CN103405756B - Medicine composition-compound digestive enzyme capsule (II) and preparation method thereof - Google Patents
Medicine composition-compound digestive enzyme capsule (II) and preparation method thereof Download PDFInfo
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- CN103405756B CN103405756B CN201310287513.0A CN201310287513A CN103405756B CN 103405756 B CN103405756 B CN 103405756B CN 201310287513 A CN201310287513 A CN 201310287513A CN 103405756 B CN103405756 B CN 103405756B
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Abstract
The invention provides a medicine composition-compound digestive enzyme capsule (II) and preparation method thereof. Pepsin granule consists of pepsin, cane sugar, dextrin and hydroxypropyl methyl cellulose; pancreatin enteric coated granule consists of a pill core and coating which coats the pill core, wherein the pill core consists of pancreatin, cane sugar, dextrin and hydroxypropyl methyl cellulose and the coating consists of polyacrylic resin, triethyl citrate and talcum powder.
Description
Technical field
The invention belongs to biomedicine technical field, specifically, the present invention relates to a kind of compound digestive enzyme capsule (II).In addition, the invention still further relates to the Preparation Method And Their Intermediate etc. of the said goods.
Background technology
The preparation of compound digestive enzyme, can be included in the enzyme that digestive tract different parts works, and as pepsin and pancreatin, also wishes that they discharge at digestive tract different parts simultaneously.Such as, Chinese patent 200710177613 discloses compound digestive enzyme capsule, but wherein pepsin and pancreatin are be present in capsule with the form of gastric solubleness coated tablet and ECT respectively, the former is to keep pepsic stability, but like this, take if chewed, ECT makes pancreatin wherein be damaged by being destroyed, if swallowed, due to the stop of gastric solubleness coating superposition capsule, make pepsin not to be discharged in gastric juice very soon, even may enter in the intestinal of alkalescence, affect pepsic service efficiency.
The present inventor, through studying for a long period of time, even if find not carry out coating to pepsin, as long as accessory formula is proper, also can keep the stable of Pepsin in the preparation of compound digestive enzyme; And in preparation technology, adjuvant and the equipment of preparing Pepsin can prepare the general of pancreatic enzymes enteric coated granule with part, further save preparation cost thus, simplify technique.In addition, the high activity coordinating the present inventor to find, the pancreatin that high self-excitation is active and activationary temperature is suitable, the optimum temperature wherein activated close to physiological temp, and does not almost have self-excitation active at low temperatures.Therefore, the compound preparation formed like this is particularly suitable for actual using and accumulating, preservation.
Summary of the invention
The technical problem that will solve of the present invention is to provide new compound digestive enzyme capsule (II).In addition, the invention still further relates to the preparation method and application etc. of this compound digestive enzyme capsule (II).
Specifically, in first aspect, the invention provides compound digestive enzyme capsule (II), it is made up of capsule shells and the Pepsin be contained in capsule shells and pancreatic enzymes enteric coated granule, and wherein Pepsin is made up of pepsin, sucrose, dextrin and hydroxypropyl methylcellulose; Wherein pancreatic enzymes enteric coated granule is made up of ball core and the coating be wrapped in outside ball core, and wherein ball core is made up of pancreatin, sucrose, dextrin and hydroxypropyl methylcellulose, and coating is made up of polyacrylic resin, triethyl citrate and Pulvis Talci.
In this article, numbering (II) is the naming rule of adopted drug name in pharmacopeia well-known to those skilled in the art, in order to distinguish existing " compound digestive enzyme capsule ".This numbering itself does not have the restriction effect of the feature such as composition and content.Preferably in the compound digestive enzyme capsule (II) of first aspect present invention, the weight ratio of Pepsin and pancreatic enzymes enteric coated granule is 0.7-1.2:8-12, is preferably 0.9-1.1:9-10, is more preferably 1:9.5.
Current pharmaceutic adjuvant is very many, chooses should have excellent agent character, also want cost cheap and can have the adjuvant of more total technique, then very difficult.So, preferably in the compound digestive enzyme capsule (II) of first aspect present invention, in Pepsin, the weight ratio of pepsin, sucrose, dextrin and hydroxypropyl methylcellulose is 40-60:28-38:13-22:0.3-1, be preferably 45-55:30-36:15-20:0.5-0.7, be more preferably 50:33:17:0.6.
