CN102379904B - Proteoglycan protein tablet and preparation method thereof - Google Patents
Proteoglycan protein tablet and preparation method thereof Download PDFInfo
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- CN102379904B CN102379904B CN201010272550.0A CN201010272550A CN102379904B CN 102379904 B CN102379904 B CN 102379904B CN 201010272550 A CN201010272550 A CN 201010272550A CN 102379904 B CN102379904 B CN 102379904B
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Abstract
The invention discloses a proteoglycan protein tablet and a preparation method thereof. The proteoglycan protein tablet is prepared from the following raw materials in percentage by weight: 10-15 percent of white mushroom extract, 5-10 percent of lucid ganoderma proteoglycan proteins, 5-10 percent of mushroom proteoglycan proteins, 5-10 percent of centipede proteoglycan protein compound, 50-60 percent of calcium sulfate, 3-10 percent of gelatin and 2-6 percent of magnesium stearate, wherein in the terms of glucose, every milliliter of white mushroom extract used in the tablet comprises 3-15 mg of proteoglycans and 8-40 mg of total amino acid, wherein the 8-40 mg of total amino acid comprises 3-20 mg of glutamic acid and 0.8-5 mg of aspartic acid. The preparation method comprises the following steps of: uniformly mixing fine powder; adding an appropriate amount of calcium sulfate for uniformly mixing to obtain particles; drying; adding an appropriate quantity of lubricating agent; and tableting with a tableting machine. The proteoglycan protein tablet can be taken as a medicament for treating or preventing tumors, a medicament for treating or preventing leukopenia, a medicament for treating or preventing light and medium icteric hepatitis, and a medicament for treating or preventing neurasthenia.
Description
Technical field:
The present invention relates to Proteoglycan protein tablet and preparation method thereof, particularly one can make leukocyte obviously rise, and liver function takes a turn for the better, nervous system regulation function, improves human body immunity, for leukopenia, infectious hepatitis, the Proteoglycan protein tablet of the auxiliary treatment of the diseases such as neurasthenia.
Background technology:
After fungus polysaccharide inhibition tumor activity is found, fungus polysaccharide causes increasing concern, becomes a very active research field.It is found that, fungus polysaccharide has complicated biological activity and function, and wherein, topmost activity is exactly immunoregulatory activity, immunity, defective disease, the clinical treatment of the diseases such as autoimmune disease and tumor are widely used in as a kind of immunomodulator fungus polysaccharide.
Mushroom polysaccharide albumen is from mushrooms sporophore, to isolate a kind of antitumor polysaccharide, and its main chain is β-(1 → 3)-D-glucosan, approximately has 23% glucose residue on main chain, passes through C
6branch point is connected with side chain.Studies confirm that afterwards, GL-PP is a kind of immunoactivator, energy activating macrophage and lymphocyte, chemotaxis and the toxic reaction level of lymphocyte to Yac-1 cell and P-815 cell of raising macrophage, the carcinogenesis of antagonism BBN to mice.Secondly it is that to induce α-interference effect more obvious, shows and can activate CD
4 +lymphocyte, impels CD
4 +propagation and the expression of IL-2R.
The special biologic activity of polysaccharide protein complex
There is bibliographical information, the polysaccharide protein complexs such as glycoprotein have antioxidation and remove the biologic activity of the harmful free radical of body, and it also plays very important effect in many biological processes such as cell recognition, signal conduction, immunne response, cell transformation.In addition, consider that its activity can be through immune system transmission, particularly by the realization that excites to immune specificity or non-specific function, therefore, this polysaccharide protein complex will have the features such as toxic and side effects is low.This is for the specific medicament of developing the treatment high, that substantially have no side effect of a kind of curative effect or preventing liver injury disease, significant.
The progress of Scolopendra extract pharmacological action
In motherland's medical science, Scolopendra is used as medicine with a long history, usually has and adjusts the effect that reaches Liver Channel.In recent years, also increasingly deep to the research of Scolopendra and extract pharmacological action thereof.There are some researches show, Scolopendra water extract can significantly reduce lipofuscin content in lipid peroxide and liver in rat blood serum, cerebral tissue, can make superoxide dismutase and blood Glutathione Peroxidase vigor in erythrocyte obviously raise.And it can make immune organ Thymus and spleen weight obviously increase, and significantly promotes body phagocyte activate the phagocytic capacity, especially phagocyte Fc receptor is had to remarkable potentiation, thereby performance improves the effect of body's immunity.(Wang Yufen, Han Shuanhong, Qu Shuming etc., the research of Scolopendra anti-aging effects, CHINA JOURNAL OF CHINESE MATERIA MEDICA, 1994,19 (11): 685) still, through retrieval, there is not up to now a kind of oral formulations such as tablet or capsule that adopts Mushroom polysaccharide albumen and centipede polysaccharide protein to be disclosed or to use.
