CN103301321A - Thrombolytic active polysaccharide mixture preparation technology - Google Patents

Thrombolytic active polysaccharide mixture preparation technology Download PDF

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CN103301321A
CN103301321A CN2013102083663A CN201310208366A CN103301321A CN 103301321 A CN103301321 A CN 103301321A CN 2013102083663 A CN2013102083663 A CN 2013102083663A CN 201310208366 A CN201310208366 A CN 201310208366A CN 103301321 A CN103301321 A CN 103301321A
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polysaccharide
liquid
weight
polysaccharide mixture
compound protease
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CN103301321B (en
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张真元
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Zhang Zhenyuan
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Abstract

The invention discloses a thrombolytic active polysaccharide mixture preparation technology. The technology is characterized by preparing a polysaccharide mixture through mixing the concentrated polysaccharide mixed liquor of dendrobium officinale, chrysanthemum and hawthorn which are extracted by adopting a composite enzymic method with the fermentation liquor of black fungus and tolypocladium sinensis mycelia. The thrombolytic active polysaccharide mixture prepared by the technology has multiple biological activities, is a Chinese herbal medicinal microbial polysaccharide mixture with good quality and no toxic and side effect in the current world, can effectively treat cerebral thrombosis acute phase diseases, and has obvious treatment and prevention functions on acute phase sequela recovery and relapse prevention as well as a special effect on the efficacy of a Chinese herbal medicinal polysaccharide and microbial mycelia polysaccharide mixture with obvious vascular wall softening and nutrition functions.

Description

A kind of processing technology of thrombolysis activity polysaccharide mixture
Technical field
The invention belongs to medical technical field, the processing technology of the thrombolysis activity polysaccharide mixture that a kind of cerebral thrombosis, the rehabilitation of myocardial infarction disease specifically used.
Background technology
As everyone knows, cardiovascular and cerebrovascular disease is the disease that global sickness rate is the highest, complication is maximum.The cardiovascular and cerebrovascular vessel eqpidemic disease has become one of principal disease that threatens the human life.In China, the sickness rate of cardiovascular and cerebrovascular disease, mortality rate cumulative year after year, and present the trend of rejuvenation.Along with the raising of living standards of the people, higher fatty acid, the excessive of high protein diet eaten, and along with the development of process of industrialization, the pollution of atmosphere, water, food has all become the more and more higher principal element of cardiovascular and cerebrovascular disease sickness rate.Cardiovascular and cerebrovascular disease still becomes harm humans health " No.1 killer ", becomes " second cancer ".Certainly, the control of cardiovascular and cerebrovascular disease has caused the extensive concern of the whole society.
Cardiovascular and cerebrovascular disease is due to blood in human body in liquid viscosity index raises, often because the rising of blood viscosity causes thrombosis, and myocardium brain severe ischemic, so that form thrombosis, threaten people's life.
Existing Western medicine is many with thrombolytic, and it is main reducing blood viscosity.The kind that reduces blood cholesterol levels and triglyceride in the existing Chinese medicine is also a lot, can both prevent the effect of heart and brain thrombosis to a certain extent.But, no matter be Chinese medicine, or Western medicine, its property of medicine effect is single, and effect is obviously but not lasting.That is to say its effect can only respite blood in abnormal index, can not thoroughly improve the index that exceeds standard in the blood and worsen once again, other complementary effects more out of the question.Therefore, research and develop a kind of when can either reduce cholesterol in the blood, triglyceride blood viscosity, blood glucose effectively and preventing its index to raise once again, again can the nutrition vessel softening, the pure Chinese medicinal preparation that replenishes the blood vessel wall nutritional labeling is extremely urgent.
Summary of the invention
The present invention is directed to the problems referred to above, researched and developed a kind of processing technology of thrombolysis activity polysaccharide mixture, utilize thrombolytic polysaccharide mixture that this processing technology makes obviously blood viscosity lowering, blood glucose, serum specific viscosity and Fibrinogen, not only blood coagulation there is certain resistancing action, simultaneously remarkable to the angiomalacia Nutrition again.
