CN101890063A - Chinese medicament for reducing blood sugar and preparation method thereof - Google Patents
Chinese medicament for reducing blood sugar and preparation method thereof Download PDFInfo
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- CN101890063A CN101890063A CN2009101433150A CN200910143315A CN101890063A CN 101890063 A CN101890063 A CN 101890063A CN 2009101433150 A CN2009101433150 A CN 2009101433150A CN 200910143315 A CN200910143315 A CN 200910143315A CN 101890063 A CN101890063 A CN 101890063A
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- Prior art keywords
- lower alcohol
- eluate
- active component
- preparation
- ethanol
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Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
The invention relates to application of an extract of oak tree leaves in preparation of a medicament for preventing and treating high blood sugar disease. The invention provides a preparation method for separating the extract from the oak tree leaves. Pharmacological experiments prove that the extract has obvious effect of reducing blood sugar. The invention also provides application of the extract in preparing a medicinal preparation for preventing and treating diabetes.
Description
Technical field
The invention belongs to new Chinese medicine research and development field.Relate to and utilize Chinese medicine to prepare blood sugar lowering and preparation method thereof, relate in particular to and adopt modern extraction separation, technology, from Chinese medicine Folium Querci Mongolicae, obtain to have the active component of hypoglycemic activity, the preparation blood sugar lowering.
Background technology
Diabetes are a kind of commonly encountered diseases, and the whole world has diabetics 1.5 hundred million now, it is predicted that patient's number in 2025 will be increased to 3.33 hundred million. the diabetes Chinese medical discrimination belongs to " quenching one's thirst " sick category.Study carefully its pathogenesis and mainly be YIN fluid deficiency, scorching and is this with the deficiency of YIN partially very, scorchingly is mark.Production of dryness-heat in the interior, the dried liquid in Tianjin is withered, and QI and blood is not smooth, is the stasis of blood for a long time.New in recent years Prevention Technique mainly contains the immunotherapy of islet cell transplantation, pancreas transplantation, insulin pump replacement injection of insulin and diabetes etc., and clinical medicine commonly used has biguanide antidiabetic medicament-metformin hydrochloride and insoral (phenformin).The insoral major side effects is a gastrointestinal reaction, and symptoms such as anorexia, bitter taste, nausea,vomiting,diarrhea are arranged, and because of through liver metabolism, easily brings out lactic acidosis.Though metformin lures the probability of lactic acidosis than the remarkable minimizing of insoral, but still this side effect is arranged.Recently, the U.S. develops medicine---the troglitazone of third generation treatment diabetes according to receptor theory, and according to reporting at present, late result is stable, but certain side effect is arranged, and large tracts of land is promoted yet.Therefore, how to make the blood glucose stable for extended periods of time of diabetic, need research and development good effect, few side effects and the modern preparation of blood-sugar lowering tcm drug little, treating both the principal and secondary aspects of a disease.
Folium Querci Mongolicae is the leaves of Fagaceae plant Mongolian oak Quercus mongolica Fisch, and mildly bitter flavor, puckery, property are flat, clearing away heat to cure dysentery, cough-relieving, removing toxic substances and promoting subsidence of swelling.Cure mainly dysentery, enteritis, dyspepsia, bronchitis, carbuncle, hemorrhoid.Both at home and abroad about the rarely seen sitosterol of its chemical constitution study, lupeol, glutinol and fat hydrocarbon composition.Referring to: " China's book on Chinese herbal medicine " (the 2nd volume, 438-440 page or leaf)
Summary of the invention
The technical problem to be solved in the present invention is from Folium Querci Mongolicae, researchs and develops the modern preparation of Chinese medicine of hypoglycemic active component.Side effect significantly reduces and reduces, and makes it easy to the patient and takes still quite safe for a long time.Can alleviate or suppress the generation and the development of diabetic complication.The technical problem to be solved in the present invention also comprises the extraction separation method of the above-mentioned blood sugar lowering Chinese medicine composition of research preparation, and this method is answered favorable reproducibility, can be used in suitability for industrialized production.
For solving the problems of the technologies described above, the present invention has studied and defined following technical scheme:
The invention provides a kind of Folium Querci Mongolicae active component with hypoglycemic activity.
The preparation method of said composition comprises the steps:
(1) get the Folium Querci Mongolicae medical material, water and/or lower alcohol extraction obtain extracting solution, and the gained extracting solution is concentrated, and drying is active component; Perhaps,
(2) the step 1) extracting solution is directly gone up macroporous adsorptive resins, perhaps with behind the earlier concentrated redispersion of step 1) extracting solution, last macroporous adsorptive resins; With the 0-95% lower alcohol macroporous adsorptive resins is carried out gradient elution successively, collect each eluate respectively; With wherein eluate of 45-55% lower alcohol and/or the eluate of 85-99% lower alcohol, be active component behind the concentrate drying; Perhaps,
(3) get step 2) in after the eluate of 45-55% lower alcohol and/or the eluate of 85-99% lower alcohol concentrate, carry out chromatography with 15-60 order polyamide, carry out gradient elution with the 0-95% lower alcohol, collect the eluate of its 30% and/or 50% concentration of lower alcohols, concentrate drying obtains active component.
