CN106474185A - A kind of application in the medicine or food of preparation reduction blood uric acid for the Folium perillae extract and combinations thereof - Google Patents
A kind of application in the medicine or food of preparation reduction blood uric acid for the Folium perillae extract and combinations thereof Download PDFInfo
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Abstract
The present invention relates to the new opplication of a kind of Chinese crude drug Folium Perillae and its Chinese medicine composition, pass through to suppress xanthine oxidase activity and promote uric acid to drain two kinds of mechanism from urine, and reduce the concentration of uric acid in internal blood, reach medicine or the food that uric acid resisting and the purpose for the treatment of gout, therefore Folium perillae extract and its Chinese medicine composition can apply to prepare the prevention and treatment disease such as hyperuricemia or gout.Other Chinese crude drugs in the Folium perillae extract of the present invention and compositionss can be all solvent using water or aquiferous ethanol, heating extraction, extract 13 times, remove medicinal residues, concentrating under reduced pressure removes solvent, it is spray-dried or lyophilization becomes powder, plus adjuvant is prepared into Chinese medicine preparation or food, concrete such as capsule, tablet, oral liquid or solid beverage etc. dosage form.
Description
Technical field
This patent is related to a kind of Folium perillae extract reducing uric acid in blood and combinations thereof, is especially applicable to
The prevention of clinical hyperuricemia or people with high uric acid or therapeutic use.
Background technology
Folium Perillae (scientific name：Perilla frutescens), ancient name is weak, You Mingsu, common perilla, osmanthus weak (《Elegant》)、
Weak sub, red Soviet Union, red Soviet Union, fragrant Soviet Union, black Soviet Union, trillium Soviet Union, blue or green Soviet Union, wild Soviet Union, Perilla frutescens, grass of reviving, Tang Zisu,
Wrinkle leaf Soviet Union, Herba Stachydis Japonicae, smelly Soviet Union, big Folium Perillae, false Folium Perillae, water Rhizoma Cimicifugae, open country numb, the deaf ear of the leaves of pulse plants are numb, diligent pearl, emerging handkerchief
Summer main officer of Tibet (Tibetan language) etc., is uniquely to plant under Labiatae Perilla, annual herb plant.Folium Perillae is also Folium Perillae,
There is the function of relieving exterior syndrome and dispelling cold, relieving QI stagnancy in the stomach, cure mainly anemofrigid cold, cough, distension and fullness of the chest and abdomen, the disease such as nausea and vomiting.
Dietary function, has an expelling cold and relieving exterior syndrome, lung qi dispersing cough-relieving, qi-regulating and in, antiabortive, removing toxic substances.
Document report Folium Perillae has refrigeration function, bacteriostasis, and blood glucose increasing acts on, the effect to blood clotting, promotes
Enterokinesia, sedation etc..But do not report that Folium Perillae and its extract have suppression hypoxanthine oxidation so far
Enzymatic activity and internal uric acid resisting activity and its application.
The Flos Sophorae Immaturus or Flos Sophorae broad sense are dry flower and the flowers for leguminous plant Chinese scholartree (Sophora japonica L.).Summer
Ji Huawei harvests its alabastrum, referred to as " Flos Sophorae Immaturus " when open；Harvesting when putting that the flowers are in blossom, referred to as " Flos Sophorae ".Flos Sophorae Immaturus master
Originate in the ground such as Henan, Shandong, Shanxi, Shaanxi, Anhui, Hebei, Jiangsu, in recent years the ground such as Ningxia, Gansu
Also have scale, also there is large-area plantation in Vietnam.Cold nature, bitter in the mouth；Cooling blood for hemostasis, purging liver-fire；With
In having blood in stool, hemorrhoidal bleeding, dysentery, metrorrhagia, haematemesis, epistaxis, the hot hot eyes of liver, dizziness of having a headache.The Flos Sophorae Immaturus contain globulariacitrin
Rutin (rutin), triterpenoid saponin (0.4%), betulin (betulin), sophoradiol (sophoradiol),
Glucose, gluconic acid aldehyde (glucuronic acid), also contain Flos Sophorae Immaturus A prime (14%) Flos Sophorae Immaturus B prime
(1.25%) be the flavone compounds different with rutin with Flos Sophorae Immaturus C prime (0.35%) A prime, B prime and
C prime is phytosterin compound.
Radix Puerariae (Lobed Kudzuvine Root), is the dry root of legume pueraria lobata, practises and claims Herba Gelsemii Elegantis.Autumn,
Season in winter two excavates, and takes advantage of fresh-cut and becomes sheet or fritter；It is dried.Sweet, pungent, cool.There are expelling pathogenic factors from muscles for reducing heat, rash, life
Quench the thirst in Tianjin, the work(of Shengyang Zhixie.It is usually used in exterior syndrome heating, stiff nape and back, measles without adequate eruption, calentura is thirsty, cloudy
Void is quenched one's thirst, diarrhea of heat type hematodiarrhoea, diarrhea due to hypofunction of the spleen.Radix Puerariae isoflavone-containing composition puerarin, puerarin xyloside, Semen sojae atricolor
Flavone, daidzin and cupreol, arachidic acid, again starch containing volume (in fresh Radix Puerariae content be 19～
20%).
