, replenish essence and blood, promote blood circulation and remove blood stasis, and regulate qi and relieve stagnation. It is used to treat diabetes mellitus with damp-heat trapping the spleen. Attached Figure Description

[0028] Figure 1 The effect of this invention on blood glucose in type 2 diabetic rats (mmol·L) -1 ). Detailed Implementation

[0029] Example 1: Take 250g of Eupatorium fortunei, 150g of Amomum villosum, 400g of Polygonatum sibiricum, 200g of Ficus hirta, 150g of Rhodiola rosea, 250g of Codonopsis pilosula, 150g of Isatis indigotica, 150g of Taraxacum mongolicum, 150g of Lophatherum gracile, 250g of Broussonetia papyrifera, 100g of Astragalus complanatus, 200g of Eclipta prostrata, 150g of Cornus officinalis, 250g of Salvia miltiorrhiza, 100g of Campsis grandiflora, and 150g of Aucklandia lappa. The preparation method includes the following steps:

[0030] S1. Supercritical fluid extraction of Eupatorium fortunei, Amomum villosum, and Salvia miltiorrhiza: Eupatorium fortunei, Amomum villosum, and Salvia miltiorrhiza were washed, dried, and pulverized to obtain powders of Eupatorium fortunei, Amomum villosum, and Salvia miltiorrhiza. These powders were mixed and subjected to supercritical fluid extraction, using ethanol as an entrainer. The ethanol was recovered to obtain oils of Eupatorium fortunei, Amomum villosum, and Salvia miltiorrhiza. The solid residue was dried and retained. The supercritical fluid extraction conditions were: extraction pressure: 28 MPa, extraction temperature: 36℃, CO2 flow rate: 10 L / h, extraction time: 2.5 h, and the amount of entrainer added was 3 wt%.

[0031] S2. Water extraction: Wash, dry, and pulverize the remaining Chinese herbal medicine pieces, mix them evenly with the solid residue from step S1 to obtain Chinese herbal medicine powder, add water and heat to boiling for 3 hours to extract. The solid-liquid ratio of the Chinese herbal medicine powder to water is 1:7 g / mL. Filter, dry the filter residue and keep it for use, and dry the filtrate to obtain the water extract.

[0032] S3. Alcohol extraction: Add the filter residue from step S2 to a 65wt% ethanol aqueous solution, wherein the solid-liquid ratio of the filter residue to the ethanol aqueous solution is 1:4 g / mL, heat to 60℃, extract for 2 hours, filter, dry and retain the filter residue, recover the ethanol from the filtrate, dry, and obtain the alcohol extract.

[0033] S4. Add excipients to the water extract obtained from S2 and the alcohol extract obtained from S3, spray in the oils of Eupatorium fortunei, Amomum villosum, and Salvia miltiorrhiza obtained from S1, add starch, and prepare granules.

[0034] Example 2: Take 200g of Eupatorium fortunei, 200g of Amomum villosum, 300g of Polygonatum sibiricum, 250g of Ficus hirta, 100g of Rhodiola rosea, 300g of Codonopsis pilosula, 100g of Isatis indigotica, 180g of Taraxacum mongolicum, 100g of Lophatherum gracile, 300g of Broussonetia papyrifera, 80g of Astragalus complanatus, 250g of Eclipta prostrata, 100g of Cornus officinalis, 300g of Salvia miltiorrhiza, 80g of Campsis grandiflora, and 200g of Aucklandia lappa. The preparation method includes the following steps:

[0035] S1. Supercritical fluid extraction of Eupatorium fortunei, Amomum villosum, and Salvia miltiorrhiza: Eupatorium fortunei, Amomum villosum, and Salvia miltiorrhiza were washed, dried, and pulverized to obtain powders of Eupatorium fortunei, Amomum villosum, and Salvia miltiorrhiza. These powders were mixed and subjected to supercritical fluid extraction, using ethanol as an entrainer. The ethanol was recovered to obtain oils of Eupatorium fortunei, Amomum villosum, and Salvia miltiorrhiza. The solid residue was dried and retained. The supercritical fluid extraction conditions were: extraction pressure: 25 MPa, extraction temperature: 40℃, CO2 flow rate: 7 L / h, extraction time: 3 h, and the amount of entrainer added was 2.5 wt%.

