WO2009135351A1

WO2009135351A1 - The use of the extract of prunus mume for preparation of compositions

Info

Publication number: WO2009135351A1
Application number: PCT/CN2008/070874
Authority: WO
Inventors: 张英; 陆柏益; 刘志河; 吴晓琴; 夏道宗; 石丽花
Original assignee: 杭州尤美特科技有限公司; 烟台新时代健康产业有限公司
Priority date: 2008-05-05
Filing date: 2008-05-05
Publication date: 2009-11-12
Also published as: KR101384410B1; JP2011522791A; JP5546039B2; KR20110021844A

Abstract

The uses of the extract of Prunus mume for preparation of compositions for treatment or prevention of gout, gouty arthritis, hyperuricemia, and for lowering blood fat and/or inhibiting inflammations are disclosed. The extracts and compositions having above mentioned effects are also disclosed.

Description

Application of plum tree extract in preparing composition

The invention relates to the field of medicine and health food. More specifically, it relates to the application of extracts of plum blossom, plum branch, plum, plum, and plum in the preparation of medicines and health foods for preventing and treating hyperuricemia and gout. Background technique

Plum is a plant of the family Rosaceae. The scientific name is Prunus m. S i eh. Et Zucc. The horticultural planting is divided into plum and plum, and plum is divided into white plum, green plum and red plum.

W000/39249 (PCT/JP99/07285) discloses a medicinal plum extract and a composition containing the same, wherein the following is disclosed: "Using 5 volumes of methanol, stems and leaves of plum Extract of plum, plum and plum, the extract has anti-oxidation, gastric mucosal damage inhibition, aldose reductase inhibition, blood glucose increase inhibition, platelet aggregation promotion, alcohol absorption inhibition and anti-inflammatory Function: "The plum extract involved is obtained by alcohol extraction or dry distillation. The methanol extract of the stem of the plum leaves contains pentacyclic triterpenoids. The methanol extract of plum blossom contains flavonoids such as quercetin glycoside. Substance, but lacks systematic exploration of the extraction process, and no quantitative data on the possible active ingredients of the plum extract, not to mention the determination of the effective site group and the standardization of the formulation. This crude methanol extract has no separation and purification, high impurity content, low content of active ingredients, deep color, strong hygroscopicity, difficulty in preservation, and poor processing adaptability. At the same time, the varieties of plum trees used are not clear. When the extracts are used in the medical field, if the source of the plants is uncertain, the three basic requirements for effective, safe and stable drugs cannot be guaranteed. Furthermore, this document does not address the role of plum extract in the prevention and treatment of hyperuricemia and gout.

Gout is a disease caused by a disorder of sputum metabolism, which leads to hyperuricemia, and/or a decrease in uric acid excretion by the kidneys, which causes urate to deposit in tissues. Its clinical features are hyperuricemia, characteristic recurrent arthritis, tophi deposits, tophus-induced chronic arthritis and joint deformities, often involving kidney-induced chronic interstitial nephritis and uric acid kidney stone formation, which has become today Common diseases in middle-aged men in the world.

The pathogenesis and treatment of gout are not fully understood by humans. Whether it is primary or secondary, most of them are caused by drugs, and most of them lack etiological treatment, so they cannot be cured. At present, there are few varieties of anti-gout drugs in the pharmaceutical market. For example, the drugs for treating acute gout attacks include colchicine, non-body analgesics and glucocorticoids. The main treatments for gout and interstitial period are: uric acid Excretion drugs (such as probenecid, sulfinpyrazone) and drugs that inhibit uric acid production (such as allopurinol). Although these drugs have a fast anti-inflammatory and analgesic effect, they have no anti-inflammatory and analgesic effects, and most of the drugs have obvious side effects. For example, the effective dose of colchicine is similar to the dose of gastrointestinal symptoms such as diarrhea. Systemic adverse reactions such as myelosuppression, liver and kidney damage, and central nervous system damage. Non-anti-inflammatory drugs are absolutely banned in the presence of active peptic ulcers and gastrointestinal bleeding. For example, phenylbutazone can cause severe neutropenia or aplastic anemia as short as 3 weeks. In the treatment of hyperuricemia, uric acid-lowering drugs have no antipyretic, analgesic, anti-inflammatory effects, not only unhelpful for acute arthritis, but also aggravate symptoms or prolong the course of disease, and early treatment with uric acid alone , there is the possibility of inducing an acute attack of gout. CN97116712. 5 discloses that tea pigment can inhibit hyperuricemia, prevent gout attack, and has therapeutic effect; CN981 10667. 6 discloses a combination of Mutong, Motherwort, Psyllium, Miren, Atractylodes, Phellodendron, Achyranthes The substance has the functions of clearing away heat and dampness, promoting blood circulation and turbidity, can reduce blood uric acid, treat gouty arthritis, prevent joint deformity and kidney disease; CN200410034933. 9 discloses a composition mainly composed of total flavonoids, total organisms, and volatile oil, It has the effect of lowering high uric acid, but it does not show the anti-inflammatory and analgesic effects.

The treatment of gout, first of all, to alleviate the pain caused by this, and then reduce the "excessive" uric acid to the normal range, but also need to actively prevent the induction and aggravation factors of gout, in order to achieve the purpose of disease treatment, disease prevention, Therefore, the prevention and treatment strategy of gout should highlight "preventing problems before they occur." However, for the characteristics of acute gout disorders, there are no drugs with significant effects in anti-inflammatory, analgesic and uric acid-lowering.

Therefore, there is an urgent need in the art to provide a novel substance which can exert an effect on anti-inflammatory, analgesic and uric acid-lowering, and is effective for treating and preventing gout. Summary of the invention

It is an object of the present invention to provide a novel substance for the treatment and prevention of gout. In a first aspect of the invention, there is provided the use of a plum tree extract for the preparation of a composition for treating or preventing gout.

