CN111529563A - Method for preparing product component for treating and preventing gastric ulcer, gastritis and other gastropathy and product - Google Patents

Method for preparing product component for treating and preventing gastric ulcer, gastritis and other gastropathy and product Download PDF

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CN111529563A
CN111529563A CN202010452793.6A CN202010452793A CN111529563A CN 111529563 A CN111529563 A CN 111529563A CN 202010452793 A CN202010452793 A CN 202010452793A CN 111529563 A CN111529563 A CN 111529563A
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gastritis
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王晓
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Zhejiang Fuheng Biotechnology Co ltd
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/39—Convolvulaceae (Morning-glory family), e.g. bindweed
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants

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Abstract

The invention discloses a method for preparing product components for treating and preventing gastric ulcer, gastritis and other stomach diseases, which comprises the steps of respectively obtaining three components, namely GP, SM and PS from sweet potatoes, mixing the three components and obtaining the product components with the functions of treating and preventing gastric ulcer, gastritis and other stomach diseases; the GP component is a substance capable of binding with gastric mucus and gastric mucosa in sweet potato, the SM component is a soluble part obtained by removing starch and structural components of cells in sweet potato, and the PS component is a polysaccharide including starch in sweet potato, and can help improve the function of gastric mucus and gastric mucosa after being mixed with GP and SM. The invention provides a brand-new option for treating and preventing the stomach illness, and better solves a plurality of problems in the aspects of effect and side effect of the product for treating the stomach illness in the prior art.

Description

Method for preparing product component for treating and preventing gastric ulcer, gastritis and other gastropathy and product
Technical Field
The invention relates to the technical field of medicines, in particular to a product component and a finished product for treating and preventing gastric ulcer, gastritis and other stomach diseases, and a preparation method thereof.
Background
Gastropathy is a frequently encountered and common disease. There are many drugs currently used for the treatment of gastric diseases, mainly including drugs that inhibit gastric acid secretion, weak base drugs that neutralize gastric acid, antibiotics against helicobacter pylori. The medicine for inhibiting gastric acid secretion has a good curative effect on gastropathy including gastric ulcer, and generally needs to be taken for a long time, but the gastric acid is needed for normal defense and digestive function of a digestive system, so that the defect of inhibiting the gastric acid secretion for a long time is caused. Weak base drugs that neutralize stomach acid have the advantage of only temporarily reducing stomach acidity, but have a low therapeutic effect. Antibiotics are only auxiliary drugs for stomach diseases, cannot be independently treated, and can also disturb the intestinal bacteria ecology. Therefore, there is a need to develop new means for achieving therapeutic objectives without inhibiting gastric acid secretion, and to provide more and better options for treating or regulating and preventing gastric diseases.
Disclosure of Invention
The invention aims to solve the defects of the prior art and provides a method for preparing a product component for treating and preventing gastric ulcer, gastritis and other stomach diseases and a finished product of the product.
The technical scheme adopted by the invention for solving the technical problems is as follows:
a method for preparing product components for treating and preventing gastric ulcer, gastritis and other gastropathy comprises respectively obtaining three components, marked as GP, SM and PS, from sweet potato, mixing the three components, and obtaining product components for treating and preventing gastric ulcer, gastritis and other gastropathy; the GP component is a substance capable of binding with gastric mucus and gastric mucosa in sweet potato, the SM component is a soluble part obtained by removing starch and structural components of cells in sweet potato, and the PS component is a polysaccharide including starch in sweet potato, and can help improve the function of gastric mucus and gastric mucosa after being mixed with GP and SM.
