JP5546039B2 - Use of plum extract to produce a composition - Google Patents

Description

  The present invention relates to the field of pharmaceuticals and health foods, and more specifically, for the production of preventive and therapeutic agents for hyperuricemia and gout and health foods, plum flowers, plum branches, plum trunks, plum roots, plum leaves Regarding the use of extracts.

  Plum is a plant of Rosaceae and its scientific name is Prunus mume Sieb. Et Zucc. In horticultural studies, plum is divided into flower plum and real plum, and real plum is divided into white plum, green plum and red plum.

  WO00 / 39249 (PCT / JP99 / 07285) discloses a plum extract having medicinal properties and a composition containing the same, from plum stems and leaves, plum nuclei and plum flowers in five times the volume of methanol. It has been disclosed that the produced extract has an antioxidant action, gastric mucosa injury inhibiting action, aldose reductase inhibiting action, blood glucose level raising inhibiting action, platelet aggregation promoting action, alcohol absorption inhibiting action and inflammation inhibiting action. The plum extract is obtained by alcohol extraction method or dry distillation method. Plum stem and leaf methanol extract contains pentacyclic triterpenoid compounds, plum flower methanol extract contains flavone substances such as quercetin glycosides. However, not only is there a systematic search for the extraction process, but there is also no quantitative data on possible active ingredients of plum extract, and of course there is no specification of the effective fraction and standardization of the formulation. Such a crude methanol extract is not separated and purified, has a high content of impurities, a low content of active ingredients, a deep color, a strong hygroscopic property of the product, is difficult to store, and has poor adaptability to processing. In addition, the plum varieties used are not clear, and when applying the extract to the pharmaceutical field, the three basic requirements of drug efficacy, safety, and stability cannot be met without identifying the origin of the plant. . In addition, this document does not relate to the action of plum extract in preventing or treating hyperuricemia and gout.

  Gout is a disease in which urate accumulates in tissues by causing hyperuricemia and / or a decrease in uric acid excreted from the kidney by purine metabolism disorders. Its clinical features include hyperuricemia, arthritis with characteristic intussusception, goutstone deposition, gouty stone chronic arthritis, and arthritis, affecting the kidneys and affecting chronic interstitial nephritis and urinary acidity Since it often causes the formation of kidney stones, it is now a common disease among middle-aged and elderly men around the world.

  The mechanism and treatment of gout are not yet fully understood, but primary gout and secondary gout, both with few drugs, are lacking treatment for the etiology. Can not be thoroughly treated. Currently, there are few types of anti-gout drugs in the pharmaceutical market, for example, there are colchicine, nonsteroidal analgesics and glucocorticoids for the treatment of acute attacks of gout, and treatments for intermittent and chronic periods of gout attacks. These include uric acid excretion promoters (eg probenecid, sulfinpyrazone) and uric acid production inhibitors (eg allopurinol). These drugs are effective in anti-inflammatory and analgesic, but have no uric acid lowering action together with anti-inflammatory and analgesic, and the toxic side effects of most drugs are quite remarkable. There are systemic adverse reactions such as close to the dose causing the symptoms, and myelosuppression, liver / kidney damage, central nervous system damage. Nonsteroidal anti-inflammatory drugs are absolutely prohibited when active gastrointestinal ulcers and gastrointestinal bleeding occur. For example, phenylbutazone can cause granulocytopenia and aplastic anemia only after 3 weeks of administration. End up. In terms of treatment of hyperuricemia, none of the uric acid-lowering drugs have antipyretic, analgesic, anti-inflammatory effects and do not contribute to acute attack arthritis. And may induce acute attacks of gout early in treatment with uric acid-lowering drugs alone.

  CN97116712.5 discloses that brown brown suppresses hyperuricemia, prevents gout attacks, and has a therapeutic effect. CN98110667.6 is a substance composed of Kidori, beneficial mother grass, car maiko, Yonejin, cocoon, jaundice, and cow knee, and has the effect of fresh heat and turbidity, lowering blood uric acid. Disclosed are those that can treat gouty arthritis and prevent joint deformities and kidney lesions. CN200410034933.9 discloses a composition mainly composed of all flavones, whole organisms, and volatile oils, which has the effect of lowering high uric acid but does not show medicinal effects in anti-inflammatory and analgesia. .

  In the treatment of gout, first of all, to reduce the pain caused by it, then to reduce the excessively high uric acid to the normal range, and to actively induce gout to achieve the purpose of treatment if there is illness and prevention if there is no illness Therefore, it is important to prevent the gout as a strategy for preventing and treating gout. However, for the disease characteristics of acute gout, there are still no drugs that have significant therapeutic effects on any of anti-inflammatory, analgesic and uric acid lowering.

  Therefore, in this field, a novel substance that exerts effects in terms of anti-inflammation, analgesia, and uric acid lowering, and can effectively treat and prevent gout is eagerly desired.

International Publication No. 00/39249

  An object of the present invention is to provide a novel substance for treating and preventing gout.

  The first of the present invention provides the use of a plum extract for producing a composition for treating and preventing gout.

