CN101086007A - Manyzoned polypore glycopeptide production method and its formulation - Google Patents
Manyzoned polypore glycopeptide production method and its formulation Download PDFInfo
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Abstract
The invention provides a method for preparing coriolan. It employs anti- chelating technology to prevent the chelating of glycopeptide with heavy metal, and makes the heavy content in coriolan meet international foodstuff sanitary standard. The coriolan prepared with method in this invention can be prepared into oral film clothing sheet tablet with medical findings, particles or oral liquid, which can be used to treat cancer and for health- care purpose.
Description
Technical field
The invention belongs to natural medicine technical field, be specifically related to a kind of polysaccharide-peptide production method, especially can reject the polysaccharide-peptide production method and the preparation thereof of excessive heavy metal.
Background technology
Polysaccharide-peptide (Polysaccharopeptide of YunZhi) tube claims PSP, is to cultivate the conjugated protein polysaccharide that mycelium extracts by the rainbow conk deep layer.Polysaccharide-peptide is one of two generally acknowledged krestin medicines of present international the world of medicine (Parris M.Kidd:The Use of Mushroom Glucans and Proteoglycans in CancerTreatment, in Alternative Medicine Review Vol.5, No.1, pp.4-27,2000.SolomonP.W.et al：Culinary-Medicinal Higher Basidiomycete Mushrooms as a ProminentSource of Dietary Supplements and Drugs for the 21
st Century.In MushroomBiology and Mushroom Products，pp.25-26，2005)。Polysaccharide-peptide is used for tumour patient, can significantly improve clinical syndromes such as spiritlessness and weakness, appetite are low, cancer pain, the toxic side effects that alleviating/radiotherapy causes improves life quality, total effective rate 82.9% (Chinese the 3rd the 4th phase of volume of cancer magazine, 1993, Yang Q.Y.:Advanced Research in PSP, 1999, p.295-303, The Hong Kong Association for HealthCare Ltd, 1999).
The production method of relevant polysaccharide-peptide, nineteen ninety the patent No.: the existing report of CN89105471, but because its production method is not done the heavy metal rejecting of (containing arsenic, lead etc.), can have influence on the polysaccharide-peptide and the quality of the pharmaceutical preparations thereof, in product, contain heavy metal probably, after human body is taken, can bring certain influence.
The Krestin (PSK) of Japan, it is the like product of polysaccharide-peptide (PSP), in the quality standard of Krestin, had the limit standard of 2 heavy metal elements, promptly require lead content among the Krestin less than 50ppm, arsenic content is less than 10ppm. (Outline of PSK, Kureha Chemical Industry Co.Ltd.1977.SankyoCo., Ltd.2004). states such as American and Britain, method, moral to the heavy metal of food and medicine also done to limit the quantity of the mark Huaihe River.As the British Commonwealth of Nations heavy metal in food and the medicine is had 8 elements of limiting the quantity of, its access is limited the quantity of and is respectively: lead should be lower than 6.0ppm, mercury should be lower than 0.5ppm, cadmium should be lower than 0.1ppm, chromium should be lower than 1.0ppm, antimony should be lower than 1.0ppm, copper should be lower than 150ppm, tin should be lower than 230ppm, arsenic should be lower than 1.4ppm (The Hong Kong standards andtesting centre:Technical guidelines for testing the safety of proprietaryChinese medicines, sanctioned by the department of health of the governmentof the HKSAR, 2004).As seen, if polysaccharide-peptide and its preparation of producing by above-mentioned patented method are to reach the limit the quantity of requirement of world market to this product heavy metal.
Owing to reject the excessive heavy metal Asia and Africa easy thing in the polysaccharide-peptide.Because of the glycopeptide molecule is the sequestrant of heavy metal, and the production of polysaccharide-peptide be a concentration process (every T rainbow conk fermentation liquid only receive polysaccharide-peptide 1Kg, promptly concentrate 1000 times), therefore, the production process of polysaccharide-peptide in fact also is chelating, the enrichment process of glycopeptide to heavy metal.Even the heavy metal content in producing in used De Pei Raising base and the solvent all is lower than the limit standard of food sanitation, but the heavy metal content in its finished product one polysaccharide-peptide, still can be and severe overweight owing to chelating, inrichment.