In another preferred embodiment, the composition is also useful for lowering blood uric acid, lowering blood lipids and/or inhibiting inflammation. In a second aspect of the invention, there is provided a use of a plum tree extract for the preparation of a composition for the treatment or prevention of hyperuricemia.

In another preferred embodiment, the composition can also be used to (a) treat gout; and/or (b) treat gouty arthritis.

In a third aspect of the invention, there is provided a use of a plum tree extract for the preparation of a composition for the treatment of gouty arthritis.

In another preferred embodiment, the composition can also be used to (a) treat gout; and/or (b) lower blood uric acid. In a fourth aspect of the invention, there is provided a use of a plum tree extract for the preparation of a blood lipid lowering composition.

In another preferred embodiment, the composition is also useful for treating gout; and/or (b) lowering blood uric acid. In a fifth aspect of the invention, there is provided a use of a plum tree extract for the preparation of a composition for reducing the frequency of gout occurrence.

In another preferred embodiment, the composition may also be used to (a) lower blood uric acid; (b) lower blood lipids; and/or (c) inhibit inflammation.

In a sixth aspect of the invention, there is provided a plum extract useful for treating, preventing gout, reducing hyperuricemia, treating gouty arthritis and/or lowering blood lipids.

In another preferred embodiment, the plum extract comprises water-soluble and/or fat-soluble extracts of flowers, branches, leaves, roots, and/or trunks of plum trees.

In another preferred embodiment, the plum tree extract is a non-fruit extract of plum, especially a flower, branch, and/or leaf extract of plum. In another preferred embodiment, the plum tree extract is supercritical (3⁄4 extract, organic solvent extract, water extract or a mixture thereof).

In another preferred embodiment, the plum extract contains 0.5-50% by weight of squalene, based on the total weight of the extract.

In another preferred embodiment, the plum tree extract contains at least one of the following ten compounds:

II Heliconone (Friedelin)

IV Glutitol (Sitosterol)

V Citric acid

VI Tartaric acid

VII Malic acid

VI I I Chlorogenic Acid (Chlorogeni c ac id)

IX succinic acid (Succ inic ac id) = H, or glycosyl

X Quercetin and its derivatives.

In another preferred embodiment, the plum tree is a plum tree of the family Rosaceae; more preferably, the plum tree is a green plum.

In a seventh aspect of the invention, there is provided a plum tree composition useful for treating, preventing gout, reducing hyperuricemia, treating gouty arthritis and/or lowering blood lipids.

In another preferred embodiment, the composition comprises a pharmaceutical composition, a food composition or a nutraceutical composition.

In another preferred embodiment, the composition comprises an additional component selected from the group consisting of plum extract, tea extract, vitamins, or a combination thereof.

In another preferred embodiment, additional components that lower blood uric acid are also included.

In another preferred embodiment, additional blood lipid lowering components are also included.

In another preferred embodiment, an additional component that inhibits inflammation is also included.

In another preferred embodiment, the composition is selected from the group consisting of

(i) powders, granules, capsules, injections, elixirs, oral solutions, tablets or lozenges;

(i i) beverages or alcohol.

In an eighth aspect of the invention, there is provided a method of treating or preventing gout comprising the steps of: administering a plum tree extract to a subject in need thereof.

In a ninth aspect of the invention, there is provided a method of reducing hyperuric acid comprising the steps of: applying a plum extract to a subject in need thereof.

In a tenth aspect of the invention, there is provided a method of treating gouty arthritis comprising the steps of: administering a plum tree extract to a subject in need thereof.

In an eleventh aspect of the invention, there is provided a method of lowering blood lipids comprising the steps of: applying a plum extract to a subject in need thereof.

In a twelfth aspect of the invention, there is provided a method of reducing the frequency of gout occurrence comprising the steps of: applying a plum extract to a subject in need thereof.

In another preferred embodiment, the application amount is 500-1000 mg/60 kg body weight per day on average, and the administration time is 1 week-1 year or longer. In another preferred embodiment, the subject is a mammal, more preferably a human.

In another preferred embodiment, the plum tree extract is a plum fruit extract. Accordingly, the present invention provides a novel substance which can exert an effect on anti-inflammatory, analgesic and uric acid-lowering, and is effective for treating and preventing gout. detailed description

After extensive and intensive research, the inventors have unexpectedly discovered that extracts of plum trees, especially water-soluble and/or fat-soluble extracts of non-fruit parts of plum trees (such as supercritical CO ₂ extracts, organic solvent extracts or / and aqueous extracts), can be used to treat gout in a variety of ways, such as effective reduction of blood uric acid, treatment of gouty arthritis, lowering blood lipids, reducing the number of gout attacks or affecting UA (blood uric acid), LP0 (plasma lipid peroxide) , SOD (peroxide deuterase), N0 ² 7N0 ³ - changes, so it can be used to prevent gout or inhibit hyperuricemia. As used herein, the term "composition" includes (a) a composition for treating, preventing gout, (b) a composition for lowering high blood uric acid, and/or (c) a composition for reducing uric acid.

As used herein, 3⁄4 Prunus mume S i eb. Et Zucc) is a TPosscese plant. Plum trees which can be used in the present invention include white plum, green plum and red plum, and more preferably green plum.

The plum tree extract provided by the present invention may be derived from all of the plum trees, preferably the non-fruit portions thereof. The non-fruit portion includes flowers, branches, rods, roots, or leaves. Plum blossoms are mainly unfruited flowers. They are dried after sun-dried, dried or dried for later use. Plum branches can be spring-cutted vegetative shoots, autumn-pruned branches, or plum-cut branches, dried, Cut off, crushed and spared; plum and plum roots are derived from plum trees after felling; plum leaves are generally collected in summer and autumn, and dried for use.

