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CN1330670C - Process for extracting polygonatum polysaccharides, preparing process for medical preparation and use thereof - Google Patents

Process for extracting polygonatum polysaccharides, preparing process for medical preparation and use thereof Download PDF

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CN1330670C
CN1330670C CNB2004100228635A CN200410022863A CN1330670C CN 1330670 C CN1330670 C CN 1330670C CN B2004100228635 A CNB2004100228635 A CN B2004100228635A CN 200410022863 A CN200410022863 A CN 200410022863A CN 1330670 C CN1330670 C CN 1330670C
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polygonatum
polysaccharide
precipitate
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CN1557842A (en
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向大雄
刘韶
李焕德
李新中
朱运贵
张毕奎
龚莉
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Second Xiangya Hospital of Central South University
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Second Xiangya Hospital of Central South University
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Abstract

本发明涉及一种玉竹多糖的提取方法、药物制剂制备方法及其用途。玉竹多糖的提取方法是将玉竹生药切成小块,加放4~16倍量水,煮沸提取1-4小时,提取液过滤,残渣另加入6~12倍的水,煮沸提取1~2小时,提取液过滤,将2次提取液合并,离心处理,得上清液减压浓缩,至相对密度1.08~1.25(45-60℃),放置至室温,加入4~8倍的95%的乙醇液,搅拌静置12-48小时,分离取沉淀物,加冷蒸馏水0.5~2倍洗涤,沉淀物加热蒸馏水溶解,加入0.5~4倍量的95%乙醇沉淀,静置12~48小时,分取沉淀物,以0.5~3倍量的95%乙醇洗涤三次,弃去醇洗液,沉淀物冷冻干燥一段时间后,再在温度为60℃下真空干燥至干,取出、粉碎,得白色粉末。玉竹多糖药物制剂的制备方法是将制得的玉竹多糖加入适当的辅料,可以制备成片剂、胶囊剂、颗粒剂、口含片、咀嚼片、分散片类的固体剂型,也可以制备成口服液、合剂类的液体剂型。玉竹多糖药物制剂用于降血糖、特别是降血脂,对高血脂及高血糖病人,可以起到降血糖和降血脂作用。The invention relates to a method for extracting polysaccharides from polygonatum polysaccharides, a method for preparing pharmaceutical preparations and uses thereof. The extraction method of Polygonatum Polysaccharides is to cut Polygonatum polysaccharide into small pieces, add 4 to 16 times the amount of water, boil and extract for 1-4 hours, filter the extract, add 6 to 12 times of water to the residue, boil and extract for 1 to 4 hours. After 2 hours, filter the extract, combine the two extracts, and centrifuge to obtain the supernatant concentrated under reduced pressure to a relative density of 1.08-1.25 (45-60°C), place it at room temperature, and add 4-8 times 95% the ethanol solution, stir and stand for 12-48 hours, separate the precipitate, add 0.5 to 2 times of cold distilled water to wash, dissolve the precipitate with distilled water, add 0.5 to 4 times the amount of 95% ethanol to precipitate, and stand for 12 to 48 hours , separate the precipitate, wash three times with 0.5 to 3 times the amount of 95% ethanol, discard the alcohol washing solution, freeze-dry the precipitate for a period of time, and then dry it in vacuum at a temperature of 60°C until dry, take it out, and crush it to obtain White powder. The preparation method of the Polygonatum polysaccharide pharmaceutical preparation is to add the obtained Polygonatum polysaccharide into appropriate excipients, which can be prepared into solid dosage forms such as tablets, capsules, granules, buccal tablets, chewable tablets, and dispersible tablets, and can also be prepared Liquid dosage form of oral liquid and mixture. Polygonatum polysaccharide pharmaceutical preparations are used to lower blood sugar, especially blood fat, and can lower blood sugar and blood fat in patients with hyperlipidemia and hyperglycemia.

Description

The extracting method of fragrant solomonseal rhizome polyoses, preparation of pharmaceutical formulations method and uses thereof
Technical field
The present invention relates to extracting method, preparation of pharmaceutical formulations method of a kind of fragrant solomonseal rhizome polyoses and uses thereof.