  In another preferred example, the composition described above is further used to reduce blood uric acid, blood lipid and / or inflammation.

  The second of the present invention provides use of a plum extract for producing a composition for treating and / or preventing hyperuricemia.

  In another preferred example, the aforementioned composition is further used for (a) treatment of gout and / or (b) treatment of gouty arthritis.

  The third aspect of the present invention provides the use of a plum extract for producing a composition for treating gouty arthritis.

  In another preferred example, the aforementioned composition is further used for (a) treating gout and / or (b) lowering blood uric acid.

  The fourth aspect of the present invention provides the use of a plum extract for producing a composition that lowers blood fat.

  In another preferred example, the aforementioned composition is further used for (a) treating gout and / or (b) lowering blood uric acid.

  The fifth aspect of the present invention provides the use of a plum extract for producing a composition for reducing the incidence of gout.

  In another preferred example, the aforementioned composition is further used for (a) lowering blood uric acid, (b) lowering blood fat and / or (c) suppressing inflammation.

  The sixth aspect of the present invention provides a plum extract used for the treatment and prevention of gout, high blood uric acid lowering, gouty arthritis treatment and / or blood lipid lowering.

  In another preferred example, the aforementioned plum extract comprises a water-soluble and / or fat-soluble extract of plum blossoms, branches, leaves, roots and / or stems.

  In another preferred example, the above-mentioned plum extract is a non-fruit extract of plum, in particular an extract of plum flowers, branches and / or leaves.

In another preferred example, the aforementioned plum extract is a supercritical CO ₂ extract, an organic solvent extract, a water extract or a mixture thereof.

  In another preferred example, the above-mentioned plum extract contains 0.5 to 50 wt% of squalene with respect to the total weight of the extract.

  In another preferred example, the above-described plum extract contains at least one selected from the following ten compounds.

  In another preferred example, the ume is a rose family ume, preferably ome.

  The seventh aspect of the present invention provides a plum composition used for the treatment and prevention of gout, high blood uric acid lowering, gouty arthritis treatment and / or blood lipid lowering.

  In another preferred example, the aforementioned composition comprises a drug composition, a food composition or a health food composition.

  In another preferred example, the composition described above comprises additional ingredients selected from the group consisting of plum fruit extract, tea extract, vitamins and combinations thereof.

  In another preferred example, the aforementioned composition further comprises an ingredient that lowers additional blood uric acid.

  In another preferred example, the aforementioned composition further comprises an additional blood lipid lowering component.

  In another preferred example, the composition described above further comprises an additional inflammation inhibiting component.

In another preferred example, the aforementioned composition is
(I) powders, granules, capsules, injections, tinctures, liquids for internal use, tablets or lozenges;
(Ii) with drinks or wine;
Is selected from the group consisting of

  The eighth aspect of the present invention provides a method for treating and preventing gout comprising the step of administering a plum extract to a subject in need thereof.

  The ninth of the present invention provides a method for lowering high blood uric acid, comprising the step of administering a plum extract to a subject in need thereof.

  The tenth aspect of the present invention provides a method for treating gouty arthritis, comprising the step of administering a plum extract to a subject in need thereof.

  The eleventh aspect of the present invention provides a method for lowering blood fat, comprising the step of administering a plum extract to a subject in need thereof.

  A twelfth aspect of the present invention provides a method for reducing the incidence of gout, comprising the step of administering a plum extract to a subject in need thereof.

  In another preferred example, the aforementioned dosage is on average 500-1000 mg / 60 kg body weight per day and the administration time is 1 week-1 year or more.

  In another preferred example, the subject is a mammal, preferably a human.

  In another preferred example, the aforementioned plum extract is a plum non-fruit extract.

  ADVANTAGE OF THE INVENTION According to this invention, the novel substance which exhibits an effect in aspects, such as anti-inflammatory, an analgesic, and a uric acid fall, can treat and prevent gout effectively is provided.

The inventor has extensively studied and surprisingly found that plum extracts, particularly water-soluble and / or fat-soluble extracts of non-fruit parts of plums (eg, supercritical CO ₂ extracts, organic solvent extracts and / or Or aqueous extract) effectively lowers blood uric acid, treats gouty arthritis, lowers blood fat, reduces the frequency of gout onset, or UA (blood uric acid), LPO (plasma lipid peroxide) Gout can be treated through various routes such as SOD (superoxide disproportionating enzyme), NO ^2- / NO ^3- changes, etc. to prevent gout and suppress hyperuricemia It was found to be used in such fields.

  As used herein, the term “composition” refers to (a) a composition that treats or prevents gout, (b) a composition that lowers high blood uric acid, and / or (c) lowers uric acid. Including a composition.

  As used herein, plum (Prunus mume Sieb. Et Zucc) is a plant of the Rosaceae family. The ume used in the present invention includes white ume, ome, and red ume, and preferably ume.

