CN100371001C - Usage of rhubarb root and its extractions in the process for preparing postprandial blood sugar decreasing medicine - Google Patents
Usage of rhubarb root and its extractions in the process for preparing postprandial blood sugar decreasing medicine Download PDFInfo
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- CN100371001C CN100371001C CNB031354521A CN03135452A CN100371001C CN 100371001 C CN100371001 C CN 100371001C CN B031354521 A CNB031354521 A CN B031354521A CN 03135452 A CN03135452 A CN 03135452A CN 100371001 C CN100371001 C CN 100371001C
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Abstract
The present invention provides usage of rhubarb and extract thereof in the process of preparing medicines for lowering postprandial blood sugar. Rhubarb crude drugs and rhubarb water or organic solvent extract can reduce postprandial blood sugar, inhibit the activity of alpha-glucosidase and show a favorable inhibitory action on the alpha-glucosidase in external experiments taking starch, maltose and sucrose as substrates. Starch load carbohydrate tolerance experiments on show that after the rhubarb extract is given, the blood sugar raising range of diabetes mice after starch load is obvious reduced, so the rhubarb extract is effective for controlling the raising of postprandial blood sugar. Therefore, the present invention provides a new medication selection for clinic and has the characteristics of obvious curative effect, low cost, safe and convenient usage, etc.
Description
Technical field
The present invention relates to the new purposes of Chinese medicine and extract thereof, specifically, the present invention relates to Chinese herb rhubarb and extract thereof the purposes in the medicine of preparation reduction post-prandial glycemia, can be used for preparing alpha-glucosidase inhibitor class medicine.
Background technology
Treatment of diabetes is a target with the control fasting glucose mainly for many years, and medicine mainly concentrates on sulphanylureas and biguanides for a long time.Recent study is found, post-prandial glycemia also is the main hazard factor that diabetic complication takes place, post-prandial glycemia is the highest stage of blood sugar level in one day during diabetes, its persistent period can be for 8 hour or is longer, long-time high-caliber post-prandial glycemia can increase the weight of diabetes itself, blood glucose is further raise, if at table with regard to energy better controlled hyperglycemia, then can avoid its after the meal the sugar in the blood circulation pile up, therefore, the control post-prandial glycemia can be described as the control hyperglycemia, prevents and treats the important behave of diabetes.In the existing Remedies for diabetes, sulfonylurea drugs is blood sugar lowering by stimulating secretion of insulin; Then by increasing peripheral tissues to the utilization of glucose and blood sugar lowering, both all have better curative effect to reducing type ii diabetes patient fasting glucose to biguanides, but very limited to the effect that reduces post-prandial glycemia.
Most carbohydrates in the food are starch and sucrose etc., starch earlier after in saliva and the pancreatic juice α-Dian Fenmei be decomposed into oligosaccharide, oligosaccharide is decomposed into glucose at intestinal epithelial cell brush border place by alpha-glucosidase and after being absorbed, cause the post-prandial glycemia peak, therefore, the activity of inhibition alpha-glucosidase becomes an effective way that reduces post-prandial glycemia.
Alpha-glucosidase inhibitor is a class new oral hypoglycemic drug of researching and developing out in the seventies later stage, its mechanism of action is: emulative inhibition alpha-glucosidase, delay and hinder the digestion of carbohydrate, delay is from disaccharidase, the absorption of the glucose of oligosaccharide and polysaccharide, effectively postpone and alleviate the time and the degree of post-prandial glycemia rising, take for a long time and can also reduce fasting blood glucose level, this type of medicine all is suitable for I, type ii diabetes.Alpha-glucosidase inhibitor not only has definite curative effect to diabetes, and for obesity, chronic viral hepatitis B, acquired immune deficiency syndrome (AIDS) and tumor certain therapeutical effect is arranged all.Be used for this type of clinical medicine at present acarbose, voglibose and miglitol are arranged.Chinese medicine and natural plant have comparatively safe and cheap characteristics, and exploitation Chinese medicine and natural plant can provide Remedies for diabetes source widely as alpha-glucosidase inhibitor.
