CN101194921A - Persimmon leaf flavone extract, preparation method and application thereof - Google Patents
Persimmon leaf flavone extract, preparation method and application thereof Download PDFInfo
- Publication number
- CN101194921A CN101194921A CNA2006101620736A CN200610162073A CN101194921A CN 101194921 A CN101194921 A CN 101194921A CN A2006101620736 A CNA2006101620736 A CN A2006101620736A CN 200610162073 A CN200610162073 A CN 200610162073A CN 101194921 A CN101194921 A CN 101194921A
- Authority
- CN
- China
- Prior art keywords
- extract
- persimmon leaf
- preparation
- group
- leaf flavone
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Abstract
The invention relates to an extract of persimmon leaves which are rich in flavones and a process for preparation, and the usage for preparing medicaments and/or health products for preventing and/or curing glucose and lipid metabolism and the relative illness, wherein glucose and lipid metabolism and the relative illness comprise hyperglycemia, diabetes mellitus and metabolism syndrome. Pharmacological researches, animal in vivo experiments and clinical researches show that the extracts of persimmon leaves which are rich in flavones have obvious functions of decompression, antihyperglycemic and antihypelipidemic, clinical curative effects for curing metabolism syndrome of diabetes, hyperlipemia, and hypertension are precise, and a toxicity test shows that the toxicity of the extracts of persimmon leaves which are rich in flavones of the invention is lower, and the security is high.
Description
Technical field
The present invention relates to derive from the medicinal extract and the Preparation method and use of vegetable material, particularly, relate to extract that Folium Kaki is rich in flavone (being called for short " persimmon leaf flavone extract ", " Folium Kaki flavone ") and preparation method and be used to prepare the medicine that prevents and/or treats glycolipid metabolism related diseases and/or the purposes of health product, wherein said glycolipid metabolism related diseases comprises hyperglycemia, diabetes and metabolism syndrome.
Background technology
Folium Kaki bitter in the mouth, cold in nature.Have the therapeutic method to keep the adverse QI flowing downwards and relieving asthma, slake thirst and help produce saliva, treat effects such as skin ulcer, have pharmacological action widely.Studies show that both at home and abroad, is that Folium Kaki preparation, persimmon leaf tea, Folium Kaki extract and Folium Kaki flavone glycoside that raw material is produced have blood pressure lowering, antibacterial, blood fat reducing, cholesterol reducing, hemostasis with the Folium Kaki, blood circulation promoting and blood stasis dispelling, suppresses many-sided physiological function such as carcinoma growth.
The chemical compound that contains in the Folium Kaki total flavones is a lot, the Folium Kaki flavone chemical compound of having found at present has astragalin, isoquercitin, nimbecetin 3-o-β-D-glycoside, nimbecetin, Quercetin, nimbecetin 3-o-α-L-rhamnoside, nimbecetin 3-β-D-xyloside, nimbecetin 3-o-α-L-arabinose glycoside, Quercetin 3-o-[2 " o-(3.4.5-trihydroxy benzene formyl)]-glycoside; rutin; hyperin (Quercetin-3-galactoside); myricitrin; astragalin etc., adopt the composition of different extracting method gained flavone and content height all to exist than big-difference.
There is bibliographical information that the ethanol extraction technology of Folium Kaki total flavones is studied.The result shows, with 15 times of 50% ethanol waters that Folium Kaki is heavy, is optimum condition at 75 ℃ of following lixiviate 3h.But this extracting method is just won crude extract, and flavones content has only about 15%, is difficult to obtain high activity and lower pair action effect, and it is medicinal to be used for human body.
Have the report water to put forward the method for resin adsorption method extraction separation Folium Kaki flavone again, it is by extracting the screening of solvent and adsorbent resin, and selecting pH for use is that 13 aqueous alkali is made solvent, extract flavone from Folium Kaki, cost is low, process safety, use the YF-I resin absorption then, ethanol elution.Extract the crude flavonoid powder that obtains, its component has antihypertensive function and promotes the activity of plant growing, but the method obtains crude extract, and impurity is still more, and it is medicinal to be used for human body.
(diabetes mellitus is a kind of very ancient and common endocrinopathy DM) to diabetes, and the traditional Chinese medical science is referred to as " quenching one's thirst ", the meaning of the excessive thirst of promptly becoming thin.Modern medicine find it be one group by the h and E factor interaction, cause the absolute and relative deficiency of insulin secretion and cell causes a series of metabolism disorders such as sugar, fat, protein, water, electrolyte to insulin sensitivity decline clinical syndrome, it is outstanding feature with the hyperglycemia, have a large amount of sugar to discharge in the urine, and polydipsia, polyuria, polyphagia occur, become thin, symptom such as dizzy, weak.It further develops and then causes the various serious acute and chronic complication of whole body, threatens healthyly, is the principal disease that person in middle and old age are disabled.
Onset diabetes mechanism more complicated has close association with plurality of enzymes and receptor.The main action target spot of Recent study has: calcium channel relevant with insulin secretion and ATP sensitive potassium channel, peroxidase paraphyte activated receptor (PPAR), the key enzyme in the insulin signaling pathway and the cytokine (as STAT5) of being correlated with insulin sensitivity enhancing, the key enzyme in the glucose metabolism etc.In recent years research is also thought: diabetes take place with the generation of interior free yl confidential relation is arranged.Free radical attack cells membrane structure, cause neuron membrane and subcellular fraction film destroy, microvascular lesions, mitochondrial function depletion and protein degradation acceleration etc., thereby make cell function lose, cause the absolute and relative deficiency of insulin secretion, finally cause metabolism obstacles of blood glucose, cause diabetes.
At present, there is number of drawbacks in the medicine that is used for the clinical treatment diabetes, so passes through constantly to find and study the related drugs target spot of diabetes, and carries out the main direction that new drug development is the exploration treating diabetes with this.
Diabetes are divided into two kinds of type 1 diabetes and type 2 diabetes mellitus usually.
1) insulin definitely lacks: promptly lack " JINYAOSHI " of opening the histiocyte gate, glucose can't utilize, and blood sugar increasing causes diabetes, belongs to type 1 diabetes.Must treat all the life with insulin.
2) insulin lacks relatively: part patient's insulin level does not reduce, and the effect of its insulin is had a greatly reduced quality, and promptly the insulin work efficiency reduces, and " JINYAOSHI " though have, but effect is little, also can cause diabetes, belongs to type 2 diabetes mellitus.This paradiabetes can be used oral drug therapy earlier, improves the work efficiency of insulin, but there have 50% type 2 diabetes mellitus patient can occur the oral drug therapy effect gradually approximately to be bad, finally have to accept insulinize.
Metabolism syndrome (metabolic syndrome, MS) be meant a series of and insulin resistant (insulin resistance, IR) metabolism and the physiologic derangement of relevant risk factor as atherosclerosis and cardiovascular diseases, be called X syndrome or IR syndrome again ", be characteristics with hyperglycemia, hypertension, high triglyceride (TG) mass formed by blood stasis and low hdl cholesterol (HDL-C) mass formed by blood stasis; In addition, metabolism syndrome comprises that also to organize insulin resistant, hyperuricemia and microalbuminuria, metabolism syndrome also to relate to continue low grade inflammation reaction and blood to coagulate molten unusual etc.