Summary of the invention:
The object of the present invention is to provide one for leukopenia, infectious hepatitis, formula of the Proteoglycan protein tablet of the auxiliary treatment of the diseases such as neurasthenia and preparation method thereof.And application in the medicine of preparation treatment or prophylaxis of tumours, application in the medicine of preparation treatment or prevention leukopenia, treat or prevent the application in light medium-sized icterohepatitis medicine in preparation, and treat or prevent the application in neurasthenic medicine in preparation.
The technical solution used in the present invention is: described a kind of Proteoglycan protein tablet, is characterized in that this tablet is made up of following raw materials by weight;
White mushroom extractum 10～15;
Ganoderan albumen 5～10;
Lentinan protein 5～10;
Centipede polysaccharide protein composition 5～10;
Calcium sulfate 50～60;
Gelatin 3～10;
Magnesium stearate 2～6;
1) to adopt the polysaccharide amount of its white mushroom extractum of every milliliter be 3-15mg with glucose meter to this tablet white mushroom extractum, is 8-40mg containing total amino acids amount, and its Glutamic Acid accounts for 3-20mg, and aspartic acid accounts for 0.8-5mg.Described Proteoglycan protein tablet, is 3-10mg containing polysaccharide amount with glucose meter preferable range, is 8-40mg containing total amino acids preferable range, is 3-20mg containing glutamic acid preferable range, is 0.8-5mg containing aspartic acid preferable range.Described white mushroom extractum be from white mushroom, extract contain polysaccharide, total amino acids, wherein there is the extract of the effective ingredient such as glutamic acid, aspartic acid, can adopt commercially available prod, as adopted in the present embodiment: the mushroom extractum that gold good biochemical company limited in Chenghai city produces, the white mushroom extractum that also can extract by other prior art, but the polysaccharide amount of every milliliter of white mushroom extractum is 3-15mg with glucose meter, 8-40mg containing total amino acids amount, glutamic acid accounts for 3-20mg, and aspartic acid accounts for 0.8-5mg.
White mushroom extractum preparation method: 1 kilogram of the mushroom that water intaking was washed, 0.4% citric acid, 0.05% interfacial agent (sucrose fatty acid ester and sorbitan trioleate span85 and sorbitan mono-laurate span20) is to mix with the ratio of 2: 1: 1, with 80% alcoholic solution dipping, at room temperature decompression, solution is easily soaked into, after 15 minutes, take out, be placed in homogenizer.Add the hot solution that contains 0.1% phytic acid, 01% vitamin C, 0.3% Polymeric sodium metaphosphate., add while homogenizing, after all (5 liters) add, be not less than 95 ℃ of heating 10 minutes with temperature, enter the heart with 4000 revs/min of centrifuges and separate, obtain 5.2 liters of Extracts.In precipitate, add 5 liters of 0.3% saline solutions that contain 0.1% sodium carbonate, extracting 20 minutes at 30 ℃, obtains 4.7 liters of Extracts after separation.Residue after secondary extracting, make to be scattered in the citrate buffer solution of 1 liter of pH4.0, add 2 grams of pectases (Macerozyme), protease YPSS5 gram, 40 ℃ of vibrations (70 revs/min) 50 minutes, fully after reaction, centrifugalize, gained extract is incorporated to the extract of above secondary, is concentrated into 2 liters with high-temperature instantaneous concentrator, after decolouring with activated carbon and nylon 66 (100 order), again concentrated, obtain 200 milliliters of extractum.
2) described centipede polysaccharide protein composition can be commercially available prod, also can adopt following technique to make: described centipede polysaccharide protein composition is that extraction from arthropod Scolopendra Scorpio, separation, purification obtain, its preparation process is: 1. using few sour jujube Scolopendra as raw material parent, clean 4 times, dry 3 hours, bake out temperature is controlled at 70 ℃; 2. grind in the 1st step dried raw material parent and cross 100 mesh sieves and obtain Scolopendra powder; 3. by 3 times of volume distilled water extracting 2 hours for the Scolopendra powder in the 2nd step, temperature is controlled at 82 ℃, and filtered through gauze obtains a extracting solution, get residue and repeat to extract three times obtaining three parts of extracting solution with 2 times of volume distilled water again, merge above four parts of extracting solution, centrifugal 25 minutes of 2500r/min, obtains supernatant; 4. the supernatant in the 3rd step is evaporated to 0.1MPa, temperature is controlled at 60 ℃, adds 5 times of volume 95% ethanol, and in 4 ℃ of hold over night, the supernatant that inclines, gets precipitation, centrifugal 10 minutes of 2500r/min, collecting precipitation; 5. the precipitation in the 4th step is dissolved with 500ml distilled water, measure the needed solid ammonium sulfate amount of 40% saturation, slowly add in 4 ℃, stir 4h, 10000r/min after centrifugal 20 minutes, collect supernatant metered volume, repeat the operation 1 time of this step, collect the precipitate of 60% saturation; 6. after the precipitate in the 5th step being dissolved with 30ml distilled water, upper DEAE-50 ion exchange column (2.6 × 40cm) purification, with distilled water balance, with 0.05～0.25mol/L NaCl eluant solution, collect eluent, the desalination in 48 hours of dialysing in distilled water with bag filter, more concentrated with PEG 20000; 7. by Sephadex G-200 chromatographic column (2.6 × 60cm) purification on the concentrated solution in the 6th step, after the Tris-HCl eluant solution that is 7.2 with 0.02mol/L, pH, through vacuum lyophilization, pre-freeze temperature is controlled at-20 ℃, heating and temperature control is at 30 ℃, and being dried must centipede polysaccharide protein composition sterling after 9 hours.