Technical scheme of the present invention is: a kind of processing technology of thrombolysis activity polysaccharide mixture, key is: this polysaccharide mixture is that the polysaccharide mixed liquor that concentrates of the Herba Dendrobii that utilizes the combined-enzyme method lixiviate, Flos Chrysanthemi, Fructus Crataegi and be mixed by the fermentation liquid of Auricularia, Cordyceps mycelium forms, and comprises in the concrete manufacturing process steps:
(1) choose Herba Dendrobii, Flos Chrysanthemi, Fructus Crataegi herbal raw material, carry out following steps respectively to obtain Dendrobium officinale polysaccharide liquid, chrysanthemum polysaccharide liquid and Fructus Crataegi polysaccharide liquid:
A, rinsing are to remove the Chinese herbal medicine surface irregularities;
Add water in b, the Chinese herbal medicine after rinsing, the reuse colloid mill grinds to form serosity;
C, in serosity, add the water of 5-30 times of weight, heat, be warming up to 100 ℃, be cooled to 85 ℃ again, under pressure 30MPa, utilize high pressure homogenizer to handle, obtain homogeneous slurry;
D, add compound protease lixiviate 1 ~ 2 hour in homogeneous slurry, wherein, homogeneous slurry with the ratio of the weight of compound protease is: 100:(1.5 ~ 2), compound protease is that cellulase, pectase and the protease of 1:1:1 is formed by weight ratio;
E, lixiviating solution are through low speed centrifuge separates, filtering and concentrating is removed 10-20% moisture and dry, and be stand-by;
(2) choose Auricularia (Auricularia auricular) (numbering AS5.452, depositary institution: institute of microbiology of the Chinese Academy of Sciences) and Cordyceps (mi litrsGordyceps) (numbering M1069, depositary institution: Guangdong Microbes Inst, Guangdong Province's culture presevation and priority application laboratory) strain, carry out following steps respectively to obtain Auricularia polycose extracting solution and Cordyceps polysaccharides extracting solution:
ⅰ, take slant strains to cultivate, the breeding of shaking table liquid, seed tank liquid spawn three-class strain is cultivated liquid spawn separately, liquid spawn being introduced supporting fermentation tank respectively fermented 3-7 days in liquid culture medium again, treat that mycelial growth concentration or weight in wet base ratio stops fermentation when reaching 65-80%, solid residue in the filtering fermentating liquid, it is stand-by to obtain the fermentation filtered solution;
ⅱ, be not less than 90 ℃ in temperature, under the ambient pressure 1.2-1.5 atmospheric pressure, in the fermentation filtered solution, add the compound protease of being formed by pepsin and papain and carry out pyrolysis, inactivation treatment, the ratio of filtered solution and the weight of compound protease of wherein fermenting is 100:(0.5 ~ 2), the ratio of the quality of pepsin and papain is 1:1;
ⅲ, will filter, concentrate to remove moisture and the miscellaneous material of 10-20% through the fermentation filtered solution of pyrolysis, inactivation treatment, stand-by;
(3) Dendrobium officinale polysaccharide liquid, chrysanthemum polysaccharide liquid, Fructus Crataegi polysaccharide liquid, Auricularia polycose extracting solution and Cordyceps polysaccharides extracting solution are mixed according to following percent by volume:
Dendrobium officinale polysaccharide liquid 5-50%,
Chrysanthemum polysaccharide liquid 10-30%,
Fructus Crataegi polysaccharide liquid 5-15%,
Auricularia polycose extracting solution 10-40%,
Cordyceps polysaccharides extracting solution 5-35%;
(4) under gnotobasis, the mixed liquor that the back that is mixed is formed carries out pressure 10 ~ 15MPa homogenizing at 60 ℃, divides bottle, encapsulation, sterilization to become finished product.
For the polysaccharide component in the dry that obtains among the further extraction step e, also improve the utilization rate of effective ingredient in the material simultaneously, dry is carried out secondary, and the extraction step of three polysaccharide components.The second extraction step is as follows:
Add the water of 5-30 times of weight in e1, the dry that obtains in step e, heat, be warming up to 100 ℃, be cooled to 85 ℃ again, under pressure 30MPa, utilize high pressure homogenizer to handle, obtain homogeneous slurry;
E2, add compound protease lixiviate 1 ~ 2 hour in homogeneous slurry, wherein, homogeneous slurry with the ratio of the weight of compound protease is: 100:(1 ~ 1.5), compound protease is that cellulase, pectase and the protease of 1:1:1 is formed by weight ratio;
E3, lixiviating solution are through low speed centrifuge separates, filtering and concentrating is removed 10-20% moisture and dry, and be stand-by.
Three times extraction step is as follows, and the dry that step e3 obtains carries out following processing again:
E31, in dry, add the water of 5-30 times of weight, heat, be warming up to 100 ℃, be cooled to 85 ℃ again, under pressure 30MPa, utilize high pressure homogenizer to handle, obtain homogeneous slurry;
E32, add compound protease lixiviate 1 ~ 2 hour in homogeneous slurry, wherein, homogeneous slurry with the ratio of the weight of compound protease is: 100:(0.5 ~ 1), compound protease is that cellulase, pectase and the protease of 1:1:1 is formed by weight ratio;
E33, lixiviating solution are through low speed centrifuge separates, filtering and concentrating is removed 10-20% moisture and dry, and be stand-by.
The fermentation temperature of described Auricularia is 24-26 degree centigrade, and the fermentation temperature of described Cordyceps is 16-18 degree centigrade.
Pressure in the described fermentation tank is 30-50MPa, and liquid culture medium carbon, nitrogen are than being 1:(16-24), inoculum concentration is 10%, ventilation be the 0.4-0.6 cubic meter/minute, mixing speed is 120-180 rev/min.
When the Auricularia strain carried out step I in the step (2), the liquid culture medium of employing was prepared by following percentage by weight:
Testa Tritici juice 8-10%,
Corn juice 5-10%,
Murphy juice 10-15%,
Bean milk 15-20%,
Yeast powder 0.5-1%,
Sucrose 0.5-3%,
Glucose sugar 0.5-2%,
Magnesium sulfate 0.02-0.05%,
Phosphoric acid phenodiazine potassium 0.05-0.1%,
Peptone 0.3-1%,
Oleum Arachidis hypogaeae semen 0.3-0.6%,
Surplus is water.