As used herein, "extracts" include water-soluble and/or fat-soluble extracts. The term also includes alcohol extracts, or aqueous extracts. Further, it also includes an effective site group, i.e., an extract containing a fat-soluble effective site and a water-soluble active site, or a mixture thereof.

The plum tree extract which can be used in the present invention is not particularly limited, and may be a water-soluble and/or fat-soluble extract obtained by a conventional method using a fruit or a non-fruit portion of plum tree as a raw material.

In a preferred embodiment, the fat-soluble active site is an extract obtained by extracting the above-mentioned non-fruit portion with supercritical CO ₂ or a non-polar organic solvent, containing long-chain alkanes, multiolefins, V _E , and alcohol compounds; The effective part is obtained by extracting the solvent by supercritical co ₂ extraction or organic solvent leaching, extracting with an aqueous solution, and obtaining by other high-efficiency extraction and separation means, containing flavonoids and triterpenoid saponins.

Preferably, the method for preparing the non-fruit partial effective portion group of the plum tree is obtained by stepwise extraction using plum, plum, plum, plum, and plum leaves as raw materials respectively:

(1) The plum, plum, plum, plum, and plum leaves are used as raw materials. After drying and crushing, they are extracted with supercritical CO ₂ fluid or non-polar organic solvent to obtain long-chain alkanes and polyenes. , extracts of triterpenoids and sterols, ie fat-soluble active parts of flowers, branches, rods, roots, leaves;

(2) The supercritical C0 ₂ extraction or organic solvent leaching material is stripped of solvent, and extracted with 0-50% by volume of ethanol-water solution, supplemented by microwave-assisted extraction or ultrasonic-assisted extraction and membrane separation. Means, obtaining an extract rich in flavonoids and triterpenoid saponins, that is, water-soluble effective parts of flowers, branches, rods, roots and leaves;

(3) Combining the fat-soluble effective parts of the flowers, branches, rods, roots and leaves with the water-soluble effective parts according to the actual crude drug extraction amount, which is the effective part group of the non-fruit part of the plum tree.

Specifically, the method for preparing the non-fruit portion of the plum tree is prepared by using plum, plum, plum, plum, and plum leaves as raw materials, and optionally, after drying and crushing, adding a certain volume of methanol or ethanol solution, Extraction, hot reflux extraction, microwave-assisted extraction or ultrasonic-assisted extraction, the extract is filtered, concentrated, and dried to obtain an alcohol extract of the non-fruit portion of the plum tree. Preferably, the methanol or ethanol solution has a volume concentration of 70-95%.

Specifically, the preparation method of the non-fruit partial water extract of plum tree is based on plum blossom, plum branch, plum, plum root, plum leaf, etc., and is immersed in water to swell and then heated to reflux, and the extract is concentrated to a certain volume (usually 1 : 1 raw dose), add alcohol alcohol precipitation (50-70% final concentration of ethanol), take the supernatant to recover ethanol under reduced pressure, and concentrate the liquid to a certain solid content (usually at 15-30) After %), spray drying or vacuum drying to obtain an aqueous extract of the non-fruit portion of the plum tree.

Extracts of the plum fruit portion can be obtained using methods commonly used in the art. Use

Plum extract can be used as an active ingredient in a composition for treating or preventing gout. The plum tree extract may include a fat-soluble effective part of the non-fruit part of the plum tree, a water-soluble effective part of the non-fruit part of the plum tree, an alcohol extract of the non-fruit part of the plum tree, a non-fruit part of the plum tree, and a plum tree fruit. Partial extract, or a mixture thereof. Preferably, the non-fruit portion of the plum tree is a fat-soluble effective portion, a water-soluble effective portion, and a plum tree fruit extract; more preferably, the non-fruit portion of the plum tree is a fat-soluble effective portion and a water-soluble effective portion.

The plum tree extract described in the composition contains at least one of the following ten compounds:

I Squalene

I I lignin (Friedel in)

I I I phytol

IV sitosterol (S i tosterol)

V citric acid (Ci tri c ac id)

VI Tartaric acid (Tartari c ac id)

VI I Malic acid (Mal ic ac i d)

VI I I Chlorogenic acid (Chlorogenic ac id)

IX succinic acid (Succ ini c ac id)

Quercetin and its derivatives.

The active ingredient in the composition may contain, in addition to the non-fruit extract of the plum tree described above, additional ingredients which are useful for treating or preventing gout, such as fruit extracts of plum trees, tea extracts, vitamins or combinations thereof.

In the composition of the present invention, other substances (extracts or compounds) having a therapeutic or preventive gout, lowering blood uric acid, inhibiting uric acid production, promoting uric acid excretion, lowering blood fat or reducing inflammation, and relieving pain, such as tea extract, may also be included. Terpenoids (such as allopurinol), probenecid, sulfinoxazolone, statins (such as simvastatin, pravastatin, lovastatin), hormones (such as glucocorticoids, steroid hormones). The plum tree extract of the present invention can also be used to lower the active ingredient in a blood uric acid composition. The plum tree extract may include a fat-soluble effective part of the non-fruit part of the plum tree, a water-soluble effective part of the non-fruit part of the plum tree, an alcohol extract of the non-fruit part of the plum tree, a non-fruit part of the plum tree, and a plum tree fruit. Partial extract, or a mixture thereof. Preferably, the non-fruit portion of the plum tree is a fat-soluble effective portion, a water-soluble effective portion, and a plum tree fruit extract; more preferably, the non-fruit portion of the plum tree is a fat-soluble effective portion and a water-soluble effective portion.

Other substances having a blood uric acid lowering effect may also be included in the composition of the present invention. The plum tree extract of the present invention can also be used as an active ingredient in a blood fat reducing composition. The plum tree extract may include a fat-soluble effective part of the non-fruit part of the plum tree, a water-soluble effective part of the non-fruit part of the plum tree, an alcohol extract of the non-fruit part of the plum tree, a non-fruit part of the plum tree, and a plum tree fruit. Partial extract, or a mixture thereof. Preferably, the non-fruit portion of the plum tree is a fat-soluble effective portion, a water-soluble effective portion, and a plum tree fruit extract; more preferably, the non-fruit portion of the plum tree is a fat-soluble effective portion and a water-soluble effective portion.