Background technology
Cardiovascular disorder has become one of main disease that influences China's people ' s health at present, hyperlipidaemia is a kind of common cardiovascular disorder, it is again the important paathogenic factor of atherosclerosis (AS) and coronary heart disease, hypolipidemic can delay to rotate with Partial Inverse the progress of pulse atherosclerosis focus, prevent plaque rupture and improve endothelial function, and obviously reduce the M ﹠ M of cardiovascular diseases.Lipid lowering agent can be divided into by its effect at present: the medicine that 1. mainly reduces blood cholesterol: comprise cholic acid complexing agent, hydroxyl first pentanedioyl acyl coenzyme (HMG-CoA) reductase inhibitor, steroid derivative, sitosterol etc.; 2. blood TG medicine falls: comprise nicotinic acid class, fibric acid, polyunsaturated fatty acid class, mucopolysaccharide and polyose etc.; 3. the medicine that has lipoid peroxidization resistant; 4. other lipid lowering agents.Wherein first kind medicine has peculiar smell or gastrointestinal reaction mostly and takes inconvenience, and costs an arm and a leg, and takes the absorption that can hinder fat-soluble A, D, E, K for a long time, uses not extensive.At present clinically widespread use be statins, belong to the HMG-CoA reductase inhibitor, transfer the blood fat determined curative effect, but prolonged application has hepatotoxicity and other side effects.In addition; nicotinic acid class, mucopolysaccharide and polyose Antiatherosclerosis medicine; as heparin; have effects such as the blood fat of accent, antithrombotic, protection arterial endothelium, inhibition arterial wall smooth muscle cell hyperplasia; but because of its blood coagulation resisting function strong; can cause the hemorrhage untoward reaction of Denging, and transformation period weak point in the body, limited its clinical application.Steroid derivative, sitosterol, fibric acid, polyunsaturated fatty acid class, probucol, vitamin medicaments then lack clinical widely support.Chinese medicine is very promising aspect the treatment of hyperlipidemia, forms unusually from improving lipoprotein metabolism and lipoprotein, and Chinese medicine has the pharmacological action characteristics that chemical synthetic drug does not possess.Hyperlipidaemia belongs to the category of traditional Chinese medicine " phlegm ", and that the rules of treatment have promoting digestion and removing indigestion, invigorating spleen to remove dampness, Wen Yangyi unit, the phlegm that slits is dispelled is turbid, the clearing liver cholagogic, protect that the moonization is turbid, diuresisization is turbid, lead to internal organs and wash turbid, the stagnation resolvation fat etc. of dispelling.The single reducing blood-fat Chinese medicine of having reported has genseng, radix bupleuri, the root of large-flowered skullcap, gynostemma pentaphylla, the root of bidentate achyranthes, garlic, hawthorn etc., and compound hypolipidemic Chinese medicine has dachaihu decoction, Herba Sidae Rhombifoliae soup etc.Gone on the market Chinese medicine and prescribed preparation has SHANZHAJING JIANGZHI PIAN, Xuezhikang etc., but effective constituent is indeterminate, lacks strict contrast and pharmacological research foundation, and mechanism is unclear, has hindered the further investigation of lipid lowering agent.
Radix polygonati officinalis Polygonatum odoratum (Mill.) Druce is the traditional Chinese medicine of China, and the beginning is stated from Shennong's Herbal, classifies as top gradely, and it derives from the dry rhizome of liliaceous plant radix polygonati officinalis.Main steroidal saponin, polysaccharide, flavones and the anthraquinone class chemical ingredients of containing.Nourishing YIN to relieve dryness is arranged, the function that promotes the production of body fluid to quench thirst.Rats gavaged radix polygonati officinalis preserved material, the hyperglycemia that suprarenin, glucose and tetraoxypyrimidine are caused all has restraining effect.Water-soluble part and propyl carbinol part has obvious restraining effect to U-9889 hyperglycemia mouse in the radix polygonati officinalis methanol extract, infers relevant with the liver glycogen glycolysis.Gavage the radix polygonati officinalis decoction for the experimental hyperlipidemia rabbit or can prevent injection liquid 3 to April blood fat to raise and alleviate atherosclerotic plaque formation, triacylglycerol, cholesterol, beta Lipoprotein are descended in the treatment group.Our experimental study shows that first isolating fragrant solomonseal rhizome polyoses can significantly reduce the blood lipid level of experimental hyperlipidemia animal from the radix polygonati officinalis aqueous extract.
Bibliographical information (see the Yu Jing chief editor. modern Chinese herbal medicine research, the Xueyuan Press, 1998) radix polygonati officinalis contains radix polygonati officinalis mucopolysaccharide (Odoratan), and it consists of D-fructose (D-Fructose), D-seminose (D-Mannose), D-glucose (D-Glucose) and D-galacturonic acid (D-Galacluronicacid); Mol ratio is 6: 3: 1: 1.5, other contains radix polygonati officinalis Polylevulosan (Polygonatum-fructan) A, B, C, D, sugar consist of fructose and glucose.
Polysaccharide has different physiological roles, and cytotoxicity is extremely low.Thereby polysaccharide medicine will have more wide prospect as biological response modifier.At present, from natural product or tunning, separate the preparation polysaccharide, the general using polysaccharide is water-soluble, diluted acid, alkali or salts solution, and be insoluble to alcohol, ether, the characteristics of acetone and other organic solvent, with the low polar organic solvent degreasing decoloring element of crude drug, in order to water the solution extraction polysaccharide of main body with residue then, be cold water, hot water, diluted acid, alkali or salts solution extract, and after extracting solution concentrates, use earlier trichoroacetic acid(TCA), Freon 113 method or Sevag method are removed foreign protein, small molecular weight impurity is removed in dialysis then, concentrates the back freeze-drying or with the methyl alcohol or the ethanol of equivalent or several times, the acetone and other organic solvent precipitation promptly obtains the polysaccharide product.Refining ion-exchange, preparation property zone electrophoresis, gel-filtration, ultrafiltration and preparation property high pressure liquid chromatography methods of adopting of polysaccharide more.Above-mentioned polyoses producing method has the following disadvantages: 1, have darker yellow, brown, and be difficult to decolouring; 2, the complicated time of leaching process is long, cost is high, and the large-scale production difficulty is big; 3, in extracting treating process, used organic solvent; 4, contain monose mostly.In a word, above method is difficult for obtaining highly purified polysaccharide.