Preferably, the method for obtaining GP fraction comprises the steps of:
s1, homogenizing and boiling sweet potatoes, mixing the sweet potatoes with concanavalin A agarose gel, and marking the component obtained after eluting the conjugate bound to the concanavalin A agarose gel as GPT;
s2, obtaining rat gastric mucus and gastric mucosa, respectively recording the gastric mucus and gastric mucosa AS S and I, respectively preparing a group of monoclonal antibodies AS-1 and a group of monoclonal antibodies AI-1 aiming at the S and the I, and respectively screening 3 monoclonal antibodies from the monoclonal antibodies, wherein the screening method comprises the following steps: when the antibody reaction of AS-1 and AI-1 is detected, component GPT is used for blocking, and when the antibody positive reaction of AS-1 or AI-1 which presents positive reaction is weakened because GPT blocking occurs, the AS-1 or AI-1 is the monoclonal antibody to be screened, so that 3 monoclonal antibodies are respectively obtained from AS-1 and AI-1 groups and are respectively marked AS AS-1a, AS-1b, AS-1c, AI-1a, AI-1b and AI-1 c;
s3, using Fc segment of common mouse antibody IgG, without adjuvant, to make tolerizing operation to mice, and using these mice to prepare 6 monoclonal antibody idiotypic antibodies aiming at AS-1a, AS-1b, AS-1c, AI-1a, AI-1b and AI-1c, respectively, which are marked AS AS-2a, AS-2b, AS-2c, AI-2a, AI-2b and AI-2 c.
S4, respectively crosslinking AS-2a, AS-2b, AS-2c, AI-2a, AI-2b and AI-2c with protein A sepharose, and respectively preparing 6 affinity chromatography media; and then taking sweet potato homogenate and boiling, separating sweet potato components G1, G2, G3, G4, G5 and G6 from the homogenate by using 6 affinity chromatography mediums respectively, and mixing G1, G2, G3, G4, G5 and G6 to obtain a component GP.
Preferably, the SM fraction is obtained by centrifuging the homogenate of sweet potatoes, recovering the supernatant, and boiling and concentrating the supernatant to obtain SM fraction.
Preferably, the method for obtaining the PS fraction comprises the steps of:
a1, taking a plurality of ileum segments of rats, ligating one end of the ileum segments of the rats, and carrying out needle punching on the ileum of the rats; adding water into sweet potato starch, stirring and boiling, performing ultrasonic beating and centrifugal treatment, and then obtaining supernatant for molecular sieve chromatography;
a2, collecting the components obtained by molecular sieve chromatography in the step A1 into a plurality of collection tubes one by one, sampling from each collection tube, adding GP-SM mixture and dye into the samples, and injecting the new mixture into a plurality of ileum segments of rats prepared in A1;
a3, observing the time and the amount of the dye penetrating through the rat ileum section perforation, finding a plurality of collecting tubes in the step A2 corresponding to ileum samples with relatively long dye penetrating time and small amount, and then mixing the components in the collecting tubes with GP-SM mixtures respectively to obtain a plurality of test examples;
a4, using a rat gastric ulcer model to sequentially detect the treatment and prevention activity of the test cases in the step A3 on gastric ulcer and determine the test cases with the treatment and prevention activity on gastric ulcer, thereby determining the components which have the treatment and prevention activity on gastric ulcer after being mixed with GP-SM mixture in each component obtained by molecular sieve chromatography in the step A2, and marking the component as PS.
The invention also discloses a finished product for treating and preventing gastric ulcer, gastritis and other stomach diseases, which is prepared by the preparation method of the product for treating and preventing gastric ulcer, gastritis and other stomach diseases, and comprises the following nutrient components in percentage by weight: 46% to 47% carbohydrate, 4.5% to 5.5% protein, 26% to 27% fat, 0.005% to 0.05% sodium
The invention has the beneficial effects that:
the invention discloses a product component for treating and preventing gastric ulcer, gastritis and other gastropathy and a finished product thereof, provides a brand new option for treating and preventing the gastropathy, and better solves a plurality of problems of the products for treating the gastropathy in the prior art in the aspects of effect and side effect.
Detailed Description
The present invention will be further described below by way of embodiments.
In the method for manufacturing the product components for treating and preventing gastric ulcer, gastritis and other stomach diseases, three components are respectively obtained from sweet potatoes and are respectively marked as GP, SM and PS, and the three components are mixed to obtain the product components with the functions of treating and preventing gastric ulcer, gastritis and other stomach diseases; the GP component is a substance capable of binding with gastric mucus and gastric mucosa in sweet potato, the SM component is a soluble part obtained by removing starch and structural components of cells in sweet potato, and the PS component is a polysaccharide including starch in sweet potato, and can help improve the function of gastric mucus and gastric mucosa after being mixed with GP and SM.
Example one (GP fraction acquisition method):
in this embodiment, the method for obtaining GP components includes the following steps:
s1, homogenizing and boiling sweet potatoes, mixing the sweet potatoes with concanavalin A agarose gel, and marking the component obtained after eluting the conjugate bound to the concanavalin A agarose gel as GPT;
s2, obtaining rat gastric mucus and gastric mucosa, respectively recording the gastric mucus and gastric mucosa AS S and I, respectively preparing a group of monoclonal antibodies AS-1 and a group of monoclonal antibodies AI-1 aiming at the S and the I, and respectively screening 3 monoclonal antibodies from the monoclonal antibodies, wherein the screening method comprises the following steps: when the antibody reaction of AS-1 and AI-1 is detected, component GPT is used for blocking, and when the antibody positive reaction of AS-1 or AI-1 which presents positive reaction is weakened because GPT blocking occurs, the AS-1 or AI-1 is the monoclonal antibody to be screened, so that 3 monoclonal antibodies are respectively obtained from AS-1 and AI-1 groups and are respectively marked AS AS-1a, AS-1b, AS-1c, AI-1a, AI-1b and AI-1 c;
s3, using Fc segment of common mouse antibody IgG, without adjuvant, to make tolerizing operation to mice, and using these mice to prepare 6 monoclonal antibody idiotypic antibodies aiming at AS-1a, AS-1b, AS-1c, AI-1a, AI-1b and AI-1c, respectively, which are marked AS AS-2a, AS-2b, AS-2c, AI-2a, AI-2b and AI-2 c.
S4, respectively crosslinking AS-2a, AS-2b, AS-2c, AI-2a, AI-2b and AI-2c with protein A sepharose, and respectively preparing 6 affinity chromatography media; and then taking sweet potato homogenate and boiling, separating sweet potato components G1, G2, G3, G4, G5 and G6 from the homogenate by using 6 affinity chromatography mediums respectively, and mixing G1, G2, G3, G4, G5 and G6 to obtain a component GP.
Specifically, 100 g of sweet potato was homogenized in 500 ml of Tris-hydrochloric acid buffer solution (containing 10 mM Tris-HCl, 10 mM NaCl, 1 mM KCl, pH 7.4), the homogenate was boiled for 10 seconds, and after 1 minute of ultrasonic beating, 1000g of centrifugation was carried out for 10 minutes, and then the supernatant was recovered, NaCl was added to the recovered supernatant to adjust the concentration to 200 mM, and then CaCl was added2Adjusted to 1 millimole and then MnCl was added2After adjusting to 1 mmol, the mixture was mixed with 5 ml concanavalin A agarose gel and stirred for 20 minutes, and then the column was loaded, and the column was washed with 25 ml Tris-HCl buffer, and eluted with 10 ml Tris-HCl buffer containing α -D-methylglucoside (0.2 mol), and the eluate was collected and dialyzed against Tris-HCl buffer to obtain GPT.
30 rat stomachs were removed, cut open in dishes and washed with phosphate buffer (containing 10 mM NaH)2PO4-Na2HPO410 mM NaCl, 1 mM KCl, pH value 7.4), scraping off gastric mucus with a glass slide, and recording as gastric mucus S; phosphate buffer containing 2% polysorbate 20 (or polysorbate 40 or polysorbate 60 or polysorbate 80) was dropped on the gastric mucosa from which the gastric mucus was scraped, and the gastric mucosa was strongly scraped with a glass slide, and the score was given as gastric mucosa I.
Preparing monoclonal antibody aiming at gastric mucus S by adopting standard monoclonal antibody preparation technology, identifying positive reaction, sealing sweet potato component GPT, selecting 3 monoclonal antibodies with positive reaction weakened by GPT sealing, and marking AS AS-1a, AS-1b and AS-1c respectively; preparing monoclonal antibody aiming at gastric mucosa I by standard monoclonal antibody preparation technology, identifying positive reaction, using sweet potato component GPT to seal, selecting 3 monoclonal antibodies whose positive reaction can be weakened by GPT seal, and marking as AI-1a, AI-1b and AI-1c respectively.