  Although the plum extract provided by the present invention may be derived from the whole plum, it is preferably derived from a non-fruit part. The aforementioned non-fruit parts include flowers, branches, trunks, roots or leaves. Plum blossoms are mainly non-fruited flowers, which are artificially collected and then dried by being exposed, fried or baked, and then prepared for use. The plum branch may be a nutrient branch cut in spring or a branch pruned in autumn, or it may be a branch after the plum tree has been cut down, but after exposure to dryness, cutting and pulverization Prepare for use. Plum trunks and plum roots are derived from felled plum trees. Plum leaves are usually collected twice in summer and autumn, exposed to dryness and ready for use.

  As used herein, the term “extract” includes water-soluble and / or fat-soluble extracts. The term also includes alcohol extracts and water extracts. Furthermore, the effective fraction group, ie, an extract of a fat-soluble effective fraction and a water-soluble effective fraction, or a mixture thereof is also included.

  The plum extract applied to this invention is not specifically limited, What is necessary is just the water-soluble and / or fat-soluble extract obtained by a normal method by using the fruit or non-fruit part of a plum.

In a preferred embodiment, the fat-soluble active fraction containing the non-fruit portion of the above obtained by extraction with supercritical CO ₂ or nonpolar organic solvent, long-chain alkanes, polyenes, V _E and sterol compounds extracted It is a thing. The water-soluble effective fraction is obtained by volatilizing the solvent from those extracted with supercritical CO ₂ or leaching with an organic solvent, leaching with an aqueous solvent, and using other high-speed extraction / separation means in combination. It contains flavones and triterpenoid saponins.

  Preferably, the method for producing an effective fraction group of plum non-fruit portions is a stepwise extraction using plum flowers, plum branches, plum trunks, plum roots, plum leaves and the like as raw materials.

(1) Plum flowers, plum branches, plum trunks, plum roots, plum leaves are dried, pulverized, extracted with supercritical CO ₂ or nonpolar organic solvents, and long-chain alkanes, polyenes, V _E , triterpenoids And an extract containing a large amount of a sterol compound, that is, a fat-soluble effective fraction of flowers, branches, stems, roots and leaves.

(2) The solvent is volatilized from the one extracted with supercritical CO ₂ or leached with an organic solvent, leached with an ethanol-water solution with a volume percentage of 0-50%, and with microwave assisted extraction, ultrasonic assisted extraction and membrane Extracts containing a large amount of flavones and triterpenoid saponins, ie, water-soluble effective fractions of flowers, branches, stems, roots, and leaves, are obtained by using means such as separation.

  (3) The above-mentioned oil-soluble effective fraction and water-soluble effective fraction of flowers, branches, stems, roots, and leaves are merged and mixed uniformly with the actual herbal extract amount to obtain a plum non-fruit portion effective fraction group. .

  Specifically, the method for producing a non-fruit part alcohol extract of plum is made from plum flowers, plum branches, plum trunks, plum roots, plum leaves, etc. as a raw material, dried and crushed by any method, and then a predetermined volume of methanol or The extract extracted by adding ethanol solution, leaching, heat reflux extraction, microwave assisted extraction or ultrasonic assisted extraction is filtered, concentrated, and dried to obtain a plum non-fruit part alcohol extract It is. The volume concentration of the methanol or ethanol solution is preferably 70-95%.

  Specifically, the method for producing a plum non-fruit part water extract is made from plum flower, plum branch, plum trunk, plum root, plum leaf, etc. After concentrating the liquid to a predetermined volume (usually 1: 1 crude drug amount), edible alcohol is added and ethanol precipitated (the final concentration of ethanol is 50-70%), the supernatant is taken, ethanol is recovered under reduced pressure, After concentrating the raw material liquid to a predetermined solid content (usually 15-30%), it is spray dried or vacuum dried to obtain a plum non-fruit part water extract.

The extract of the plum fruit part is obtained by a method commonly used in this field.
Use Plum extract can be used as an active ingredient in a composition for treating and preventing gout. The above-mentioned plum extract is a plum non-fruit part fat-soluble effective fraction, plum non-fruit part water-soluble effective fraction, plum non-fruit part alcohol extract, plum non-fruit part water extract, plum fruit part extract or their Mixtures may be included. It preferably contains a fat-soluble effective fraction of ume non-fruit part, a water-soluble effective fraction and a plum fruit extract, and more preferably contains a fat-soluble effective fraction and a water-soluble effective fraction of ume non-fruit part. .

The aforementioned plum extract in the composition contains at least one selected from the following ten compounds.
I Squalene
II Friedelin
III Phytol
IV Sitosterol
V Citric acid
VI Tartaric acid
VII Malic acid
VIII Chlorogenic acid
IX Succinic acid
X Quercetin and its derivatives.

  As an active ingredient in the composition, in addition to the above-mentioned plum non-fruit extract, for example, an additional ingredient that contributes to the treatment / prevention of gout such as plum fruit extract, tea extract, vitamins or a combination thereof may be contained. .

  In the composition according to the present invention, tea leaf extract, purine compound (for example, allopurinol), probenecid, which has further effects of gout treatment / prevention, blood uric acid lowering, uric acid production suppression, uric acid excretion promotion, blood lipid lowering or anti-inflammatory / analgesic effect, Other substances (extracts and compounds) such as sulfinpyrazone, statin compounds (for example, simvastatin, pravastatin, lovastatin) and hormones (for example, glucocorticoid, steroid hormone) may be included.

