CN104610461A - Preparation method of carboxylmethyl-CHTAC (3-chloro-2-hydroxypropyl trimethyl ammonium chloride) quaternary ammonium bagasse xylan used for drug carrier - Google Patents

Abstract

The invention discloses a preparation method of carboxylmethyl-CHTAC (3-chloro-2-hydroxypropyl trimethyl ammonium chloride) quaternary ammonium bagasse xylan used for a drug carrier. The amphiprotic carboxylmethyl-CHTAC quaternary ammonium bagasse xylan used for the drug carrier is prepared through a catalytic carboxymethylation and cationization binary denaturation technological method by taking bagasse xylan as a starting raw material, taking water and 95% alcohol as a mixed solvent, taking sodium hydroxide as an etherification activator and taking monochloroacetic acid and 3-chloro-2-hydroxypropyl trimethyl ammonium chloride (CHTAC for short) as an amphiprotic modifying reagent. An anionic group carboxymethyl and a cationic CHTAC group are introduced into an amphiprotic bagasse xylan molecule prepared with the method, so that a bagasse xylan derivative molecule has not only properties of anionic xylan but also properties of cationic xylan, has performances of no toxicity, biodegradability and the like, does not have toxic or side effects on a human body, and can serve as the excellent drug carrier.

Description

For the preparation method of the quaternized bagasse xylan of carboxymethylation-CHTAC of pharmaceutical carrier

Technical field

The present invention relates to a kind of preparation method of the quaternized bagasse xylan of carboxymethylation-CHTAC for pharmaceutical carrier.

Background technology

Guangxi, as one of important sugarcane production base of China, has the abundant bagasse xylan resource had compared with the character such as high biological activity and biological degradability.Mainly by the active group of bagasse xylan, modification is carried out to the research of bagasse xylan chemically modified aspect, to reach the object that there is greater functionality character He widen its Application Areas at present.Both sexes xylan derivative is the class xylan derivative that xylan is obtained by two kinds of modification mode, combine the double properties of positively charged ion and negatively charged ion xylan derivative, not only have anionic group but also have cation group, certain basis has been established in the practical application research for xylan.

The domestic and international research to both sexes xylan at present is still in the starting stage, and its application potential waits exploitation.The composition principle of both sexes xylan mainly forms the modification of ehter bond, ester bond etc. by the active function groups of xylanase activity group alcoholic extract hydroxyl group and anions and canons reagent.Quaternary ammonium salts etc. can be used as the cationoid reagent of modification, and metal carboxylate etc. can be used as the reagents for anion of modification.Research in polymer drug carrier mainly concentrates on the material such as chitosan, polyvinyl alcohol at present, and chitin medicine carrier also has relevant clinical application research.But chitosan is a cationoid type polymkeric substance, has certain limitation for medicine carrying; Polyvinyl alcohol belongs to a kind of water-soluble polymers simultaneously, also has certain limitation.And for both sexes bagasse xylan, because it has no side effect and the performance such as excellent biocompatibility, be a kind of excellent new drug carrier.

The present invention take bagasse xylan as starting raw material, aqueous ethanolic solution is solvent, respectively through carboxymethylation, 3-chloro-2-hydroxypropyl-trimethyl ammonium chloride (3-chloro-2-hydroxypropyl trimethyl ammoniumchloride, being called for short CHTAC) cationization introduces anions and canons on bagasse xylan, prepares a kind of quaternized bagasse xylan of both sexes carboxymethylation-CHTAC for pharmaceutical carrier.

Summary of the invention

The object of the invention is the apparent property by modification bagasse xylan, to reach the object of bagasse xylan modification, thus make it have the performance himself do not possessed, a kind of method preparing the quaternized bagasse xylan of pharmaceutical carrier carboxymethylation-CHTAC is provided.

Concrete steps are:

(1) bagasse xylan is dried to constant weight in 60 DEG C of vacuum drying ovens, obtains butt bagasse xylan.

(2) by step (1) gained butt bagasse xylan and volume ratio be 4: 1 dehydrated alcohol and distilled water add in reactor the bagasse xylan suspension being made into 30 ~ 50mL and mixing.