Other substances having a blood lipid lowering action may also be included in the compositions of the present invention. The plum tree extract of the present invention is also useful as an active ingredient in the treatment of gouty arthritis compositions. The plum tree extract may include a fat-soluble effective part of the non-fruit part of the plum tree, a water-soluble effective part of the non-fruit part of the plum tree, an alcohol extract of the non-fruit part of the plum tree, a non-fruit part of the plum tree, and a plum tree fruit. Partial extract, or a mixture thereof. Preferably, the non-fruit portion of the plum tree is a fat-soluble effective portion, a water-soluble effective portion, and a plum tree fruit extract; more preferably, the non-fruit portion of the plum tree is a fat-soluble effective portion and a water-soluble effective portion.

Other substances having the effect of treating gouty arthritis may also be included in the composition of the present invention. In the present invention, various compositions may be formulated according to methods well known in the art, and the active ingredients may be combined with conventional excipients, flavoring agents, disintegrating agents, preservatives, lubricants, wetting agents, binders, solvents A pharmaceutical excipient such as a thickener or a solubilizing agent is mixed to prepare any dosage form suitable for clinical use, such as a powder, a tablet, a capsule, a granule, an injection, an oral liquid preparation, and the like.

The composition may be a health food or a functional food, or a dietary supplement; it may be a health drink, alcohol, or the like.

The composition for use in the treatment or prevention of gout according to the present invention is preferably 0.1 to 5 g / 60 kg body weight per day, based on the active ingredient (non-fruit extract of plum tree) contained therein. 0. 1-2. 0 g / 60 kg body weight. The main advantages of the invention are:

1. Plum tree extract has obvious effects of treating or preventing gout;

2. Plum tree extract has obvious functions of lowering blood uric acid;

3. Plum tree extract has obvious functions of lowering blood lipids;

4. Plum tree extract has obvious functions for treating gouty arthritis;

5. Make full use of the non-fruit part of the plum tree that was previously discarded, which reduces waste of resources and is conducive to the environment. 6. Increased the utilization of plum resources, improved the economic benefits of Meilin, and benefited farmers' income. The invention is further illustrated below in conjunction with specific embodiments. It is to be understood that the examples are merely illustrative of the invention and are not intended to limit the scope of the invention. The experimental methods in the following examples which do not specify the specific conditions are usually carried out according to conventional conditions or according to the conditions recommended by the manufacturer. All percentages and parts are by weight unless otherwise stated.

Unless otherwise defined, all professional and scientific terms used herein have the same meaning as those skilled in the art. In addition, any methods and materials similar or equivalent to those described may be employed in the methods of the invention. The preferred embodiments and materials described herein are for illustrative purposes only. Example 1

The flower of the plum blossom extract, Xiaoshuang Daqingmei, Primus mume 'Da Ye Qing', is collected and dried, and then pulverized into a coarse powder of about 10 mesh, and 15 kg is taken in a supercritical extraction kettle for extraction.

Extraction conditions: extraction pressure 35 MPa, extraction temperature 60 ° C, separation temperature 40 ° C, separation pressure 4 MPa, cyclic dynamic extraction for 2 hours, in the separation kettle to obtain plum soluble extract 720g (DietmateTM (Hangzhou Youmet Technology Co., Ltd.) The company's trademark) -F01).

It was analyzed by GC-MS and mainly contained long-chain alkanes, polyenes, V _E , plant alcohols and triterpenoids. The content of the characteristic compound squalene (stearyl hexene) in the fat-soluble effective part was mass fraction. 1·04%

The raffinate was taken out from the extraction vessel, and the raffinate was extracted by hot reflux with a 30% ethanol-water solution.

Extraction conditions: temperature 80 ° C, ratio of material to liquid 1: 10 (W / V), hot reflux extraction for 2 hours, to obtain plum water soluble extract 1140g (DietmateTM-F02).

The total flavonoid content was 18.84%, total triterpenoid saponin 7.08%, total acid 5.64%; infrared spectrum analysis showed that the extract was at 3404, 2929, 1606, 1516, 1403, 1270, 1078, 868,

There are characteristic absorption peaks near 818, 780 and 612 cm- ¹ ; UV spectrum analysis shows that it has strong absorption at 327 nm and sub-absorption at 290 nm.

Combine F01 and F02 to obtain the effective part group of Plum blossom (Dietmat _e ^TM -F0). Example 2

The branch of the green plum branch, the branch of Prunus mume 3⁄4i Ye Qing', is collected and dried, and then pulverized into a coarse powder of about 10 mesh, and 15 kg is taken in a supercritical extraction kettle for extraction.

Extraction conditions: extraction pressure 30 MPa, extraction temperature 55 ° C, separation temperature 45 ° C, separation pressure

4 MPa, cyclic dynamic extraction for 2 hours, to obtain 645 g (Dietmat _e ^TM -B01).

It was analyzed by GC-MS and mainly contained long-chain alkanes, polyenes, V _E , plant alcohols and triterpenoids. The content of the characteristic compound squalene (stearyl hexene) in the fat-soluble effective part was mass fraction. 4· 87% The raffinate was taken out from the extraction vessel, and the raffinate was extracted by hot reflux with a 30% ethanol-water solution.

Extraction conditions: temperature 80 ° C, ratio of material to liquid 1: 15 (W / V), reflux extraction for 2 hours], to obtain 2400g (DietmateTM-B02) water-soluble extract of plum.