Simultaneously, the research of radix polygonati officinalis is also had the following disadvantages: 1, more to the Chinese medicine compound prescription research that contains radix polygonati officinalis, few to single radix polygonati officinalis research; Though the report of 2 and blood fat hypoglycemic relevant for radix polygonati officinalis, the activeconstituents or the activeconstituents group that do not understand the radix polygonati officinalis pharmacological action.3, do not see that fragrant solomonseal rhizome polyoses extracts, preparation method's report; 4, radix polygonati officinalis mainly is enriching yin and nourishing kidney in traditional traditional Chinese medical science, in Chinese medicine compound prescription, can be used for hypoglycemic, relevant for the oral report that blood sugar is fallen after rising of radix polygonati officinalis medicinal extract, and the hyperglycemia that medicinal extract causes suprarenin, glucose, tetraoxypyrimidine has inhibiting report (to see the clear an ancient unit of weight of horse, the Wang Shuling chief editor. the clinical practice Chinese materia medica, Jiangxi science tech publishing house, 2002.), but do not see hypoglycemic, the bibliographical information of reducing blood-fat particularly of fragrant solomonseal rhizome polyoses; 5, do not see report about fragrant solomonseal rhizome polyoses composition, molecular weight and pharmacological action relation.The fragrant solomonseal rhizome polyoses molecular weight of the present invention's preparation is 3000~40, and 000 has hypoglycemic and reducing blood lipid, and purity of polysaccharide height (more than 98%).
Summary of the invention
Technical problem to be solved by this invention is the characteristic according to the contained polysaccharide of radix polygonati officinalis, and exploitation is the former extracting method of expecting the fragrant solomonseal rhizome polyoses that is applicable to industrialized production of high purity fragrant solomonseal rhizome polyoses, preparation of pharmaceutical formulations method and uses thereof with the radix polygonati officinalis crude drug.
The technical scheme that solution the technology of the present invention problem is adopted is that the extracting method of this fragrant solomonseal rhizome polyoses has following two kinds:
1. be that the radix polygonati officinalis crude drug is cut into small pieces, place 4~16 times of water gagings, boil and extracted 1-4 hour, extracting liquid filtering, residue add 6~12 times water in addition, boil and extract 1~2 hour, extracting liquid filtering, No. 2 extracting solutions are merged, and centrifugal treating gets the supernatant liquor concentrating under reduced pressure, to relative density 1.08~1.25 (45-60 ℃), be placed to room temperature, add 4~8 times 95% ethanol liquid, stir and left standstill 12-48 hour, separate taking precipitate, add 0.5~2 times of washing of cold distilled water, throw out heating dissolved in distilled water, 95% ethanol sedimentation of 0.5~4 times of amount of adding, left standstill 12~48 hours, divide taking precipitate,, discard pure washing lotion with 95% washing with alcohol of 0.5~3 times of amount three times, after throw out lyophilize for some time, be that 60 ℃ of following vacuum-dryings are to doing taking-up in temperature again, pulverize, get white powder.
2. ultrafiltration process: the extracting solution that gets relative density 1.08~1.25 (45-60 ℃) by 1 legal system is placed room temperature, and adding 95% medical ethanol to determining alcohol is 80%, places 8-16 hour (spending the night).Abandoning supernatant, with the dissolving of pure hypostasis water, be made into 1: 10 (pure hypostasis: suspension water), centrifugal, remove insolubles.Be that 40,000 Hollow Fiber Ultrafiltration post is removed relative molecular weight greater than 40,000 macromolecular substance such as natural gum with the relative molecular weight cutoff value earlier, flow velocity is 20ml/min, and pressure is 0.15 * 10 6Pa; Be that 3000 hollow fiber membrane ultrafiltration devices are removed relative molecular weight less than 3000 small-molecule substance with the relative molecular weight cutoff value again, flow velocity is 15ml/min, and pressure is 0.1 * 10 6Pa.Merge, concentrate relative molecular weight 3000~40,000 fractions, freezing, dry, get fragrant solomonseal rhizome polyoses.
The fragrant solomonseal rhizome polyoses that obtains with method of the present invention is white powder, and is water-soluble, is soluble in hot water especially, is insoluble to the ethanol and the acetone of high density, and the Molish reaction becomes positive with anthrone-strong sulfuric acid response, illustrate to contain polysaccharide in the white powder; Ninhydrin reaction is negative, and no protein is described.Do not contain monose after testing, molecular weight is that 3000~40,000 fragrant solomonseal rhizome polyoses becomes to hive off, and polysaccharide content is more than 98%.
The preparation method of fragrant solomonseal rhizome polyoses pharmaceutical preparation: the above-mentioned fragrant solomonseal rhizome polyoses that makes is added suitable auxiliary material, can be prepared into solid dosages such as tablet, capsule, granule, buccal tablet, chewable tablet, dispersible tablet class, also can be prepared into liquid dosage forms such as oral liquid, mixture class.
The preparation prescription and the technology of pharmaceutical preparation:
Capsule prescription (weight part): 50~300 parts of fragrant solomonseal rhizome polyoses
50~200 parts of micropowder silica gels
50~200 parts in dextrin
Micropowder silica gel, dextrin mixing with recipe quantity join in the polysaccharide of recipe quantity again, mixing, and vacuum-drying (vacuum tightness 0.08-0.09Mpa) is pulverized, mixing, encapsulated (zero~No. 2) get 1000 approximately.Every capsules weighs 0.15~0.7g, contains fragrant solomonseal rhizome polyoses 0.05 g~0.3g.