  The plum extract according to the present invention may be used as an active ingredient in a composition that lowers blood uric acid. The above-mentioned plum extract is a plum non-fruit part fat-soluble effective fraction, plum non-fruit part water-soluble effective fraction, plum non-fruit part alcohol extract, plum non-fruit part water extract, plum fruit part extract or their Mixtures may be included. It preferably contains a fat-soluble effective fraction of ume non-fruit part, a water-soluble effective fraction and a plum fruit extract, and more preferably contains a fat-soluble effective fraction and a water-soluble effective fraction of ume non-fruit part. .

  The composition according to the present invention may further contain another substance having a blood uric acid lowering action.

  The plum extract according to the present invention may be used as an active ingredient in a composition that lowers blood fat. The above-mentioned plum extract is a plum non-fruit part fat-soluble effective fraction, plum non-fruit part water-soluble effective fraction, plum non-fruit part alcohol extract, plum non-fruit part water extract, plum fruit part extract or their Mixtures may be included. It preferably contains a fat-soluble effective fraction of ume non-fruit part, a water-soluble effective fraction and a plum fruit extract, and more preferably contains a fat-soluble effective fraction and a water-soluble effective fraction of ume non-fruit part. .

  The composition according to the present invention may further contain other substances having a hypolipidemic action.

  The plum extract according to the present invention may be used as an active ingredient in a composition for treating gouty arthritis. The above-mentioned plum extract is a plum non-fruit part fat-soluble effective fraction, plum non-fruit part water-soluble effective fraction, plum non-fruit part alcohol extract, plum non-fruit part water extract, plum fruit part extract or their Mixtures may be included. It preferably contains a fat-soluble effective fraction of ume non-fruit part, a water-soluble effective fraction and a plum fruit extract, and more preferably contains a fat-soluble effective fraction and a water-soluble effective fraction of ume non-fruit part. .

  The composition according to the present invention may further contain another substance having a therapeutic action for gouty arthritis.

  In the present invention, various compositions can be prepared by methods well known in the art, and the active ingredients are ordinary excipients, flavoring agents, disintegrating agents, preservatives, lubricants, wetting agents, binders, It can be mixed with a drug adjuvant such as a solvent, a thickener or a compatibilizing agent to form a dosage form for clinical application such as powder, tablet, capsule, granule, injection, oral liquid preparation and the like.

  The aforementioned composition may be a health food, a functional food or a supplement, and may be a health drink, wine or the like.

  The composition for treating / preventing gout provided by the present invention has an effective dose of 0.01-5 g / 60 kg body weight per day with an active ingredient (plum non-fruit extract) contained therein. Preferably, it is 0.1-2.0 grams / 60 kilogram body weight.

The main advantages of the present invention are:
1. Plum extract has a remarkable gout treatment / prevention function.
2. Plum extract has a remarkable blood uric acid lowering function.
3. Plum extract has a remarkable blood lipid lowering function.
4). Plum extract has a remarkable therapeutic function for gouty arthritis.
5. We will make full use of the conventional non-fruit portion of ume to reduce waste of resources and contribute to environmental conservation.
6). Improve the utilization rate of plum resources, improve the economic benefits of plum forests, and contribute to increasing farmers' income.

  Hereinafter, the present invention will be further described with reference to specific examples. It should be understood that these examples are only used to illustrate the invention and do not limit the scope of the invention. Experimental methods that do not describe specific conditions in the following examples are performed under normal conditions or conditions recommended by the manufacturer. Unless otherwise stated, all percentages and parts are by weight.

  Unless otherwise defined, all technical and scientific terms used in the sentence have the same meanings as are well known to those skilled in the art. In addition, any methods and materials similar or equivalent to those described can be used in the methods of the present invention. The preferred embodiments and materials described in the text are for listing only.

[Example 1]
Ome Flower Extract The flower of Prunus mume 'Da Ye Qing', which is a cultivar of Ulsan Dai Ome, is collected, dried, pulverized into a coarse powder of about 10 mesh, 15 kg is taken, and a supercritical extraction clave And extracted.

  Dynamic circulation extraction was performed for 2 hours under the extraction conditions of an extraction pressure of 35 MPa, an extraction temperature of 60 ° C., a separation temperature of 40 ° C., and a separation pressure of 4 MPa, and 720 g of a plum-soluble fat-soluble extract was obtained in a separation clave (Dietmate® ) (Trademark of Hangzhou Yumi Special Technology Co., Ltd.)-F01).

According to GC-MS analysis, this extract contains mainly long-chain alkanes, polyenes, V _E , plant sterols, and triterpenoid compounds, of which squalene (tetracosahexaene) is a fat-soluble effective The content in the fraction was 1.04% by mass fraction.

  The extraction residue was taken out from the extraction clave and subjected to hot reflux extraction with a 30% ethanol-water solution.

  Thermal reflux extraction was performed for 2 hours under the extraction conditions of a temperature of 80 ° C. and a raw material-solution ratio of 1:10 (W / V) to obtain 1140 g of a water-soluble extract of plum flowers (Dietmate (registered trademark) -F02).

