HK40000985A

HK40000985A - Application of pithecellobium clypearia extract in the prevention and/or treatment of hyperuricemia as well as its metabolic complications

Info

Publication number: HK40000985A
Application number: HK19124194.2A
Authority: HK
Inventors: 何翔; 何学桢
Original assignee: 广州安加农业发展有限公司
Filing date: 2019-05-22
Publication date: 2020-02-21

Description

Use of extract of Pithecellobium clypearia for preventing and/or treating hyperuricemia and metabolic disorders associated with hyperuricemia

Technical Field

The invention relates to a novel application of a monkey ear ring, in particular to an application of the monkey ear ring and a composition thereof in preventing and/or treating hyperuricemia and metabolic disorders related to the hyperuricemia.

Background

Hyperuricemia (HUA) is a heterogeneous disease caused by purine metabolic disorder and/or uric acid excretion disorder, and is characterized mainly by elevated blood uric acid. In recent years, with the improvement of living standard of people and the change of dietary structure, the prevalence rate of hyperuricemia in China has a very obvious rising trend.

At present, no method for radically treating hyperuricemia and gouty arthritis pain exists, and only western medicines can be taken to relieve acute disease pain. The ear loops of monkeys, known as pinang (yawning) trees, are called grandma, pistachio, shampoo, and christina loosestrife, and perennial arbors grow in the north hui fairy line. The anti-inflammatory drug of the pithecellobium clypearia is the only pithecellobium clypearia monomer traditional Chinese medicine which has acquired a drug batch. Modern pharmacology proves that the pithecellobium clypearia has the antibacterial and anti-inflammatory effects, has obvious curative effects on upper respiratory tract infection, acute pharyngolaryngitis, acute tonsillitis, acute gastroenteritis, bacillary dysentery and other diseases, and has no adverse drug reaction report. Therefore, the pithecellobium clypearia is proved to belong to a traditional Chinese medicinal material with safe drug properties, but no literature data reporting that pithecellobium clypearia has the effects of reducing uric acid and preventing and treating gout symptoms is found.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provides the application of the pithecellobium clypearia and the composition thereof in preventing and/or treating hyperuricemia and metabolic diseases related to the hyperuricemia.

In order to achieve the purpose, the invention adopts the technical scheme that: use of extract of Pithecellobium clypearia in preparing medicine, food and health product for preventing and/or treating hyperuricemia and metabolic disorder related to hyperuricemia.

The inventor unexpectedly finds that the pithecellobium clypearia extract can inhibit the activity of xanthine oxidase and has the effect of reducing the level of hematuria acid.

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

The invention also aims to provide the application of the pithecellobium clypearia extract in preparing xanthine oxidase inhibitors.

The invention also aims to provide a medicine, food or health-care product composition for preventing and/or treating hyperuricemia and metabolic disorders related to the hyperuricemia, wherein the composition comprises pithecellobium clypearia and/or pithecellobium clypearia extracts, and acceptable auxiliary materials or auxiliary components in the medicine, food or health-care product.

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

Preferably, the preparation method of the pithecellobium clypearia extract comprises the following steps:

(1) and preparing an extract: extracting fresh leaves of pithecellobium clypearia twice with water at 95-100 ℃, wherein the amount of water for the first extraction is 4-10 times of the weight of the fresh leaves, the time is 1-3 hours, the amount of water for the second extraction is 3-8 times of the weight of the fresh leaves, and the time is 0.5-2 hours, and concentrating to obtain an extract;

(2) spray drying, and rapidly cooling to obtain the extract.

Preferably, the composition further comprises coconut extract and papaya extract, wherein the weight ratio of the pithecellobium clypearia extract to the coconut extract to the papaya extract is: extract of Pithecellobium clypearia: coconut extract: the ratio of the green papaya extract to 2: 0.5-2.

The coconut extract and the papaya extract are matched with the pithecellobium clypearia extract, and have certain promotion effects on the uric acid reduction effect and the xanthine oxidase activity inhibition effect of the pithecellobium clypearia extract.