3) ganoderan albumen is a kind of in conjunction with proteoglycan, is called for short GL-PP.The product that can adopt existing product or following methods to make.
The preparation method of ganoderan Protein G L-PP:
1, select grass planted ganoderma, Ganoderma dry product sporophore is clean after, dry, be broken into 20 object cigarette ropes with coarse granule pulverizer.
2, take the tobacco shred shape Ganoderma of having pulverized of 300 grams, 3000～4000 milliliters of backflows of ethanol with 95% 3 hours, reclaim ethanol, dry Ganoderma filament.Adopt Ganoderma filament: hot water=1: 15 ratio is carried out hot water return extraction 3 times to Ganoderma filament, and the time is respectively 2.5 hours, 2 hours, 1 hour, and merge the aqueous extract after filtering.
3, at the temperature of 90 ℃ condensed water extracting solution to 1/10th of original volume, then with speed be 3000r/min, the centrifuge that the time is 15min carries out centrifugalize, is standard by supernatant concentration to being equivalent to every milliliter containing 1 gram of Ganoderma crude drug amount.
4, with 95% Ethanol Treatment concentrated solution of triplication, stir 5 ℃ of standing first precipitate that to obtain of constant temperature.By the first precipitate centrifugal second precipitate that obtains again, the second precipitate is dissolved in to appropriate distilled water, and the 95% ethanol precipitation by this solution by 2～3 times of amounts, stirs, 5 ℃ of left and right leave standstill 24 hours and obtain the 3rd precipitate, and the 3rd precipitate is centrifugal that the first GL-PP precipitates again.
5, by the first GL-PP precipitation 95% ethanol, the each washing of acetone and ether 3 times, with speed be 3000r/min, the centrifuge that the time is 15min carries out centrifugalize, removes supernatant, taking precipitate is dried and obtains the first GL-PP in 5 ℃ of low temperature.
6, the first GL-PP is dissolved in to distilled water, is positioned in bag filter, adverse current dialysis 48 hours dialysis solution, by dialysis solution at 90 ℃ concentrated and concentrated solution.
7, by triplication in 95% Ethanol Treatment concentrated solution of concentrated solution, obtain the second GL-PP precipitation, by the second GL-PP precipitation 95% ethanol, the each washing of acetone and ether 3 times, with speed be 3000r/min, time is that the centrifuge of 15min carries out centrifugalize, remove supernatant, taking precipitate is drying to obtain ganoderan albumen in 5 ℃ of low temperature, the weight average molecular weight Mw of this ganoderan albumen is between 450,000～540,000, GL-PP is yellowish-brown to brown powder shape, its composition of Salvia polysaccharide is rhamnose, xylose, fructose, galactose, glucose, and each sugared mol ratio is 0.549: 3.614: 3.167: 0.556: 6.89.
4) lentinan protein
1. the processing of raw material
Get 1000 grams of the Lentinus Edodes bodies of having dried, grind to Lentinus Edodes powder more than 30 orders.
2, the preparation of compound enzyme
Get 59 grams of pectases, 2.0 grams of cellulase, 1.5 grams of amylase, 3.5 grams of hemicellulases, 4.0 grams, protease, 2.0 grams of compound enzyme liquid that are mixed into 70 grammes per square metres of saccharifying enzyme are stand-by.
3. hot water lixiviate
The Lentinus Edodes powder of 1000 grams is added to the water of 7000 milliliters, be heated to 90 ℃, after stirring, keep 90 ℃, 60 minutes time to carry out hot water lixiviate.
4. enzymolysis, deactivation
Lixiviate mixed liquor is dropped to 90 ℃ from 90 ℃, add 70 grams of the compound enzyme liquid that prepare in advance, after stirring, keep 43 ℃, carry out 60 minutes enzymolysis.Then be warming up to rapidly 95 ℃ and carry out quick inactivating, deactivation is natural cooling cooling after 1 minute.
5. centrifugal, concentrated
Utilize frame centrifuge, with 3000r.p.n rotating speed rejection filter, remove slag: filtrate is with the concentrated 7-8 hour of vacuum film.
6. dry
In concentrated solution, add and under 70 ℃ of conditions, spray after appropriate amount of starch dryly, obtain GL-PP dry product.
5) calcium sulfate, gelatin, magnesium stearate are food grade product or pharmaceutical grade product, as gelatin adopts pharmagel.
