CN101002858A - Medicine composition for enhancing immunity, and its preparing method and use - Google Patents
Medicine composition for enhancing immunity, and its preparing method and use Download PDFInfo
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- CN101002858A CN101002858A CNA2006101713336A CN200610171333A CN101002858A CN 101002858 A CN101002858 A CN 101002858A CN A2006101713336 A CNA2006101713336 A CN A2006101713336A CN 200610171333 A CN200610171333 A CN 200610171333A CN 101002858 A CN101002858 A CN 101002858A
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Abstract
A medical composition for improving immunity, relieving fatigue, delaying sanility and promoting appetite is proportionally prepared from tuckahoe, ginseng and wolfberry fruits. Its preparing process is also disclosed.
Description
Technical field
The present invention relates to a kind of compositions of health-care effect, particularly a kind of composition and method of making the same and its purposes with enhance immunity effect.
Background technology
Chinese medicine Radix Ginseng, Poria preparation patent medicine are seen in Chinese medicine already, as decoction of four noble drugs, Liujunzi Tang, BAZHEN TANG, SHENLING BAISHU SAN, bolus of ten powerful tonics or the king pellet that nourishes heart, or be used to strengthen the spleen and stomach, or be used for vigorate qi and replenish the blood, or being used for strongly invigorating primordial QI, nourishing kidney is established the yang function and is mended the congenital foundation with training.
The main functional component of Radix Ginseng is ginsenoside and ginseng polysaccharide.Ginsenoside and ginseng polysaccharide have the effect of irritation cell immunity and humoral immunization, can strengthen the phagocytic rate and the phagocytic index of Turnover of Mouse Peritoneal Macrophages, promote peripheral blood leucocyte to increase, and effect is particularly evident when leukopenia, can also generate by enhancing antibody, increase the content of serum immunoglobulin IgG, IgA.
The main functional component of Poria is the water solublity pachyman.The water solublity pachyman can be adjusted the ratio of T cell subsets, promotes T
4/ T
8Ratio, strengthen the NK cytoactive, improve the phagocytic index of macrophage, impel cancer patient's interleukin II (IL-2) to be increased to normal level, and, promote macrophage to discharge the activity of TNF and enhance TNF by strengthening tumor necrosis factor (TNF) gene transcription.
Fructus Lycii is traditional tonic Chinese medicine and famous and precious tonification class Chinese medicine, has effects such as the moon of invigorating the liver and kidney, building body, enrich and benefit essence and blood, enhance immunity, its main functional component be lycium barbarum polysaccharide (Lyceum barbarum Polysaccharide, LBP).LBP is made up of 6 kinds of monosaccharide such as arabinose, glucose, galactose, mannose, xylose, rhamnose.Fructus Lycii also contains albumen heteropolysaccharide, aminoacid and various trace elements.Shennong's Herbal is classified Fructus Lycii as top grade, says its " it is anti-old to make light of one's life by commiting suicide for clothes of a specified duration, hard muscles and bones "." property of medicine opinion " say its " mend the vital essence various symptoms and signs of deficiency, easily color, bleach, make eye bright and calm the nerves, make us long-lived ".LBP obviously promotes LACA mouse boosting cell propagation and antibody to generate, and obviously increases the mice (SAMP of quick aging model
8) number of spleen antibody-producting cell, increase the level that splenocyte produces IgG antibody, significantly promote the function of mouse thymus T cell proliferation and enhancing NK cell, increase macrophage quantity and the remarkable activity that strengthens DNA, RNA, glycogen content, main metabolic enzyme in the macrophage, significantly strengthen its phagocytic function.
The hypoimmunity crowd easily catches a cold, diseases such as chronic bronchitis, chronic hepatitis, chronic nephritis, shows as that peripheral blood NK cell actively reduces, t lymphocyte subset group T
4/ T
8Ratio reduces, the function of macrophage reduces, change of serum C
3Cellular immune functions such as complement level reduction are low, even the part crowd perplexed by tumor because of hypoimmunity, and tumor patient also often follows the serum interleukin II (IL-2) and the level of tumor necrosis factor (TNF) to reduce.
Summary of the invention
The object of the present invention is to provide a kind of compositions with enhance immunity effect, its effective ingredient is made up of Poria, Radix Ginseng and Fructus Lycii.
Further, preparation compositions raw materials of effective components composition is counted by weight, Poria 30-3000 part, Radix Ginseng 10-1000 part, Fructus Lycii 20-2000 part, be preferably Poria 60-1500 part, Radix Ginseng 20-500 part, Fructus Lycii 40-1000 part, more preferably Poria 120-750 part, Radix Ginseng 40-250 part, Fructus Lycii 80-500 part most preferably are 300 parts in Poria, 100 parts of Radix Ginsengs, 200 parts of Fructus Lyciis.
Further, in the ginsenoside, the percentage composition of total saponins is not less than 1% in the compositions.
Further, poly-in the Portugal, the percentage composition of crude polysaccharides is not less than 5% in the compositions.
Further, the effective ingredient of described Poria is a Poria extract, is preferably the pachyman in the extract; Described pachyman can be made by method well known in the art, and pachyman extract that makes as the alkaline extraction acid precipitation method or carboxymethyl pachyman (Carboxymethylpachymaran, CMP) or high substituted degree CMP.
Described alkaline extraction acid precipitation method is meant: Poria powder concentration is that the alkaline solution of 1.0-4.0mol/L or 2.0-3.0mol/L stirs extraction, and supernatant is got in centrifugalize; Supernatant adds acid (as acetic acid, hydrochloric acid, sulphuric acid or nitric acid), gets acid deposit; Precipitate promptly gets the pachyman crude product through centrifugal, washing.
Purpose one of the present invention provides a kind of preparation high substituted degree CMP, made by following method: 1) pachyman joins in water or the water alcohol mixed liquor, after stirring, adds the alkaline solution of pachyman quality 1-8% or 2-6% or 3-5%, be stirred to dissolving fully, get the pachyman alkaline solution; 2) after the 1.0-10mol/L monoxone fully reacts with suitably excessive 2.0-10mol/L alkaline solution, join 1) in the pachyman alkaline solution of step gained, carry out substitution reaction, the CMP that separation and purification generates, promptly.
Further, described pachyman is made by method well known in the art, and the pachyman alkalization extracting solution as the alkalization extraction method makes is equivalent to 1) the pachyman alkaline solution that makes of step; Or the pachyman extract that makes of alkaline extraction acid precipitation method.
Described alkalization extraction method is meant: it is extractions of alkalizing of the alkaline solution of 1.0-4.0mol/L or 2.0-3.0mol/L that Poria powder adds concentration, and supernatant is got in centrifugalize, promptly gets the pachyman extracting solution that alkalizes.
Further, described water-alcohol solution is that alcoholic solvent well known in the art adds the solution that water makes, and described alcoholic solvent is selected from any or its combination of methanol, ethanol, propylene glycol, ethyl acetate, acetone, dimethyl sulfoxide, ether, isopropyl alcohol, dimethyl formamide.
Alkaline solution of the present invention is dissolved in water by alkaline matter well known in the art and makes, and described alkaline matter is selected from any or its combination of sodium hydroxide, potassium hydroxide, sodium carbonate or potassium carbonate, is preferably sodium hydroxide or potassium hydroxide.
Further, the concentration of chloroacetic acid solution is 2.0-9.0mol/L, is preferably 3.0-8.0mol/L, and more preferably 4.0-7.0mol/L most preferably is 4.5-6.0mol/L.
Further, 2) concentration of step alkaline solution is 3.0-9.0mol/L, is preferably 4.0-8.0mol/L, and more preferably 5.0-7.0mol/L most preferably is 5.5-6.5mol/L.
Further, the described suitably excessive actual amount that is meant alkaline solution neutral and alkali material is than itself and the excessive 0.5-40% of the required theoretical consumption of monoxone generation neutralization reaction, preferred excessive 5-30%, more preferably excessive 10-25%, most preferably excessive 15-20%.