More preferably, the weight ratio of the pithecellobium clypearia extract to the coconut extract to the papaya extract is: extract of Pithecellobium clypearia: coconut extract: the ratio of the green papaya extract to the green papaya extract is 2:1: 1. Particularly, when the mixture ratio is adopted, the combined effect of the three on reducing uric acid and the effect on inhibiting the activity of xanthine oxidase are optimal.

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

composition A: winter honey, semen Cuscutae, and Eucommiae cortex;

composition B: dodder seed and eucommia bark.

The property of the pithecellobium clypearia is cold and cool, the composition A or the composition B can be added for compatibility, the pithecellobium clypearia is more suitable for the physique of a human body, the composition A can be selected by non-diabetic patients, and the composition B can be selected by diabetic patients.

Preferably, the weight ratio of the pithecellobium clypearia extract to the components of the composition A is as follows: the extract of the pithecellobium clypearia is winter honey, dodder and eucommia ulmoides are 1: 4-7: 0.5-2; the weight ratio of the pithecellobium clypearia extract to the B composition is as follows: the extract of the pithecellobium clypearia is semen cuscutae and eucommia ulmoides in a ratio of 1: 2-3. When the composition is prepared according to the proportion, the effect of the pithecellobium clypearia extract can be exerted, and the overall medicine property of the composition is milder.

The invention also aims to provide a medicine, food or health-care product containing the medicine, food or health-care product composition for preventing and/or treating hyperuricemia and metabolic disorders related to the hyperuricemia.

The invention has the beneficial effects that: the invention provides application of a pithecellobium clypearia extract in preventing and/or treating hyperuricemia and metabolic disorders related to the hyperuricemia. The pithecellobium clypearia extract has a remarkable uric acid reducing effect, is small in side effect, has no toxicity to liver and kidney, can be used for preparing a medicine for relieving gout diseases, and provides a new direction for improving the phenomenon of large side effect of the existing gout disease medicine.

Detailed Description

In the examples, coconut extract, papaya extract, dodder seed, eucommia bark and other raw materials were purchased from the market.

To better illustrate the objects, aspects and advantages of the present invention, the present invention will be further described with reference to specific examples.

Example 1

An embodiment of a method for preparing an extract of Pithecellobium clypearia comprises the following steps:

(1) and preparing an extract: extracting 56g of fresh leaves of Pithecellobium clypearia twice with water at 100 deg.C, the amount of water extracted for the first time is 8 times of the weight of the fresh leaves, the time is 2h, the amount of water extracted for the second time is 6 times of the weight of the fresh leaves, the time is 1h, and concentrating to obtain 10.2g of extract;

(2) spray drying, and rapidly cooling to obtain 5.1g of Pithecellobium clypearia extract.

Example 2

(1) and preparing an extract: extracting 44g of fresh leaves of pithecellobium clypearia twice with water at 95 ℃, wherein the amount of water extracted for the first time is 10 times of the weight of the fresh leaves, the time is 3 hours, the amount of water extracted for the second time is 3 times of the weight of the fresh leaves, the time is 0.5 hour, and concentrating to obtain 8.2g of extract;

(2) spray drying, and rapidly cooling to obtain 3.8g of Pithecellobium clypearia extract.

Example 3

(1) and preparing an extract: extracting 60g of fresh leaves of pithecellobium clypearia twice with water at 100 ℃, wherein the amount of water for the first extraction is 4 times of the weight of the fresh leaves, the time is 1 hour, the amount of water for the second extraction is 8 times of the weight of the fresh leaves, the time is 2 hours, and concentrating to obtain 10.5g of extract;

(2) spray drying, and rapidly cooling to obtain the extract 4.8 g.

Example 4

The pharmacological experiment of the pithecellobium clypearia extract for reducing uric acid is finished by a third party organization.