Tablet formulation (weight part):
50~300 parts of fragrant solomonseal rhizome polyoses
30~60 parts of hypromelloses (K4M)
50~240 parts of lactose
The 3% hypromellose aqueous solution is an amount of
1~5 part of Magnesium Stearate
Every heavy 0.13~0.60g, every contains fragrant solomonseal rhizome polyoses 0.05g~0.3g
Making step comprises in detail:
A, get fragrant solomonseal rhizome polyoses, lactose, hypromellose, Magnesium Stearate respectively and cross 120 mesh sieves, at 105 ℃ of baking 1h, standby.
B, take by weighing main ingredient, lactose, hypromellose by formula rate, thorough mixing is even;
C, add the roughly 3% hypromellose aqueous solution of recipe quantity, thorough mixing is even, the system softwood;
D, 16 mesh sieves are granulated, and 60 ℃ of dryings with the whole grain of order, add the Magnesium Stearate mixing, compressing tablet;
E, quality inspection, packing, signature, promptly.
Purposes of the present invention and service requirements: the present invention has extracted molecular weight from the radix polygonati officinalis medicinal material be 3000~40,000 fragrant solomonseal rhizome polyoses becomes to hive off, purity is more than 98%, above-mentioned polysaccharide is added suitable auxiliary material, solid dosages such as tablet, capsule, granule, buccal tablet, chewable tablet, dispersible tablet can be prepared into, also liquid dosage forms such as oral liquid, mixture can be prepared into.Hypoglycemic, particularly reducing blood-fat that the fragrant solomonseal rhizome polyoses medicament is used for to hyperlipidemia and hyperglycemia patient, can be played hypoglycemic and reducing blood lipid.Above preparation is all with the oral way administration.Usage and consumption: oral, take fragrant solomonseal rhizome polyoses 0.1~0.5g, three times on the one at every turn.
The present invention from radix polygonati officinalis separation and Extraction fragrant solomonseal rhizome polyoses, and it is prepared into oral administration solid or liquid preparation by certain requirement, can reduce blood sugar and the blood fat of hyperglycemia, hyperlipidemia animal, be applicable to diabetic subject and hyperlipemic patients.The present invention has confirmed the above-mentioned beneficial effect of the fragrant solomonseal rhizome polyoses of extraction with experimentation on animals described below.
(1) experimental study of fragrant solomonseal rhizome polyoses effect for reducing fat
1, materials and methods
1.1 laboratory animal
30 of purebred new zealand rabbits, half and half, 5 monthly age of male and female, body weight (2.4 ± 0.2) kg.Divide 5 groups at random: 3 groups of Xuezhikang group, Zocor group, 1 group of radix polygonati officinalis, 2 groups of radix polygonati officinalis and radix polygonati officinalis, 6 every group.
1.2 method
1.2.1 the foundation of hyperlipemia model adds 5% lard and 0.5% cholesterol nutrition purposes, especially for feeding animals with conventional feed, serum lipid concentrations was measured in fasting in 10 hours after 10 days, treat to give lipopenicillinase and experiment medicine after it has significant blood fat to raise, and keep high fat diet to experiment and finish.
1.2.2 medication Xuezhikang group: 300mgkg -1D -1Xuezhikang adds the dissolving of 40ml tap water, divides two inferior to feeding after the animal feed; Zocor group: 5mgkg -1D -1Zocor is dissolved in the 20ml tap water, once feeds after the animal feed; 1,2,3 groups of radix polygonati officinalis: respectively with 0.2g, 0.4g, 0.4gkg -1D -1Fragrant solomonseal rhizome polyoses be dissolved in the 40ml tap water, divide two inferior to feeding after the animal feed.
1.2.3 select 12 animal fasting to measure its blood-sugar content in 10 hours at random before the lipid determination experiment, to test last fasting and checked whole laboratory animal lipids contents in 10 hours, measuring method is the hour method.
1.2.4 all animals is put to death in aorta form and om observation experiment back, get its aorta and carry out general form and observe, and get its part aorta with 10% formaldehyde fixed after the paraffin look bury section, HE dyes and om observation.
1.3 statistical treatment
Experimental data represents that with x ± s statistical study is q check and a plurality of sample χ relatively that compares in twos between paired t-test, a plurality of mean 2Check.
2 results
2.1 animal lipid changes (table 1) after the hypercholesterolemia diet
Can find out that from table 1 after the hypercholesterolemia diet was fed, experimental animal CHO, LDL, Lp (a) all significantly raise, and have formed tangible hyperlipidaemia.
2.2 respectively organize the Blood Lipid (table 2) before and after the laboratory animal medication
Can find out that from table 2 blood fat CHO, LDL, Lp (a) concentration significantly reduce before and after 3 groups of treatments of fragrant solomonseal rhizome polyoses; Except that Lpa) descend, each index does not all have noticeable change before and after 1,2 groups of treatments of radix polygonati officinalis.
2.3 each treated animal Blood Lipid of experiment back is (table 3) relatively
The variation of serum lipid concentrations does not have significant difference between each treatment group of table 3 expression experiment end, illustrates that each group all has reducing blood lipid.
2.4 the situation of atherosclerosis of aorta
Have the visible a small amount of lipid striped of a routine sample aorta to form 2.4.1 general form is observed the Xuezhikang group, surplus laboratory animal there is no tangible lipid striped or atheromatous plaque forms.
2.4.2 om observation part laboratory animal aortic tunica intima sees that foam inner membrance in various degree forms, it the results are shown in Table 4.
