CN1100063C - Ginkgo Testa Polysaccharide and the preparation of pharmaceutical thereof - Google Patents
Ginkgo Testa Polysaccharide and the preparation of pharmaceutical thereof Download PDFInfo
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- CN1100063C CN1100063C CN00134363A CN00134363A CN1100063C CN 1100063 C CN1100063 C CN 1100063C CN 00134363 A CN00134363 A CN 00134363A CN 00134363 A CN00134363 A CN 00134363A CN 1100063 C CN1100063 C CN 1100063C
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Abstract
The present invention relates to ginkgo testa polysaccharide and a preparation method of a ginkgo testa polysaccharide preparation. The present invention is characterized in that the gingko testa is put in a boiling and extracting pan, water is conventionally added into the pan to cause the gingko testa to be decocted for 2 to 3 times, and the solutions which are generated in each decocting process are respectively filtered; the filtered solutions are mixed, the pressure of the mixed filtered solution is reduced, and then, the mixed filtered solution is concentrated into the solution whose specific weight is from 1.05 to 1.20; the concentrated solution is added into ethanol to cause the final concentration of the ethanol to be from 50 to 85%, and the solution is stirred when the concentrated solution is added into the ethanol; after the solution is statically placed, sediments are washed for many times by the ethanol of high concentration, and then, the solution is dried in a vacuum mode or dried in a freezing mode; thus, a crude product of the ginkgo testa polysaccharide is formed. After the ginkgo testa polysaccharide is pulverized, an excipient is added into the powder, and then, solid dosage forms, such as tablets, capsules, etc., can be formed.
Description
The present invention relates to from gingko episperm to extract polysaccharide and be the technology that raw material is processed into anti-tumor agent with this polysaccharide.Belong to the biochemical technology field.
Polyose is the widest compounds of bio distribution.Because its toxic side effect is little, can improve body's immunological function, and suppresses growth of tumor, so be subjected to various countries scholar's attention (seeing " anti-tumor botanical and effective constituent thereof ", China Traditional Chinese Medicine Publishing House, the 17th page of December nineteen ninety-five) deeply.The more fungus polysaccharide of present domestic research has lentinan, krestin, Pachymose and polyporusum bellatus etc.; Vegetable polysaccharides has panaxan, Radix Et Caulis Acanthopanacis Senticosi polysaccharide and wolfberry fruit polysaccharide etc.Yet, really be used for clinical polyose medicament but seldom.This is lower with above-mentioned polysaccharide yield, Chinese medicinal materials consumes the more and relative higher certain relation that has of cost.Therefore, how seeking active polysaccharide from plant cheapness, resourceful should come into one's own.Existing people extracts from rice straw and straw and has obtained the inhibited hemicellulose polysaccharide of animal tumor, and this resource to the exploitation vegetable polysaccharides has certain positive effect.
Ginkgo has another name called gingko, is the special product of China, abounds with in Jiangsu Province.Compendium of Material Medica record, ginkgo have that " prepared food warming the lung and benefiting QI, relieving asthma and cough dwindle just, end gonorrhoea; Eat raw and fall phlegm, the detoxicating desinsection " etc. effect, be integration of drinking and medicinal herbs treasure world-famous.The annual a large amount of outlets of the gingko of China can be created considerable foreign exchange.Contain brass compounds isoreactivity composition in the Ginkgo Leaf, be developed and be applied to treat cardiovascular and cerebrovascular diseases.
Gingko episperm is commonly called as the gingko clothing.People are to its total some " prejudice " for many years, think meeting " corrosion skin ", have " stink " etc., so be regarded as the thing disliked and avoided or discarded thing always.We have at first found gingko exocarp polysaccharide in the process of gingko episperm being carried out synthetic study.Studies show that this polysaccharide is a kind of peptide polysaccharide of α-glycosidic bond, and is inhibited to kinds of tumors, can promote body's immunological function, also have activity of fighting against senium and (see " Pharmacology and Clinics of Chinese Materia Medica " magazine, 1996 the 5th phase 24-26 pages or leaves; " new Chinese medicine and clinical pharmacology " magazine, 1996 the 3rd phase 21-24 pages or leaves; " Chinese medicinal materials " magazine, 1996 the 9th phase 466-468 pages or leaves).There is no any toxic side effects in animal experiment and the clinic trial process.