The test method comprises the following steps:

(1) 90 male SPF Kunming mice (20 ± 2g) were taken and randomly divided into 9 groups: a normal control group, a hyperuricemia model group, an allopurinol positive control group, a low, medium and high simian ear loop extract test group (low dose is test group 1, medium dose is test group 2, and high dose is test group 3), a simian ear loop extract and papaw extract mixture test group is test group 4 (weight ratio of simian ear loop extract to papaw extract is 2:1), a simian ear loop extract and coconut extract mixture test group is test group 5 (weight ratio of simian ear loop extract to coconut extract is 2:1), and a simian ear loop extract, papaw extract and coconut extract mixture is test group 6 (weight ratio of simian ear loop extract, papaw extract and coconut extract is 2:1: 1). Except for normal control group, the other groups were injected with 100mg/kg/d dose of Potassium Oxonate and injected with 600mg/kg/d dose of hypoxanthine for molding. The mice were administered allopurinol by gavage with allopurinol (5mg/kg) 1 hour after the molding, without water deprivation for one hour before the molding. The extract of the pithecellobium clypearia of the test groups 1-3 is respectively administrated by gavage at the dose of 100mg/kg/d for the pithecellobium clypearia extract prepared in the example 1 with the concentration of 50mg/kg, the extract of the pithecellobium clypearia prepared in the example 1 with the concentration of 50mg/kg/d for the test groups 4-6 is administrated at the dose of 50mg/kg/d for the test groups 4-6, and the pure water with the same volume as the gavage is gavage for 7 days continuously, and the mice are weighed and recorded on the days 1, 4 and 7.

(2) After 1 hour of intragastric administration on day 7, blood samples obtained by centrifuging blood and urine for 10min at 3500r/min using a centrifuge were separated to obtain serum stored at-20 ℃. Mouse liver and kidney were excised and washed with physiological saline solution.

(3) And (3) taking the serum obtained in the step (2) to measure the serum uric acid level.

(4) The organs obtained in (2) were used to calculate the kidney factor by dividing the weight of individual mice by the weight of individual organs of individual mice, liver and kidney tissues were excised, weighed and homogenized with cold physiological saline (0.9%) and centrifuged at 2000rpm for 10 minutes at 4 ℃ and the supernatant was retained for XOD activity analysis.

The test results are shown in tables 1-4.

TABLE 1 Effect of Pithecellobium clypearia extracts on the serum uric acid content of mice with hyperuricemia induced by Potassium Oxonate and hypoxanthine

Note: the letters a, b, c and d in the same column represent significant difference (p < 0.05) between the data, and the same letter represents no significant difference (p >0.05) between the data.

As can be seen from the data in Table 1, the serum uric acid level of the hyperuricemia model group induced by the combination of Potassium Oxonate and hypoxanthine is increased compared with that of the normal mice, and the success of modeling is proved. The experimental groups of the low, medium and high doses of the pithecellobium clypearia extracts can obviously reduce the serum uric acid content of mice with high uric acid, and the pithecellobium clypearia extracts have good effect of reducing uric acid. Compared with the single pithecellobium clypearia extract, the papaya extract and the coconut extract can still keep a good uric acid reducing effect and have a better effect under the condition that the dosage of the pithecellobium clypearia extract is reduced by half.

TABLE 2 Effect of Pithecellobium clypearia extracts on Potassium Oxonate and hypoxanthine induced hyperuricemia mouse liver XOD Activity

Note: the letters a and b in the same column indicate significant difference (p < 0.05), and the same letter indicates no significant difference (p > 0.05).

The data in table 2 show that the low, medium and high doses of the pithecellobium clypearia extracts in the experimental groups can significantly reduce the liver XOD activity of the mouse with high uric acid content, which indicates that the uric acid reducing effect of the pithecellobium clypearia extracts can be realized by inhibiting the XOD activity, and the pithecellobium clypearia extracts in the experimental groups 4-6 can still significantly reduce the liver XOD activity of the mouse with high uric acid content after the dosage of the pithecellobium clypearia extracts is reduced by half, which indicates that the chaenomeles sinensis extracts and the coconut extracts have certain promotion effect.