Semen Coiciss, Chinese medicine name.For grass Semen Coiciss Coix lacryma-jobi L.var.mayuen
(Roman.) dry mature kernal of Stapf.Tap plant during autumn fruit maturation, dry, lay fruit,
Dry again, except decapsidate, yellowish-brown kind skin and impurity, collect kernel.Cool in nature, sweet in the mouth, light；There is spleen invigorating
Eliminating dampness by diuresis, remove numbness antidiarrheal.Semen Coicis can be used for treating edema, tinea pedis, dysuria.Semen Coicis contains protein 16.2%,
Fat 4.6%, saccharide 79.2%.
Hyperuricemia, also known as gout (gout), is the disease caused by one group of purine metabolic disturbance, its clinical characters
For hyperuricemia.(hyperuricemia) the gouty acute arthritises recurrent exerbation that causes and therefrom, bitterly
Wind stone deposits, tophaceous chronic arthritiss and joint deformity, often involve kidney cause chronic interstitial nephritiss and
Uric acid kidney stones are formed.Hyperuricemia, also known as gout (gout), is the disease caused by one group of purine metabolic disturbance,
Its clinical characters be hyperuricemia (hyperuricemia) and the gouty acute arthritises that cause therefrom repeatedly
Outbreak, tophaceous deposition, tophaceous chronic arthritiss and joint deformity, often involve kidney and cause chronic interstitial
Property nephritis and uric acid kidney stones are formed.
Xanthine oxidase is important oxidase in human body, is primarily involved in the metabolism of nucleic acid, can be catalyzed time Huang
Purine generates xanthine, further generates uric acid and free radical.It by 1330 Amino acid profiles, its
Aminoacid sequence has 90% homology between Mus and people, is made up of two full symmetric construction units.
Each construction unit be 145, its catalytic center include a molybdenum pterin center, two ferrum-sulfur centers and
One flavin adenine dinucleotide (FAD), wherein molybdenum pterin center are that xanthine oxidase catalysis xanthine generates uric acid
Critical sites.Effectively suppression XOD activity can reduce the conversion to uric acid for the xanthine, thus high urine can be treated
Acidemia.
Drug therapy, non-steroid antiinflammatory drug, Colchicine, sugared cortical hormone should be given as early as possible after gout acute onset
Element, is the first-line treatment medicine of gouty arthritises acute attack.The selection of medicine depends on the journey of arthralgia
Degree and affected joints position.For joint light moderate pain patient, one or several Minor articulus, or 1-2 big
Joint involvement, optional non-steroid antiinflammatory drug, Colchicine or glucocorticoid.To joint severe pain patient,
Multi-joint involvement or 1～2 large joint involvement, can be used in combination non-steroid antiinflammatory drug and Colchicine, or sugar
17-hydroxy-11-dehydrocorticosterone and Effects of Colchicine In Treating.For initial therapy, invalid patient can be selected for interleukin 1 receptor antagonism
Agent.The medicine of suppression blood uric acid synthesis is by suppressing xanthine oxidase, block hypoxanthine to xanthine and
Uric acid converts, thus reducing serum Uric Acid Concentration, reducing urate and depositing in joint and its surrounding tissue, finally subtracting
The outbreak of few gout.Representing medicine is allopurinol and Febustat.Allopurinol (allopurin01) is competing
Striving property xanthine oxidase inhibitor, is just approved for treating gout early in the sixties in 20th century, in clinic
On frequently as uric acid resisting choice drug.
Although clinically having developed the medicine of multiple treatment hyperuricemias, these medicines are respectively provided with larger
Side effect, clinical practice is subject to a definite limitation；Find that new medicine has from natural plants or Chinese crude drug
Good development prospect Chinese invention patent CN104162063 reports a kind of middle recurrence due to taking drug treating hyperuricemia
Square preparation and preparation method thereof, with natural Chinese medicine Radix Gentianae as primary raw material；Chinese patent CN103372159A
A kind of SEMEN COICIS extract with uric acid resisting effect of report and preparation method thereof etc..At present, domestic and foreign literature does not have
Have been reported that Folium perillae extract has blood uric acid activity and its containing Folium Perillae, SEMEN COICIS, Radix Puerariae, the Flos Sophorae Immaturus and Stigma Maydis
Chinese medicine preparation have reduce blood uric acid and treatment gout purposes.This research is passed through to screen external xanthine oxidase
Find during enzyme inhibitor that Folium perillae extract has significant enzyme inhibition activity, and be further discovered that its Mice Body
The activity of interior uric acid resisting；Folium Perillae, SEMEN COICIS, Radix Puerariae, the Flos Sophorae Immaturus and Semen Maydiss are found in Chinese medicine composition screening process
Must compositionss there is significant uric acid resisting activity, and obtain checking in mouse model it was demonstrated that independent Folium Perillae
The compositionss of extract or inclusion Folium Perillae, SEMEN COICIS, Radix Puerariae, the Flos Sophorae Immaturus and Stigma Maydis etc. all can be used in clinical height
Lithemic treatment or the dietetic therapy of people with high uric acid.