Metabolism syndrome is a kind of state that multiple diseases such as hypertension, pathoglycemia, blood fat disorder and obesity are assembled in human body, it mainly comprises: obesity especially visceral adiposity, diabetes or IGR, be the blood fat disorder and the hypertension of characteristics with high TG mass formed by blood stasis and low HDL-C mass formed by blood stasis, wherein unusual and four of dyslipidemia are more outstanding with overweight, fat, hypertension, blood glucose regulation, be called as " dead quartet ".
Diabetes branch of Chinese Medical Association had determined diagnosis metabolism syndrome standard in 2004, possessed in following four compositions 3 or all the person is diagnosable is metabolism syndrome.
1) waistline increase, overweight, fat: Body Mass Index BMI 〉=25.0kg/m
2
2) hyperglycemia: fasting plasma sugar 〉=6.1mmol/L and (or) blood plasma sugar 〉=7.8mmol/L behind the glucose load;
3) hypertension: systolic pressure/diastolic pressure 〉=140/90mmHg and (or) confirmed as the hyperpietic;
4) blood fat disorder: fasting blood triglyceride 〉=1.7mmol/L and (or) on an empty stomach HDL-C＜0.9mmol/L (male),＜1.0mmol/L (women).
The main purpose that prevents and/or treats metabolism syndrome is the morbidity of clinical cardiovascular diseases of prevention and type 2 diabetes mellitus.
Summary of the invention
The purpose of this invention is to provide a kind of persimmon leaf flavone extract, wherein comprise total flavones in the weight 60-90% of extract dry product, and contain in total flavones in the Quercetin of the weight 8-14% of extract dry product and the nimbecetin of 12-23%, its structural formula is:
Wherein, for Quercetin, R1, R2, R3, R4, R5 and R be respectively-OH ,-OH ,-OH ,-OH ,-H and-OH; For nimbecetin, R1, R2, R3, R4, R5 and R be respectively-OH ,-OH ,-H ,-OH ,-H and-OH.
In a preferred embodiment of the invention, weight in the extract dry product, the total flavones that preferably contains 77-86% in the gained persimmon leaf flavone extract, the content of Quercetin in the gained persimmon leaf flavone extract is preferably 13-14%, and the content of nimbecetin in the gained persimmon leaf flavone extract is preferably 15-20%.
Another object of the present invention provides the preparation method of persimmon leaf flavone extract, comprise that adopting the leaf of Ebenaceae (Ebenaceae) Diospyros (Diospyros L.) plant Fructus Kaki (Diospyros Kaki L.) is raw material, the process following steps: (1) decocting in water, filter (2), (3) precipitate with ethanol, (4) ethyl acetate extraction, (5) macroporous resin adsorption, (6) ethanol elution, (7) are reclaimed ethanol and are obtained concentrate, with optional (8) drying, thereby obtain the extract that Folium Kaki is rich in flavone.
Preparation in accordance with the present invention wherein decocts with water raw material 1-3 time in step (1), each 0.2-3 hour.
Preparation in accordance with the present invention is wherein filtered step (1) gained decocting liquid in step (2), and filtrate is concentrated into that relative density is the clear paste 1 of 1.05-1.2 in the time of 60 ℃.
Preparation in accordance with the present invention wherein adds ethanol precipitation in step (2) gained clear paste 1 in step (3), get supernatant and reclaim ethanol, obtains extractum 2.
Preparation in accordance with the present invention, ethyl acetate extraction use in the back that wherein in step (4) step (3) gained extractum 2 is dissolved in water, and gets extract recovery ethyl acetate, obtains thick paste 3.
Preparation in accordance with the present invention wherein will go up macroporous resin column absorption behind step (4) the gained thick paste 3 usefulness water dissolutioies in step (5), described macroporous resin is preferably polyamide type or polystyrene resin series.
Preparation in accordance with the present invention is wherein used the alcoholic solution eluting in step (6).
Preparation in accordance with the present invention is wherein collected ethanol liquid in step (7), obtain concentrate 4 behind the recovery ethanol, is Folium Kaki extract.
Preparation in accordance with the present invention, wherein step (8) is chosen wantonly, this is because described extract water content height, be difficult for preserving, thereby can described extract is further dry, obtain the xeraphium of moisture≤8%, preferred moisture≤1.5%, more convenient and can guarantee the content of effective of medicine when preparing various preparation with dry powder.Drying can adopt several different methods to carry out, as adopting methods such as hyperthermia drying, thin film evaporation drying or cold drying.The present invention preferably adopts spray drying method to carry out drying, and its inlet temperature is 60-180 ℃, and outlet temperature is 45-80 ℃, and wind speed is 5-10m/s, pressure is 0.01-0.8MPa, and preferably, its inlet temperature is 120-130 ℃, outlet temperature is 50-70 ℃, and wind speed is 7-9m/s, and pressure is 0.5MPa.
Preparation in accordance with the present invention wherein in the weight of extract dry product, contains the total flavones of 60-90%, preferred 77-86% in the gained persimmon leaf flavone extract.
Preparation in accordance with the present invention wherein contains Quercetin, nimbecetin in total flavones, its structural formula is:
Wherein, for Quercetin, R1, R2, R3, R4, R5 and R be respectively-OH ,-OH ,-OH ,-OH ,-H and-OH; For nimbecetin, R1, R2, R3, R4, R5 and R be respectively-OH ,-OH ,-H ,-OH ,-H and-OH.
Preparation in accordance with the present invention, wherein in the weight of extract dry product, the content of Quercetin in the gained persimmon leaf flavone extract is 8-14%, be preferably 13-14%.
Preparation in accordance with the present invention, wherein in the weight of extract dry product, the content of nimbecetin in the gained persimmon leaf flavone extract is 12-23%, be preferably 15-20%.
Another purpose of the present invention provides the purposes of persimmon leaf flavone extract, is used to prepare the medicine and/or the health product that prevent and/or treat glycolipid metabolism related diseases.
Glycolipid metabolism related diseases according to purposes of the present invention comprises hyperglycemia, diabetes and metabolism syndrome.
According to purposes of the present invention, persimmon leaf flavone extract can be used for promoting insulin secretion, increases the content of serum insulin.
At first, persimmon leaf flavone extract active cell Ca
2+Ion channel also increases Ca in the cell
2+Ca in the concentration, cell
2+The rising of concentration just can make and contain the secretion of insulin vesicle and shift and insulin is discharged into outside the born of the same parents to cell membrane from endoplasmic reticulum.