When Cordyceps strain carried out step I in the step (2), the liquid culture medium of employing was prepared by following percentage by weight:
Dried silkworm chrysalis meal 1-2%,
Milk powder 2-3%,
Murphy juice 20-30%,
Bean milk 25-35%,
Semen setariae juice 10-20%,
Corn juice 10-20%,
Yeast powder 1-2%,
Sucrose 0.5-2%,
Glucose 1-3%,
Peptone 0.5-1%,
Magnesium sulfate 0.05-0.1%,
Phosphoric acid phenodiazine potassium 0.15-0.18%,
Vitamin B1 0.5-1%
Oleum Arachidis hypogaeae semen 0.5-0.8%,
Surplus is water.
Described Herba Dendrobii is that the 4-5 of artificial growth gives birth to.
Also comprise in the described step (4) with at mixed liquor at 60 ℃, the active polysaccharide liquid that carries out after the pressure 15MPa homogenizing forms powder through drying process with atomizing, powder is packed to form capsule or electuary or tablet again.
The filtration operation of described lixiviating solution is to adopt ultrafilter membrane or reverse osmosis membrane filtration.
The invention has the beneficial effects as follows: 1, key of the present invention is to generate the compatibility complementation of being rich in microbial activity polysaccharide composition by effective polysaccharide composition and the filtration of microbial fermentation solution, concentrated back that medium-height grass property of medicine enzyme process is carried, reaches definite target of the present invention; 2, discover, Herba Dendrobii is formed complicated, the polysaccharide cell is unsuitable permeable, except polysaccharide, also contain materials such as dendrobine, dendrophnol, hincky acid, pectin, cellulose, the existence of these materials all can influence the leaching of polysaccharide, therefore in polysaccharide deduction process, select mechanical-physical breaking cellular wall, virgin pulp liquid 3-5 sub-high pressure breaking cellular wall repeatedly for use, add the lixiviate under suitable temperature of suitable compound enzymic preparation, lixiviating solution is through low speed centrifuge separates, filtering and concentrating is removed 10-20% moisture and dry, dry lixiviate 2-3 times repeatedly.Through experimental results demonstrate, combined-enzyme method lixiviate simple and fast and polysaccharide extraction rate are up to 15.67%, and the effective content of Dendrobium officinale polysaccharide is enough to produce tangible drug effect.3, the selected Flos Chrysanthemi that can strengthen curative effect, the Fructus Crataegi polysaccharide of proportioning carries out compatibility and can strengthen medicinal effects effectively and reach ultimate attainment; 4, Auricularia, Cordyceps mycelium carry out degree of depth fermentation process in fermentation tank, and when weight in wet base reached 65-80%, the effective content of its polysaccharide was enough to produce tangible drug effect.Active polysaccharide mixture of the present invention empirical tests in the pharmacological evaluation that rabbit is cooked: the injection rate of 4.5-5 grams/kilogram can make the poly-reaction of loosing of platelet produce, show the obvious inhibition to ADP, to plasma viscosity, it is obvious that serum specific viscosity celloglobulin index is improved statistical significance, cholesterol and triglyceride growth in the high lipid food rabbit there is remarkable inhibitory action, and thrombotic speed and size are had significant curative effect.
The specific embodiment
Key problem in technology of the present invention is that Herba Dendrobii, Flos Chrysanthemi, Fructus Crataegi polysaccharide and Auricularia, Cordyceps mycelium polyoses content reach specified standard in the mixture of institute's proportioning, and the content of medium-height grass property of medicine polysaccharide and Auricularia, Cordyceps mycelial concentration in liquid fermentation tank are depended in the realization of this standard fully, realize that the concrete grammar of this index is:
Choose the bright product of Herba Dendrobii of growth in 4-5 years, add the suitable quantity of water chopping, behind the colloid mill defibrination, carry out three grades of processing of extracting polysaccharide liquid.One-level is treated to: the water that adds 5-30 times of weight in the serosity behind the colloid mill defibrination is warming up to 100 ℃, when being down to 85 ℃ again, utilizes high pressure homogenizer to carry out broken wall treatment under high pressure 30MPa pressure, obtains homogeneous slurry; Add compound protease lixiviate 1 ~ 2 hour in homogeneous slurry, wherein, homogeneous slurry with the ratio of the weight of compound protease is: 100:(1.5 ~ 2), compound protease is that cellulase, pectase and the protease of 1:1:1 is formed by weight ratio; Lixiviating solution obtains one-level Dendrobium officinale polysaccharide liquid through low speed centrifuge separates, filtering and concentrating is removed 10-20% moisture and dry.Two stage treatment is: add water, intensification again, lower the temperature and utilize high pressure homogenizer to carry out broken wall treatment to the dry that leaches in the above-mentioned one-level treatment step, in homogeneous slurry, add aforesaid compound protease lixiviate 1 ~ 2 hour again, wherein, homogeneous slurry with the ratio of the weight of compound protease is: 100:(1 ~ 1.5), and then separation, filtering and concentrating remove moisture and the dry of 10-20%, obtains secondary Dendrobium officinale polysaccharide liquid; Then, aforementioned dry is carried out tertiary treatment again, utilize high pressure homogenizer to carry out broken wall treatment to adding water, intensification, cooling in the dry caught on a filter in the two stage treatment again, in homogeneous slurry, add aforesaid compound protease lixiviate 1 ~ 2 hour again, wherein, homogeneous slurry with the ratio of the weight of compound protease is: 100:(0.5 ~ 1), and then separation, filtering and concentrating remove moisture and the dry of 10-20%, obtains three grades of Dendrobium officinale polysaccharide liquid.The above-mentioned one-level that obtains, secondary, three grades of Dendrobium officinale polysaccharide liquid are mixed with as stand-by Dendrobium officinale polysaccharide liquid.