[0036] S2. Water extraction: Wash, dry, and pulverize the remaining Chinese herbal medicine pieces separately, mix them evenly with the solid residue in step S1 to obtain Chinese herbal medicine powder, add water and heat to boiling for 4 hours to extract. The solid-liquid ratio of the Chinese herbal medicine powder to water is 1:7 g / mL. Filter, dry the filter residue and keep it for use, and dry the filtrate to obtain the water extract.

[0037] S3. Alcohol extraction: Add the filter residue from step S2 to a 60wt% ethanol aqueous solution, wherein the solid-liquid ratio of the filter residue to the ethanol aqueous solution is 1:5 g / mL, heat to 50℃, extract for 3 hours, filter, dry and retain the filter residue, recover the ethanol from the filtrate, dry, and obtain the alcohol extract.

[0038] S4. Add excipients to the water extract obtained in S2 and the alcohol extract obtained in S3, spray in the oils of Eupatorium fortunei, Amomum villosum and Salvia miltiorrhiza obtained in S1, add dextrin, and prepare tablets.

[0039] Example 3: Take 300g of Eupatorium fortunei, 100g of Amomum villosum, 500g of Polygonatum sibiricum, 150g of Ficus hirta, 200g of Rhodiola rosea, 200g of Codonopsis pilosula, 200g of Isatis indigotica, 120g of Taraxacum mongolicum, 200g of Lophatherum gracile, 200g of Broussonetia papyrifera, 120g of Astragalus complanatus, 150g of Eclipta prostrata, 200g of Cornus officinalis, 200g of Salvia miltiorrhiza, 120g of Campsis grandiflora, and 100g of Aucklandia lappa. The preparation method includes the following steps:

[0040] S1. Supercritical fluid extraction of Eupatorium fortunei, Amomum villosum, and Salvia miltiorrhiza: Eupatorium fortunei, Amomum villosum, and Salvia miltiorrhiza were washed, dried, and pulverized to obtain powders of Eupatorium fortunei, Amomum villosum, and Salvia miltiorrhiza. These powders were mixed and subjected to supercritical fluid extraction, using ethanol as an entrainer. The ethanol was recovered to obtain oils of Eupatorium fortunei, Amomum villosum, and Salvia miltiorrhiza. The solid residue was dried and retained. The conditions for supercritical fluid extraction were: extraction pressure: 30 MPa, extraction temperature: 32℃, CO2 flow rate: 12 L / h, extraction time: 2 h, and the amount of entrainer added was 4 wt%.

[0041] S2. Water extraction: Wash, dry, and pulverize the remaining Chinese herbal medicine pieces, mix them evenly with the solid residue from step S1 to obtain Chinese herbal medicine powder, add water and heat to boiling for 2 hours to extract. The solid-liquid ratio of the Chinese herbal medicine powder to water is 1:10 g / mL. Filter, dry the filter residue and keep it for use, and dry the filtrate to obtain the water extract.

[0042] S3. Alcohol extraction: Add the filter residue from step S2 to a 60wt% ethanol aqueous solution, wherein the solid-liquid ratio of the filter residue to the ethanol aqueous solution is 1:5 g / mL, heat to 50℃, extract for 3 hours, filter, dry and retain the filter residue, recover the ethanol from the filtrate, dry, and obtain the alcohol extract.

[0043] S4. Add excipients to the water extract obtained in S2 and the alcohol extract obtained in S3, spray in the oils of Eupatorium fortunei, Amomum villosum and Salvia miltiorrhiza obtained in S1, add microcrystalline cellulose, and prepare capsules.