The manufacture method of Proteoglycan protein tablet of the present invention, comprises the steps:
(1) pour white mushroom extractum into evaporating dish, heating is also constantly stirred, and makes into thick paste;
(2) add appropriate calcium sulfate, gelatin to mix, continue heated and stirred, make mixture become thick paste;
(3) thick paste in step (2) is spread out in stainless steel disc, put in baking oven and be dried, get dry extract;
(4) dried cream powder in step (3) is broken into fine powder;
(5) centipede polysaccharide protein composition that takes above-mentioned formula ratio is worn into fine powder;
(6) lentinan protein, the ganoderan albumen that take above-mentioned formula ratio are worn into fine powder;
(7) by the fine powder mix homogeneously of step (4), (5) and (6), add appropriate calcium sulfate mix homogeneously, granulation, after dried, add appropriate lubricant, carry out tabletting with tablet machine, the plain sheet after punching press is placed in to coating pan and is bundled into coated tablet.
The heating-up temperature of above-mentioned steps (1) is 60-80 ℃, and mixing time is 1.5-2.5 hour.The heating-up temperature of step (2) is 60-80 ℃, and mixing time is 0.5-1 hour.In above-mentioned steps (3), baking temperature is 80-90 ℃, and be 16-24 hour drying time.
The effective ingredient polysaccharide of Proteoglycan protein tablet of the present invention, total amino acids, glutamic acid, aspartic acid etc., in above-described content range, there is good pharmacological action, it can be as the medicine for the treatment of or prophylaxis of tumours, the medicine for the treatment of or prevention leukopenia, treat or prevent light medium-sized icterohepatitis medicine, and treat or prevent neurasthenic medicine, concrete pharmacological action refers to as described below.
Proteoglycan protein tablet pharmacological action of the present invention
1, antitumor action
Allogene and the original tumor that occurs are had to significant inhibitory action, can prevent the carcinogenesis that chemical factor or virus cause, suppress the transfer of tumor.
2, strengthening immune function of human body lowly acts on
That a kind of host defends reinforcing agent.It can recover or strengthen the reaction of host to lymphocyte, hormone and other biological active factors, by maturation, differentiation and the breeding of immune stimulating activity cell.
3, immunoregulation effect
Classical pathway or change approach that can activating complement system, strengthen the infiltration of neutrophilic leukocyte to tumor knot, impels host to recover as early as possible the homoiostasis imbalance situation causing because of cancer and infection.
4, anti-HIV and hepatitis virus resisting effect, strengthens immunity, promotes hepatic injury repair, contributes to liver function recovery.Particularly centipede polysaccharide protein composition has following characteristics in control liver damage disease: 1. can not only treat number of chemical liver damage, as alcoholic liver injury, carbon tetrachloride hepatic injury, High dose dexamethasone hepatic injury, and immunologic liver injury is also had to significant curative effect; 2. above-mentioned antihepatitis activity is directly relevant with a series of function for protecting liver and reducing enzyme activity such as its removing free radical, the activity that improves antioxidant enzyme, reduction LPO levels and immunomodulating; 3. acute toxicity test shows that its toxic and side effects is low.
5, reduce hyperlipidemia effect
6, anti-aging effects
Proteoglycan protein tablet pharmacodynamics test of the present invention
Table 1 GL-PP is to mice (lotus H
22) impact of body weight
n＝6?
1)P＜0.05
Animal experiment has proved: 1. lotus liver cancer mouse in this experiment, belong to compared with late period, and tumor is 1cm roughly
3left and right.Medication latter two medicine (Fw and Fb) all has obvious cancer suppressing ratio, administration group mice does not only have cancerometastasis situation to occur, and body weight also has obvious increase than matched group, this has proved the cancer suppressing action of two kinds of GL-PP to rat liver cancer H22 from another angle.The alkali solubility glycoprotein (Fb) that Proteoglycan protein tablet of the present invention is made and the water-soluble sugar albumen (Fw) of making.
Table 2 GL-PP is to rat liver cancer H22 inhibitory action
Note: 1. 2. dosage contrast is for to outside normal saline 0.4ml (kgd) for n=6, and standby group is 20mg/ (kgd).
Administration 10 days altogether
1)p < 0.05
2)p < 0.001.
2. in this experiment, from suppressing the effect of hepatocarcinoma H22, alkali solubility glycoprotein (Fb) is better than water-soluble sugar albumen (Fw); Substantially similar from the cancer suppressing ratio of administering mode.Illustrate that oral process Chinese medicine is not subject to the impact of gastric juice.Oral administration has a lot of conveniences, and the selection that this experiment is route of administration provides foundation.
Proteoglycan protein tablet clinical efficacy of the present invention
Comprehensive 5 pilot medical sites, use Proteoglycan protein tablet, to diseases such as leukopenia, acute icterohepatitis, neurasthenias, through observation in 6 months, all obtain certain curative effect.
(1) treatment leukopenia
Comprehensive 5 pilot medical sites, through 5 years, treat 68 people altogether.Cause the reason that leukocyte declines: major part is cancerous protuberance patient because radiotherapy or chemotherapy cause, also have because benzolism or other chronic diseases cause, its curative effect is consistent substantially, only has indivedual patients invalid.
1. observation of curative effect standard after medication:
Effective: lencocyte count, than rising 2000 or above person before medication.
Effective: lencocyte count, than the 1000-2000 person that rises before medication.
Slightly effect: lencocyte count, than the 500-1000 person that rises before medication.
Invalid: lencocyte count, than the < 500 or constant that rises before medication.
2. total effective rate: 76.4%, add slightly efficiency, account for 86.7%, inefficiency: 13.3%, see the following form in detail 3.
Table 3
Note: 1. accumulated result: effective 31 examples, obvious effective rate 45.6%, effective 21 examples, effective percentage 30.8%, slightly imitates 7 examples, slightly efficiency 10.3%, no effect 9, inefficiency 13.3%.
2. effective percentage (adding slightly effect) is 86.7%.
3. in invalid 4 examples in three places, have that 2 examples are nauseating because having, vomiting drug withdrawal.
(2) treat light medium-sized icterohepatitis
I am through clinical verification for many years, with Proteoglycan protein tablet be gently medium-sized, icterohepatitis 18 examples of main treatment, wherein acute hepatitis 15 examples, chronic hepatitis acute attack 3 examples.Treatment most patients symptom through 10-14 days is clearly better, and feels sick, vomits disappearance, and appetite takes a turn for the better, and liver function also takes an evident turn for the better, and jaundice disappears, liver retraction.
Before and after Proteoglycan protein tablet (slurry) treatment, liver function changes
Before and after (Continued) Proteoglycan protein tablet (slurry) treatment, liver function changes
Note: a 1. routine palpation of liver situation is not recorded, therefore only 17 examples take statistics
2. in icteric index inspection, there is a routine haemolysis.
(3) treatment neurasthenia
Through the treatment in 1-2 week, patient's sleep state all improves, and dizziness headache is uncomfortable in chest etc., and symptom subtracts greatly.
Proteoglycan protein tablet is to have certain curative effect to treatment leukopenia.After clothes, appetite increases.Spirit takes a turn for the better.To the acute icteric infectious hepatitis overwhelming majority effectively.The conscious spirit ground of patient after medication, appetite is promoted, and hepatalgia alleviates or disappears, and liver has and dwindles, liver function improvement.Improving cancerous protuberance because of the leukopenia that chemotherapy, radiotherapy cause, be to have sure curative effect.After many clothes for patients, spirit takes a turn for the better, and appetite increases, and leukocyte has obvious rising.Subjective symptoms is improved, and dwindles though lump has no, and the active ingredients such as the aminoacid wherein containing are played raising resistance against diseases to human body, reaches righting and gets rid of evils.Improve the inhibition tumor of human body inherence or strengthened the rejection of body, and reaching the object of anti-curing oncoma.
The specific embodiment:
The centipede polysaccharide protein composition of following embodiment is that extraction from arthropod Scolopendra Scorpio, separation, purification obtain, and its preparation process is: 1. using few sour jujube Scolopendra as raw material parent, clean 4 times, dry 3 hours, bake out temperature is controlled at 70 ℃; 2. grind in the 1st step dried raw material parent and cross 100 mesh sieves and obtain Scolopendra powder; 3. by 3 times of volume distilled water extracting 2 hours for the Scolopendra powder in the 2nd step, temperature is controlled at 82 ℃, and filtered through gauze obtains a extracting solution, get residue and repeat to extract three times obtaining three parts of extracting solution with 2 times of volume distilled water again, merge above four parts of extracting solution, centrifugal 25 minutes of 2500r/min, obtains supernatant; 4. the supernatant in the 3rd step is evaporated to 0.1MPa, temperature is controlled at 60 ℃, adds 5 times of volume 95% ethanol, and in 4 ℃ of hold over night, the supernatant that inclines, gets precipitation, centrifugal 10 minutes of 2500r/min, collecting precipitation; 5. the precipitation in the 4th step is dissolved with 500ml distilled water, measure the needed solid ammonium sulfate amount of 40% saturation, slowly add in 4 ℃, stir 4h, 10000r/min after centrifugal 20 minutes, collect supernatant metered volume, repeat the operation of this step once, collect the precipitate of 60% saturation; 6. after the precipitate in the 5th step being dissolved with 30ml distilled water, upper DEAE-50 ion exchange column (2.6 × 40cm) purification, with distilled water balance, with 0.05～0.25mol/L NaCl eluant solution, collect eluent, the desalination in 48 hours of dialysing in distilled water with bag filter, more concentrated with PEG 20000; 7. by Sephadex G-200 chromatographic column (2.6 × 60cm) purification on the concentrated solution in the 6th step, after the Tris-HCl eluant solution that is 7.2 with 0.02mol/L, pH, through vacuum lyophilization, pre-freeze temperature is controlled at-20 ℃, heating and temperature control is at 30 ℃, and being dried must centipede polysaccharide protein composition sterling after 9 hours.
Embodiment mono-
(1) pour 2 kilograms of white mushroom extractum into evaporating dish, heat 80 ℃ and continuous stirring 2 hours, make into thick paste shape;
(2) add 3.0 kilo sulfuric acid calcium, 0.3 kilogram of gelatin, continue 80 ℃ of heating and stir 2 hours, make mixture become thick paste;
(3) thick paste in step (2) is spread out in stainless steel disc, put in baking oven in 80 ℃ dry 24 hours, get dry extract;
(4) dried cream powder in step (3) is broken into fine powder;
(5) take 0.6 kilogram of the above-mentioned centipede polysaccharide protein composition making and grind to form fine powder;
(6) take the lentinan protein of 0.7 kilogram, the ganoderan albumen of 0.5 kilogram is worn into fine powder;
(7) by the fine powder mix homogeneously of step (4), (5) and (6), add again 2.5 kilo sulfuric acid calcium to be mixed, granulation, at 80 ℃ after dried, add the magnesium of 0.4 kilogram, carry out tabletting with tablet machine, the plain sheet after punching press is placed in to coating pan and is bundled into coated tablet.
Polysaccharide amount in its every milliliter of above-mentioned white mushroom extractum used is 10mg with glucose meter, is 20mg containing total amino acids amount, and its Glutamic Acid accounts for 10mg, and aspartic acid accounts for 2mg.
Embodiment bis-
(1) pour 2.5 kilograms of white mushroom extractum into evaporating dish, heat 90 ℃ and continuous stirring 2 hours, make into thick paste shape;
(2) add 3 kilo sulfuric acid calcium, 0.8 kilogram of gelatin, continue 80 ℃ of heating and stir 1 hour, make mixture become thick paste;
(3) thick paste in step (2) is spread out in stainless steel disc, put in baking oven in 70 ℃ dry 24 hours, get dry extract;
(4) dried cream powder in step (3) is broken into fine powder;
(5) take 0.7 kilogram of the above-mentioned centipede polysaccharide protein composition making and grind to form fine powder;
(6) take the lentinan protein of 0.8 kilogram, the ganoderan albumen of 0.6 kilogram is worn into fine powder;
(7) by the fine powder mix homogeneously of step (4), (5) and (6), add 1.1 kilo sulfuric acid calcium to be mixed, granulation, at 70 ℃ after dried, add the magnesium of 0.5 kilogram, carry out tabletting with tablet machine, the plain sheet after punching press is placed in to coating pan and is bundled into coated tablet.
Polysaccharide amount in its every milliliter of above-mentioned white mushroom extractum used is 8mg with glucose meter, is 30mg containing total amino acids amount, and its Glutamic Acid accounts for 15mg, and aspartic acid accounts for 3mg.
Embodiment tri-
(1) pour 2.2 kilograms of white mushroom extractum into evaporating dish, heat 70 ℃ and continuous stirring 2 hours, make into thick paste shape;
(2) add 2.5 kilo sulfuric acid calcium, 0.9 kilogram of gelatin, continue 60 ℃ of heating and stir 1 hour, make mixture become thick paste;
(3) thick paste in step (2) is spread out in stainless steel disc, put in baking oven in 70 ℃ dry 24 hours, get dry extract;
(4) dried cream powder in step (3) is broken into fine powder;
(5) take 0.9 kilogram of the above-mentioned centipede polysaccharide protein composition making and grind to form fine powder;
(6) take the lentinan protein of 0.5 kilogram, the ganoderan albumen of 0.8 kilogram is worn into fine powder;
(7) by the fine powder mix homogeneously of step (4), (5) and (6), add 1.9 kilo sulfuric acid calcium to be mixed, granulation, at 70 ℃ after dried, add the magnesium of 0.3 kilogram, carry out tabletting with tablet machine, the plain sheet after punching press is placed in to coating pan and is bundled into coated tablet.
Polysaccharide amount in its every milliliter of above-mentioned white mushroom extractum used is 8mg with glucose meter, is 20mg containing total amino acids amount, and its Glutamic Acid accounts for 10mg, and aspartic acid accounts for 3mg.