Content of the invention
It is an object of the invention to provide the new pharmacology of traditional Chinese medicine Folium perillae extract and its Chinese medicine composition is made
With, and prepare the various dosage form of Chinese medicine composition containing Folium perillae extract or containing Folium Perillae.
The present inventor finds Folium perillae extract during screening xanthine oxidase inhibitor in vitro
And its Chinese medicine composition has significant xanthine oxidase inhibitory activity, imply that it has internal suppression blood uric acid
The function of synthesis, and prove its internal function of reducing blood uric acid using mouse in vivo models further.
The technical solution used in the present invention is as follows：
The present invention provides a kind of Folium Perillae or Folium perillae extract in medicine or the food that preparation reduces blood uric acid
Application.
Wherein, described food includes bread and cheese, health food and special medicine purposes formula food.
Wherein, described Folium Perillae or Folium perillae extract are applied to preparation treatment or prevention hyperuricemia or gout
Medicine or food.
Wherein, described Folium perillae extract is adopted and is prepared with the following method：With Folium Perillae as raw material, carried by solvent
Take, concentrate and be dried, obtain described Folium perillae extract.
Wherein, the described solvent of use is water or aquiferous ethanol, and described solvent is equal with the ratio of weight and number of Folium Perillae
For 5-50:1.
Preferably, when described solvent is aquiferous ethanol, aquiferous ethanol with the ratio of weight and number of Folium Perillae is
30-50:1；The volumn concentration of aquiferous ethanol is 10%-90%；It is preferably 20%-70%.
Wherein, the mode of extraction used be heated to reflux, microwave or ultrasound assisted extraction.
Preferably, described extraction time is 1-4 hour every time；It is preferably 2 hours；Extraction time is 1-3 time,
Preferably extract 2 times.
The present invention also provides a kind of application of the compositionss containing Folium perillae extract, and described compositionss are by such as lower section
Prepared by method：The raw material of Folium Perillae, SEMEN COICIS, the Flos Sophorae Immaturus and Radix Puerariae will be included, by solvent mixed extraction, concentration
With drying, obtain described compositionss.
Preferably, described raw material also includes Stigma Maydis.
Preferably, according to weight, described compositionss comprise Folium Perillae 10%～40%, SEMEN COICIS
10%～50%, the Flos Sophorae Immaturus 20%～50%, Radix Puerariae 10%～40%, Stigma Maydis 0～30%.
Wherein, described compositionss are prepared by way of mixed extraction for the treatment of different things alike after by all raw material pulverizing or will be every
Prepared by the mode planting mixing after raw material individually extracts；The mode of extraction used is for being heated to reflux, microwave or ultrasonic auxiliary
Help extraction；
Preferably, described extraction time is 1-4 hour every time, preferably 2 hours；Extraction time is 1-3 time,
Preferably extract 2 times；The described solvent using is water or aquiferous ethanol, the ratio of weight and number of described solvent and raw material
It is 5-50:1.
It is highly preferred that when described solvent is aquiferous ethanol, the volumn concentration of aquiferous ethanol is 10%-90%,
It is preferably 20-70%, described aquiferous ethanol is 30-50 with the ratio of weight and number of described raw material:1.
Wherein, by adding the adjuvant allowing in pharmaceuticss or food, by described Folium Perillae or Folium perillae extract
Or the compositionss containing Folium perillae extract are made for the solid beverage of corresponding pharmaceutical preparation or food.
Wherein, described pharmaceutical preparation is tablet, capsule, oral liquid.
The present invention is proved by test, and the Folium perillae extract of the present invention has and significantly inhibits the oxidation of external xanthine
Enzymatic activity and the pharmacologically active reducing the synthesis of blood uric acid in mice body；Chinese medicine composition containing Folium perillae extract
Not only there is suppression internal uric acid synthesis additionally it is possible to diuresis promote internal urate excretion effect.
Specific embodiment
Mode below by embodiment further illustrates the present invention, but does not therefore limit the present invention to described
Scope of embodiments among.The experimental technique of unreceipted actual conditions in the following example, all conventionally
And condition, or select according to catalogue.Raw material in following examples is commercially available.
Embodiment 1
The preparation of Folium perillae extract capsule
Weigh 100 grams of Folium Perillae, add water 500ml mineral water or deionized water, soak 2 hours, be heated to reflux extracting
2 hours, take out extracting solution；Plus 500ml water equally extracts 1 time again, combining extraction liquid, it is evaporated to slurry
Shape thing；According to 1：1 ratio adds Microcrystalline Cellulose, mixing, drying, pulverizing, plus 1% stearic acid, and dress is hard
Capsule, obtains the Folium perillae extract capsule of embodiment 1.