Excessive heavy metal in the polysaccharide-peptide has become the major obstacle that polysaccharide-peptide is produced.
How rejecting excessive heavy metal, also is that important topic to be solved is compeled in the current modernization of Chinese medicine.Still last both at home and abroad so far See rejects the technology and the method for excessive heavy metal in polysaccharide-peptide or other rainbow conk series products.
At present; polysaccharide-peptide has a kind of formulation one capsule [the polysaccharide-peptide national drug standards WS3-228 of National Drug Administration (Z-047)-2003 (Z)]; the capsule that belongs to polyose; because Duo Tang Very easily absorbs water; airborne moisture regular meeting invades between capsular capsule cap and capsule body; make polysaccharide-peptide suction Wet and go bad poor stability.The Polysaccharide-peptide capsule preservation period that China checks and approves only 2 years.In addition, the volume of capsule is bigger, the patient with esophageal carcinoma dysphagia; Capsule is polyphyly gelatin goods again, and gelatin is made by cow hoof or angle, and the vegetarian avoids; Moreover capsule easily sticks to again on the coat of the stomach after going into stomach, stimulates body of stomach to stir, and also is unfavorable for cancer of the stomach or stomach ulcer patient.
Based on above reason, polysaccharide-peptide is badly in need of the new formulation of exploitation.
Summary of the invention:
The technical problem to be solved in the present invention is to overcome the problem that exceeds standard of heavy metal content in the polysaccharide-peptide, the production method and the preparation thereof of a kind of polysaccharide-peptide that can the excessive heavy metal of deletion of research and design.
The invention provides a kind of production method of polysaccharide-peptide.
Adopt anti-chelating technology in the production process of the present invention,, make the heavy metal content in the polysaccharide-peptide reach international limit standard with the chelating of blocking-up glycopeptide molecule to heavy metal.
So-called anti-chelating technology promptly requires the fermentation of polysaccharide-peptide aborning and extracts water, all takes deionized water, but makes glycopeptide molecule non-metallic ion chelating.Concrete grammar is to fermentation and extracts water, adopt Zeo-karb (as strongly acidic styrene's Zeo-karb Dowex 50, Amberlite IR-120,732, polystyrene macroporous strong-acid cation-exchange resin AmberliteIR-200 etc.), anionite-exchange resin is (as strong basicity quaternary ammonium I type vinylbenzene anionite-exchange resin Dowex 1x4, Amberlite IRA-401,717, benzene etc.--) and the dechromisation resin (as weakly alkaline vinylbenzene anionite-exchange resin Amberlite-IRA45, macroreticular weakly base vinylbenzene anionite-exchange resin 710A etc.) handle, to reject the heavy metal that exists in the water, the specific conductivity that requires water of productive use makes this water not have positively charged ion or negatively charged ion basically and exists below 20 μ S/cm.Like this, polysaccharide-peptide synthetic and extract all to be in and do not have substantially in the ionic water surrounding, Cong Er 8 heavy metal content the Indeed capital preservation product, all in the limit standard of international heavy metal.
