CN101439183A - Method for preparing medicament adjuvant from starch - Google Patents
Method for preparing medicament adjuvant from starch Download PDFInfo
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- CN101439183A CN101439183A CNA2008102201828A CN200810220182A CN101439183A CN 101439183 A CN101439183 A CN 101439183A CN A2008102201828 A CNA2008102201828 A CN A2008102201828A CN 200810220182 A CN200810220182 A CN 200810220182A CN 101439183 A CN101439183 A CN 101439183A
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Abstract
The invention discloses a method for preparing a pharmaceutical excipient by using starch. The method comprises the following steps: pullulanase or isoamylase and alpha-amylase are added into starch milk for reaction for a period of time, enzymes is inactivated, the pH value is regulated, and a product is prepared by standing, condensation, deposition, filtration, drying and smashing. The method takes the starch as raw material, adopts the biological technology and the physical treatment means to greatly improve the content of amylase molecular crystals of the starch and proposes a new pharmaceutical excipient preparation process, and the production process has no waste liquid or pollution. The prepared crystallized amylase can fully or partly substitute microcrystalline cellulose to be applied in the dry preparation of tablets as a filler or a binder.
Description
Technical field
The present invention relates to a kind of method of producing pharmaceutic adjuvant and food additive, be specifically related to a kind of method for preparing excipient substance with starch.
Background technology
The straight chain crystal starch is to rearrange a kind of enzyme process modified starch product with certain crystalline texture that forms at low temperatures by the short-chain amylose molecule.Because of it has good filling property, cohesive, flowability and self-lubricity, and disintegrating property preferably being arranged, can be used for particularly direct powder compression of medicaments preparation, serve as filler and binding agent, is a kind of quite promising multi-functional pharmaceutic adjuvant.
Adjuvant commonly used in the medicinal tablets comprises microcrystalline Cellulose, cane sugar powder, calcium salt, lactose and glucose etc., and wherein microcrystalline Cellulose is first-selected adjuvant, can serve as filler, binding agent and disintegrating agent.But microcrystalline Cellulose price comparison costliness, other adjuvants such as calcium hydrogen phosphate, sucrose, lactose (anhydrous or hydras) all have its weak point.Calcium salt is to many medicaments insensitives, the medicine stability susceptible to, and itself do not have a disintegrating property; Cane sugar powder has hygroscopicity, and tablet can the hardening with the passing of period of storage; Lactose can with various amine drug generation browning reactions, particularly under the influence of alkaline lubricant can the aggravation, in addition, it costs an arm and a leg; Though it is sweet that mannitol and sorbitol are distinguished the flavor of, the former is mobile poor, the easy moisture absorption of the latter, and the two price is all expensive.
Microcrystalline Cellulose is cellulose partial hydrolysis and the less crystallinity cellulose of the degree of polymerization that makes, product is the useful as drug excipient on medical industry, it is one of the best pharmaceutic adjuvant, external commodity Avicel by name, according to the particle diameter difference some specifications are arranged, homemade microcrystalline Cellulose also is used widely at home, but quality haves much room for improvement and improve, and product category also remains to be enriched.Microcrystalline Cellulose has good compressibility and stronger adhesion, and the tablet hardness that is pressed into is bigger, and " dry adhesives " that can be used as direct powder compression uses.Owing to cost an arm and a leg (imported product price per ton is above 40,000 yuan), its consumption is restricted always.If can adopt straight chain crystal starch cheap, function admirable to substitute microcrystalline Cellulose, can reduce the production cost of medicament undoubtedly greatly.Therefore, purpose of the present invention is exactly the preparation method and the functional character of a kind of new type medicinal stuff of research straight chain crystal starch, and substitutes expensive microcrystalline Cellulose with it, is applied in the tablet product.This method utilizes Renewable resource starch to be raw material, produces the straight chain crystal starch, and is applied in excipient substance and the tablet product, can partly or entirely substitute expensive microcrystalline Cellulose.To the research of straight chain crystal starch, can not only enrich the research intension of starch science and excipient substance chemistry, and a kind of raw material of industry of cheapness can be provided for industries such as medicine, have important academic significance and industrial application value.