Secondly, persimmon leaf flavone extract increases the content of serum insulin by protection, reparation B cell.In one embodiment of the invention, light microscopic is observed the obvious swelling of model group rat insulin endocrine cell down, and endochylema reduces, and cell is arranged sparse, and is disorderly uneven, sees the vacuolar degeneration that differs in size, and nuclear differs in size; And the pancreatic islet endocrine morphosis of the heavy dose of group of Folium Kaki flavone mice is basic near normal, and swelling reduces, and vacuolar degeneration reduces, and secretory cell increases than model group, thereby has increased serum insulin concentration.
The 3rd, persimmon leaf flavone extract by antioxidation, remove free radical, prevent the apoptosis of B cell, and promote insulin secretion.Persimmon leaf flavone extract is to neurocyte H
2O
2Due to oxidation significant inhibitory effect is all arranged, and the activity of certain removing hydroxyl radical free radical is arranged, can suppress lipid peroxidation and remove hydroxyl radical free radical.Participate in removing reactive oxygen free radical and protect superoxide dismutase (SOD), catalase (CAT) and glutathion peroxidase (GSH-Px) etc. to remove the enzyme of free radical; reduce lipid peroxide and generate, improve glutathion (GSH) content and SOD activity.In another embodiment of the present invention, Folium Kaki extract increases mice bcl-2 expression of gene, reduce the Bax expression of gene, Fas protein positive expression rate is compared remarkable reduction (P＜0101) with model group, thereby reduce the generation of apoptosis, stimulate normal B cell excreting insulin, promote B cell regeneration.
The 4th, persimmon leaf flavone extract has the antagonism role of cytokines.Some inflammatory factors play an important role for insulin resistant, and tumor necrosis factor (TNF-α) increases the output of free fatty (FFA), causes insulin resistant.Persimmon leaf flavone extract can suppress intercellular adhesion molecule-1 (ICAM-1) and the activated cell adhesion of TNF-α, these two kinds of effect of cytokines of antagonism, and suppress the apoptosis that TNF-α, ICAM-1 induce the B cell.
According to purposes of the present invention, persimmon leaf flavone extract is used to improve drug-induced insulin resistance.In another embodiment of the present invention, persimmon leaf flavone extract can improve the plain resistance of mouse islets that hydrocortisone brings out.
According to purposes of the present invention, persimmon leaf flavone extract is as alpha-glucosidase inhibitor.Amylase, saccharase, the maltase of persimmon leaf flavone extract by suppressing small intestinal competitively, suppress glucides such as starch and resolve into glucose, delay the Absorption of carbohydrate, postpone the glucose absorption of disaccharidase, oligosaccharide, polysaccharide, reduce post-prandial glycemia and raise.
According to purposes of the present invention, persimmon leaf flavone extract is used to promote the utilization to sugar of peripheral tissues and target organ.In another embodiment of the present invention, persimmon leaf flavone extract can reduce the blood sugar content of epinephrine hyperglycemia mouse model significantly.
According to purposes of the present invention, persimmon leaf flavone extract is used to correct lipid metabolic disorder.In another embodiment of the present invention, persimmon leaf flavone extract helps to improve diabetes rat model or patient's lipid metabolic disorder, reduces the content of serum cholesterol, triglyceride.
According to purposes of the present invention, the medicine and/or the health product that wherein prevent and/or treat glycolipid metabolism related diseases can be by adding various adjuvants such as lubricant, filler, binding agent, disintegrating agent etc. in described persimmon leaf flavone extract, utilize conventional pharmaceutical preparation technology and the method for preparing food, be made for the form of tablet, dispersible tablet, controlled release tablet, capsule, powder, pill, drop pill, powder, granule, crystal, solution, extractum, outstanding agent, soup, syrup, elixir, tea, wet goods.
A further object of the present invention provides the purposes of persimmon leaf flavone extract, is used for preparation and prevents and/or treats brain soldier's sequela and function of nervous system's degeneration disease, cerebral arteriosclerosis, coronary heart disease, anginal medicine and/or health product.Can be by in described persimmon leaf flavone extract, adding various adjuvants such as lubricant, filler, binding agent, disintegrating agent etc., utilize conventional pharmaceutical preparation technology and the method for preparing food, be made for the form of tablet, dispersible tablet, controlled release tablet, capsule, powder, pill, drop pill, pill, powder, granule, crystal, solution, extractum, outstanding agent, soup, syrup, elixir, tea, wet goods, realize this purpose.
The invention has the advantages that provides persimmon leaf flavone extract and preparation method thereof, and provides a kind of new product for preventing and/or treating glycolipid metabolism related diseases.1) the present invention confirms that through the modern Chinese medicine pharmacological research persimmon leaf flavone extract has blood pressure lowering, blood fat reducing, blood sugar lowering, improves the effect of insulin resistant; 2) animal vivo test shows, persimmon leaf flavone extract has obvious reduction effect to experimental hyperlipidemia, and the effect of energy cholesterol reducing, improve lipid metabolism, have blood sugar lowering, coronary artery dilator and significant diuretic antihypertensive effect simultaneously and same function is arranged with the blood sugar lowering effect of insulin; 3) clinical research result shows that Folium Kaki extract has significant blood pressure lowering, blood fat reducing, blood sugar reducing function, and the metabolism syndrome clinical efficacy of treatment diabetes, hyperlipidemia, hypertension is definite, and does not observe apparent side effect.
Description of drawings
Fig. 1 has described according to the persimmon leaf flavone extract of the eighth embodiment of the invention inhibitory action to alpha-glucosidase activity.
The specific embodiment
In order to understand essence of the present invention better, further specify the present invention below by embodiment, but protection scope of the present invention is not limited to this.
Embodiment 1: the preparation persimmon leaf flavone extract
Get dried Folium Kaki 150Kg, add water 3500L and decoct 2 times, each 1.5 hours, collecting decoction filtered, and it is 1.15 (60 ℃) that filtrate is concentrated into relative density, fluid extract 40kg adds ethanol 120L and reaches 65% to containing the alcohol amount, standing over night, the leaching supernatant is standby; Precipitation is with twice of 85% washing with alcohol, collect cleaning mixture, leave standstill, draw supernatant and preceding supernatant and merge, reclaim ethanol, gained extractum 6kg, add water 80kg dissolving, filter, filtrate is extracted 3 times with ethyl acetate 120L, merge ethyl acetate liquid, reclaim ethyl acetate, get thick paste 4kg and be dissolved in water last macroporous resin column (macroporous resin is the polyamide type), wash with water to eluent colourless, reuse 75% ethanol elution is collected eluent, recovered alcohol, obtain 60 ℃ of following relative densities and be 1.10 the dope spray drying that reduces pressure and promptly get the dry powder of 1800g, spray-dired condition is: 128 ℃ of inlet temperature; 65 ℃ of outlet temperatures; Wind speed 8m/s; Pressure 0.5MPa, 1 drying, moisture is 1.05% in the gained dry powder.Folium Kaki extract is 77.4% (in the extract dry product) with containing total flavones in high performance liquid chromatography (HPLC) the mensuration extract, after the hydrolysis, the content of Quercetin, nimbecetin is measured to be respectively with the HPLC method and is rich in 13.6%, 16.5% of flavone extract gross weight.