Radix Et Rhizoma Rhei is the dry root and rhizome of polygonum rheum palmatum Rheum palmatum L. Rheum tanguticum Rheumtanguticum Maxim ex Balf. or Rheum officinale Rheum officinale Baill., bitter in the mouth cold in nature, has heat and toxic materials clearing away, clearing away heat-fire, the hemostasis detoxifcation, the effect of blood circulation promoting and blood stasis dispelling.Be usually used in treating constipation with heat retention, gastrointestinal retention; Bleeding due to blood-heat hemorrhage; Pathopyretic ulcer, burn and scald and blood stasis symptom.Modern study shows: Radix Et Rhizoma Rhei mainly contains anthraquinone derivative, also contains rhatannin, fatty acid, calcium oxalate, glucose, fructose and a large amount of starch.Modern pharmacological research shows that Radix Et Rhizoma Rhei decoct and extract thereof have pharmacological action widely." Chinese medicine modern study and application " (first volume) (Zheng Huzhan chief editor, the Xueyuan Press publishes 425-426) report: the Radix Et Rhizoma Rhei water decoction has the type ii diabetes of elimination insulin resistance, improves the effect of glycolipid metabolism; The Radix Et Rhizoma Rhei ethanol extract can obviously improve the renal function of experimental rat, suppresses the kidney hypertrophy, reduces albuminuria, improves the disorders of lipid metabolism of diabetic nephropathy, and blood sugar lowering and sugar are for hemoglobin level; Radix Et Rhizoma Rhei and other medicines (glycosuria is peaceful) share, and can obviously reduce hyperinsulinemia, improve impaired glucose tolerance and the multiple lipoidosis index of disease Mus.Effective ingredient in the Radix Et Rhizoma Rhei can increase enterokinesia inhibition enteral moisture absorption in addition, promotes defecation; Also have anti-infectious function, multiple Gram-positive and negative bacteria are all had inhibitory action; Have be good for the stomach, function of gallbladder promoting, protect the liver, effect such as blood pressure lowering (Shanghai science tech publishing house publishes 98-99 for Chinese materia medica, Lei Zaiquan chief editor).The progress of Radix Et Rhizoma Rhei has reported that Radix Et Rhizoma Rhei has the effect of removing oxygen-derived free radicals, suppressing vascular smooth muscle cell proliferation, has effects such as two-ways regulation to immune system in [Chinese pharmacy progress, 1998,10 (33)].But having not yet to see Radix Et Rhizoma Rhei has alpha-glucosidase in preparation and suppresses active medicine and reduce application report in the medicine of post-prandial glycemia.
Summary of the invention
The inventor finds that through a large amount of screening experiment Chinese herb rhubarb has the effect of good reduction post-prandial glycemia, can suppress the activity of alpha-glucosidase.The purpose of this invention is to provide Chinese herb rhubarb and extract thereof the purposes in the medicine of preparation reduction post-prandial glycemia.
Technical scheme: the invention provides Radix Et Rhizoma Rhei and extract thereof the purposes in the medicine of preparation reduction post-prandial glycemia.Further, provide Radix Et Rhizoma Rhei and extract thereof the purposes in preparation alpha-glucosidase inhibitor class medicine.Described Radix Et Rhizoma Rhei comes from the dry root and rhizome of polygonum rheum palmatum Rheum palmatum L. Rheum tanguticum Rheum tanguticum Maxim ex Balf. or Rheum officinale Rheumofficinale Baill..
Chinese herb rhubarb is when being used to prepare the medicine that reduces post-prandial glycemia, can be that the Radix Et Rhizoma Rhei crude drug in whole directly is processed into medicine, also can be that the Radix Et Rhizoma Rhei crude drug in whole is carried out separation and Extraction, its extract (water or extractive with organic solvent) is prepared into medicine, also can be that Chinese herb rhubarb and other medicines are formed compound preparation.