Further, 2) reactant liquor carries out substitution reaction 1-5h the step under 30-100 ℃ of condition, and preferable reaction temperature is 40-90 ℃, and other is preferably 50-85 ℃, more preferably 60-82 ℃, most preferably is 75-80 ℃; The preferred reaction time is 2-4h, more preferably 2.5-3.5h.
Further, described separation is meant 2) add the acid solution of 1.0-10mol/L in the step reaction solution, transfer its pH value 5.0-7.0 after, add the alcoholic solvent of 3-5 times of volume, separate out the CMP crude product; Described alcoholic solvent is selected from any or its combination of methanol, ethanol, propylene glycol, ethyl acetate, isopropyl alcohol, ether, acetone.
Acid solution of the present invention is dissolved in water by acidic materials well known in the art and makes, and preferred described acidic materials are selected from any or its combination of acetic acid, hydrochloric acid, sulphuric acid or nitric acid, are preferably hydrochloric acid or nitric acid.
Further, described purification is meant that the CMP crude product adds the aqueous solution that water is made into 1.0%-6.0% or 2.0%-5.0% or 3%-4%, adds the alkaline solution adjust pH 9.0-12.0 of 1.0mol/L-10mol/L, is stirred to the CMP crude product and dissolves fully; Add 30%H
2O
2Solution, its consumption are lysate total measurement (volume) 0.1 ‰-2.0 ‰ or 0.5 ‰-1.0 ‰, carry out decoloring reaction; The acid solution adjust pH 5.0-7.0 that adds 1.0-10mol/L, ultrafiltration is removed molecular weight less than 0.7 * 10
4Daltonian CMP and other small molecular weight impurities.
Further, the concentration of alkaline solution is 2.0-9.0mol/L, is preferably 3.0-8.0mol/L, and more preferably 4.0-7.0mol/L most preferably is 5.0-6.0mol/L.
Further, the temperature of decoloring reaction is 10 ℃-70 ℃, is preferably 15 ℃-60 ℃, more preferably 20 ℃-50 ℃.The time of decoloring reaction decides according to the performance level of decoloring reaction, is generally 2-48h, is preferably 5-40h, and more preferably 10-30h most preferably is 15-25h.
Further, the concentration of acid solution is 1.0-9.0mol/L, is preferably 2.0-8.0mol/L, and more preferably 3.0-7.0mol/L most preferably is 4.0-6.0mol/L.
Further, described ultrafiltration is to carry out ultrafiltration with the DH-UF hollow fiber membrane ultrafiltration device.
According to actual needs, can carry out the separating for several times purification to the high substituted degree CMP that reaction is produced, to improve its purity.
Further, the degree of substitution by carboxymethyl of described CMP is not less than 1.0, preferably is not less than 1.05, more preferably is not less than 1.10, most preferably is not less than 1.2.
Further, the molecular weight of high substituted degree CMP is 0.7 * 10
4-1.0 * 10
6Dalton is preferably 3.0 * 10
4-8 * 10
5Dalton, more preferably 6.0 * 10
4-5.0 * 10
5Dalton most preferably is 8.0 * 10
4-3.0 * 10
5Dalton.
Further, the degree of polymerization of high substituted degree CMP is 32＜n＜4545, is preferably 136＜n＜3636, and more preferably 272＜n＜2272 most preferably are 363＜n＜1363.
Further, the effective ingredient of described Radix Ginseng is the Radix Ginseng powder, can be made by preparation method well known in the art, or be made by following method: the Radix Ginseng drying, pulverize behind the sterilizing, and sieve, promptly.
Further, the effective ingredient of described Fructus Lycii is a wolfberry fruit extract, and can be made by preparation method well known in the art, or be made by following method: 1) Fructus Lycii powder is soaked, and water-bath is extracted repeatedly, and merging filtrate gets crude extract; 2) behind the concentrating under reduced pressure crude extract, carry out alcohol and analyse, dry alcohol is analysed precipitate promptly.It is to precipitate the effective ingredient that concentrates in the crude extract with alcoholic solvent well known in the art that described alcohol is analysed; Described alcoholic solvent is selected from any or its combination of methanol, ethanol, propylene glycol, ethyl acetate, isopropyl alcohol, ether, acetone.
Except as otherwise noted, percentage composition of the present invention is weight percentage; Described molecular weight is relative molecular weight, and its unit is dalton.
Compositions of the present invention has effects such as resisting fatigue, defying age, appetite strengthening, can improve the immunocompetence of body comprehensively, be applicable to the immunity that strengthens various hypoimmunity crowds, especially be fit to middle-aged and elderly people immunity reduction person, and hypoimmunity crowds such as chronic bronchitis, chronic hepatitis, chronic nephritis and tumor.Poria extract, Radix Ginseng powder and wolfberry fruit extract all contain potent enhance immunity composition in the compositions, and three medicine prescriptions have synergistic function.
1, Poria is the dry sclerotia of Poria cocos (Schw.) Wolf, sweet in the mouth, and property is flat, and Shennong's Herbal is classified it as top grade, says its " clothes peace soul is reposed for a long time, and is not hungry, prolongs life ".Poria has the effect of spleen invigorating invigorating middle warmer, tranquilizing by nourishing the heart, promoting diuresis to eliminate damp pathogen.Its chemical constituent is comparatively complicated, contains β-pachyman, pachyman, pachymic acid, acetyl pachymic acid, the acid of loose Siberian cocklebur and layer hole acid etc., and wherein pachyman is the main active of enhance immunity.
Pachyman is to S in the mice body
180The suppression ratio of sarcoma cell can reach 48%, can promote cellular immunization person's on the low side cellular immune function to strengthen.Clinical research to patients with lung cancer shows, the immunity of pachyman pair cell has very strong facilitation, can adjust the ratio of T cell subsets especially, the enhancing human body immunity function is improved body condition, strengthen anti-infection ability, pachyman can strengthen the macrophage recognition function, improves the phagocytic rate and the phagocytic index of macrophage, and can be by strengthening tumor necrosis factor (TNF) gene transcription, promote macrophage to discharge TNF, and the activity of enhance TNF.TNF is the excretory peptide species of macrophage, is a kind of cytokine that can directly cause death of neoplastic cells.TNF not only participates in mononuclear cell directly to the killing and wounding of tumor cell, and can pass through the suppressor gene transcriptional activity, reduces the expression of myc gene mRNA specifically.
2, Radix Ginseng is the dry root of araliaceae ginseng plant's Radix Ginseng Panax Ginseng C.A.Mey, is traditional rare Chinese medicine, and Shennong's Herbal is classified it as top grade, and " tonifying five ZANG-organs is pacified spirit, decides soul, and spasmolytic is throbbed with fear, and removes pathogen, makes eye bright, happy Fructus Alpiniae Oxyphyllae to say it.Clothes are made light of one's life by commiting suicide and are prolonged life for a long time ".The Radix Ginseng sweet in the mouth, little hardship, slightly warm in nature has strongly invigorating primordial QI, recuperating depleted YANG and rescuing the patient from collapse, a function of the Fructus Alpiniae Oxyphyllae of calming the nerves, promoting the production of body fluid to quench thirst, and is chronic deficient and celebrated treating always clinically.Contain ginsenoside, several amino acids, polysaccharide, low molecular peptide class, organic acid, fatty acid, V in the Radix Ginseng
B, V
C, Yan acid, choline, pectin, trace element etc.Monomer has ginsenoside Ro, Ra1, Ra2, Rb1, Rb2, Rb3, Rc, Rd, Re, Rf, Rg1 etc., and the ginsenoside is the main component of its raise immunity.