Analysis showed that the total flavone content was 18.84%, the total triterpenoid saponin content was 7.08%, and the total acid was 5.64%. By infrared spectrum, this extract had characteristic absorption pork around 3404, 2929, 1606, 1516, 1403, 1270, 1078, 868, 818, 780, 612 cm ⁻¹ . According to the ultraviolet spectrum, this extract showed a strong absorption at 327 nm and a second strong absorption at 290 nm.

F01 and F02 were merged to obtain an effective fraction group of plum flowers (Dietmate (registered trademark) -F0).
[Example 2]
Extract of Ome branch Extracts of Prunus mume 'Xi Ye Qing', which is a cultivar of Ulsan Dai Ome, are collected, dried, crushed to a coarse powder of about 10 mesh, and 15 kg is taken for supercritical extraction. Extracted in a clave.

  Dynamic circulation extraction was performed for 2 hours under the extraction conditions of an extraction pressure of 30 MPa, an extraction temperature of 55 ° C., a separation temperature of 45 ° C., and a separation pressure of 4 MPa, to obtain 645 g of a fat-soluble extract of plum branch (Dietmate®-B01).

According to GC-MS analysis, this extract contains mainly long-chain alkanes, polyenes, V _E , plant sterols, and triterpenoid compounds, of which squalene (tetracosahexaene) is a fat-soluble effective The content in the fraction was 4.87% by mass fraction.

  The extraction residue was taken out from the extraction clave and subjected to hot reflux extraction with a 30% ethanol-water solution.

  Reflux extraction was performed for 2 hours under the extraction conditions of a temperature of 80 ° C. and a raw material-solution ratio of 1:15 (W / V) to obtain 2400 g of a water-soluble extract of plum branch (Dietmate®-B02).

Analysis revealed that the total flavone content was 40.59%, the total triterpenoid saponin content was 19.07%, and the total acid was 3.70%. According to the infrared spectrum, this extract had characteristic absorption pork around 3406, 2926, 1609, 1519, 1447, 1394, 1284, 1070, 611 cm ⁻¹ . As a result of scanning this extract within the wavelength range of 190-700 nm according to the ultraviolet spectrum, it showed a strong absorption at 280 nm and a second strong absorption at 320 nm.

B01 and B02 were merged to obtain an effective fraction group of Umeda (Dietmate (registered trademark) -B0).
[Example 3]
Ome leaf extract The leaves of Prunus mume 'Hong Ding', the cultivar of Ulsan Dai Ome, are collected, dried, ground into a coarse powder of about 10 mesh, and 15 kg is taken into a supercritical extraction clave. Extracted.

  Dynamic circulation extraction was performed for 2 hours under the extraction conditions of extraction pressure of 35 MPa, extraction temperature of 55 ° C., separation temperature of 40 ° C., and separation pressure of 6 MPa to obtain 975 g of a fat-soluble extract of plum leaves (Dietmate (registered trademark) -L01). .

According to GC-MS analysis, this extract contains mainly long-chain alkanes, polyenes, V _E , plant sterols, and triterpenoid compounds, of which squalene (triacontahexaene) is a fat-soluble compound. The content in the fraction was 44.15% by mass fraction.

  The extraction residue was taken out from the extraction clave and subjected to hot reflux extraction with 30% ethanol-water solution.

Extraction was performed for 3 hours under the extraction conditions of a temperature of 70 ° C. and a raw material-solution ratio of 1:12 (W / V) to obtain 1680 g of a water-soluble extract of plum leaves (Dietmate (registered trademark) -L02). According to the analysis, the total flavone content was 30.46%, the total triterpenoid saponin content was 4.93%, and the total acid was 5.96%. By infrared spectrum, this extract had characteristic absorption pork around 3386, 2932, 1596, 1516, 1404, 1314, 1074, 776, 721, 611, 527 cm ⁻¹ . According to the UV spectrum, this extract showed a strong absorption at 322 nm and a second strong absorption at 285 nm.

L01 and L02 were merged to obtain an effective fraction group of plum leaves (Dietmate (registered trademark) -L0).
[ Reference Example 4]
Ome trunk extract Prunus mume 'Hong Feng' Plum trunk (Prunus mume 'Hong Feng') is collected, dried, crushed to a coarse powder of about 10 mesh, 15kg is taken, 30% 150 L of ethanol solution was added, and the mixture was extracted with reflux under heat.

The extract obtained by performing extraction for 3 hours under the extraction conditions of a temperature of 70 ° C. and a raw material-solution ratio of 1:10 (W / V) was filtered, concentrated under reduced pressure, and spray-dried to obtain 584 g of plum stem alcohol extract. Obtained (Dietmate®-H1).
[ Reference Example 5]
Extract from Ome-root Extract from the root of Prunus mume 'Da Ye Qing', which is a cultivar of Ulsan Dai-Ome, collected, dried, crushed to a coarse powder of about 10 mesh, 15 kg taken, and pure water After adding 250 L and impregnating for 3 hours, microwave assisted extraction was performed.

Output power is 1000 W, raw material-solution ratio is 1:10 (W / V), the extract obtained under the extraction condition for 1 hour is filtered, concentrated to a crude drug volume of about 1: 1, and 3 times the volume of edible alcohol is added. In addition, after stirring uniformly, leave it overnight in a refrigerator at about 4 ° C., remove the supernatant, collect ethanol under reduced pressure, concentrate the extract to a solid content of 20%, and spray dry. As a result, 467 g of an aqueous extract of plum root (Dietmate (registered trademark) -R2) was obtained.
[ Reference Example 6]
Dietmate (registered trademark) -F02, B02, and L02 produced in Examples 1, 2, and 3 were mixed with ingredients such as vitamins A and B according to the formulation shown in Table 1, and 100 mL of internal solution per bottle was used. did.

[Example 7]
Anti-gout animal test with ume non-fruit extract 1. Experimental materials Rat footpad volume measuring device (purchased from Zhejiang Chugaku Pharmaceutical University) 4 ° C refrigerator, 1 mL syringe, 6 ^# injection needle, filter paper; uric acid, NaOH, HCl, physiological saline, distilled water, etc.

Male SD rat (purchased from Zhejiang Medical Science Laboratory Animal Center)
Plum non-fruit part extract sample: Dietmate (registered trademark) -F0, B0, L0 produced in Examples 1, 2, and 3, respectively.
2. Experimental method (1) Preparation of sodium urate crystals and sodium urate solution Take 194 mL of distilled water, add 6 mL of NaOH (1 mol / L), boil and add 1 g of uric acid, and adjust the pH to 7.2 with HCl (1 mol / L). Adjust, stir at room temperature, cool, store in a refrigerator at 4 ° C for 24 hours, discard the supernatant, absorb moisture in the precipitate with filter paper, dry in oven (70 ° C) for 2 hours, take powder, It is put into a mortar, polished to a fine powder, filtered through a metal mesh having an opening of 250 μm, and put into a bottle for use.

  Take 500 mg of sodium urate crystals (MSU), add 9 mL of physiological saline and 1 mL of Tween-80, heat and stir to prepare 10 mL of sodium urate solution for use.

(2) Construction of animal model 6 ^# Inserted into the anterior tibia tendon from the 45 ° C. direction of the right hind limb of the right hind limb of the test rat using an injection needle, and 0.1 mL of MSU suspension (50 mg / mL) ) Was injected into the ankle joint space.

(3) Animal test Take 30 male SD rats and divide them randomly into 5 groups (Dietmate (registered trademark) -F0, B0, L0 group, model control group, normal control group). From the previous 2 days, gastric perfusion administration (500 mg / kg) was started once a day. In the model control group and the normal control group, gastric perfusion was performed with the same volume of physiological saline.

On the day of the experiment, 1 hour after gastric perfusion administration, a 6 ^# injection needle was used to insert the test rat right hindlimb tibial tarsal joint from the dorsal side of 45 ° C. into the anterior tibia tendon and MSU suspension 0. 1 mL (50 mg / mL) was injected into the ankle joint space to cause inflammation.

  For each group of rats, the footpad volume of each test rat was measured before model construction and at 1 hour, 2 hours, 4 hours, 6 hours, 24 hours, 48 hours, and 72 hours after model construction. Comparison between groups was performed using the difference in footpad volume before and after inflammation as the swelling rate.

3. Test Results and Analysis As shown in Table 2, in the model control group, Dietmate (registered trademark) -B0, F0, and L0 groups, the swelling degree was highest at 6 hours, and disappeared significantly at 24 hours or 48 hours. However, in the Dietmate (registered trademark) -B0 group, the degree of swelling was highest in 4 hours, disappearing in 6 hours, and disappearing significantly in 24 hours.

  As shown in Table 3, regarding the effect on the footpad swelling rate, the difference between Dietmate (registered trademark) -F0 group and model control was significantly significant at 1 hour from the onset of inflammation, and Dietmate was at 2 hours from the onset of inflammation. (R) -F0, L0 group and model control swell difference are extremely significant, and between 4 and 48 hours after inflammation, the difference between Dietmate (registered trademark) -F0 group and model control swell is extremely significant At 6 hours after the onset of inflammation, the difference between the Dietmate (registered trademark) -B0, F0, and L0 groups and the model control detachment was extremely significant.

  As is clear from the results, the Plum flower effective fraction group Dietmate (registered trademark) -F0 can remarkably reduce the footpad swelling of gouty arthritic rats, and the footpad swelling disappears markedly in 6 hours. Since the pre-inflammation level was reached at 48 hours, and the footpad swelling started 2 hours after the inflammation, the swelling period was greatly reduced.

  Umeha effective fraction group Dietmate (registered trademark) -L0 significantly reduced the footpad swelling of rats with gouty arthritis in 2 hours after inflammation, but the inhibitory effect decreased in 6 hours after inflammation. there were.

Umeda effective fraction group Dietmate (registered trademark) -B0 markedly decreased the footpad swelling of rats with gouty arthritis 6 hours after inflammation, but its inhibitory action was decreasing 48 hours after inflammation. .
[Example 8]
Clinical observation on the treatment of hyperuricemia with plum extract Case Selection All cases were confirmed to have high blood fat by two or more blood draws before being selected, and the blood uric acid content was higher than normal. A total of 60 cases were selected, of which 45 were males and 15 were females, the ages were 38-75 years, and the average was 58.6 years. Selected cases included 10 with hyperglycemia, 25 with hypertension, and 9 with coronary heart disease.

2. Diagnostic criteria Blood uric acid (HUA) concentration: male ≧ 417 μmol / L, female ≧ 339 μmol / L (blood uric acid was measured by enzymatic method).

3. Method of administration All administrations of hypolipidemic drugs and drugs affecting purine metabolism were stopped for 4 weeks before treatment. Two capsules each day containing the effective plum group (Dietmate (registered trademark) -F0) produced in Example 1 were administered at a dose of 400 mg / day / person in terms of dietmate (registered trademark) -F0 for 30 days. .

4). Observation method All cases were examined for blood uric acid before and after administration, blood fat, blood rheology, blood glucose, liver / kidney function, routine blood / urine examination, electrocardiogram, fundus, and microcirculation of the left hand fingernail.

5. result
After administration of Dietmate®-F0, 58 cases had a significant drop in blood uric acid (p <0.01), and 2 cases had no significant change. The therapeutic effects are shown in Table 4. All cases were treated with Dietmate®-F0 and had no adverse reactions in terms of symptoms and biochemistry.

  Uric acid is trioxypurine, and enhancement of purine synthetic metabolism and reduction of uric acid excretion are important mechanisms for increasing blood uric acid. Hyperuricemia is a common disease in internal medicine and can be divided into two types: primary and secondary. Usually treated with alkaline drugs and allopurinol.

In the present invention, hyperuricemia was treated by applying the plum flower extract Dietmate (registered trademark) -F0. As is apparent from the results, the blood was collected before and after the treatment with Dietmate (registered trademark) -F0. There are very significant differences in uric acid levels and no side effects. Dietmate (registered trademark) -F0 was suggested to have an effect of treating and preventing gout.
[ Reference Example 9]
Clinical observation on suppression of hyperuricemia and prevention of gout attacks by non-plum extract. Experimental Method According to the American College of Rheumatology gout diagnostic criteria, patients with primary gout were observed for a total of 60 cases, all males, 42-65 years old, with an average of 50.2 ± 7.6. I was old. There were 42 cases with hyperlipidemia, 10 cases with hypertension, and 6 cases with coronary heart disease. There were 3 diabetic patients with normal liver / kidney function.

2. Treatment method After suppressing the acute seizure period of gout, the observation subjects were randomly divided into two groups according to the visit number.

Group A is an experimental group, the number of which is 30, and the internal solution prepared in Reference Example 6 is 10 mL twice a day (equivalent to a daily extract dose of 1.2 g / 60 kg body weight). ) For 60 days.

  Group B was a control group and the number was 30. Probenecid (500 mg, 3 times a day, continued for 60 days) and allopurinol (0.1 g, 2 times a day, 60 days) were orally administered.

  Both groups forced patients to stop drinking and avoid high pudding. Three months later, the patient's status of acute gout attacks was followed to compare the therapeutic effects on the two groups of patients.

3. Laboratory Examination Before and after treatment, peripheral venous blood samples to be observed were taken and examined by tests as follows.

Blood fat was measured by measuring the total serum cholesterol (CH), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) using an enzyme-linked reagent colorimetric method (the kit was purchased from Shanghai Eighteenth Pharmaceutical Factory). Low density lipoprotein cholesterol (LDL-C) was calculated by the formula. Blood uric acid (UA) was measured by the phosphotungstic acid reduction method. Blood creatinine (CRE) was measured by the picric acid method. Serum total protein (SP) was measured by the biuret method. Serum albumin (A) was measured by the bromocresol green method. Globulin (G) was obtained by subtracting albumin from serum total protein. Glutamate pyruvate transaminase (GPT) was measured by the Lightman-Frankel method. Bilirubin was measured by an enzymatic method. Serum glucose was measured by the oxidase method. Plasma lipid peroxide (LPO) was measured by thiobarbituric acid fluorescence method. Superoxide disproportionation enzyme (SOD) in erythrocytes was measured by the pyrogallol auto-oxidation method. For plasma carbon monoxide (NO), the NO ²⁻ / NO ^{3 −} concentration of the plasma sample was detected by a copper cadmium column reduction method.

4). Results and analysis (comparison of gout attack frequency before and after treatment)
(1) Table 5 shows the results of comparison of gout attack frequency before and after treatment.

As is clear from the results, the group A was treated with the internal solution produced in Reference Example 6, and after that, the number of gout attacks was less than before the treatment, there was a significant difference (P <0.05), and the positive control There was a comparison with the group.

  (2) The results of changes in blood fat before and after treatment are shown in Table 6.

  As can be seen from the results, blood fat before and after treatment of group I patients is significantly different (P <0.05), and blood fat of group I patients after treatment is significantly different from blood fat of group B patients. (P <0.05).