It was analyzed to contain 40.59% of total flavonoids, 19.07% of total triterpenoid saponins, and 3.70% of total acid. Infrared spectroscopy indicated that the extract had near 3406, 2926, 1609, 1519, 1447, 1394, 1284, 1070 and 611 cm- ¹ . Characteristic absorption peak; UV spectrum analysis showed that it was scanned in the wavelength range of 190-700 nm. The results showed: strong absorption at 280 nm and sub-absorption at 320 nm.

Combine B01 and B02 to obtain the effective part group of Plum branch (Dietmat _e ^TM -B0). Example 3

Green plum leaf extract

The leaves of Xiaoshan Daqingmei variety Primus mume 'Hong Ding' are collected and dried, and then pulverized into a coarse powder of about 10 mesh, and 15 kg is taken in a supercritical extraction kettle for extraction.

Extraction conditions: extraction pressure 35 MPa, extraction temperature 55 ° C, separation temperature 40 ° C, separation pressure 6 MPa, cyclic dynamic extraction for 2 hours, to obtain plum emulsifiable extract 975 g (DietmateTM-L01).

It was analyzed by GC-MS and mainly contained long-chain alkanes, polyenes, V _E , plant alcohols and triterpenoids. The content of the characteristic compound squalene (stearyl hexene) in the fat-soluble effective part was mass fraction. 44·15%.

Extraction conditions: temperature 70 ° C, ratio of material to liquid 1: 12 (W / V), extraction for 3 hours], obtained 1680g (DietmateTM-L02) water-soluble extract of plum leaves; analyzed containing 30.46% of total flavonoids, Total triterpenoid saponin 4.93%, total acid 5.96%; infrared spectrum analysis showed that the extract had characteristic absorption peaks around 3386, 2932, 1596, 1516, 1404, 1314, 1074, 776, 721, 611, 527 cm-1; The results of UV spectroscopy showed strong absorption at 322 nm and sub-absorption at 285 nm.

Combining L01 and L02 is the effective part group of the plum leaf (Dietmate ^TM -L0).

Example 4

Green plum extract

The raw rod of Xiaoshan Daqingmei variety Prunus mume 'Hong Feng' is used as raw material. After collecting and drying, it is pulverized into a coarse powder of about 10 mesh, taken 15kg, and added with 30% ethanol solution 150 heat reflux extraction.

Extraction conditions: The temperature is 70 ° C, the ratio of material to liquid is 1: 10 (W / V), extraction for 3 hours], the extract is filtered, concentrated under reduced pressure, spray dried to obtain plum alcohol extraction (Dietmat _e ^TM - Hl) 584g. Example 5

Green plum root extract

Based on the roots of iPrunus mume Da Ye Qing', Xiaoqingqing After collecting and drying, it is pulverized into a coarse powder of about 10 mesh, taken 15 kg, and immersed in 250 L of pure water for 3 hours, and then microwave-assisted extraction.

Extraction conditions: The power is 1000W, the ratio of material to liquid is 1: 10 (W/V), 1 hour, after the extract is filtered, it is concentrated to a volume of about 1:1 of the crude drug, and 3 times the volume of edible alcohol is mixed. After being placed in a cold storage at about 4 ° C overnight, the supernatant is taken, the ethanol is recovered under reduced pressure, and the extract is concentrated to a solid content of about 20%, and spray-dried to obtain a water extract of Meigen (Dietmat _e ^TM -R2) 467g. Example 6

Examples 1, 2, 3 Dietmate ^TM -F02 prepared, B02, L02 and the vitamins A, B and other materials according to the formulations of Table 1 were mixed to prepare oral liquid bottle 100mL.

Table 1 Dietmat _e ^TM anti-gout oral liquid formula

Example 7

Anti-gout animal test of non-fruit extract of plum tree

1. Experimental materials

Rat toe volume measuring instrument (purchased from Zhejiang University of Traditional Chinese Medicine), 4 °C refrigerator, ImL syringe, 6 ^# injection needle, filter paper; uric acid, NaOH, HCl, normal saline, distilled water, etc.

SD male rats (purchased from the Experimental Animal Center of Zhejiang Academy of Medical Sciences)

Plum fruit non-fruit extract sample: Dietmat _e ^T prepared in Examples 1, 2, and 3, respectively

^M -F0, B0, L0.

2, the experimental method

(1) Preparation of sodium urate crystal and sodium urate solution

Take 194mL distilled water and 6mL NaOH (lmol / L), add lg uric acid after boiling, adjust 11 to 7.2 with HCl (lmol / L), stir at room temperature, store in a refrigerator at 4 ° C for 24 hours, remove the supernatant, use The filter paper blotted the water of the precipitate, and dried it in a dry box (7CTC) for 2 hours. The powder was removed and placed in a mortar and ground into fine powder. The mixture was filtered through a metal mesh having a pore size of 250 μm, and bottled for use.

Take 500mg sodium urate crystal (MSU), add 9mL of normal saline, add ImL Tween-80 at the same time, heat and stir, and prepare 10mL sodium urate solution for use.

(2) Animal model making

The inside of the tibialis anterior tendon was inserted into the right posterior tibial joint of the right hind limb of the test rat with a 6-gauge needle. The 0.1 mL (50 mg/mL) MSU suspension was injected into the ankle joint cavity. (3) Animal testing

Thirty SD male rats were randomly divided into 5 groups (Dietmat _e ^TM -FO, B0, L0 group, model control group, normal control group), 5 rats in each group, and intragastric administration was started 2 days before modeling. (500mg/kg), once a day. The model control group and the normal control group were intragastrically administered with the same volume of normal saline.

On the day of the experiment, 1 hour after intragastric administration, a 6-injection needle was inserted into the anterior tendon of the tibia in the 45° angle of the dorsal aspect of the right hind leg of the right hind limb of the test rats, and 0.1 mL (50 mg/mL) of MSU suspension was added. Inject into the ankle joint cavity, causing inflammation.