Radix Ginseng has nonspecific resistivity to various destructive stimulus factors such as physics, chemistry or biologies, makes disorderly functional recovery normal, mainly shows the dual regulation of blood pressure, adrenal gland, thyroid function and blood glucose aspect.Existing animal experiment proves that the ginsenoside all has stimulation to humoral immunization and the cellular immunization of mice, can promote that the leukocyte in the peripheral blood increases, and when leukopenia, acts on particularly evident; Can also increase the phagocytic function of Turnover of Mouse Peritoneal Macrophages, improve inertia colloid carbon granule, staphylococcus aureus, Sanguis Gallus domesticus cell etc. in the blood are engulfed the ability of cleaning up.Dosage increases, administration number of times increases, and acts on strong more.Confirmed the effect that the ginsenoside has stimulates humoral immunization and cellular immunization already, energy enhancing human body immunity function is prevented and treated the leukopenia that multiple reason causes.Radix Ginseng can strengthen the phagocytic function of reticuloendothelial system and macrophage, and RES still can keep state of activation about about 1 week after the drug withdrawal.But Radix Ginseng is the generation of enhancing antibody also, increases the content of serum immunoglobulin IgG, IgA, IgM.The ginsenoside Rg1 can strengthen the senile rat immunologic function by selectivity; improve the behavioral activity and the operational capacity of senile rat; improve the hippocampal neurons function; promote c-fos expression of gene in the rat hippocampus neurocyte; to the neurotoxicity of antiglutamic acid mediation, and former rat hippocampus neurocyte of being commissioned to train foster shown the certain protection effect.
3, Fructus Lycii is traditional tonic Chinese medicine and famous and precious tonification class Chinese medicine, has effects such as the moon of invigorating the liver and kidney, building body, enrich and benefit essence and blood, enhance immunity, its main functional component be lycium barbarum polysaccharide (Lyceum barbarum Polysaccharide, LBP).LBP is made up of 6 kinds of monosaccharide such as arabinose, glucose, galactose, mannose, xylose, rhamnose.Fructus Lycii also contains albumen heteropolysaccharide, aminoacid and various trace elements.Shennong's Herbal is classified Fructus Lycii as top grade, says its " it is anti-old to make light of one's life by commiting suicide for clothes of a specified duration, hard muscles and bones "." property of medicine opinion " say its " mend the vital essence various symptoms and signs of deficiency, easily color, bleach, make eye bright and calm the nerves, make us long-lived ".LBP obviously promotes LACA mouse boosting cell propagation and antibody to generate, and obviously increases the mice (SAMP of quick aging model
8) number of spleen antibody-producting cell, increase the level that splenocyte produces IgG antibody, significantly promote the function of mouse thymus T cell proliferation and enhancing NK cell, increase macrophage quantity and the remarkable activity that strengthens DNA, RNA, glycogen content, main metabolic enzyme in the macrophage, significantly strengthen its phagocytic function.
Result of study shows: lycium barbarum polysaccharide promotes mouse lymphocyte propagation and IL-2 to produce, obviously strengthen the lymphproliferation response that ConA excites, significantly strengthen T lymphocyte function and B cellular immune function, also promote IL-2 to produce and the IR-2R expression, promote the release of cytokines such as IL-2 and IL-3, enhancing human body immunity function and delay body aging.
Clinical research shows, malignant tumor patient lymphocyte T
3/ T
4And T
4/ T
8Ratio, lymhocyte transformation rate and macrophage phagocytic rate are starkly lower than the normal person.After tumor patient carries out radiation alone, patient's T
3/ T
4And T
4/ T
8Ratio, lymhocyte transformation rate and macrophage phagocytic rate obviously descend before than radiotherapy, and peripheral white blood cell and lymphocyte absolute value also obviously reduce.And tumor patient is taken LBP, can keep the former level of peripheral white blood cell and lymphocyte absolute value, and than obviously increasing before the radiotherapy, has the effect that improves and strengthen the radiotherapy patient immunologic function, can be used as the adjuvant therapy medicaments of tumor patient.
The mechanism of LBP raise immunity: part is by regulating maincenter hypothalamus and peripheral immune organ spleen sympathetic nerve, discharge monoamine neurotransmitters such as norepinephrine, and adrenal cortex discharges links such as corticosterone, transfers plasma corticosterone with the performance hypothalmus-pituitary-adrenal axis and participates in immunoreation.
The present composition can be various dosage form well known in the art, and being suitable for dosage form of the present invention can be preferably oral formulations for oral formulations, external preparation or injection.Oral formulations can be selected from oral liquid, tablet, capsule, granule, pill, powder, syrup, mixture, distillate medicinal water, suspending agent (doing outstanding agent or suspension), Emulsion or medicinal tea etc.; External preparation is optional from gel, unguentum (emplastrum, coagulate unguentum or ointment), liniment, lotion, liniment etc.; Injection can be selected from injection, transfusion or freeze-dried powder etc.Can adopt preparation technique means well known in the art to prepare compositions of the present invention.
In case of necessity, also comprise pharmaceutically acceptable carrier in the present composition, the consumption of described pharmaceutically acceptable carrier, kind are decided according to the physicochemical property and the factors such as content, preparation type of effective ingredient in the compositions.
Described pharmaceutically acceptable carrier is usual excipients or the adjuvant that is used to prepare above-mentioned preparation well known in the art.Excipient or adjuvant that oral formulations or external preparation are commonly used include but are not limited to filler (diluent), lubricant (fluidizer or antitack agent), dispersant, wetting agent, binding agent, regulator, solubilizing agent, antioxidant, antibacterial, emulsifying agent etc.Binding agent, for example syrup, arabic gum, gelatin, sorbitol, tragacanth, cellulose and derivant thereof, gelatine size, syrup, starch slurry or polyvinylpyrrolidone, the preferred cellulose derivant is microcrystalline Cellulose, sodium carboxymethyl cellulose, ethyl cellulose or hydroxypropyl methylcellulose; Filler, for example lactose, Icing Sugar, dextrin, starch and derivant thereof, cellulose and derivant thereof, inorganic calcium salt, sorbitol or glycine, preferred inorganic calcium salt is calcium sulfate, calcium phosphate, calcium hydrogen phosphate, precipitated calcium carbonate; Lubricant, for example micropowder silica gel, magnesium stearate, Pulvis Talci, aluminium hydroxide, boric acid, hydrogenated vegetable oil, Polyethylene Glycol; Disintegrating agent, for example starch and derivant thereof, polyvinylpyrrolidone or microcrystalline Cellulose, preferred starch derivatives is carboxymethyl starch sodium, Explotab, pregelatinized Starch, modified starch, hydroxypropyl starch, corn starch; Wetting agent, for example sodium lauryl sulphate, water or alcohol etc.; The pharmaceutically acceptable carrier of preferred oral preparation is microcrystalline Cellulose, magnesium stearate or ethanol etc.
Excipient or adjuvant that described injection is commonly used include but are not limited to: antioxidant, for example sodium sulfite, sodium sulfite and sodium pyrosulfite; Antibacterial, for example 0.5% phenol, 0.3% cresol, 0.5% chlorobutanol; Regulator, for example hydrochloric acid, citric acid, potassium hydroxide (sodium), sodium citrate and buffer agent phosphoric acid dioxy sodium and sodium hydrogen phosphate; Emulsifying agent, for example Tween-80, do not have that sour Pyrusussuriensis is smooth, pluronic gram F-68, lecithin, fabaceous lecithin; Antioxidant, for example sodium sulfite, sodium pyrosulfite, dibutyl benzoic acid etc.; Solubilizing agent, for example tween 80, bile, glycerol etc.