TABLE 3 weight gain of mice compared to before administration

Group of	Day 1 (%)	Day 4 (%)	Day 7 (%)
				Blank group	99^a	144^b	169^c
Model set	98^a	125^b	136^c
				Allopurinol group	101^a	126^b	130^d
Test group 1	100^a	137^b	149^c
				Test group 2	97^a	132^b	146^c
Test group 3	99^a	135^b	150^c
				Test group 4	98^a	138^b	146^c
Test group 5	99^a	136^b	148^c
				Test group 6	100^a	139^b	145^c

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

As can be seen from the results in Table 3, the weight of the mice in the test groups 1-6 was not affected (P >0.05), and allopurinol inhibited the weight increase of the mice and had a certain toxicity, indicating that the extract of Pithecellobium clypearum has no toxicity overall.

TABLE 4 Kidney coefficients of mice

Group of	Kidney coefficient (%)
		Blank group	1.29±0.03^a
Model set	1.36±0.04^a
		Allopurinol group	1.45±0.05^b
Test group 1	1.31±0.05^a
		Test group 2	1.34±0.03^a
Test group 3	1.30±0.04^a
		Test group 4	1.33±0.03^a
Test group 5	1.31±0.05^a
		Test group 6	1.33±0.04^a

The results in table 4 show that the kidney coefficient of the allopurinol group is obviously higher than that of the blank group, which indicates that allopurinol has a toxicological effect on the kidney, and the comparison difference between the test groups 1-6 and the blank group has no statistical significance, which indicates that the pithecellobium clypearia extract has no or little influence on the renal function.

The results show that the pithecellobium clypearia extract can obviously reduce the serum uric acid level of a hyperuricemia mouse, is close to the level of a normal group, has an inhibition effect on XOD activity, has no toxicity on kidney compared with the existing clinical medicine with stronger side effect, and can be used for preparing medicines, foods, health care products or auxiliary medicaments for reducing uric acid and improving gout. The inventors speculate that gallic acid and methyl gallate in the extract of pithecellobium clypearia exert uric acid lowering effect.

Example 5

A medicament for preventing and/or treating hyperuricemia and metabolic disorders related to the hyperuricemia, wherein the medicament comprises the following components in parts by weight: 2 parts of the extract of Pithecellobium clypearia, 1 part of the extract of coconut and 1 part of the extract of Chaenomeles speciosa obtained in example 1.

Example 6

A medicament for preventing and/or treating hyperuricemia and metabolic disorders related to the hyperuricemia, wherein the medicament comprises the following components in parts by weight: 2 parts of pithecellobium clypearia extract, 1 part of coconut extract, 1 part of green papaya extract, 10 parts of winter honey, 2 parts of semen cuscutae and 2 parts of eucommia ulmoides prepared in example 1.

Example 7

A medicament for preventing and/or treating hyperuricemia and metabolic disorders related to the hyperuricemia, wherein the medicament comprises the following components in parts by weight: 2 parts of pithecellobium clypearia extract, 1 part of coconut extract, 1 part of green papaya extract, 1.5 parts of dodder and 1.5 parts of eucommia ulmoides prepared in example 1.

Example 8

And (3) clinical trials:

case 1: the female king, age 48, has acute gout symptom, before treatment, the content of serum uric acid is tested to be 529.7 mu mol/L, and the medicine, the use method and the dosage are as follows: 10g of the composition is taken with boiled water every time, the composition is taken once a day, no pain is caused for 7 days, slight pain occurs when the composition is not taken for 7 days, the pain is basically eliminated after the composition is continuously taken for 15 days, the composition is basically cured after the composition is taken for 25 days, and the content of uric acid in blood serum is displayed to be 310.8 mu mol/L by blood drawing detection on 25 days.

Case 2: high birth, age 52, with acute gout symptoms, before treatment, serum uric acid test content of 562.1 μmol/L, taking the medicine described in example 6, using and dose: 45g of the Chinese medicinal composition is decocted every time (firstly, the dodder and the eucommia are decocted for about 1 hour, dregs of a decoction are removed, and the honey of winter, the pithecellobium clypearia extract, the coconut extract and the green papaya extract are added), the Chinese medicinal composition is taken once a day on 10 th days, no pain is caused, slight pain occurs when the Chinese medicinal composition is taken after 10 th days, the pain is basically eliminated after the Chinese medicinal composition is continuously taken for 30 days, the Chinese medicinal composition is basically healed after 40 th days, and the content of uric acid in blood serum is 331.4 mu mol/L through.