Claims (3)
1. a Proteoglycan protein tablet, this tablet is made up of following raw materials by weight;
White mushroom extractum 10～15;
Ganoderan albumen 5～10;
Lentinan protein 5～10;
Centipede polysaccharide protein composition 5～10;
Calcium sulfate 50～60;
Gelatin 3～10;
Magnesium stearate 2～6;
1) this tablet white mushroom extractum used, in its white mushroom extractum of every milliliter, the amount of polysaccharide is 3-15mg with glucose meter; In the white mushroom extractum of every milliliter, containing amino acid whose total amount is 8-40mg, and its Glutamic Acid accounts for 3-20mg, and aspartic acid accounts for 0.8-5mg;
Described white mushroom extractum is made up of following technique: the mushroom that water intaking was washed adds 0.4% citric acid and 0.05% interfacial agent, interfacial agent is mixed with the ratio of 2: 1: 1 by sucrose fatty acid ester and sorbitan trioleate span85 and sorbitan mono-laurate span20, with 80% alcoholic solution dipping, at room temperature decompression, solution is easily soaked into, after 15 minutes, take out, be placed in homogenizer; Add the hot solution that contains 0.1% phytic acid, 01% vitamin C, 0.3% Polymeric sodium metaphosphate., add while homogenizing, after all adding, be not less than 95 ℃ of heating 10 minutes with temperature, enter the heart with 4000 revs/min of centrifuges and separate, obtain Extract; In precipitate, add 0.3% saline solution that contains 0.1% sodium carbonate, extracting 20 minutes at 30 ℃, obtains Extract after separation; Residue after secondary extracting, make to be scattered in the citrate buffer solution of 1 liter of pH4.0, add pectase, protease, vibrate 50 minutes with 70 revs/min at 40 ℃, fully after reaction, centrifugalize, gained extract is incorporated in the extract of above secondary, concentrates to obtain concentrated solution, after decolouring with activated carbon and 100 order nylon 66 with high-temperature instantaneous concentrator, again concentrated, obtain extractum;
2) weight average molecular weight of described ganoderan albumen is between 450,000～540,000, and its composition of Salvia polysaccharide is rhamnose, xylose, fructose, galactose and glucose, and each sugared mol ratio is 0.549: 3.614: 3.167: 0.556: 6.89; Described ganoderan albumen is made up of following technique:
1. select grass planted ganoderma, Ganoderma dry product sporophore is clean after, dry, be broken into 20 object cigarette ropes with coarse granule pulverizer;
2. take the tobacco shred shape Ganoderma of having pulverized of 300 grams, 3000～4000 milliliters of backflows of ethanol with 95% 3 hours, reclaim ethanol, dry Ganoderma filament, adopt Ganoderma filament: the ratio that hot water is 1: 15 is carried out hot water return to Ganoderma filament and extracted 3 times, time is respectively 2.5 hours, 2 hours, 1 hour, and merges the aqueous extract after filtering;
3. at the temperature of 90 ℃ condensed water extracting solution to 1/10th of original volume, then with speed be 3000r/min, the centrifuge that the time is 15min carries out centrifugalize, is standard by supernatant concentration to being equivalent to every milliliter containing 1 gram of Ganoderma crude drug amount;
4. use 95% Ethanol Treatment concentrated solution of triplication, stir, 5 ℃ of standing first precipitate that to obtain of constant temperature; By the first precipitate centrifugal second precipitate that obtains again, the second precipitate is dissolved in to appropriate distilled water, and the 95% ethanol precipitation by this solution by 2～3 times of amounts, stirs, 5 ℃ of left and right leave standstill 24 hours and obtain the 3rd precipitate, and the 3rd precipitate is centrifugal that the first GL-PP precipitates again;
5. by the first GL-PP precipitation 95% ethanol, the each washing of acetone and ether 3 times, with speed be 3000r/min, the centrifuge that the time is 15min carries out centrifugalize, removes supernatant, taking precipitate is dried and obtains the first GL-PP in 5 ℃ of low temperature;
6. the first GL-PP is dissolved in to distilled water, is positioned in bag filter, adverse current dialysis 48 hours dialysis solution, by dialysis solution at 90 ℃ concentrated and concentrated solution;
7. use triplication in 95% Ethanol Treatment concentrated solution of concentrated solution, obtain the second GL-PP precipitation, by the second GL-PP precipitation 95% ethanol, the each washing of acetone and ether 3 times, with speed be 3000r/min, time is that the centrifuge of 15min carries out centrifugalize, remove supernatant, taking precipitate is drying to obtain ganoderan albumen in 5 ℃ of low temperature, the weight average molecular weight Mw of this ganoderan albumen is between 450,000～540,000, GL-PP is yellowish-brown to brown powder shape, its composition of Salvia polysaccharide is rhamnose, xylose, fructose, galactose, glucose, and each sugared mol ratio is 0.549: 3.614: 3.167: 0.556: 6.89,
3) described lentinan protein is made up of following technique:
1. the processing of raw material
Get 1000 grams of the Lentinus Edodes bodies of having dried, grind to Lentinus Edodes powder more than 30 orders;
2. the preparation of compound enzyme