(3) step (2) system is warming up to 40 ~ 45 DEG C, slowly drips the sodium hydroxide solution that 10 ~ 15mL massfraction is 25%, continue stir-activating after dropwising through 30 ~ 50 minutes 1 ~ 3 hour.

(4) take that to dewater xylose units amount of substance with bagasse xylan more miscible than the sodium hydroxide and Monochloro Acetic Acid that are 1.50 times in 10 ~ 20mL distilled water; Control temperature of reaction 60 ~ 65 DEG C, by constant pressure funnel, this mixed solution is dripped in step (3), control to drip off at 1 ~ 2 hour, then continue 6 ~ 8 hours reaction times.

(5) to measure volume ratio be respectively the massfraction of 3 ︰ 1 ︰ 2 ~ 3 be 30% trimethylamine aqueous solution, massfraction be 36% concentrated hydrochloric acid and analytical pure epoxy chloropropane; By massfraction be 36% concentrated hydrochloric acid be added drop-wise to that to add massfraction be in another reactor of 30% trimethylamine aqueous solution, stir 10 ~ 15 minutes to evenly; Add analytical pure epoxy chloropropane again, control temperature of reaction 25 ~ 35 DEG C, in 1 ~ 2 hour reaction times, obtain liquid cation etherifying agent 3-chloro-2-hydroxypropyl-trimethyl ammonium chloride (3-chloro-2-hydroxypropyltrimethyl ammonium chloride is called for short CHTAC).

(6) step (5) gained CHTAC is slowly added drop-wise in step (4) products therefrom, at temperature of reaction 50 ~ 60 DEG C, controls to dropwise for 2 ~ 3 hours, continue reaction 6 ~ 9 hours.

(7) with 30 ~ 50mL dehydrated alcohol settling step (6) gained solution, suction filtration, obtains filter cake; Use 20 ~ 30mL distilled water, 15 ~ 25mL absolute ethanol washing filter cake successively respectively each 2 ~ 3 times, detect the filtrate after washing without white precipitate to the silver nitrate solution by concentration being 0.05mol/L.

(8) the washed filter cake of step (7) gained is put into glass dish, the vacuum drying oven being placed in 50 DEG C is dried to constant weight and namely obtains the quaternized bagasse xylan of both sexes carboxymethylation-CHTAC.

(9) with the Anion substituting degree of complexometric titration product, concrete operation method is as follows: the quaternized bagasse xylan of both sexes carboxymethylation-CHTAC accurately taking 1.0g puts into 50mL beaker, add the commercially available cupric ion standardized solution of 20mL, regulate pH to 6.0 ~ 7.0 by the NaOH solution that concentration is 0.5mol/L; When solid precipitation is separated out, leach throw out; Get filtrate, regulate pH to 7.5 ~ 8.0 by the NaOH solution that concentration is 0.5mol/L, instill 2 ~ 3 Peroxyacetyl nitrate (PAN) indicator, be titrated to green with ethylenediamine tetraacetic acid (EDTA) (EDTA) standardized solution.Under the same conditions, blank titration is carried out.Mass percent (B) in sample contained by anionic carboxyl group and the calculation formula of substitution value (DS) as follows:

B=c _eDTA× (V _blank-V _sample) × 10 ^-3× 2 × 81 × m _sample× 100%

DS＝132×81×B-(81-1)×B

In formula: B---the massfraction of sodium acetate base, %;

M _sample---the quality of sample, unit g;

C _eDTA---the concentration of EDTA standardized solution, unit mol/L;

V _blank---the blank volume consuming EDTA standardized solution of record, Unit/mL;

V _sample---record sample consumes the volume of EDTA standardized solution, Unit/mL;

132 and 81---the relative molecular mass of bagasse xylan dehydration xylose units and Monochloro Acetic Acid dewatering unit.