In addition, also active component can be mixed by its preparation requirement with pharmaceutically acceptable slow controlled release carrier, again according to the preparation method of sustained-release preparation well known in the art, as adding the blocker coating or with making micropill after the active principle microcapsulesization again, as slow-release micro-pill or controlled release micro pill; Described slow controlled release carrier includes but are not limited to oil agent, hydrophilic colloid or the coating blocker etc. of mixing, and described oil to mix agent be glyceryl monostearate, castor oil hydrogenated, Dormant oils, polysiloxanes, dimethyl siloxane; Described hydrophilic colloid is cellulose derivatives such as sodium carboxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl emthylcellulose, or PVP, arabic gum, tragcanth or carbopol etc.; Described coating blocker is ethyl cellulose (EC), hydroxypropyl methylcellulose (HMPC), polyvinylpyrrolidone (PVP), cellulose acetate-phthalate (CAP), acrylic acid resinoid etc.
The daily dosage of the present composition can be decided according to factors such as age of the crowd of taking, sex, body constitution, health status, and common dose is 0.9-1.35g/ time, 3 times/day, is preferably 1.35g/ day, 2 times/day.
The present composition has special effect, bioavailability height, good stability, good looking appearance, characteristics such as easy to carry and use.
Another object of the present invention is to provide a kind of preparation to have enhance immunity effect method for compositions, the effective ingredient of uniform mixing Poria, Radix Ginseng and Fructus Lycii, promptly.
Further, preparation compositions raw materials of effective components composition is counted by weight, Poria 30-3000 part, Radix Ginseng 10-1000 part, Fructus Lycii 20-2000 part, be preferably Poria 60-1500 part, Radix Ginseng 20-500 part, Fructus Lycii 40-1000 part, more preferably Poria 120-750 part, Radix Ginseng 40-250 part, Fructus Lycii 80-500 part most preferably are 300 parts in Poria, 100 parts of Radix Ginsengs, 200 parts of Fructus Lyciis.
Further, in the ginsenoside, the percentage composition of total saponins is not less than 1% in the compositions.
Further, poly-in the Portugal, the percentage composition of crude polysaccharides is not less than 5% in the compositions.
Further, the effective ingredient of described Poria is a Poria extract, is preferably the pachyman in the extract; Described pachyman can be made by method well known in the art, and pachyman extract that makes as the alkaline extraction acid precipitation method or carboxymethyl pachyman (Carboxymethylpachymaran, CMP) or high substituted degree CMP.
Described alkaline extraction acid precipitation method is meant: Poria powder concentration is that the alkaline solution of 1.0-4.0mol/L or 2.0-3.0mol/L stirs extraction, and supernatant is got in centrifugalize; Supernatant adds acid (as acetic acid, hydrochloric acid, sulphuric acid or nitric acid), gets acid deposit; Precipitate promptly gets the pachyman crude product through centrifugal, washing.
Purpose one of the present invention provides a kind of method for preparing high substituted degree CMP, comprising the steps: 1) pachyman joins in water or the water alcohol mixed liquor, after stirring, the alkaline solution that adds pachyman quality 1-8% or 2-6% or 3-5%, be stirred to dissolving fully, get the pachyman alkaline solution; 2) after the 1.0-10mol/L monoxone fully reacts with suitably excessive 2.0-10mol/L alkaline solution, join 1) in the pachyman alkaline solution of step gained, carry out substitution reaction, the CMP that separation and purification generates, promptly.
Further, described pachyman is made by method well known in the art, and the pachyman alkalization extracting solution as the alkalization extraction method makes is equivalent to 1) the pachyman alkaline solution that makes of step; Or the pachyman extract that makes of alkaline extraction acid precipitation method.
Described alkalization extraction method is meant: it is extractions of alkalizing of the alkaline solution of 1.0-4.0mol/L or 2.0-3.0mol/L that Poria powder adds concentration, and supernatant is got in centrifugalize, promptly gets the pachyman extracting solution that alkalizes.
Further, described water-alcohol solution is that alcoholic solvent well known in the art adds the solution that water makes, and described alcoholic solvent is selected from any or its combination of methanol, ethanol, propylene glycol, ethyl acetate, acetone, dimethyl sulfoxide, ether, isopropyl alcohol, dimethyl formamide.
Alkaline solution of the present invention is dissolved in water by alkaline matter well known in the art and makes, and described alkaline matter is selected from any or its combination of sodium hydroxide, potassium hydroxide, sodium carbonate or potassium carbonate, is preferably sodium hydroxide or potassium hydroxide.
Further, the concentration of chloroacetic acid solution is 2.0-9.0mol/L, is preferably 3.0-8.0mol/L, and more preferably 4.0-7.0mol/L most preferably is 4.5-6.0mol/L.
Further, 2) concentration of step alkaline solution is 3.0-9.0mol/L, is preferably 4.0-8.0mol/L, and more preferably 5.0-7.0mol/L most preferably is 5.5-6.5mol/L.
Further, the described suitably excessive actual amount that is meant alkaline solution neutral and alkali material is than itself and the excessive 0.5-40% of the required theoretical consumption of monoxone generation neutralization reaction, preferred excessive 5-30%, more preferably excessive 10-25%, most preferably excessive 15-20%.
Further, 2) reactant liquor carries out substitution reaction 1-5h the step under 30-100 ℃ of condition, and preferable reaction temperature is 40-90 ℃, and other is preferably 50-85 ℃, more preferably 60-82 ℃, most preferably is 75-80 ℃; The preferred reaction time is 2-4h, more preferably 2.5-3.5h.
Further, described separation is meant 2) add the acid solution of 1.0-10mol/L in the step reaction solution, transfer its pH value 5.0-7.0 after, add the alcoholic solvent of 3-5 times of volume, separate out the CMP crude product; Described alcoholic solvent is selected from any or its combination of methanol, ethanol, propylene glycol, ethyl acetate, isopropyl alcohol, ether, acetone.
Acid solution of the present invention is dissolved in water by acidic materials well known in the art and makes, and preferred described acidic materials are selected from any or its combination of acetic acid, hydrochloric acid, sulphuric acid or nitric acid, are preferably hydrochloric acid or nitric acid.
Further, described purification is meant that the CMP crude product adds the aqueous solution that water is made into 1.0%-6.0% or 2.0%-5.0% or 3%-4%, adds the alkaline solution adjust pH 9.0-12.0 of 1.0mol/L-10mol/L, is stirred to the CMP crude product and dissolves fully; Add 30%H
2O
2Solution, its consumption are lysate total measurement (volume) 0.1 ‰-2.0 ‰ or 0.5 ‰-1.0 ‰, carry out decoloring reaction; The acid solution adjust pH 5.0-7.0 that adds 1.0-10mol/L, ultrafiltration is removed molecular weight less than 0.7 * 10
4Daltonian CMP and other small molecular weight impurities.
Further, the concentration of alkaline solution is 2.0-9.0mol/L, is preferably 3.0-8.0mol/L, and more preferably 4.0-7.0mol/L most preferably is 5.0-6.0mol/L.
Further, the temperature of decoloring reaction is 10 ℃-70 ℃, is preferably 15 ℃-60 ℃, more preferably 20 ℃-50 ℃.The time of decoloring reaction decides according to the performance level of decoloring reaction, is generally 2-48h, is preferably 5-40h, and more preferably 10-30h most preferably is 15-25h.
Further, the concentration of acid solution is 1.0-9.0mol/L, is preferably 2.0-8.0mol/L, and more preferably 3.0-7.0mol/L most preferably is 4.0-6.0mol/L.
Further, described ultrafiltration is to carry out ultrafiltration with the DH-UF hollow fiber membrane ultrafiltration device.
According to actual needs, can carry out the separating for several times purification to the high substituted degree CMP that reaction is produced, to improve its purity.
Further, the degree of substitution by carboxymethyl of described CMP is not less than 1.0, preferably is not less than 1.05, more preferably is not less than 1.10, most preferably is not less than 1.2.
Further, the molecular weight of high substituted degree CMP is 0.7 * 10
4-1.0 * 10
6Dalton is preferably 3.0 * 10
4-8 * 10
5Dalton, more preferably 6.0 * 10
4-5.0 * 10
5Dalton most preferably is 8.0 * 10
4-3.0 * 10
5Dalton.