Choose Flos Chrysanthemi, processing with above-mentioned Herba Dendrobii is the same, just carry out the polysaccharide liquid that one-level handles to obtain Flos Chrysanthemi at high pressure 30MPa pressure, and no longer carry out the processing procedures that secondary, three grades extract the polysaccharide liquid, choose Fructus Crataegi again, also carry out the treatment step of above-mentioned same Flos Chrysanthemi to obtain the polysaccharide liquid of Fructus Crataegi.Stand-by Dendrobium officinale polysaccharide liquid, chrysanthemum polysaccharide liquid, Fructus Crataegi polysaccharide liquid is incorporated in the holding vessel keeps 60 ℃ of temperature stand-by.Polyoses content is respectively that Dendrobium officinale polysaccharide liquid 15.67%, chrysanthemum polysaccharide liquid 6.32%, Fructus Crataegi polysaccharide liquid are 8.43%.
Choose edible Auricularia strain (Auricularia auricular), the concrete optional bacterium numbering that is used in the preservation of Institute of Micro-biology of the Chinese Academy of Sciences is the AS5.452 kind, Cordyceps strain (mi litrsGordyceps), specifically can select the Guangdong Microbes Inst for use, Guangdong Province's culture presevation and priority application laboratory bacterium numbering are the M1069 kind, select the strain of new fertile shape to do the cultivation strain, take slant strains to cultivate, the breeding of shaking table liquid, seed tank liquid spawn three-class strain is cultivated the liquid spawn of each separately, liquid spawn being introduced supporting fermentation tank respectively fermented 3-7 days in supporting liquid culture medium again, treat that mycelial growth concentration or weight in wet base ratio stops fermentation when reaching 65-80%, the solid residue in the filtering fermentating liquid obtains corresponding strain fermentation filtered solution.Be not less than 90 ℃ in temperature, under 1.2-1.5 atmospheric pressure of ambient pressure with add in above two kinds of fermentation filtered solutions concentration be 0.5-1.5% by etc. the pepsin of weight and the compound protease that papain is formed, carry out pyrolysis, inactivation treatment afterwards, will further filter through two kinds of strain fermentation filtered solutions of pyrolysis, inactivation treatment, concentrate to remove 10-20% moisture content and foreign material be incorporated in the storage tank temperature keep 60 ℃ stand-by.
Then with above said by two class polysaccharide extraction liquids (Chinese herbal medicine polysaccharide liquid and microbial activity polysaccharide extraction liquid) according to the following percent by volume homogenizing (pressure is mixed into mixture for 10 ~ 15 kilograms) that is mixed, form the thrombolysis activity polysaccharide mixture:
Dendrobium officinale polysaccharide liquid 5-50%,
Chrysanthemum polysaccharide liquid 10-30%,
Fructus Crataegi polysaccharide liquid 5-15%,
Auricularia polycose extracting solution 10-40%,
Cordyceps polysaccharides extracting solution 5-35%;
The dosage form of this thrombolysis activity polysaccharide mixture can be liquid syrup, also can be powder or capsule or electuary or the tablet of making by spray drying.