[0044] Example 4: Pharmacodynamic Study

[0045] A high-sugar, high-fat diet combined with STZ induced an experimental type 2 diabetic rat model. Specific methods: Male SD rats, acclimatized for 7 days, weighing (200±20) g, were randomly divided into a normal group (n=10) and a diabetic group (n=50). The normal group was fed a standard diet, while the model group was fed a high-fat diet. This feeding regimen continued for 4 weeks. On the evening of day 28, the rats were fasted overnight. On the morning of day 29, the model group rats were given a single intraperitoneal injection of STZ 35 mg / kg, while the normal group received only an equal volume of citrate-sodium citrate buffer solution. Three days later, all rats were fasted but allowed free water overnight, and their fasting blood glucose was measured. Two days later, the fasting blood glucose level was measured again. Rats with the lowest average fasting blood glucose level were selected and given another intraperitoneal injection of STZ 15 mg / kg to improve the model success rate. The model success rate was 97.8%.

[0046] After successful modeling, rats were randomly divided into three groups: a model group (n=10), a high-dose group (n=10), a low-dose group (n=10), and a metformin group (n=10). The high-dose and low-dose groups were administered 20g / kg and 10g / kg of the drug (n=10) via intragastric gavage, respectively. The model and normal groups were administered an equal volume of distilled water via intragastric gavage, while the metformin group received 200 mg / kg of metformin via intragastric gavage. This administration was continued for 8 weeks.

[0047] Rats were fasted for 12 hours after the last administration of the drug. After anesthesia with 10% chloral hydrate, the rats were fixed supine on a rat-fixing board, and blood was collected from the abdominal aorta in a blood collection tube. The blood was centrifuged at 14,500 r / min for 10 min at 4℃, and the supernatant was collected in an EP tube and stored at -80℃ for later use. Changes in the rats' demeanor, coat color, food intake, water intake, body weight, and activity were observed before and after modeling and after drug administration. The body weight, food intake, and average water intake of the rats were measured and recorded weekly. After modeling, all rats were fasted for 12 hours every week but allowed free water intake, and their fasting blood glucose levels were measured.

[0048] Table 1. Effects of the present invention on blood glucose levels in type 2 diabetic rats (mmol·L⁻¹) -1 )

[0049]

[0050] (Compared to the normal group, ## P<0.01, compared with the model group * P<0.05, ** (P<0.01)

[0051] The results are shown in Table 1. After modeling, except for the normal group, blood glucose levels in all other groups increased significantly, and the difference between the model group and the normal group was statistically significant (P < 0.01). The metformin group and the high- and low-dose groups of Example 1 of this invention were all statistically significantly different from the model group (P < 0.01). The experimental results indicate that Example 1 of this invention can effectively reduce fasting blood glucose levels in type 2 diabetic rats.

[0052] Example 5: Clinical Study

[0053] Case selection: Diabetic patients with damp-heat syndrome affecting the spleen who visited the outpatient department of Luquan Yi and Miao Autonomous County Traditional Chinese Medicine Hospital between March 2023 and August 2024 were collected. One hundred patients aged 59 to 78 years were selected and divided into a control group and Example 1 group. Complete clinical data were recorded for all enrolled patients, including medical history and physical examination, examination results, and follow-up on treatment response.

[0054] Diagnostic criteria: First, the patient is diagnosed with diabetes using Western medical indicators, including fasting blood glucose ≥7.0 mmol / L, 2-hour postprandial blood glucose ≥11.1 mmol / L, or glycated hemoglobin ≥6.5%. In Traditional Chinese Medicine (TCM), the diagnosis is diabetes due to damp-heat affecting the spleen, manifested by: primary symptoms: chest and abdominal distension, or fullness after meals, and heaviness in the head and body; secondary symptoms: obesity, chest tightness and irritability, fatigue in the limbs, dark yellow urine, and incomplete bowel movements. Tongue and pulse: red tongue with a yellow, greasy coating, and a slippery, rapid pulse.

[0055] Treatment methods: The control group took metformin hydrochloride tablets (National Drug Approval Number H11020127, Beijing Sihuan Pharmaceutical Co., Ltd.), orally, 0.25g each time, twice a day, for 4 weeks; the Example 1 group, in addition to the control group, took the granules prepared in Example 1 orally, with the daily dosage (Eupatorium fortunei 25g, Amomum villosum 15g, Polygonatum sibiricum 40g, Ficus hirta 20g, Rhodiola rosea 15g, Codonopsis pilosula 25g, Isatis indigotica 15g, Taraxacum mongolicum 15g, Lophatherum gracile 15g, Broussonetia papyrifera 25g, Astragalus complanatus 10g, Eclipta prostrata 20g, Cornus officinalis 15g, Salvia miltiorrhiza 25g, Campsis grandiflora 10g, Aucklandia lappa 15g), 3 times a day, for 4 weeks.