The object of the present invention is to provide a kind of processing method of from gingko episperm, extracting polysaccharide and being processed into anti-tumor agent, gingko resource is made full use of, turn waste into wealth, thereby obtain that a kind of cost is lower than other polyose and the effective gingko exocarp polysaccharide preparation of kinds of tumors.
The object of the present invention is achieved like this:
Gingko episperm placed to boil propose the conventional boiling of pot 2-3 time and filter respectively, filtrate merging is evaporated to proportion at 1.05-1.20, concentrated solution is added in the ethanol, make the ethanol final concentration at 50-85%, the limit edged stirs, after leaving standstill throw out is washed final vacuum drying or lyophilize for several times with high concentration ethanol again, this is the gingko exocarp polysaccharide raw product.
Gingko exocarp polysaccharide is pulverized the back add vehicle, can be made into solid dosages such as tablet or capsule.
The present invention compared with prior art has following advantage:
The desired raw material aboundresources is turned waste into wealth, and can increase ginkgo orchard worker's income; The extraction process simple possible, the yield of polysaccharide and content are all higher; Can reduce the cost of medicine, alleviate patient's economical load; Result of treatment to kinds of tumors is better; Toxic side effect is little.See following explanation for details.1. gingko episperm aboundresources
The old family of Yangzi Evening A1 version on February 20th, 2000 root is entitled as in the report of " area of our province ginkgo account for the whole world half " to be pointed out: " according to province agricultural Room relevant department recent statistics: at present; all there is the ginkgo plantation the nearly all cities and counties of our province; the cultivated area of ginkgo has reached 200,000 hectares; account for global half, the annual production of ginkgo reaches 4200 tons." yield and the content of 2. various exosper polysaccharide is all higher
For the ease of expressing, the exosper that now sophisticated ginkgo is stripped out behind the gingko claims " bright exosper ", the title of bright exosper chilled storage " freezes exosper ", and bright exosper drying in the sun claims " dried exosper ", and dried exosper is removed the title " pure exosper " of pure soluble components through alcohol immersion.The yield and the content of above-mentioned various exosper polysaccharide see Table 1.
The polysaccharide yield of the more various gingko episperms of table 1 and content
Exosper kind polysaccharide yield (%) polysaccharide content (%)
Bright exosper 6.58 84.6
Freeze exosper 6.38 82.2
Dried exosper 4.40 80.2
Alcohol exosper 4.69 84.6
Annotate: 1. because of 5 kilograms of bright exospers are about 1 kilogram of dried exosper after drying, so bright exosper in showing
And the polysaccharide yield that freezes exosper has enlarged 5 times on original basis.
2. polysaccharide content=total sugar content (anthrone method mensuration)-reducing sugar content (Wu Xianfa mensuration)
Table 1 result shows that bright exosper is close with the polysaccharide yield that freezes exosper and dried exosper and pure exosper; And bright exosper and freeze the polysaccharide yield of the polysaccharide yield of exosper apparently higher than dried exosper and pure exosper, may be relevant with bright exosper a part of polysaccharide that in the drying in the sun process, can run off.But the polysaccharide yield of above-mentioned various exospers is all higher.Polysaccharide content is also higher, all more than 80%.3. can reduce the cost of medicine, alleviate patient's economical load
If this polysaccharide is processed into capsule preparations, every contains 100 milligrams of polysaccharide, and now by each 2, every day, 2 oral continuous uses calculated in 1 month, and needing the polysaccharide raw material is 100 * 2 * 2 * 30=12000. (milligram)=12 (gram)
If by polysaccharide yield is 5% calculating, the bright exosper of need be 12 ÷, 5 * 100 * 5=1200 (gram)=1.2 (kilogram), and the ethanol of need 95% is 1200 * 200 ÷ 100+500+500=3400 (milliliter)=3.4 (liter)
If will decoct used coal of extraction or expenses such as electric and Capsules wouldn't calculate, gingko episperm is by 3 yuan every kilogram, 95% ethanol is by every kilogram of 8 yuan of calculating, the cost price of then above-mentioned 30 days required medicines is 1.2 * 3+3.4 * 8=30.8 (unit), need 1 yuan every day approximately, even add other various expenses, the expenses for medicine of every day also should be in 2-3 unit, alleviated patient's economical load greatly, the general common people all can bear, compare with now general every 2-3 unit of antineoplastic Chinese traditional medicine, have significant difference.4. better to the clinical efficacy of kinds of tumors, and can alleviate or resist the clinical observation on the therapeutic effect of 4.1 pairs of tumor in upper digestive tract of radiotherapy side effect
Select not underwent operative and chemotherapy or radiotherapy, the esophagus cancer and patients with gastric cancer 16 examples of taking said preparation are separately carried out gastroscopy and are made a definite diagnosis one month, two months and/or capable respectively again gastroscopy in three months after the medication, measurement knurl piece size through pathology before the medication voluntarily.After 16 routine patient's medications, appetite, spirit etc. are all obviously improved as a result, pain and swallow sense of obstruction and significantly alleviate weight increase.Gastroscope is measured down and is shown that the focus area significantly dwindles, and average tumour inhibiting rate is 47.5%, and wherein 2 examples are alleviated fully.Relevant statistics sees Table 2.