Described Radix Et Rhizoma Rhei extractive with organic solvent is methanol, ethanol, aquiferous ethanol extract.
The preparation method of described Radix Et Rhizoma Rhei extract may further comprise the steps:
A, Chinese herb rhubarb is pulverized, water, methanol or ethanol, or concentration is that 20～95% aquiferous ethanol extracts, is condensed into extractum, and extractum is dissolved in distilled water, and is centrifugal, and it is standby to get supernatant;
B, with the supernatant that obtains after a step process, after macroporous adsorptive resins, to wash clean non-adsorbable impurity, reuse alcohol, ketone or concentration are 25～95% aqueous alcohol eluting, collect eluent, concentrate drying obtains finished product.
Chinese herb rhubarb, the dry root and rhizome that is sorrel (Rheum palmatum L.) Rheum tanguticum (Rheumtanguticum Maxim ex Balf.) or Rheum officinale (Rheum officinale Baill.) is a raw material, directly processing and preparing becomes medicine, can be that the directly clean system of above-mentioned crude drug in whole back is pulverized, cross the 80-120 mesh sieve, make fine powder, again that fine powder is encapsulated, or be prepared into tablet, pill, granule, powder.
With the Chinese herb rhubarb crude drug in whole is raw material, is prepared into medicine after tentatively extracting.Can adopt the various conventional extracting method in the modern technologies to extract, for example, be solvent extraction with water, and perhaps with organic solvent extraction such as ethanol, methanol, preferred alcohol extracts.Also can adopt following method to prepare Radix Et Rhizoma Rhei extract: a, Chinese herb rhubarb is pulverized, water, methanol or ethanol, or the aquiferous ethanol class is extracted, concentrated, precipitation is centrifugal, supernatant is standby; Particularly, with the suitable pulverizing of raw material process, water, methanol or ethanol, or aquiferous ethanol is under quiet or dynamic environment, room temperature or heating and refluxing extraction, 5～12 times of extracting solvent and be crude drug in whole weight, can repeat to extract 1～3 time, merge extractive liquid,, elimination medicinal residues concentrate under normal pressure or decompression state and cause finite concentration, by methods such as precipitate with ethanol, flocculations, make contamination precipitation, through centrifugal or filtration (comprising normal pressure, decompression, microfiltration, ultrafiltration), remove insoluble matter again, it is standby to get supernatant; B, with the supernatant that a step process obtains, go up macroporous resin column again, washing clean non-adsorbable impurity, reuse alcohol, ketone or aqueous alcohol eluting are collected eluent, concentrate, and vacuum drying, freezingly, dry collect the direct spray drying of liquid and get dry powder.
It is a kind of as the pharmaceutical composition that reduces post-prandial glycemia that the present invention also provides, and it contains described Radix Et Rhizoma Rhei protogenic medicinal powder or its water or extractive with organic solvent.
Further, it is to be active component with described Radix Et Rhizoma Rhei protogenic medicinal powder or its water or extractive with organic solvent, adds the pharmaceutical preparation that pharmaceutically acceptable carrier or complementary composition are prepared from.
Described pharmaceutical preparation is capsule, granule, tablet, powder, oral liquid, syrup.
Beneficial effect: Chinese herb rhubarb, or its water extract, or its extractive with organic solvent, or the medicine and the preparation thereof of the preparation of extract or its medicaments compound have good reduction post-prandial glycemia, suppress the effect of alpha-glucosidase.Chinese herb rhubarb derives from natural plants, medicine source abundance, the extraction preparation method is simple and easy to do, can be made into capsule, tablet, granule, the multiple dosage form of oral liquid, can suppress alpha-glucosidase activity effectively, reduce post-prandial glycemia, have advantageous feature such as evident in efficacy, cheap, safe and convenient to use.
Obviously, according to foregoing of the present invention,, under the prerequisite that does not break away from the above-mentioned basic thought of the present invention, can also make modification, replacement and the change of other various ways according to the ordinary skill and the customary means of this area.
The specific embodiment of form is described in further detail foregoing of the present invention again by the following examples.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following example.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.