Provide the embodiment that the percent by volume of two class polysaccharide extraction liquids is mixed below:
Table 1
Title Embodiment 1 Embodiment 2 Embodiment 3 Embodiment 4 Embodiment 5 Embodiment 6 Embodiment 7
Herba Dendrobii 5 10 15 20 30 40 50
Flos Chrysanthemi 24 28 22 30 10 10 15
Fructus Crataegi 6 12 8 15 10 15 5
Auricularia 37 25 20 10 40 30 10
Cordyceps 28 25 35 25 10 5 20
The liquid culture medium proportioning embodiment following (percentage by weight) of Auricularia:
Table 2
Embodiment Testa Tritici juice Corn juice Murphy juice Bean milk Yeast powder Sucrose Glucose Magnesium sulfate Potassium dihydrogen phosphate Peptone Oleum Arachidis hypogaeae semen Water
1 10 5 15 20 0.5 0.5 1 0.02 0.05 0.5 0.3 Surplus
2 15 10 20 25 0.8 1 0.8 0.05 0.1 0.8 0.5 Surplus
3 20 15 25 30 1 1.5 1.5 0.08 0.15 1 0.8 Surplus
4 25 20 30 35 1.5 2 0.5 0.1 0.2 1.5 1 Surplus
The liquid culture medium proportioning embodiment following (percentage by weight) of Cordyceps:
Table 3
Embodiment Dried silkworm chrysalis meal Milk powder Murphy juice Bean milk Semen setariae juice Corn juice Yeast powder Sucrose Glucose Peptone Magnesium sulfate Potassium dihydrogen phosphate Vitamin B1 Oleum Arachidis hypogaeae semen Water
1 0.5 1.5 15 20 5 10 0.5 0.3 1 0.5 0.05 0.15 0.2 0.2 Surplus
2 1 2 20 25 10 15 1 0.5 1.5 0.8 0.06 0.18 0.5 0.3 Surplus
3 1.5 2.5 25 30 15 20 1.5 1 2 1 0.08 0.2 1 0.5 Surplus
4 2 3 35 35 20 25 2 1.5 2.5 1.5 0.1 0.2 1 0.8 Surplus
More than said Auricularia, in the liquid culture medium layoutprocedure in the Cordyceps breeding jar, with peeling potatoes and eye, section adds 6-10 times of weight water boils stirrings and is pasty state, Semen Maydis powder adds 25-30 times of weight water boils of water, Semen setariae adds 30-40 times of weight water boils, the Testa Tritici skin kept 30 minutes after adding 20-25 times of weight water boils, make 100 jin of bean milk with 4-6 jin of Semen Glyciness, above semi-finished product form said potato juice through getting filtrate with 6-8 layers of filtered through gauze, corn juice, Semen setariae juice, Testa Tritici juice, bean milk, accurately take by weighing required various compound according to the above proportion compatibility that provides then, carry out steam high-voltage sterilizing at last, be cooled to below 30 ℃ standby.
The clinical use result of thrombolysis activity polysaccharide mixture of the present invention shows to have following advantage:
1, the thrombolysis activity polysaccharide mixture made from the inventive method, through the corresponding property of medicine, pharmacological testing, effective medicinal component polysaccharide of polysaccharide mixture, dendrobine, the total hincky acid of dendrophnol, pectin, cellulose etc. can powerfully be cleared up blood toxicity, improve the blood of human body microcirculation, hepatoprotective function of gallbladder promoting, strong muscle blood fat reducing, benefiting qi and nourishing blood, balancing blood pressure, powerful blood sugar lowering.Polysaccharide mixture can significantly increase the activity of being tried rabbit anticoagulation kinase, prolong clotting time, suppress the formation of thrombosis, can significantly suppress the activity of platelet activating factor, suppressed the platelet aggregation that collagen and arachidonic acid are induced, improved microcirculation, accelerated blood flow, prevented thrombosis, made blood mobility index super normal, thereby prevented heart infarction, cerebral infarction, coronary atherosclerosis, so therapeutic effect is remarkable.
2, bring high blood pressure down, blood sugar lowering: experimentize with spontaneous hypertensive rat, the administration group adds 5% polysaccharide mixture in feedstuff, and matched group does not add, and the visible administration group blood pressure in back obviously reduces all around, and the cholesterol level in blood plasma and the liver also descends.
3, this thrombolysis activity polysaccharide mixture proves by further toxicological test, does not contain antiseptic.Strengthening under 60 times of situations of human clinical's dose, diet, feces, hair matter activity characteristic to the examination rabbit, body weight gain all loses obvious influence, each organizes experimental animal routine blood test (leukocyte, erythrocyte number, platelet, reticulocyte, hematochrome) all within normal range, the hepatic and renal function of each matched group rabbit is all in normal range, other internal organs are observed all no abnormal through prolonged application, as seen this polysaccharide mixture has no side effect.
4, this mixture has passed through further acute toxicological experiment: press human dose and be standard for 80 milliliters/day, amount to 100 milliliters of/day maximal doses and irritate 100 milliliters, 140 milliliters no abnormal performances of continuous quadratic of stomach to experimental rabbits.180 milliliters of rabbit performances for the third time are quiet few moving, and recovering normal after 30 minutes, analyzing reason is due to stomach rises.Diet, feces, hair color, respiratory activity are all normal in seven days, and test of many times does not also have dead the generation, clinical 200 milliliters/kilogram of the dosage human body maximum amounts of restraining oneself that provide, visible property of medicine safety.
For showing the therapeutic effect of thrombolysis activity polysaccharide mixture of the present invention, select cardiovascular and cerebrovascular disease acute stage 180 of convalescents later, be divided into two groups, experimental group 100 examples, matched group 80 examples.
Therapeutic scheme:
Experimental group: 100 examples are inactive conventional thromboembolism treatment medicine all, takes polysaccharide mixture of the present invention, every day 3 times, and each 20-40 milliliter, one day one-period, 4 days is 1 course for the treatment of.
Matched group: 80 examples are all taken the conventional therapy product, and wherein drug dosage and test group are complementary, and take four days.
Curative effect judging standard:
((the relevant efficacy assessment standard in the new Chinese medicine clinical guidance principle) of WHO and China's health formulation (is nimodipine [integration before the treatment-treatment back integration]/preceding integration for the treatment of in A World Health Organization (WHO) *100%.
Produce effects: than following more than 2/3 before the medicine, the neurologic defect integration descends 〉=50% behind the tcm symptom integration medicine.
Effectively: Chinese medicine symptom integral decline 1/3-2/3, the neurologic defect integration descends<20%.