Embodiment 2: the preparation persimmon leaf flavone extract
Get dried Folium Kaki 350Kg, add water 5500L and decoct 3 times, each 1 hour, collecting decoction filtered, and it is 1.18 (60 ℃) that filtrate is concentrated into relative density, fluid extract 100kg adds ethanol 450L and reaches 80% to containing the alcohol amount, standing over night, the leaching supernatant is standby; Precipitation is with twice of 85% washing with alcohol, collect cleaning mixture, leave standstill, draw supernatant and preceding supernatant and merge, reclaim ethanol, gained extractum 5.6kg adds water 95kg dissolving, filters, filtrate is extracted 3 times with ethyl acetate 300L, merge ethyl acetate liquid, reclaim ethyl acetate, get thick paste 6kg and be dissolved in water, last macroporous resin column (macroporous resin is the polyamide type), wash with water to eluent colourlessly, reuse 80% ethanol elution is collected eluent to colourless, recovered alcohol, getting relative density is 1.18 (60 ℃) dope, and the decompression spray drying promptly gets 4800g, and spray-dired condition is: 120 ℃ of inlet temperature; 55 ℃ of outlet temperatures; Wind speed 7.5m/s; Pressure 0.5MPa, 1 drying, moisture is 1.12% in the gained dry powder, Folium Kaki extract is measured with the HPLC method and is contained that total flavones is 85.2% (in the extract dry product) in the described extract, after the hydrolysis, the content of Quercetin, nimbecetin is measured to be respectively with the HPLC method and is rich in 13.9%, 19.6% of flavone extract gross weight.
Embodiment 3: preparation contains the medicine or the health product of persimmon leaf flavone extract
Get dried Folium Kaki 500Kg, add water 5500L and decoct 2 times, each 2.5 hours, collecting decoction filtered, and it is 1.12 (60 ℃) that filtrate is concentrated into relative density, fluid extract 100kg adds ethanol 320L and reaches 75% to containing the alcohol amount, the leaching supernatant is standby; Precipitation is with twice of 75% washing with alcohol, collect cleaning mixture, reclaim ethanol, gained extractum 11.6kg adds water 150kg dissolving, filter, filtrate is extracted 3 times with ethyl acetate 320L, merges ethyl acetate liquid, reclaims ethyl acetate, getting thick paste 14kg is dissolved in water, last macroporous resin column (macroporous resin is the AB-8 type) washes with water to eluent colourlessly, and reuse 55% ethanol elution is to colourless, collect eluent, recovered alcohol, getting relative density is the dope of 1.13 (60 ℃), the decompression spray drying promptly gets 6800g, it is 66.6% (in the extract dry product) that the mensuration Folium Kaki extract contains total flavones, Quercetin, the content of nimbecetin is respectively 8.3% of extract gross weight, 17.6%.Get dry powder 1000g and add appropriate amount of starch 1000g, mixing adds the general ball of Mel 20.0kg and becomes water pill, and the dry ball of dry 2.5kg is packaged into the pill of 10,000 parcels, promptly get 0.25g/ bag (whenever comprise extraction dry powder 100mg, be about as much as crude drug 20g).Oral dose: one time 1 pouch, 3 times on the one.
Embodiment 4: acute toxicity and long term toxicity test
The chmice acute toxicity research: 120 19～21g NIH mices (male and female half and half) are divided into 6 groups, and 20 every group, the Folium Kaki with five kinds of variable concentrations is rich in flavone extract p.o. administration, NS negative control respectively.Observe the reaction of mice and write down the mortality of every group of mice, adopt the linear regression software of Microsoft Excel, draw straight line, calculate LD according to log10 dose and empirical probability
50Folium Kaki is rich in flavone extract the LD50 of white mice P.O is respectively 32.88～38.50g/kg.
The rat long term toxicity test: get 120 male and female half and half of Wistar rat and be divided into 4 groups, 30 every group, P.O. gives 1.5g/kg, 0.50g/kg, 0.10g/kg persimmon leaf flavone extract (FEDk) respectively, NS negative control P.O. normal saline.It is unusual that successive administration 90 days, three dosage group rats there is no obvious hemogram, cardiopulmonary hepatic and renal function and nervous system merit, and also vitals such as the heart, lung, spleen, stomach, brain, intestinal do not have obvious pathological change.
Therefore, to be rich in flavone extract toxicity very low, safe for Folium Kaki of the present invention.
Embodiment 5: persimmon leaf flavone extract is to the blood glucose of diabetic mice, the influence of blood fat
Medicine and reagent: persimmon leaf flavone extract; Folium Kaki water extract (WEDkL), self-control, every gram extract is equivalent to Folium Kaki 12.5g); Blood glucose test kit (the safe reagent company limited of Beijing northization); T-CHOL, triglyceride, determine cholesterol with high density lipoprotein test kit; Streptozotocin (STZ), U.S. Sigma company product; The peace of quenching one's thirst capsule, Tonghua Baishan Pharmaceutical Ltd's product.
Adopt Advantage electronic induction blood glucose meter and supporting paper slip (Switzerland Roche company product) to measure blood glucose.
Experimental subject is to economize the cleaning level Male Kunming strain mice that Experimental Animal Center provides by Nanfang Medical Univ, and body weight is 22-25g.
A) to the blood glucose of streptozotocin (STZ) type diabetic mice and the influence of blood fat
Be divided into 8 groups at random after 80 mices numbering weighed, 10 every group, get wherein 1 group as the normal control group.All the other respectively organized the mice fasting after 16 hours, the freshly prepared 1% streptozotocin solution 150mg/kg of lumbar injection, after 72 hours, the ophthalmic corner of the eyes is got blood, adopt Advantage electronic induction blood glucose meter and supporting paper slip (Switzerland Roche company product) to measure blood glucose, blood glucose value is defined as the diabetes model Mus greater than 16.7mmol/L person.The diabetes model Mus is divided into 8 groups at random by after the blood glucose value numbering, 3 treatment groups of Folium Kaki flavone (10,20,40mg/kg), 2 treatment groups of Folium Kaki water extract (WEDkL) (40,80mg/kg); The peace of quenching one's thirst Capsules group (500mg/kg), model control group (+).Each group is gastric infusion 1 time/day respectively, and successive administration 30 days was plucked eye in 2 hours and got blood after the last administration played animal fasting, administration in preceding 12 hours, separation of serum, measures blood glucose and blood fat.
B) influence of the blood glucose of the hyperglycemia mice that epinephrine is caused
Be divided into 6 groups at random after 60 mices numbering weighed, 10 every group, get wherein 1 group as normal control group, epinephrine group, the big low dose of Folium Kaki flavone (20,40mg/kg) group, Folium Kaki water extract 80mg/kg group, the peace of quenching one's thirst Capsules group (500mg/kg).Each group difference gastric infusion 1 time/day, normal control group and epinephrine group give the equal-volume normal saline, successive administration 7 days, behind last administration 2h, matched group ip equal-volume normal saline, all the other respectively organize ip epinephrine (240 μ g/kg) solution, and 0.5h, 1h pluck eye and get blood behind the ip epinephrine respectively, separation of serum, mensuration blood glucose.