Can find out that from table 4 fragrant solomonseal rhizome polyoses group aortic tunica intima foam cell forms and significantly is less than Xuezhikang group, Zocor group (P<0.05), and be dose-dependence between each group of fragrant solomonseal rhizome polyoses group.
(2) experimental study of fragrant solomonseal rhizome polyoses blood sugar reducing function
1, materials and methods
1.1 laboratory animal
24 of BALB/C mice, at half and half, 2 monthly age of male and female, body weight (25.2 ± 2.4) g divides 4 groups: 1,2 groups of glipizide groups, TANGMAIKANG group, fragrant solomonseal rhizome polyoses, 6 every group at random.
1.2 method
1.2.1 the mouse peritoneal injection urea of setting up of diabetes model is helped rhzomorph 40mgkg -1D -1, continuous 5 days.Fasting was cut tail in 6 hours and is measured its blood-sugar content after 10 days, had treated to contrast and test medicine behind the obvious blood sugar increasing.
1.2.2 medication glipizide group: 8mgkg -1D -1Glipizide adds physiological saline 0.5ml dissolving, irritates stomach once a day and gives; TANGMAIKANG group: 12.5gkg -1D -1TANGMAIKANG adds the 1ml physiological saline solution, divides secondary to irritate stomach and gives, and 1,2 groups of fragrant solomonseal rhizome polyoses are respectively with 0.2g, 1gkg -1.d -1Fragrant solomonseal rhizome polyoses dissolve in physiological saline 1ml, divide secondary to irritate stomach and give.
1.2.3 select 3 animal fasting to cut tail after 6 hours at random to measure its blood-sugar content for every group before the detection method experiment, the same method test experience animal blood glucose content behind the injection streptozotocin is tested last fasting and was got the socket of the eye arterial blood in 6 hours and measure blood sugar and HbA 1CAmount.Detection method is respectively glucose oxidase method and chromatography column method.
1.3 statistical treatment
Experimental data represents that with x ± s statistical study is relatively q check in twos between paired t-test and a plurality of mean.
2 results
2.1 change of blood sugar (table 5) behind the laboratory animal injection streptozotocin
Can find out that from table 5 fasting plasma glucose significantly raises behind the experiment mice injection streptozotocin, has formed typical experimental diabetes disease model.
2.2 respectively organize laboratory animal treatment front and back change of blood sugar (table 6)
Can find out that from table 6 after fragrant solomonseal rhizome polyoses and glipizide treatment, FBS has significant differences (p<0.01), TANGMAIKANG group treatment back FBS decline no significance meaning (P>0.05).
2.3 experiment back each treated animal FBS and HbA 1CThe variation (table 7) of content
Can find out that from table 7 hypoglycemic effect of each treatment group does not relatively have significance meaning (P>0.05); But radix polygonati officinalis reduces HbA for 1,2 groups 1cEffect and glipizide group and TANGMAIKANG group meaning (P<0.01) that highly significant is relatively arranged.
Embodiment
The invention will be further described below in conjunction with embodiment.
Specific embodiment 1
Dry radix polygonati officinalis crude drug 9Kg is cut into small pieces, and places 10 times of water gagings, boils and extracts 1 hour, extracting liquid filtering, the dregs of a decoction add 10 times water in addition, boil and extract 1 hour, extracting liquid filtering merges centrifugal treating with No. 2 extracting solutions, get the supernatant liquor concentrating under reduced pressure,, be placed to room temperature to relative density 1.15 (50 ℃), it is 80% that the ethanol liquid of adding 95% makes it to contain the alcohol amount, stirring was left standstill 12 hours, separated taking precipitate, added 1.5 times of washings of cold distilled water, throw out heating dissolved in distilled water, adding 95% ethanol, to make it to contain alcohol amount be 70%, left standstill 12 hours, divides taking precipitate, with 95% washing with alcohol of 3 times of amounts three times, discard pure washing lotion, the throw out lyophilize is that 60 ℃ of following vacuum-dryings are to doing in temperature again after 12 hours, take out, pulverize, get white powder 340 grams, yield 3.8%, polysaccharide content is 98.6%.
Specific embodiment 2
Dry radix polygonati officinalis crude drug 10Kg is cut into small pieces, place 10 times of water gagings, boil and extracted 1 hour, extracting liquid filtering, the dregs of a decoction add 10 times water in addition, boil and extracted 1 hour, extracting liquid filtering merges No. 2 extracting solutions, centrifugal treating, get the supernatant liquor concentrating under reduced pressure,, be placed to room temperature to relative density 1.15 (50 ℃), it is 80% that the ethanol liquid of adding 95% makes it to contain the alcohol amount, left standstill 12 hours, and separated taking precipitate, add 1.5 times of washings of cold distilled water, with pure hypostasis water dissolving, be made into 1: 10 (pure hypostasis: suspension water), centrifugal, remove insolubles.Be that 40,000 Hollow Fiber Ultrafiltration post is removed relative molecular weight greater than 40,000 macromolecular substance such as natural gum with the relative molecular weight cutoff value earlier, flow velocity is 20ml/min, and pressure is 0.15 * 10 6Pa; Be that 3000 hollow fiber membrane ultrafiltration devices are removed relative molecular weight less than 3000 small-molecule substance with the relative molecular weight cutoff value again, flow velocity is 15ml/min, and pressure is 0.1 * 10 6Pa.Merge, concentrate relative molecular weight 3000~40,000 fractions, freezing, dry, get fragrant solomonseal rhizome polyoses 400 grams, yield 4.0%, polysaccharide content is 98.5%.
