CN104530247A

CN104530247A - Preparation method of carboxymethyl starch sodium

Info

Publication number: CN104530247A
Application number: CN201410810885.1A
Authority: CN
Inventors: 尹建; 刘明根
Original assignee: 尹建; 刘明根
Current assignee: Shandong Liaocheng A Hua Pharmaceutical Co., Ltd.
Priority date: 2014-12-22
Filing date: 2014-12-22
Publication date: 2015-04-22
Anticipated expiration: 2034-12-22
Also published as: CN104530247B

Abstract

The invention belongs to the technical field of pharmacy and particularly relates to a preparation method of carboxymethyl starch sodium. The preparation method comprises the following steps: alkalizing starch and sodium hydroxide at 38-42 DEG C in an ethanol solution, and adding alkalization accelerating catalyst epoxy chloropropane in the alkalization process; carrying out etherification by virtue of chloroacetic acid, and adding an etherification accelerating catalyst quaternary ammonium salt in the etherification process. According to the preparation method, comprehensive utilization and 'three wastes' treatment are achieved, namely ethoanol in filtrate can be recycled by virtue of an alcohol recycling tower and can be used for preparing (91%-92%) ethanol and (80%-83%) ethanol; cooling water can be repeatedly used after being cooled; ground materials in a clean region and retentate on a sieve can be used as industrial grade adhesives.

Description

A kind of carboxymethylstach sodium preparation method

Technical field:

The invention belongs to pharmaceutical technology sectors, particularly relate to a kind of carboxymethylstach sodium preparation method.

Background technology:

Carboxymethylstach sodium is one of principal item in modified starch, and outward appearance is white or off-white powder.Disintegrating agent as capsule and tablet is widely used in oral drug preparation.Can be used in the tablet of direct compression or wet granulation.In water, be dispersed into thick colloidal solution, there is good wetting ability, water-absorbent and swelling property, by quick water suction, reach quick and significantly swelling, thus play disintegration.The height of swelling capacity is the important performance index of carboxymethylstach sodium.

The development of current carboxymethylstach sodium is relatively slow, and kind is single, industrial scale is little, target level of product quality is low, performance and result of use and abroad differ greatly, and this situation has had a strong impact on the raising of China's preparation level.Improve the swelling capacity that first pharmaceutical preparation quality must improve carboxymethylstach sodium product.

Existing carboxymethylstach sodium preparation adopts reaction, centrifugal, dry respective independently equipment is produced, and production unit is relatively backward, and labour intensity is large.Production process alkalization, etherification reaction are not thorough, and therefore produced unstable product quality, swelling capacity is the highest only can reach 12mL.The requirement of numerous pharmacy corporation can not be met, had a strong impact on the prestige of product and the confidence of application units.

Goal of the invention:

The invention provides the preparation method of the more excellent carboxymethylstach sodium of a kind of swelling capacity.Improve carboxymethylstach sodium production equipment level, the operation adopt continuously to the operation such as centrifugal, dry, screening, packaging from reaction, closed also is strengthened instrument control and detects, and reduces labour intensity, improves work situation.Production process adds two kinds of catalyzer epoxy chloropropane and quaternary ammonium salt, and make level of response more thorough, swelling capacity increases, and quality improves further.

Technical scheme:

The present invention is achieved by the following technical solutions:

Starch and sodium hydroxide alkalize in ethanolic soln at 38 DEG C-42 DEG C, and alkalinization adds the catalyzer epoxy chloropropane promoting alkalization; Again with Mono Chloro Acetic Acid etherificate, etherification procedure adds the catalyzer quaternary ammonium salt promoting etherificate.