Further, the degree of polymerization of high substituted degree CMP is 32＜n＜4545, is preferably 136＜n＜3636, and more preferably 272＜n＜2272 most preferably are 363＜n＜1363.
Further, the effective ingredient of described Radix Ginseng is the Radix Ginseng powder, can be made by preparation method well known in the art, or be made by following method: the Radix Ginseng drying, pulverize behind the sterilizing, and sieve, promptly.
Further, the effective ingredient of described Fructus Lycii is a wolfberry fruit extract, and can be made by preparation method well known in the art, or be made by following method: 1) Fructus Lycii powder is soaked, and water-bath is extracted repeatedly, and merging filtrate gets crude extract; 2) behind the concentrating under reduced pressure crude extract, carry out alcohol and analyse, dry alcohol is analysed precipitate promptly.It is to precipitate the effective ingredient that concentrates in the crude extract with alcoholic solvent well known in the art that described alcohol is analysed; Described alcoholic solvent is selected from any or its combination of methanol, ethanol, propylene glycol, ethyl acetate, isopropyl alcohol, ether, acetone.
In case of necessity, also comprise pharmaceutically acceptable carrier in the present composition, the consumption of described pharmaceutically acceptable carrier, kind are decided according to the physicochemical property and the factors such as content, preparation type of effective ingredient in the compositions.
The food that another object of the present invention is to provide the present composition to be used for preparing and have the enhance immunity effect or the application of medicine are preferably food or medicine with health care.
Further, described enhance immunity is used and is meant the immunity that is used for the low crowd of enhancing immunity, described hypoimmunity crowd is selected from middle-aged and elderly people, chronic bronchitis patient, chronic hepatitis patient, chronic nephritis patient, tumor patient or HIV sufferers, is preferred for preventing and treating or diseases such as chronic bronchitis, chronic hepatitis, chronic nephritis, malignant tumor or acquired immune deficiency syndrome (AIDS) that the auxiliary treatment hypoimmunity causes.
Description of drawings
The standard polysaccharide Dexfran of Fig. 1 known molecular amount presses the molecular weight standard curve of Ka.v logarithm Log Mw mapping;
The elution curve of the carboxymethyl pachyman that Fig. 2 the present invention makes on the SephadexG-200 chromatographic column, according to the Ka.v value that records, trying to achieve its molecular weight is 0.7 * 10
4-1.0 * 10
6Dalton.
The specific embodiment
Specify the present invention below with reference to embodiment, embodiments of the invention only are used to technical scheme of the present invention is described, and non-limiting essence of the present invention.
Embodiment 1The preparation of high substituted degree CMP
1) dried Poria 75kg is ground into fine powder, puts in the steeping tank, pumps into 400L water, stirs, and soaks 12h;
2) be that the sodium hydroxide solution of 2.25mol/L slowly pumps in the steeping tank with 400L concentration, stirring reaction 1h filters, and gets filtrate;
3) in neutralizing tank, drop into after 300L concentration is the chloroacetic acid solution of 5.3mol/L, slowly add the sodium hydroxide solution that 300L concentration is 6.25mol/L again, be stirred to sufficient reacting, be cooled to room temperature;
4) with 3) the step reactant liquor pumps into 2) in the step gained filtrate, fully behind the mixing, slowly be warming up to 75 ℃, isothermal reaction 2.5h;
5) transfer 4 with the hydrochloric acid solution of 6mol/L) the pH value 5.0-7.0 of step gained reactant liquor, add 95% ethanol that is equivalent to 3 times of volumes of reactant liquor, stir, filter, washing, get CMP alcohol and analyse thing;
9) CMP alcohol is analysed thing behind 60 ℃ of dry 4h, and 105
cDry 2h gets CMP semifinished product 37.5kg.
10) the 7.5kgCMP semifinished product is scattered in the 250L distilled water, the sodium hydroxide solution that adds 6mol/L is transferred pH to 10.0-13.0; Adding 1.25L concentration is 30% H
2O
2Solution, 15
cDecoloring reaction 36h removes foreign pigment; Add 6.0,3000 rev/mins of centrifugalize 30min of hydrochloric acid solution adjust pH of 6mol/L, get filtrate, filtrate is used DH-UF hollow fiber membrane ultrafiltration device filtering molecular weight 0.7 * 10
4Following CMP, and behind the impurity such as sodium chloride, sodium chloroacetate and glycolic sodium of trace, 95% ethanol that adds 3 times of filtrate volumes in the filtrate, carry out alcohol and analyse, filtration or centrifugal is got CMP alcohol and is analysed thing behind 60 ℃ of dry 4h, 105 ℃ of dry 2h, pulverize, get the pure product of CMP of 6.0kg degree of substitution by carboxymethyl 1.0, its physicochemical property is as follows:
Character: white powder, odorless slightly draws moist.
Molecular formula: (C
8H
12O
7) the n degree of polymerization (n): 32＜n＜4545
Molecular weight: 0.7 * 10
4-1.0 * 10
6Dalton
IR[KBr](cm
1)：3700-3000，2900，1600.7，1425.2，1324.9，1078.0，891.0。
UV (0.1mol/L HCl solution, H
2O, 0.1mol/LNaOH solution): no absworption peak.
13C-NMP[H
2D](ppm)：180.078，104.870，87.697，86.667，84.935，83.145，77.851，76.490，75.669，73.273，72.296，70.345，62.975。
[a]
20D：-1.70-1.90(C＝5，H
2O)
1% pH value of aqueous solution 5.0-7.0
Moisture content percentage composition＜8.0%
In sodium chloride, chloride %＜0.01%; With P
bMeter, heavy metal %＜0.001%, in As, arsenic %＜0.0001%.
Embodiment 2The mensuration of carboxymethyl pachyman molecular weight
Condition determination: instrument is a LKB column chromatography system, the SephadexG-200 post.Mobile phase is NaCl solution (pH value 7.0) buffer solution of 0.2mol/L, flow velocity 0.5ml/min, sample size (W/V) 1mg/ml, constant temperature 10
℃The differential refraction detects automatically, monitor record peak position.
Standard curve: with standard polysaccharide Dexfran T2000 (Mw2000000), T500 (Mw500000), T40 (Mw40000), T20 (Mw20000), T10 (Mw10000), T5 (Mw5000) the production standard curve of known molecular amount, press Ka.v logarithm LogMw mapping, standard curve is seen Fig. 1.
The elution curve of the carboxymethyl pachyman that the present invention makes on the SephadexG-200 chromatographic column is referring to Fig. 2, and according to the Ka.v value that records, trying to achieve its molecular weight (Mw) is 0.7 * 10
4-1.0 * 10
6Dalton.
Molecular formula according to carboxymethyl pachyman is (C
8H
12O
7) n, its molecule measuring definite value is 0.7 * 10
4-1.0 * 10
6, the degree of polymerization (n) 0.7 * 10
4/ Mw
C8H12O7＜n＜1.0 * 10
6/ Mw
C8H12O7, promptly the degree of polymerization of carboxymethyl pachyman of the present invention (n) is 32＜n＜4545.
Embodiment 3Acidization is measured the degree of substitution by carboxymethyl (DS) of carboxymethyl pachyman
Precision takes by weighing carboxymethyl pachyman sample 0.4041g, place the beaker of 150ml, 80 ℃ of heating in water bath stir and make dissolving, after the cooling, hydrochloric acid solution with 2mol/L is transferred pH to 4.0, adds dehydrated alcohol 100ml, stirs, standing over night, centrifugalize alcohol is analysed thing, and alcohol is analysed thing with 95% ethanol cyclic washing, chloride ion-containing not to the cleaning mixture.Clean alcohol is analysed the NaoH standard solution 40.00ml dissolving of thing with 0.1000mol/L, after treating that solution is transparence, use the standard salt acid solution back titration of 0.1000mol/L immediately, redness to phenolphthalein indicator is just decorporated, and the volume of the hydrochloric acid standard solution of record 0.1000mol/L that back titration consumes is 21.60ml.