[0056] Therapeutic criteria: Table 2 Syndrome score assessment table

[0057]

[0058] Calculation formula:

[0059] Syndrome score (total score) = (Main symptoms 1+2+3) + (Secondary symptoms 4+5+6+7+8) + (Tongue and pulse 9+10)

[0060] Therapeutic effect index (n) = [(Pre-treatment score - Post-treatment score) ÷ Pre-treatment score] × 100%

[0061] Therapeutic efficacy rating: Determined based on the efficacy index (n): Clinically cured: Symptoms of damp-heat trapping the spleen have essentially disappeared, n≥95%. Significantly effective: Symptoms of damp-heat trapping the spleen have significantly improved, 70%≤n<95%. Effective: Symptoms of damp-heat trapping the spleen have improved, 30%≤n<70%. Ineffective: Symptoms of damp-heat trapping the spleen have not significantly improved, or have even worsened, n<30%.

[0062] Clinical results:

[0063] Table 3 Clinical Results of the Invention (Number of People)

[0064]

[0065] After 4 weeks of treatment, in Example 1 group (50 cases), 4 cases were ineffective, 16 cases were effective, 12 cases showed significant improvement, and 18 cases were cured, with a total effective rate of 92%. In the control group (50 cases), 8 cases were ineffective, 15 cases were effective, 16 cases showed significant improvement, and 11 cases were cured, with a total effective rate of 84%. The efficacy of Example 1 group was significantly better than that of the control group, indicating that the present invention is effective in treating diabetes mellitus with damp-heat syndrome.

[0066] In summary, the results of this study show that the formulation of the present invention has beneficial effects such as good efficacy, low recurrence rate, and no toxic side effects. Compared with the prior art, it has achieved unexpected technical effects in terms of both safety and efficacy.

[0067] The above description is only a preferred embodiment of the present invention. Without departing from the principle of the present invention, all technical solutions formed by equivalent substitution or equivalent transformation fall within the scope of protection claimed by the present invention.

Claims

1. A traditional Chinese medicine composition of Polygonatum sibiricum for treating diabetes mellitus due to damp-heat in the spleen, characterized in that, It is prepared by extracting the following Chinese medicinal herbs in parts by weight: 20-30 parts of Eupatorium fortunei, 10-20 parts of Amomum villosum, 30-50 parts of Polygonatum sibiricum, 15-25 parts of Ficus hirta, 10-20 parts of Rhodiola rosea, 20-30 parts of Codonopsis pilosula, 10-20 parts of Isatis indigotica, 12-18 parts of Taraxacum mongolicum, 10-20 parts of Lophatherum gracile, 20-30 parts of Broussonetia papyrifera, 8-12 parts of Astragalus complanatus, 15-25 parts of Eclipta prostrata, 10-20 parts of Cornus officinalis, 20-30 parts of Salvia miltiorrhiza, 8-12 parts of Campsis grandiflora, and 10-20 parts of Aucklandia lappa.

2. The Polygonatum sibiricum composition for treating diabetes mellitus due to damp-heat invading the spleen as described in claim 1, characterized in that, It is prepared by extracting the following Chinese medicinal herbs in the indicated weight parts: 25 parts of Eupatorium fortunei, 15 parts of Amomum villosum, 40 parts of Polygonatum sibiricum, 20 parts of Ficus hirta, 15 parts of Rhodiola rosea, 25 parts of Codonopsis pilosula, 15 parts of Isatis indigotica, 15 parts of Taraxacum mongolicum, 15 parts of Lophatherum gracile, 25 parts of Broussonetia papyrifera, 10 parts of Astragalus complanatus, 20 parts of Eclipta prostrata, 15 parts of Cornus officinalis, 25 parts of Salvia miltiorrhiza, 10 parts of Campsis grandiflora, and 15 parts of Aucklandia lappa.