After the course for the treatment of, the clinical effectiveness evaluation:
1, to the blood flow degree learn index to influence evaluation result as shown in table 4:
Table 4
Group Produce effects (routine number) Effectively (routine number) Invalid (routine number) Worsen (routine number) Total effective rate
Experimental group 81 17 2 0 98%
Matched group 7 26 47 0 41.25%
As can be seen from Table 4,100 cardiovascular and cerebrovascular diseases acute stages convalescent are later taken polysaccharide mixture of the present invention do therapeutic test, total effective rate is up to 98% after 4 days course for the treatment of.
2、
Table 5
Group Whole blood contrast viscosity Plasma viscosity The nearly former viscosity of whole blood
Experimental group (before taking) 5.88±1.03 2.43±0.54 8.24±1.84
Experimental group (taking the back) 5.00±1.42 1.39±0.37 7.31±1.63
Matched group (before the medicine) 5.02±1.59 1.96±0.79 8.05±1.75
Matched group (behind the medicine) 4.97±1.32 1.81±0.58 7.62±1.47
As can be seen from Table 5,100 cardiovascular and cerebrovascular diseases acute stages convalescent are later taken polysaccharide mixture of the present invention do therapeutic test, whole blood contrast viscosity, plasma viscosity, the nearly former viscosity of whole blood all have remarkable reduction after the course for the treatment of.
Table 6
Group Packed cell volume Celloglobulin mg% Erythrocyte electrophoretic time
Experimental group (before taking) 43.24±4.25 348.46±71.96 23.19±3.56
Experimental group (taking the back) 44.85±3.58 311.98±68.26 21.57±4.48
Matched group (before the medicine) 45.37±5.86 389.87±84.06 23.84±4.25
Matched group (behind the medicine) 43.56±6.12 341.78±76.36 22.53±3.88
Experimental group (taking the back) P<0.05, matched group (behind the medicine) P<0.01.
As can be seen from Table 6,100 cardiovascular and cerebrovascular diseases acute stages convalescent are later taken polysaccharide mixture of the present invention do therapeutic test, packed cell volume, celloglobulin, erythrocyte electrophoretic time all have remarkable reduction after the course for the treatment of.
In addition, for showing thrombolysis activity polysaccharide mixture of the present invention to the therapeutic effect of hyperlipidemia disease, select 100 of hyperlipidemia patients, be divided into two groups, experimental group 50 examples, matched group 50 examples.
Therapeutic scheme:
Experimental group: 50 examples are inactive conventional hyperlipidemia medicine all, takes polysaccharide mixture of the present invention, every day 3 times, and each 20-40 milliliter, one day one-period, 4 days is 1 course for the treatment of.
Matched group: 50 examples are not all taken any hyperlipidemia treatment product.
Curative effect judging standard:
Tried the standard that relevant adjustment hypolipidemic medicine is studied and defined in the 15 class clinical drugs research guidelines (trying) with reference to Ministry of Public Health.
Produce effects: reach following each person: TC decline 〉=20, TG decline 〉=40, TDG-C rising 〉=10mg/dl, AL descends 〉=20%.
Effectively: reach following each person: TC decline 10-19%, TG decline 20-39%, HDG-C rising 1-9mc/dl, AL decline 10-20%.
Invalid: as not reach effective standard person.
Worsen: reach following each person: TC rising 〉=10%, TG rising 10%, HDC-C decline 〉=4mg/dl, AL rises 〉=10%.
After the course for the treatment of, the clinical effectiveness evaluation:
Table 7
Group Produce effects (routine number) Effectively (routine number) Invalid (routine number) Total effective rate
Experimental group 23 26 1 98%
Matched group 6 21 23 54%
As can be seen from Table 7,50 hyperlipidemia patients are taken polysaccharide mixture of the present invention do therapeutic test, total effective rate is up to 98% after 4 days course for the treatment of.
Table 8
Group TC TG HDL-C AL
Experimental group 184.54±18.65 172.56±14.49 39.54±2.72 4.29±1.02
Matched group 184.54±18.65 163.92±11.38 39.99±2.57 3.78±0.84
Experimental group P<0.05, matched group P<0.01.
By above every evidence, Chinese herbal medicine polysaccharide and microbial activity polysaccharide mixture are as a kind of newtype drug, suitable hyperlipemia index in five of the blood fat reducing there is fairly obvious effect, further contain abundant total amino acids in this polysaccharide mixture of analytical proof, dendrobine, dendrophnol, Herba Dendrobii ammonia, various trace elements, cellulose etc., so this active polysaccharide mixture has powerful cleaning blood toxicity, improve the blood of human body microcirculation, the hepatoprotective function of gallbladder promoting, strong muscle blood fat reducing, nourish cloudy Tianjin, strengthen the spleen and stomach benefiting qi and nourishing blood, balancing blood pressure, potent blood sugar lowering, strong thrombus-dissolving, further the mixture of analytical proof thrombolytic mixing polysaccharide has many-sided biological activity, is high-quality and Chinese herbal medicine microbial polysaccharide mixture without any side effects in the world today.Can effectively treat heart and brain thrombosis acute stage disease, the sequela of acute stage is recovered and prevented that recurrence from having significant treatment preventive effect, has special effect to angiomalacia Nutrition significant medium-height grass property of medicine polysaccharide and microbial bacteria mycelium polysaccharide mixture pharmacodynamic feature again simultaneously.