C) influence of the blood glucose of the hyperglycemia mice that glucose is caused
Be divided into 5 groups at random after 50 mices numbering weighed, every group 10, get wherein 1 group as normal control group, glucose group, the big low dose of Folium Kaki flavone (20,40mg/kg) group, Folium Kaki water extract (WEDkL) 80mg/kg group, the peace of quenching one's thirst Capsules group (500mg/kg).Each group difference gastric infusion 1 time/day, normal control group and glucose group give the equal-volume normal saline, successive administration 7 days, behind last administration 2h, matched group lumbar injection (ip) equal-volume normal saline, all the other respectively organize ip glucose (2g/kg) solution, respectively behind the ip glucose 0.5,1,2h plucks eye and gets blood, separation of serum, measures blood glucose.
(x ± s) expression carries out multiple comparisons between variance analysis and mean with SSP10.0 software to experimental data with means standard deviation.
The result shows, Folium Kaki flavone can obviously reduce blood glucose in diabetic mice (table 1) due to the streptozotocin, obviously reduce T-CHOL, triglyceride and low-density lipoprotein cholesterol in the diabetic mice serum, obviously high density lipoprotein increasing has the effect (table 2) of regulating the blood ester; In addition, Folium Kaki flavone can obviously reduce the blood glucose (table 3) of the hyperglycemia mice that epinephrine causes, obviously reduces the blood glucose (table 4) of the hyperglycemia mice that glucose causes.
Table 1 Folium Kaki flavone is to the influence of the blood glucose of streptozotocin (STZ) type diabetic mice (n=10, x ± s)
Annotate: compare with matched group
*P＜0.01; With the comparison of STZ model group, F=5.52,
▲ ▲P＜0.01,
▲P＜0.05
Table 2 Folium Kaki flavone is to the influence of the blood fat of streptozotocin (STZ) type diabetic mice
Annotate: compare with matched group
*P＜0.01; With the comparison of STZ model group, F=3.82,
▲ ▲P＜0.01,
▲P＜0.05
The influence of the blood glucose of the hyperglycemia mice that table 3 Folium Kaki flavone causes epinephrine (n=10, x ± s)
Annotate: compare with matched group
*P＜0.01; With the comparison of epinephrine model group, F=4.52,
▲ ▲P＜0.01,
▲P＜0.05
The influence of the blood glucose of the hyperglycemia mice that table 4 Folium Kaki flavone causes glucose (n=10, x ± s)
Annotate: compare with matched group
*P＜0.01; With the comparison of glucose model group, F=5.12,
▲ ▲P＜0.01,
▲P＜0.05
Embodiment 6: Folium Kaki flavone brings out the influence of the plain resistance of mouse islets to hydrocortisone
Be divided into 4 groups at random after 40 mices numbering weighed, every group 10, get wherein one group of subcutaneous injection normal saline as normal control group, one group of subcutaneous injection hydrocortisone (36mg/kg), in addition two groups of subcutaneous injection hydrocortisone (36mg/kg) irritate respectively the bigger low dose of stomach Folium Kaki flavone (20,40mg/kg).Each group difference gastric infusion 1 time/day, normal control group and hydrocortisone group give the equal-volume normal saline, successive administration 10 days, behind last administration 2h, matched group ip equal-volume normal saline, all the other respectively organize ip insulin (0.5g/kg), respectively behind the ip glucose 0.5,2h plucks eye and gets blood, separation of serum, measures blood glucose.The result is as shown in table 5.
Table 5 Folium Kaki flavone brings out influence (n=10, the x ± s) of the plain resistance of mouse islets to the oxidation cortisone
Annotate: compare with matched group
*P＜0.01; With the comparison of hydrocortisone model group,
▲ ▲P＜0.01,
▲P＜0.05
Embodiment 7: Folium Kaki flavone is to the effect of streptozotocin type diabetes model rat
Medicine and reagent: Folium Kaki flavone; Streptozotocin (STZ), U.S. Sigma company product.
Experimental subject be Wistar be 7 the week age male rat, conjuncted heavy 220～250g.
Getting 7 rats is normal group, other rat disposable celiac injections 50mg/kg STZ, and FBG is a hyperglycemia diabetes model rat greater than 16.7mmol/L person behind the 72h.Diabetes rat is divided into model group, the big small dose group of Folium Kaki flavone at random.Big agent group by people and rat dose,equivalent than 40mg/kg administration every day, little dose of group 20mg/kg every day, model group and normal group are given the 10ml/kg distilled water every day, irritate stomach the morning once, treat 15 days.Before each organizes modeling, after the modeling, the docking of treatment back gets blood and surveys blood glucose (FBG), serum insulin (Ins), get the rat pancreas at last and carry out HE dyeing and immunohistochemical staining as specimen.
Immunohistochemical staining is the anti-B of demonstration of I cell with strepto-avidin method with the Ins antiserum, is the anti-A of demonstration of I cell with the glucagon antiserum, and the positive reaction thing is a brown yellow granule.The blood glucose glucose oxidase method, serum insulin is with putting the method for exempting from.
(x ± s) expression carries out significance test with variance analysis method to experimental data with means standard deviation.
Influence to blood glucose the results are shown in Table 6, and model group and normal group compare, and FBG significantly raises (P＜0.01), significantly descends (P＜0.01) with model group comparison FBG after the big or small dosage treatment, illustrates that Folium Kaki flavone has remarkable hypoglycemic activity.
Table 6 Folium Kaki flavone is respectively organized rat blood sugar change list (mmol/L) to the STZ model
Annotate: compare with normal group,
*P＜0.05,
*P＜0.01; Compare with model group,
△P＜0.05,
△ △P＜0.01.
Influence to serum insulin the results are shown in Table 7, model group and normal group are relatively, Ins significantly reduces (P＜0.01), and serum Ins level shows that than the remarkable rising of model group (P＜0.05) secretion has certain facilitation to Folium Kaki flavone to Ins after the big or small dosage treatment.
Table 7 Folium Kaki flavone is respectively organized rat blood serum insulin change list (mU/L) to the STZ model
Annotate: compare with normal group,
*P＜0.05,
*P＜0.01; Compare with model group,
△P＜0.05,
△ △P＜0.01; With comparing before the treatment
▲P＜0.05
▲ ▲P＜0.01 (following table is identical).
HE dyeing histological observation is found: the normal group islets of langerhans is circular, elliptical erythrocyte group, and boundary is clear, and islets of langerhans number and island inner cell number are more, and kytoplasm is abundant; STZ model group islets of langerhans number and island inner cell number reduce, and cellular morphology is irregular, and nuclear differs in size, form differs, the part karyopycnosis, and a few cell is the cavity shape; Big agent group islets of langerhans number and island inner cell are counted showed increased, and cell distribution is even, and the nuclear size is equal substantially, no karyopycnosis; Little dose of group islets of langerhans number and island inner cell number increase, and form is rule comparatively, the small part karyopycnosis.This explanation Folium Kaki flavone has significant protective effect to the islet cells tissue of STZ MODEL DAMAGE, and can promote secretion of insulin.