Case 3: mr. plum, 50 years old, with acute gout symptoms, with mild diabetes, pre-treatment, serum uric acid test level of 580.2 μmol/L, taking the drugs described in example 7, methods and amounts: the medicine is decocted 18g each time (firstly, dodder and eucommia are decocted for about 1 hour, dregs of a decoction are removed, and pithecellobium clypearia extract, coconut extract and green papaya extract are added), the medicine is taken once a day, no pain is caused on the 12 th day, slight pain occurs when the medicine is taken no longer on the 12 th day, the pain is basically eliminated after the medicine is taken for 30 days continuously, the medicine is basically cured on the 45 th day, and the content of uric acid in blood serum is shown to be 306.3 mu mol/L after blood drawing detection on the 45 th day.

Finally, it should be noted that the above embodiments are only used for illustrating the technical solutions of the present invention and not for limiting the protection scope of the present invention, and although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions can be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.

Claims

1. Use of extract of Pithecellobium clypearia in preparing medicine, food and health product for preventing and/or treating hyperuricemia and metabolic disorder related to hyperuricemia.

2. The use of claim 1, wherein the metabolic disorder associated with hyperuricemia comprises at least one of acute gout, chronic gout, gouty arthritis, gout flares, uric acid nephrolithiasis, and gouty nephropathy.

3. Application of Pithecellobium clypearia extract in preparing xanthine oxidase inhibitor is provided.

4. A medicine, food or health-care product composition for preventing and/or treating hyperuricemia and metabolic disorders related to the hyperuricemia, which is characterized by comprising an extract of Pithecellobium clypearia and auxiliary materials or auxiliary components acceptable in the medicine, food or health-care product.

5. The pharmaceutical, food or health care composition for preventing and/or treating hyperuricemia and metabolic disorders related to hyperuricemia according to claim 4, wherein the extract of Pithecellobium clypearia is prepared by extracting fresh Pithecellobium clypearia leaves with a solvent.

6. The pharmaceutical, food or nutraceutical composition for preventing and/or treating hyperuricemia and metabolic disorders related to hyperuricemia according to claim 4, wherein the preparation method of the pithecellobium clypearia extract comprises the following steps:

(2) spray drying, and rapidly cooling to obtain the extract.

7. The pharmaceutical, food or nutraceutical composition for preventing and/or treating hyperuricemia and metabolic disorders related to hyperuricemia according to claim 4, wherein the composition further comprises the coconut extract and the chaenomeles speciosa extract, and the weight ratio of the pittosporum clypearia extract, the coconut extract and the chaenomeles speciosa extract is: extract of Pithecellobium clypearia: coconut extract: the ratio of the green papaya extract to 2: 0.5-2; preferably, the weight ratio of the pithecellobium clypearia extract to the coconut extract to the papaya extract is: extract of Pithecellobium clypearia: coconut extract: the ratio of the green papaya extract to the green papaya extract is 2:1: 1.

8. The pharmaceutical, food or nutraceutical composition for the prevention and/or treatment of hyperuricemia and metabolic disorders associated with hyperuricemia according to claim 7, wherein the composition further comprises the following A or B composition:

composition A: winter honey, semen Cuscutae, and Eucommiae cortex;

composition B: dodder seed and eucommia bark.

9. The pharmaceutical, food or nutraceutical composition for preventing and/or treating hyperuricemia and metabolic disorders related to hyperuricemia according to claim 8, wherein the weight ratio of the pithecellobium clypearia extract to the components of the composition a is: the extract of the pithecellobium clypearia is winter honey, dodder and eucommia ulmoides are 1: 4-7: 0.5-2; the weight ratio of the pithecellobium clypearia extract to the B composition is as follows: the extract of the pithecellobium clypearia is semen cuscutae and eucommia ulmoides in a ratio of 1: 2-3.

10. A pharmaceutical, food or health product comprising the pharmaceutical, food or health product composition for preventing and/or treating hyperuricemia and a metabolic disorder associated with hyperuricemia according to any one of claims 4 to 9.