CN100400081C - Medicine for treating diabetes and production method thereof - Google Patents
Medicine for treating diabetes and production method thereof Download PDFInfo
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- CN100400081C CN100400081C CNB2004100920876A CN200410092087A CN100400081C CN 100400081 C CN100400081 C CN 100400081C CN B2004100920876 A CNB2004100920876 A CN B2004100920876A CN 200410092087 A CN200410092087 A CN 200410092087A CN 100400081 C CN100400081 C CN 100400081C
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Abstract
The present invention provides a medicine for curing diabetes. The active substance of the medicine comprises corn stigma total saponin and simultaneously comprises corn stigma total flavonoid. The better range of the weight ratio of corn stigma total saponin to corn stigma total flavonoid is from 1:1.5 to 1:0.001, and the best range is preferably from 1:1 to 1:0.1. The active substance can simultaneously comprise corn stigma crude polysaccharide. The better range of the weight ratio of corn stigma total saponin to corn stigma crude polysaccharide is from 1:1.5 to 1:0.001, and the best range is preferably from 1:1 to 1:0.1. The active substance can be composed of corn stigma total saponin, corn stigma total flavonoid and corn stigma crude polysaccharide. The better range of the weight ratio of corn stigma total saponin to corn stigma total flavonoid and corn stigma crude polysaccharide is 1:1.5 to 1:0.001, and the best range is preferably 1:1 to 1:0.1.
Description
Technical field
The present invention relates to the medicine of treatment diabetes in the field of Chinese medicines.The invention still further relates to the preparation method of this medicine.
Background technology
Diabetes are endocrine metabolism diseases of one group of general, its pathophysiological change is that insulin secretion is relative or absolute not enough, cause vitamin, water, the metabolic disturbance of electrolyte of sugar, fat, protein and secondary, cause the rising of hyperglycemia, hyperlipidemia and blood viscosity, extensively microangiopathies of the whole body appears in middle and advanced stage, shows as blood glucose, glucose in urine rising, and patient shows as polydipsia, polyphagia, polyuria, symptom such as xerostomia and general weakness is that a class is difficult to the disease of curing at present.
Onset diabetes rate and case fatality rate are all very high.Crowd's sickness rate is 1%-5%, and the sickness rate of developed country is higher relatively, is 6%-7% as the U.S., at present, the whole world has diabetics 1.75 hundred million, from now by 2025, diabetes prevalence will raise 72% in the world wide, predict 2025 and will reach 300,000,000.The number of China's actual trouble diabetes has reached more than 4,000 ten thousand, and wherein 95% belongs to type 2 diabetes mellitus.3.2 hundred million more than impaired glucose tolerance crowd is arranged in the world wide, and China simple property impaired glucose tolerance patient accounts for about 75% of IGR total number of persons.The onset diabetes rate has the trend that day by day increases, and it and cancer, cardiovascular disease are referred to as worldwide three big diseases, and the case fatality rate of diabetes is only second to malignant tumor and cardiovascular disease, is human life's the third-largest cause of the death.
Doctor trained in Western medicine antidiabetic drug treatment diabetes curative effect is affirmed, but life-time service needs dosage gradually, and Western medicine has untoward reaction in various degree mostly, and can not control complication effectively.Conclude and get up to have following defective and toxic and side effects: (1) sulfonylurea drugs with easily damaging liver, kidney and hemocyte, brings out hypoglycemic reaction, and develops immunity to drugs for a long time; (2) the biguanides curative effect is low, and side effect is big, and is heavy dose of for a long time with producing high lactic acidosis, the infringement liver function; (3) insulin usefulness for a long time produces antibody, and biological activity reduces, if dosage increases, can produce hyperinsulinemia, impels microangiopathies to take place and development; (4) Thiazolidine, thiazolidone, toxic and side effects is big, and is particularly serious to the infringement of liver, even can cause hepatic necrosis, is not suitable for the patient who suffers from heart and hepatic disease; (5) glucosidase inhibitor disturbs digestion process, reduces the absorption of glucose, only in the reduction of level of postprandial blood sugar.
The Chinese medicine diabetes are drawn materials conveniently, stable curative effect, and untoward reaction is few, prevents and treats the generation of complication effectively, and the irreplaceable advantage of Western medicine is arranged.The prescription of Chinese medicine diabetes and the kind of Chinese patent medicine are quite various, but curative effect is not ideal enough, and subject matter is that Chinese medicine lacks modernization, and effective ingredient is difficult to determine in the compound recipe, and quality standard lacks scientific, the curative effect instability.
Summary of the invention
Technical problem to be solved by this invention provides a kind of medicine of new treatment diabetes.For this reason, the present invention by the following technical solutions: its active substance comprises Stigma Maydis total saponins.
Its active substance also can comprise Stigma Maydis total flavones simultaneously.The preferred range of the weight ratio of Stigma Maydis total saponins and Stigma Maydis total flavones is 1: 1.5～1: 0.001, and optimum range is preferably 1: 1～1: 0.1.
Its active substance also can comprise Stigma Maydis crude polysaccharides simultaneously.The preferred range of the weight ratio of Stigma Maydis total saponins and Stigma Maydis crude polysaccharides is 1: 1.5～1: 0.001, and optimum range is preferably 1: 1～1: 0.1.
Its active substance also can be made up of Stigma Maydis total saponins, Stigma Maydis total flavones, Stigma Maydis crude polysaccharides.Stigma Maydis total saponins weight: the preferred range of the gross weight of Stigma Maydis total flavones and Stigma Maydis crude polysaccharides is 1: 1.5～1: 0.001, and optimum range is preferably 1: 1～1: 0.1.
Thereby medicine provided by the present invention can add pharmaceutically acceptable adjuvant makes capsule, tablet, granule or other common formulations.
Another technical problem to be solved of the present invention provides the production method of above-mentioned treatment diabetes medicament.It may further comprise the steps:
1) preparation Stigma Maydis total saponins with ethanol reflux extraction or decocting extraction method, obtains extracting solution with Stigma Maydis, and the extraction of reuse water-saturated n-butanol obtains Stigma Maydis total saponins;
2) the preparation Stigma Maydis total flavones obtains extracting solution with Stigma Maydis with ethanol reflux extraction, water precipitating, and supernatant concentration obtains Stigma Maydis total flavones;
3) preparation Stigma Maydis crude polysaccharides, with the Stigma Maydis decoction alcohol precipitation method, precipitate washs 1～2 time with 40～65 ℃ warm water, and supernatant concentration obtains Stigma Maydis crude polysaccharides;
4) with the Stigma Maydis total saponins that makes, Stigma Maydis total flavones, Stigma Maydis crude polysaccharides by weight ratio and add after corresponding adjuvant mixes, promptly can be made into corresponding preparations.
Above-mentioned steps " 1) " can the branch following steps be carried out: is that 40～95% soak with ethanol are more than 2 hours with Stigma Maydis with the concentration of 8～25 times of weight, reflux, extract, 2～3 times, each 1～2.5 hour, merge extractive liquid,, relative density 1.05～1.3g/cm when decompression recycling ethanol, concentrated solution are concentrated into 50 ℃
3, use the water saturation n-butanol extraction then, extract 3～4 times, reclaim n-butyl alcohol, the aqueous solution oven dry promptly gets Stigma Maydis total saponins; Or, Stigma Maydis is extracted with decocting, precipitate with ethanol, supernatant is used the water saturation n-butanol extraction after reclaiming ethanol, reclaims n-butyl alcohol, and the aqueous solution oven dry promptly gets Stigma Maydis total saponins.
Above-mentioned steps " 2) " can the branch following steps be carried out: is that 40～95% soak with ethanol are more than 2 hours with Stigma Maydis with the concentration of 8～25 times of weight, 50 ℃～80 ℃ reflux, extract,, the extracting solution water precipitating, supernatant reclaims ethanol, and the concentrated solution oven dry promptly gets Stigma Maydis total flavones.
Above-mentioned steps " 3) " can the branch following steps carry out: with the water of Stigma Maydis with 8～25 times of weight, soaking corn must be more than 2 hours, and decocting boils 2～3 times, each 0.5～1.5 hour, merging filtrate with the decolouring of 2% medical active carbon, filters, filtrate is with 40～95% ethanol precipitations, taking precipitate reclaims ethanol, and the washing of reuse warm water for several times, remove insoluble impurities, concentrate drying promptly gets Stigma Maydis crude polysaccharides.
Stigma Maydis (Corn silk) is style and the stigma of grass corn (Zea mays L.).Gather during harvesting corn autumn, dries.Yellow green, light green are to yellowish-brown when bright, and dried back is brown.Its chemical constituent is: fatty oil 2.5%, and volatile oil 0.12%, gummy sample material 3.8%, resin 2.7%, bitterness glucoside 1.15%, Saponin 3.18%, flavone 0.48-0.77% has report 0.11-1.43%.Alkaloid 0.05%, allantoin, cryptoxanthine, ascorbic acid, pantothenic acid, inositol, V.K, sitosterol, malic acid, citric acid, tartaric acid, oxalic acid, caffeic acid, ferulic acid, linoleic acid, flavone pigment, tannic acid, aminoacid, poly pentose etc.
Stigma Maydis has recorded the Pharmacopoeia of the People's Republic of China (one one), feeble QI, and it is little sweet to distinguish the flavor of.
Stigma Maydis has diuresis.Such as, it is oral to make decoct with Stigma Maydis 8-10g, and the normal person is had slight diuresis.Zoopery: Stigma Maydis decocting liquid low dosage (crude drug 5g/kg body weight) is irritated stomach, compare with matched group, back first and second hour voided volume of taking medicine all obviously increases, high dose group (crude drug 10g/kg body weight) is compared with low dose group, first hour urine amount do not increase after the administration, and at second hour voided volume apparently higher than low dose group.Stigma Maydis is almost non-toxic, has no adverse effects to heart, breathing, peripheral vessel and myenteron are several, and Stigma Maydis can be used as a kind of lasting, mild, safe diuretic.
Stigma Maydis has hypotensive activity.The water-leach liquor of Stigma Maydis, alcohol-water leachate and alcohol leaching liquid all have the reduction effect to the blood pressure of anaesthetizing Canis familiaris L., cat, rabbit.
Stigma Maydis has choleretic effect.The contraction of gallbladder reflexive occurred in 15-30 minute behind the human oral Stigma Maydis preparation, bile is discharged to be increased.
The Stigma Maydis avirulence.The various preparation orals of Stigma Maydis, several avirulences.The lethal dose of the insoluble part of water extract methanol (main diuresis composition) the quiet notes of rabbit is 250mg/kg, and diuresis dosage, quiet notes are 1.5mg/kg, but 6mg/kg when oral.Above-mentioned diuresis dosage is to a few nothing influences of heart, breathing, peripheral vessel and myenteron.Stigma Maydis is confirmed as safe, nontoxic material by Food and Drug Administration.The chmice acute toxicity test is once irritated stomach Stigma Maydis water decoction 171g/kg (pressing the crude drug amount calculates), observes a week, and animal behavior is all normal as a result, and none is poisoned to death.
Stigma Maydis is used as medicine and starts from the end of the Ming Dynasty " the southern regions of the Yunnan Province book on Chinese herbal medicine ", and " sweet in the mouth, slightly warm in nature are gone into positive bright stomach warp." " the wide intestinal therapeutic method to keep the adverse QI flowing downwards.Control married woman's breast knot, galactostasis, congestion and swelling pain, the heating of being afraid of cold, the headache body is stranded.”
" modern practical Chinese medicine " points out that Stigma Maydis is a diuretic, and is effective to nephropathy, edema illness, diabetes etc.
Stigma Maydis is clinical to be usually used in diuresis, calculus, blood pressure lowering.
The present invention is on the basis of traditional Chinese medicine theory, the utilization modern medical theory, determined treatment diabetic activity material in the Stigma Maydis, and form medicine with this, the effect that not only has obvious treatment and prevent diabetes, and Western medicine preparation more in the past has no side effect, the medicine source is abundant, cheap, Chinese medicine preparation prescription is more in the past simplified, effective ingredient clear and definite, determined curative effect, quality controllable.And preparation method provided by the invention is easy to suitability for industrialized production.
The specific embodiment
The extraction of embodiment 1.1 Stigma Maydis total saponins:
Take by weighing Chinese medicine Stigma Maydis dry product and make conventional decoction pieces, the alcohol reflux of the 60-95% that doubly measures with 10-14 2-3 time; Or extract with decocting, the decocting of doubly measuring with 10-12 boils 3 times, each one hour, extracting solution 6095% ethanol precipitation, supernatant decolours with 2% medical active carbon, filter, reclaim ethanol, to not having the alcohol flavor, reuse water-saturated n-butanol extraction 2-3 time, the reclaim under reduced pressure n-butyl alcohol, the dry Stigma Maydis total saponins that gets of concentrated solution.The total saponins that takes a morsel adopts the Libermann-Burcherd chromogenic reaction to carry out discrimination test: the aubergine reaction to occur between chloroform and developer, show that this material is a triterpene saponin.Adopt as seen---ultraviolet spectrophotometer, with the ginsenoside Rg
1Be standard substance, measure trap at the 530nm place, its content is 0.08～0.13mg/ml.
The alcohol extracting method of embodiment 1.2 Stigma Maydis total saponins extracts:
Select the fresh corn silk dry product, processing is cut off, long 3～5cm, use 70% ethanol, the ratio of feed liquid is 1: 12, soaks 2 hours, put into the extraction tube of apparatus,Soxhlet's again, reflux, extract, 2 times, each 1.5 hours, merge alcohol extract twice, high speed centrifugation, 3000～3500r/min, 15 ', get supernatant, distilling under reduced pressure, reclaim ethanol, the proportion during 50 ℃ of concentrated solutions is 1.10～1.25g/cm
3, the extraction of reuse water-saturated n-butanol, n-butanol layer is collected in coextraction 3 times, n-butyl alcohol is reclaimed in distilling under reduced pressure, and its concentrated solution places in the vacuum drying oven, 60 ℃ of temperature, vacuum pressure is 0.08～0.1mpa, and vacuum drying obtains dried thick paste, is Stigma Maydis total saponins.
Selecting concentration of alcohol, return time, backflow number of times, four factors of feed liquid multiple as the investigation factor, serves as to investigate index with ginsenoside Rg1's content, selects orthogonal table Lg (3 for use
4) investigate the optimum process condition of alcohol extraction total saponins.Experimental result shows, determining alcohol 70% refluxes 3 times, and each 2 hours, the feed liquid multiple was 1: 10-20.Ginsenoside Rg1's standard substance can be used as the standard substance of measuring the Stigma Maydis saponin content and carry out Quality Control.
The alcohol extracting method of embodiment 1.3 Stigma Maydis total saponins extracts:
Select the fresh corn silk dry product,, take by weighing 250kg, put into the multipotency extraction pot, use 70% ethanol through after cutting off, for the 11-12 of medical material weight doubly, soaked 2 hours, 50 ℃ of jar interior temperature are carried out reflux, extract,, extract altogether 2 times, at every turn 2h.Ethanol extract concentrates through adding the heat-circulation type concentrator, reclaims ethanol, is concentrated into the proportion 1.08～1.15g/cm under 50 ℃
3, use the water saturation n-butanol extraction, extract 2 times, n-butyl alcohol is reclaimed in the n-butanol extracting liquid distilling under reduced pressure, and concentrated solution is put into vacuum desiccator, and vacuum pressure is 0.08-0.09mpa, and temperature is 60 ℃, oven dry gets the Powdered dry product of yellowish-brown, is Stigma Maydis total saponins.This method particularly is suitable for suitability for industrialized production.
The decoction and alcohol sedimentation technique of embodiment 1.4 Stigma Maydis total saponins extracts:
Stigma Maydis is through after cutting off, and the ratio of medical material and water is 1: 10-12, soaked 2 hours, medical material is put into the extraction pot, and after being fried boiling, little boiling kept 1.5 hours, pour out extracting solution, same method decocts 2 times again, each 1 hour, with eight layers of filtered through gauze, filtrate concentrated, be concentrated to 1/10 of original volume, add 75% ethanol and carry out precipitate with ethanol, place in 4 ℃ of refrigerators, spend the night, use high speed centrifugation, 3000～3500r/min, 15 ', get supernatant, decompression recycling ethanol, till nothing alcohol flavor, use the water saturation n-butanol extraction, coextraction 3 times, combining extraction liquid, the reclaim under reduced pressure n-butyl alcohol, its aqueous solution is put into vacuum drying oven, and pressure is 0.08-0.09mpa, temperature is 60 ℃, oven dry, it is Powdered to be yellowish-brown, is Stigma Maydis total saponins.
Orthogonal test: the factor of selecting to influence the total saponins extraction serves as to investigate index for decocting number of times, decocting time, concentration of alcohol and n-butanol extraction number of times with ginsenoside Rg1's content in the extracting solution, and selecting orthogonal table for use is Lg (3
4) the screening optimum extraction condition.Experimental result shows: concentration of alcohol is 65%, and n-butanol extraction 2 times decocts 3 times, decocts each 2 hours, owing to decoct number of times and the non-principal element of decocting time, adopts to decoct each 1 hour 2 times.
The decoction and alcohol sedimentation technique of embodiment 1.5 Stigma Maydis total saponins extracts:
Stigma Maydis 250kg is through after cutting off, pour 3 tons of multipotency extraction pot into, in medical material and water ratio is 1: 12-14 doubly puts into water, and the water surface surpasses about the 2cm of Stigma Maydis surface, soaked 2 hours, boil, water temperature reaches 100 ℃ in jar, then cooling naturally, drop to 80 ℃, kept 80 ℃ of water temperatures 1 hour, and emitted extracting solution, filter with 150 orders and the two-layer sieve of 250 orders, draw supernatant, process adds thermo cycler, 60 ℃ of temperature, and pressure is 0.3-0.4mpa, concentrate, the proportion during 50 ℃ of concentrated solutions is 1.15-1.2g/cm
3, becoming extractum, 2 times of 95% ethanol with concentrated solution carries out precipitate with ethanol then, precipitate with ethanol 24-48 hour, the supernatant decompression recycling ethanol, concentrating becomes thick paste, add the water-saturated n-butanol extraction then, coextraction 2 times, n-butanol extracting liquid reclaim under reduced pressure n-butyl alcohol, concentrated solution is thick paste, puts into vacuum desiccator, 60 ℃ of temperature, pressure is 0.08-0.1mpa, vacuum drying, it is Powdered that dry product is yellowish-brown, is Stigma Maydis total saponins.This method particularly is suitable for suitability for industrialized production.
The extraction of embodiment 2.1 total flavones:
Get Chinese medicine Stigma Maydis dry product and make conventional decoction pieces.Use solvent extraction method, 10-12 doubly measures 50～80% ethanol and carries out reflux, extract,, and 2～3 times, each 2～3 hours, reflux temperature was controlled at 50 ℃～80 ℃.Merge alcohol extract, add water and precipitate, centrifugal, get its supernatant, concentrate drying promptly gets Stigma Maydis total flavones.
Adopt hydrochloric acid-magnesium powder reaction to carry out discrimination test, sample thief is dissolved in methanol, adds a small amount of magnesium powder, several concentrated sulphuric acids are dripped in jolting, spend a few minutes, produce steam bubble, it is orange red that steam bubble is, and Stigma Maydis total flavones may contain flavone, flavonol, flavanone and flavanone alcohol compound.
The ethanol extract from water precipitation of embodiment 2.2 total flavones extracts:
Stigma Maydis is used 60% ethanol through after cutting off, and medical material is 1 with the ratio of ethanol: 10-12, soaked 2 hours, and poured Soxhlet into and extract in the tube reflux, extract,, extract altogether 2 times, each 1.5 hours, merge extracted twice liquid, pour 1/3 volume water into, put into refrigerator and carry out water precipitating for 4 ℃, spend the night, orange-yellow liposoluble substance precipitation is arranged, high speed centrifugation, 3000～3500r/min, 15 ', get supernatant, concentrating under reduced pressure reclaims ethanol, till nothing alcohol flavor, concentrated solution becomes thick paste, puts into vacuum drying oven, and pressure is 0.08-0.1mpa, temperature is 60 ℃ and carries out vacuum drying that dry product is Stigma Maydis flavonoid product.Extract hydrochloric acid---discrimination test is carried out in the magnesium powder reaction, according to color reaction, contains flavonoid materials such as flavone, flavonol in the prompting alcohol extract.
The ethanol extract from water precipitation of embodiment 2.3 total flavones extracts:
Take by weighing Chinese medicine Stigma Maydis 250kg, after cutting off, put into 3 tons of multipotency extraction pot, use 60% ethanol, soaked 2 hours, solid-liquid ratio is 1: 10-12, heating, the jar temperature reaches 50 ℃, reflux, extract, 1 time, time remaining 3 hours, emit extracting solution, cooling, the adding water yield are 1-2 times of extracting solution, standing over night, after treating layering, filter, get supernatant, the decompression recycling ethanol aqueous solution adds thermo cycler and concentrates, 50 ℃ of temperature, pressure is 0.32mpa, reclaims ethanol, the proportion 1.08-1.15g/cm under 50 ℃ of the concentrated solutions
3, concentrated solution is thick paste, puts into the vacuum desiccator oven dry, and temperature is 60 ℃, and pressure is 0.08-0.1mpa, becomes dry product after the oven dry, pulverizes, and is total flavones.This method particularly is suitable for suitability for industrialized production.
The extraction of embodiment 3.1 Stigma Maydis crude polysaccharidess:
Get Chinese medicine Stigma Maydis dry product and make conventional decoction pieces.Adopt decoction alcohol precipitation method to extract crude polysaccharides.Medical material is put into decoction pot, adds medical material weight 10-14 water doubly, and 60 ℃ of constant temperature soaked after 2 hours, decocted one hour, and inclining medicinal liquid, and same method decocts 2 times again, merges three times medicinal liquid, and the dense proportion 1.1～1.25g/cm that is concentrated under 50 ℃ reduces pressure
3, staticly settle 24～48 hours with 60～80% ethanol, centrifugal, get its precipitate, precipitate once more, get its precipitate with 95% ethanol, dissolve with hot water, centrifugal its insoluble matter that goes, the aqueous solution concentrating under reduced pressure promptly gets dried thick paste, put into vacuum desiccator, 60 ℃ of temperature, pressure is 0.08～0.1mpa, bakes dry product and promptly gets Stigma Maydis crude polysaccharides.
Adopt the phenolsulfuric acid colorimetry, as seen instrument is---ultraviolet spectrophotometer, and with glucose as a standard product are measured trap at the 490nm place, and the concentration of crude polysaccharides is 3～4mg/ml.
The decoction and alcohol sedimentation technique of embodiment 3.2 Stigma Maydis crude polysaccharidess extracts:
Get Chinese medicine Stigma Maydis dry product, after cutting off, put into the jar of boiling medicine, add the water of 12～14 times of medical material weight, the water surface exceeds medical material surface 2～3cm, soaks 2 hours, heating decocts then, after boiling, little boil to boil fry in shallow oil 1 hour, same method decocts 2～3 times, merges 2～3 times extracting solution, with eight layers of filtered through gauze, high speed centrifugation, 3000～3500r/min, 15 ', get its supernatant, concentrating under reduced pressure, concentrated solution adds 70～80% ethanol, and stand at low temperature is spent the night, precipitate with ethanol, high speed centrifugation, 3000r/min, 15 ', get the precipitation part, reuse 95% washing with alcohol precipitation, centrifugal, take out precipitate, add 60 ℃ of hot water dissolvings then, centrifugal, remove insoluble impurities, aqueous solution concentrating under reduced pressure, concentrated solution vacuum drying, 60 ℃ of temperature, pressure is 0.08-0.1mpa, dry product is crude polysaccharides.Extract phenol---sulphuric acid colorimetry is measured crude polysaccharides content, carries out Quality Control.
Selecting and decoct number of times, decocting time, add water multiple and concentration of alcohol for use as the investigation factor, serves as to investigate index with glucose content in the extracting solution, selects Lg (3 for use
4) orthogonal table test, result of the test shows that the optimum condition that extracts crude polysaccharides is: medical material decoction 3 times, decocted 1 hour at every turn, and concentration of alcohol is 60%, adds water at every turn and be 14 times of medical material.
The decoction and alcohol sedimentation technique of embodiment 3.3 Stigma Maydis crude polysaccharidess extracts:
Chinese medicine Stigma Maydis dry product 250kg after cutting off, puts into 3 tons of multipotency extraction pot, is 1 by solid-liquid ratio: 12-14, put into 50 ℃ of warm water, soaked 2 hours, logical then steam is heated, and a jar temperature reaches 100 ℃, again steam off, naturally cooling when dropping to 80 ℃, was kept 1 hour, emitted extracting solution.Fry in shallow oil with method and to boil 1 time again.Merge extracted twice liquid, filter with 150 orders and the two-layer sieve of 250 orders, remove its impurity, filtrate entering adds thermo cycler, 60 ℃ of temperature, and pressure is 0.34mpa, concentrated solution is concentrated into the proportion 1.08～1.1g/cm under 50 ℃
3Add 2 times 95% ethanol of concentrated solution volume again, carry out the low temperature precipitate with ethanol, precipitate with ethanol 24 hours-48 hours, centrifugal, get its precipitate, precipitate reuse 95% washing with alcohol is once, centrifugal, get its precipitate and dissolve centrifugal its insoluble matter that goes with 50 ℃ of-60 ℃ of warm water, aqueous solution concentrates, concentrated solution is put into vacuum drying oven, 60 ℃ of temperature, and pressure is 0.08-0.1mpa, oven dry is pulverized and is crude polysaccharides.This method particularly is suitable for suitability for industrialized production.
The capsule preparation of embodiment 4 medicines provided by the invention
It is broken to get Stigma Maydis total saponins, total flavones, crude polysaccharides dried cream powder in proportion, and porphyrize is crossed the 80-100 mesh sieve, and mix homogeneously is crossed 80 mesh sieves, is sub-packed in the 1# capsule, and every capsule content is the 0.3g medicine.
The test of pesticide effectiveness of embodiment 5 medicines provided by the invention
Animal is Kunming mouse, and body weight 18-22g is male, and the animal quality quality certification is numbered ZYID10016, is provided by the institute for drug control, Zhejiang Province.
Statistical result is all through " " check, the result represents with X ± S t.
5.1 Stigma Maydis total saponins is to alloxan diabetes mice hypoglycemic activity
Get 40 of mices, tell 10 at random and be the blank group, all the other mice fasting (can't help water) 15-16 hour, subcutaneous injection alloxan (ALX) 250mg/kg, injected back 72 hours, and surveyed fasting glucose, the mice of getting FBC 〉=11.1mmol/l, be divided into 3 groups at random, animal grouping and drug dose such as table 1.Normal group, model group are irritated stomach equivalent normal saline, and experimental group is irritated the Stigma Maydis total saponins of stomach various dose, once a day, continuous 7 days, before the last administration, fasting 14 hours, 2 hours tail vein bloods after the last administration are surveyed FBC, the results are shown in Table 1.
Table 1 Stigma Maydis total saponins influences the alloxan diabetes mouse blood sugar
With the alloxan group than * P＜0.05 * * P＜0.01 * * * P＜0.001
Middle dosage group and high dose group ratio ▲ P＞0.05
The result shows: the hypoglycemic activity of dosage, high dose is compared with the alloxan group in the total Saponin of Stigma Maydis, the difference (P＜0.001) that highly significant is arranged, middle dosage treated animal hypoglycemic activity is stronger than high dose group, but does not have difference (P＞0.05) statistically.
5.2 Stigma Maydis total saponins is to the influence of mice carbohydrate tolerance
Get 30 of normal mouses, be divided into 3 groups at random, fasting (can't help water) 12 hours, survey FBC, be the oh blood glucose value, experimental group is irritated stomach once with Stigma Maydis total saponins 800mg/kg, and model group is irritated stomach once with the equivalent normal saline, behind the 1h, two groups of equal lumbar injection glucoses, dosage is 2.5g/kg, respectively at 0.5,1 and 2h three groups of mices are surveyed blood glucose, result such as table 2.
Table 2 Stigma Maydis total saponins influences glucose hyperglycemia mouse blood sugar
Model group and normal group are than △ P＜0.05 △ △ P＜0.01 △ △ △ P＜0.001
Total saponins group and model group are than * P＜0.05 * * P＜0.01 * * * P＜0.001
The total saponins group, behind the glucose injection 30 ', the mouse blood sugar level raises very fast, than glucose group height, highly significant difference (P＜0.001) is arranged.1h behind the glucose injection, two groups level is zero difference (P＞0.05), 2h behind the glucose injection, total saponins treated animal blood sugar level is lower than glucose group, and highly significant difference (P＜0.01) is arranged.Experimental result shows: total saponins can improve the effect of mice carbohydrate tolerance.
5.3 Stigma Maydis total saponins is to the ag(e)ing test of alloxan diabetes mice blood sugar lowering
Get 30 of mices, be divided into 3 groups at random, one group is normal group, and all the other mices are copied into hyperglycemia model with alloxan, and method is the same, and (FBC 〉=11.1mmol/L), being divided into two groups one group is model group, and another group is experimental group to select qualified animal model.Three treated animals are all surveyed FBC, are the oh blood glucose value, and experimental group is with Stigma Maydis total saponins 400mg/kg, irritate stomach once, all irritate stomach once with the equal-volume normal saline for all the other two groups, respectively to three treated animals in 3h, 7h, 24h respectively survey blood glucose one time, experimental result sees Table 3.
Table 3 Stigma Maydis total saponins is to alloxan diabetes mice blood sugar lowering ag(e)ing test (X ± S)
Total saponins and model group be * P＜0.05 * * P＜0.01 * * * P＜0.001 relatively
Model group and normal group be △ P＜0.05 △ △ P＜0.01 △ △ △ P＜0.001 relatively
The total Saponin of Stigma Maydis was taken medicine back 3 hours to diabetic mice, and blood sugar decreasing effect highly significant (P＜0.01) is to 7h hypoglycemic activity still highly significant (P＜0.01).The prediction hypoglycemic activity can continue until 10h, rises to the 24h blood sugar level, and therefore, the result shows from the total Saponin ag(e)ing test of Stigma Maydis, takes three medicines and is advisable in 1st.
Embodiment 5.4 Stigma Maydis total saponins, total flavones and crude polysaccharides are to the sick mice blood sugar lowering test of epinephrine glycosuria
Get 60 of mices, be divided into 6 groups at random, animal grouping and drug dose such as table 4.Each group is gastric infusion or normal saline respectively, once a day, continuous use 7 days, the 6th day fasting 14-15 hour, after the last administration in the 7th day 3 hours, the lumbar injection adrenalin hydrochloride was injected back 1 hour, adopted the quiet blood of tail and surveyed blood glucose, the results are shown in Table 4.
Table 4 Stigma Maydis total saponins, total flavones, crude polysaccharides are to the influence of adrenal gland's disposition hyperglycemia mouse blood sugar
Organize comparison * P ≈ 0.05 * * P＜0.02 * * * P＜0.001 with the adrenal gland
Compare △ P＞0.05 △ △ P＜0.05 △ △ △ P＜0.01 with the diabetes pill group
With normal group comparison ▲ P＜0.05 ▲ ▲ P＜0.01 ▲ ▲ ▲ P＜0.001
Total saponins group hypoglycemic activity is compared the difference (P＜0.02) that highly significant is arranged with the epinephrine group, also there were significant differences for the blood sugar reducing function of total flavones group (P ≈ 0.05).
Total saponins, total flavones, crude polysaccharides three all have hypoglycemic activity, and wherein the total saponins hypoglycemic activity is the strongest, and total flavones is stronger.Total saponins, total flavones are compared with diabetes pill, and both do not have significant difference (P＞0.05).
Embodiment 5.5 Stigma Maydis total saponins, flavonid composition are tested alloxan diabetes mice blood sugar lowering
Medicine: constitute 5 groups of medicines by the Different Weight proportioning respectively by Stigma Maydis total saponins, total flavones
1 group of medicine: total saponins: total flavones 1: 0.1;
2 groups of medicines: total saponins: total flavones 1: 0.5;
3 groups of medicines: total saponins: total flavones 1: 0.9;
4 groups of medicines: total saponins: total flavones 1: 1.3;
5 groups of medicines: total saponins: total flavones 1: 1.8.
Get 70 of Kunming mouses, take out 10 at random and be blank group, all the other mice fasting (can't help water) 15-16 hour, subcutaneous injection ALX250mg/kg injected back 72 hours, surveyed fasting glucose, get the mice of FBC 〉=11.1mmol/l, be divided into 6 groups at random, animal grouping and drug dose such as table 5.Normal group, model group are irritated stomach equivalent normal saline, and experimental group is pressed the medicine gastric infusion of different proportionings, once a day, continuous 7 days, before the last administration, fasting (can't help water) 14 hours, 2 hours tail vein bloods after the last administration are surveyed FBC, the results are shown in Table 5.
Table 5 Stigma Maydis total saponins, flavonid composition influence the alloxan diabetes mouse blood sugar
Medicine group and alloxan group ratio: * P＜0.05 * * P＜0.01 * * * P＜0.001
1 group of medicine and 3 groups, 5 groups ratios: △ P＜0.05 △ △ P＜0.01 △ △ △ P＜0.001
Embodiment 5.6 Stigma Maydis total saponins, crude polysaccharides compositions are tested alloxan diabetes mice blood sugar lowering
Medicine: constitute 5 groups of medicines by the Different Weight proportioning respectively by Stigma Maydis total saponins, crude polysaccharides
1 group of medicine: total saponins: crude polysaccharides 1: 0.1
2 groups of medicines: total saponins: crude polysaccharides 1: 0.5
3 groups of medicines: total saponins: crude polysaccharides 1: 0.9
4 groups of medicines: total saponins: crude polysaccharides 1: 1.3
5 groups of medicines: total saponins: crude polysaccharides 1: 1.8
Get 70 of Kunming mouses, take out 10 at random and be blank group, all the other mice fasting (can't help water) 15-16 hour, subcutaneous injection ALX250mg/kg injected back 72 hours, surveyed fasting glucose, get the mice of FBC 〉=11.1mmol/l, be divided into 6 groups at random, animal grouping and drug dose such as table 5.Normal group, model group are irritated stomach equivalent normal saline, and experimental group is pressed the medicine gastric infusion of different proportionings, once a day, continuous 7 days, before the last administration, fasting (can't help water) 14 hours, 2 hours tail vein bloods after the last administration are surveyed FBC, the results are shown in Table 5.
Table 6 Stigma Maydis total saponins, crude polysaccharides compositions influence the alloxan diabetes mouse blood sugar
Drug study group and alloxan group ratio: * P＜0.05 * * P＜0.01 * * * P＜0.001
1 group of medicine and 3 groups, 5 groups ratios: △ P＜0.05 △ △ P＜0.01 △ △ △ P＜0.001
The test of pesticide effectiveness of embodiment 5.7 medicines provided by the invention
Constitute 5 groups of medicines by the Different Weight proportioning respectively by Stigma Maydis total saponins, total flavones and crude polysaccharides.
1 group of medicine: total saponins: the weight of total flavones and crude polysaccharides and 1: 0.1, wherein the weight ratio of total flavones and crude polysaccharides is 1: 1.
2 groups of medicines: total saponins: the weight of total flavones and crude polysaccharides and 1: 0.5, wherein the weight ratio of total flavones and crude polysaccharides is 1: 0.5.
3 groups of medicines: total saponins: the weight of total flavones and crude polysaccharides and 1: 0.9, wherein the weight ratio of total flavones and crude polysaccharides is 0.5: 1.
4 groups of medicines: total saponins: the weight of total flavones and crude polysaccharides and 1: 1.3, wherein the weight ratio of total flavones and crude polysaccharides is 0.2: 1.
5 groups of medicines: total saponins: the weight of total flavones and crude polysaccharides and 1: 2, wherein the weight ratio of total flavones and crude polysaccharides is 1: 0.2.
Get 70 of Kunming mouses, take out 10 at random and be blank group, all the other mice fasting (can't help water) 15-16 hour, subcutaneous injection ALX250mg/kg injected back 72 hours, surveyed fasting glucose, get the mice of FBC 〉=11.1mmol/L, be divided into 6 groups at random, animal grouping and drug dose such as table 7.Normal group, model group are irritated stomach equivalent normal saline, and experimental group is pressed the medicine gastric infusion of different proportionings, once a day, continuous 7 days, before the last administration, fasting (can't help water) 14 hours, 2 hours tail vein bloods after the last administration are surveyed FBC, the results are shown in Table 7.
Table 7 new drug is to the alloxan diabetes mouse blood sugar test of pesticide effectiveness
1,2,3,4,5 groups of medicines and alloxan group ratio: * P＜0.05 * * P＜0.01***P＜0.001
5 groups of ratios of 2 groups of medicines and medicine: △ P＞0.05
The hypoglycemic activity that medicine is 1,2,3,4,5 groups has been compared highly significant difference (P＜0.001) with the alloxan group, the hypoglycemic activity that medicine is 2 groups is compared for 5 groups with medicine does not have significant difference (P＞0.05).But the hypoglycemic drug effect that medicine is 2 groups is stronger than 5 groups of medicines.
Embodiment 5.8 new drug I numbers to normal mouse blood sugar influence
Give the normal mouse gastric infusion for 2 groups with the medicine of embodiment 5.7, continuous 7 days, to 2 hours survey blood glucose values behind the medicamental pulverata sky gastric infusion, experimental result saw Table 8.
2 groups of table 8 medicines are to normal mouse blood sugar influence
Self compares: *＞0.05
Experimental result shows: blood glucose value changes before and after the administration does not have significant difference, and its blood sugar lowering pharmacology mechanism is similar to biguanides.
Conclusion
The foregoing description shows, total saponins, total flavones, crude polysaccharides three all have hypoglycemic activity, the blood sugar reducing function of total saponins is stronger than total flavones, crude polysaccharides, therefore, total saponins is as the main effective ingredient of Stigma Maydis blood sugar lowering, simultaneously, find that also total saponins, total flavones and crude polysaccharides three are used, just can bring into play complementary action, strengthen the blood sugar lowering drug effect, and can reduce manufacturing cost.Particularly total saponins and total flavones are or/and the weight ratio of crude polysaccharides reaches optimization at 1: 1 its therapeutic effect between 1: 0.1 time and production cost.
Total saponins can significantly reduce the blood sugar level of the various hyperglycemia mouse models due to glucose, adrenal gland's disposition and the alloxan, and the prompting total saponins is from various approach blood sugar lowering levels.
Flavonoid not only has the blood sugar lowering effect, also has antioxidation; Polysaccharide not only has hypoglycemic activity, also has immunoregulation effect.
By the new drug of Stigma Maydis total saponins, total flavones and crude polysaccharides combination the blood glucose of normal mouse there is not obvious influence, point out the blood sugar lowering mechanism of this medicine similar to biguanides blood sugar lowering mechanism, promptly inhibition or delay glucose are in the absorption of mouse intestinal, promote peripheral organization to glucose uptake, zymolysis and utilization, suppress the heteroplasia effect of liver glycogen decomposition and glucose.Flavonoid has antioxidation, and ultra-oxygen anion free radical, hydroxy radical are had scavenging action, can alleviate the damage to beta Cell of islet, improve the function of the beta Cell of islet of damaged, promote secretion of insulin, strengthened catabolism of carbohydrate, thereby reduced blood sugar level.
Stigma Maydis total saponins can reduce the blood sugar level of glucose hyperglycemia mouse model, has the effect that improves the mice carbohydrate tolerance, this to diabetes patient's early stage (being impaired glucose tolerance person) or diabetics after treatment, even fasting glucose is reduced to normally, but most post-prandial glycemia are still very high, and the Stigma Maydis preparation can improve patient's carbohydrate tolerance level.Current medical science thinks that it is the basis that the treatment diabetes reduce fasting glucose, and the control post-prandial glycemia is a crux, and both have concurrently the present invention, and this is the desirable new drug for the treatment of diabetes in the present Chinese medicine like product simply.
China abounds with corn, the resource of Stigma Maydis is extremely abundant, up to the present do not obtain development and use as yet, the present invention utilizes Stigma Maydis to do the raw material pharmacy, Stigma Maydis is turned waste into wealth, not only can low cost of manufacture, simultaneously also to revitalizing agricultural economy, reducing environmental pollution and also have suitable social meaning.
Claims (8)
1. the medicine of treatment diabetes is characterized in that its active substance is made up of at least a and Stigma Maydis total saponins in Stigma Maydis total flavones and the Stigma Maydis crude polysaccharides; When the weight of Stigma Maydis crude polysaccharides was zero, the scope of the weight ratio of Stigma Maydis total saponins and Stigma Maydis total flavones was 1: 1.5～1: 0.1; When the weight of Stigma Maydis total flavones was zero, the scope of the weight ratio of Stigma Maydis total saponins and Stigma Maydis crude polysaccharides was 1: 1.5～1: 0.1; When the weight of Stigma Maydis total flavones and Stigma Maydis crude polysaccharides was non-vanishing, Stigma Maydis total saponins weight: the gross weight of Stigma Maydis total flavones and Stigma Maydis crude polysaccharides was 1: 1.5～1: 0.1.
2. the medicine of treatment diabetes as claimed in claim 1 is characterized in that the scope of the weight ratio of Stigma Maydis total saponins and Stigma Maydis total flavones is 1: 1～1: 0.1 when the weight of Stigma Maydis crude polysaccharides is zero.
3. the medicine of treatment diabetes as claimed in claim 1 is characterized in that the scope of the weight ratio of Stigma Maydis total saponins and Stigma Maydis crude polysaccharides is 1: 1～1: 0.1 when the weight of Stigma Maydis total flavones is zero.
4. the medicine of treatment diabetes as claimed in claim 1, it is characterized in that when the weight of Stigma Maydis total flavones and Stigma Maydis crude polysaccharides is non-vanishing Stigma Maydis total saponins weight: the gross weight of Stigma Maydis total flavones and Stigma Maydis crude polysaccharides is 1: 1～1: 0.1.
5. treat the production method of diabetes medicament, it is characterized in that it may further comprise the steps:
1) preparation Stigma Maydis total saponins with ethanol reflux extraction or decocting extraction method, obtains extracting solution with Stigma Maydis, and the extraction of reuse water-saturated n-butanol obtains Stigma Maydis total saponins;
2) the preparation Stigma Maydis total flavones obtains extracting solution with Stigma Maydis with ethanol reflux extraction, water precipitating, and supernatant concentration obtains Stigma Maydis total flavones;
3) preparation Stigma Maydis crude polysaccharides, with the Stigma Maydis decoction alcohol precipitation method, precipitate washs 1～2 time with 40～65 ℃ warm water, and supernatant concentration obtains Stigma Maydis crude polysaccharides;
4) with the Stigma Maydis total saponins that makes, Stigma Maydis total flavones, Stigma Maydis crude polysaccharides by the described weight proportion of claim 1 and add after corresponding adjuvant mixes, promptly can be made into corresponding preparations.
6. the production method of treatment diabetes medicament as claimed in claim 5, it is characterized in that being prepared as of Stigma Maydis total saponins: is that 40～95% soak with ethanol are more than 2 hours with Stigma Maydis with the concentration of 8～25 times of weight, reflux, extract, 2～3 times, each 1～2.5 hour, merge extractive liquid,, relative density 1.05～1.3g/cm when decompression recycling ethanol, concentrated solution are concentrated into 50 ℃
3, use the water saturation n-butanol extraction then, extract 3～4 times, reclaim n-butyl alcohol, the aqueous solution oven dry promptly gets Stigma Maydis total saponins; Or, Stigma Maydis is extracted with decocting, precipitate with ethanol, supernatant is used the water saturation n-butanol extraction after reclaiming ethanol, reclaims n-butyl alcohol, and the aqueous solution oven dry promptly gets Stigma Maydis total saponins.
7. the production method of treatment diabetes medicament as claimed in claim 5, it is characterized in that the method for preparing Stigma Maydis total flavones is: is that 40～95% soak with ethanol are more than 2 hours with Stigma Maydis with the concentration of 8～25 times of weight, 50 ℃～80 ℃ reflux, extract,, the extracting solution water precipitating, supernatant reclaims ethanol, and the concentrated solution oven dry promptly gets Stigma Maydis total flavones.
8. the production method of treatment diabetes medicament as claimed in claim 5 is characterized in that the method for preparing Stigma Maydis crude polysaccharides is: with the water of Stigma Maydis with 8～25 times of weight ratios, soaking corn must be more than 2 hours, decocting boils 2～3 times, and each 0.5～1.5 hour, merging filtrate, decolour with 2% medical active carbon, filter, filtrate is with 40～95% ethanol precipitations, taking precipitate, reclaim ethanol, the washing of reuse warm water is removed insoluble impurities for several times, and concentrate drying promptly gets Stigma Maydis crude polysaccharides.
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| CN101748173B (en) * | 2009-12-03 | 2012-11-28 | 渤海大学 | Corn silk polysaccharide separation and decoloring method |
| CN102309694B (en) * | 2011-08-29 | 2014-04-16 | 安徽农业大学 | Method for extraction and purification of corn silk general flavone, and use of corn silk general flavone |
| CN103316233A (en) * | 2013-05-20 | 2013-09-25 | 缪长法 | Traditional Chinese medicine used for treating diabetes, and preparation method thereof |
| CN105726624A (en) * | 2016-05-04 | 2016-07-06 | 吉林大学 | Pharmaceutical composition for treating diabetes |
| CN108338359B (en) * | 2018-06-25 | 2018-09-11 | 上海欣百诺生物科技有限公司 | The production technology and application thereof of Stigma Maydis total saponins highly finished product |
| CN109771579A (en) * | 2019-03-29 | 2019-05-21 | 吉林鑫水科技开发有限公司 | The method of orthogonal experiment method optimization birch young pilose antler and corn stigma sugar-lowering components extraction process |
| CN111504997B (en) * | 2020-05-15 | 2022-10-18 | 吉林鑫水科技开发有限公司 | Method for extracting components of corn stigma and straws and testing in-vitro hypoglycemic activity of components |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1297353A (en) * | 1998-04-17 | 2001-05-30 | 上海明治健康医药有限公司 | Hypoylycemic agents |
-
2004
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1297353A (en) * | 1998-04-17 | 2001-05-30 | 上海明治健康医药有限公司 | Hypoylycemic agents |
Non-Patent Citations (10)
| Title |
|---|
| 玉米须中总黄酮的提取分离与结构鉴定. 任顺成等.中草药，第35卷第8期. 2004 |
| 玉米须中总黄酮的提取分离与结构鉴定. 任顺成等.中草药，第35卷第8期. 2004 * |
| 玉米须中总黄酮的提取及树脂精制. 任顺成等.中草药，第34卷第12期. 2003 |
| 玉米须中总黄酮的提取及树脂精制. 任顺成等.中草药，第34卷第12期. 2003 * |
| 玉米须化学成分和药理作用研究进展. 王英平等.特产研究，第2期. 2004 |
| 玉米须化学成分和药理作用研究进展. 王英平等.特产研究，第2期. 2004 * |
| 玉米须多糖的提取及含量测定. 刘媛等.南京中医药大学学报，第15卷第2期. 1999 |
| 玉米须多糖的提取及含量测定. 刘媛等.南京中医药大学学报，第15卷第2期. 1999 * |
| 玉米须总皂苷降糖作用研究. 苗明三等.中国中药杂志，第29卷第7期. 2004 |
| 玉米须总皂苷降糖作用研究. 苗明三等.中国中药杂志，第29卷第7期. 2004 * |
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