Embodiment 2
The preparation of Folium perillae extract capsule
Weigh 50 grams of Folium Perillae, add water 1500ml mineral water or deionized water, soak 2 hours, be heated to reflux extracting
2 hours, take out extracting solution；Plus 1500ml water equally extracts 1 time again, combining extraction liquid, it is evaporated to
Slurry；According to 1：1 ratio adds Microcrystalline Cellulose, mixing, drying, pulverizing, plus 1% stearic acid, dress
Hard capsule, obtains the Folium perillae extract capsule of embodiment 2.
Embodiment 3
The preparation of Folium perillae extract tablet
Weigh 50 grams of Folium Perillaes, plus 2500ml mineral water or deionized water, soak 2 hours, be heated to reflux extracting 2
Hour, take out extract；Plus 2500ml mineral water or deionized water equally extract once again, united extraction liquid
It is evaporated to slurry, according to 1:1 ratio adds Microcrystalline Cellulose, mixing, drying, pulverizing, plus disintegrate
Agent and other adjuvants, mix homogeneously, pelletize, tabletting, obtain the Folium perillae extract tablet of embodiment 3.
Embodiment 4
The preparation of Folium perillae extract capsule
Weigh 100 grams of Folium Perillae, add water 500ml90% ethanol water, soak 2 hours, be heated to reflux extracting 2
Hour, take out extracting solution；Plus 500ml90% ethanol water extracts 1 time again, combining extraction liquid, decompression is dense
It is reduced to slurry；According to 1：1 ratio adds Microcrystalline Cellulose, mixes, dries, pulverizes, plus 1% stearic acid,
Dress hard capsule, obtains the Folium perillae extract capsule of embodiment 4.
Embodiment 5
The preparation of Folium perillae extract tablet
Weigh 50 grams of Folium Perillaes, plus 1500ml 90% ethanol water, soak 2 hours, be heated to reflux extracting 2 little
When, take out extract；Extract again once, united extraction liquid is evaporated to slurry, according to 1:1 ratio adds
Enter Microcrystalline Cellulose, mixing, drying, pulverizing, with disintegrating agent and other adjuvants, mix homogeneously, pelletize, pressure
Piece, obtains the Folium perillae extract tablet of embodiment 5.
Embodiment 6
The preparation of Folium perillae extract tablet
Weigh 50 grams of Folium Perillaes, plus 1500ml 70% ethanol water, soak 2 hours, be heated to reflux extracting 2 little
When, take out extract；Extract again once, united extraction liquid is evaporated to slurry, according to 1:1 ratio adds
Enter Microcrystalline Cellulose, mixing, drying, pulverizing, with disintegrating agent and other adjuvants, mix homogeneously, pelletize, pressure
Piece, obtains the Folium perillae extract tablet of embodiment 6.
Embodiment 7
The preparation of Folium perillae extract solid beverage
Weigh 50 grams of Folium Perillaes, plus 2500ml 40% ethanol water, soak 2 hours, ultrasonic and microwave-assisted
Extraction 2 hours, takes out extract；Extract again once, united extraction liquid is evaporated to slurry, according to
1:1 ratio adds Microcrystalline Cellulose, mixing, drying, pulverizing, plus other adjuvants, pelletizes, and pack obtains
The Folium perillae extract solid beverage of embodiment 7.
Embodiment 8
The preparation of Folium perillae extract solid beverage
Weigh 50 grams of Folium Perillaes, plus 2500ml 20% ethanol water, soak 2 hours, ultrasonic and microwave-assisted
Extraction 2 hours, takes out extract；Extract again once, united extraction liquid is evaporated to slurry, according to
1:1 ratio adds Microcrystalline Cellulose, mixing, drying, pulverizing, plus other adjuvants, pelletizes, and pack obtains
The Folium perillae extract solid beverage of embodiment 8.
Embodiment 9
The preparation of Folium perillae extract oral liquid
Weigh 50 grams of Folium Perillaes, plus 2500ml 10% ethanol water, soak 2 hours, be heated to reflux extracting 2
Hour, take out extract；Extract again once, united extraction liquid is evaporated to slurry, according to 1:1 ratio
Add Microcrystalline Cellulose, mixing, drying, pulverizing, with disintegrating agent and other adjuvants, mix homogeneously, make mouth
Take liquid, obtain the Folium perillae extract oral liquid of embodiment 9.
Embodiment 10
The preparation of Chinese medicinal composition capsules
Weigh 10 grams of Folium Perillae, 50 grams of SEMEN COICIS, the Flos Sophorae Immaturus 20,10 grams of Radix Puerariae, 10 grams of Stigma Maydis, plus 500ml
Mineral water or deionized water, soak 2 hours, are heated to reflux extracting 2 hours, take out extracting solution；Plus 500ml
Water equally extracts 1 time again, obtains 950ml extract, be evaporated to slurry after merging；According to 1：1
Ratio adds Microcrystalline Cellulose, mixing, drying, pulverizing, plus 1% magnesium stearate, fills hard capsule, obtains reality
Apply the Chinese medicinal composition capsules of example 10.