In the described method for preparing extractive, when extraction or gradient elution, used lower alcohol is meant that carbon number is the straight or branched lower alcohol (described lower alcohol particular methanol, ethanol, propanol or n-butyl alcohol) of C1-C5; Water and lower alcohol are that V/V mixes (for example, in the lower alcohol of certain milliliter number, adding the water of certain milliliter number).
Concentration of lower alcohols was 0-95% during step (1) was extracted; With backflow, dipping, percolation or decocting method
Extract; Step 2) macroporous resin described in is that in polystyrene type, polyacrylate or the polymethacrylates type any one or a few is the resin of framework material; Step 2) in the macroporous adsorptive resins gradient elution preferably method be earlier to remove impurity with the lower alcohol below 5%, reuse 5-95% lower alcohol eluting; Collect 50% lower alcohol eluate and/or 95% lower alcohol eluate, concentrate, promptly get the Folium Querci Mongolicae active component;
Polyamide chromatography gradient elution is to be lower than 5% lower alcohol to remove impurity with concentration preferably in the step 3),
Reuse concentration 5-95% lower alcohol; Collect the eluate of 30% and/or 50% concentration of lower alcohols, concentrate, promptly get the Folium Querci Mongolicae active component;
Preferred in the aforementioned preparation method: extracting solvent for use is 0-95% ethanol; The extraction solvent load is a medical material
The 10-12 of consumption doubly; Extraction time is 2h/ time; Extract altogether 3 times; The gradient elution of macroporous adsorptive resins is earlier to remove impurity with 0-40% ethanol, and reuse 50-95% ethanol elution is collected 50% lower alcohol eluate and/or 95% lower alcohol eluate, concentrated active component; Extract or when macroporous adsorptive resins or polyamide chromatography carried out gradient elution, used lower alcohol is selected from the mixture of any one or they in methanol, ethanol, propanol or the n-butyl alcohol; When macroporous adsorptive resins was carried out eluting, the consumption of eluting solvent was that the 8-12 of used resin volume doubly measures, preferred 10 times of amounts; During to the polyamide column eluting, the consumption of each eluting solvent is that the 2-5 of used polyamide volume doubly measures, preferred 3 times of amounts.Described macroporous resin is selected from AB-8, D101 type resin; Concentrate drying selects for use any one method in decompression, vacuum, the freezing or spray method to carry out.
In the preferred preparation method, gradient elution is earlier with 0-5% ethanol impurity, reuse 10%-20% ethanol elution impurity; Reuse 50%-95% ethanol elution is collected 50% lower alcohol eluate and/or 95% lower alcohol eluate, concentrate active component.
Aforementioned any prevention or treatment hyperglycemia group active component with a kind of Folium Querci Mongolicae active component of aforementioned people, mix with pharmaceutically acceptable carrier, make oral formulations or injection.Described pharmaceutical acceptable carrier, adjuvant and drug effect of the present invention is not had antioxidant, aminoacid, vitamin, carbohydrate or the plant extract of obviously influence.Described oral formulations is capsule, soft capsule, granule, oral liquid, tablet or drop pill, and described injection comprises lyophilized injectable powder or injection.
Aforementioned blood-sugar-reducing effective components is formed compound recipe with aforementioned any Folium Querci Mongolicae active component and other Chinese medicine, and described Chinese medicine comprises promoting blood flow and remove blood stasis drug Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, Testudinis fletching, Radix Paeoniae Rubra, Cortex Moutan, Hirudo, Radix Angelicae Sinensis; The supplementing QI and nourishing YIN medicine Radix Astragali, Radix Ginseng, Fructus Corni, Fructus Lycii; And nourishing YIN and clearing away heat medicine: Rhizoma Coptidis, Radix Ophiopogonis, Cortex Lycii, the Rhizoma Anemarrhenae, Radix Rehmanniae, Rhizoma Polygonati Odorati, Rhizoma Polygonati.
Aforementioned any Folium Querci Mongolicae active component is in preparation prevention or the medicine of treatment hyperglycemia disease or the application in the health product, and described hyperglycemia disease comprises diabetes.
The present invention follows the trail of the active component of Folium Querci Mongolicae blood sugar lowering based on activity.Experiment is set about from different extract parts, selects normal and chemical diabetes mouse model for use, carries out the blood sugar lowering pharmacy relatively in integral level, tentatively determines the active component of Folium Querci Mongolicae blood sugar lowering.
In order to obtain having the Folium Querci Mongolicae active component of hypoglycemic activity, the inventor utilizes Folium Querci Mongolicae to be raw material, and process water or polar organic solvent extraction, macroporous adsorbent resin eluting, eluent concentrate drying obtain the Folium Querci Mongolicae active component.The present invention is the effective active component with the Folium Querci Mongolicae active component, be used for preparation prevention or treatment hypoglycemic drug or health product, this medicine or health product mix with Folium Querci Mongolicae active component and pharmaceutically acceptable carrier, and pharmaceutically acceptable carrier comprises the adjuvant of oral formulations adjuvant or parenteral administration.Route of administration can be oral, injection, topical etc.