Production method of the present invention comprises the following steps:
(1) production of rainbow conk Shen Ceng Pei Raising Jun Silk body: get rainbow conk (Trametes versicolor Fr.=Coriolusversicolor Quel.) Coy-1 bacterial strain, by shaking the ventilation Pei Raising of bottle Zhen Dang Pei Raising and seeding tank, breeding jar, fermentor tank, enlarge step by step fermentation liquid, mash through centrifugal or filter after promptly get rainbow conk Shen Ceng Pei Raising Jun Silk body.Used matrix of Shen Ceng Pei Raising and condition are: carbon source is 3-5% with glucose or Semen Maydis powder, consumption, and nitrogenous source is 1-2% with soybean cake powder or groundnut meal, consumption; No Ji salt dipotassium hydrogen phosphate, potassium primary phosphate and sal epsom, consumption respectively is 0.05-0.1%; Pei Raising temperature: 24～28 ℃, inoculum size: 5～10%, air flow: 1: 0.5～1: 1.0 (v/v), the Yao Ping Pei Raising time: 5～7 days, seeding tank, breeding jar and fermentor tank De Pei Raising time respectively were 36～72 hours.Used water ferments, all need be with the deionized water of having rejected heavy metal, promptly this water should be earlier through the cation exchange plastic resin treatment, and then through Yin Li Jiao Change plastic resin treatment, at last again through the dechromisation plastic resin treatment, to reject the heavy metal ion in its water,, require this electrical conductivity of water less than 20 μ S/cm with the conductivity meter monitoring.
(2) extraction of polysaccharide-peptide: extract the used solvent of polysaccharide-peptide from rainbow conk Shen Ceng Pei Raising Jun Silk body, also should take the deionized water that above-mentioned spent ion exchange resin was handled, its specific conductivity should be less than 15 μ S/cm, near the standard of distilled water.The water consumption of extracting is about 20～30 times (g/v) of Jun Silk body (with dry weight basis), temperature: 90～100 ℃, and the time: 1～3 hour;
(3) separation of polysaccharide-peptide: the solvent that separates polysaccharide-peptide from Yun Zhi Jun Silk body aqueous extract is an alcohol, concentration 95%, rank: food grade.Divide from Time earlier above-mentioned aqueous extract through concentrating under reduced pressure, to specific density be 1.04～1.10 (60 ℃), add 95% alcohol of 3～5 times (v/v) then, make the amount of alcohol that contains of solution reach 70～75%. and put then under-5～0 ℃, suction filtration after 6～12 hours, pure hypostasis.The alcohol hypostasis through vacuum-drying, be the bulk drug of polysaccharide-peptide film coated tablet and capsule; The alcohol hypostasis is used water dissolution again, and the aqueous solution promptly can be used as the raw material of granule, oral liquid or powder injection behind spray Mist drying or frost drying.
Polysaccharide-peptide by the inventive method production, its lead (Pb) content is lower than 6ppm after testing, mercury (Hg) content is lower than 0.5ppm, cadmium (Cd) content is lower than 0.1ppm, chromium (Cr) content is lower than 1.0ppm, and antimony (Sb) content is lower than 1.0ppm, and copper (Cu) content is lower than 150ppm, WU (Sn) content is lower than 230ppm, and arsenic (As) content is lower than the limit standard that 1.4ppm. reaches relevant heavy metal in international food and the medicine sanitary standard.。
Another object of the present invention has provided the polysaccharide-peptide preparation.
The present invention is for overcoming Polysaccharide-peptide capsule agent poor stability, and the defective that it is inconvenient that oesophagus and stomach disorder person swallow adopts the polysaccharide-peptide of having rejected excessive heavy metal, makes the novel form of polysaccharide-peptide film coated tablet, granule and oral liquid.
Polysaccharide-peptide book film garment piece is to have rejected the polysaccharide-peptide of excessive heavy metal, behind granulation, compressing tablet, and the novel form of outsourcing film-coat.Film-coat is by membrane-forming agent, softening agent, and pharmaceutical excipients such as tinting material are formed, and membrane-forming agent commonly used is homopolymer class and ether of cellulose compounds.The former is as polyoxyethylene glycol-6000 (PEG-6000), polyvinylpyrrolidone (pvp) etc., and typical concentrations is 5-25%; The latter such as Vltra tears (HPMC), (HEC) such as methylcellulose gum (MC), Natvosols etc., typical concentrations is 2-4%.Softening agent commonly used is glycerine, Oleum Cocois, polyoxyethylene glycol-600 etc., and tinting material is used amaranth, ferric oxide, carotene, Capsorubin etc. always.The pharmaceutical excipient composition of above-mentioned film coated tablet, the existing procucts supply of many businessmans as Opadry (Opadry) series of Britain Colorcon company etc., can commercially availablely obtain.