Specific embodiment 3
Capsule preparation: fragrant solomonseal rhizome polyoses 50g
Micropowder silica gel 50g
Dextrin 50g
Can make 1000 approximately
Micropowder silica gel, dextrin mixing with recipe quantity join in the polysaccharide of recipe quantity again, mixing, and vacuum-drying (vacuum tightness 0.08-0.09Mpa) is pulverized, mixing, encapsulated (No. 2) get 1000 approximately.The heavy 0.15g of every capsules, every contains fragrant solomonseal rhizome polyoses 0.05g.
Specific embodiment 4
Capsule preparation: fragrant solomonseal rhizome polyoses 300g
Micropowder silica gel 200g
Dextrin 200g
Make 1000 approximately
Micropowder silica gel, dextrin mixing with recipe quantity join in the polysaccharide of recipe quantity again, mixing, and vacuum-drying (vacuum tightness 0.08-0.09Mpa) is pulverized, mixing, encapsulated (No. zero) gets 1000 approximately.The heavy 0.7g of every capsules contains fragrant solomonseal rhizome polyoses 0.3g.
Specific embodiment 5
Tablet formulation, technology:
Fragrant solomonseal rhizome polyoses 50g
Hypromellose (K4M) 30g
Lactose 50g
The 3% hypromellose aqueous solution is an amount of
Magnesium Stearate 1g
Make 1000 altogether, every heavy 0.13g, every contains fragrant solomonseal rhizome polyoses 0.05g.
The detail operations step
1, get fragrant solomonseal rhizome polyoses, lactose, hypromellose, Magnesium Stearate respectively and cross 120 mesh sieves, at 105 ℃ of baking 1h, standby.
2, the prescription ratio takes by weighing main ingredient, lactose, hypromellose, and thorough mixing is even;
3, add the roughly 3% hypromellose aqueous solution of recipe quantity, thorough mixing is even, the system softwood;
4,16 mesh sieves are granulated, and 60 ℃ of dryings with the whole grain of order, add the Magnesium Stearate mixing, compressing tablet;
5, quality inspection, packing, signature, promptly.
Specific embodiment 6
Tablet formulation, technology:
Fragrant solomonseal rhizome polyoses 300g
Hypromellose (K4M) 60g
Lactose 240g
The 3% hypromellose aqueous solution is an amount of
Magnesium Stearate 5g
Make 1000 altogether, every heavy 0.60g, every contains fragrant solomonseal rhizome polyoses 0.3g
The detail operations step
1, get main ingredient, lactose, hypromellose, Magnesium Stearate respectively and cross 120 mesh sieves, at 105 ℃ of baking 1h, standby.
2, take by weighing main ingredient, lactose, hypromellose in the prescription ratio, thorough mixing is even;
3, add the roughly 3% hypromellose aqueous solution of recipe quantity, thorough mixing is even, the system softwood;
4,16 mesh sieves are granulated, and 60 ℃ of dryings with the whole grain of order, add the Magnesium Stearate mixing, compressing tablet;
5, quality inspection, packing, signature, promptly.
Usage and consumption: this product is oral, takes fragrant solomonseal rhizome polyoses 0.1~0.5g at every turn.
Animal lipid changes after table 1 high fat diet
n TG(mmol/L) CHO(mmol/L) HDL(mmol/L) LDL(mmol/L) Lp(a)(mg/L)
Before the high fat diet 12 0.68±0.23 1.38±0.27 0.63±0.13 0.46±0.20 163.7±25.3
After the high fat diet 30 0.41±0.12 11.32±1.34 * 0.91±0.14 9.18±124 * 681.5±124.3 *
*P<0.01
Blood Lipid before and after each experimental group treatment of table 2
n TG CHO HDL LDL Lp(a)
Before the treatment After the treatment Before the treatment After the treatment Before the treatment After the treatment Before the treatment After the treatment Before the treatment After the treatment
The Xuezhikang group 6 0.39±0.67 0.27±0.07 11.45±1.67 8.33±5.12 0.85±0.14 1.14±0.36 10.25±2.12 7.31±5.25 752.4±111.3 37.4±10.5 *
The Zocor group 6 0.46±0.15 0.37±0.10 10.73±1.54 6.41±3.66 0.81±0.08 0.97±0.22 9.87±1.41 5.24±3.52 727.1±125.3 477+12.8 *
1 group of radix polygonati officinalis 6 0.48±0.08 0.53±0.12 11.21±1.21 12.4±5.84 0.78±0.08 0.66±0.21 9.48±1.32 10.36±5.48 613.5±137.3 44.7+8.6 *
2 groups of radix polygonati officinalis 6 0.54±0.06 0.41±0.23 10.92±1.38 6.83±3.87 0.84±0.14 1.46±0.27 9.56±1.24 5.27±3.13 652.8±134.8 49.6+2.4 *
3 groups of radix polygonati officinalis 6 0.51±0.06 0.69±0.31 11.71±1.75 5.42±1.63 * 0.87±0.12 1.62±0.43 10.63±1.48 4.51±1.34 * 640.5±107.8 35.8+13.1 *