According to technical scheme of the present invention, this Chinese medicine preparation or health-care preparation, wherein preparation is used in oral formulations or refraction, and wherein oral formulations comprises capsule, soft capsule, granule, oral liquid, tablet or drop pill etc.Described injection comprises lyophilized injectable powder or injection.Used adjuvant comprises, as conventional adjuvants such as starch, sucrose, lactose, Icing Sugar, glucose, mannitol, xylitol, Polyethylene Glycol, isopropyl alcohol, soil temperature-80, glycerol, propylene glycol, microcrystalline Cellulose sodium, dextrin, cyclodextrin, sodium chloride, vitamin C, cysteine, citric acid, sodium thiosulfate, sodium sulfite, stearate and gelatin.Also comprise the antioxidant, aminoacid, vitamin, carbohydrate or the plant extract that drug effect of the present invention are not had obviously influence.Described pharmaceutical formulation is an oral formulations, comprises capsule, soft capsule, granule, oral liquid, tablet or drop pill etc.; Be injection perhaps, comprise lyophilized injectable powder and injection etc.; Be local administration preparation perhaps, comprise cream, ointment, patch, spray, subcutaneous implant etc.The later stage preparation technology of preparation all belongs to the routine techniques of pharmaceutical field, and the present invention does not limit this.
The diabetes islet cells is impaired, hypoinsulinism and a kind of endocrinopathy of the metabolism disorder that causes it is generally acknowledged that hypoglycemic mechanism of action relates generally to two aspects: the one, promote secretion of insulin and the release or the secretion of glicentin; The 2nd, influence metabolic some link behind the Insulin receptor INSR, mainly be the glyconeogenesis that suppresses liver, its purpose all is to reduce and glucose level control.Result of study demonstration Folium Querci Mongolicae does not have obvious influence to healthy mice blood glucose, points out it significantly not stimulate insulin release action or ILA; The active component of extraction separation has tangible reduction effect to the blood sugar increasing due to the alloxan in the Folium Querci Mongolicae under the low dosage condition, and this shows the function of the B cell that it all has repairing damage and reduces the antagonism of body to insulin.
The diabetes Chinese medical discrimination belongs to " quenching one's thirst " sick category.Study carefully its pathogenesis and mainly be YIN fluid deficiency, scorching and is this with the deficiency of YIN partially very, scorchingly is mark.Production of dryness-heat in the interior, the dried liquid in Tianjin is withered, and QI and blood is not smooth, is the stasis of blood for a long time.So the treatment diabetes are worked as based on replenishing YIN and removing heat, activating blood circulation to dissipate blood stasis.Folium Querci Mongolicae is flat, mildly bitter flavor, puckery, tool clearing away heat to cure dysentery, cough-relieving, removing toxic substances and promoting subsidence of swelling.The active component of extraction separation in the Folium Querci Mongolicae, its treatment are quenched one's thirst and can be taken into account specimen, and the diabetes pathogenesis hits.The present invention discovers, Folium Querci Mongolicae can with Chinese medicines such as Radix Ginseng, Rhizoma Coptidis, Cortex Cinnamomi, the Radix Astragali, Fructus Corni, Radix Angelicae Sinensis, form compound recipe with blood sugar reducing function, hypoglycemic effect is obvious.
Because adopted the resin technology in the modernization of Chinese medicine technology, preparation technology is simple, cost is low, is fit to suitability for industrialized production.
The specific embodiment
The inventor describes the enforcement of technical solution of the present invention in detail by following examples, but should not limit practical range of the present invention with this.
Embodiment 1: the preparation method of Folium Querci Mongolicae active component
Take by weighing the 5kg medical material, extract medical materials with 10 times of medical material water gagings, reflux, extract, three times, each 1 hour, merges three times extracting solution, the sucking filtration extracting solution, be concentrated into dried, must the 210g sample, promptly.After the sample dissolution, carry out alphanaphthol test (Molish) reaction: get solution 1ml, add 1 of 10% alpha-Naphthol alcohol liquid, shake up, slowly add dense H along tube wall
2SO
410, not jolting is observed between two liquid interfaces and is occurred the aubergine cup, illustrates to have sugar, glycoside composition; Utilize TLC (thin layer chromatography) inspection to know (developing solvent: n-BuOH: HAc: H
2O=4: 1: 5, V/V), under 254nm, skin dark stain is arranged, FeCl
3Spray solution shows the navy blue speckle; Embodiment 2: the preparation method of Folium Querci Mongolicae active component
Take by weighing the 5kg medical material, with 10 times of medical material amounts, 95% ethanol extraction medical material, reflux, extract, three times, each 1 hour, merge three times extracting solution, the sucking filtration extracting solution, be concentrated into dried, the 143g sample, promptly.After the sample dissolution, carry out alphanaphthol test (Molish) reaction: get solution 1ml, add 1 of 10% alpha-Naphthol alcohol liquid, shake up, slowly add dense H along tube wall
2SO
410, not jolting is observed between two liquid interfaces and is occurred the aubergine cup, illustrates to have sugar, glycoside composition; Utilize TLC (thin layer chromatography) inspection to know (developing solvent: CHCl
3: MeOH=9: 1, V/V)), under 254nm, skin dark stain being arranged, 4-hydroxyl-3-methoxylbenxaldehyde-sulfuric acid solution sprays, and post-heating has the peony speckle to occur.
Embodiment 3: the preparation method of Folium Querci Mongolicae active component
Take by weighing the 5kg medical material, extract medical material with 10 times of medical material water gagings, reflux, extract, three times, each 1 hour, merge three times extracting solution, the sucking filtration extracting solution, be splined on the D101 macroporous resin that 5kg handles well, flow velocity 15ml/min, after the completion of the sample, water elution is closely colourless to eluent, 50 liters in shared water, 20% ethanol elution is closely colourless to eluent, eluting 40 liters, 50% ethanol elution is closely colourless to eluent, eluting 40 liters, 80% ethanol elution is closely colourless to eluent, eluting 30 liters, use 30 liters of 95% ethanol elutions at last.Concentrate, drying is collected sample.Each eluate concentrates back gained example weight and is respectively 2.60g, 157.5g, 22.40g, 4.60g and 3.7g.After the sample dissolution, carry out alphanaphthol test (Molish) reaction: get solution 1ml, add 1 of 10% alpha-Naphthol alcohol liquid, shake up, slowly add dense H along tube wall
2SO
410, not jolting is observed between two liquid interfaces and is occurred the aubergine cup, illustrates to have sugar, glycoside composition.
Embodiment 4: the preparation method of Folium Querci Mongolicae active component
Take by weighing the 5kg medical material, extract medical material with 10 times of medical material water gagings, reflux, extract, three times, each 1 hour, merge three times extracting solution, the sucking filtration extracting solution, be splined on the AB-8 macroporous resin that 5kg handles well, flow velocity 15ml/min, after the completion of the sample, water elution is closely colourless to eluent, 50 liters in shared water, 20% ethanol elution is closely colourless to eluent, eluting 40 liters, 50% ethanol elution is closely colourless to eluent, eluting 40 liters, 80% ethanol elution is closely colourless to eluent, eluting 30 liters, use 30 liters of 95% ethanol elutions at last.Concentrate drying is collected sample.Each eluate concentrates back gained example weight and is respectively 3.20g, 130.0g, 26.40g, 8.60g and 5.3g.After the sample dissolution, carry out alphanaphthol test (Molish) reaction: get solution 1ml, add 1 of 10% alpha-Naphthol alcohol liquid, shake up, slowly add dense H along tube wall
2SO
410, not jolting is observed between two liquid interfaces and is occurred the aubergine cup, illustrates to have sugar, glycoside composition; Utilize TLC (thin layer chromatography) inspection to know (developing solvent: CHCl
3: MeOH=9: 1, V/V)), under 254nm, skin dark stain being arranged, 4-hydroxyl-3-methoxylbenxaldehyde-sulfuric acid solution sprays, and post-heating has the peony speckle to occur.
Embodiment 5: the preparation method of the isolating active component of Folium Querci Mongolicae polyamide chromatography
Take by weighing the 5kg medical material, extract medical material with 10 times of medical material water gagings, reflux, extract, three times, each 1 hour, merge three times extracting solution, the sucking filtration extracting solution, be splined on the D101 macroporous resin that 5kg handles well, flow velocity 15ml/min, after the completion of the sample, water elution is closely colourless to eluent, 50 liters in shared water, 20% ethanol elution is closely colourless to eluent, eluting 40 liters, 50% ethanol elution is closely colourless to eluent, eluting 40 liters, 80% ethanol elution is closely colourless to eluent, eluting 30 liters, use 30 liters of 95% ethanol elutions at last.Concentrate, drying is collected sample, promptly.Get above-mentioned Folium Querci Mongolicae 50% ethanol elution thing component, carry out chromatography, use the aquiferous ethanol gradient elution, collect the eluting position of its 30% concentration of alcohol respectively, obtain active component 6.4g with 15-60 order polyamide; Utilize TLC (thin layer chromatography) inspection to know (developing solvent: n-BuOH: HAc: H
2O=4: 1: 5, V/V), under 254nm, skin dark stain is arranged, FeCl
3Spray solution shows the navy blue speckle.
Embodiment 6: the preparation method of the isolating active component of Folium Querci Mongolicae polyamide chromatography
Take by weighing the 5kg medical material, extract medical material with 10 times of medical material water gagings, reflux, extract, three times, each 1 hour, merge three times extracting solution, the sucking filtration extracting solution, be splined on the D101 macroporous resin that 5kg handles well, flow velocity 15ml/min, after the completion of the sample, water elution is closely colourless to eluent, 50 liters in shared water, 20% ethanol elution is closely colourless to eluent, eluting 40 liters, 50% ethanol elution is closely colourless to eluent, eluting 40 liters, 80% ethanol elution is closely colourless to eluent, eluting 30 liters, use 30 liters of 95% ethanol elutions at last.Concentrate, drying is collected sample, promptly.Get above-mentioned Folium Querci Mongolicae 50% ethanol elution thing component, carry out chromatography, use the aquiferous ethanol gradient elution, collect the eluting position of its 50% concentration of alcohol respectively, obtain active component 9.6g with 15-60 order polyamide; Utilize TLC (thin layer chromatography) inspection to know (developing solvent: n-BuOH: HAc: H
2O=4: 1: 5, V/V), under 254nm, skin dark stain is arranged, FeCl
3Spray solution shows the navy blue speckle.
Embodiment 7: the capsule preparation of Folium Querci Mongolicae active component
Get the Folium Querci Mongolicae active component 100g of embodiment 5 or embodiment 6 methods preparation, 60 ℃ of dryings grind, and cross 80 mesh sieves, the microcrystalline Cellulose 100g that added 80 mesh sieves, mix homogeneously is made soft material in right amount with 70% ethanol, crosses 30 mesh sieve system granules, oven dry, make moisture less than 5%, cross 40 mesh sieve granulate, be sub-packed in No. 3 capsules.Every capsules contains Folium Querci Mongolicae active component 0.1g, uses aluminium plastic composite packaging, promptly.Oral administration, every day 3 times, each 1.
Embodiment 8: the preparation tablets of Folium Querci Mongolicae active component
Get the Folium Querci Mongolicae active component 60g of embodiment 5 or embodiment 6 methods preparation, add microcrystalline Cellulose 60g, hypromellose with 2% is as binding agent system soft material, the dry granulate of granulating adds 4% disintegrating agent carboxymethyl base Starch Sodium and lubricant 0.5% magnesium stearate and fine powder mix homogeneously, dry granular adding magnesium stearate, granulate, mixing, tabletting, promptly.Every contains Folium Querci Mongolicae active component 0.1g.Oral administration, every day 3 times, each 1.
Embodiment 9: Folium Querci Mongolicae water, alcohol extract cause the influence of mice hyperglycemia to alloxan
Get 88 of healthy ICR mices, wherein the normal control group is 10, tail vein injection saline 0.1ml/10g, all the other mouse tail vein injection alloxan normal saline solutions (45mg/kg) (modeling dosage is fixed according to the trial test result), survey fasting glucose behind the modeling 72h, blood glucose value is a diabetes animal model greater than the mice of 11.1mmol/L, be divided at random by blood glucose value: model control group, positive controls (insoral 150mg/kg), little (the 10g crude drug/kg) of Folium Querci Mongolicae water extract (embodiment 1 gained sample), (the dosage group of 20g crude drug/kg), little (the 10g crude drug/kg) of Folium Querci Mongolicae alcohol extract (embodiment 2 gained samples) greatly, (totally 6 groups of dosage groups of 20g crude drug/kg) greatly.Each administration group is all by 0.2ml/10g volume gastric infusion, and every day 1 time, continuous 14 days, normal control group and model control group gave the equal-volume normal saline.Administration was got blood on the 7th day and is surveyed fasting glucose behind the socket of the eye, plucked eyeball and get blood, the survey fasting blood sugar in the 14th day.Experimental data is used
Expression is carried out statistical procedures with the t check between group.
Table 1 Folium Querci Mongolicae water, alcohol extract cause the influence of mice hyperglycemia, 7 days and 14 days mouse blood sugar results behind the medicine to alloxan
Annotate: compare with model control group
*P<0.05
*P<0.01
* *Compare with the normal control group P<0.001
△ △ △P<0.001 by table 1 blood glucose value result as can be known, model group and normal group relatively, blood glucose value obviously raises, and learns by statistics to handle difference utmost point significance (P<0.001) is arranged; Positive group obviously reduces with model group comparison blood glucose value, and learning processing difference by statistics has utmost point significance (P<0.001); The heavy dose of group of Folium Querci Mongolicae water extract compares with model group, and 14 days blood glucose values of administration obviously reduce, and handle difference by statistics significance (P<0.05), and the blood sugar lowering rate is 20.49%; Little, the heavy dose of group of Folium Querci Mongolicae alcohol extract compares with model group, and 14 days blood glucose values of administration obviously reduce, and handle difference by statistics significance (P<0.05-P<0.01), and the blood sugar lowering rate is respectively 12.13% and 22.49%.
Embodiment 10: the eluate of Folium Querci Mongolicae macroporous adsorbent resin causes the influence of mice hyperglycemia to alloxan
Get 87 of healthy ICR mices, wherein the normal control group is 10, tail vein injection saline 0.1ml/10g, all the other mouse tail vein injection alloxan normal saline solutions (45mg/kg) (modeling dosage is fixed according to the trial test result), survey fasting glucose behind the modeling 72h, blood glucose value is a diabetes animal model greater than the mice of 11.1mmol/L, is divided at random by blood glucose value: model control group, positive controls (insoral 150mg/kg), Folium Querci Mongolicae (embodiment 3 gained samples) water elution thing group (200mg/kg), 20% ethanol elution thing group (200mg/kg), 50% ethanol elution thing group (200mg/kg), 80% ethanol elution thing group (200mg/kg), totally 7 groups of 95% ethanol elution thing groups (200mg/kg).Each administration group is all by 0.2ml/10g volume gastric infusion, and every day 1 time, continuous 14 days, normal control group and model control group gave the equal-volume normal saline.Administration was got blood on the 7th day and is surveyed fasting glucose behind the socket of the eye, plucked eyeball and get blood, the survey fasting blood sugar in the 14th day.Experimental data is used
Expression is carried out statistical procedures with the t check between group.
7 days and the influence to model induced by alloxan hyperglycemia mouse blood sugar in 14 days behind the table 2 Folium Querci Mongolicae macroporous adsorbent resin eluate medicine
Annotate: compare with model control group,
* *P<0.001,
*P<0.01,
*P<0.05; Compare with the blank group,
△ △ △P<0.001. by table 2 blood glucose value result as can be known, blood glucose value before the medicine: each modeling group and the comparison of blank group, the mouse blood sugar value obviously raises, difference has significance (P<0.001), meets the random packet requirement.7 days blood glucose values of administration: model control group and blank group compare, and the blood glucose value of mice obviously raises, and difference has significance (P<0.001); Insoral group and model control group compare, and the blood glucose value of mice obviously reduces, and difference has significance (P<0.001), and the blood sugar lowering rate is 56.2%; Folium Querci Mongolicae 50% ethanol elution thing group, 95% ethanol elution thing group and model control group compare, and the blood glucose value of mice decreases, and significant difference (P<0.05) occurs, and the blood sugar lowering rate is respectively 21.6%, 23.6%; Folium Querci Mongolicae water elution thing group, Folium Querci Mongolicae 20% ethanol elution thing group, Folium Querci Mongolicae 80% ethanol elution thing group and model control group are relatively, the blood glucose value of mice decreases, but significant difference (P>0.05) all do not occur, the blood sugar lowering rate is respectively 9.0%, 3.4%, 9.9%.14 days blood glucose values of administration: model control group and blank group compare, and the blood glucose value of mice obviously raises, and difference has significance (P<0.001); Insoral group and model control group compare, and the blood glucose value of mice obviously reduces, and difference has significance (P<0.001), and the blood sugar lowering rate is 50.6%; Folium Querci Mongolicae 50% ethanol elution thing group, 95% ethanol elution thing group and model control group compare, and the blood glucose value of mice decreases, and significant difference (P<0.05) occurs, and the blood sugar lowering rate is respectively 25.3%, 24.9%; Folium Querci Mongolicae water elution thing group, Folium Querci Mongolicae 20% ethanol elution thing group, Folium Querci Mongolicae 80% ethanol elution thing group and model control group are relatively, the blood glucose value of mice decreases, but significant difference (P>0.05) all do not occur, the blood sugar lowering rate is respectively 5.4%, 11.4%, 11.7%.
Embodiment 11: the eluate of Folium Querci Mongolicae polyamide column causes the influence of mice hyperglycemia to alloxan
Get 54 of healthy ICR mices, wherein the normal control group is 10, tail vein injection saline 0.1ml/10g, all the other mouse tail vein injection alloxan normal saline solutions (45mg/kg) (modeling dosage is fixed according to the trial test result), survey fasting glucose behind the modeling 72h, blood glucose value is a diabetes animal model greater than the mice of 11.1mmol/L, is divided at random by blood glucose value: model control group, positive controls (insoral 150mg/kg), Folium Querci Mongolicae (embodiment 5 and 6 gained samples) 30% ethanol elution thing group (200mg/kg) and 50% ethanol alcohol eluate group (200mg/kg) totally 4 groups.Each administration group is all by 0.2ml/10g volume gastric infusion, and every day 1 time, continuous 14 days, normal control group and model control group gave the equal-volume normal saline.Administration was got blood on the 7th day and is surveyed fasting glucose behind the socket of the eye, plucked eyeball and get blood, the survey fasting blood sugar in the 14th day.Experimental data is used
Expression is carried out statistical procedures with the t check between group.