Also preferred in the compound digestive enzyme capsule (II) of first aspect present invention, in pancreatic enzymes enteric coated granule, the weight ratio of pancreatin, sucrose, dextrin and hydroxypropyl methylcellulose is 23-35:3-12:2-7:0.3-1, be preferably 25-30:6-10:3-5:0.5-0.7, be more preferably 28:8:4:0.6.
Also preferred in the compound digestive enzyme capsule (II) of first aspect present invention, in pancreatic enzymes enteric coated granule, polyacrylic resin, triethyl citrate and talcous weight ratio are 23-35:1-5:5-12, are preferably 27-31:2-4:6-9, are more preferably 29:3:7.5.
Preferred in the compound digestive enzyme capsule (II) of first aspect present invention in addition, in pancreatic enzymes enteric coated granule, the weight ratio of ball core and coating, for being preferably 2-8:1-3, being preferably 4-6:1.5-2.5, being more preferably 5:2.
Preferably in the compound digestive enzyme capsule (II) of first aspect present invention, the aminoacid sequence of pancreatin as shown in SEQ ID NO:2, or adds in sequence shown in SEQ ID NO:2, really and/or replace one or several amino acid residue and obtain.
In the specific embodiment of the present invention, the aminoacid sequence of pancreatin is as shown in SEQ ID NO:2.This pancreatin, except having high activity, also has high self-excitation active, and the optimum temperature activated is close to physiological temp, and does not almost have self-excitation active at low temperatures, is therefore particularly suitable for actual using and accumulating, preservation.This pancreatin can be chemosynthesis, but obtain preferably through recombinant DNA technology expression, as expressed preparation by the gene of nucleotide sequence as shown in SEQ ID NO:1.
In second aspect, the invention provides the preparation method of the compound digestive enzyme capsule (II) of first aspect present invention, it comprises,
(1) hydroxypropyl methylcellulose is dissolved in the mixed solution of second alcohol and water, is mixed with the ethanol water of hydroxypropyl methylcellulose, be preferably mixed with 1.5-3%(as 2%) ethanol water of (W/W) hydroxypropyl methylcellulose;
(2) the ethanol water centrifugal granulating of the hydroxypropyl methylcellulose obtained with step (1) after the mixing of pepsin, sucrose and dextrin is become Pepsin, being preferably a granulated into particle diameter is the preferred 0.95mm of 0.9-1mm() Pepsin;
(3) the ethanol water centrifugal granulating of the hydroxypropyl methylcellulose obtained with step (1) after the mixing of pancreatin, sucrose and dextrin is become ball core, being preferably a granulated into particle diameter is the preferred 0.9mm of 0.85-0.95mm() ball core;
(4) by triethyl citrate and water, (preferably wherein the weight ratio of lemon triethylenetetraminehexaacetic acid ester and water is 2-4:450-550, be more preferably 3:500) mixing after, call in polyacrylic acid resin emulsion (preferably wherein polyacrylic resin concentration is 27-32%(W/W), be more preferably 29%(W/W)) in, add Pulvis Talci mixing again, be mixed with enteric coating liquid;
(5) enteric coating liquid that step (4) obtains be wrapped in outside the ball core that step (3) obtains by boiling seed-coating machine, obtain granule, preferably obtaining particle diameter is the preferred 1.1mm of 1-1.2mm() pancreatic enzymes enteric coated granule; With
(6) the pancreatic enzymes enteric coated granule that Pepsin step (2) obtained and step (5) obtain incapsulates in (shell).
In the third aspect, the invention provides the preparation method of Pepsin, it comprises,
(1) hydroxypropyl methylcellulose is dissolved in the mixed solution of second alcohol and water, is mixed with the ethanol water of hydroxypropyl methylcellulose, be preferably mixed with 1.5-3%(as 2%) ethanol water of (W/W) hydroxypropyl methylcellulose; With
(2) the ethanol water centrifugal granulating of the hydroxypropyl methylcellulose obtained with step (1) after the mixing of pepsin, sucrose and dextrin is become Pepsin, being preferably a granulated into particle diameter is the preferred 0.95mm of 0.9-1mm() Pepsin.
Pepsin prepared by the preparation method of third aspect present invention can be the Pepsin in the compound digestive enzyme capsule (II) of first aspect present invention, also can be independent use.
So, in fourth aspect, the application of Pepsin in the medicine for the preparation for the treatment of or prevention gastroenteropathy prepared by the preparation method that the invention provides third aspect present invention.In this article, as without contrary instruction, gastroenteropathy refers to pepsin and pancreatin can the intestinal tract disease of independence or therapeutic alliance or prevention, preferably dyspepsia.So preferably its Chinese medicine is used for the treatment of or prevents dyspepsia.
In the 5th, the invention provides the application of pancreatin in the medicine for the preparation for the treatment of or prevention gastroenteropathy, wherein the aminoacid sequence of pancreatin is as shown in SEQ ID NO:2, or to add in sequence shown in SEQ ID NO:2, really and/or replace one or several amino acid residue and obtain.
In application preferably in the present invention the 4th or the 5th, medicine is the compound digestive enzyme capsule (II) of first aspect present invention.
The beneficial effect that the present invention obtains is: the long-term stability that still can ensure Pepsin without the need to coating; In preparation technology, adjuvant and the equipment of preparing Pepsin can prepare the general of pancreatic enzymes enteric coated granule with part, further save preparation cost thus, simplify technique; The high activity coordinating the present inventor to find, the pancreatin that high self-excitation is active and activationary temperature is suitable, using and accumulating, preservation of more convenient reality.
For the ease of understanding, the present invention refer to open source literature, and these documents are to more clearly describe the present invention, and its entire contents is all included in and carried out reference herein.Below will be described in detail the present invention by specific embodiment.It is important to note that these descriptions are only exemplary descriptions, do not form limitation of the scope of the invention.According to the discussion of this description, many changes of the present invention, to change concerning one of ordinary skill in the art be all obviously.
Detailed description of the invention
Experimental technique described in following examples, do not illustrate, according to " Molecular Cloning: A Laboratory guide " (2002, the third edition, Science Press), " cell experiment guide " (calendar year 2001, Science Press) etc. the method described in laboratory manual carry out, or experimentally in reagent, the description that provides of manufacturer of instrument or the handbook specifically used carry out.
the preparation of embodiment 1 pancreatin
We devise the optimization expression sequence of pancreatin gene of the present invention in yeast, and its nucleotide is as shown in SEQ ID NO:1, and the aminoacid sequence of the pancreatin of its coding is as shown in SEQ ID NO:2.We entrust Shanghai Sheng Gong company this gene order of synthetic and are cloned into yeast cells with reference to conventional method and are built into expression engineering bacteria, in brief, with the gene order of synthesis for template, with the upstream and downstream primer PCR amplification such as shown in SEQ ID NO:3 and 4, then being connected to pPICZ α A(can purchased from American Invitrogen company) EcoR I and Xba I between, positive construct electricity is transformed in yeast GS115 strain (can purchased from American Invitrogen company), filters out positive yeast cell as engineering bacteria using Zeocin.
The engineering bacteria built is inoculated in 25ml seed culture medium (formula is: 2%(W/W) peptone, 1%(W/W) yeast extract, 1.34%(W/W) YNB(is without amino yeast nitrogen), 4*10
-5%(W/W) biotin and pH3.2 sodium hydrogen phosphate-citrate buffer solution (0.2M sodium hydrogen phosphate: 0.1M citric acid (volume ratio)=1:3)), in 30 DEG C, 200rpm shakes cultivation, until OD600 reaches 3.Then, 25ml seed culture product is inoculated into 100ml fermentation medium (formula is: 2%(W/W) peptone, 1%(W/W) yeast extract, 1.34%(V/V) YNB(is without amino yeast nitrogen), 4*10
-5%(W/W) biotin, 0.5%(V/V) methanol and pH3.2 sodium hydrogen phosphate-citrate buffer solution) in, in 30 DEG C, 150rpm shakes cultivation, within every 12 hours, adds methanol to 0.5%(V/V), cultivate 96 hours.Then, in 4 DEG C, the centrifugal fermentation culture product of 1500rpm, retain supernatant, be splined on Sephadex G-75 chromatographic column, carry out eluting with pH3.2 sodium hydrogen phosphate-citrate buffer solution, collect the maximum elution peak that 280nm ultraviolet detection goes out, then lyophilization, in 4 DEG C of preservations, namely prepare pancreatin of the present invention.After testing, pancreatin expression is 3g/L.
the character research of embodiment 2 pancreatin
Pancreatin prepared by embodiment 1 is dissolved in the pH8.0 Tris-HCl buffer containing 20mM calcium chloride, load bag filter, dialyse twice in pH8.0 Tris-HCl buffer (0.1M) in 4 DEG C, each 15 minutes, then Tos-Gly-Pro-Arg-4-pNA(Chromozym TRY is added) as substrate, make pancreatin self-activation after 1 hour with different temperatures, detect its activity.Result is as shown in table 1, and it is active that pancreatin of the present invention has high self-excitation under physiological temp, and almost do not have activity at low temperatures, and the enzymatic activity of 37 DEG C just can reach more than 300U/mg at short notice.