(10) with reference to the degree ofacationic substitution of Kjeldahl nitrogen determination product, concrete grammar is as follows: 250mL there-necked flask put into by the sample accurately taking 1.0g, add 0.5g catalyst sulfuric acid copper, 10g potassium sulfate, a little zeolite, add that to get 20mL massfraction be 98% vitriol oil again, shake up gently.Under slight boiling condition, nitrated cracking to reaction solution is blue-greenish colour.With the sodium hydroxide solution alkalization that 20mL massfraction is 40%, distillation release ammonia, the boric acid solution with 4% absorbs; Be titrated to colourless with the HCl standardized solution of 0.01mol/L again.Under the same conditions, blank titration is carried out.Nitrogen content (n), xylan degree ofacationic substitution (DS) method of calculation are as follows:

$n=\frac{1.4\×C\×(V_1-V_0)}{121.5}$

$\mathrm{DS}=\frac{132\×(n-n_0)}{m-121.5\×(n-n_0)}$

In formula: n---the nitrogen content of sample, unit mol;

C---the concentration of HCl standardized solution, unit mol/L;

V ₀---the blank volume consuming HCl standardized solution of record, Unit/mL;

V ₁---record sample consumes the volume of HCl standardized solution, Unit/mL;

N ₀---the nitrogen content of blank sample, unit mol;

The quality of m---sample, unit g.

By in the both sexes bagasse xylan molecule that above-mentioned processing method is obtained, namely anionic group carboxymethyl is introduced, introduce again positively charged ion CHTAC group, make xylan derivative molecule not only have the character of negatively charged ion xylan but also have the character of positively charged ion xylan, can be used for field of medicaments especially pharmaceutical carrier aspect.

Accompanying drawing explanation

Fig. 1 is the IR figure of former bagasse xylan.

Fig. 2 is the IR figure of the quaternized bagasse xylan of both sexes carboxymethylation-CHTAC prepared by the embodiment of the present invention.

Fig. 3 is the SEM figure of former bagasse xylan.

Fig. 4 is the SEM figure of the quaternized bagasse xylan of both sexes carboxymethylation-CHTAC prepared by the embodiment of the present invention.

Embodiment

Embodiment 1:

(1) bagasse xylan is dried to constant weight in 60 DEG C of vacuum drying ovens, obtains butt bagasse xylan.

(2) 3.0g step (1) gained butt bagasse xylan, 6mL distilled water and 24mL dehydrated alcohol are added in reactor, be made into the bagasse xylan suspension mixed.

(3) step (2) system is warming up to 40 DEG C, slowly dripping 12mL massfraction is the sodium hydroxide solution of 25%, continues stir-activating 2 hours through 35 minutes after dropwising.

(4) take 1.36g sodium hydroxide and 3.22g Monochloro Acetic Acid, be dissolved in 10mL distilled water in the lump; Control temperature of reaction 60 DEG C, by constant pressure funnel, this mixed solution is dripped in step (3) gains, control to drip off at 2 hours, then continue 7 hours reaction times.

(5) measure 9mL massfraction be 30% trimethylamine aqueous solution join in another reactor, by 3mL massfraction be 36% concentrated hydrochloric acid to be added drop-wise to massfraction be in 30% trimethylamine aqueous solution, stir 10 minutes to evenly; Add 7.8mL analytical pure epoxy chloropropane again, control temperature of reaction 25 DEG C, in 2 hours reaction times, obtain liquid cation etherifying agent CHTAC.

(6) step (5) gained cationic etherifying agent CHTMAC is slowly added drop-wise in step (4) gains, at temperature of reaction 50 DEG C, controls to dropwise for 3 hours, continue reaction 8 hours.

(7) with 30mL dehydrated alcohol settling step (6) gained solution, suction filtration, obtains filter cake; Use 20mL distilled water, 15mL absolute ethanol washing filter cake successively respectively each 3 times, detect the filtrate after washing without white precipitate to the silver nitrate solution by concentration being 0.05mol/L.

(8) the washed filter cake of step (7) gained is put into glass dish, the vacuum drying oven being placed in 50 DEG C is dried to constant weight and namely obtains the quaternized bagasse xylan of both sexes carboxymethylation-CHTAC.

(10) Anion substituting degree measuring the quaternized bagasse xylan product of both sexes carboxymethylation-CHTAC is 0.54, and degree ofacationic substitution is 0.044.

Embodiment 2:

(1) bagasse xylan is dried to constant weight in 60 DEG C of vacuum drying ovens, obtains butt bagasse xylan.