Get 59 grams of pectases, 2.0 grams of cellulase, 1.5 grams of amylase, 3.5 grams of hemicellulases, 4.0 grams, protease, 2.0 grams of compound enzyme liquid that are mixed into 70 grammes per square metres of saccharifying enzyme are stand-by;
9. hot water lixiviate
The Lentinus Edodes powder of 1000 grams is added to the water of 7000 milliliters, be heated to 90 ℃, after stirring, keep 90 ℃, 60 minutes time to carry out hot water lixiviate;
4. enzymolysis, deactivation
Lixiviate mixed liquor is kept to 90 ℃, adds 70 grams of the compound enzyme liquid that prepare in advance, after stirring 43 ℃, carry out 60 minutes enzymolysis, be then warming up to rapidly 95 ℃ and carry out quick inactivating, deactivation is natural cooling cooling after 1 minute;
5. centrifugal, concentrated
Utilize frame centrifuge, with 3000r.p.n rotating speed rejection filter, remove slag: filtrate is with the concentrated 7-8 hour of vacuum film;
6. dry
In concentrated solution, add and under 70 ℃ of conditions, spray after appropriate amount of starch dryly, obtain GL-PP dry product;
4) described centipede polysaccharide protein composition is made up of following technique, 1. using few sour jujube Scolopendra as raw material parent, cleans 4 times, dries 3 hours, and bake out temperature is controlled at 70 ℃; 2. grind in the 1st step dried raw material parent and cross 100 mesh sieves and obtain Scolopendra powder; 3. by 3 times of volume distilled water extracting 2 hours for the Scolopendra powder in the 2nd step, temperature is controlled at 82 ℃, and filtered through gauze obtains a extracting solution, get residue and repeat to extract three times obtaining three parts of extracting solution with 2 times of volume distilled water again, merge above four parts of extracting solution, centrifugal 25 minutes of 2500r/min, obtains supernatant; 4. the supernatant in the 3rd step is evaporated to 0.1MPa, temperature is controlled at 60 ℃, adds 5 times of volume 95% ethanol, and in 4 ℃ of hold over night, the supernatant that inclines, gets precipitation, centrifugal 10 minutes of 2500r/min, collecting precipitation; 5. the precipitation in the 4th step is dissolved with 500ml distilled water, measure the needed solid ammonium sulfate amount of 40% saturation, slowly add in 4 ℃, stir 4h, 10000r/min after centrifugal 20 minutes, collect supernatant metered volume, repeat the operation 1 time of this step, collect the precipitate of 60% saturation; 6. after the precipitate in the 5th step being dissolved with 30ml distilled water, upper DEAE-50 ion exchange column (2.6 × 40cm) purification, with distilled water balance, with 0.05～0.25mol/L NaCl eluant solution, collect eluent, the desalination in 48 hours of dialysing in distilled water with bag filter, more concentrated with PEG 20000; 7. by Sephadex G-200 chromatographic column (2.6 × 60cm) purification on the concentrated solution in the 6th step, after the Tris-HCl eluant solution that is 7.2 with 0.02mol/L, pH, through vacuum lyophilization, pre-freeze temperature is controlled at-20 ℃, heating and temperature control is at 30 ℃, dry after 9 hours centipede polysaccharide protein composition sterling;
5) in the white mushroom extractum of every milliliter, containing amino acid whose total amount is 8-40mg, and its Glutamic Acid accounts for 3-20mg, and aspartic acid accounts for 0.8-5mg;
6) weight average molecular weight of described ganoderan albumen is between 450,000～540,000, and its composition of Salvia polysaccharide is rhamnose, xylose, fructose, galactose and glucose, and each sugared mol ratio is 0.549: 3.614: 3.167: 0.556: 6.89.
2. the manufacture method of Proteoglycan protein tablet claimed in claim 1, comprises the steps:
(1) pour the white mushroom extractum of formula ratio into evaporating dish, heating is also constantly stirred, and makes into thick paste;
(2) add appropriate calcium sulfate, gelatin to mix, continue heated and stirred, make mixture become thick paste;
(3) thick paste in step (2) is spread out in stainless steel disc, put in baking oven and be dried, get dry extract;
(4) dried cream powder in step (3) is broken into fine powder;
(5) centipede polysaccharide protein composition that takes formula ratio is worn into fine powder;
(6) lentinan protein, the ganoderan albumen that take formula ratio are worn into fine powder;
(7) by the fine powder mix homogeneously of step (4), (5) and (6), add remaining calcium sulfate mix homogeneously, granulation, after dried, add lubricant tabletting, the plain sheet after punching press is placed in to coating pan and is bundled into coated tablet;
The heating-up temperature of step (1) is 60-80 ℃, and mixing time is 1.5-2.5 hour;
The heating-up temperature of step (2) is 60-80 ℃, and mixing time is 0.5-1 hour.
3. Proteoglycan protein tablet claimed in claim 1, the application in the medicine of preparation treatment or prevention leukopenia and in preparation treatment or prevent application in light medium-sized icterohepatitis medicine and in preparation treatment or prevent the application in neurasthenic medicine.
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| CN101167755A (en) * | 2007-10-18 | 2008-04-30 | 武汉大学 | Method for preparing centipede polysaccharide protein composition with anti-tumor active and use |
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| 王贺祥.食用菌浸膏、冲剂加工.《食用菌栽培学》.2008,259. * |
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