Summary of the invention
The objective of the invention is to overcome the shortcoming of existing cellulose family pharmaceutic adjuvant price comparison costliness, provide a kind of and prepare the method for excipient substance with starch, this method relative low price, performance are good equally.With starch is raw material, adopt α-amylase and pullulanase or isoamylase to prepare the straight chain crystal starch, the product property that makes is good, can partly or entirely substitute expensive microcrystalline Cellulose, with reducing the production cost of tablet medicine greatly, increase economic efficiency.The present invention simultaneously adopts process for cleanly preparing, realizes the organic wastewater zero-emission, environment is not had any harmful effect.
Principle of the present invention: the present invention is a raw material with representational starch (comprising high chain corn starch, conventional corn starch, waxy corn starch, tapioca, potato starch, bean starch, rice starch, waxiness rice starch, sorghum starch and sago starch etc.), adopt α-amylase liquefaction under certain condition, take off branching with blue enzyme in Shandong or isoamylase, the excision of branched chain molecule in the starch is many straight chain molecules, make the starch molecule amount be distributed in certain limit, these molecules obtain the straight chain crystal starch through rearrangement, crystallization under the low temperature.Measure the degree of crystallinity of straight chain crystal starch with the X-ray diffraction analytical technology.Concrete grammar is that starch is scattered in the water, and its solids content is 5～40%, adds α-amylase liquefaction 10～20min under-fixed condition, with temperature, the pH regulator best enzyme activity condition to pullulanase or isoamylase.Vigor, substrate and concentration of substrate etc. according to the source of enzyme, type, enzyme decide these parameter conditions.An enzyme denaturing immediately after taking off adopts and is heated to 80～90 ℃, keeps 20min, makes enzyme deactivation, adds a certain amount of NaOH, in and pH value to 6.5～7.0, under 4 ℃, leave standstill retrogradation 24h, filter, dry, pulverize and obtain product.
Purpose of the present invention is achieved through the following technical solutions:
A kind ofly prepare the method for excipient substance, it is characterized in that comprising the steps: with starch
(1) starch is scattered in the water, is made into the starch milk of 5～40% quality, heating starch milk to 90～95 ℃ add resistant to elevated temperatures α-amylase under this temperature, and consumption is 10～25 unit of activity/g dried starch, liquefaction 10～20min;
(2) add acetic acid-sodium-acetate buffer, regulator solution pH adds blue enzyme in general Shandong or isoamylase to acid down at 40～70 ℃, and consumption is 1～12 unit of activity/g dried starch, insulation 1～24h;
(3) heating steps (2) gained solution to 80 ℃～90 ℃, and keep 20min to carry out enzyme denaturing;
(4) add NaOH solution, regulate pH value to 6.5～7.0, under 4 ℃, leave standstill retrogradation 24～48h;
(5) after filtration, dry, pulverizing promptly obtains product of the present invention.
Described starch comprises one or more in high chain corn starch, conventional corn starch, waxy corn starch, tapioca, potato starch, bean starch, rice starch, waxiness rice starch, sorghum starch and the sago starch.
The pH value of the described acetic acid-sodium-acetate buffer of step (2) is 3.6～6.0, the pH to 3.5 of regulator solution～6.5.
The described filtration of step (5) is to adopt the hydrocone type centrifuge, and rotating speed is 3000rpm; Centrifugation time is 30min.
The described drying of step (5) is to adopt hot air drying, spray drying or lyophilization; Wherein the hot air drying temperature is 105 ℃; The import of spray drying temperature is 185 ℃, and outlet temperature is 85 ℃; The lyophilization temperature is-40 ℃.
The described NaOH solution of step (4) is 5%～10% quality.
The described drying of step (4) is to adopt hot air drying, spray drying or lyophilization; Wherein the hot air drying temperature is at 105 ℃; The import of spray drying temperature is 185 ℃, and outlet temperature is 85 ℃; The lyophilization temperature is-40 ℃.