Embodiment 8: persimmon leaf flavone extract is to the inhibitory action of alpha-glucosidase
To the active influence of small intestinal mucosa enzyme (saccharase, maltase): be modulated into saccharase, maltase with the rat mucous membrane of small intestine, get substrate (50mM sucrose, 50mM maltose) liquid 400 μ L, add small intestinal mucosa enzyme liquid 50 μ L, tried thing with the persimmon leaf flavone extract (FEDk) of 50 μ L variable concentrations (1-1000mg/ml), matched group adds the equal-volume normal saline, 37 ℃ of reaction 30min.Use 0.75ml 2mol/LTris liquid cessation reaction behind the reaction terminating.Afterwards, get 50 μ l reactant liquors, the glucose content (enzyme dosage is 350 ± 1.5 μ g) that utilizes glucose color development test kit (Wako) to generate with determination of glucose oxidase, maltase is with determination of glucose oxidase (enzyme dosage is 35.0 ± 0.05 μ g).N=9, specific activity are 150 ± 5nmol/min/ μ g protein, measure saccharase and maltase activity respectively, obtain the IC of FEDk to saccharase and maltase activity
50(μ g/ml).
The mensuration of amylase activity then adopts [Watanabe J such as crossing the limit, Kawabata J, Kurihara H, et al.Isolation and identification of alpha-glucosidaseinhibitors from Tochu-cha (Eucommia ulmoides) [J] .BiosciBiotechnol Biochem, 1997,61 (1): 177-178] method is carried out.That is, get 10 μ l test fluid and 240 μ l enzyme liquid (0.053U), behind 37 ℃ of preheating 5min, adding 750 μ l10mmol/L 4-nitrophenols-α-D-pyranglucoside solution is substrate, puts 37 ℃ and continues reaction 15min.With 0.5ml Tris solution cessation reaction, survey 400nm place's light absorption value and calculate IC
50Value.
The result is shown in Fig. 1 and table 8, and as seen, the brain heart is clear and bright to show reduction rat small intestine mucosa saccharase and maltase activity, and is the dose dependent relation.Therefore, the brain heart can suppress the activity of alpha-glucosidase, small intestinal mucosa enzyme (saccharase, maltase) clearly, not only hinders the intestinal absorption of sugar, and suppresses the intestinal absorption of its catabolite glucose.
Table 8FEDk is to the IC of alpha-glucosidase activity
50(μ g/ml)
Embodiment 9: prevent and/or treat the syndromic clinical verification Folium Kaki flavone of hyperglycemia, diabetes and glycolipid sheet treatment diabetes 60 examples and analyze
Test is with reference to Zheng Xiao cornel chief editor, new Chinese medicine clinical research guideline (try), Chinese Medicine science and technology publishing house, 2002 the 1st edition, 233-237: new Chinese medicine is treated the clinical research guideline of diabetes and is carried out.
1. clinical data
60 routine patients all are the non-insulin-dependent diabetes mellitus patient who makes a definite diagnosis according to the Western medicine diagnose standard of WHO expert consulting report in 1999, wherein, and outpatient service 38 examples, 22 examples of being in hospital; Be divided into two groups at random, treatment is organized in 30 examples, male 15 examples, women 15 examples; 39～66 years old age, year mean age (51.5 ± 8.8).Diabetic duration 3～16 years, average course of disease (7.0 ± 3.0) year; Merge hyperlipidemia person's 20 examples, coronary disease patient 11 examples, hyperpietic's 19 examples; In matched group 30 examples, male 15 examples, women 15 examples; 38～65 years old age; Year mean age (51.5 ± 6.8); Diabetic duration 2.5～16 years, average course of disease (6.9 ± 3.1) year; Merge hyperlipidemia person's 20 examples, coronary disease patient 9 examples, hyperpietic's 17 examples.Learning processing aspect sex, age, the course of disease, the complication by statistics for two groups, no significant difference (P＞0.05) has comparability.
2. diagnostic criteria
Western medicine diagnose standard (according to WHO expert consulting report in 1999): fasting glucose (FPG) 〉=7.0mmol/L and 2 hours after the meal blood glucose (2HPG) 〉=7.0mmol/L, random blood sugar 〉=11.1mmol/L.
The high pressure Herba Wedeliae Wallichii according to hypertension alliance of World Health Organization (WHO) in 1999/international about hypertensive classification by stages method formulate [hypertension alliance of World Health Organization (WHO) in 1999/international is about the hypertension therapeutic guide. hypertension magazine, 1999,7 (2): 9].
The clinical research guideline of tcm diagnosis standard reference nineteen ninety-five Ministry of Health of the People's Republic of China traditional Chinese medical science new drug treatment diabetes (diabetes): all have or dry mouth and throat, fatigue and weakness, polyorexia, thirst and liking drink, the lazy speech of breathing hard, dysphoria with feverish sensation in the chest palms and soles, palpitation and insomnia, pain in chest and hypochondrium, dark coloured urine constipation, red tongue or dim red, pale purple or the petechia ecchymosis arranged, deep-thready pulse or string are puckery, and Chinese medical discrimination is deficiency of both QI and YIN, blood stasis venation card person.
3. Therapeutic Method
The treatment group is taken persimmon leaf flavone extract sheet (being called for short the Folium Kaki flavone sheet), and each 2, every day 3 times, 2 months was 1 course of treatment, stop using therebetween other hypoglycemic medicine and blood pressure lowering, hypolipidemic.
Matched group is taked to quench one's thirst and is pacified capsule (0.4g/ grain) treatment, and each 3, every day 3 times, 2 months was 1 course of treatment, the treatment type 2 diabetes mellitus.
Two groups of patients all carry out diabetes education, diet control, moderate exercise.All case observation is 2 months.
4. observation index
Measuring blood pressure, fasting glucose (FBG) and 2 hours after the meal blood glucose (2HFBG) (glucose oxidase method), glycosylated hemoglobin (HbALc) and blood fat before and after the treatment: T-CHOL, triglyceride, low density lipoprotein, LDL and high density lipoprotein level Pseudobulbus Bletillae (Rhizoma Bletillae) hemorheology index (whole blood viscosity, height is cut (200/s), whole blood viscosity, low (3/s), plasma viscosity, Fibrinogen of cutting), 2,4,6 weeks detected blood pressure simultaneously during hepatic and renal function, routine urinalysis, the treatment.
5. clinical efficacy
Clinical research guideline (1993) criterion of therapeutical effect with reference to Ministry of Health of the People's Republic of China's traditional Chinese medical science new drug treatment diabetes (diabetes) is evaluated.Produce effects: transference cure, lab testing are repeatedly normal; Effectively: cardinal symptom and relevant lab testing have improvement; Invalid: symptom and relevant lab testing no change.