Description of drawings
Fig. 1 is the measurement result of Radix Et Rhizoma Rhei extract to the depression effect of alpha-glucosidase activity.Vertical coordinate is represented the enzymatic activity suppression ratio, and abscissa is represented DH-01, DH-02, DH-03, acarbose.Compared among the figure with maltose, sucrose, when starch is substrate, Radix Et Rhizoma Rhei extract DH-01, DH-02, DH-03, acarbose are to the inhibition activity of alpha-glucosidase.
The specific embodiment
The preparation of embodiment 1 Radix Et Rhizoma Rhei crude drug in whole medicine
Get the Chinese herb rhubarb crude drug in whole, be after the clean system of dry root and rhizome of sorrel (Rheum palmatum L.) Rheum tanguticum (Rheum tanguticum Maxim ex Balf.) or Rheum officinale (Rheum officinaleBaill.), pulverize according to a conventional method, sieve, making granularity is 60-80 purpose Radix Et Rhizoma Rhei fine powder, fine powder incapsulates, sterilization, packing.
The preparation of embodiment 2 Radix Et Rhizoma Rhei water extract, Radix Et Rhizoma Rhei ethanol extraction
Chinese herb rhubarb, promptly the dry root and rhizome of sorrel (Rheum palmatum L.) Rheum tanguticum (Rheumtanguticum Maxim ex Balf.) or Rheum officinale (Rheum officinale Baill.) is a raw material, removes impurity.Get Radix Et Rhizoma Rhei crude drug in whole 500g, pulverize the back and add 10 times of water gagings, heating and refluxing extraction 2 hours, filtering residue adds ten times of water gagings again, heating and refluxing extraction 2 hours is filtered, and merges filtrate twice, concentrate Radix Et Rhizoma Rhei water extract (to call DH-1 in the following text).Other gets Radix Et Rhizoma Rhei crude drug in whole 1000g, pulverize the back and add 70% alcoholic solution 10L, heating and refluxing extraction 2 hours, filtering residue adds 70% alcoholic solution 6L again, heating and refluxing extraction 2 hours is filtered, and merges filtrate twice, concentrate Radix Et Rhizoma Rhei ethanol extraction (to call DH-2 in the following text).
The preparation of embodiment 3 Radix Et Rhizoma Rhei extracts
Get 200g Radix Et Rhizoma Rhei crude drug in whole, after the pulverizing, use twice of 1600ml95% and 30% alcohol dipping respectively, each 12 hours, merge impregnation liquid, concentrating under reduced pressure is made extractum, extractum is dissolved in the 2L distilled water, gets supernatant, supernatant is flowed through nonpolar (D-140) and polarity (D-160) macroporous adsorptive resins successively, with 3 times of column volume distilled water, it is colourless that the polar resin post is eluted to effluent, uses 75% and 25% ethanol elution more respectively, collects eluent, the concentrating under reduced pressure drying obtains pressed powder 630mg (to call DH-3 in the following text).
Embodiment 4 Radix Et Rhizoma Rhei extract DH-1, DH-2, DH-3 are to the vitro inhibition effect of alpha-glucosidase
When 1) being substrate with starch, Radix Et Rhizoma Rhei extract suppresses determination of activity to alpha-glucosidase:
Take by weighing a certain amount of Radix Et Rhizoma Rhei extract DH-1, DH-2, DH-3 respectively, all be configured to the drug solution that concentration is 0.1mg/ml with normal saline, get again each 20 μ l of three kinds of solution respectively with 2 μ l α-Dian Fenmei (0.4U/ μ l, available from SIGMA company) mix, hatched 10 minutes at 37 ℃, the starch solution room temperature of adding 1% was placed 3-5 minute, used the iodometric titration development process, under the 630nm wavelength, measure the 0D value, calculate the alpha-glucosidase activity suppression ratio by the consumption of starch amount; Set blank, negative control, positive control (acarbose, Beijing Bayer HealthCare Co produces), suppression ratio=((sample-feminine gender)/(blank-feminine gender)) * 100% the results are shown in Figure 1.