The preparation method of carboxymethylstach sodium provided by the present invention, comprises the following steps:

(1), get the raw materials ready: 1. 33.8 parts of sodium hydroxide are dropped into and fill in the choline still of 25 parts of purified water, add 225 parts of (90-91%) ethanol, fully dissolve for subsequent use;

2. fully dissolved by 90-110 part Mono Chloro Acetic Acid 125 parts of (90-91%) ethanol, suction filtration is for subsequent use;

(2), in glass-lined reactor, add the ethanol 650 parts of 90-91%, hydro-oxidation sodium 40-60 part makes abundant dissolving, drops into starch 550 parts, catalyzer epoxy chloropropane 1000ml, control temperature 38-42 DEG C, alkalizes 1 hour, an every 20 minutes records temperature;

(3), by chloroacetic acid solution, sodium hydroxide solution add glass-lined reactor successively, catalyzer quaternary ammonium salt 800ml, control temperature of reaction 53-56 DEG C, etherificate 6 hours, an every 30 minutes records temperature;

(4) in glass-lined reactor, add the ethanol 700 parts of 80-83%, detect sodium chloride content (≤5.8%), pH value (5.8-7.3), carry out solid-liquid separation after qualified, filtrate is squeezed into recovery tower in time and is carried out recycling;

(5), control temperature 60-70 DEG C drying, dry 3 hours, shut down and proceed to screening packaging process;

(6), after product crosses 120 eye mesh screens, the finished product of carboxymethylstach sodium is.

The present invention is in manufacture method, applicant tests plurality of devices, finally determines reaction, separation, drying integrated equipment, solves reaction, equipment waste and material secondary pollution problem that separation, drying plant cause separately, shorten the time, simplify flow process.In the preparation process in accordance with the present invention, add catalyzer epoxy chloropropane, quaternary ammonium salt makes level of response more abundant, the most high energy of the swelling capacity of product reaches 19mL.

Comprehensive utilization and " three wastes " process: in filtrate, ethanol can utilize alcohol distillation column to reclaim, can in order to preparation (91-92%) ethanol, also can in order to preparation (80-83%) ethanol; Temperature lowering water is by repeating recycling after cooling; Sweep the floor material and the upper retentate of sieve of clean area can be used as technical grade tackiness agent.

The quality standard of carboxymethylstach sodium product of the present invention is as shown in table 1.

Table 1 carboxymethylstach sodium target level of product quality

The raw materials used quality standard of carboxymethylstach sodium product of the present invention is as shown in table 2,3,4,5,6.

Table 2 starch quality standard

interventions Requested	index
		proterties	white powder, odorless, tasteless.All do not dissolve in cold water or ethanol.
potential of hydrogen	4.5-7.5
		weight loss on drying	≤ 14.0%
ash content	≤ 0.2%
		molysite	≤ 0.0015%
sulfurous gas	≤ 0.004%
		oxidizing substance	≤ 0.002%
spot	≤ 30
		whiteness	>=87 °

Table 3 sodium hydroxide quality standard

Interventions Requested	Index
		Proterties	White dried particle, block, rod or the thin slice founded
The clarity of solution and color	Clear, colorless
		Molysite	≤0.002％
Heavy metal	≤0.003％
		Sodium hydrate content	≥96.0％
Carbonate content	≤2.6％

Table 4 quality of chloroacetic acid standard

Interventions Requested	Index
		Proterties	Colourless or light yellow crystal, without impurity such as stains
Molysite	≤0.0015％
		Heavy metal	≤0.0015％
Content	≥96.0％

Table 5 ethanol quality standard

Experiment: product technology performance level compares with similar products at home and abroad

The swelling capacity experiment of product of the present invention proves, this product has reached or has been better than foreign level.Compare experiment through Shandong Taibang Biological Products Co., Ltd. and same kind of products at abroad partial properties, experimental result is as follows: (A-other producers domestic.B-German company, C product of the present invention)

Test 1. swelling capacity experiments

Take carboxymethylstach sodium 1.0 grams, put in the dry colorimetric cylinder of 50ml, rap tube wall, make this product be laid at the bottom of pipe, slowly add distilled water under room temperature to scale along tube wall, leave standstill, measured at 30 minutes the height expanded, repeat 2 times, average, swelling height should be less than 12ml.

Each producer carboxymethylstach sodium swelling capacity, as shown in table 6.

The swelling capacity experimental result of table 6 each producer carboxymethylstach sodium

Producer

A

B

C

Swelling capacity

8±3ml

9±3ml

16±3ml

As can be seen from experimental result: the swelling capacity of this product is more excellent than domestic and international identical product.There is a lot of producer progressively to be used by the like product of my this product of company import as an alternative so domestic.