Blood glucose, blood fat, HbALc are relatively before and after the table 9 liang group treatment
Annotate: relatively preceding with the treatment of this group
*P＜0.01,
★P＜0.05, with the comparison of treatment of control group,
▲P＜0.01
Hemorheology changes before and after table 10 treatment group and the treatment of control group
Annotate: relatively preceding with the treatment of this group
*P＜0.01, with the comparison after the treatment of control group,
★P＜0.01,
▲P＜0.05
By table 10 as seen, Folium Kaki flavone sheet treatment type 2 diabetes mellitus has significant curative effect aspect the diabetic hemorheology index improving.
Table 11 illustrates the hypertension curative effect statistics of Folium Kaki flavone sheet to diabetes, patients with metabolic syndrome, and as seen, the Folium Kaki flavone sheet has the curative effect of blood pressure lowering to the hypertension of diabetes, patients with metabolic syndrome.
Table 11 Folium Kaki flavone sheet is to the hypertensive curative effect statistics of diabetes, patients with metabolic syndrome
Annotate: compare with the peace Capsules group of quenching one's thirst,
*) P＜0.01,
*) P＜0.05
Table 12 illustrates the comprehensive therapeutic effect statistics of Folium Kaki flavone sheet to diabetes, patients with metabolic syndrome, as seen, the total effective rate that Folium Kaki flavone thanks to syndrome to the metabolism of hyperglycemia hyperlipidemia complicated hypertension is 93.3%, produce effects 60.0%, 87% total effective rate than present medicine commonly used is slightly high, and does not observe apparent side effect.
Table 12 Folium Kaki flavone sheet is to the comprehensive therapeutic effect statistics of diabetes, patients with metabolic syndrome
Claims (9)
1. a persimmon leaf flavone extract wherein comprises the total flavones in the weight 60-90% of extract dry product, and contains in total flavones in the Quercetin of the weight 8-14% of extract dry product and the nimbecetin of 12-23%.
2. according to the persimmon leaf flavone extract of claim 1, wherein comprise total flavones, and in total flavones, contain in the Quercetin of the weight 13-14% of extract dry product and the nimbecetin of 15-20% in the weight 77-86% of extract dry product.
3. the preparation method of persimmon leaf flavone extract, comprise that adopting the leaf of Ebenaceae calamander Fructus Kaki is raw material, the process following steps: (1) decocting in water, filter (2), (3) precipitate with ethanol, (4) ethyl acetate extraction, (5) macroporous resin adsorption, (6) ethanol elution, (7) are reclaimed ethanol and are obtained concentrate, with optional (8) drying, thereby obtain the extract that Folium Kaki is rich in flavone.
4. according to the preparation method of claim 3, wherein in step (1), raw material is decocted with water 1-3 time each 0.2-3 hour; Decocting liquid filters, and filtrate is concentrated into that relative density is the clear paste of 1.05-1.2 in the time of 60 ℃; Ethanol precipitation is got supernatant and is reclaimed ethanol, obtains extractum; Use ethyl acetate extraction after being dissolved in water, get extract and reclaim ethyl acetate, obtain thick paste; With going up macroporous resin column absorption behind the water dissolution; Use the alcoholic solution eluting, collect ethanol liquid, obtain persimmon leaf flavone extract behind the recovery ethanol.
5. according to the preparation method of claim 3 or 4, wherein macroporous resin is polyamide type or polystyrene resin series.
6. according to the preparation method of claim 3 or 4, wherein adopt method, preferably spray drying methods such as hyperthermia drying, thin film evaporation drying or cold drying to carry out drying, and when spray drying, inlet temperature is 60-180 ℃, outlet temperature is 45-80 ℃, wind speed is 5-10m/s, and pressure is 0.01-0.8MPa.
7. according to each preparation method of claim 3-6, wherein comprise the weight 60-90% in the extract dry product, the total flavones of preferred 77-86% in the gained persimmon leaf flavone extract, and in total flavones, contain the Quercetin of the weight 8-14% in the extract dry product, preferred 13-14% and the nimbecetin of 12-23%, preferred 15-20%.
8. the purposes of persimmon leaf flavone extract is used to prepare the medicine and/or the health product that prevent and/or treat glycolipid metabolism related diseases, and described glycolipid metabolism related diseases comprises hyperglycemia, diabetes and metabolism syndrome.
9. purposes according to Claim 8, wherein prevent and/or treat the medicine of glycolipid metabolism related diseases and/or health product by in described persimmon leaf flavone extract, adding various adjuvants such as lubricant, filler, binding agent, disintegrating agent etc., utilize conventional pharmaceutical preparation technology and the method for preparing food, be made for the form of tablet, dispersible tablet, controlled release tablet, capsule, powder, pill, drop pill, powder, granule, crystal, solution, extractum, outstanding agent, soup, syrup, elixir, tea, wet goods.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2006101620736A CN101194921B (en) | 2006-12-08 | 2006-12-08 | Application of persimmon leaf flavone extract |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2006101620736A CN101194921B (en) | 2006-12-08 | 2006-12-08 | Application of persimmon leaf flavone extract |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101194921A true CN101194921A (en) | 2008-06-11 |
| CN101194921B CN101194921B (en) | 2011-12-21 |
Family
ID=39545667
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2006101620736A Active CN101194921B (en) | 2006-12-08 | 2006-12-08 | Application of persimmon leaf flavone extract |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101194921B (en) |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101322737B (en) * | 2008-07-25 | 2010-08-25 | 卢照凯 | Persimmon leaf flavones extract and preparation thereof |
| CN101845467A (en) * | 2010-05-10 | 2010-09-29 | 苏州瑞蓝博中药技术开发有限公司 | Method for extracting kaempferol |
| WO2010042886A3 (en) * | 2008-10-10 | 2010-11-11 | Limerick Biopharma, Inc. | Pyrones for the treatment of metabolic disorders |
| CN102068484A (en) * | 2011-01-08 | 2011-05-25 | 桂林普兰德生物科技有限公司 | Method for extracting persimmon leaf flavone with content of more than or equal to 85 to 98 percent from persimmon leaf |
| CN102949435A (en) * | 2012-11-20 | 2013-03-06 | 西安交通大学 | Application of persimmon leaf general flavone in inhibiting pancreatic beta cell apoptosis and extraction method thereof |
| CN104606276A (en) * | 2014-12-30 | 2015-05-13 | 桂林得坤生物科技股份有限公司 | Method for extracting micromolecular persimmon leaf flavones from persimmon leaves |