When 2) being substrate with maltose, Radix Et Rhizoma Rhei extract suppresses determination of activity to alpha-glucosidase:
Take by weighing a certain amount of Radix Et Rhizoma Rhei extract DH-1, DH-2, DH-3 respectively, all be configured to the drug solution that concentration is 0.28mg/ml with normal saline, get again each 20 μ l of three kinds of solution respectively with 2 μ l alpha-glucosidase (0.02U/ μ l, available from SIGMA company) mix, hatched 10 minutes at 37 ℃, add maltose, 37 ℃ were continued to hatch 10 minutes; Adopt glucose oxidase method, under 490nm wavelength condition, measure the 0D value, with the growing amount calculating alpha-glucosidase activity suppression ratio of glucose; Set blank, negative control, positive control (acarbose, Beijing Bayer HealthCare Co produces), suppression ratio=((feminine gender-sample)/(feminine gender-blank)) * 100% the results are shown in Figure 1.
When 3) sucrose was substrate, Radix Et Rhizoma Rhei extract suppressed determination of activity to alpha-glucosidase:
Take by weighing a certain amount of Radix Et Rhizoma Rhei extract DH-1, DH-2, DH-3 respectively, all be configured to the drug solution that concentration is 0.28mg/ml with normal saline, get again each 20 μ l of three kinds of solution respectively with 2 μ l α-invertase (0.106U/ μ l, available from SIGMA company) mix, hatched 10 minutes at 37 ℃, add sucrose, 37 ℃ were continued to hatch 10 minutes; Adopt glucose oxidase method, under 490nm wavelength condition, measure the OD value, with the growing amount calculating alpha-glucosidase activity suppression ratio of glucose; Set blank, negative control, positive control (acarbose, Beijing Bayer HealthCare Co produces), suppression ratio=((feminine gender-sample)/(feminine gender-blank)) * 100% the results are shown in Figure 1.
By Fig. 1 result as can be seen, Radix Et Rhizoma Rhei extract DH-1, DH-2, DH-3 have remarkable inhibitory action external to alpha-glucosidase.
Embodiment 5 Radix Et Rhizoma Rhei extract DH-3 induce diabetic mice starch-bearing carbohydrate tolerance influence test to alloxan
Get body weight 22-26g Kunming mouse, lumbar injection 200mg/kg alloxan, measure blood glucose after 72 hours, choose the mice of blood glucose value more than 13mM, by 10 every group, male and female half and half are divided into 6 groups, i.e. diabetic model group, acarbose group, Radix Et Rhizoma Rhei extract DH-3 high dose group, middle dosage group, low dose group, acarbose dosage is 20mg/kg (body weight), and Radix Et Rhizoma Rhei extract DH-3 high dose group is that 400mg/kg, middle dosage group are that 200mg/kg, low dose group are 100mg/kg; Measure fasting glucose (0min), administration is (model group is irritated stomach with normal saline) after ten minutes, and each group is all irritated stomach with starch 5g/kg, gets vena orbitalis posterior clump blood respectively at 30min, 60min, 90min, 120min, in 96 orifice plates, measure blood sugar content with glucose oxidase method, the results are shown in Table 1.