The test rats were tested for toe volume before modeling, 1 hour, 2 hours, 4 hours, 6 hours, 24 hours, 48 hours, and 72 hours after modeling. The difference in toe volume before and after inflammation is the swelling rate, and the difference ratio between groups is performed.

Swelling rate (%) = ^^xl00%

Vn and Vt represent the toe volume values before and after the 3⁄4 inflammatory agent.

3. Test results and analysis

As shown in Table 2, the model control group, Dietmat _e ^TM -B0, L0, F0 group had the highest degree of swelling at 6 hours, and disappeared at 24 hours or 48 hours; while the Dietmate ^TM -B0 group reached the highest at 4 hours, and gradually became 6 hours. Regression, 24 hours subsided significantly. ―

Table 2 Effects of DietmateTM-B0, F0, L0 on the toe swelling of rats with gouty arthritis (X±^D, n=5)

As shown in Table 3, in the effect on the rate of swelling of the toes, the Dietmat _e ^TM -F0 group was significantly different from the model control group 1 hour after the inflammation; 2 hours after the inflammation, Dietmat _e ^TM -F0, L0 group The difference was significant between the model control group and the model control group at 4 hours and 48 hours after inflammation. Dietmat _e ^TM -F0 group was significantly different from the model control group; Dietmat _e ^TM -B0, F0, L0 group and model 6 hours after inflammation There was a significant difference in the control group. ―

Table 3 Effects of DietmateTM-B0, F0, L0 on the rate of swollen toe in rats with gouty arthritis (X±5D, n=5)

Swelling rate at different times after inflammation

Group

Lh 2h 4h 6h 24h 48h 72h

8.44% ± 17.14% ± 24.20% ± 25.73% 12.79% 7.43% + 7.98Q / o model control group

0.041 0.043 0.070 0.073 ±0.083 0.056 0.101 DietmateTM 6.57% ± 15.09% ± 20.58% ± 17.11% ± 6.92% ± 4.09% ± 2.16% ± BO 0.051 0.038 0.013 0.025 0.018 * 0.008 0.014

DietmateTM -2.01% 士5.57% 9.76% 士 15.16%士 2.45% + -1.19%士 -2.95% + -F0 0.008 0.054 * 0.057*** 0.103 0.096* 0.021 0.019

DietmateTM 4.53% ± 7.99. / ₀士15.66%士14.76%士8.79%士3.09Q/o士2.65%士-L0 0.041* 0.049 0.111* 0.080 0.088 0.039* 0.037 Compared with the model group, /^^CO.01; compared with the model group, <0.05; * Compared with the model group, /3⁄4<0.1. The results showed that Dietmat _e ^TM -F0 can effectively reduce the degree of toe swelling in gouty arthritis rats, and the swelling of the toes is obviously reduced in 6 hours, the pre-inflammatory level is reached in 48 hours, and the toes are The swelling starts from 2 hours after the inflammation, which greatly shortens the swelling period;

The effective site group Dietmat _e ^TM -L0 can significantly reduce the degree of swollen toe in gouty arthritis rats 2 hours after inflammation, but the inhibition is gradually weakened after 6 hours of inflammation;

Dietmat _e ^TM -B0, a effective part of plum branch, significantly reduced the degree of swollen toe in gouty arthritis rats 6 hours after inflammation, but the inhibitory effect gradually decreased after 48 hours of inflammation. Example 8

Clinical observation of plum extract in the treatment of hyperuricemia

Case selection

All cases were confirmed to have hyperlipidemia after more than two blood tests before enrollment, and the blood uric acid content was higher than normal. A total of 60 cases were selected, including 45 males and 15 females, aged 38-75 years, with an average of 58.6 years. Among the selected cases, there were 10 cases of hyperglycemia, 25 cases of hypertension, and 9 cases of coronary heart disease.

2. Diagnostic criteria

Blood uric acid (HUA) concentration: male ≥ 417 11101 / 1 ^ female ≥ 339 μηιοΙ / L (blood uric acid by enzymatic method). 3. Medication method

Four weeks before treatment, all drugs that lower lipids and affect sputum metabolism are stopped. The capsule containing the plum effective fraction group (Dietmat _e ^TM -F0) prepared in Example 1 was administered twice a day, and the dose of Di _e tmat _e ^TM -F0 was 400 mg/day/person, and it was continuously administered for 30 days.

4. Observation method

Blood uric acid, blood lipids, blood rheology and blood glucose, liver and kidney function and blood and urine routine, electrocardiogram, fundus, and left hand unnamed nail microcirculation were detected before and after taking the drug.

5. Results

After taking Dietmat _e ^TM -F0, 58 cases of blood uric acid decreased significantly (p <0.01) in 2 cases without significant changes, the efficacy is shown in Table 4. No adverse reactions were observed in all of the symptoms and assays during the course of taking Dietmat _e ^TM -F0 in all cases.

Effect of DietmateTM-F0 on blood uric acid ( ^x± ^*, μπιοΙ/L)

Female 15 435.19±86.27 324.08 + 88.95* compared with before treatment, p<0.01

Uric acid is trioxane, and increased anabolic metabolism and decreased uric acid excretion are important mechanisms of increased blood uric acid. Hyperuricemia is a common medical condition and can be divided into primary and secondary. Commonly used alkaline drugs and allopurinol treatment.

The present invention uses the plum extract Dietmat _e ^TM -F0 to treat hyperuricemia, and the results show that the blood uric acid level before and after Dietm _a t _e ^TM -F0 treatment is extremely significant (p < 0.0) 1, and has no side effects. Description Dietmat _e ^TM -F0 has the effect of treating or preventing gout. Experimental Example 9

Clinical observation of non-fruit extract of plum tree inhibiting hyperuricemia and preventing gout attack

Experimental method

According to the American College of Rheumatology's diagnosis of gout, the patients diagnosed with primary gout were observed in 60 patients, all male, aged 42-65 years, with an average of 50.2 ± 7.6 years. There were 42 patients with hyperlipidemia, 10 patients with hypertension, 6 patients with coronary heart disease, and 3 patients with diabetes, with normal liver and kidney function.