Table 2 couple tumor in upper digestive tract patient's the tumour inhibiting rate and the influence of body weight
Knurl body (cm
2(kg, 23.57 ± 27.70 47.5 67.90 ± 6.76 3.34.2 are to the Ultrastructural observation of tumor in upper digestive tract oncocyte after preceding 44.92 ± 42.37/65.73 ± 6.31/medication of body weight gain rate (%) medication of x ± s) for knurl body inhibiting rate (%) body weight of x ± s)
Draw materials with gastroscope before and after tumour patient in above-mentioned 4.1 taken medicine, fixing, ultrathin section(ing) carries out Ultrastructural observation.Electron microscope showed, great majority are taken the patient of said preparation, and oncocyte nucleus heteromorphism reduces, and nuclear-cytoplasmic ratio reduces, and heterochromatin increases, and is deposited under the nuclear membrane, occur pyknosis, reticulum dilatation and plastosome vacuolation phenomenon simultaneously.Show that said preparation has direct killing and apoptosis-induced effect to oncocyte.4.3 antagonistic action to radiotherapy side effect
60The Co Continuous irradiation can cause appetite stimulator under certain dosage, in addition feel sick, digestive tract reaction and hemopoietic function inhibited reactions such as white corpuscle, red corpuscle, hemochrome and thrombopenia such as vomiting.Radiocurable to give said preparation simultaneously oral carrying out to 32 routine esophagus cancer patients for we, and 2, Bid.As a result, patient's digestive tract reaction significantly alleviates, and significantly increases than not medication appetite after the radiotherapy after wherein most of radiotherapy patient medication.The hemopoietic function that this medicine causes radiotherapy suppresses and weight loss also has antagonistic action, and relevant statistics sees Table 3.
Table 3 couple esophagus cancer patient
60The influence of Co caused by radiation hemopoietic function inhibited reaction and body weight
White corpuscle red corpuscle hemochrome thrombocyte body weight
(10
9/ L) (10
12/ L) (g/L) (10
9/ traditional Chinese medical science observation of curative effect that L) 5.49 ± 2.84 4.05 ± 0.35 118.8 ± 16.0 163.3 ± 78.0 54.1 ± 8.24.4 shift malignant tumour after preceding 6.39 ± 2.31 4.09 ± 0.63 118.9 ± 20.3 162.4 ± 71.5 54.0 ± 6.7 medications of (kg) medication
Various tumour patient 36 examples such as esophagus cancer, cancer of the stomach, colorectal carcinoma, lung cancer and liver cancer that selection is not suitable for performing the operation, chemotherapy or radiotherapy and postoperative comprise existing metastatic lesion, press tcm syndrome differentiation and typing before the medication, take said preparation separately, usage is the same, one month is a course of treatment, take 2~3 courses of treatment continuously, can continue when needing to take.The result shows, and is better to qi stagnation and blood stasis type and stagnation of phlegm-damp in middle-JIAO type curative effect.Can make patient's sx, spirit takes a turn for the better, and the difference of receiving is improved, and promotes hematopoiesis and immunologic function, quality of life improve (the Ka Shi scoring, treat preceding 60.56 ± 5.83, after treating 76.67 ± 6.76).Through inspections such as B ultrasonic, X lines, part patient's knurl body dwindles, and can also delay the metastases time, to the existing patient who shifts, primary tumor and metastasis knurl body is dwindled, and prolong lifetime.The sings and symptoms changing conditions sees Table 4 before and after relevant cancerous swelling patient's medication.