It is relatively preceding with treatment, *P<0.01, P<0.05
Each treated animal Blood Lipid of table 3 experiment back relatively
n TG CHO HDL LDL Lp(a)
The Xuezhikang group 6 0.27±0.07 8.33±5.12 1.14±0.36 7.31±5.25 37.4±10.5
The Zocor group 6 0.37±0.10 6.41±3.66 0.97±0.22 5.24±3.52 47.7±12.8
1 group of radix polygonati officinalis 6 0.53±0.12 12.47±5.84 0.66±0.21 10.36±5.48 44.7±8.6
2 groups of radix polygonati officinalis 6 0.41±0.23 6.83±3.87 1.46±0.27 5.27±3.13 49.6±12.4
3 groups of radix polygonati officinalis 6 0.69±0.31 5.42±1.63 1.62±0.43 4.51±1.34 35.8±12.1
P all>0.05
Table 4 aortic tunica intima foam cell forms situation
Grouping The test samples number Add up to Incidence
There is foam cell to form The non-foam cell forms
The Xuezhikang group 5 1 6 83.3%
The Zocor group 3 3 6 50%
1 group of radix polygonati officinalis 2 4 6 33.3%
2 groups of radix polygonati officinalis 1 5 6 16.7% *
3 groups of radix polygonati officinalis 1 5 6 16.7% *
Compare for 1 group with Xuezhikang group, Zocor group, radix polygonati officinalis, *P<0.05
Table 5 experimental diabetic animal change of blood sugar
n FBS(mmol/L) The P value
Before the injection 12 5.83±0.44 0.001
After the injection 24 9.14±0.82
Change of blood sugar before and after each experimental group medication of table 6
n FBS(mmol/L) The P value
Before the treatment After the treatment
Glipizide group 6 8.71±0.54 6.12±0.93 0.001
TANGMAIKANG group 6 8.21±0.37 7.47±2.03 0.587
1 group 6 of radix polygonati officinalis 9.22±0.61 6.17±0.94 0.001
2 group 6 of radix polygonati officinalis 8.84±0.46 7.37±0.45 0.005
Respectively organize FBS, HbA after table 7 experiment 1CContent
n FBS(mmol/L) HbA 1C(%)
The glipizide group 6 6.18±0.87 * 3.08±0.36
The TANGMAIKANG group 6 7.52±2.18 * 3.23±0.16
1 group of radix polygonati officinalis 6 6.33±1.12 * 2.31±0.33
2 groups of radix polygonati officinalis 6 7.25±0.38 * 1.94±0.27
*Compare P>0.05 between each group
△ and glipizide group and TANGMAIKANG group compare, P<0.01

Claims (6)

1、一种玉竹多糖的提取方法,其特征在于将玉竹生药切成小块,加放4~16倍量水,煮沸提取1~4小时,提取液过滤,残渣另加入6~12倍的水,煮沸提取1~2小时,提取液过滤,将2次提取液合并,离心处理,得上清液减压浓缩,至45~60℃时的相对密度1.08~1.25,放置至室温,加入4~8倍的95%的乙醇液,搅拌静置12~48小时,分离取沉淀物,加冷蒸馏水0.5~2倍洗涤,沉淀物加热蒸馏水溶解,加入0.5~4倍量的95%乙醇沉淀,静置12~48小时,分取沉淀物,以0.5~3倍量的95%乙醇洗涤三次,弃去醇洗液,沉淀物冷冻干燥一段时间后,再在温度为60℃下真空干燥至干,取出、粉碎,得白色粉末。1. A method for extracting Polygonatum Polysaccharides, which is characterized in that cutting Polygonatum Polygonatum into small pieces, adding 4 to 16 times the amount of water, boiling and extracting for 1 to 4 hours, filtering the extract, and adding 6 to 12 times the residue boiled and extracted for 1-2 hours, the extract was filtered, the two extracts were combined, centrifuged, the supernatant was concentrated under reduced pressure, and the relative density at 45-60°C was 1.08-1.25, placed at room temperature, added 4-8 times of 95% ethanol solution, stirring and standing for 12-48 hours, separate the precipitate, add 0.5-2 times of cold distilled water to wash, heat the precipitate to dissolve in distilled water, add 0.5-4 times of 95% ethanol to precipitate , stand still for 12-48 hours, separate the precipitate, wash three times with 0.5-3 times the amount of 95% ethanol, discard the alcohol washing solution, freeze-dry the precipitate for a period of time, and then vacuum-dry the precipitate at a temperature of 60°C to Dry, take out and crush to get white powder. 2、一种玉竹多糖的提取方法,其特征在于将玉竹生药切成小块,加放4~16倍量水,煮沸提取1~4小时,提取液过滤,残渣另加入6~12倍的水,煮沸提取1~2小时,提取液过滤,将2次提取液合并,离心处理,得上清液减压浓缩,至45-60℃时的相对密度1.08~1.25的提取液放置室温,加95%医用乙醇至醇浓度为80%,放置8-16个小时,弃去上清液,将醇沉物用水溶解,配成醇沉物∶水=1∶10的混悬液,离心,除去不溶物,先用相对分子量截留值为4万的中空纤维超滤柱除去相对分子量大于4万的树胶大分子物质,流速为20ml/min,压力为0.15×106Pa:再用相对分子量截留值为3000中空纤维超滤器除去相对分子量小于3000的小分子物质,流速为15ml/min,压力为0.1×106Pa,合并、浓缩相对分子量3000~4万馏份,冷冻、干燥,得玉竹多糖。2. A method for extracting polygonatum polysaccharides, which is characterized in that the crude drug Polygonatum polysaccharides is cut into small pieces, 4 to 16 times the amount of water is added, the extraction is boiled for 1 to 4 hours, the extract is filtered, and the residue is added 6 to 12 times more water, boiled for 1-2 hours, the extract was filtered, the two extracts were combined, centrifuged, the supernatant was concentrated under reduced pressure, and the extract with a relative density of 1.08-1.25 at 45-60°C was placed at room temperature. Add 95% medical ethanol until the alcohol concentration is 80%, leave it for 8-16 hours, discard the supernatant, dissolve the alcohol precipitate in water, make a suspension of alcohol precipitate: water=1:10, centrifuge, To remove insoluble matter, first use a hollow fiber ultrafiltration column with a relative molecular weight cut-off value of 40,000 to remove gum macromolecules with a relative molecular weight greater than 40,000, with a flow rate of 20ml/min and a pressure of 0.15×10 6 Pa: The value is 3000 hollow fiber ultrafilters to remove small molecular substances with a relative molecular weight less than 3000. The flow rate is 15ml/min and the pressure is 0.1×10 6 Pa. Merge and concentrate fractions with a relative molecular weight of 3000 to 40,000, freeze and dry to obtain jade Bamboo polysaccharides. 3、根据权利要求1或2所述的玉竹多糖的提取方法所制得的玉竹多糖,其特征在于为白色粉末,溶于水,不溶于高浓度的乙醇和丙酮,Molish反应和蒽酮一浓硫酸反应呈阳性,说明白色粉末中含多糖:茚三酮反应为阴性,说明无蛋白质,经检测不含单糖,分子量为3000~40,000的玉竹多糖成分群,多糖含量为98%以上。3. Polygonatum polysaccharide obtained by the polysaccharide extraction method according to claim 1 or 2 is characterized in that it is a white powder, soluble in water, insoluble in high concentrations of ethanol and acetone, Molish reaction and anthrone A concentrated sulfuric acid reaction is positive, indicating that the white powder contains polysaccharides; ninhydrin reaction is negative, indicating that there is no protein, no monosaccharides after testing, polysaccharide components of Polygonatum polysaccharides with a molecular weight of 3000-40,000, and the polysaccharide content is more than 98% . 4、一种采用权利要求3所述的玉竹多糖用于制备药物制剂的方法,其特征在于胶囊剂重量份配方:4. A method for preparing pharmaceutical preparations by using Polygonatum polysaccharide according to claim 3, characterized in that the formula in weight parts of capsules: 玉竹多糖  50~300份Polygonatum Polysaccharide 50~300 parts 微粉硅胶  50~200份Micropowder silica gel 50~200 parts 糊精    50~200份Dextrin 50~200 parts 将处方量的微粉硅胶、糊精混匀,再加入到处方量的多糖中,混匀,真空干燥,真空度0.08-0.09Mpa,粉碎,混匀,装胶囊,每粒胶囊重0.15~0.7g,含玉竹多糖0.05g~0.3g。Mix the prescription amount of micro-powder silica gel and dextrin, then add it to the prescription amount of polysaccharide, mix well, vacuum dry at a vacuum degree of 0.08-0.09Mpa, crush, mix well, and pack into capsules, each capsule weighs 0.15-0.7g , containing Polygonatum polysaccharide 0.05g ~ 0.3g. 5、一种采用权利要求3所述的玉竹多糖用于制备药物制剂的方法,其特征在于片剂重量份配方:5. A method for preparing pharmaceutical preparations using Polygonatum polysaccharide according to claim 3, characterized in that the formula of the tablet weight part: 玉竹多糖               50~300份Polysaccharide Polygonatum 50~300 parts 羟丙甲纤维素           30~60份Hypromellose 30-60 parts 乳糖                   50~240份Lactose 50~240 parts 3%羟丙甲纤维素水溶液  适量3% hypromellose aqueous solution Appropriate amount 硬脂酸镁               1~5份Magnesium stearate 1-5 parts 每片重0.13~0.60g,每片含玉竹多糖0.05g~0.3g。Each tablet weighs 0.13-0.60g, and each tablet contains 0.05g-0.3g polysaccharide from Polygonatum polysaccharide. 6、根据权利要求5所述的玉竹多糖用于制备药物制剂的方法,其特征在于片剂制作步骤包括:6. The method for preparing polysaccharides from Polygonatum polysaccharide according to claim 5, characterized in that the tablet making step comprises: a、分别取玉竹多糖、乳糖、羟丙甲纤维素、硬脂酸镁过120目筛,在105℃烘烤1h,备用;a. Polygonatum polysaccharides, lactose, hypromellose, and magnesium stearate were respectively passed through a 120-mesh sieve, baked at 105°C for 1 hour, and set aside; b、按配方比例称取玉竹多糖、乳糖、羟丙甲纤维素,充分混合均匀;b. Weigh Polygonatum polysaccharide, lactose, and hypromellose according to the formula ratio, and fully mix them evenly; c、加入大致处方量的3%羟丙甲纤维素水溶液,充分混合均匀,制软材;c. Add 3% hypromellose aqueous solution of approximate prescription amount, mix well and evenly, and make soft material; d、16目筛制粒,60℃干燥,同目整粒,加硬脂酸镁混匀,压片;d. Granulate with a 16-mesh sieve, dry at 60°C, granulate with the same mesh, mix with magnesium stearate, and tablet; e、质检、包装,印签,即得。e. Quality inspection, packaging, printing and signing.
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