Embodiment 11
The preparation of Chinese medicine composition tablet
Weigh 10 grams of Folium Perillae, 30 grams of SEMEN COICIS, the Flos Sophorae Immaturus 20,10 grams of Radix Puerariae, 30 grams of Stigma Maydis, plus 1000ml
20% ethanol water, soaks 2 hours, is heated to reflux extracting 2 hours, takes out extracting solution；Plus 1000ml 20%
Ethanol water equally extracts 1 time again, and combining extraction liquid is evaporated to slurry；According to 1：1 ratio
Add Microcrystalline Cellulose, mixing, drying, pulverizing, with disintegrating agent and other adjuvants, mix homogeneously, pelletize,
Tabletting, obtains the Chinese medicine composition tablet of embodiment 11.
Embodiment 12
The preparation of Chinese medicine composition solid beverage 1
Weigh 40 grams of Folium Perillae, 10 grams of SEMEN COICIS, the Flos Sophorae Immaturus 20,20 grams of Radix Puerariae, 10 grams of Stigma Maydis, plus 3000ml
90% ethanol water, soaks 2 hours, is heated to reflux extracting 2 hours, takes out extracting solution；Plus 3000ml 90%
Ethanol water equally extracts 1 time again；Residue adds 1500ml 90% ethanol water again and equally extracts 1 time,
Combining extraction liquid, is evaporated to slurry；According to 1：1 ratio adds Microcrystalline Cellulose, mix, dry,
Pulverize, plus other adjuvants, pelletize, pack, obtain described Chinese medicine composition solid beverage 1.
Embodiment 13
The preparation of Chinese medicine composition oral liquid
Weigh 20 grams of Folium Perillae, 10 grams of SEMEN COICIS, the Flos Sophorae Immaturus 50,20 grams of Radix Puerariae, plus 5000ml 70% ethanol water
Solution, soaks 2 hours, is heated to reflux extracting 2 hours, takes out extracting solution 4500ml extract, and decompression is dense
It is reduced to slurry；According to 1：1 ratio adds Microcrystalline Cellulose, mixing, makes the Chinese medicine composition of embodiment 13
Thing oral liquid.
Embodiment 14
The preparation of Chinese medicine composition solid beverage 2
Weigh 40 grams of Folium Perillae, 10 grams of SEMEN COICIS, the Flos Sophorae Immaturus 10,40 grams of Radix Puerariae, add water 500ml 90% ethanol water
Solution, soaks 2 hours, is heated to reflux extracting 2 hours, takes out extracting solution；Plus 500ml 90% ethanol water
Solution equally extracts 1 time again；Residue adds 500ml 90% ethanol water again and equally extracts 1 time, merges
Obtain 1350ml extract afterwards, be evaporated to slurry；According to 1：1 ratio adds Microcrystalline Cellulose, mixes
Close, dry, pulverize, plus other adjuvants, pelletize, pack, make the Chinese medicine composition solid of embodiment 14
Beverage 2.
Embodiment 15
The preparation of Chinese medicine composition solid beverage 3
Weigh 30 grams of Folium Perillae, 10 grams of SEMEN COICIS, the Flos Sophorae Immaturus 50,10 grams of Radix Puerariae, add water 2000ml 60% ethanol
Aqueous solution, soaks 2 hours, is heated to reflux extracting 2 hours, takes out extracting solution；Plus 2000ml60% ethanol
Aqueous solution equally extracts 1 time again；Residue adds 1000ml60% ethanol water again and equally extracts 1 time, closes
And obtain 1350ml extract afterwards, it is evaporated to slurry；According to 1：1 ratio adds Microcrystalline Cellulose,
Mixing, drying, pulverizing, plus other adjuvants, pelletize, pack, and the Chinese medicine composition making embodiment 15 is solid
Body beverage 3.
Embodiment 16
The preparation of Chinese medicine composition solid beverage 4
Weigh 10 grams of Folium Perillae, 50 grams of SEMEN COICIS, the Flos Sophorae Immaturus 20,20 grams of Radix Puerariae, add water 500ml 90% ethanol water
Solution, soaks 2 hours, is heated to reflux extracting 2 hours, takes out extracting solution；Plus 500ml90% ethanol is water-soluble
Liquid equally extracts 1 time again；Residue adds 500ml90% ethanol water again and equally extracts 1 time, obtains after merging
Obtain 1350ml extract, be evaporated to slurry；According to 1：1 ratio adds Microcrystalline Cellulose, mix,
Dry, pulverize, plus other adjuvants, pelletize, pack, make the Chinese medicine composition solid beverage of embodiment 16
4.