Calculate the substitution value (DS) of carboxymethyl pachyman according to following formula:
In the formula: A be in and the mmol number of the NaOH that consumed of 1g acid carboxymethyl pachyman sample;
C
NaOHConcentration (0.1000mol/L) for the NaOH standard solution;
V
NaOHVolume number (40.00ml) for the NaOH standard solution that adds 0.1000mol/L;
C
HClThe concentration (0.1000mol/L) of the hydrochloric acid standard solution of using for back titration;
V
HClVolume number (21.60ml) for the hydrochloric acid standard solution of 0.1000mol/L that back titration consumes;
M is the quality (g) of sample;
0.162 be the mmol quality of the dehydration glucose unit of pachyman;
0.058 after a hydroxyl is replaced by carboxymethyl in the dehydration glucose unit, the net added value of dehydration glucose unit mmol quality.
The degree of substitution by carboxymethyl of gained carboxymethyl pachyman of the present invention (D.S) is 1.0, and computational process is as follows:
Embodiment 4The preparation of high substituted degree CMP
1) the dried Poria fine powder of 75kg pumps into 400L water, stirs, and soaks 14h;
2) be that the sodium hydroxide solution of 3mol/L slowly pumps in the steeping tank with 400L concentration, stirring reaction 1h filters, and gets filtrate;
3) in neutralizing tank, drop into after 300L concentration is the chloroacetic acid solution of 5.5mol/L, slowly add the sodium hydroxide solution that 300L concentration is 6.5mol/L again, be stirred to sufficient reacting, be cooled to room temperature;
4) with 3) the step reactant liquor pumps into 2) in the step gained filtrate, fully behind the mixing, slowly be warming up to 78
℃, isothermal reaction 2h;
5) transfer 4 with the hydrochloric acid solution of 6mol/L) pH value 6.0 of step gained reactant liquor, add 95% ethanol that is equivalent to 3 times of volumes of reactant liquor, stir, filter, washing, get CMP alcohol and analyse thing;
9) CMP alcohol is analysed thing 60
℃Behind the dry 4h, 105
℃Dry 2h gets CMP semifinished product 37.8kg.
10) the 7.5kgCMP semifinished product is scattered in the 250L distilled water, the sodium hydroxide solution that adds 6.5mol/L is transferred pH to 10.0-13.0; Adding 1.5L concentration is 30% H
2O
2Solution, 25
℃Decoloring reaction 20h removes foreign pigment; Add 6.0,3000 rev/mins of centrifugalize 30min of hydrochloric acid solution adjust pH of 6.5mol/L, get filtrate, filtrate is used DH-UF hollow fiber membrane ultrafiltration device filtering molecular weight 0.7 * 10
4Following CMP and other small molecular weight impurities, 95% ethanol of 3.2 times of filtrate volumes of adding carries out alcohol and analyses in the filtrate, and filtration or centrifugal is got CMP alcohol and is analysed thing successively 60
℃Dry 4h and 105
℃Dry 2h pulverizes, and gets the pure product of CMP of 6.1kg degree of substitution by carboxymethyl 1.05, and its relative molecular weight is 0.7 * 10
4-1.0 * 10
6Dalton.
Embodiment 5The preparation of high substituted degree CMP
1) the dried Poria fine powder of 75kg pumps into 400L water, stirs, and soaks 16h;
2) be that the sodium hydroxide solution of 4mol/L slowly pumps in the steeping tank with 400L concentration, stirring reaction 1h filters, and gets filtrate;
3) in neutralizing tank, drop into after 300L concentration is the chloroacetic acid solution of 6.0mol/L, slowly add the sodium hydroxide solution that 300L concentration is 6.8mol/L again, be stirred to sufficient reacting, be cooled to room temperature;
4) with 3) the step reactant liquor pumps into 2) in the step gained filtrate, fully behind the mixing, slowly be warming up to 82 ℃, isothermal reaction 1.5h;
5) transfer 4 with the hydrochloric acid solution of 6mol/L) pH value 6.0 of step gained reactant liquor, add 95% ethanol that is equivalent to 3 times of volumes of reactant liquor, stir, filter, washing, get CMP alcohol and analyse thing;
9) CMP alcohol is analysed thing successively 60
℃Dry 4h and 105
℃Dry 2h gets CMP semifinished product 37.9kg.
10) the 7.5kgCMP semifinished product is scattered in the 250L distilled water, the sodium hydroxide solution that adds 6.5mol/L is transferred pH to 10.0-13.0; Adding 1.6L concentration is 30% H
2O
2Solution, 30
℃Decoloring reaction 18h removes foreign pigment; Add 6.0,3000 rev/mins of centrifugalize 30min of hydrochloric acid solution adjust pH of 6.5mol/L, get filtrate, filtrate is used DH-UF hollow fiber membrane ultrafiltration device filtering molecular weight 0.7 * 10
4Following CMP and other small molecular weight impurities, 95% ethanol that adds 3.2 times of filtrate volumes in the filtrate, carrying out alcohol analyses, filtration or centrifugal, get CMP alcohol and analyse thing successively at 60 ℃ of dry 4h and 105 ℃ of dry 2h, pulverize, get the pure product of CMP of 6.15kg degree of substitution by carboxymethyl 1.10, its relative molecular weight is 0.7 * 10
4-1.0 * 10
6Dalton.
Embodiment 6The preparation of high substituted degree CMP
1) the dried Poria fine powder of 75kg pumps into 400L water, stirs, and soaks 16h;
2) be that the sodium hydroxide solution of 4mol/L slowly pumps in the steeping tank with 400L concentration, stirring reaction 1h filters, and gets filtrate;
3) in neutralizing tank, drop into after 300L concentration is the chloroacetic acid solution of 5.8mol/L, slowly add the sodium hydroxide solution that 300L concentration is 7.0mol/L again, be stirred to sufficient reacting, be cooled to room temperature;
4) with 3) the step reactant liquor pumps into 2) in the step gained filtrate, fully behind the mixing, slowly be warming up to 82
℃, isothermal reaction 1h;
5) transfer 4 with the hydrochloric acid solution of 6mol/L) pH value 6.0 of step gained reactant liquor, add 95% ethanol that is equivalent to 3 times of volumes of reactant liquor, stir, filter, washing, get CMP alcohol and analyse thing;
9) CMP alcohol is analysed thing successively at 60 ℃ of dry 4h and 105 ℃ of dry 2h, gets CMP semifinished product 38.1kg.
10) the 7.5kgCMP semifinished product is scattered in the 250L distilled water, the sodium hydroxide solution that adds 6.5mol/L is transferred pH to 10.0-13.0; Adding 1.6L concentration is 30% H
2O
2Solution, 30
℃Decoloring reaction 18h removes foreign pigment; Add 6.0,3000 rev/mins of centrifugalize 30min of hydrochloric acid solution adjust pH of 6.5mol/L, get filtrate, filtrate is used DH-UF hollow fiber membrane ultrafiltration device filtering molecular weight 0.7 * 10
4Following CMP and other small molecular weight impurities, 95% ethanol that adds 3.2 times of filtrate volumes in the filtrate, carrying out alcohol analyses, filtration or centrifugal, get CMP alcohol and analyse thing successively at 60 ℃ of dry 4h and 105 ℃ of dry 2h, pulverize, get the pure product of CMP of 6.18kg degree of substitution by carboxymethyl 1.15, its relative molecular weight is 0.7 * 10
4-1.0 * 10
6Dalton.