Application example: carboxymethylstach sodium of the present invention is in the application of pharmaceutical industry

Example 1, abacin: carboxymethylstach sodium 1.5g of the present invention, trimethoprim-sulfamethoxazole 200g, TMP40g, starch 20g, paste producing starch 11.5g, MS0.8%, starch 26g.Well-established law superzapping tablet and get final product.Because the swelling capacity of carboxymethylstach sodium is high, tablet can disintegration in 2min.

Conventional prescription case at present: abacin: the common carboxymethylstach sodium 4g in market, trimethoprim-sulfamethoxazole 200g, TMP40g, starch 20g, paste producing starch 11.5g, MS0.8%, starch 26g.Well-established law superzapping tablet and get final product.Because the swelling capacity of carboxymethylstach sodium is high, tablet can disintegration in 5min.

Disintegration effect can be significantly improved with this patent product, and reduce usage quantity.

Example 2, Furazolidone tablet gets Nifurazolidone 0.1g, starch 0.3g, and 12% starch slurry is appropriate, MS0.0025g, CMS-Na0.005g.The former two mixes, and adds the appropriate mixing granulation of 12% starch slurry, crosses 14 mesh sieves, after 14 mesh sieves after drying, finally adds MS and carboxymethylstach sodium of the present invention, mixes compressing tablet and get final product.Obtained tablet disintegration is excellent.

Embodiment:

Further illustrate technical scheme of the present invention below by specific embodiment, but concrete scheme of the present invention is not limited with embodiment.

Embodiment 1

2. fully dissolved by 90 parts of Mono Chloro Acetic Acids, 125 parts of (90-91%) ethanol, suction filtration is for subsequent use;

(2), in glass-lined reactor, add the ethanol 650 parts of 90-91%, 40 parts, hydro-oxidation sodium makes abundant dissolving, and drop into starch 550 parts, catalyzer epoxy chloropropane 1000ml, control temperature 38-42 DEG C, alkalize 1 hour, within every 20 minutes, records a temperature;

(4), in glass-lined reactor, add the ethanol 700 parts of 80-83%, detect sodium chloride content 4.9%, pH value 6.5, carry out solid-liquid separation after qualified, filtrate is squeezed into recovery tower in time and is carried out recycling;

(6), after product crosses 120 eye mesh screens, the finished product of carboxymethylstach sodium is.Detecting finished product swelling capacity is 15mL

Embodiment 2

2. fully dissolved by 100 parts of Mono Chloro Acetic Acids, 125 parts of (90-91%) ethanol, suction filtration is for subsequent use;

(2), in glass-lined reactor, add the ethanol 650 parts of 90-91%, 50 parts, hydro-oxidation sodium makes abundant dissolving, and drop into starch 550 parts, catalyzer epoxy chloropropane 1000ml, control temperature 38-42 DEG C, alkalize 1 hour, within every 20 minutes, records a temperature;

(4), in glass-lined reactor, add the ethanol 700 parts of 80-83%, detect sodium chloride content 4.6%, pH value 6.4, carry out solid-liquid separation after qualified, filtrate is squeezed into recovery tower in time and is carried out recycling;

(6), after product crosses 120 eye mesh screens, the finished product of carboxymethylstach sodium is.Detecting finished product swelling capacity is 19mL

Embodiment 3

2. fully dissolved by 110 parts of Mono Chloro Acetic Acids, 125 parts of (90-91%) ethanol, suction filtration is for subsequent use;

(2), in glass-lined reactor, add the ethanol 650 parts of 90-91%, 60 parts, hydro-oxidation sodium makes abundant dissolving, and drop into starch 550 parts, catalyzer epoxy chloropropane 1000ml, control temperature 38-42 DEG C, alkalize 1 hour, within every 20 minutes, records a temperature;

(4), in glass-lined reactor, add the ethanol 700 parts of 80-83%, detect sodium chloride content 4.7%, pH value 6.3, carry out solid-liquid separation after qualified, filtrate is squeezed into recovery tower in time and is carried out recycling;

(6), after product crosses 120 eye mesh screens, the finished product of carboxymethylstach sodium is.Detecting finished product swelling capacity is 14mL