Claims (9)

1. the processing technology of a thrombolysis activity polysaccharide mixture, it is characterized in that: this polysaccharide mixture is that the polysaccharide mixed liquor that concentrates of the Herba Dendrobii that utilizes the combined-enzyme method lixiviate, Flos Chrysanthemi, Fructus Crataegi and be mixed by the fermentation liquid of Auricularia, Cordyceps mycelium forms, and comprises in the concrete manufacturing process steps:
(1) choose Herba Dendrobii, Flos Chrysanthemi, Fructus Crataegi herbal raw material, carry out following steps respectively to obtain Dendrobium officinale polysaccharide liquid, chrysanthemum polysaccharide liquid and Fructus Crataegi polysaccharide liquid:
A, rinsing are to remove the Chinese herbal medicine surface irregularities;
Add water in b, the Chinese herbal medicine after rinsing, the reuse colloid mill grinds to form serosity;
C, in serosity, add the water of 5-30 times of weight, heat, be warming up to 100 ℃, be cooled to 85 ℃ again, under pressure 30MPa, utilize high pressure homogenizer to handle, obtain homogeneous slurry;
D, add compound protease lixiviate 1 ~ 2 hour in homogeneous slurry, wherein, homogeneous slurry with the ratio of the weight of compound protease is: 100:(1.5 ~ 2), compound protease is that cellulase, pectase and the protease of 1:1:1 is formed by weight ratio;
E, lixiviating solution are through low speed centrifuge separates, filtering and concentrating is removed 10-20% moisture and dry, and be stand-by;
(2) choose the strain of Auricularia and Cordyceps, carry out following steps respectively to obtain Auricularia polycose extracting solution and Cordyceps polysaccharides extracting solution:
ⅰ, take slant strains to cultivate, the breeding of shaking table liquid, seed tank liquid spawn three-class strain is cultivated liquid spawn separately, liquid spawn being introduced supporting fermentation tank respectively fermented 3-7 days in liquid culture medium again, treat that mycelial growth concentration or weight in wet base ratio stops fermentation when reaching 65-80%, solid residue in the filtering fermentating liquid, it is stand-by to obtain the fermentation filtered solution;
ⅱ, be not less than 90 ℃ in temperature, under the ambient pressure 1.2-1.5 atmospheric pressure, in the fermentation filtered solution, add the compound protease of being formed by pepsin and papain and carry out pyrolysis, inactivation treatment, the ratio of filtered solution and the weight of compound protease of wherein fermenting is 100:(0.5 ~ 2), the ratio of the quality of pepsin and papain is 1:1;
ⅲ, will filter, concentrate to remove moisture and the miscellaneous material of 10-20% through the fermentation filtered solution of pyrolysis, inactivation treatment, stand-by;
(3) Dendrobium officinale polysaccharide liquid, chrysanthemum polysaccharide liquid, Fructus Crataegi polysaccharide liquid, Auricularia polycose extracting solution and Cordyceps polysaccharides extracting solution are mixed according to following percent by volume:
Dendrobium officinale polysaccharide liquid 5-50%,
Chrysanthemum polysaccharide liquid 10-30%,
Fructus Crataegi polysaccharide liquid 5-15%,
Auricularia polycose extracting solution 10-40%,
Cordyceps polysaccharides extracting solution 5-35%;
(4) under gnotobasis, the mixed liquor that the back that is mixed is formed carries out pressure 10 ~ 15MPa homogenizing at 60 ℃, divides bottle, encapsulation, sterilization to become finished product.
2. the processing technology of a kind of thrombolysis activity polysaccharide mixture according to claim 1, it is characterized in that: among the step e, described dry carries out following processing again:
E1, in dry, add the water of 5-30 times of weight, heat, be warming up to 100 ℃, be cooled to 85 ℃ again, under pressure 30MPa, utilize high pressure homogenizer to handle, obtain homogeneous slurry;
E2, add compound protease lixiviate 1 ~ 2 hour in homogeneous slurry, wherein, homogeneous slurry with the ratio of the weight of compound protease is: 100:(1 ~ 1.5), compound protease is that cellulase, pectase and the protease of 1:1:1 is formed by weight ratio;
E3, lixiviating solution are through low speed centrifuge separates, filtering and concentrating is removed 10-20% moisture and dry, and be stand-by.
3. the processing technology of a kind of thrombolysis activity polysaccharide mixture according to claim 2, it is characterized in that: among the step e3, described dry carries out following processing again:
E31, in dry, add the water of 5-30 times of weight, heat, be warming up to 100 ℃, be cooled to 85 ℃ again, under pressure 30MPa, utilize high pressure homogenizer to handle, obtain homogeneous slurry;
E32, add compound protease lixiviate 1 ~ 2 hour in homogeneous slurry, wherein, homogeneous slurry with the ratio of the weight of compound protease is: 100:(0.5 ~ 1), compound protease is that cellulase, pectase and the protease of 1:1:1 is formed by weight ratio;
E33, lixiviating solution are through low speed centrifuge separates, filtering and concentrating is removed 10-20% moisture and dry, and be stand-by.