Embodiment 7The preparation of high substituted degree CMP
1) the dried Poria fine powder of 75kg pumps into 400L water, stirs, and soaks 16h;
2) be that the sodium hydroxide solution of 5mol/L slowly pumps in the steeping tank with 400L concentration, stirring reaction 1h filters, and gets filtrate;
3) in neutralizing tank, drop into after 300L concentration is the chloroacetic acid solution of 6.0mol/L, slowly add the sodium hydroxide solution that 300L concentration is 7.2mol/L again, be stirred to sufficient reacting, be cooled to room temperature;
4) with 3) the step reactant liquor pumps into 2) in the step gained filtrate, fully behind the mixing, slowly be warming up to 85 ℃, isothermal reaction 1h;
5) transfer 4 with the hydrochloric acid solution of 6mol/L) pH value 6.0 of step gained reactant liquor, add 95% ethanol that is equivalent to 3 times of volumes of reactant liquor, stir, filter, washing, get CMP alcohol and analyse thing;
9) CMP alcohol is analysed thing successively at 60 ℃ of dry 4h and 105 ℃ of dry 2h, gets CMP semifinished product 40.0kg.
10) the 7.5kgCMP semifinished product is scattered in the 250L distilled water, the sodium hydroxide solution that adds 6.5mol/L is transferred pH to 10.0-13.0; Adding 1.6L concentration is 30% H
2O
2Solution, 30
℃Decoloring reaction 15h removes foreign pigment; Add 6.0,3000 rev/mins of centrifugalize 30min of hydrochloric acid solution adjust pH of 6.5mol/L, get filtrate, filtrate is used DH-UF hollow fiber membrane ultrafiltration device filtering molecular weight 0.7 * 10
4Following CMP and other small molecular weight impurities, 95% ethanol that adds 3.2 times of filtrate volumes in the filtrate, carrying out alcohol analyses, filtration or centrifugal, get CMP alcohol and analyse thing successively at 60 ℃ of dry 4h and 105 ℃ of dry 2h, pulverize, get the pure product of CMP of 6.2kg degree of substitution by carboxymethyl 1.20, its relative molecular weight is 0.7 * 10
4-1.0 * 10
6Dalton.
Embodiment 8The preparation of capsule
The composition of capsule:
Poria 300g
Fructus Lycii 200g
Radix Ginseng 100g
Preparation method:
1, the Poria extract powder prepares according to embodiment 1 method.
2, Radix Ginseng powder's preparation: after the Radix Ginseng drying, carry out ultraviolet radiation for sterilizing and disinfecting, pulverize, cross 80 mesh sieves, promptly.
3, the preparation of wolfberry fruit extract powder: 1) Fructus Lycii powder adds 10 times of distilled water immersion 2h, extracts 1 hour in 90 ℃ of water-baths, and filtered while hot is extracted 3 times, merges 3 filtrates and gets crude extract; 2) crude extract is evaporated to 1/6 of original volume, after the cooling, under agitation adds 95% ethanol, reach 80%, leave standstill filtering-depositing up to concentration of alcohol; 3) precipitation adding distil water dissolving adds 95% ethanol again and repeats precipitation operation 1 time, centrifugalize, and 60 ℃ of dry 10h of gained precipitate, 105 ℃ of dry 2h pulverize, and cross 80 mesh sieves, promptly.
4, behind abundant mixing Poria extract powder, wolfberry fruit extract powder and the Radix Ginseng powder, encapsulated with capsule filling machine, every the 0.45g that packs into.
Embodiment 9The preparation of granule
Poria 600g
Fructus Lycii 400g
Radix Ginseng 200g
1, the Poria extract powder prepares according to embodiment 2 methods; Wolfberry fruit extract powder and Radix Ginseng powder's preparation method is with embodiment 8;
2, behind abundant mixing Poria extract powder, wolfberry fruit extract powder and the Radix Ginseng powder, add appropriate amount of starch slurry and ethanol, granulation, granulate, oven dry, promptly.
Below verify the immunoenhancement result of pharmaceutical composition of the present invention by test of pesticide effectiveness example.
Test example 1The present composition improves delayed allergy (DTH) ability (the sufficient sole of the foot thickens method) of mice
Body weight is 40 of the cleaning level Male Kunming strain mice of 18-22g, is provided by the laboratory animal department of the Chinese Academy of Sciences of Central South University, and approval number is the moving word of Hunan Province doctor 20-011 number, is divided into distilled water matched group and test group at random, 10 every group.Test group comprises the basic, normal, high dosage group of the present composition, and used dosage is respectively 0.185g/kg.bw, 0.370g/kg.bw and 1.110g/kg.bw, is equivalent to 5,10,30 times of human body recommended dose respectively.
Get present composition sample adding distil water and be assigned to desired concn, matched group gives isometric distilled water, irritates stomach and is tried mice, irritates stomach every day 1 time, and irritating the stomach volume is 0.2ml/10g.bw, continuous 30 days.After the test, each organizes after the equal lumbar injection 2% of mice (v/v) SRBC (the every Mus of the 0.2 μ l/) sensitization 4, measure left back sufficient sole of the foot thickness, then measuring point subcutaneous injection 20% (v/v) SRBC (the every Mus of 20 μ l/), measured left back sufficient sole of the foot portion thickness in back 24 hours in injection, same position is measured 3 times, averages.The degree of representing DTH with sufficient sole of the foot thickness difference (swelling degree of the paw) before and after attacking.
Result of the test is: the low dose group of the present composition, middle dosage group, high dose group and distilled water mice in control group inject back 24 hours swelling degree of the paw (mm) be respectively 0.358 ± 0.101,0.445 ± 0.119,0.452 ± 0.136 and 0.308 ± 0.121, each dosage group is compared with the distilled water matched group, swelling degree of the paw all has the trend of increasing, middle and high dosage group and matched group ratio, the P value all＜0.05 has significant difference.
Test example 2The present composition improves mice half hemolysis value (HC
50) test
Body weight is 40 of the cleaning level Male Kunming strain mice of 18-22g, is provided by the experimental animal department of the Chinese Academy of Sciences of Central South University, and to be that the Hunan Province doctor is moving learn 20-011 number approval number.Be divided into distilled water matched group and test group at random, 10 every group.Test group comprises the basic, normal, high dosage group of the present composition, and used dosage is respectively 0.185g/kg.bw, 0.370g/kg.bw and 1.110g/kg.bw, is equivalent to 5,10,30 times of human body recommended dose respectively.
Get present composition sample adding distil water and be assigned to desired concn, matched group gives isometric distilled water, irritates stomach and is tried mice, irritates stomach every day 1 time, and irritating the stomach volume is 0.2ml/10g.bw, continuous 30 days.After the test, respectively be subjected to the half hemolysis value (HC of examination group mice according to following method mensuration
50) mensuration.
HC
50Assay method as follows: get Sanguis caprae seu ovis, with normal saline washing 3 times, every mice carries out immunity through lumbar injection 2% (v/v prepares with normal saline) hematocrit RBC0.2ml.After 5 days, extract eyeball and get blood in centrifuge tube, places about 1h, with solidification blood and tube wall cut open from, serum is fully separated out, the centrifugal 10min of 2000rpm, collection serum.With the SA buffer serum is diluted to 200 times, gets 1ml and put in vitro, add 10% (v/v is with the preparation of SA buffer) hematocrit SRBC0.5ml successively, complement 1ml (diluting by 1: 10) with the SA buffer.Other establishes the not control tube of increase serum (replacing with the SA buffer).After putting in 37 ℃ of waters bath with thermostatic control insulation 30min, the ice bath cessation reaction.The centrifugal 10min of 2000rpm gets supernatant 1ml, adds Dou Shi reagent 3ml.(v/v is with the preparation of SA buffer) the hematocrit SRBC0.25ml that gets 10% simultaneously, add Dou Shi reagent to 4ml in another test tube, abundant mixing, place 10min after, sentence control tube in 540nm and do blankly, measure respectively and respectively manage optical density value.The amount of hemolysin is with half hemolysis value (HC
50) expression, computing formula is:
Half hemolysis value (HC
50Optical density value * extension rate during)=sample shading value/SRBC HD50.