The product of the present invention preparation, technical specification is as follows: product is free from extraneous odour, do not have the white powder of husky tooth, no-sundries.Straight chain crystal starch DE (dextrose equivalent value) value 5.0～7.0, degree of crystallinity 40～65%.
The present invention compared with prior art has the following advantages and beneficial effect:
(1) the present invention uses starch and the blue enzyme of Pu Lu or isoamylase to prepare the newtype drug adjuvant and substitutes microcrystalline Cellulose, is domestic and international initiative.
(2) functional character of product is easy to control.
(3) production efficiency height, the yield height, cost is low.
(4) use of the technology of the present invention has realized serialization production, and operation is simplified, and is easy to automatic control.
The specific embodiment
For better understanding the present invention, the present invention is done into-goes on foot detailed description below in conjunction with embodiment.Enumerate specific embodiment below, but the scope of protection of present invention is not limited to the scope of embodiment.
Embodiment 1:
(1) be raw material with high chain corn starch, being made into concentration is 5% quality starch milk, is heated to 95 ℃, adds α-amylase under this temperature, and consumption is 20 unit of activity/g dried starch, liquefaction 20min;
(2) CH of adding pH=3.6
3COOH-CH
3COONa buffer regulator solution is regulated pH to 5.5, adds pullulanase down at 40 ℃, and consumption is 6 unit of activity/g dried starch, keeps 8h;
(3) heating steps (2) gained solution to 80 ℃, and keep 20min to carry out enzyme denaturing;
(4) NaOH of adding 8% quality regulates pH value to 6.5, leaves standstill retrogradation 24h under 4 ℃;
(5) filter through the hydrocone type centrifuge, rotating speed is 3000rpm; Centrifugal 30min will leach thing and adopt the hot air drying temperature to obtain product in 105 ℃ of dry 2h, pulverizing.
The degree of crystallinity of measuring the straight chain crystal starch with the X-ray diffraction analytical technology is 64.80%.
Embodiment 2:
(1) mixture with waxy corn starch and tapioca is a raw material, is made into concentration and is 25% starch milk, is heated to 90 ℃, adds α-amylase liquefaction, and consumption is 10 unit of activity/g dried starch, liquefaction 10min;
(2) CH of adding pH=6.0
3COOH-CH
3COONa buffer regulator solution is regulated pH to 6.5, adds isoamylase down at 55 ℃, and consumption is 12 unit of activity/g dried starch, keeps 1h;
(3) heating steps (2) gained solution to 90 ℃, and keep 20min to carry out enzyme denaturing;
(4) NaOH of adding 5% quality regulates pH value to 7.0, leaves standstill retrogradation 30h under 4 ℃;
(5) filter through the hydrocone type centrifuge, rotating speed is 3000rpm; Behind the centrifugal 30min, will leach thing and adopt spray drying 2h, inlet temperature is 185 ℃, and outlet temperature is 85 ℃, pulverizes, and obtains degree of crystallinity and be 55% straight chain crystal starch product.
Embodiment 3:
(1) is raw material with waxiness rice starch, sorghum starch and three kinds of mixture of sago starch, is made in the starch milk that concentration is 40% quality and is heated to 95 ℃ that add α-amylase under this temperature, consumption is 15 unit of activity/g dried starch, liquefaction 15min;
(2) CH of adding pH=4.5
3COOH-CH
3COONa buffer regulator solution is regulated pH to 5.5, adds pullulanase down at 70 ℃, and consumption is 4 unit of activity/g dried starch, keeps 24h;
(3) heating steps (2) gained solution to 85 ℃, and keep 20min to carry out enzyme denaturing;
(4) NaOH of adding 10% quality regulates pH value to 6.5, leaves standstill retrogradation 48h under 4 ℃;
(5) filter through the hydrocone type centrifuge, rotating speed is 3000rpm; Centrifugal 30min will leach thing and adopt lyophilization 2h, and temperature is-40 ℃, pulverizes to obtain product.