Claims

1. a preparation method for carboxymethylstach sodium, comprises the following steps:

(1) get the raw materials ready: 1. 33.8 parts of sodium hydroxide are dropped into and fill in the choline still of 25 parts of purified water, add 225 parts of (90-91%) ethanol, fully dissolve for subsequent use; 2. fully dissolved by 90-110 part Mono Chloro Acetic Acid 125 parts of (90-91%) ethanol, suction filtration is for subsequent use;

(2) in glass-lined reactor, add the ethanol 650 parts of 90-91%, hydro-oxidation sodium 40-60 part makes abundant dissolving, and drop into starch 550 parts, catalyzer epoxy chloropropane 1000ml, control temperature 38-42 DEG C, alkalize 1 hour, an every 20 minutes records temperature;

(3) chloroacetic acid solution, sodium hydroxide solution are added glass-lined reactor successively, catalyzer quaternary ammonium salt 800ml, control temperature of reaction 53-56 DEG C, etherificate 6 hours, an every 30 minutes records temperature;

(5) control temperature 60-70 DEG C of drying, dry 3 hours, shuts down and proceeds to screening packaging process;

2. the preparation method of carboxymethylstach sodium as claimed in claim 1, is characterized in that: comprise the following steps:

(1) get the raw materials ready: 1. 33.8 parts of sodium hydroxide are dropped into and fill in the choline still of 25 parts of purified water, add 225 parts of (90-91%) ethanol, fully dissolve for subsequent use; 2. fully dissolved by 90 parts of Mono Chloro Acetic Acids, 125 parts of (90-91%) ethanol, suction filtration is for subsequent use;

(2) in glass-lined reactor, add the ethanol 650 parts of 90-91%, 40 parts, hydro-oxidation sodium makes abundant dissolving, and drop into starch 550 parts, catalyzer epoxy chloropropane 1000ml, control temperature 38-42 DEG C, alkalize 1 hour, an every 20 minutes records temperature;

(4) in glass-lined reactor, add the ethanol 700 parts of 80-83%, detect sodium chloride content 4.9%, pH value 6.5, carry out solid-liquid separation after qualified, filtrate is squeezed into recovery tower in time and is carried out recycling;

3. the preparation method of carboxymethylstach sodium as claimed in claim 1, is characterized in that: comprise the following steps:

(1) get the raw materials ready: 1. 33.8 parts of sodium hydroxide are dropped into and fill in the choline still of 25 parts of purified water, add 225 parts of (90-91%) ethanol, fully dissolve for subsequent use; 2. fully dissolved by 100 parts of Mono Chloro Acetic Acids, 125 parts of (90-91%) ethanol, suction filtration is for subsequent use;

(2) in glass-lined reactor, add the ethanol 650 parts of 90-91%, 50 parts, hydro-oxidation sodium makes abundant dissolving, and drop into starch 550 parts, catalyzer epoxy chloropropane 1000ml, control temperature 38-42 DEG C, alkalize 1 hour, an every 20 minutes records temperature;

(4) in glass-lined reactor, add the ethanol 700 parts of 80-83%, detect sodium chloride content 4.6%, pH value 6.4, carry out solid-liquid separation after qualified, filtrate is squeezed into recovery tower in time and is carried out recycling;

4. the preparation method of carboxymethylstach sodium as claimed in claim 1, is characterized in that: comprise the following steps:

(1) get the raw materials ready: 1. 33.8 parts of sodium hydroxide are dropped into and fill in the choline still of 25 parts of purified water, add 225 parts of (90-91%) ethanol, fully dissolve for subsequent use;

(2) in glass-lined reactor, add the ethanol 650 parts of 90-91%, 60 parts, hydro-oxidation sodium makes abundant dissolving, and drop into starch 550 parts, catalyzer epoxy chloropropane 1000ml, control temperature 38-42 DEG C, alkalize 1 hour, an every 20 minutes records temperature;

(4) in glass-lined reactor, add the ethanol 700 parts of 80-83%, detect sodium chloride content 4.7%, pH value 6.3, carry out solid-liquid separation after qualified, filtrate is squeezed into recovery tower in time and is carried out recycling;