Result of the test is as follows: the mice half hemolysis value (HC of the low dose group of the present composition, middle dosage group, high dose group and distilled water group
50) be respectively 177.8 ± 27.9,179.9 ± 23.7,192.5 ± 24.1,158.4 ± 23.7.Each dosage group mice haemolysis value (HC of the present composition
50) with distilled water matched group ratio, the trend of increasing is all arranged, high dose group and matched group ratio, P＜0.05 has significant difference.
Test example 3The present composition improves mouse antibodies cellulation [hemolysis plaque number (* 10
3Individual/full spleen)]
Body weight is 40 of the cleaning level Male Kunming strain mice of 18-22g, is provided by the laboratory animal department of the Chinese Academy of Sciences of Central South University, and to be that the Hunan Province doctor is moving learn 20-011 number approval number.Be divided into distilled water matched group and test group at random, 10 every group.Test group comprises the basic, normal, high dosage group of the present composition, and used dosage is respectively 0.185g/kg.bw, 0.370g/kg.bw and 1.110g/kg.bw, is equivalent to 5,10,30 times of human body recommended dose respectively.
Get present composition sample adding distil water and be assigned to desired concn, matched group gives isometric distilled water, irritates stomach and is tried mice, irritates stomach every day 1 time, and irritating the stomach volume is 0.2ml/10g.bw, continuous 30 days.After the test, respectively be subjected to the antibody-producting cell of examination group mice with Jerne improvement slide method mensuration.
The mensuration process of Jerne improvement slide method is as follows: get Sanguis caprae seu ovis, with normal saline washing 3 times, centrifugal at every turn (2000r/min) 10min is made into the cell suspension of 2% (v/v), every mouse peritoneal injection 0.2ml with hematocrit SRBC with normal saline.Mice that immunity is back 4 days is put to death, and gets spleen, tears up gently, makes cell suspension with Hanks liquid, and 200 eye mesh screens filter, wash, centrifugal 2 times, at last with cell suspension in 5ml Hanks liquid.To mix with the pH7.4 of equivalent, the Hanks liquid of 2 times of concentration after the culture medium heating for dissolving of top layer, the packing small test tube, every pipe 0.5ml, in pipe, add again with the 10%SRBC50 μ L (V/V) of SA liquid preparation, the splenocyte suspension of 20 μ L, be poured on the slide of brushing the thin layer agarose behind the mixing rapidly, treat after agarose solidifies the slide level to be buckled and be placed on the slide frame, put incubation 1.5h in the CO2 gas incubator, complement (1: 10) with the dilution of SA liquid joins in the slide groove then, continues to count the hemolysis plaque number behind the incubation 1.5h.
Result of the test is as follows: the low dose group of the present composition, middle dosage group, high dose group and distilled water mice in control group hemolysis plaque number (x10
3Individual/full spleen) count results be respectively 21.78 ± 9.96,29.03 ± 10.48,31.35 ± 10.51,19.03 ± 8.19, the present composition each dosage group mouse antibodies cellulation number and matched group ratio, the trend of increasing is all arranged, high dose group and matched group, P＜0.05 has significant difference.
Test example 4The present composition improves the ability that mouse monokaryon one macrophage carbon is cleaned up
40 of the cleaning level Male Kunming strain mice of body weight 18～22g are provided by the laboratory animal department of the Chinese Academy of Sciences of Central South University, and approval number is the moving word of Hunan Province doctor 20-011 number.Be divided into distilled water matched group and test group at random, 10 every group.Test group comprises the basic, normal, high dosage group of the present composition, and used dosage is respectively 0.185g/kg.bw, 0.370g/kg.bw and 1.110g/kg.bw, is equivalent to 5,10,30 times of human body recommended dose respectively.
Get present composition sample adding distil water and be assigned to desired concn, matched group gives isometric distilled water, irritates stomach and is tried mice, irritates stomach every day 1 time, and irritating the stomach volume is 0.2ml/10g.bw, continuous 30 days.After the test, respectively be subjected to the india ink of examination group mouse tail vein injection, every 10g body weight injection 0.1ml with 4 times of normal saline dilutions, timing immediately after prepared Chinese ink injects, 2min, 10min after injecting black juice get blood 20 μ l from interior order than venous plexus respectively, join 2mlNa
2CO
3In the solution, shake up.With Na
2CO
3Solution is made blank, with 722 type spectrophotometers in 600nm wavelength place's colorimetric determination optical density value (OD).Mice is put to death, get liver, spleen, weigh, calculate phagocytic index a.
Result of the test is as follows: the low dose group of the present composition, middle dosage group, high dose group and distilled water matched group ratio, have the exponential trend of the monokaryon of increasing-macrophage phagocytic, and high dose group and matched group ratio, P＜0.05 has significant difference.
In sum, the present composition is irritated the stomach mice by 0.185～1.110g/kg.bw dosage, took continuously 30, can significantly improve the ability that delayed allergy, half hemolysis value, antibody-producting cell number and monokaryon-macrophage carbon is cleaned up of mice, show that the present composition has significant enhance immunity effect.
Claims (10)
1, a kind of compositions with enhance immunity effect, its effective ingredient is made up of Poria, Radix Ginseng and Fructus Lycii.
2, compositions according to claim 1, preparation compositions raw materials of effective components composition is counted by weight, Poria 30-3000 part, Radix Ginseng 10-1000 part, Fructus Lycii 20-2000 part, be preferably Poria 60-1500 part, Radix Ginseng 20-500 part, Fructus Lycii 40-1000 part, more preferably Poria 120-750 part, Radix Ginseng 40-250 part, Fructus Lycii 80-500 part most preferably are 300 parts in Poria, 100 parts of Radix Ginsengs, 200 parts of Fructus Lyciis.
3, compositions according to claim 1, the dosage form of described compositions is selected from oral formulations, external preparation or injection, is preferably oral formulations.
4, compositions according to claim 3, described oral formulations is selected from oral liquid, tablet, capsule, granule, pill, powder, syrup, mixture, distillate medicinal water, suspending agent, Emulsion or medicinal tea, and preferred suspending agent selects outstanding agent of white spirit or suspension.
5, compositions according to claim 3, described external preparation is selected from gel, unguentum, liniment, lotion or liniment, and preferred unguentum is selected from emplastrum, coagulates unguentum or ointment.
6, compositions according to claim 3, described injection is selected from injection, transfusion or freeze-dried powder.
7, a kind of preparation has enhance immunity effect method for compositions, the effective ingredient in uniform mixing Poria, Radix Ginseng and the Fructus Lycii, promptly.
8, method according to claim 7, the effective ingredient of described Poria is a Poria extract, is preferably the pachyman in the extract; Described pachyman can be made by method well known in the art, is selected from pachyman extract or carboxymethyl pachyman or high-substitution carboxymethyl pachyman that the alkaline extraction acid precipitation method makes.
9, a kind of method for preparing high substituted degree CMP, comprising the steps: 1) pachyman joins in water or the water alcohol mixed liquor, after stirring, adds the alkaline solution of pachyman quality 1-8% or 2-6% or 3-5%, be stirred to dissolving fully, get the pachyman alkaline solution; 2) after the 1.0-10mol/L monoxone fully reacts with suitably excessive 2.0-10mol/L alkaline solution, join 1) in the pachyman alkaline solution of step gained, carry out substitution reaction, the CMP that separation and purification generates, promptly.
10, each described compositions of claim 1-6 is used for preparing the food with enhance immunity effect or the application of medicine, is preferably food or medicine with health care.
Priority Applications (1)
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| CN109970880A (en) * | 2019-04-02 | 2019-07-05 | 广州华农大实验兽药有限公司 | A kind of preparation method of ginseng leaf polyose |
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| CN110613793A (en) * | 2019-10-14 | 2019-12-27 | 福建省中医药研究院(福建省青草药开发服务中心） | Anti-tumor composition and preparation method and application thereof |
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| CN100534474C (en) | 2009-09-02 |
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