  (3) Table 7 shows the results of changes in blood UA, LPO, SOD, and NO before and after treatment.

As can be seen from the results, Lee group patients before and after treatment ^{UA, LPO, SOD, NO 2-} / NO 3- is a significant difference, Lee group patients UA after treatment, LPO, SOD, NO ^{2 -} / NO ^3- was significantly different from UA, LPO, SOD and NO ^2- / NO ^3- in patients in group B.

(4) Association analysis of gout attack and blood fat, UA, LPO, NO As is clear from the association analysis, gout attack showed a positive correlation with the content of blood fat, UA, LPO, NO.

  Gout is caused by disorder of purine metabolism and gout stone formation formed from sodium urate salt, characterized by goutstone chronic arthritis and gout nephropathy, and hyperlipidemia, hypertension, diabetes Often associated with arteriosclerosis, coronary heart disease, etc. Plum extract provided by the present invention, in particular, plum non-fruit part extract is mainly composed of active substances such as flavone glycosides, triterpenoid saponins, organic acids, lipid peroxidation prevention, blood lipid lowering, immune enhancement, etc. Has pharmacological action.

The inventor applied this to the prevention of intussusception of primary gout, so that the internal use liquid produced in Reference Example 6 for patients with primary gout with hyperlipidemia and normal liver / kidney function was 3 When the follow-up was conducted after administration for a month, the number of gout recurrences of the patient who received this internal solution was significantly reduced compared with that before treatment. Blood fat, UA, LPO, NO of the patient who received this internal solution Such indicators have also been improved.

As is clear from the results, the plum extract provided by the present invention, particularly the plum non-fruit portion effective fraction group (the fat-soluble effective fraction and the water-soluble effective fraction) has a remarkable anti-gout activity and its blood fat There is a possibility of descent action.
[Example 10]
500 g of Dietmate (registered trademark) -F0 produced in Example 1 and 500 g of medicinal starch were used as raw materials, and no other ingredients were added, and a 0 ^# capsule of 300 mg per capsule in terms of net weight was produced.

Nine patients with gout were administered this capsule twice a day, 2 capsules at a time. One month later, if they did not change their eating and drinking habits, the average number of gout attacks in 10 gout patients was significantly reduced, so the plum flower effective fraction group (Dietmate®-F0) 500 g was prominent. It was suggested that it has a function to reduce the number of gout attacks.
[Example 11]
Dietmate (registered trademark) -F0, B0, and L0 manufactured in Examples 1, 2, and 3 and konjac fine powder, raw material such as dietary fiber fine powder, and medicinal starch are compounded according to the composition shown in Table 8. And made into tablets.

The corresponding tablets were administered to 5 gout patients twice a day, 1 tablet at a time (2 grams per tablet). One month later, when other eating and drinking / activity habits were not changed, the gout symptoms of 6 gout patients were remarkably improved, suggesting that the tablet has a remarkable anti-gout effect.
[ Reference Example 12]
Using Dietmate (registered trademark) -H1 (100 g) produced in Reference Example 4 as a raw material, add it to 1000 L of Shaoxing liquor with an alcohol content of 18% as it is, dissolve thoroughly, mix uniformly, and put into a can. If you always take a small amount of ume health sake, you will have a remarkable anti-gout effect.

  What has been described above is only a preferred embodiment of the present invention, and the scope of the substantial technical contents according to the present invention is not limited thereto. The substantial technical content of the present invention is broadly defined in the claims. Any technical entities and methods completed by others are exactly the same as those defined in the claims, or are included in the claims if the equivalent effect is changed.

Claims (9)

Use of plum extract to produce a composition to treat and prevent gout,
The aforementioned plum extract contains water-soluble and fat-soluble extracts of plum blossoms, branches, leaves, roots and / or stems,
Use of a plum extract characterized by containing squalene 0.5-50 wt% with respect to the total weight of an extract.   Use according to claim 1, characterized in that the composition is further used for the reduction of blood uric acid, the lowering of blood fat and / or the suppression of inflammation. A plum composition used for the treatment and prevention of gout, high blood uric acid lowering, gouty arthritis treatment and / or blood lipid lowering,
The aforementioned plum composition includes plum extract containing water-soluble and fat-soluble extracts of plum blossoms, branches, leaves, roots and / or stems,
A plum composition comprising 0.5 to 50 wt% of squalene with respect to the total weight of the extract. The plum composition according to claim 3 , wherein the composition comprises a drug composition, a food composition or a health food composition. 4. The plum composition according to claim 3 , wherein the composition comprises an additional component selected from the group consisting of plum fruit extract, tea extract, vitamins and combinations thereof. The plum composition according to claim 3 , wherein the composition further comprises a component that lowers additional blood uric acid. The plum composition according to claim 3 , wherein the composition further comprises a component that lowers additional blood fat. The plum composition according to claim 3 , wherein the composition further comprises an ingredient that suppresses additional inflammation. The aforementioned composition is:
(I) powders, granules, capsules, injections, tinctures, liquids for internal use, tablets or lozenges;
(Ii) with drinks or wine;
The plum composition according to claim 3 , wherein the plum composition is selected from the group consisting of: