CN1981814A - Use and production for mulberry leaf in treatment of diabetes - Google Patents
Use and production for mulberry leaf in treatment of diabetes Download PDFInfo
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Abstract
An extract of mulberry leaf contains general alkaloid and general flavone, and is prepared through extracting, removing impurities, concentrating, eluting, drying and mixing. It can be used to prepare the medicines for preventing and treating diabetes and its complications.
Description
Technical field
The present invention relates to a kind of Folium Mori extract and application and preparation method in preparation treatment diabetes and complication medicine thereof, belong to modern Chinese traditional medicine field.
Background technology
Diabetes are a kind of common endocrinopathyes, and its cause mainly is because due to inherited genetic factors and environmental factors such as dietetic life custom bad (surfeit, smart food etc.), quantity of motion deficiency, obesity and the stress etc.Along with the aging of world population, diabetes have become a kind of commonly encountered diseases, frequently-occurring disease, and sickness rate is remarkable ascendant trend.
Diabetes are that a class causes to have the chronic hyperglycemia of obvious heterogeneity and the syndrome that complication is formed by factors such as heredity, environment, immunity.Mainly be divided into two kinds on I type and II type, the insulin that type i diabetes (insulin dependent diabetes mellitus (IDDM)) patient pancreas produces seldom or does not fully produce insulin; Type ii diabetes (non-insulin-dependent diabetes mellitus) patient pancreas can continue to produce insulin, sometimes in addition insulin level surpass the normal person, yet body produces opposing to the effect of insulin, causes insulin to lack relatively.Based on noninsulin dependent II type, about 80% is the type ii diabetes patient.Long-term hyperglycemia infringement blood vessel, nerve and other internal organs structures, compound glycosyl material is deposited in little blood vessel wall, makes its thickening and easy to leak.The blood vessel wall thickening, the blood vessel amount of blood supply is fewer and feweri, and the blood vessel of especially arranging skin and nerve changes more obvious.Poor blood glucose control also can cause that fatty material raises in the blood, quickens atherosclerosis (forming speckle in blood vessel wall).In the diabetics, atherosclerosis is 2～6 times of non-diabetic persons, and men and women's both sexes all can take place.The inadequate circulatory blood volume of large and small blood vessel can be damaged heart, brain, two lower limb, eye, kidney, nerve, skin etc., makes wound healing slow.Just because of above reason, diabetics easily merges many severe chronic complication, and heart attack and apoplexy are very common; The vascular lesion of eyes can cause visual loss (diabetic retinopathy); Renal function is unusual, causes renal failure, needs dialysis treatment; Nervous lesion has several performances, and both hands, two lower limb, biped nerve damage (diabetic polyneuropathy) paraesthesia and acupuncture can occur or burn sample pain, myasthenia of limbs; If cutaneous nerve is impaired, patient can not feel extruding or variations in temperature, makes the skin may be injured repeatedly; SkBF is under-supply also can to cause ulcer, and wound healing is slow.
Folium Mori are as the raw material of medicine-food two-purpose, already in extensive use among the people.Since ancient times, the traditional Chinese medical science just is applied to its Chinese medicine as treatment diabete (diabetes that are equivalent to modern medicine) clinical, puts down in writing in the Compendium of Material Medica: " juice is fried in shallow oil Dai Ming, can only quench one's thirst "; " the ripe drink of frying in shallow oil of moxibustion quenches the thirst for tea ".Modern study shows, mainly contains steroidal and triterpenoid compound, flavone compound, alkaloid, aminoacid, organic acid and other chemical compounds in the Folium Mori.
Since the seventies year in last century, the Japan scholar got 1-deoxynojirimycin (DeoxyjirimicinDNJ) from plant, the polyhydroxylated alkaloid compounds is with its stereochemical structure multiformity, multiple biological activity, become the research focus, especially this compounds causes the very big interest of people as the analog of sugar and have glucoside inhibiting activity.Studies show that multiple glycosidase inhibitor such as 1-deoxynojirimycin (DNJ), fagomine etc. are arranged in the Folium Mori.Pharmacological research confirms, thereby the polyhydroxylated alkaloid compounds suppresses the absorption of small intestinal to disaccharidase to the active inhibitory action of disaccharides catabolic enzyme, reduces the peak value of post-prandial glycemia.Flavone compound has also been reported hypoglycemic activity in the Folium Mori, and the atherosclerotic infringement of reduction is arranged, and reduces small intestinal capillary permeability isoreactivity.Total alkaloids of Folium Mori and total flavones be as effective part group, not only can blood sugar lowering and improve carbohydrate tolerance and reduce effects such as atherosclerotic infringement simultaneously in addition, diabetic vascular complications there are prevention and therapeutical effect.
Application number is the Chinese patent of CN 01113191.8, " Preparation method and use with Chinese medicine extract of alpha-glucoside inhibiting activity " disclosed, this patent relates to from Chinese medicine Folium Mori, Ramulus Mori, Cortex Mori and Fructus Mori and prepares total alkaloids, does not still relate to the application as the extract of effective part group of total alkaloids of Folium Mori and total flavones.Application number is that the Chinese patent of CN 200410018677.4 discloses " medical composition and its use with alpha-glucoside inhibiting activity ", and this patent has related to the application in treatment diabetes, treatment hyperlipidemia, antioxidation and antiaging agent of total alkaloids for preparing in Chinese medicine Folium Mori, Ramulus Mori, Cortex Mori and the Fructus Mori and the compositions that adds flavone compound Quercetin, catechin and tea polyphenols.The invention provides a kind of method of alkaloid and flavone effective part and extract that this method obtains of from Folium Mori, obtaining simultaneously.
The objective of the invention is to, from Folium Mori, extract preparation total alkaloids and total flavones as effective part group, as the medicine of treatment and prevent diabetes and complication thereof.
Summary of the invention
The object of the invention is to provide a kind of Folium Mori extract, it is characterized in that wherein total alkaloids and content of total flavone sum are greater than 50%.
The present invention also provides the preparation method of said extracted thing.
Another object of the present invention is to provide the application of this Folium Mori extract in the preparation diabetes medicament.
For achieving the above object, the present invention is by the following technical solutions:
A kind of preparation method of Folium Mori extract may further comprise the steps:
1) extract: with Folium Mori is raw material, water, lower alcohol or moisture lower alcohol extraction;
2) remove impurity: extracting solution is concentrated, and concentrated solution precipitate with ethanol or adding flocculating agent make contamination precipitation, filter;
3) enrichment: filtrate is through cation exchange resin column, and effluent passes through macroporous resin column again;
4) eluting: be adsorbed in Folium Mori total flavonoids on the macroporous resin with moisture lower alcohol eluting, be adsorbed in total alkaloids of Folium Mori on the cation exchange resin with volatility aqueous slkali eluting;
5) drying: eluent is evaporated to dried, and drying is pulverized and promptly obtained Folium Mori total flavonoids and total alkaloids of Folium Mori respectively.
6) mix: resulting total flavones and total alkaloids are mixed, make total alkaloids and content of total flavone sum, promptly get Folium Mori extract of the present invention greater than 50%.
Obtain Folium Mori total flavonoids and total alkaloids of Folium Mori also can be further purified by polyamide and anion exchange resin respectively through said method.
Described extraction is C1-C5 with the carbon number of moisture lower alcohol, for example: methanol, ethanol, propanol, n-butyl alcohol, isobutanol etc.; Concentration is X, 0＜X≤95%, preferred 0＜X≤30%.
In the described removal step, it is X that the adding high concentration ethanol makes the solution concentration of alcohol, 40%≤X≤90%, preferred 50≤X≤60%.
In the described removal step, the flocculating agent of adding can be gelatin, chitosan, agar, ZTC1+1, chitin and derivant thereof, is preferably chitosan.
Described macroporous resin can be for any one or a few is the polarity or the non-polar resin of framework material in styrene, divinylbenzene, acrylate and the methacrylate.For example D101, D201, AB-8, HP-20, XAD-4 and XAD-16 etc.Be preferably styrene tyle macroporous adsorption resin.
Described cation exchange resin can be polystyrene or macroporous ion-exchange resin, for example 001X4,001X7,001X14.5, Dowex50, Amberlite IR120 or Amberlite252 etc.Preferred 001X4, the 001X7 type.
Described volatility alkali is the aqueous solution of 0.1%～1 ammonia, diethylamino, triethylamine, pyridine, is preferably 0.5% ammonia spirit.
Described eluting is C1-C5 with the carbon number of moisture lower alcohol, for example: methanol, ethanol, propanol, n-butyl alcohol, isobutanol etc.; Concentration is X, 45≤X≤100%, preferred 50≤X≤80%.
The drying means of Folium Mori extract is vacuum drying, lyophilization, spray drying etc., is preferably vacuum drying or lyophilization.
A kind of Folium Mori extract, this Folium Mori extract adopt method for preparing to obtain.
A kind of application of Folium Mori extract is used to described Folium Mori extract to prepare the application of the medicine aspect of treatment and prevent diabetes and complication thereof.
A kind of Folium Mori extract preparation, the described Folium Mori extract of said preparation is a main active, adds the pharmaceutics acceptable auxiliary, makes the pharmaceutics acceptable forms.Described adjuvant is selected from any one or a few in starch, microcrystalline Cellulose, sucrose, dextrin, lactose, Icing Sugar, glucose, sodium chloride, vitamin C, cysteine, citric acid and the sodium sulfite.
Described pharmaceutics acceptable forms is oral agents or injection, is tablet, pill, capsule, drop pill, liquid drugs injection, powder pin or transfusion.
When the Folium Mori extract that utilizes the present invention to obtain prepares the various dosage form of required medicine, can be according to the conventional production method preparation in pharmaceutics field.As this extract is mixed with one or more carriers, make corresponding dosage forms then.
Advantage of the present invention is: Folium Mori extract provided by the present invention, its preparation technology is simple, content is high, safety, easy operating, do not need High Temperature High Pressure and special installation, with low cost.
Describe technical solution of the present invention by the following examples in detail, do not limit practical range of the present invention with this.
The specific embodiment
Embodiment 1
Folium Mori 10kg pulverizes, with 30% alcohol reflux 3 times, and 50L at every turn; Merge 30% ethanol extract, be evaporated to 10L, proportion is 1.18, adds 95% ethanol 20L, makes concentration of alcohol reach about 60%, leaves standstill 24h, the filtering precipitation; After supernatant concentration was removed alcohol, thin up was crossed the D101 resin column to 100L, and column volume is 10L, and last sample after washing 30L merges effluent and water lotion; D101 resin reuse 60% ethanol elution 50L, 60% ethanol elution concentrate the back drying under reduced pressure and promptly get total flavones 130g (content is 57%); Effluent and water lotion add hydrochloric acid transfer pH4 after, cross 001 * 7 polystyrolsulfon acid hydrogen type cation exchange resin of 10L, be washed to colourless after, with the ammonia eluting 80L of 0.5N, ammonia eluent concentrate drying promptly gets total alkaloids 65g (content is 65%); Mix the Folium Mori extract that total flavones and total alkaloids promptly get indication of the present invention.
The Folium Mori extract 100g that obtains adds starch 15000g, microcrystalline Cellulose 70g, and with 50%7 alcohol granulations, tabletting gets tablet, and every is 10mg.
Embodiment 2
Folium Mori 5kg pulverizes, with 50% alcohol reflux 3 times, and 10L at every turn; Merge 50% ethanol extract, be evaporated to 10L, proportion is 1.17, adds 95% ethanol 7L, makes concentration of alcohol reach about 70%, leaves standstill 24h, the filtering precipitation; After supernatant concentration was removed alcohol, thin up was crossed the AB8 resin column to 100L, and column volume is 5L, and last sample after washing 20L merges effluent and water lotion; AB8 resin reuse 70% ethanol elution 30L, 70% ethanol elution concentrate the back drying under reduced pressure and promptly get total flavones 70g (content is 62.5%); Effluent and water lotion add hydrochloric acid transfer pH5 after, cross the 001X14.5 polystyrolsulfon acid hydrogen type cation exchange resin of 6L, be washed to colourless after, with the ammonia eluting 40L of 0.5N, ammonia eluent concentrate drying promptly gets total alkaloids 32.5g (content is 57%); Mix the Folium Mori extract that total flavones and total alkaloids promptly get indication of the present invention.
Embodiment 3
Folium Mori 1kg pulverizes, with 70% alcohol reflux 3 times, and 5L at every turn; Merge 70% ethanol extract, be evaporated to 1.5L, proportion is 1.16, adds the flocculating agent chitosan, leaves standstill 24h, the filtering precipitation; After supernatant concentration was removed alcohol, thin up was crossed the HP20 resin column to 10L, and column volume is 2L, and last sample after washing 5L merges effluent and water lotion; HP20 resin reuse 60% ethanol elution 5L, 60% ethanol elution concentrate the back drying under reduced pressure and promptly get total flavones 11g; Effluent and water lotion add hydrochloric acid transfer pH4 after, cross 001 * 7 polystyrolsulfon acid hydrogen type cation exchange resin of 10L, be washed to colourless after, with the ammonia eluting 8L of 0.5N, ammonia eluent concentrate drying promptly gets total alkaloids 5g (content is 73%); Mix the Folium Mori extract that total flavones and total alkaloids promptly get indication of the present invention.
Embodiment 4
Normal mouse post-prandial glycemia time graph: the Male Kunming strain mice body weight is 22-25g, overnight fasting, irritate stomach starch 10g/kg and irritate the Folium Mori extract 150mg/kg that stomach embodiment 1 obtains simultaneously, 0min, 30min, 60min, 90min, 120min survey blood sugar level, result such as accompanying drawing after the administration.
Embodiment 5
40 of Kunming mouses are divided into 40 groups at random, and 10 every group, male and female half and half, (1) matched group (distilled water); (2) hyperglycemia model group (distilled water); (3) Folium Mori extract low dose group (50mg/kg); (4) Folium Mori extract high dose group (150mg/kg).Except that the normal control group, all the other respectively organize lumbar injection streptozotocin (200mg/kg), survey blood glucose (12h on an empty stomach) after 72 hours, then with (2)-(4) group, according to the balanced group of adjusting of blood glucose value.Irritate stomach by above dosage simultaneously and give the Folium Mori extract that embodiment 1 obtains, continuous 7 days, empty stomach 12h before the administration in the 7th day, 1h measures blood glucose after the last administration.The results are shown in Table
The table Folium Mori extract brings out the influence of mice hyperglycemia to streptozotocin
| Group | Dosage (mg/kg) | Blood glucose before the medicine | Blood glucose behind the medicine | Rate of change |
| (mmol/L) | (mmol/L) | (％) | ||
| Normal control group hyperglycemia model group Folium Mori extract (low dose group) Folium Mori extract (high dose group) | --- --- 50 150 | 4.73±1.01 9.34±2.23** 9.60±2.68 9.76±2.60 | 4.86±1.02 9.49±2.04** 7.59±2.41 7.39±1.80** | +3.1±7.8 +2.1±5.8 -21.3±5.5 -23.8±7.8 |
Annotate: data are X ± SD (n=10) in (1) table
Compare P＜0.01 with normal group; Compare P＜0.05, * * P＜0.01 (t check) with model group.
Conclusion: mouse peritoneal registration streptozotocin can make blood sugar increasing, and after giving Folium Mori extract, have hypoglycemic effect.Wherein dosage is that (150mg/kg) compares with model group, and difference has the significance meaning.
Claims (19)
1, a kind of Folium Mori extract is characterized in that wherein total alkaloids and content of total flavone sum are greater than 50%.
2, a kind of preparation method of Folium Mori extract may further comprise the steps:
1) extract: with Folium Mori is raw material, water, lower alcohol or moisture lower alcohol extraction;
2) remove impurity: extracting solution is concentrated, and concentrated solution precipitate with ethanol or adding flocculating agent make contamination precipitation, filter;
3) enrichment: filtrate is through macroporous resin column, and effluent passes through cation exchange resin column again;
4) eluting: be adsorbed in Folium Mori total flavonoids on the macroporous resin with moisture lower alcohol eluting, be adsorbed in total alkaloids of Folium Mori on the cation exchange resin with volatility aqueous slkali eluting;
5) drying: eluent is evaporated to dried, and drying is pulverized and promptly obtained Folium Mori total flavonoids and total alkaloids of Folium Mori respectively.
6) mix: resulting total flavones and total alkaloids are mixed, make total alkaloids and content of total flavone sum, promptly get Folium Mori extract of the present invention greater than 50%.
3, the preparation method of Folium Mori extract according to claim 2 is characterized in that: described extraction is C1-C5 with the carbon number of moisture lower alcohol, and concentration is X, 0＜X≤95%.
4, the preparation method of Folium Mori extract according to claim 3 is characterized in that: described extraction is X with the concentration of moisture lower alcohol, 0＜X≤30%.
5, the preparation method of Folium Mori extract according to claim 2 is characterized in that: it is X that described precipitate with ethanol makes the solution concentration of alcohol, 40%≤X≤90%.
6, the preparation method of Folium Mori extract according to claim 2 is characterized in that: it is X that described precipitate with ethanol makes the solution concentration of alcohol, 50≤X≤60%.
7, the preparation method of Folium Mori extract according to claim 2 is characterized in that: described flocculating agent can be one or more in gelatin, chitosan, agar, ZTCl+1, chitin and the derivant thereof.
8, the preparation method of Folium Mori extract according to claim 2 is characterized in that: described macroporous resin can be so that any one or a few is the polarity or the non-polar resin of framework material in styrene, divinylbenzene, acrylate and the methacrylate.
9, the preparation method of Folium Mori extract according to claim 8 is characterized in that: described macroporous resin is the styrene type resin.
10, the preparation method of Folium Mori extract according to claim 2 is characterized in that: described cation exchange resin can be polystyrene or macroporous ion-exchange resin.
11, the preparation method of Folium Mori extract according to claim 2 is characterized in that: described volatility alkali is the aqueous solution of 0.1%～1% ammonia, diethylamino, triethylamine, pyridine.
12, the preparation method of Folium Mori extract according to claim 11 is characterized in that: described volatility alkali is 0.5% ammonia spirit.
13, the preparation method of Folium Mori extract according to claim 2 is characterized in that: described eluting is C1-C5 with the carbon number of moisture lower alcohol, and concentration is X, 40≤X＜100%.
14, the preparation method of Folium Mori extract according to claim 13 is characterized in that: described concentration is X, 50≤X≤80%.
15, a kind of Folium Mori extract is characterized in that: any one described method prepares in this Folium Mori extract employing claim 1 to 14.
16, a kind of Folium Mori extract preparation is characterized in that: said preparation is a main active with the described Folium Mori extract of claim 15, adds the pharmaceutics acceptable auxiliary, makes the pharmaceutics acceptable forms.
17, Folium Mori extract preparation according to claim 16, it is characterized in that: described adjuvant is selected from any one or a few in starch, microcrystalline Cellulose, sucrose, dextrin, lactose, Icing Sugar, glucose, sodium chloride, vitamin C, cysteine, citric acid and the sodium sulfite.
18, Folium Mori extract according to claim 17 is characterized in that: described pharmaceutics acceptable forms is oral agents or injection, is tablet, pill, capsule, drop pill, liquid drugs injection, powder pin or transfusion.
19, a kind of application of Folium Mori extract is characterized in that: the described Folium Mori extract of claim 18 is used to prepare prevention and treats the extremely medicament of complication of diabetes.
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| CN 200510122356 CN1981814A (en) | 2005-12-15 | 2005-12-15 | Use and production for mulberry leaf in treatment of diabetes |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101780147A (en) * | 2010-03-12 | 2010-07-21 | 广西药用植物园制药厂 | Anti-inflammatory and hypoglycemic mulberry leave extract and preparation method of preparation thereof |
| CN101869605A (en) * | 2010-07-02 | 2010-10-27 | 安徽济人药业有限公司 | Method for extracting and separating mulberry leaf flavone and alkaloid composite |
| CN102228513A (en) * | 2011-06-29 | 2011-11-02 | 江苏大学 | Medicinal composition for treating diabetes or diabetic complications and preparation method thereof |
| CN101278977B (en) * | 2008-03-31 | 2012-05-30 | 广州唐百服生物科技有限公司 | Method for extracting main active components of mulberry leaf and application of its extract |
| CN102872203A (en) * | 2012-10-30 | 2013-01-16 | 广州牌牌生物科技有限公司 | Technology for synchronously producing total flavone, total alkaloid and total polysaccharide in mulberry bark |
| CN105535112A (en) * | 2015-12-29 | 2016-05-04 | 浙江省农业科学院 | Extraction technology of hypoglycemic medicinal active substances of mulberry leaves and mulberries and formula |
| CN107362200A (en) * | 2017-08-08 | 2017-11-21 | 南京中医药大学 | A kind of method that isolating alkaloids and flavones are extracted from mulberry leaf |
| CN110393738A (en) * | 2019-08-27 | 2019-11-01 | 北京五和博澳药业有限公司 | A kind of plant extraction process |
-
2005
- 2005-12-15 CN CN 200510122356 patent/CN1981814A/en active Pending
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101278977B (en) * | 2008-03-31 | 2012-05-30 | 广州唐百服生物科技有限公司 | Method for extracting main active components of mulberry leaf and application of its extract |
| CN101780147A (en) * | 2010-03-12 | 2010-07-21 | 广西药用植物园制药厂 | Anti-inflammatory and hypoglycemic mulberry leave extract and preparation method of preparation thereof |
| CN101869605A (en) * | 2010-07-02 | 2010-10-27 | 安徽济人药业有限公司 | Method for extracting and separating mulberry leaf flavone and alkaloid composite |
| CN101869605B (en) * | 2010-07-02 | 2012-05-02 | 安徽济人药业有限公司 | Method for extracting and separating mulberry leaf flavone and alkaloid composite |
| CN102228513A (en) * | 2011-06-29 | 2011-11-02 | 江苏大学 | Medicinal composition for treating diabetes or diabetic complications and preparation method thereof |
| CN102228513B (en) * | 2011-06-29 | 2013-04-17 | 江苏大学 | Medicinal composition for treating diabetes or diabetic complications and preparation method thereof |
| CN102872203A (en) * | 2012-10-30 | 2013-01-16 | 广州牌牌生物科技有限公司 | Technology for synchronously producing total flavone, total alkaloid and total polysaccharide in mulberry bark |
| CN105535112A (en) * | 2015-12-29 | 2016-05-04 | 浙江省农业科学院 | Extraction technology of hypoglycemic medicinal active substances of mulberry leaves and mulberries and formula |
| CN107362200A (en) * | 2017-08-08 | 2017-11-21 | 南京中医药大学 | A kind of method that isolating alkaloids and flavones are extracted from mulberry leaf |
| CN110393738A (en) * | 2019-08-27 | 2019-11-01 | 北京五和博澳药业有限公司 | A kind of plant extraction process |
| CN110393738B (en) * | 2019-08-27 | 2022-09-20 | 北京五和博澳药业股份有限公司 | Plant extraction method |
| US11779041B2 (en) | 2019-08-27 | 2023-10-10 | Beijing Wehand-Bio Pharmaceutical Co., Ltd | Plant extraction method |
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