7 days and the influence to model induced by alloxan hyperglycemia mouse blood sugar in 14 days behind the table 3 Folium Querci Mongolicae polyamide column eluate medicine
Annotate: compare with model control group,
* *P<0.001,
*P<0.01,
*P<0.05; Compare with the blank group,
△ △ △P<0.001. by table 2 blood glucose value result as can be known, blood glucose value before the medicine: model control group and blank group are relatively, the mouse blood sugar value obviously raises, difference has significance (P<0.001), each administration group and model control group are relatively, the mouse blood sugar value does not have significant change, significant difference (P>0.05) do not occur, meets the random packet requirement.7 days blood glucose values of administration: model control group and blank group compare, and the blood glucose value of mice obviously raises, and difference has significance (P<0.001); Insoral group and model control group compare, and the blood glucose value of mice obviously reduces, and difference has significance (P<0.001), and the blood sugar lowering rate is 54.8%; Folium Querci Mongolicae 30% ethanol elution thing group, 50% ethanol elution thing group and model control group compare, and the blood glucose value of mice obviously reduces, and significant difference (P<0.01) occurs, and the blood sugar lowering rate is respectively 23.1%, 25.8%.14 days blood glucose values of administration: model control group and blank group compare, and the blood glucose value of mice obviously raises, and difference has significance (P<0.001); Insoral group and model control group compare, and the blood glucose value of mice obviously reduces, and difference has significance (P<0.001), and the blood sugar lowering rate is 56.5%; Folium Querci Mongolicae 30% ethanol elution thing group, 50% ethanol elution thing group and model control group compare, and the blood glucose value of mice obviously reduces, and significant difference (P<0.01-P<0.001) occurs, and the blood sugar lowering rate is respectively 25.2%, 27.1%.
Embodiment 12: the hypoglycemic compound that contains Folium Querci Mongolicae
Concrete prescription is composed as follows:
Folium Querci Mongolicae 20g|, Radix Ginseng 15g, Rhizoma Coptidis 5g
After the medicine of below respectively distinguishing the flavor of is mixed in proportion, add 500-600ml water, slow fire boiling 30min filters medicinal residues, decocts twice.Sooner or later respectively once, oral.
Embodiment 13: the hypoglycemic compound that contains Folium Querci Mongolicae
Concrete prescription is composed as follows:
Folium Querci Mongolicae 30g|, Cortex Cinnamomi 5g, Radix Rehmanniae 10g, Rhizoma Anemarrhenae 10g, Flos Carthami 5g
After the medicine of below respectively distinguishing the flavor of is mixed in proportion, add 800-1000ml water, slow fire boiling 30min filters medicinal residues, decocts twice.Sooner or later respectively once, oral.
Embodiment 14: the hypoglycemic compound that contains Folium Querci Mongolicae
Concrete prescription is composed as follows:
Folium Querci Mongolicae 20g|, Radix Ginseng 15g, Rhizoma Coptidis 5g, Fructus Corni 10g
After the medicine of below respectively distinguishing the flavor of is mixed in proportion, add 500-600ml water, slow fire boiling 30min filters medicinal residues, decocts twice.Sooner or later respectively once, oral.
Embodiment 15: the hypoglycemic compound that contains Folium Querci Mongolicae
Concrete prescription is composed as follows:
Folium Querci Mongolicae 30g|, Radix Astragali 20g, Radix Puerariae 10, Fructus Corni 10, Rhizoma Coptidis 5g
After the medicine of below respectively distinguishing the flavor of is mixed in proportion, add 600-800ml water, slow fire boiling 30min filters medicinal residues, decocts twice.Sooner or later respectively once, oral.
Embodiment 16: the hypoglycemic compound that contains Folium Querci Mongolicae
Concrete prescription is composed as follows:
Folium Querci Mongolicae 30g|, Radix Astragali 20g, Herba Epimedii 10g, Radix Angelicae Sinensis 10g, Rhizoma Coptidis 5g
After the medicine of below respectively distinguishing the flavor of is mixed in proportion, add 800-1000ml water, slow fire boiling 30min filters medicinal residues, decocts twice.Sooner or later respectively once, oral.
Claims (11)
1. a hypoglycemic pharmaceutical composition is characterized in that comprising the active component for the treatment of effective dose, and described active component is selected from following extract: the water of Folium Querci Mongolicae and/or lower alcohol extraction thing.
2. the pharmaceutical composition of claim 1 is characterized in that it is the straight or branched lower alcohol that C foretells C5 that lower alcohol is selected from carbon number; Wherein water and lower alcohol are that V/V mixes.
3. the pharmaceutical composition of claim 2, wherein lower alcohol is selected from the mixture of any one or they in methanol, ethanol, propanol or the n-butyl alcohol.
4. a hypoglycemic preparation of drug combination method is characterized in that the active component and the pharmaceutically acceptable carrier of treatment effective dose are mixed, and described active component makes with the following method:
1) get the Folium Querci Mongolicae medical material, water and/or lower alcohol extraction obtain extracting solution, and the gained extracting solution is concentrated, and drying is active component; Perhaps,
2) the step 1) extracting solution is directly gone up macroporous adsorptive resins, perhaps with behind the earlier concentrated redispersion of step 1) extracting solution, last macroporous adsorptive resins; With the 0-95% lower alcohol macroporous adsorptive resins is carried out gradient elution successively, collect each eluate respectively; With wherein eluate of 45-55% lower alcohol and/or the eluate of 85-99% lower alcohol, be active component behind the concentrate drying; Perhaps,
3) get step 2) in after the eluate of 45-55% lower alcohol and/or the eluate of 85-99% lower alcohol concentrate, carry out chromatography with 15-60 order polyamide, carry out gradient elution with the 0-95% lower alcohol, collect the eluate of its 30% and/or 50% concentration of lower alcohols, concentrate drying obtains active component.