Embodiment 17
The vitro inhibition xanthine oxidase activity of Folium perillae extract and Chinese herbal compounds
1. preparation of reagents
Prepare：70mM phosphate buffer (pH 6.5)；(2.28mg xanthine is dissolved in 0.3mM xanthine solution
In 50ml 70mM phosphate buffer)；(0.01U/ml is in 70mM phosphoric acid to prepare xanthine oxidase solution
In buffer)；1N HCL solution (in 8.5ml dense .HCL 91.5ml water).
Positive control drug：Allopurinol
Other medicines：DMSO solution
Given the test agent：By the preparation of embodiment 1-16.
2. it is administered the preparation test sample solution of solution:By the sample of embodiment 1-9, (2mg containing Folium perillae extract is molten
In 1ml DMSO, it is configured to 2mg/ml solution.Dilute 10 times (200 μ g/ml) with PBS again, obtain
To the solution containing Folium perillae extract 200 μ g/ml.The sample of embodiment 10-16 takes appropriate amount of sample 2mg to be dissolved in
1mlDMSO, is configured to 2mg/ml solution, then dilutes 10 times (200 μ g/ml) with PBS, is contained
The solution (oral liquid lyophilization obtains pressed powder, weighs 2mg) of Chinese medicine composition 200 μ g/ml.Sun
Property reference substance solution：1mg allopurinol is dissolved in 1ml DMSO, then with, after 180 times of PBS dilution, obtaining
Solution containing 40 μm of ol/mL of allopurinol.
3. step operation：
Carry out enzyme reaction using 96 hole versions, take 70mM phosphate buffer, the 50 μ l tests of 35 μ l successively
Sample solution or positive reference substance solution and 30 μ l enzymatic solution add a reaction tank, and positive control adds not fast
Purine solution；Enzyme reaction compound is incubated 15 minutes at 37 DEG C, in addition 60 μ l xanthine substrate solutions,
React 30 minutes at 25 DEG C, add 25 μ l 1N HCL terminating reactions.Read in Bio-Tek microplate reader
The absorbance data of solution in each reaction tank under 295nm.Calculate the suppression ratio of each sample.
Calculate the suppression ratio to XOD for the extract sample according to formula.
Suppression ratio (%)=[(EStandard substance-ESample)]/EStandard substance× 100%
4. measurement result：
Table 1 Folium perillae extract and Chinese medicine composition are to xanthine oxidase external activity inhibitory activity (enzyme linked immunosorbent assay)
| Example weight：2mg | Suppression ratio (%) |
| Other purine (positive control) | 95 |
| The Folium Perillae capsule of embodiment 1 | 65 |
| The Folium Perillae capsule of embodiment 2 | 60 |
| The Folium Perillae tablet of embodiment 3 | 61 |
| The Folium Perillae capsule of embodiment 4 | 62 |
| The Folium Perillae tablet of embodiment 5 | 62 |
| The Folium Perillae tablet of embodiment 6 | 58 |
| The Folium Perillae solid beverage of embodiment 7 | 65 |
| The Folium Perillae solid beverage of embodiment 8 | 64 |
| The Folium Perillae oral liquid of embodiment 9 | 62 |
| The Chinese medicinal composition capsules of embodiment 10 | 75 |
| The Chinese medicine composition tablet of embodiment 11 | 78 |
| The Chinese medicine composition solid beverage 1 of embodiment 12 | 77 |
| The Chinese medicine composition oral liquid of embodiment 13 | 68 |
| The Chinese medicine composition solid beverage 2 of embodiment 14 | 75 |
| The Chinese medicine composition solid beverage 3 of embodiment 15 | 78 |
| The Chinese medicine composition solid beverage 4 of embodiment 16 | 71 |
Result shows, the Folium Perillae and various extracting method of Chinese medicine composition prepares extract and various dosage form all shows
Go out stronger xanthine oxidase inhibitory activity, more slightly lower than the other purine of clinical chemical medicine.
Embodiment 18 suppression uric acid synthesis animal model
1st, laboratory animal ICR, male, body weight 22g about.By the limited public affairs of Shanghai western pul-Bi Kai laboratory animal
Department provides, animal productiong licensing number：SCXK (Shanghai) 2013-0016.
2nd, test sample
Embodiment 1-16 positive control drug：Allopurinol
3rd, instrument and reagent
Automatic clinical chemistry analyzer ZY-260, China of section
4th, it is administered the preparation of solution
Test sample solution:The sample preparation of embodiment 1-9 is become 75mg/ml containing Folium perillae extract 0.5% fiber
Plain sodium solution；Embodiment 10-16 Chinese medicine composition is configured to containing 75mg/ml Chinese medicinal composition preparation
0.5% sodium cellulosate solution
Positive reference substance solution：The 0.5% sodium cellulosate solution of allopurinol 12.5mg/ml
5th, experimental technique：
Mice is divided into model group, positive drug allopurinol (50mg/kg) group, above sample sets.Each mouse peritoneal is noted
Penetrate hypoxanthine 1000mg/kg (0.2ml/10g), normal group injection water；Model group gavage isometric(al) distilled water,
Other sample sets give corresponding test sample medicinal liquid and positive reference substance solution, and administered volume is 0.2ml/10g,
1 time/d of each group gavage, continuous 5d.
