HK40000985B - Application of pithecellobium clypearia extract in the prevention and/or treatment of hyperuricemia as well as its metabolic complications - Google Patents

Description

Use of monkey earring extract in preventing and/or treating hyperuricemia and metabolic disorders associated with hyperuricemia

Technical Field

The present invention relates to a new application of monkey earrings, and in particular to an application of monkey earrings and a composition thereof in preventing and/or treating hyperuricemia and metabolic disorders associated with hyperuricemia.

Background Art

Hyperuricemia (HUA) is a heterogeneous disease caused by impaired purine metabolism and/or uric acid excretion, characterized by elevated serum uric acid levels. In recent years, with improvements in living standards and changes in dietary patterns, the prevalence of hyperuricemia in my country has shown a significant upward trend.

Currently, there is no definitive cure for the symptoms of hyperuricemia and gouty arthritis, and Western medicine is the only treatment available to alleviate the pain of acute attacks. Monkey earrings, scientifically known as the bib (xianyin) tree, also known as the po-splitting tree, the chicken heart tree, the shampoo tree, and the falling money tree, are perennial trees that grow near the Tropic of Cancer. Monkey earrings are a botanical anti-inflammatory drug and the only monkey earring-based Chinese medicine to have received a drug approval. Modern pharmacology has demonstrated that monkey earrings have antibacterial and anti-inflammatory effects, with significant therapeutic effects for upper respiratory tract infections, acute pharyngitis, acute tonsillitis, acute gastroenteritis, bacterial dysentery, and other conditions, with no reports of adverse drug reactions. Therefore, it can be demonstrated that monkey earrings are a safe Chinese medicinal material, but no literature has been found reporting that monkey earrings can lower uric acid or prevent or treat gout symptoms.

Summary of the Invention

The purpose of the present invention is to overcome the shortcomings of the prior art and provide the use of monkey earrings and compositions thereof in preventing and/or treating hyperuricemia and metabolic disorders associated with hyperuricemia.

To achieve the above-mentioned object, the technical solution adopted by the present invention is: use of monkey earring extract in the preparation of drugs for preventing and/or treating hyperuricemia and metabolic disorders related to hyperuricemia.

The inventors unexpectedly discovered that monkey earring extract can inhibit the activity of xanthine oxidase and has the effect of lowering blood uric acid levels.

Preferably, the metabolic disorder associated with hyperuricemia includes at least one of acute gout, chronic gout, gouty arthritis, gout attack, uric acid nephrolithiasis and gouty nephropathy.

The present invention also aims to provide the use of the monkey earring extract in the preparation of xanthine oxidase inhibitors.

The present invention also aims to provide a pharmaceutical composition for preventing and/or treating hyperuricemia and metabolic disorders associated with hyperuricemia, wherein the composition comprises monkey earrings and/or monkey earring extracts, and excipients or auxiliary ingredients acceptable in medicines.

Preferably, the monkey earring extract is prepared by extracting fresh monkey earring leaves with a solvent. The monkey earring extract can be extracted with water or other organic solvents.

Preferably, the preparation method of the monkey earring extract comprises the following steps:

(1) Preparation of extract: Extract fresh leaves of the monkey earring twice with water at 95-100°C, with the amount of water used for the first extraction being 4-10 times the weight of the fresh leaves for 1-3 hours, and the amount of water used for the second extraction being 3-8 times the weight of the fresh leaves for 0.5-2 hours, and then concentrate to obtain the extract;

(2) spray drying and rapid cooling to obtain the monkey earring extract.

Preferably, the composition further comprises coconut extract and green papaya extract, and the weight ratio of the monkey earring extract, coconut extract and green papaya extract is: monkey earring extract: coconut extract: green papaya extract = 2:0.5-2:0.5-2.

The combination of coconut extract and green papaya extract with monkey earring extract has a certain promoting effect on the uric acid-lowering effect and the inhibition of xanthine oxidase activity of monkey earring extract.

More preferably, the weight ratio of the monkey earring extract, coconut extract, and green papaya extract is: monkey earring extract: coconut extract: green papaya extract = 2:1:1. In particular, when this ratio is used, the combined effect of the three ingredients on lowering uric acid and inhibiting xanthine oxidase activity is optimal.

Preferably, the composition further comprises the following A composition or B composition:

Composition A: winter honey, dodder seeds, and eucommia bark;

Composition B: Cuscuta seeds and Eucommia ulmoides.

Monkey earrings have a cold medicinal property, and can be added with composition A or composition B to be more suitable for human constitution. Non-diabetic patients can choose composition A, and diabetic patients can choose composition B.

Preferably, the weight ratio of the monkey earring extract to the components of composition A is: monkey earring extract: winter honey: dodder seed: eucommia bark = 1:4-7:0.5-2:0.5-2; and the weight ratio of the monkey earring extract to the components of composition B is: monkey earring extract: dodder seed: eucommia bark = 1:2-3:2-3. When used in this ratio, the effectiveness of the monkey earring extract is maximized, and the overall medicinal properties of the composition are more mild.

The present invention also aims to provide a medicine comprising the above-mentioned pharmaceutical composition for preventing and/or treating hyperuricemia and metabolic disorders associated with hyperuricemia.

The present invention provides the beneficial effects of using a monkey earring extract in the preparation of a drug for preventing and/or treating hyperuricemia and metabolic disorders associated with hyperuricemia. The monkey earring extract has a significant uric acid-lowering effect with minimal side effects and is non-toxic to the liver and kidneys. It can be used to prepare a drug for alleviating gout symptoms, providing a new approach to addressing the significant side effects of current gout medications.

DETAILED DESCRIPTION

The raw materials such as coconut extract, green papaya extract, dodder seed and eucommia bark in the examples were purchased from the market.

In order to better illustrate the purpose, technical solutions and advantages of the present invention, the present invention will be further described below in conjunction with specific embodiments.

Example 1

An embodiment of a method for preparing a monkey earring extract comprises the following steps:

(1) Preparation of extract: 56 g of fresh leaves of the monkey earring were extracted twice with water at 100°C. The amount of water used in the first extraction was 8 times the weight of the fresh leaves, and the time was 2 h. The amount of water used in the second extraction was 6 times the weight of the fresh leaves, and the time was 1 h. The extract was concentrated to obtain 10.2 g of extract.

(2) spray drying and rapid cooling to obtain 5.1 g of the monkey earring extract.

Example 2

An embodiment of a method for preparing a monkey earring extract comprises the following steps:

(1) Preparation of extract: 44 g of fresh leaves of the monkey earring were extracted twice with water at 95°C. The amount of water used in the first extraction was 10 times the weight of the fresh leaves, and the time was 3 h. The amount of water used in the second extraction was 3 times the weight of the fresh leaves, and the time was 0.5 h. The extract was concentrated to obtain 8.2 g of extract.

(2) spray drying and rapid cooling to obtain 3.8 g of the monkey earring extract.

Example 3

An embodiment of a method for preparing a monkey earring extract comprises the following steps:

(1) Preparation of extract: 60 g of fresh leaves of the monkey earring were extracted twice with water at 100°C. The amount of water used in the first extraction was 4 times the weight of the fresh leaves, and the time was 1 h. The amount of water used in the second extraction was 8 times the weight of the fresh leaves, and the time was 2 h. The extract was concentrated to obtain 10.5 g of extract.

(2) spray drying and rapid cooling to obtain 4.8 g of the monkey earring extract.

Example 4

The pharmacological experiment on the uric acid lowering effect of monkey earring extract was commissioned to a third-party organization.

Test method:

(1) 90 male SPF Kunming mice (20±2g) were randomly divided into 9 groups: normal control group, hyperuricemia model group, allopurinol positive control group, low, medium and high monkey earring extract test groups (low dose as test group 1, medium dose as test group 2, high dose as test group 3), monkey earring extract and green papaya extract mixture test group as test group 4 (the weight ratio of monkey earring extract to green papaya extract was 2:1), monkey earring extract and coconut extract mixture test group as test group 5 (the weight ratio of monkey earring extract to coconut extract was 2:1), monkey earring extract, green papaya extract and coconut extract mixture test group 6 (the weight ratio of monkey earring extract, green papaya extract and coconut extract was 2:1:1). Except for the normal control group, which was intraperitoneally injected with distilled water and gavaged with it, the other groups were intraperitoneally injected with potassium salt of oxonate at a dose of 100mg/kg/d and gavaged with hypoxanthine at a dose of 600mg/kg/d to establish the model. One hour before modeling, the mice were fasted but not watered. One hour after modeling, allopurinol (5 mg/kg) was administered orally to the mice. Experimental groups 1 to 3 were administered orally with 50, 100, and 200 mg/kg of the monkey earring extract prepared in Example 1 at a dose of 100 mg/kg/day. Experimental groups 4 to 6 were administered orally with 50 mg/kg of the monkey earring extract prepared in Example 1 at a dose of 50 mg/kg/day. The normal control group and the hyperuricemia model control group were administered orally with the same volume of pure water for 7 consecutive days. The mice were weighed and recorded on days 1, 4, and 7.

(2) On the 7th day, one hour after oral administration, the mice were sacrificed and blood and urine were collected. The blood samples were centrifuged at 3500 rpm for 10 min. The serum was separated and stored at -20°C. The liver and kidneys of the mice were removed and washed with saline solution.

(3) Take the serum obtained in (2) and measure the serum uric acid level.

(4) The organs obtained in (2) were taken and the kidney coefficient was calculated by dividing the body weight of a single mouse by the weight of each organ of a single mouse. The liver and kidney tissues were removed and weighed. The liver was homogenized with cold saline (0.9%) and centrifuged at 2000 rpm for 10 minutes at 4°C. The supernatant was retained for XOD activity analysis.

The test results are shown in Tables 1 to 4.

Table 1 Effects of monkey earring extract on serum uric acid levels in mice with hyperuricemia induced by potassium oxonate and hypoxanthine

Note: Different letters a, b, c, d in the same column indicate significant differences between the data (p < 0.05), and the same letters indicate no significant differences between the data (p > 0.05).

As shown in Table 1, serum uric acid levels were elevated in the hyperuricemia model group induced by potassium oxonate and hypoxanthine compared to normal mice, demonstrating successful model establishment. Low, medium, and high doses of monkey earring extract significantly reduced serum uric acid levels in hyperuricemic mice, demonstrating its potent uric acid-lowering efficacy. Furthermore, even at half the dose of monkey earring extract alone, the combination of monkey earring extract, green papaya extract, and coconut extract maintained a significant uric acid-lowering effect, achieving even greater efficacy.

Table 2 Effects of monkey earring extract on XOD activity in the liver of mice with hyperuricemia induced by potassium oxonate and hypoxanthine

Note: Different letters a and b in the same column indicate significant differences between the data (p < 0.05), and the same letters indicate no significant differences between the data (p > 0.05).

From the data in Table 2, it can be seen that the low, medium and high doses of monkey earring extract experimental groups can significantly reduce the XOD activity in the liver of hyperuricemia mice, indicating that the uric acid-lowering effect of monkey earring extract may be achieved by inhibiting XOD activity. Moreover, after the dosage of monkey earring extract in experimental groups 4 to 6 was halved, it can still significantly reduce the XOD activity in the liver of hyperuricemia mice, indicating that green papaya extract and coconut extract have a certain promoting effect on reducing the XOD activity in the liver of mice.

Table 3 Weight gain of mice compared with before administration

Group Day 1 (%) Day 4 (%) Day 7 (%) Blank group Model Group Allopurinol group Experimental group 1 Experimental Group 2 Experimental Group 3 Experimental Group 4 Experimental Group 5 Experimental Group 6

Note: Different letters a, b, c in the same column indicate significant differences between the data (p < 0.05), and the same letters indicate no significant differences between the data (p > 0.05).

From the results in Table 3, it can be seen that compared with the normal group of mice, the body weight of test groups 1 to 6 was not affected (P>0.05), while allopurinol inhibited the weight gain of mice and had certain toxicity, indicating that the monkey earring extract was generally non-toxic.

Table 4 Kidney coefficients of mice

Group Kidney coefficient (%) Blank group Model Group Allopurinol group Experimental group 1 Experimental Group 2 Experimental Group 3 Experimental Group 4 Experimental Group 5 Experimental Group 6

Note: Different letters a and b in the same column indicate significant differences between the data (p < 0.05), and the same letters indicate no significant differences between the data (p > 0.05).

From the results in Table 4, it can be seen that the kidney coefficient of the allopurinol group was significantly higher than that of the blank group, indicating that allopurinol has toxic effects on the kidneys. There was no statistically significant difference between the test groups 1 to 6 and the blank group, indicating that the monkey earring extract had no effect or little effect on renal function.

These results demonstrate that monkey earring extract significantly reduces serum uric acid levels in hyperuricemic mice, approaching normal levels, and inhibits XOD activity. Compared to existing clinical drugs with significant side effects, monkey earring extract is non-toxic to the kidneys and can be used in the preparation of uric acid-lowering and gout-alleviating drugs, foods, health supplements, or supplemental agents. The inventors speculate that the methyl gallate and gallic acid in the monkey earring extract may be responsible for the uric acid-lowering effect.

Example 5

A drug for preventing and/or treating hyperuricemia and metabolic disorders associated with hyperuricemia, comprising the following components in parts by weight: 2 parts of the monkey earring extract prepared in Example 1, 1 part of coconut extract, and 1 part of green papaya extract.

Example 6

A drug for preventing and/or treating hyperuricemia and metabolic disorders associated with hyperuricemia, comprising the following components in parts by weight: 2 parts of the monkey earring extract prepared in Example 1, 1 part of coconut extract, 1 part of green papaya extract, 10 parts of winter honey, 2 parts of Cuscuta australis, and 2 parts of Eucommia ulmoides.

Example 7

A drug for preventing and/or treating hyperuricemia and metabolic disorders associated with hyperuricemia, comprising the following components in parts by weight: 2 parts of the monkey earring extract prepared in Example 1, 1 part of coconut extract, 1 part of green papaya extract, 1.5 parts of Cuscuta australis seeds, and 1.5 parts of Eucommia ulmoides.

Example 8

Clinical trials:

Case 1: Ms. Wang, 48 years old, had symptoms of acute gout. Before treatment, the serum uric acid test content was 529.7μmol/L. She took the drug described in Example 5, usage and dosage: 10g each time with boiled water, once a day. There was no pain for 7 days. After stopping taking it on the 7th day, slight pain appeared. After taking it for 15 consecutive days, the pain was basically eliminated. On the 25th day, she was basically cured. On the 25th day, blood test for serum uric acid content showed 310.8μmol/L.

Case 2: Mr. Gao, 52 years old, had symptoms of acute gout. Before treatment, the serum uric acid test content was 562.1 μmol/L. He took the medicine described in Example 6, with the following usage and dosage: 45 g each time (first decocted Cuscuta seeds and Eucommia ulmoides for about 1 hour, removed the residue, and then added winter honey, monkey earring extract, coconut extract and green papaya extract), once a day. There was no pain on the 10th day, but slight pain would occur after stopping taking the medicine on the 10th day. After taking the medicine for 30 consecutive days, the pain was basically eliminated, and the patient was basically cured on the 40th day. On the 40th day, a blood test showed that the serum uric acid content was 331.4 μmol/L.

Case 3: Mr. Li, 50 years old, had symptoms of acute gout and mild diabetes. Before treatment, the serum uric acid test content was 580.2 μmol/L. He took the medicine described in Example 7, with the following usage and dosage: 18 g each time (first decocted Cuscuta seeds and Eucommia ulmoides for about 1 hour, removed the residue, and then added monkey earring extract, coconut extract and green papaya extract), once a day. There was no pain on the 12th day, but slight pain appeared after stopping taking the medicine on the 12th day. After taking the medicine for 30 consecutive days, the pain was basically eliminated, and he was basically cured on the 45th day. On the 45th day, a blood test showed that the serum uric acid content was 306.3 μmol/L.

Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the essence and scope of the technical solutions of the present invention.

Claims (3)

1. A pharmaceutical composition for the prevention and/or treatment of hyperuricemia and metabolic disorders associated with hyperuricemia, characterized in that the composition comprises a monkey earring extract, and excipients or auxiliary components acceptable in pharmaceuticals; the monkey earring extract is prepared by solvent extraction of fresh monkey earring leaves; the method for preparing the monkey earring extract includes the following steps: (1) Preparation of extract: Fresh leaves of monkey ear ring are extracted twice with water at 95~100℃. The amount of water used for the first extraction is 4~10 times the weight of the fresh leaves, and the time is 1~3h. The amount of water used for the second extraction is 3~8 times the weight of the fresh leaves, and the time is 0.5~2h. The extract is then concentrated. (2) Spray drying and rapid cooling are used to obtain the monkey earring extract; The composition also comprises coconut extract and green papaya extract, wherein the weight ratio of the monkey earring extract, coconut extract and green papaya extract is: monkey earring extract: coconut extract: green papaya extract = 2:1:1. 2. The pharmaceutical composition for the prevention and/or treatment of hyperuricemia and metabolic disorders associated with hyperuricemia as described in claim 1, characterized in that the composition further comprises either composition A or composition B: Composition A: Winter honey, dodder seed, and eucommia bark; Composition B: Cuscuta chinensis and Eucommia ulmoides; The weight ratio of the monkey earring extract to each component of composition A is: monkey earring extract: winter honey: dodder seed: eucommia bark = 1:4~7:0.5~2:0.5~2; the weight ratio of the monkey earring extract to each component of composition B is: monkey earring extract: dodder seed: eucommia bark = 1:2~3:2~3. 3. A medicine comprising the pharmaceutical composition of any one of claims 1 to 2 for the prevention and/or treatment of hyperuricemia and metabolic disorders associated with hyperuricemia.