2. Treatment

After the acute gout control period, the subjects were randomly divided into 2 groups according to the number of the visit: Group A was the experimental group, 30 cases, and the oral solution prepared in Example 6 was taken orally twice a day, 10 mL each time (equivalent to daily Extract dose 1.2 g / 60 kg body weight), for 60 consecutive days;

Group B was the control group, 30 cases, oral probenecid (500mg, 3 times a day for 60 days), and other sterols (0. lg, 2 times a day, 60 days).

Both groups of patients abstained from alcohol and avoided sorghum diet. After 3 months, the patients were followed up for acute gout attack to compare the efficacy of the two groups.

3. Laboratory inspection

Before and after treatment, the peripheral venous blood samples of the observed subjects were taken as follows.

Determination of serum total cholesterol (CH), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) by enzyme-linked reagent colorimetric method (kit purchased from Shanghai Shiba Pharmaceutical Factory), calculated according to the Friedewald formula Density lipoprotein cholesterol (LDL-C); blood uric acid (UA) with phosphotungstic acid reduction; serum creatinine (CRE) with picric acid method; serum total protein (SP) with double urinary method; serum albumin (A) Using bromocresol green method; globulin (G) is obtained by subtracting albumin from total serum protein; adenine aminotransferase (GPT) by Rydney method; enzymatic method of bilirubin; oxidase method using serum glucose; plasma peroxidation Lipid (LP0) using thiobarbituric acid fluorescence method; erythrocyte intracellular superoxide dismutase (SOD) with pyrogallol autooxidation; plasma nitric oxide (NO) using copper-plated cadmium reduction method for plasma samples N0 ² 7N0 ³ - concentration.

4. Results and analysis (compared with frequency of gout attacks before and after treatment)

(1) Comparison of the frequency of gout attacks before and after treatment. The results are shown in Table 5.

Table 5 Effect of oral liquid prepared in Example 6 on the number of gout attacks

Case number of gout attacks (times / day) Group A 30 after treatment before treatment 1.19±0.23 0.69±0.24* Group B 30 1.05±0.18 0.67±0.32* Compared with before treatment, *p<0.05 The results showed that group A was treated with oral liquid prepared in Example 6, The number of gout attacks was less than that before treatment, and the difference was significant (p<0.05), and it was comparable with the positive control group.

(2) Changes in blood lipids before and after treatment, the results are shown in Table 6.

Table 6 Comparison of changes in blood lipids before and after treatment (mmol/L)

* p<0.05 compared to before treatment;

#p<0.05 compared with group B patients.

The results showed that there was significant difference in blood lipids between group A and before treatment (p<0.05). There was significant difference in blood lipid between group A and group B after treatment (p<0.05).

The changes of blood UA, LP0, SOD and NO before and after treatment are shown in Table 7.

* p<0.05 compared to before treatment;

#p<0.05 compared with group B patients.

The results showed that patients with group A had UA, LP0, SOD before and after treatment. After significant treatment, group A and group B patients had UA, LP0, SOD, and significant differences.

(4) Correlation analysis between gout attack and blood lipids, UA, LP0 and NO

Correlation analysis showed that the gout attack was positively correlated with the content of blood lipids, UA, LP0, and NO: :. Gout is caused by dyslipidemia and sulphate sodium salt formation, and it is clinically characterized by tophus-induced chronic arthritis and gout nephropathy, and is often accompanied by hyperlipidemia, hypertension, diabetes, arteriosclerosis, and coronary heart disease. Etc., the extract of plum tree provided by the present invention, especially the extract of non-fruit portion of plum tree The main components are flavonoid glycosides, triterpenoid saponins, organic acids and other active substances, and have pharmacological effects such as anti-lipid peroxidation, hypolipidemic, and enhanced immunity.

The inventors used it to prevent recurrent episodes of primary gout. After 30 patients with primary gout with hyperlipidemia and normal liver and kidney function, the oral solution prepared in Example 6 was followed up for 3 months. The number of gout recurrences in patients taking this oral solution was significantly lower than before treatment. The blood lipids, UA, LP0, NO and other indicators of patients taking this oral liquid have also been comprehensively improved.

The results show that the extract of plum tree provided by the present invention, especially the effective fraction of the non-fruit portion of the plum tree (the fat-soluble effective fraction and the water-soluble effective fraction) has a significant anti-gout effect and may be related to its lipid-lowering effect. Example 10

Dietmat _e ^TM prepared in Example 1 -F0 500g 500g with a pharmaceutically acceptable starch as raw materials, without adding any other ingredients, 0 capsule filling made, each and weight 300mg.

The capsule was taken to 9 gout patients twice a day, two times a day. After one month, the average number of gout attacks in 10 gout patients decreased significantly without changing their diet and activity habits, indicating that plum blossoms were effective. The site group (Di etmat _e ^TM -F0) 500g has the effect of significantly reducing the number of gout attacks. Example 11

The Dietmat _e ^TM -F0, B0, L0 prepared in Examples 1, 2, and 3 were mixed with konjac flour, bamboo shoot dietary fiber powder, medicinal starch and the like according to the formula of Table 8, and were made into tablets.

Table 8 Dietmatn C Gout Tablet Formulation

The tablets were taken for 5 gout patients, taken twice a day, 1 tablet each time (2 grams per tablet); one month later, the gout symptoms of 6 gout patients were obvious without changing other diets and activities. The improvement indicates that the above tablet has a remarkable anti-gout effect. Example 12

Example Dietmate ^TM -Hl (100g) prepared as a raw material 4, 1000L was added directly to 18% of the alcohol in wine, sufficiently dissolved, mixing, filling, i.e. prepared Meibao Jian liquor, a small amount of wine drunk, Has a significant anti-gout effect. The above is only the preferred embodiment of the present invention, and is not intended to limit the essential technology of the present invention. The technical content of the present invention is broadly defined in the scope of the claims of the application, and any technical entity or method completed by another person is exactly the same as defined in the scope of the claims of the application, or is equivalent. Changes are considered to be covered by the claims.