The degree of crystallinity of measuring the straight chain crystal starch with the X-ray diffraction analytical technology is 43.77%.
Embodiment 4:
Each set of dispense than (weight ratio) as following table:
(1) it is standby that saccharin sodium is crossed 80 mesh sieves;
(2) aspirin, microcrystalline Cellulose, lactose and mannitol are pressed last table proportioning mix homogeneously, cross 60 mesh sieves and obtain siftage;
(3) add saccharin sodium in proportion in siftage, in addition mixing is crossed 60 mesh sieves;
(4) mixture direct compression on tablet machine, adjustment sheet is every 500mg heavily approximately, and it is 50～80N that adjusting pressure makes slice, thin piece hardness;
By " 2005 editions regulations of Chinese pharmacopoeia are tested to making tablet, and the result is:
Embodiment 5:
Each set of dispense than (weight ratio) as following table:
(1) it is standby that saccharin sodium is crossed 80 mesh sieves;
(2) aspirin, microcrystalline Cellulose, straight chain crystal starch, lactose and mannitol are pressed last table proportioning mix homogeneously, cross 60 mesh sieves and obtain siftage;
(3) add saccharin sodium in proportion in siftage, in addition mixing is crossed 60 mesh sieves;
(4) mixture direct compression on tablet machine, adjustment sheet is every 500mg heavily approximately, and it is 50～80N that adjusting pressure makes slice, thin piece hardness;
By " 2005 editions regulations of Chinese pharmacopoeia are tested to making tablet, and the result is:
Embodiment 6:
Each set of dispense than (weight ratio) as following table:
(1) it is standby that saccharin sodium is crossed 80 mesh sieves;
(2) aspirin, microcrystalline Cellulose, straight chain crystal starch, lactose and mannitol are pressed last table proportioning mix homogeneously, cross 60 mesh sieves and obtain siftage;
(3) add saccharin sodium in proportion in siftage, in addition mixing is crossed 60 mesh sieves;
(4) mixture direct compression on tablet machine, adjustment sheet is every 500mg heavily approximately, and it is 50～80N that adjusting pressure makes slice, thin piece hardness;
By " 2005 editions regulations of Chinese pharmacopoeia are tested to making tablet, and the result is:
Embodiment 7:
Each set of dispense than (weight ratio) as following table:
(1) it is standby that saccharin sodium is crossed 80 mesh sieves;
(2) aspirin, microcrystalline Cellulose, straight chain crystal starch, lactose and mannitol are pressed last table proportioning mix homogeneously, cross 60 mesh sieves and obtain siftage;
(3) add saccharin sodium in proportion in siftage, in addition mixing is crossed 60 mesh sieves;
(4) mixture direct compression on tablet machine, adjustment sheet is every 500mg heavily approximately, and it is 50～80N that adjusting pressure makes slice, thin piece hardness;
By " 2005 editions regulations of Chinese pharmacopoeia are tested to making tablet, and the result is:
Illustrate: the straight chain crystal starch degree of crystallinity that is adopted is 55%
Embodiment 4～7 shows: the tablet that makes, its tablet weight variation, hardness, friability and dissolution all meet the requirements, and illustrate that the straight chain crystal starch can be applied to direct compression by all or part of alternative microcrystalline Cellulose, serves as filler and binding agent.
Claims (6)
1, a kind ofly prepares the method for excipient substance, it is characterized in that comprising the steps: with starch
(1) starch is scattered in the water, is made into the starch milk of 5～40% quality, heating starch milk to 90～95 ℃ add resistant to elevated temperatures α-amylase under this temperature, and consumption is 10～25 unit of activity/g dried starch, liquefaction 10～20min;
(2) add acetic acid-sodium-acetate buffer and come the pH of regulating step (1) gained solution extremely acid, add blue enzyme in general Shandong or isoamylase down at 40～70 ℃, consumption is 1～12 unit of activity/g dried starch, is incubated 1～24h;
(3) heating steps (2) gained solution to 80 ℃～90 ℃, and keep 20min to carry out enzyme denaturing;
(4) add NaOH solution, regulate pH value to 6.5～7.0, under 4 ℃, leave standstill retrogradation 24～48h;
(5) after filtration, dry, pulverizing promptly obtains product of the present invention.