3. The Polygonatum sibiricum composition for treating diabetes mellitus due to damp-heat invading the spleen as described in claim 1, characterized in that, It is prepared by extracting the following Chinese medicinal herbs in the indicated weight parts: 20 parts of Eupatorium fortunei, 20 parts of Amomum villosum, 30 parts of Polygonatum sibiricum, 25 parts of Ficus hirta, 10 parts of Rhodiola rosea, 30 parts of Codonopsis pilosula, 10 parts of Isatis indigotica, 18 parts of Taraxacum mongolicum, 10 parts of Lophatherum gracile, 30 parts of Broussonetia papyrifera, 8 parts of Astragalus complanatus, 25 parts of Eclipta prostrata, 10 parts of Cornus officinalis, 30 parts of Salvia miltiorrhiza, 8 parts of Campsis grandiflora, and 20 parts of Aucklandia lappa.

4. The Polygonatum sibiricum composition for treating diabetes mellitus due to damp-heat invading the spleen as described in claim 1, characterized in that, It is prepared by extracting the following Chinese medicinal herbs in the indicated weight parts: 30 parts of Eupatorium fortunei, 10 parts of Amomum villosum, 50 parts of Polygonatum sibiricum, 15 parts of Ficus hirta, 20 parts of Rhodiola rosea, 20 parts of Codonopsis pilosula, 20 parts of Isatis indigotica, 12 parts of Taraxacum mongolicum, 20 parts of Lophatherum gracile, 20 parts of Broussonetia papyrifera, 12 parts of Astragalus complanatus, 15 parts of Eclipta prostrata, 20 parts of Cornus officinalis, 20 parts of Salvia miltiorrhiza, 12 parts of Campsis grandiflora, and 10 parts of Aucklandia lappa.

5. The Polygonatum sibiricum composition for treating diabetes mellitus due to damp-heat invading the spleen as described in claim 1, characterized in that, The preparation method includes the following steps: S1. Supercritical fluid extraction of Eupatorium fortunei, Amomum villosum, and Salvia miltiorrhiza: Eupatorium fortunei, Amomum villosum, and Salvia miltiorrhiza were washed, dried, and pulverized to obtain powders of Eupatorium fortunei, Amomum villosum, and Salvia miltiorrhiza. These powders were mixed and subjected to supercritical fluid extraction, using ethanol as an entrainer. The ethanol was recovered to obtain oils of Eupatorium fortunei, Amomum villosum, and Salvia miltiorrhiza. The solid residue was dried and retained. The supercritical fluid extraction conditions were: extraction pressure: 25-30 MPa, extraction temperature: 32-40℃, CO2 flow rate: 7-12 L / h, extraction time: 2-3 h, and the amount of entrainer added was 2.5-4 wt%. S2. Water extraction: Wash, dry, and pulverize the remaining Chinese herbal medicine pieces, mix them evenly with the solid residue from step S1 to obtain Chinese herbal medicine powder, add water and heat to boiling to extract for 2-4 hours. The solid-liquid ratio of the Chinese herbal medicine powder to water is 1:7-10 g / mL. Filter, dry the filter residue and keep it for use, and dry the filtrate to obtain the water extract. S3. Alcohol extraction: Add the filter residue from step S2 to a 60-70 wt% ethanol aqueous solution, wherein the solid-liquid ratio of the filter residue to the ethanol aqueous solution is 1:3-5 g / mL, heat to 50-70℃, extract for 1-3 h, filter, dry and retain the filter residue, recover the ethanol from the filtrate, dry, and obtain the alcohol extract. S4. Add excipients to the water extract obtained in S2 and the alcohol extract obtained in S3, and spray in the oils of Eupatorium fortunei, Amomum villosum and Salvia miltiorrhiza obtained in S1 to prepare an oral solid dosage form.

6. The Polygonatum sibiricum composition for treating diabetes mellitus due to damp-heat invading the spleen as described in claim 5, characterized in that, In step S4 of the preparation method, the oral solid dosage form is one of granules, tablets, or syrup.

7. The use of the Polygonatum sibiricum composition for treating diabetes mellitus due to damp-heat in claim 1 in the preparation of a drug for treating diabetes mellitus due to damp-heat in the spleen.

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