Claims

Rights request

A use of a plum tree extract for the preparation of a composition for treating or preventing gout.

2. Use according to claim 1 wherein the composition is also for lowering blood uric acid, lowering blood lipids and/or inhibiting inflammation.

3. Use of a plum tree extract for the preparation of a composition for treating or preventing hyperuricemia.

4. Use according to claim 3, wherein said composition is further useful for (a) treating gout; and/or (b) treating gouty arthritis.

5. Use of a plum tree extract for the preparation of a composition for the treatment of gouty arthritis.

6. Use according to claim 5, wherein said composition is further useful for (a) treating gout; and/or (b) lowering blood uric acid.

7. Use of a plum tree extract for the preparation of a composition for lowering blood lipids.

8. Use according to claim 7, wherein said composition is further useful for treating gout; and / or (b) lowering blood uric acid.

9. Use of a plum tree extract for the preparation of a composition for reducing the frequency of gout.

10. Use according to claim 9, wherein the composition is further useful for (a) lowering blood uric acid; (b) lowering blood lipids; and / or (c) inhibiting inflammation.

The use according to any one of claims 1 to 10, characterized in that the composition comprises a pharmaceutical composition, a food composition or a health care composition.

The use according to any one of claims 1 to 10, wherein the plum tree extract comprises water-soluble and/or fat of flowers, branches, leaves, roots, and/or trunks of plum trees. Soluble extract.

The use according to any one of claims 1 to 10, characterized in that the plum tree is a plum tree of the family Rosaceae; more preferably, the plum tree is a green plum.

14. Use according to any of claims 1-10, characterized in that the composition comprises additional components selected from the group consisting of plum extract, tea extract, vitamins or a combination thereof.

The use according to any one of claims 1 to 10, wherein the plum tree extract contains at least one of the following ten compounds:

I Squalene

IV Glutitol (Sitosterol)

V Citric acid

VI Tartaric acid

VII Malic acid

VIII Chlorogenic acid

IX Succinic acid = H, or glycosyl

X Quercetin and its derivatives.

The use according to any one of claims 1 to 10, wherein the composition is selected from the group consisting of: (i) a powder, a granule, a capsule, an injection, an expectorant, an oral solution, a tablet or a tablet. (ii) Beverage or alcohol.

17. A plum extract for the treatment, prevention of gout, reduction of hyperuricemia, treatment of gouty arthritis and/or reduction of blood lipids.

The plum tree extract according to claim 17, wherein the plum tree extract comprises water-soluble and/or fat-soluble of flowers, branches, leaves, roots, and/or trunks of plum trees. Extract.

The plum tree extract according to claim 17, wherein the plum tree extract is a non-fruit extract of plum, especially a flower, branch, and/or leaf extract of plum.

The plum tree extract according to claim 17, wherein the plum tree extract is supercritical (3⁄4 extract, organic solvent extract, water extract or a mixture thereof).

The extract of plum tree according to claim 17, wherein the extract of plum tree contains 0.5-50% by mole of squalene, based on the total weight of the extract.

The plum tree extract according to claim 17, wherein the plum tree extract contains at least one of the following ten compounds:

II Heliconone (Friedel in)

I I I phytol

IV sterol (Si tosterol)

V citric acid (Ci tric ac id) VI Tartaric acid (Tartaric ac id)

VI I Malic acid (Mal ic ac id)

VI I I Chlorogenic Acid (Chlorogeni c ac id)

IX succinic acid (Succ inic ac id) = H, or glycosyl

Quercetin and its derivatives.

The plum tree extract according to claim 17, wherein the plum tree is a plum tree of the family Rosaceae; more preferably, the plum tree is a green plum.

24. A plum tree composition for use in the treatment, prevention of gout, reduction of hyperuricemia, treatment of gouty arthritis and/or reduction of blood lipids.

The plum tree composition according to claim 24, wherein the composition comprises a pharmaceutical composition, a food composition or a health care product composition.

26. The plum tree composition of claim 24, wherein the composition comprises an additional component selected from the group consisting of plum extract, tea extract, vitamins, or a combination thereof.

27. The plum tree composition of claim 24, wherein said composition further comprises an additional blood uric acid lowering component.

28. The plum tree composition of claim 24, wherein said composition further comprises an additional blood lipid lowering component.

The plum tree composition according to claim 24, wherein the composition further contains an additional component which inhibits inflammation.

The plum tree composition according to claim 24, wherein the composition is selected from the group consisting of: (i) a powder, a granule, a capsule, an injection, an expectorant, an oral solution, a tablet or a tablet; (ii) beverages or alcohol.

31. A method of treating or preventing gout, comprising the steps of: administering a plum tree extract to a subject in need thereof.

32. A method of reducing hyperuricemia, comprising the steps of: applying a plum extract to a subject in need thereof.

33. A method of treating gouty arthritis, comprising the steps of: applying plum trees to a subject in need thereof Extract.

34. A method of lowering blood lipids, comprising the steps of: applying plum tree extract to a subject in need thereof.

35. A method of reducing the frequency of gout, which comprises the steps of: applying a plum extract to a subject in need thereof.

The method according to any one of claims 31 to 35, wherein the application amount is 500-1000 mg / 60 kg body weight per day on average, and the administration time is 1 week - 1 year or longer.

37. A method according to any one of claims 31 to 35, wherein the subject is a mammal, more preferably a human.

The method according to any one of claims 31 to 35, wherein the plum tree extract is a plum fruit extract.