4. the processing technology of a kind of thrombolysis activity polysaccharide mixture according to claim 1, it is characterized in that: the fermentation temperature of described Auricularia is 24-26 degree centigrade, the fermentation temperature of described Cordyceps is 16-18 degree centigrade.
5. the processing technology of a kind of thrombolysis activity polysaccharide mixture according to claim 1, it is characterized in that: the pressure in the described fermentation tank is 30-50MPa, liquid culture medium carbon, nitrogen are than being 1:(16-24), inoculum concentration is 10%, ventilation be the 0.4-0.6 cubic meter/minute, mixing speed is 120-180 rev/min.
6. the processing technology of a kind of thrombolysis activity polysaccharide mixture according to claim 1 is characterized in that: when the Auricularia strain carried out step I in the step (2), the liquid culture medium of employing was prepared by following percentage by weight:
Testa Tritici juice 8-10%,
Corn juice 5-10%,
Murphy juice 10-15%,
Bean milk 15-20%,
Yeast powder 0.5-1%,
Sucrose 0.5-3%,
Glucose sugar 0.5-2%,
Magnesium sulfate 0.02-0.05%,
Phosphoric acid phenodiazine potassium 0.05-0.1%,
Peptone 0.3-1%,
Oleum Arachidis hypogaeae semen 0.3-0.6%,
Surplus is water.
7. the processing technology of a kind of thrombolysis activity polysaccharide mixture according to claim 1 is characterized in that: when Cordyceps strain carried out step I in the step (2), the liquid culture medium of employing was prepared by following percentage by weight:
Dried silkworm chrysalis meal 1-2%,
Milk powder 2-3%,
Murphy juice 20-30%,
Bean milk 25-35%,
Semen setariae juice 10-20%,
Corn juice 10-20%,
Yeast powder 1-2%,
Sucrose 0.5-2%,
Glucose 1-3%,
Peptone 0.5-1%,
Magnesium sulfate 0.05-0.1%,
Phosphoric acid phenodiazine potassium 0.15-0.18%,
Vitamin B1 0.5-1%
Oleum Arachidis hypogaeae semen 0.5-0.8%,
Surplus is water.
8. the processing technology of a kind of thrombolysis activity polysaccharide mixture according to claim 1, it is characterized in that: also comprise in the described step (4) with at mixed liquor at 60 ℃, carry out pressure 15MPa homogenizing active polysaccharide liquid afterwards and form powder through drying process with atomizing, powder is packed formed capsule or electuary or tablet again.
9. the processing technology of a kind of thrombolysis activity polysaccharide mixture according to claim 1 is characterized in that: the filtration operation of described lixiviating solution is to adopt ultrafilter membrane or reverse osmosis membrane filtration.
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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106074713A (en) * 2016-08-10 2016-11-09 翔天农业开发集团股份有限公司 A kind of antihypertensive health care oral liquid and preparation method thereof
CN107974475A (en) * 2017-12-29 2018-05-01 贺州市星辉科技有限公司 A kind of technique of enzyme edman degradation Edman from dendrobium candidum leaf extraction polysaccharide
CN111334540A (en) * 2020-03-31 2020-06-26 泉后(广州)生物科技研究院有限公司 Method for extracting dendrobium officinale polysaccharide by utilizing biological fermentation
CN112646726A (en) * 2019-10-11 2021-04-13 孙傲 Culture medium for black fungus fermentation, fermentation method and fermented beverage
CN113563488A (en) * 2021-01-26 2021-10-29 宁波希诺亚海洋生物科技有限公司 Preparation method of pharmaceutical-grade micromolecular marine organism polysaccharide

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1377679A (en) * 2002-03-18 2002-11-06 刘鑫隆 Traditional Chinese medicine particulate preparation for curing cardiovascular and cerebrovascular diseases and its preparing method

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1377679A (en) * 2002-03-18 2002-11-06 刘鑫隆 Traditional Chinese medicine particulate preparation for curing cardiovascular and cerebrovascular diseases and its preparing method

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
巫少青: "中药治疗29例脑血栓形成临床小结", 《江西中医药》 *
珊瑚: "食疗脑血栓", 《健身科学》 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106074713A (en) * 2016-08-10 2016-11-09 翔天农业开发集团股份有限公司 A kind of antihypertensive health care oral liquid and preparation method thereof
CN107974475A (en) * 2017-12-29 2018-05-01 贺州市星辉科技有限公司 A kind of technique of enzyme edman degradation Edman from dendrobium candidum leaf extraction polysaccharide
CN112646726A (en) * 2019-10-11 2021-04-13 孙傲 Culture medium for black fungus fermentation, fermentation method and fermented beverage
CN111334540A (en) * 2020-03-31 2020-06-26 泉后(广州)生物科技研究院有限公司 Method for extracting dendrobium officinale polysaccharide by utilizing biological fermentation
CN113563488A (en) * 2021-01-26 2021-10-29 宁波希诺亚海洋生物科技有限公司 Preparation method of pharmaceutical-grade micromolecular marine organism polysaccharide

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