6th, serum uric acid
Mice fasting can't help water 16 hours, after last dose 30min, each group lumbar injection
The aqueous suspension (600mg/kg) of HX (Hypoxanthlne, hypoxanthine), volume injected is 0.2mL/10g.
Pluck eyeball after injection HX 45min and take blood 0.5mL, place 30 minutes, 5000rpm), it is centrifuged 5min, separate
Serum, measures serum uric acid concentration using automatic clinical chemistry analyzer and its imported reagents.
Table 2 Folium perillae extract causes antihyperuricemic disease mouse model serum to ip HX (Intraperitoneal injection of hypoxanthine)
The impact of UA (uric acid)
##p ＜ 0.01vs normal group, * p ＜ 0.05, * * p ＜ 0.01vs model group.
Result shows, the various extracting method of Folium Perillae and Chinese medicine composition prepare extract and the equal table of various dosage form
Reveal in stronger mice body and reduce hematuria acid activity, be respectively provided with significant difference with model, than positive drug activity
Weak.
Embodiment 19 diuresis animal model
Laboratory animal ICR, male, body weight 22g about.By the limited public affairs of Shanghai western pul-Bi Kai laboratory animal
Department provides, animal productiong licensing number：SCXK (Shanghai) 2013-0016.
2nd, test sample
Embodiment 1-16 positive control drug：Benzbromarone
3rd, instrument and reagent
Automatic clinical chemistry analyzer ZY-260, China of section
4th, it is administered the preparation of solution
Test sample solution:The sample preparation of embodiment 1-9 is become 75mg/ml containing Folium perillae extract 0.5% carboxymethyl
Sodium cellulosate solution；Embodiment 10-16 Chinese medicine composition is configured to Chinese medicinal composition preparation containing 75mg/ml
0.5% carboxymethylcellulose sodium solution
Positive reference substance solution：0.5% carboxymethylcellulose sodium solution of Benzbromarone 2.5mg/ml
5th, experimental technique：
Mice is divided into normal group, model group, positive drug Benzbromarone (50mg/kg) group, test sample group.
Model group, positive drug group and test sample group each mouse peritoneal injection uric acid 250mg/kg (0.2ml/10g),
0.5% carboxymethylcellulose sodium solution of normal injection same volume；Model group gavage isometric(al) 0.5% sodium cellulosate
Solution, positive drug group tank stomach Benzbromarone, other sample sets give corresponding test sample medicinal liquid and positive reference substance
Solution, administered volume is 0.2ml/10g, 1 time/d of each group gavage, continuous 5d.
6th, serum uric acid
Mice fasting can't help water 16 hours, after last dose 30min, the 0.5% of each group lumbar injection uric acid
Sodium carboxymethyl cellulose suspension liquid (250mg/kg), volume injected is 0.2mL/10g.Injection uric acid 60min
After pluck eyeball and take blood 0.5mL, place 30 minutes, 5000rpm), be centrifuged 5min, separate serum, using complete
Automatic biochemistry analyzer and its imported reagents measure serum uric acid concentration.
Table 3 Folium perillae extract and Chinese medicine composition cause antihyperuricemic disease mouse model serum to lumbar injection uric acid
The impact of UA (uric acid)
##p ＜ 0.01vs normal group, * p ＜ 0.05, * * p ＜ 0.01vs model group.
Result shows, the various extracting method of Folium Perillae and Chinese medicine composition prepare extract and the equal table of various dosage form
Reveal diuresis biological activity in stronger mice body, be respectively provided with significant difference compared with model group, compare positive drug
Activity is quite；And Chinese medicine composition embodiment is expressively more excellent than Folium Perillae embodiment.
Claims (14)
1. a kind of Folium Perillae or Folium perillae extract application in the medicine or food of preparation reduction blood uric acid.
2. application according to claim 1 is it is characterised in that described food includes bread and cheese, health food
And special medicine purposes formula food.
3. application according to claim 1 is it is characterised in that it is applied to preparation treatment or prevention antihyperuricemic
The medicine of disease or gout or food.
4. according to claim 1 application it is characterised in that：Described Folium perillae extract is adopted with the following method
Preparation：With Folium Perillae as raw material, by solvent extraction, concentrate and dry, obtain described Folium perillae extract.
5. according to claim 4 application it is characterised in that use described solvent be water or aquiferous ethanol,
Described solvent is 5-50 with the ratio of weight and number of Folium Perillae:1.
6. according to claim 4 application it is characterised in that described solvent be aquiferous ethanol when, aqueous second
Alcohol is 30-50 with the ratio of weight and number of Folium Perillae:1；The volumn concentration of aquiferous ethanol is 10%-90%；Excellent
Elect 20%-70% as.
7. according to claim 4 application it is characterised in that extraction used mode be heated to reflux, micro-
Ripple or ultrasound assisted extraction；Described extraction time is 1-4 hour every time, preferably 2 hours；Extraction time is
1-3 time, preferably extract 2 times.