| CN104666391A (en) * | 2015-03-10 | 2015-06-03 | 沈阳东新药业有限公司 | Solid dispersion dropping pill adopting persimmon leaf total flavonoids and preparation method of solid dispersion dropping pill |
| CN105012372A (en) * | 2015-07-21 | 2015-11-04 | 西安交通大学 | Method for extracting total flavones of persimmon leaves by semi-bionic enzyme extraction and application of total flavones |
| CN105535947A (en) * | 2016-01-20 | 2016-05-04 | 孔德华 | Pharmaceutical composition for treating II-type diabetes and preparation method of pharmaceutical composition |
| EP3042661A1 (en) * | 2013-09-03 | 2016-07-13 | Sunstar Inc. | Composition for improving blood sugar metabolism |
| CN111298110A (en) * | 2020-03-07 | 2020-06-19 | 石家庄瑞思达生物技术有限公司 | Immunologic adjuvant containing flavone saponin and application thereof |
| CN114224933A (en) * | 2022-01-17 | 2022-03-25 | 广州思沛医药科技股份有限公司 | Persimmon leaf flavone extract and preparation method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1230161C (en) * | 2003-12-03 | 2005-12-07 | 广州白云山制药股份有限公司广州白云山中药厂 | Persimmon leaf extract and its preparation and its usage |
-
2006
- 2006-12-08 CN CN2006101620736A patent/CN101194921B/en active Active
Cited By (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101322737B (en) * | 2008-07-25 | 2010-08-25 | 卢照凯 | Persimmon leaf flavones extract and preparation thereof |
| WO2010042886A3 (en) * | 2008-10-10 | 2010-11-11 | Limerick Biopharma, Inc. | Pyrones for the treatment of metabolic disorders |
| CN101845467A (en) * | 2010-05-10 | 2010-09-29 | 苏州瑞蓝博中药技术开发有限公司 | Method for extracting kaempferol |
| CN102068484A (en) * | 2011-01-08 | 2011-05-25 | 桂林普兰德生物科技有限公司 | Method for extracting persimmon leaf flavone with content of more than or equal to 85 to 98 percent from persimmon leaf |
| CN102068484B (en) * | 2011-01-08 | 2012-05-23 | 桂林普兰德生物科技有限公司 | Method for extracting persimmon leaf flavone with content of more than or equal to 85 to 98 percent from persimmon leaf |
| CN102949435A (en) * | 2012-11-20 | 2013-03-06 | 西安交通大学 | Application of persimmon leaf general flavone in inhibiting pancreatic beta cell apoptosis and extraction method thereof |
| US9801917B2 (en) | 2013-09-03 | 2017-10-31 | Sunstar Inc. | Composition for improving blood sugar metabolism |
| EP3042661A1 (en) * | 2013-09-03 | 2016-07-13 | Sunstar Inc. | Composition for improving blood sugar metabolism |
| EP3042661A4 (en) * | 2013-09-03 | 2017-05-17 | Sunstar Inc. | Composition for improving blood sugar metabolism |
| CN104606276A (en) * | 2014-12-30 | 2015-05-13 | 桂林得坤生物科技股份有限公司 | Method for extracting micromolecular persimmon leaf flavones from persimmon leaves |
| CN104606276B (en) * | 2014-12-30 | 2019-04-26 | 桂林得坤生物科技股份有限公司 | A method of extracting small molecule persimmon leaf flavone from persimmon leaf |
| CN104666391A (en) * | 2015-03-10 | 2015-06-03 | 沈阳东新药业有限公司 | Solid dispersion dropping pill adopting persimmon leaf total flavonoids and preparation method of solid dispersion dropping pill |
| CN104666391B (en) * | 2015-03-10 | 2018-10-30 | 沈阳东新药业有限公司 | Persimmon leaf general flavone solid dispersions dripping pill and preparation method thereof |
| CN105012372A (en) * | 2015-07-21 | 2015-11-04 | 西安交通大学 | Method for extracting total flavones of persimmon leaves by semi-bionic enzyme extraction and application of total flavones |
| CN105012372B (en) * | 2015-07-21 | 2021-12-28 | 西安交通大学 | Method for extracting persimmon leaf total flavonoids by semi-bionic enzymatic method and application |
| CN105535947A (en) * | 2016-01-20 | 2016-05-04 | 孔德华 | Pharmaceutical composition for treating II-type diabetes and preparation method of pharmaceutical composition |
| CN111298110A (en) * | 2020-03-07 | 2020-06-19 | 石家庄瑞思达生物技术有限公司 | Immunologic adjuvant containing flavone saponin and application thereof |
| CN114224933A (en) * | 2022-01-17 | 2022-03-25 | 广州思沛医药科技股份有限公司 | Persimmon leaf flavone extract and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101194921B (en) | 2011-12-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101194921B (en) | Application of persimmon leaf flavone extract | |
| CN104225456B (en) | A kind of hypoglycemic pharmaceutical composition | |
| CN102091083B (en) | Petroleum ether extract of traditional Chinese medicine for preventing and treating glucose and lipid metabolic disturbance and preparation method thereof | |
| CN102366595B (en) | Medicine for treating diabetes and preparation method thereof | |
| CN103446385A (en) | Traditional Chinese medicine preparation for treating diabetic complications | |
| CN104688822A (en) | Tablet for assisting to reduce blood glucose and preparation method | |
| CN103417749A (en) | Preparing method of herba violae extract and application of herba violae extract in hypoglycemic agents | |
| CN1310668C (en) | Medicine for treating diabetes, and its prepn. method | |
| CN101045076B (en) | Extractive of persimmon leaves ethyl acetate used for prevention and/or treatment of glycolipid metabolism related diseases | |
| CN101816719B (en) | Peach blossom or peach leaf general flavone and application thereof in preparing medicines or health care products for lowering blood sugar and fat and preventing and/or treating diabetes and complications | |
| CN100333758C (en) | Gout resisting Chinese medicine composition and its prepn process | |
| CN102579587B (en) | Traditional Chinese medicine composition for preventing and treating diabetes and complications thereof | |
| CN105708934A (en) | Composition capable of stabilizing blood glucose and reducing blood glucose and preparation process thereof | |
| CN103055176B (en) | Traditional Chinese medicine for treating diabetes mellitus and preparation method thereof | |
| CN101411781A (en) | Use of pu'er tea in preparing medicament for treating or preventing diabetes | |
| CN104042928B (en) | A kind of pharmaceutical composition for treating diabetes and its production and use | |
| CN100484555C (en) | Application of Aloe vera L. extract in preparing medicament and health products for preventing and curing diabetes | |
| CN106109767A (en) | A kind of compound preparation preventing and treating non-alcohol fatty liver | |
| CN102366540B (en) | Medicine for treating diabetes and its preparation method | |
| JP2004331635A (en) | Cytogenetic information normalization material and method for preparing the same | |
| CN102579589B (en) | Application of Chinese medicinal composition in preparing hypoglycemic drugs or health-promoting products | |
| CN108143756A (en) | A kind of plant hypoglycemic agent and preparation method thereof | |
| CN102366481B (en) | Medicine for treating diabetes and preparation method thereof | |
| CN101380353B (en) | Pharmaceutical composition for preventing and curing 2-type diabetes and preparation method thereof | |
| CN1463734A (en) | A prepared Chinese medicine for treating diabetes mellitus and method for preparing same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |