CN101108251B - Preparation of medicinal disintegrating agent with biological enzymatic isolation method - Google Patents
Preparation of medicinal disintegrating agent with biological enzymatic isolation method Download PDFInfo
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- CN101108251B CN101108251B CN2006100170506A CN200610017050A CN101108251B CN 101108251 B CN101108251 B CN 101108251B CN 2006100170506 A CN2006100170506 A CN 2006100170506A CN 200610017050 A CN200610017050 A CN 200610017050A CN 101108251 B CN101108251 B CN 101108251B
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Abstract
The invention discloses a medical additives added into a medicine, in particular to a method to produce medicinal disintegration by biological enzymic method. The main technique is that: taking corn starch as the main material and ethanol as the dispersing agent. Making use of the selectivity of the biological enzyme Alpha-amylase to make the starch interrupt the chain structure under the effect of the biological active enzyme. By means of a plurality of compound degeneration ways such as alkalization, crosslinking and etherification, the starch is made into a new network structure and strong suction group. The invention has the advantages of the excellent efficacy, high absorbent, quick disintegration and controllable release, and can be widely used as releasing medicinal disintegration in tablets, capsules, controlled-release agent and granules.
Description
Technical field
The present invention relates to a kind of adjuvant that adds in medicine, more particularly, it can play and make the medicine solid preparation, has the method for a kind of preparation of medicinal disintegrating agent with biological enzymatic isolation method of quick disintegrate and slow control slow releasing function.
Background technology
The method of preparation of medicinal disintegrating agent with biological enzymatic isolation method is the external slow-releasing medicated disintegrating agent of developing in recent years of efficient, powerful, slow control.Because this disintegrating agent has the premium properties of powerful suction, quick disintegrate and controllable sustained-release, in preparations such as tablet, capsule, slow control releasing agent and granule, obtain to use widely, become excipient substance important in the domestic and international solid pharmaceutical preparation.The present invention is primary raw material with the corn starch, adopts bio-enzyme degradation complex denaturation technology to produce, and is a fundamental change to conventional production methods.
Pharmaceutical preparation is the final products of being made by principal agent, disintegrating agent and other adjuvant.Disintegrating agent is indispensable important component in preparation, and quality, the performance of disintegrating agent play crucial effects to drug quality, and the development of disintegrating agent is the basis of novel formulation and novel form development especially.
Oral Pharmaceutical dosage forms is more, as the pill in tablet, granule, capsule and the Chinese patent medicine, powder etc., its effective ingredient, curative effect takes place in human body, after will passing through digestive organs absorptions such as stomach, intestinal, again through the blood loop distribution at each position of body, want to make effective ingredient to be absorbed in the scientific and reasonable body, must scientifically use disintegrating agent.
At home, be subjected to the restriction of aspects such as economic condition, technical merit and product variety, the Application and Development of disintegrating agent is just at the early-stage.Not seeing as yet with the corn starch is raw material, adopts the disintegrating agent of the powerful suction of having of biologic enzymolysis method production, quick disintegrate and controllable sustained-release premium properties.Therefore, traditional disintegrating agent product is still being used in the pharmaceutical factory that has, and disintegrating property is poor, influences curative effect of medication and normally brings into play.In order to improve the class of medicine, domestic each pharmacy group uses the import disintegrating agent, and cost is significantly risen, and it is in line with international standards to have restricted China's pharmaceutical industry to a certain extent.Be the present situation of the long-term dependence on import of alleviation high-quality disintegrating agent, biologic enzymolysis method disintegrating agent product of the present invention, the demand that solves pharmaceutical industry is very important.
Summary of the invention
The objective of the invention is to overcome the deficiency that existing disintegrating agent exists in solid drugs is used, providing a kind of is primary raw material with the corn starch, adopt bio-enzyme degradation complex denaturation route, production has efficiently, powerful suction, the disintegrating agent of disintegrate and controllable sustained-release premium properties fast, and obtains extensive uses at tablet, capsule, slow control releasing agent and granule etc.
Purpose of the present invention is achieved by following technical proposals.
Major technique of the present invention is with the corn starch to be primary raw material, ethanol is made dispersant, is utilized enzyme, the selectivity of α-Dian Fenmei, make starch under the effect of bioactive enzyme, chain structure is interrupted, by complex denaturation means such as alkalization, crosslinked, etherificates, make starch form new network structure and strong suction group.
Beneficial effect of the present invention is that enzymatic degradation complex denaturation technology path falls in the employing biology, and biotechnology is combined with starch chemical modification technology, and is different with traditional single modified production process.
(1) utilizes the selectivity of enzyme, make starch under the effect of enzyme, chain structure is disconnected, form uniform micromolecule granule, increase reaction uniformity and activity;
(2) adopt complex denaturation technology, make several single reaction of degeneration in same medium, by control, simultaneously or carry out in succession, and mutual restriction not generates medicinal disintegrating agent, and its structure is the build network structure;
(3) multiple reaction of degeneration has the multi-point sensing device, carries out in the same set of device that multiple spot shows.
The present invention:
(1) (bio-enzyme degradation complex denaturation technology) adopts biotechnology on technology, utilizes the selectivity of enzyme, and the chain structure evenly disconnection under the effect of bioactive enzyme with starch by the complex denaturation to starch, forms new build network structure again.Improve the bioavailability of solid medicine, must make medicine disintegrate absorption rapidly at short notice, and in blood, reach certain concentration.Have only to form cancellated disintegrating agent, just can reach this purpose, and the disintegrating agent that traditional single denatured technology is produced, can't satisfy the demand of pharmaceutical industry at all;
(2) in theory, produce the disintegrating agent of function admirable, satisfy two conditions, the one, the macromolecule of straight chain type or branched chain type is by after degrading, and complex denaturation forms the build network structure; The 2nd, have the hydrophilic group of some on the network.Medicinal disintegrating agent of the present invention is at above condition, and single linear chain structure by the bio-enzyme degradation complex denaturation, is formed the build network structure and introduces hydrophilic sodium carboxymethyl (CH simultaneously
2COONa), carboxyl (COOH) group, reach quick disintegrate and slow control slow releasing function.
(3) structurally, the medicinal disintegrating agent of single degeneration is the line style chain structure,, water sorption is limited, does not possess slow control slow releasing function.And there is the build network structure in the medicinal disintegrating agent that adopts bio-enzyme degradation complex denaturation technical matters to produce, and a large amount of electric charge hydrophilic radicals that have are arranged, and not only has the super-strong moisture absorbing characteristic, also can reach slow control slow releasing function by the control rate of water absorption.
Description of drawings
Fig. 1 is a process chart of the present invention;
Fig. 2 is the disintegrating agent structural representation;
Fig. 3 tradition disintegrating agent structural representation.
The specific embodiment
Below in conjunction with the accompanying drawing and the specific embodiment the present invention is described in further detail.
In conjunction with Fig. 1 process chart technology of the present invention is illustrated.
Enzyme digestion reaction:
In rustless steel enzymolysis still, at first add 100 parts of (weight) starch, be made into 40% starch milk, open and stir, add 5-10 part (weight) α-Dian Fenmei, be warming up to 40-50 ℃, reacted centrifugal dewatering, discharging 5-20 minute.
The etherifying agent preparation:
In rustless steel preparation still, at first add 50-100 part (weight) ethanol, chuck feeds cooling water, opens and stirs, and adds 20-40 part (weight) monoxone, drips 40-80 part (weight) 25% sodium hydroxide solution, and temperature is controlled between 20-30 ℃.
Alkalization, crosslinked, etherificate:
In rustless steel etherificate still, add 200-260 part ethanol, open and stir, add above-mentioned starch behind enzyme digestion reaction, drip 40-80 part (weight) 25% sodium hydroxide solution, 0.2-1 part (weight) cross-linking agent, (cross-linking agent is: in sodium trimetaphosphate, epoxychloropropane and the phosphorus oxychloride a kind of); After alkalizing crosslinked 1 hour in the time of 40 ℃, divide to drip etherifying agent every 20 minutes three times and carry out etherificate, chuck feeds hot water heating, and the material temperature maintains between 48-55 ℃, is incubated 10 hours, reduces to the room temperature discharging.
Neutralization;
With in the dilute hydrochloric acid and excess base.
Washing:
Add the ethanol of 80% concentration in stainless steel cauldron, stir and take off liquid after 30 minutes, the material that washing is good takes off liquid with the explosion-proof centrifugal machine.
Dry:
Material after centrifugal is delivered to the vacuum desiccator drying, material moisture to 13%, dry discharging.
Pulverize:
The material that drying is good is pulverized and is reached 80 orders, and finished product is through packing after the assay was approved.
Embodiment 1:
In rustless steel enzymolysis still, add 100Kg starch, be made into 40% starch milk, open and stir, add α-Dian Fenmei 5Kg, be warming up to 50 ℃, reacted 5 minutes, and behind the centrifugal dewatering, added again in the rustless steel etherificate still, add 250Kg ethanol, 0.25Kg sodium trimetaphosphate drips 25% sodium hydroxide solution 52Kg, 40 ℃ of alkalization, crosslinked 1 hour, whenever the 20 minutes branches of being separated by drip for three times etherifying agent (by, 50Kg ethanol, the 30Kg monoxone, 25% sodium hydroxide solution 52Kg is formulated) carry out etherificate, chuck feeds hot water heating, the material temperature maintains 50 ℃, is incubated after 10 hours, reduces to room temperature, neutralization, washing, drying, pulverize finished product.
Embodiment 2:
With the preparation method of producing 1 ton of superpower disintegrating agent is example, in rustless steel enzymolysis still, add 1000Kg starch and be made into 40% starch milk, open and stir, add the 50Kg α-Dian Fenmei, be warming up to 50 ℃, reacted 5 minutes, behind the centrifugal dewatering, add again in the rustless steel etherificate still, add 2500Kg ethanol, the 2.5Kg sodium trimetaphosphate, 520 kilograms of 25% sodium hydroxide solutions are 40 ℃ of alkalization, crosslinked 1 hour, the 20 minutes branches of at every turn being separated by drip etherifying agent (500 kilograms of ethanol, 300 kilograms of monoxones, 520 kilograms of 25% sodium hydroxide solutions) for three times and carry out etherificate, chuck feeds hot water heating, the material temperature maintains 50 ℃, is incubated after 10 hours, reduces to room temperature, neutralization, washing, drying, pulverize finished product.
Fig. 2 is the disintegrating agent structural representation, with Fig. 3 tradition disintegrating agent structural representation be different, single linear chain structure forms the build network structure and introduces hydrophilic sodium carboxymethyl (CH simultaneously by the bio-enzyme degradation complex denaturation
2COONa) reach quick disintegrate and slow control slow releasing function.Structurally, the medicinal disintegrating agent of the single degeneration of Fig. 2 is the line style chain structure, and water sorption is limited, and rate of water absorption can not be controlled, and can not form stable structure.And not only there is the build network structure in the medicinal superpower disintegrating agent that adopts bio-enzyme degradation complex denaturation technical matters to produce, has the hydrophilic radical of electric charge in addition, has super-strong moisture absorbing, can reach slow controlled release and put by the control rate of water absorption.
Claims (3)
1. the method for a preparation of medicinal disintegrating agent with biological enzymatic isolation method, adopt bio-enzyme degradation complex denaturation technology, it is characterized in that with the corn starch being primary raw material, ethanol is made dispersant, utilize the selectivity of α-Dian Fenmei, make starch under the effect of bioactive enzyme, chain structure is interrupted, form even micromolecule group, again by alkalization, crosslinked, etherificate, make starch form new network structure and strong suction group, form medicinal disintegrating agent with the powerful disintegrate of quick suction and controllable sustained-release premium properties;
Concrete processing step is as follows:
A, enzymolysis: in 40% starch milk, add α-Dian Fenmei, be warming up to 40-55 ℃, reacted 5-10 minute;
B, alkalization, crosslinked: add 25%NaOH solution in the starch behind enzymolysis, 95% alcohol mixed solution, epoxychloropropane, in the time of 40 ℃, alkalization, crosslinked 1 hour;
C, etherificate: with the NaOH solution preparation etherifying agent of 50-100 parts by weight of ethanol, 20-40 weight portion monoxone and 40-80 weight portion 25%, described etherifying agent is divided three times, be separated by added in above-mentioned alkalization, the solution after crosslinked at every turn in 20 minutes, 50 ℃ of reactions 10 hours.
2. a kind of method for preparing medicinal disintegrating agent according to claim 1 is characterized in that parts by weight of raw materials consists of:
The starch consumption is: 100 parts;
α-Dian Fenmei: 5-10 part;
Cross-linking agent: consumption is 0.2-1 part;
Ethanol: consumption is 150-250 part.
3. the method for a kind of preparation of medicinal disintegrating agent with biological enzymatic isolation method as claimed in claim 1 or 2 is characterized in that also having following processing step:
D, neutralization: in etherificate gained solution, add in the dilute hydrochloric acid and remaining alkali;
E, washing: after neutralization, add 80% ethanol in the solution, stirred 30 minutes;
F, centrifugal: will wash good material and be placed on and take off liquid on the explosion-proof centrifugal machine;
G, drying: the material after centrifugal is delivered to vacuum desiccator drying, material moisture to 13%, discharging;
H, pulverizing: the material that drying is good is pulverized and is reached 80 orders;
I, packing: the finished product after the pulverizing is through packing after the assay was approved.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2006100170506A CN101108251B (en) | 2006-07-20 | 2006-07-20 | Preparation of medicinal disintegrating agent with biological enzymatic isolation method |
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| CN2006100170506A CN101108251B (en) | 2006-07-20 | 2006-07-20 | Preparation of medicinal disintegrating agent with biological enzymatic isolation method |
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| CN101108251A CN101108251A (en) | 2008-01-23 |
| CN101108251B true CN101108251B (en) | 2011-03-30 |
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| CN103554279B (en) * | 2013-10-24 | 2016-07-27 | 李国桐 | The composite modified starch of alternative gelatin and application |
| CN107595797A (en) * | 2017-09-25 | 2018-01-19 | 四川摩尔生物制药有限公司 | A kind of Nifuratel tablet and preparation method thereof |
| CN113121709B (en) * | 2019-12-30 | 2022-08-26 | 仙乐健康科技股份有限公司 | Preparation method and application of modified starch |
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