The character of table 1 pancreatin of the present invention
| Temperature (DEG C) | 4 | 25 | 37 | 50 |
| Active (U/mg) | 2.8 | 276 | 311 | 65 |
the preparation of the pancreatic enzymes enteric coated granule of embodiment 3
(1) hydroxypropyl methylcellulose is water-soluble, then add 95% alcoholic solution, 2%(W/W is mixed with) ethanol water (ethanol: water (volume ratio)=1:1) of hydroxypropyl methylcellulose.
(2) pancreatin 28 parts, sucrose 8 parts and the dextrin 4 parts of mix homogeneously that prepared by Example 1 are placed on centrifugal granulator (can purchased from Linyi, Shandong ring generation micropill equipment company limited; BZL-300 type) in; according to manufacturers instruction; the ethanol water 32 parts (after measured, about having 0.6 part of hydroxypropyl methylcellulose to be adhered in ball core) of the hydroxypropyl methylcellulose of injecting step (1), carries out pelletize; form ball core; after oven dry, its particle diameter average out to 0.9mm, for subsequent use.
(3) triethyl citrate 3 parts is joined in distilled water 500 parts, (purchasing can from Lianyun Harbour Wan Tai medical material company limited to call in polyacrylic acid resin emulsion after mix homogeneously, the aqueous suspensions of solid content 29%) in 100 parts, add Pulvis Talci 7.5 parts again, mix homogeneously, obtain enteric coating liquid, for subsequent use.
(4) ball core prepared by step (2) being placed in boiling seed-coating machine (can purchased from Linyi, Shandong ring generation micropill equipment company limited, LBY-1 type) in, enteric coating liquid step (3) prepared is sprayed on this micropill surface equably by spray gun, wherein, atomizing pressure 0.1Mpa, regulates and makes inlet temperature (50-55 DEG C) stabilize to about 40 DEG C to keep leaving air temp, carry out 25 minutes, complete coating, prepare enteric coated particles.Coated, increase weight about 40%, its particle diameter average out to 1.1mm after the ball core drying that obtained enteric coated particles is prepared than step (2).
Pancreatic enzymes enteric coated granule of the present invention is placed in respectively the phosphate buffer of pH3 and pH5, stirs with 50rpm in 37 DEG C, detect antiacid stability.Result is as shown in table 2, and stability can reach the level of international large factory, especially kept stable between pH3-5.5, and wherein along with acidity increases, stability slightly strengthens.In addition, the pancreatin of pharmacopeia is used by above technique, the pancreatic enzymes enteric coated capsule obtained carries out antiacid Detection of Stability, and the stability of its pH3-5.5 is all greater than 97%, shows that (supplementary material) composition and engineering of pancreatic enzymes enteric coated capsule of the present invention can be generalized on other pancreatin.
The antiacid stability of table 2 pancreatic enzymes enteric coated granule of the present invention
| pH | 3 | 5 |
| Stability (%) | 99.3 | 98.0 |
the preparation of embodiment 4 compound digestive enzyme capsule (II)
(1) hydroxypropyl methylcellulose is water-soluble, then add 95% alcoholic solution, 2%(W/W is mixed with) ethanol water (ethanol: water (volume ratio)=1:1) of hydroxypropyl methylcellulose.
(2) getting pepsin 50 parts (can purchased from Beijing Saier Bio-Pharmaceutical Co., Ltd.; pharmaceutical grade), sucrose 33 parts and dextrin 17 parts of mix homogeneously are placed on centrifugal granulator (can purchased from Linyi, Shandong ring generation micropill equipment company limited; BZL-300 type) in; according to manufacturers instruction; the ethanol water 30 parts (about having 0.6 part of hydroxypropyl methylcellulose to be adhered in ball core) of the hydroxypropyl methylcellulose of injecting step (1); carry out pelletize; form Pepsin; after oven dry; its particle diameter average out to 0.95mm, for subsequent use.
(3) Pepsin prepared by pancreatic enzymes enteric coated granule embodiment 3 prepared and step (2) incapsulates with the weight ratio of 9.5:1, i.e. obtained compound digestive enzyme capsule (II) of the present invention.
Pepsin in compound digestive enzyme capsule (II) of the present invention is placed in the accelerated test environment of the dummy packages of 40 DEG C, measures the activity of pepsin different times, to analyze the stability that it is preserved.Result is as shown in table 3, and long-term stability of preserving can reach more than 99% all the time, especially preserves activity after month and changes hardly.
The stability of table 3 pepsin of the present invention
| Standing time (moon) | 0 | 1 | 2 | 3 | 6 |
| Active (U/mg) | 9.86 | 9.85 | 9.83 | 9.83 | 9.81 |
| Stability (%) | - | 99.9 | 99.7 | 99.7 | 99.5 |
Sequence table
<110> Zhejiang Zhongyi Pharmaceutical Co., Ltd.
<120> medicine composition-compounddigestive digestive enzyme capsule (II) and preparation method thereof
<130> CN
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<170> PatentIn version 3.5
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Claims (31)
1. compound digestive enzyme capsule, it is made up of capsule shells and the Pepsin be contained in capsule shells and pancreatic enzymes enteric coated granule, and wherein Pepsin is made up of pepsin, sucrose, dextrin and hydroxypropyl methylcellulose; Wherein pancreatic enzymes enteric coated granule is made up of ball core and the coating be wrapped in outside ball core, and wherein ball core is made up of pancreatin, sucrose, dextrin and hydroxypropyl methylcellulose, and coating is made up of polyacrylic resin, triethyl citrate and Pulvis Talci,
Wherein, the weight ratio of Pepsin and pancreatic enzymes enteric coated granule is 0.7-1.2:8-12; In Pepsin, the weight ratio of pepsin, sucrose, dextrin and hydroxypropyl methylcellulose is 40-60:28-38:13-22:0.3-1; In pancreatic enzymes enteric coated granule, the weight ratio of pancreatin, sucrose, dextrin and hydroxypropyl methylcellulose is 23-35:3-12:2-7:0.3-1; In pancreatic enzymes enteric coated granule, polyacrylic resin, triethyl citrate and talcous weight ratio are 23-35:1-5:5-12; In pancreatic enzymes enteric coated granule, the weight ratio of ball core and coating is 2-8:1-3; And the aminoacid sequence of pancreatin is as shown in SEQ ID NO:2.
2. compound digestive enzyme capsule according to claim 1, wherein, the weight ratio of Pepsin and pancreatic enzymes enteric coated granule is 0.9-1.1:9-10.
3. compound digestive enzyme capsule according to claim 2, wherein, the weight ratio of Pepsin and pancreatic enzymes enteric coated granule is 1:9.5.
4. compound digestive enzyme capsule according to claim 1, wherein, in Pepsin, the weight ratio of pepsin, sucrose, dextrin and hydroxypropyl methylcellulose is 45-55:30-36:15-20:0.5-0.7.
5. compound digestive enzyme capsule according to claim 4, wherein, in Pepsin, the weight ratio of pepsin, sucrose, dextrin and hydroxypropyl methylcellulose is 50:33:17:0.6.
6. compound digestive enzyme capsule according to claim 1, wherein, in pancreatic enzymes enteric coated granule, the weight ratio of pancreatin, sucrose, dextrin and hydroxypropyl methylcellulose is 25-30:6-10:3-5:0.5-0.7.
7. compound digestive enzyme capsule according to claim 6, wherein, in pancreatic enzymes enteric coated granule, the weight ratio of pancreatin, sucrose, dextrin and hydroxypropyl methylcellulose is 28:8:4:0.6.
8. compound digestive enzyme capsule according to claim 1, wherein, in pancreatic enzymes enteric coated granule, polyacrylic resin, triethyl citrate and talcous weight ratio are 27-31:2-4:6-9.
9. compound digestive enzyme capsule according to claim 8, wherein, in pancreatic enzymes enteric coated granule, polyacrylic resin, triethyl citrate and talcous weight ratio are 29:3:7.5.
10. compound digestive enzyme capsule according to claim 1, wherein, in pancreatic enzymes enteric coated granule, the weight ratio of ball core and coating is 4-6:1.5-2.5.
11. compound digestive enzyme capsules according to claim 10, wherein, in pancreatic enzymes enteric coated granule, the weight ratio of ball core and coating is 5:2.
The preparation method of 12. compound digestive enzyme capsules according to claim 1, it comprises,
(1) hydroxypropyl methylcellulose is dissolved in the mixed solution of second alcohol and water, is mixed with the ethanol water of hydroxypropyl methylcellulose;
(2) the ethanol water centrifugal granulating of the hydroxypropyl methylcellulose obtained with step (1) after pepsin, sucrose and dextrin mixing is become Pepsin;
(3) the ethanol water centrifugal granulating of the hydroxypropyl methylcellulose obtained with step (1) after pancreatin, sucrose and dextrin mixing is become ball core;
(4) after triethyl citrate being mixed with water, call in polyacrylic acid resin emulsion, then add Pulvis Talci mixing, be mixed with enteric coating liquid;
(5) enteric coating liquid that step (4) obtains is wrapped in outside the ball core that step (3) obtains by boiling seed-coating machine, obtains granule; With
(6) the pancreatic enzymes enteric coated granule that Pepsin step (2) obtained and step (5) obtain incapsulates in shell.
13. preparation method according to claim 12, wherein, in step (1), be mixed with 1.5-3%(W/W) ethanol water of hydroxypropyl methylcellulose.
14. preparation method according to claim 13, wherein, in step (1), be mixed with 2%(W/W) ethanol water of hydroxypropyl methylcellulose.
15. preparation methoies according to claim 12, wherein, in step (2), are a granulated into the Pepsin that particle diameter is 0.9-1mm.
16. preparation methoies according to claim 15, wherein, in step (2), are a granulated into the Pepsin that particle diameter is 0.95mm.
17. preparation method according to claim 12, wherein, in step (3), the ball core that particle diameter is 0.85-0.95mm is a granulated into.
18. preparation method according to claim 17, wherein, in step (3), the ball core that particle diameter is 0.9mm is a granulated into.
19. preparation methoies according to claim 12, wherein, in step (4), wherein the weight ratio of triethyl citrate and water is 2-4:450-550.
20. preparation methoies according to claim 19, wherein, in step (4), wherein the weight ratio of triethyl citrate and water is 3:500.
21. preparation methoies according to claim 12, wherein, in step (4), wherein polyacrylic resin concentration is 27-32%(W/W).
22. preparation methoies according to claim 21, wherein, in step (4), wherein polyacrylic resin concentration is 29%(W/W).
23. preparation methoies according to claim 12, wherein, in step (4), obtain the pancreatic enzymes enteric coated granule that particle diameter is 1-1.2mm.
24. preparation methoies according to claim 23, wherein, in step (4), obtain the pancreatic enzymes enteric coated granule that particle diameter is 1.1mm.
The application of Pepsin in the medicine for the preparation for the treatment of or prevention gastroenteropathy prepared by 25. following preparation methoies, its Chinese medicine is arbitrary described compound digestive enzyme capsule of claim 1-11, and described preparation method comprises,
(1) hydroxypropyl methylcellulose is dissolved in the mixed solution of second alcohol and water, is mixed with the ethanol water of hydroxypropyl methylcellulose; With
(2) the ethanol water centrifugal granulating of the hydroxypropyl methylcellulose obtained with step (1) after pepsin, sucrose and dextrin mixing is become Pepsin.
26. application according to claim 25, wherein, in step (1), be mixed with 1.5-3%(W/W) ethanol water of hydroxypropyl methylcellulose.
27. application according to claim 26, wherein, in step (1), be mixed with 2%(W/W) ethanol water of hydroxypropyl methylcellulose.
28. application according to claim 25, wherein, in step (2), are a granulated into the Pepsin that particle diameter is 0.9-1mm.
29. application according to claim 28, wherein, in step (2), are a granulated into the Pepsin that particle diameter is 0.95mm.
30. application according to claim 25, wherein, medicine is used for the treatment of or prevents dyspepsia.
The application of 31. pancreatin in the medicine for the preparation for the treatment of or prevention gastroenteropathy, wherein the aminoacid sequence of pancreatin is as shown in SEQ ID NO:2, and its Chinese medicine is arbitrary described compound digestive enzyme capsule of claim 1-11.
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| WO2022201056A1 (en) * | 2021-03-23 | 2022-09-29 | Kashiv Biosciences, Llc | An extraction process of pancrelipase and evaluation threof |
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|---|---|---|---|---|
| CN107823174A (en) * | 2017-12-04 | 2018-03-23 | 安徽金太阳生化药业有限公司 | A kind of preparation method of pancreatic enzymes enteric coated capsule |
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| CN101242812A (en) * | 2005-08-15 | 2008-08-13 | 索尔瓦药物有限公司 | Pancreatin micropellets suitable for enteric coating |
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| CN103405756A (en) | 2013-11-27 |
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