2, method according to claim 1 is characterized in that described starch comprises one or more in high chain corn starch, conventional corn starch, waxy corn starch, tapioca, potato starch, bean starch, rice starch, waxiness rice starch, sorghum starch or the sago starch.
3, method according to claim 2 is characterized in that the pH value of the described acetic acid-sodium-acetate buffer of step (2) is 3.6～6.0, pH to 3.5～6.5 of the solution of regulating step (1).
4, method according to claim 3 is characterized in that the described filtration of step (5) is to adopt the hydrocone type centrifuge, and rotating speed is 3000rpm; Centrifugation time is 30min.
5, method according to claim 4 is characterized in that the described drying of step (5) is to adopt hot air drying, spray drying or lyophilization; Wherein the hot air drying temperature is 105 ℃; The import of spray drying temperature is 185 ℃, and outlet temperature is 85 ℃; The lyophilization temperature is-40 ℃.
6, method according to claim 5 is characterized in that the described NaOH solution of step (4) is 5%～10% quality.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2008102201828A CN101439183B (en) | 2008-12-19 | 2008-12-19 | Method for preparing medicament adjuvant from starch |
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| CN2008102201828A CN101439183B (en) | 2008-12-19 | 2008-12-19 | Method for preparing medicament adjuvant from starch |
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| CN101439183A true CN101439183A (en) | 2009-05-27 |
| CN101439183B CN101439183B (en) | 2010-12-29 |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101712723B (en) * | 2009-10-30 | 2011-07-06 | 华南理工大学 | Method for processing and preparing resistant starch by Pullulanase cooperated with acid alcohol |
| CN102050880B (en) * | 2009-10-29 | 2012-11-14 | 黄雅典 | Method for preparing soluble starch |
| CN104263782A (en) * | 2014-08-19 | 2015-01-07 | 华南理工大学 | Drug excipient and preparation method thereof |
| CN104666832A (en) * | 2015-03-20 | 2015-06-03 | 广州一品红制药有限公司 | Traditional Chinese medicinal granule for treating cold and repeated cold, and preparation method for traditional Chinese medicinal granule |
| CN106397616A (en) * | 2016-08-30 | 2017-02-15 | 华南理工大学 | Preparation method of icodextrin for starch-based peritoneal dialysis solution |
| CN114306256A (en) * | 2022-01-13 | 2022-04-12 | 山东新时代药业有限公司 | Isosorbide mononitrate tablet and preparation process thereof |
-
2008
- 2008-12-19 CN CN2008102201828A patent/CN101439183B/en not_active Expired - Fee Related
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102050880B (en) * | 2009-10-29 | 2012-11-14 | 黄雅典 | Method for preparing soluble starch |
| CN101712723B (en) * | 2009-10-30 | 2011-07-06 | 华南理工大学 | Method for processing and preparing resistant starch by Pullulanase cooperated with acid alcohol |
| CN104263782A (en) * | 2014-08-19 | 2015-01-07 | 华南理工大学 | Drug excipient and preparation method thereof |
| CN104263782B (en) * | 2014-08-19 | 2017-04-05 | 华南理工大学 | A kind of drug excipient and preparation method thereof |
| CN104666832A (en) * | 2015-03-20 | 2015-06-03 | 广州一品红制药有限公司 | Traditional Chinese medicinal granule for treating cold and repeated cold, and preparation method for traditional Chinese medicinal granule |
| CN106397616A (en) * | 2016-08-30 | 2017-02-15 | 华南理工大学 | Preparation method of icodextrin for starch-based peritoneal dialysis solution |
| CN114306256A (en) * | 2022-01-13 | 2022-04-12 | 山东新时代药业有限公司 | Isosorbide mononitrate tablet and preparation process thereof |
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| CN101439183B (en) | 2010-12-29 |
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Granted publication date: 20101229 Termination date: 20131219 |