Sings and symptoms changing conditions before and after the relevant cancerous swelling patient medication of table 4
After treating before the treatment
Example number transference cure is clearly better and improves invalid dysphagia 12 732 cancer pains 21 12 531 abdominal distension and suffer from diarrhoea and 13 931 cough saliva 8521 weak 19 13 42 insomnias, 9621 appetite 36 of spitting and increase substantially unchanged 7 examples of the 26 examples 3 routine body weight 36 that go down and increase substantially unchanged 6 examples of 28 examples and alleviate 2 examples, 4.5 Anticancer Effect and Mechanism
According to clinical data,, point out the antitumor mechanism of this polysaccharide may set upright with promoting body's immunological function and to the direct killing effect of oncocyte and eliminating evil relevant in conjunction with animal test results.Ultrastructural observation thinks that said preparation can be induced apoptosis of tumor.Little 5.1 acute toxicity tests of 5 toxic side effecties
Get 40 of ICR mouse, be equally divided into 2 groups, 20 every group, male and female half and half.Wherein one group gives physiological saline, and another group gives 10% gingko exocarp polysaccharide filling stomach, is all 0.4ml/10g (maximum volume), observes a week after the administration, and it is existing to find no dead mouse and other exception table.Body weight and food-intake see Table 5
Table 5 gingko exocarp polysaccharide influences group dosage number of animals body weight (g) food-intake (g) to mouse body weight and food-intake
(g/kg) the 1st day the 3rd day the 5th day the 7th day control group/20 19.8 ± 1.0 24.3 ± 1.0 42.5 49.5 48.5 56.0 polysaccharide group 4.0 20 19.7 ± 1.1 24.7 ± 1.2 34.5 41.0 50.5 57.8 after the preceding medication of (only) medication
The result finds out from table 5, and the preceding two groups of mouse body weight of administration do not have significant difference, and body weight increases all to some extent after the administration.Growth along with body weight, food-intake also constantly increases, though first day polysaccharide group of administration mouse food-intake lack than control group, may be with irritate the gingko exocarp polysaccharide of having fed a large amount of high densitys to mouse relevant, beginning in the 5th day after the administration, the food-intake of administration group mouse is all more than control group mice.
The clinical consumption of said preparation is 400mg every day, calculates by 60 kg body weight, and be 6.7mg/kg every day, and the animal maximum tolerated dose is 4.0g, i.e. 4000mg is 600 times of people's consumption approximately.5.2 clinical toxic side effects is observed
In the whole medication process, patient do not reflect have any because of this drug-induced discomfort.On inspection, also do not see the infringement of important organ functions such as patient's heart, liver, kidney or form aspect.
Narrate 4 embodiment of the present invention below.
Embodiment 1
Get fresh gingko exosper double centner, place to boil and carry pot and add 500 kilograms of decoctions of water, boiling the back continues to decoct 1 hour, cross out with screen and to continue to add water after the filtrate and repeat above-mentioned decocting method 1 time and filter, 2 times filtrates are merged, being evaporated to proportion in 70 ℃ is 1.05, in the ethanol with concentrated solution adding 95%, make the ethanol final concentration 60%, the limit edged stirs, leave standstill after 4 hours the throw out centrifuge dripping, use 80% 2 final vacuum dryings of washing with alcohol or lyophilize again, this is a gingko exocarp polysaccharide.Gingko exocarp polysaccharide is ground into dry powder with micropulverizer, gets 1 kilogram in this dry powder, add 1.5 kilograms in dextrin, mix thoroughly, pack in the Capsules by every 250mg, this is the gingko exocarp polysaccharide capsule preparations.
Embodiment 2
Get 200 kilograms of refrigerated gingko episperms, place to boil and carry pot and add 1000 kilograms of decoctions of water, boiling the back continues to decoct 1 hour, cross out with screen and to continue to add water after the filtrate and repeat above-mentioned decocting method 1 time and filter, 2 times filtrates are merged, being evaporated to proportion in 70 ℃ is 1.10, in the ethanol with concentrated solution adding 90%, make the ethanol final concentration 65%, the limit edged stirs, leave standstill after 6 hours the throw out centrifuge dripping, use 85% 3 final vacuum dryings of washing with alcohol or lyophilize again, this is a gingko exocarp polysaccharide.Gingko exocarp polysaccharide is ground into dry powder with micropulverizer, gets 2 kilograms in this dry powder, add 3 kilograms in dextrin, mix thoroughly, pack in the Capsules by every 125mg, this is the gingko exocarp polysaccharide capsule preparations.