Mice were subjected to tolerization procedures (tolerization) using the Fc portion of the common mouse antibody IgG without adjuvant. Using the thus obtained tolerant mice, preparing monoclonal anti-idiotypic antibodies (anti-idiotypic antibodies) against AS-1a, AS-1b, AS-1c using these mice, and selecting one antibody each, AS AS-2a, AS-2b, AS-2 c; monoclonal antibodies specific to AI-1a, AI-1b, AI-1c were prepared from tolerant mice, and one antibody was selected and designated AI-2a, AI-2b, AI-2c, respectively.
100 mg of each of AS-2a, AS-2b, AS-2c, AI-2a, AI-2b, and AI-2c was cross-linked with 5 ml of protein A Sepharose to prepare affinity chromatography media. Homogenizing 2000G sweet potato in 6000 ml phosphate buffer solution, boiling for 10 s, ultrasonic beating for 1 min, centrifuging for 10 min at 1000G, recovering supernatant, sequentially separating with the 6 affinity chromatography media to obtain sweet potato components G1, G2, G3, G4, G5 and G6, mixing G1, G2, G3, G4, G5 and G6 to obtain component GP, and adjusting volume to 10 ml with phosphate buffer solution.
Example two (method for obtaining SM fraction):
in this example, the method of obtaining SM fraction comprises centrifuging the sweet potato homogenate, recovering the supernatant, and boiling and concentrating the supernatant to obtain SM fraction.
More specifically, 200 g of sweet potato was homogenized in 600 ml of distilled water, centrifuged at 1000g for 10 minutes, the supernatant was recovered, boiled and concentrated to 20 ml, centrifuged at 9000g for 20 minutes, the supernatant was recovered again, and then distilled water was added to adjust the volume to 20 ml, to obtain an aqueous SM solution.
Example iii (method for obtaining PS component):
in this embodiment, the method for obtaining the PS component includes the following steps:
a1, taking a plurality of ileum segments of rats, ligating one end of the ileum segment of the rats, and carrying out needle punching on the ileum segment of the rats; adding water into sweet potato starch, stirring and boiling, performing ultrasonic beating and centrifugal treatment, and then obtaining supernatant for molecular sieve chromatography;
a2, collecting the components obtained by molecular sieve chromatography in the step A1 into a plurality of collection tubes one by one, sampling from each collection tube, adding GP-SM mixture and dye into the samples, and injecting the new mixture into a plurality of ileum segments of rats prepared in A1;
a3, observing the time and the amount of the dye penetrating through the rat ileum section perforation, finding a plurality of collecting tubes in the step A2 corresponding to ileum samples with relatively long dye penetrating time and small amount, and then mixing the components in the collecting tubes with GP-SM mixtures respectively to obtain a plurality of test examples;
a4, using a rat gastric ulcer model to sequentially detect the treatment and prevention activity of the test cases in the step A3 on gastric ulcer and determine the test cases with the treatment and prevention activity on gastric ulcer, thereby determining the components which have the treatment and prevention activity on gastric ulcer after being mixed with GP-SM mixture in each component obtained by molecular sieve chromatography in the step A2, and marking the component as PS.
More specifically, 100G of sweet potato starch is taken, 200 ml of distilled water is added and stirred, the mixture is boiled for 10 seconds, ultrasonic beating is carried out for 1 minute, centrifugation is carried out for 20 minutes at 5000G, supernatant is recovered, the mixture is boiled and concentrated to 10 ml, sephadex G-100 molecular sieve chromatography is carried out, a chromatographic column with the diameter of 3 cm and the column length of 55 cm is adopted, the chromatographic column is eluted by distilled water with the elution speed of 1 ml/minute, elution is collected by a plurality of collecting pipes, 5 ml of elution is collected in each pipe, and the components in the collecting pipes are marked as PPS 1.
0.9 ml of PPS1 was taken in a collection tube, 0.1 ml of GP and 0.01 ml of SM were added to obtain GP-SM-PPS1 mixture, and 0.1 ml of carbon ink was added.
A rat ileum section is cut into 2 cm-long segments, one end of the segment is tied, a 4-gauge injection needle is used for perforating the part of the segment close to the tied end of the segment, GP-SM-PPS1 mixture containing carbon ink is added into the segment, and the height of the segment above the liquid level of the segment is 1 cm. The intestine was then suspended in distilled water in test tubes and the time and amount of penetration of the black fluid through the perforations of the intestine was observed to determine the number of relatively long-penetrating, relatively small-volume ileal segments corresponding GP-SM-PPS1 blends and their corresponding PPS1 collection tubes, the PPS1 fraction in these tubes being otherwise designated PPS 2.
0.9 ml of PPS2 is taken in each collecting pipe respectively, 0.1 ml of GP and 0.01 ml of SM are added to obtain GP-SM-PPS2 mixture, the treatment and prevention activity of the GP-SM-PPS2 mixture on gastric ulcer is detected by a rat water immersion restraint gastric ulcer model, the GP-SM-PPS2 mixture obtained by mixing the PPS2 and the GP-SM mixture of which collecting pipe has the treatment and prevention activity on gastric ulcer is determined, and the PPS2 component is marked as PS.
Example four (method for obtaining sweet potato fraction having therapeutic activity on gastric ulcer):
in this example, the method of obtaining the sweet potato fraction having therapeutic activity on gastric ulcer includes mixing 0.1 ml of GP, 0.01 ml of SM, and 0.9 ml of PS among the fractions prepared in examples 1, 2, and 3 to obtain the sweet potato fraction having therapeutic and prophylactic effects on gastric ulcer.
Example five:
the finished product of the product for treating and preventing gastric ulcer, gastritis and other stomach diseases comprises the following nutrient components in percentage by weight: 46% to 47% carbohydrate, 4.5% to 5.5% protein, 26% to 27% fat, 0.005% to 0.05% sodium.
Simple substitutions without changing the inventive content of the present invention are considered to be the same. The embodiments are described in a progressive mode in the specification, each embodiment focuses on differences from other embodiments, and the same and similar parts among the embodiments are referred to each other. The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims (5)

1. A method for preparing a product component for treating and preventing gastric ulcer, gastritis and other stomach diseases is characterized in that: comprises respectively obtaining three components from sweet potato, respectively recording as GP, SM and PS, mixing the three components, and obtaining product components with effects of treating and preventing gastric ulcer, gastritis and other gastropathy; the GP component is a substance capable of binding with gastric mucus and gastric mucosa in sweet potato, the SM component is a soluble part obtained by removing starch and structural components of cells in sweet potato, and the PS component is a polysaccharide including starch in sweet potato, and can help improve the function of gastric mucus and gastric mucosa after being mixed with GP and SM.
2. The process for the manufacture of a product component for the treatment and prevention of gastric ulcers, gastritis and other gastric diseases, according to claim 1, characterized in that: the method for obtaining GP components comprises the following steps:
s1, homogenizing and boiling sweet potatoes, mixing the sweet potatoes with concanavalin A agarose gel, and marking the component obtained after eluting the conjugate bound to the concanavalin A agarose gel as GPT;
s2, obtaining rat gastric mucus and gastric mucosa, respectively recording the gastric mucus and gastric mucosa AS S and I, respectively preparing a group of monoclonal antibodies AS-1 and a group of monoclonal antibodies AI-1 aiming at the S and the I, and respectively screening 3 monoclonal antibodies from the monoclonal antibodies, wherein the screening method comprises the following steps: when the antibody reaction of AS-1 and AI-1 is detected, component GPT is used for blocking, and when the antibody positive reaction of AS-1 or AI-1 which presents positive reaction is weakened because GPT blocking occurs, the AS-1 or AI-1 is the monoclonal antibody to be screened, so that 3 monoclonal antibodies are respectively obtained from AS-1 and AI-1 groups and are respectively marked AS AS-1a, AS-1b, AS-1c, AI-1a, AI-1b and AI-1 c;
s3, using Fc segment of common mouse antibody IgG, without adjuvant, to make tolerizing operation to mice, and using these mice to prepare 6 monoclonal antibody idiotypic antibodies aiming at AS-1a, AS-1b, AS-1c, AI-1a, AI-1b and AI-1c, respectively, which are marked AS AS-2a, AS-2b, AS-2c, AI-2a, AI-2b and AI-2 c.
S4, respectively crosslinking AS-2a, AS-2b, AS-2c, AI-2a, AI-2b and AI-2c with protein A sepharose to respectively prepare 6 affinity chromatography media; and then taking sweet potato homogenate and boiling, separating sweet potato components G1, G2, G3, G4, G5 and G6 from the homogenate by using the 6 affinity chromatography mediums respectively, and mixing G1, G2, G3, G4, G5 and G6 to obtain a component GP.
3. A method of manufacturing a product component for the treatment and prevention of gastric ulcers, gastritis and other gastric diseases, according to claim 1 or 2, characterized in that: the method for obtaining SM component comprises centrifuging the homogenate of sweet potato, recovering the supernatant, boiling the supernatant, and concentrating to obtain SM component.
4. A process for the manufacture of a product composition for the treatment and prevention of gastric ulcers, gastritis and other gastric disorders, according to claim 3, characterized by: the method for obtaining the PS component comprises the following steps:
a1, taking a plurality of ileum segments of rats, ligating one end of the ileum segments of the rats, and carrying out needle punching on the ileum of the rats; adding water into sweet potato starch, stirring and boiling, performing ultrasonic beating and centrifugal treatment, and then obtaining supernatant for molecular sieve chromatography;
a2, collecting the components obtained by molecular sieve chromatography in the step A1 into a plurality of collection tubes one by one, sampling from each collection tube, adding GP-SM mixture and dye into the samples, and injecting the new mixture into a plurality of ileum segments of rats prepared in A1;
a3, observing the time and the amount of the dye penetrating through the rat ileum section perforation, finding a plurality of collecting tubes in the step A2 corresponding to ileum samples with relatively long dye penetrating time and small amount, and then mixing the components in the collecting tubes with GP-SM mixtures respectively to obtain a plurality of test examples;
a4, using a rat gastric ulcer model to sequentially detect the treatment and prevention activity of the test cases in the step A3 on gastric ulcer and determine the test cases with the treatment and prevention activity on gastric ulcer, thereby determining the components which have the treatment and prevention activity on gastric ulcer after being mixed with GP-SM mixture in each component obtained by molecular sieve chromatography in the step A2, and marking the component as PS.
5. A finished product for treating and preventing gastric ulcer, gastritis and other stomach diseases is characterized in that: comprises the following nutrient components in percentage by weight: 46% to 47% carbohydrate, 4.5% to 5.5% protein, 26% to 27% fat, 0.005% to 0.05% sodium.
CN202010452793.6A 2020-05-26 2020-05-26 Method for preparing product component for treating and preventing gastric ulcer, gastritis and other gastropathy and product Pending CN111529563A (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104397525A (en) * 2014-11-24 2015-03-11 王之永 Preparation process of sweet potato vermicelli
CN105249154A (en) * 2015-09-26 2016-01-20 袁恩灵 Dietary therapy formula and preparation method for sweet potatoes and medicinal materials
CN109206508A (en) * 2018-08-27 2019-01-15 深圳市菲鹏生物制药股份有限公司 The screening technique of affinity chromatography filler

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104397525A (en) * 2014-11-24 2015-03-11 王之永 Preparation process of sweet potato vermicelli
CN105249154A (en) * 2015-09-26 2016-01-20 袁恩灵 Dietary therapy formula and preparation method for sweet potatoes and medicinal materials
CN109206508A (en) * 2018-08-27 2019-01-15 深圳市菲鹏生物制药股份有限公司 The screening technique of affinity chromatography filler

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