8. a kind of application of the compositionss containing Folium perillae extract it is characterised in that：Described compositionss are by such as lower section
Prepared by method：The raw material of Folium Perillae, SEMEN COICIS, the Flos Sophorae Immaturus and Radix Puerariae will be included, by solvent mixed extraction, concentration
With drying, obtain described compositionss.
9. compositionss according to claim 8 application it is characterised in that：Described raw material also includes Stigma Maydis.
10. compositionss according to claim 8 or claim 9 application it is characterised in that：According to weight percentage
Meter, described compositionss comprise Folium Perillae 10%～40%, SEMEN COICIS 10%～50%, the Flos Sophorae Immaturus 20%～50%, Pueraria lobota
Root 10%～40%, Stigma Maydis 0～30%.
11. according to claim 8 compositionss application it is characterised in that described compositionss pass through will be all former
The mode of mixed extraction for the treatment of different things alike after feed powder is broken is prepared or is prepared the mode of mixing after every kind of raw material individually extraction；
The mode of extraction used be heated to reflux, microwave or ultrasound assisted extraction；Described extraction time is that 1-4 is little every time
When, preferably 2 hours；Extraction time is 1-3 time, preferably extracts 2 times；Use described solvent be water or
Aquiferous ethanol, described solvent is 5-50 with the ratio of weight and number of raw material:1.
12. according to claim 8 compositionss application it is characterised in that described solvent be aquiferous ethanol when,
The volumn concentration of aquiferous ethanol be 10%-90%, preferably 20%-70%, described aquiferous ethanol with described
The ratio of weight and number of raw material is 30-50：1.
13. according to any one of claim 1-8 the application of Folium Perillae or Folium perillae extract or according to right will
Ask the application of compositionss described in 9-12 it is characterised in that by adding allow in pharmaceuticss or food auxiliary
Material, described Folium Perillae or Folium perillae extract or the compositionss containing Folium perillae extract are made for corresponding medicine
Thing preparation or the solid beverage of food.
14. according to claim 13 application it is characterised in that described pharmaceutical preparation be tablet, capsule,
Oral liquid.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2683570C1 (en) * | 2018-05-23 | 2019-03-29 | Евгений Иванович Верещагин | Composition for vegetable components, which has the ability to reduce the level of uric acid in blood serum |
| CN110840930A (en) * | 2019-12-11 | 2020-02-28 | 中北大学 | Method for extracting xanthine oxidase inhibitor from perilla leaves with assistance of ultrasonic waves |
| CN111939235A (en) * | 2020-08-24 | 2020-11-17 | 柳州市中医医院 | Forming process method of compound gout granules |
| CN113082012A (en) * | 2021-04-26 | 2021-07-09 | 北京亿药科技有限公司 | Application of perillene in preparation of medicine for preventing and/or treating hyperuricemia |
| WO2022021778A1 (en) * | 2020-07-28 | 2022-02-03 | 深圳市老年医学研究所 | Medicated diet dietotherapy composition for preventing and treating hyperuricemia and gout and preparation method for medicated diet dietotherapy composition |
| CN115919927A (en) * | 2022-12-26 | 2023-04-07 | 兰州理工大学 | Traditional Chinese medicine composition and application |
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| CN103417873A (en) * | 2013-08-21 | 2013-12-04 | 宋立学 | Traditional Chinese medicine composition for treating gout and preparation method thereof |
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2015
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103417873A (en) * | 2013-08-21 | 2013-12-04 | 宋立学 | Traditional Chinese medicine composition for treating gout and preparation method thereof |
Non-Patent Citations (1)
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| MI-HYANG KIM ET AL: "Antioxidant Acitivities of Extact With water and Ethanol of Perilla frutescens var. acuta kudo Leaf", 《J. KOREAN SOC. APPL. BIOL. CHEM.》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2683570C1 (en) * | 2018-05-23 | 2019-03-29 | Евгений Иванович Верещагин | Composition for vegetable components, which has the ability to reduce the level of uric acid in blood serum |
| CN110840930A (en) * | 2019-12-11 | 2020-02-28 | 中北大学 | Method for extracting xanthine oxidase inhibitor from perilla leaves with assistance of ultrasonic waves |
| WO2022021778A1 (en) * | 2020-07-28 | 2022-02-03 | 深圳市老年医学研究所 | Medicated diet dietotherapy composition for preventing and treating hyperuricemia and gout and preparation method for medicated diet dietotherapy composition |
| CN111939235A (en) * | 2020-08-24 | 2020-11-17 | 柳州市中医医院 | Forming process method of compound gout granules |
| CN113082012A (en) * | 2021-04-26 | 2021-07-09 | 北京亿药科技有限公司 | Application of perillene in preparation of medicine for preventing and/or treating hyperuricemia |
| CN115919927A (en) * | 2022-12-26 | 2023-04-07 | 兰州理工大学 | Traditional Chinese medicine composition and application |
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