Embodiment 3
Get 50 kilograms of drying in the sun gingko episperms, place to boil and carry pot and add 800 kilograms of decoctions of water, boiling the back continues to decoct 1.5 hours, cross out with screen and to continue to add water after the filtrate and repeat above-mentioned decocting method 1 time and filter, 2 times filtrates are merged, being evaporated to proportion in 70 ℃ is 1.15, in the ethanol with concentrated solution adding 95%, make the ethanol final concentration 70%, the limit edged stirs, leave standstill after 8 hours the throw out centrifuge dripping, use 85% 2 final vacuum dryings of washing with alcohol or lyophilize again, this is a gingko exocarp polysaccharide.Gingko exocarp polysaccharide is ground into dry powder with micropulverizer, gets 3 kilograms in this dry powder, add 4.5 kilograms of excipient, mix thoroughly, make tablet by every 250mg, this is the gingko exocarp polysaccharide tablet.
Embodiment 4
The gingko episperm double centner that the high concentration ethanol of learning from else's experience soaked, place to boil and carry pot and add 2000 kilograms of decoctions of water, boiling the back continues to decoct 1 hour, cross out with screen and to continue to add water after the filtrate and repeat above-mentioned decocting method 1 time and filter, 2 times filtrates are merged, being evaporated to proportion in 70 ℃ is 1.20, in the ethanol with concentrated solution adding 95%, make the ethanol final concentration 70%, the limit edged stirs, leave standstill after 12 hours and throw out to be used 95% 2 final vacuum dryings of washing with alcohol or lyophilize again, this is a gingko exocarp polysaccharide.Gingko exocarp polysaccharide is ground into dry powder with micropulverizer, gets 4 kilograms in this dry powder, add 6 kilograms of excipient, mix thoroughly, make tablet by every 125mg, this is the gingko exocarp polysaccharide tablet.
Claims (2)
1, a kind of preparation method of gingko exocarp polysaccharide, it is characterized in that gingko episperm placed to boil proposing the conventional boiling of pot 2-3 time and filtering respectively, filtrate merging is evaporated to proportion at 1.05-1.20, concentrated solution is added in the ethanol, make the ethanol final concentration in 50-85% (weight), the limit edged stirs, and after leaving standstill throw out is washed final vacuum drying or lyophilize for several times with high concentration ethanol again, and this is the gingko exocarp polysaccharide raw product.
2, a kind of preparation method of gingko exocarp polysaccharide preparation is characterized in that adding vehicle with pulverizing the back with the gingko exocarp polysaccharide of method for preparing, makes tablet or capsule.
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Cited By (1)
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CN101912426A (en) * | 2010-08-06 | 2010-12-15 | 扬州大学 | Method for preparing ginkgo exocarp anti-tumor effective part and preparation thereof |
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CN101912425B (en) * | 2010-08-06 | 2011-12-14 | 扬州大学 | Ginkgo episperm extract with antitumor and immunostimulating activity and preparation method of effective part thereof |
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CN105477026B (en) * | 2016-02-02 | 2019-10-01 | 武汉理工大学 | A kind of technique of combined extracting ginkgoic acid, flavones and terpene lactones and polysaccharide from gingko episperm |
CN106265779A (en) * | 2016-10-21 | 2017-01-04 | 扬州大学 | The extraction fromginkgoseed coat with anti-tumor activity of a kind of decolouring and the preparation method of preparation thereof |
CN106317247B (en) * | 2016-10-21 | 2018-12-21 | 扬州大学 | A kind of preparation method of water-solubility ginkgo exosper polysaccharide and its preparation |
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CN106389484A (en) * | 2016-10-21 | 2017-02-15 | 扬州大学 | Methods for preparing water-soluble ginkgo exopleura extract and preparation thereof |
CN106616372A (en) * | 2016-12-02 | 2017-05-10 | 佳木斯大学 | Inonotus obliquus polysaccharide composite bean flour and preparation method thereof |
CN110577607A (en) * | 2018-06-11 | 2019-12-17 | 郑州师范学院 | method for extracting seed coat polysaccharide from ginkgo biloba |
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CN101912426A (en) * | 2010-08-06 | 2010-12-15 | 扬州大学 | Method for preparing ginkgo exocarp anti-tumor effective part and preparation thereof |
CN101912426B (en) * | 2010-08-06 | 2012-07-04 | 扬州大学 | Method for preparing ginkgo exocarp anti-tumor effective part and preparation thereof |
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