Table 1 Radix Et Rhizoma Rhei extract DH-3 induces the influence of diabetic mice starch-bearing carbohydrate tolerance to alloxan
| Group | Example number (only) | Dosage (mg/kg) | Blood glucose value (mM) | ||||
| 0min | 30min | 60min | 90min | 120min | |||
| Model group acarbose DH-3 (height) DH-3 (in) DH-3 (low) | 10 10 10 10 10 | 20 400 200 100 | 25.42±8.30 26.57±4.76 26.16±4.12 27.32±4.58 25.98±8.34 | 42.43±7.10 28.57±3.53** 30.75±4.57** 32.95±5.83* 34.83±5.78* | 41.37±7.25 30.85±5.54** 31.98±5.19** 35.62±7.35* 37.32±6.44 | 37.83 ±8.25 30.64±4.51* 31.54±5.21* 35.62±5.33 36.79±5.98 | 36.14±8.73 31.32±5.31 32.05±4.56 33.41±4.68 36.10±5.46 |
Compare * P＜0.05, * * P＜0.01 with matched group
As can be seen from Table 1: diabetic mice is after giving starch, and blood glucose value (model group) obviously raises.Radix Et Rhizoma Rhei extract DH-3 high dose group all significantly suppresses the blood sugar increasing of diabetic mice at each time point, and except that the 30min effect was more weak, the effect and the acarbose of all the other time points were suitable; Compare with model group, among the DH-3, low dose group all has certain inhibitory action to the blood sugar increasing of each time point diabetic mice, but effect is not as good as the DH-3 high dose group.
By above-mentioned in vitro tests and pharmacodynamics test, proof Radix Et Rhizoma Rhei and extract thereof have the effect that reduces post-prandial glycemia, the activity that can suppress alpha-glucosidase provides a kind of new medication to select, and has characteristics such as evident in efficacy, cheap, safe and convenient to use.
Claims (9)
1. Radix Et Rhizoma Rhei and extract thereof the purposes in preparation alpha-glucosidase inhibitor class medicine.
2. purposes according to claim 1 is characterized in that: described medicine is the medicine that reduces post-prandial glycemia.
3. purposes according to claim 1 and 2 is characterized in that: described Radix Et Rhizoma Rhei comes from the dry root and rhizome of polygonum rheum palmatum Rheum palmatum L. Rheum tanguticum Rheum tanguticum Maxim exBalf. or Rheum officinale Rheum officinale Baill..
4. purposes according to claim 1 and 2 is characterized in that: described Radix Et Rhizoma Rhei is the protogenic medicinal powder of Radix Et Rhizoma Rhei.
5. purposes according to claim 1 and 2 is characterized in that: described Radix Et Rhizoma Rhei extract is water or extractive with organic solvent.
6. purposes according to claim 5 is characterized in that: described Radix Et Rhizoma Rhei extractive with organic solvent is methanol, ethanol, aquiferous ethanol extract.
7. purposes according to claim 5 is characterized in that: the preparation method of described Radix Et Rhizoma Rhei extract may further comprise the steps:
A, Chinese herb rhubarb is pulverized, water, methanol or ethanol, or concentration is that 20～95% aquiferous ethanol extracts, is condensed into extractum, and extractum is dissolved in distilled water, and is centrifugal, and it is standby to get supernatant;
B, with the supernatant that obtains after a step process, after macroporous adsorptive resins, to wash clean non-adsorbable impurity, reuse alcohol, ketone or concentration are the aqueous alcohol eluting of 25-95%, collect eluent, concentrate drying obtains finished product.
8. according to each described purposes of claim 4-6, it is characterized in that: it is to be active component with Radix Et Rhizoma Rhei protogenic medicinal powder or its water or extractive with organic solvent, adds the pharmaceutical preparation that pharmaceutically acceptable carrier or complementary composition are prepared from.
9. purposes according to claim 8 is characterized in that: described pharmaceutical preparation is capsule, granule, tablet, powder, oral liquid, syrup.
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| CN114601144A (en) * | 2022-03-15 | 2022-06-10 | 黄晓川 | Process for applying capsicum containing alpha-glucosidase inhibitor as raw material to food |
| CN114832035A (en) * | 2022-05-09 | 2022-08-02 | 中国科学院西北高原生物研究所 | Rheum officinale petiole procyanidine extract and preparation method and application thereof |
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| CN1457807A (en) * | 2002-05-13 | 2003-11-26 | 黄勤 | Medicine for curing diabetes |
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| CN1457807A (en) * | 2002-05-13 | 2003-11-26 | 黄勤 | Medicine for curing diabetes |
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| 大黄的药理研究概述. 周远鹏，江京莉.中药药理与临床，第7卷第4期. 1991 * |
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