This formulation product factors sheet does not absorb water outward, light tight, air-locked book film is made seamless parcel, extraneous moisture is difficult for invading, empty Gas, light are not entered thoroughly yet, so the polysaccharide-peptide in the sheet is difficult for the moisture absorption and oxidation, good stability, the product preservation term can extend to 3 years by 2 years, and book film garment piece when film-making medicinal powder through extruding, volume-diminished, it is more convenient to swallow.In addition, polysaccharide-peptide has special smelly, and book film garment piece can also be covered its bad stink.
The polysaccharide-peptide granule is after polysaccharide-peptide adds auxiliary materials such as a small amount of disintegrating agent, tackiness agent, wetting agent, effect such as, kneading mixed through nodulizer, cutting, rubbing and the fine particle that makes.But can seals in aluminium foil bag or aluminium foil tube and gets.
Disintegrating agent commonly used is Microcrystalline Cellulose, carboxymethyl cellulose, ethyl cellulose, dextrin, lactose, sucrose etc., and consumption is that 0.7-15% does not wait.Tackiness agent commonly used is Vltra tears (HPMC), polyvinylpyrrolidone water (PVP has another name called polyvidone), 30-75% aqueous ethanolic solution etc., and consumption is 1-10%.
Granulation has dry method, wet method, spray dew and fluidized bed granulation etc. multiple.The available dry granulation of absence of liquid in all auxiliary materials after soon polysaccharide-peptide and auxiliary material will fully mix, is squeezed into sheet with the dry granulation machine, and then shakes and sieve into particle; Wet granulation is the first synthetic softwood of fully mixed Hou Pinch in the high efficient mixed nodulizer with polysaccharide-peptide and auxiliary material, makes wet granular through waving granulator then, and is dry and get.The polysaccharide-peptide extracting solution also directly Yong Pen Mist drying tower Pen Mist is dry after adding suitable auxiliary material must particle; Fluidized bed granulation is to utilize hot gas flow to make medicinal powder become the boiling shape at the fluidized-bed inner suspension, evenly sprays into binding agent and wetting agent then, makes powder be bonded to particle, is drying to obtain.Bi is Yaoed Time and also can further be sprayed into book film dress material, makes the film coating particle.Above-mentioned mixing, granulation, drying, dressing also can be granulated in an equipment and be finished.
The particle that polysaccharide-peptide makes by last method method, particle diameter can directly be filled in aluminium foil bag or the aluminium foil tube between 100 μ-3000 μ, make the polysaccharide-peptide granule.The particle loading amount of every bag (tube) is 1.1g, includes polysaccharide-peptide bulk drug 1g, is equivalent to 3 of Polysaccharide-peptide capsules, and this formulation need not used capsule, and extraneous moisture can not invaded by aluminium pool bag yet, and method for making is simple, and is easy to carry.
Polysaccharide-peptide mixture (oral liquid) be through flavoring polysaccharide-peptide.Correctives is made up of the agent of sweeting agent, Fresh flavor, acidic flavoring agent etc., can add an amount of functional oligose in addition, to regulate intestinal flora, catharsis and toxin expelling, the function of increase polysaccharide-peptide oral liquid.Sweeting agent also can be taken non-Raising of battalion or aspartame (Aspartame), red Fresh sugar alcohol (Erythriol), Sucralose (Sucralose), Mai Litian (Magnasweet) and composite sweetener thereof low in calories except that with sucrose, maltose, trehalose, the honey etc.; Acidic flavoring agent can be used citric acid, oxysuccinic acid, tartaric acid etc.; The available Sodium L-aspartate of Fresh flavor agent, Sodium Glutamate, flavour nucleotide (5 ' 1: 1 mixture of black thuja acid and 5 ' t-inosinic acid) etc.Functional oligose, available oligofructose (Fructoologaosaccharide), xylo-oligosaccharide (xylooligosaccharide), oligomeric isomaltose (Isomaltooligosaccharide), oligomeric galactose (Galactooligosaccharide) etc.Preparation polysaccharide-peptide oral liquid need not to add auxiliary materials such as disintegrating agent, tackiness agent, lubricant, swallows conveniently, and taste is good.
After the polysaccharide-peptide that production method of the present invention makes has been rejected excessive heavy metal, reach international limit standard, its preparation can also broadened application in non-tumour patient.The immune smelting that both can be used as tumour patient is treated, and also can be used for the disease prevention to healthy people and subhealth state people.
Embodiment:
Embodiment one: the polysaccharide-peptide film coated tablet of rejecting excessive heavy metal
The technological process of production of polysaccharide-peptide film coated tablet is as follows:
The rainbow conk deep layer is cultivated mycelium → hot water extraction, ethanol sedimentation, the label (plain sheet) of granulating → be pressed into behind polysaccharide-peptide → auxiliary materials such as interpolations Microcrystalline Cellulose → → dressing, polysaccharide-peptide film coated tablet intermediate → intermediate through bottling after the assay was approved, finished product.
1. the rainbow conk deep layer is cultivated mycelial production
The rainbow conk deep layer is cultivated mycelium and is adopted three grade fermemtation production: bacterial strain: Cov-1, it is Semen Maydis powder 5% that slant strains inserts earlier in the Erlenmeyer flask at 25 ℃ of following shaking culture Pei Raising bases, glucose 1%, pH6.5, oscillation frequency is 200rpm, shaking culture after 7 days moves into culture and enlarges Pei Raising in the 200 liter seeding tanks, substratum is glucose 3%. soybean cake powders 1.2%, dipotassium hydrogen phosphate 0.05%, potassium primary phosphate 0.05% and sal epsom 0.05%. culture temperature are 26 ± 2 ℃, air flow is: 1: 1.0 (v/v), logical Gas is moved into the seed tank culture thing in 5 tons of breeding jars after cultivating 36 ± 2h, logical Gas cultivated behind 36 ± 2h in 30 tons of fermentor tanks enlarged culturing 40-48 hour again, and the inoculum size of every grade of expanding propagation is 5-10%, and used substratum Pei Raising temperature is all identical with seeding tank Pei Raising with logical Gas amount.But the water of preparation Pei Raising base, the essential deionized water of using.Through cation exchange resin (732), Yin Li Jiao Change resin (717) and macroreticular weakly base vinylbenzene anionite-exchange resin (710A) purifying treatment and getting step by step, specific conductivity is 15 μ s/cm to this water by tap water.The mash of fermentation tank Pei Raising gained promptly gets the rainbow conk deep layer and cultivates mycelium behind centrifugal, press filtration or suction filtration.
The extraction of polysaccharide-peptide with separate: the rainbow conk deep layer is cultivated mycelium is handed over the Change plastic resin treatment from son with above-mentioned warp deionized water extraction, water consumption is about 20～30 times (g/v) of Jun Silk body (with dry weight basis), extracting temperature is between 98 ± 2 ℃ of Time: 3 Xiao Time get Yun Zhi Jun Silk body aqueous extract after the filtration;
Aqueous extract is under reduced pressure concentrated, to specific density be 1.04; 95% edible ethanol that adds 4 times (v/v) then makes the amount of alcohol that contains of solution reach 75%. and put then under 0 ℃, 12 hours, behind the suction filtration pure hypostasis.The alcohol hypostasis after vacuum-drying, be the bulk drug of polysaccharide-peptide film coated tablet.
3. granulate: in polysaccharide-peptide, add the Microcrystalline Cellulose of 0.9% (w/w), add 8% Vltra tears (HPMC) solution 0.3L/Kg behind the thorough mixing again, move into then that Stir mixes, granulates in the wet granulator with 75% dissolve with ethanol.The softwood that granulation obtains sieves through 14 order nylon mesh, becomes particle.Behind the whole grain of particle drying, can be on tabletting machine compressing tablet, plain sheet.Require plain sheet heavily to be 0.37g-0.38g, every contains polysaccharide-peptide and is no less than 0.34g.
4. compressing tablet: in above-mentioned particle, add lubricant-Magnesium Stearate of 0.1%, after fully mixing on automatic tableting press compressing tablet, the punch die diameter is 10mm, hardness should be greater than 4Kg/cm behind the gained label;
5. dressing: the polysaccharide-peptide label is put in the high-efficiency coating pot, and the coating pan rotating speed is 30-50 time/minute, blasts hot blast simultaneously, and plain sheet is heated to 50 ℃, regulates spray gun pressure, makes lysed coating material--Opadry (OY-C)
*Atomisation in coating pan, inferior evenly spray cloth is at the sheet wicking surface, improve hot blast temperature to 60 ℃ then, thereby make Opadry become film in the rapid drying of sheet wicking surface. make any surface finish, every wet, shading, the good polysaccharide-peptide thin membrane coated tablet of antioxidant property.
The polysaccharide-peptide film coated tablet that present embodiment makes contains moisture 4.3% after testing, and friability is 0.005%; collapse and separate Time and be limited to 31 fens kinds, the heavy 0.384g of average sheet, tablet weight variation 2.4%, all meet p. appendix 7 of Pharmacopoeia of People's Republic of China version in 2005, appendix XII related standards.By Polysaccharide-peptide capsule this product is made polysaccharide and determining content of peptides in addition, polysaccharide and protein content in every rainbow conk glycopeptide of the result film coated tablet are respectively 108.1mg and 81.7mg, all meet Polysaccharide-peptide capsule national drug standards relevant regulations (table 1)
The proterties and the assay of table 1 polysaccharide-peptide thin membrane coated tablet
| Lot number | 070301 | 070401 | 070501 | On average | Remarks |
| The average heavy amount difference of the sheet Beng Xie Time branch hardness friability polyoses content protein content of restricting water supply | 0.382g ± 2.4% 34 fen 4.6% 10.3Kg/cm, 0.004% 104.4mg/ sheet 80.9mg/ sheet | 0.384g ± 3.8% 29 fen 4,2% 12.4Kg/cm, 0.002% 109.9mg/ sheet 81.9mg/ sheet | 0.386g ± 2.6% 30 fen 4.3% 10.9Kg/cm, 0.009% 110.0mg/ sheet 82.4mg/ sheet | 0.384g ± 2.9% 31 fen 4.3% 11.2Kg/cm, 0.005% 108.1mg/ sheet 81.7mg/ sheet | Annotate 1 notes, 2 notes, 3 notes, 4 notes 5 and annotate 6 |
Annotate 1: pharmacopeia version regulation in 2005, the limit test of weight variation of tablet is ± 5%
Annotate 2: pharmacopeia version regulation in 2005, the Beng Xie Time of thin membrane coated tablet is limited to 60 minutes
Annotate 3: National Drug Administration, polysaccharide-peptide national drug standards regulation, moisture must not cross 7,0%
Annotate 4: press Nat'l Pharmaceutical ﹠ Biological Products Control Institute: Chinese drug inspection standard operation standard version in 2005, stipulate that p.261-263 the tablet friability should be less than 1%
Annotate 5: National Drug Administration, Polysaccharide-peptide capsule national drug standards regulation, every contains polysaccharide and must not be less than 100mg
Annotate 6: National Drug Administration, Polysaccharide-peptide capsule national drug standards regulation, every contains protein and must not be less than 44mg
This product is checked through units such as St Foods Q Supervision ﹠ Testing Centers, its lead (Pb) content is 0.2ppm, mercury (Hg) content＜0.01ppm, arsenic (As) content is 0.4ppm, and cadmium (Cd) content is 0.02ppm, and antimony (Sb) content is 0.7ppm, WU (Sn) content is 0.2ppm, chromium (Cr) content is 0.8ppm, and copper (Cu) content is 35ppm, and the content of 8 heavy metals all is lower than international limit standard to heavy metal.Other pesticide residue and microbial limit also all meet food and medicine health standard (table 2).