5. the preparation method of claim 4, wherein,
Extract or when macroporous adsorptive resins or polyamide chromatography carried out gradient elution, described lower alcohol was that carbon number is C
1-C
5The straight or branched lower alcohol; Wherein water and lower alcohol are that V/V mixes;
Concentration of lower alcohols was 0-95% during step 1) was extracted; Extract with backflow, dipping, percolation or decocting method;
Step 2) macroporous resin described in is that in polystyrene type, polyacrylate or the polymethacrylates type any one or a few is the resin of framework material; Step 2) the macroporous adsorptive resins gradient elution is to be to be lower than 5% lower alcohol eluting to remove impurity with concentration earlier in, and reuse concentration is the lower alcohol eluting of X, wherein 5%≤X≤95%; Collect 50% lower alcohol eluate and/or 95% lower alcohol eluate, concentrate;
Polyamide chromatography gradient elution is to be to be lower than 5% lower alcohol eluting to remove impurity with concentration earlier in the step 3), and reuse concentration is the lower alcohol eluting of X, wherein 5%≤X≤95%; Collect the eluate of its 30% and/or 50% concentration of lower alcohols, concentrate.
6. the preparation method of claim 4 wherein, is extracted or when macroporous adsorptive resins or polyamide chromatography carried out gradient elution, and used lower alcohol is selected from the mixture of any one or they in methanol, ethanol, propanol or the n-butyl alcohol; Described macroporous resin is selected from AB-8, D101 type resin; Concentrate drying selects for use any one method in decompression, vacuum, the freezing or spray method to carry out.
7. the preparation method of claim 4, wherein, extracting solvent for use is 0-95% ethanol; The gradient elution of macroporous adsorptive resins is earlier to remove impurity with 0-40% ethanol, and reuse 50-95% ethanol elution is collected 50% lower alcohol eluate and/or 95% lower alcohol eluate, concentrated active component.
8. claim 7 preparation method, the gradient elution of macroporous adsorptive resins are to remove impurity with 0-5% ethanol earlier, then remove impurity with the 10%-20% ethanol elution; Reuse 50%-95% ethanol elution is collected 50% lower alcohol eluate and/or 95% lower alcohol eluate, concentrate active component.
9. the preparation method of claim 4, described pharmaceutically acceptable carrier comprises conventional oral formulations adjuvant, perhaps comprises conventional oral formulations adjuvant and drug effect of the present invention is not had obvious antioxidant, aminoacid, vitamin, carbohydrate or the plant extract that influences.
10. the Folium Querci Mongolicae active component of claim 1 to 9 in each is in preparation prevention or the medicine of treatment hyperglycemia disease or the application in the health product.
11. the application of claim 10, described hyperglycemia disease comprises diabetes.
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
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CN104606265A (en) * | 2014-12-30 | 2015-05-13 | 辽宁省农业科学院大连生物技术研究所 | Oak leaf extract, as well as preparation method and application thereof |
CN105434518A (en) * | 2015-12-28 | 2016-03-30 | 常熟雷允上制药有限公司 | Traditional Chinese medicine preparation for treating hepatitis |
CN108159112A (en) * | 2018-03-13 | 2018-06-15 | 辽宁省农业科学院大连生物技术研究所 | A kind of preparation method of mongolian oak leaf extractive of general flavone |
CN109793073A (en) * | 2019-03-21 | 2019-05-24 | 苏州美稀生物科技有限公司 | The extracting method at Ilex paraguarensis drink Lipid-lowering activities position and hypoglycemic activity position |
-
2009
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Title |
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刘长珍: "<柞树叶药水洗穴位治疗嬰儿腹泻100例疗效观察>", <中国医师进修杂志> * |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104606265A (en) * | 2014-12-30 | 2015-05-13 | 辽宁省农业科学院大连生物技术研究所 | Oak leaf extract, as well as preparation method and application thereof |
CN104606265B (en) * | 2014-12-30 | 2017-12-08 | 辽宁省农业科学院大连生物技术研究所 | A kind of mongolian oak leaf extract and preparation method and application |
CN105434518A (en) * | 2015-12-28 | 2016-03-30 | 常熟雷允上制药有限公司 | Traditional Chinese medicine preparation for treating hepatitis |
CN108159112A (en) * | 2018-03-13 | 2018-06-15 | 辽宁省农业科学院大连生物技术研究所 | A kind of preparation method of mongolian oak leaf extractive of general flavone |
CN109793073A (en) * | 2019-03-21 | 2019-05-24 | 苏州美稀生物科技有限公司 | The extracting method at Ilex paraguarensis drink Lipid-lowering activities position and hypoglycemic activity position |
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