……………………………………………………………………………………
* Opadry coating liquid preparation: earlier 80% ethanol is heated to 40 ℃, under whipped state, gently continue to be sprinkled into Opadry then, reach 6% up to concentration, add 0.3-0.4% ferric oxide tinting material then, continue to stir 45 minutes, until dissolving fully, screen out block with 100 mesh sieves in addition in case of necessity.
The polysaccharide-peptide granule of embodiment two, the excessive heavy metal of rejecting
The polysaccharide-peptide 50Kg of the excessive heavy metal of rejecting that embodiment one is made; drop in the high-speed mixing granulating machine (HzSg-200 type); other drops into Microcrystalline Cellulose 4.0Kg; high-speed stirring is mixed after 30 minutes; progressively add the 75% spirituous solution 15L that contains the 75g Vltra tears again; start simultaneously and stir and granulation fly cutter button, stir and granulated 30 minutes.Above-mentioned granulation thing is crossed 14 order medicines sieve, dried 1 hour down, must do particle 57Kg in 60 ℃.Add 0.14Kg lubricant--Magnesium Stearate in dried particle, can be packed in the aluminium foil bag by the sack packer branch after mixed, every packed polysaccharide-peptide 1.1g seals promptly.
Every bag of polysaccharide-peptide granule contains polysaccharide-peptide 1.0g, is equivalent to the clinical dosage of 3 of Polysaccharide-peptide capsules.Instructions about how to take medicine: one day 3 bag, divide and take after mixing it with water for 3 times.
Embodiment three: the polysaccharide-peptide oral liquid of having rejected excessive heavy metal
The polysaccharide-peptide 20Kg of excessive heavy metal that got the rejecting that makes by embodiment one, trehalose 30Kg Chi Fresh sugar alcohol 10Kg, xylo-oligosaccharide 6.5Kg, Monosodium L-aspartate 0.2Kg and flavour nucleotide (1: 1 mixture of 5 ' black thuja acid and 5 ' Sodium Inosinate) 0.2Kg, fully mix the back, add pure water 1000L dissolving, use 0.3 μ millipore filtration press filtration then, filtrate is heated to 98 ℃, kept 60 minutes, be filled into then in advance in the vial through sterilizing, after adding a cover again behind sterilization promptly.Every bottled amount 50ml includes the many 300mg of polysaccharide-peptide (with glucose meter).Consumption: every day 3 times, each 1 bottle (50ml).This dosage is identical with a daily clinical dosage of Polysaccharide-peptide capsule.
The performance of former formulation of table 2. polysaccharide-peptide and formulation of the present invention relatively
| Former formulation | Product of the present invention | |
| Formulation | Capsule | Thin membrane coated tablet, granule, oral liquid |
| Stability | 2 years | 3 years, 3 years, 1 year |
| Excessive heavy metal in the polysaccharide-peptide | Do not deal with | Reject.Lead＜6.0ppm, mercury＜0.5ppm cadmium＜0.1ppm, arsenic＜1.4ppm chromium＜1.0ppm antimony＜1.0ppm copper＜150ppm, WU＜230ppm |
| The export trade standard | Not up to standard | Up to standard, can sell and countries in the world |
| The adaptation population | Tumour patient | Tumour patient, health and Ami healthy population |
| Whether easy administration | The esophageal carcinoma and other esophageal disease change person difficulty of swallowing, also be not suitable for cancer of the stomach, stomach ulcer patient, with the inapplicable vegetarian of the capsule of gelatin system | Swallow conveniently, be suitable for all kinds of crowds |
Claims (4)
1, a kind of polysaccharide-peptide production method is characterized in that this method comprises the following steps:
(1) production of rainbow conk Shen Ceng Pei Raising Jun Silk body: get rainbow conk Cov-1 bacterial strain, by shaking the ventilation Pei Raising of bottle Zhen Dang Pei Raising and seeding tank, breeding jar, fermentor tank, enlarge step by step fermentation liquid, mash through centrifugal or filter after promptly get rainbow conk Shen Ceng Pei Raising Jun Silk body; Described used matrix of Shen Ceng Pei Raising and condition are: carbon source is 3-5% with glucose or Semen Maydis powder, consumption, and nitrogenous source is 1-2% with soybean cake powder or groundnut meal, consumption; No Ji salt dipotassium hydrogen phosphate, potassium primary phosphate and sal epsom, consumption respectively is 0.05-0.1%; Pei Raising temperature: 24～28 ℃, inoculum size: 5～10%, air flow: 1: 0.5～1: 1.0v/v; The Yao Ping Pei Raising time: 5～7 days, seeding tank, breeding jar and fermentation tank Pei Raising time respectively were 36～72 hours;
(2) extraction of polysaccharide-peptide: should take the deionized water that above-mentioned spent ion exchange resin was handled, from rainbow conk Shen Ceng Pei Raising Jun Silk body, extract and obtain the polysaccharide-peptide aqueous extract, the water consumption Wei Jun Silk body of described extraction is with 20～30 times of g/v of dry weight basis, temperature: 90～100 ℃, the time: 2～5 hours;
(3) separation of polysaccharide-peptide:, from the polysaccharide-peptide aqueous extract, separate polysaccharide-peptide with concentration 95% food grade ethanol; Fen Li Time presses above-mentioned aqueous extract Jing Minus earlier and concentrates, to specific density be 1.04～1.10 60 ℃, then with 95% ethanol of 3～5 times of v/v of concentrated solution, make the amount of alcohol that contains of solution reach 70～75%, put then under-5～0 ℃, suction filtration after 6～12 hours, pure hypostasis, pure hypostasis through vacuum-drying, be polysaccharide-peptide.
2, a kind of polysaccharide-peptide production method according to claim 1, the used water that it is characterized in that fermenting should be handled through Zeo-karb earlier, and then through anion exchange process, at last again through the dechromisation plastic resin treatment, to reject the heavy metal ion in its water, monitor this electrical conductivity of water less than 20 μ S/cm with conductivity meter.
3, a kind of polysaccharide-peptide production method according to claim 1, heavy metal content in the polysaccharide-peptide that it is characterized in that making by this method, lead content should be lower than 6.0ppm, mercury content is lower than 0.5ppm, and cadmium content is lower than 0.1ppm, and chromium content is lower than 1.0ppm, antimony content is lower than 1.0ppm, copper content is lower than 150ppm, and tin content is lower than 230ppm, and white arsenic content is lower than 1.4ppm.
4, a kind of polysaccharide-peptide preparation is characterized in that thin membrane coated tablet, granule or oral liquid that polysaccharide-peptide that said preparation is made by the described method of claim 1 and pharmaceutical excipient are made.
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| CN102863549A (en) * | 2012-09-27 | 2013-01-09 | 上海师范大学 | Method of using by-product fermentation broth generated in production of posaverptidum to produce extracellular posaverptidum |
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| CN1008537B (en) * | 1989-02-01 | 1990-06-27 | 上海师范大学 | Process for producing polystictus glycopeptide |
| CN1631373A (en) * | 2004-12-02 | 2005-06-29 | 马青 | Enteric coated formulation of Coriolus Versicolor Polysaccharide and its preparation process |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN113754737A (en) * | 2020-10-26 | 2021-12-07 | 北京市农林科学院 | Medicine for treating lead poisoning and glycopeptide used by same and preparation method of glycopeptide |
| CN113754737B (en) * | 2020-10-26 | 2024-02-20 | 北京市农林科学院 | Medicament for treating lead poisoning, glycopeptides used by medicament and preparation method of glycopeptides |
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