(2) 4.0g step (1) gained butt bagasse xylan, 8mL distilled water and 42mL dehydrated alcohol are added in reactor, be made into the bagasse xylan suspension mixed.

(3) step (2) system is warming up to 45 DEG C, slowly dripping 15mL massfraction is the sodium hydroxide solution of 25%, continues stir-activating 3 hours through 45 minutes after dropwising.

(4) take 1.36g sodium hydroxide and 3.22g Monochloro Acetic Acid, be dissolved in 20mL distilled water in the lump; Control temperature of reaction 55 DEG C, by constant pressure funnel, this mixed solution is dripped in step (3) gains, control to drip off at 2 hours, then continue 8 hours reaction times.

(5) measure 9mL massfraction be 30% trimethylamine aqueous solution join in another reactor, by 3mL massfraction be 36% concentrated hydrochloric acid to be added drop-wise to massfraction be in 30% trimethylamine aqueous solution, stir 10 minutes to evenly; Add 7.8mL analytical pure epoxy chloropropane again, control temperature of reaction 25 DEG C, in 2 hours reaction times, obtain liquid cation reagent C HTAC.

(6) step (5) gained cationic etherifying agent CHTMAC is slowly added drop-wise in step (4), at temperature of reaction 60 DEG C, controls to dropwise for 4 hours, continue reaction 8 hours.

(7) with 40mL dehydrated alcohol settling step (6) gained solution, suction filtration, obtains filter cake; Use 30mL distilled water, 25mL absolute ethanol washing filter cake successively respectively each 3 times, detect the filtrate after washing without white precipitate to the silver nitrate solution by concentration being 0.05mol/L.

(8) the washed filter cake of step (7) gained is put into glass dish, the vacuum drying oven being placed in 50 DEG C is dried to constant weight and namely obtains the quaternized bagasse xylan of both sexes carboxymethylation-CHTAC.

(9) Anion substituting degree measuring the quaternized bagasse xylan product of both sexes carboxymethylation-CHTAC is 0.63, and degree ofacationic substitution is 0.042.

Product is analyzed through IR, 1253cm ^-1place is the vibration absorption peak of C-N key, 1613cm ^-1, 1417cm ^-1and 1327cm ^-1place is the vibration absorption peak of carboxymethyl; 3550cm ^-1~ 3400cm ^-1scope absorption peak obviously broadens, and this is the introducing due to carboxyl and quaternary ammonium group, and the association of hydroxyl causes.3431cm ^-1near broad peak, this is-stretching vibration of OH causes.Sem analysis result shows the particle surface pattern before modified, and the granule-morphology of obvious former bagasse xylan is more coarse, belongs to noncrystal, in amorphous state; Both sexes bagasse xylan particle surface is smoother, and the structure of obvious former bagasse xylan is damaged or considerable change occurs.

Claims (1)

1., for a preparation method for the quaternized bagasse xylan of carboxymethylation-CHTAC of pharmaceutical carrier, it is characterized in that concrete steps are:

(1) bagasse xylan is dried to constant weight in 60 DEG C of vacuum drying ovens, obtains butt bagasse xylan;

(2) by step (1) gained butt bagasse xylan and volume ratio be 4: 1 dehydrated alcohol and distilled water add in reactor the bagasse xylan suspension being made into 30 ~ 50mL and mixing;

(3) step (2) system is warming up to 40 ~ 45 DEG C, slowly drips the sodium hydroxide solution that 10 ~ 15mL massfraction is 25%, continuation stir-activating 1 ~ 3 hour after dropwising through 30 ~ 50 minutes;

(4) take that to dewater xylose units amount of substance with bagasse xylan more miscible than the sodium hydroxide and Monochloro Acetic Acid that are 1.50 times in 10 ~ 20mL distilled water; Control temperature of reaction 60 ~ 65 DEG C, by constant pressure funnel, this mixed solution is dripped in step (3), control to drip off at 1 ~ 2 hour, then continue 6 ~ 8 hours reaction times;

(5) to measure volume ratio be respectively the massfraction of 3 ︰ 1 ︰ 2 ~ 3 be 30% trimethylamine aqueous solution, massfraction be 36% concentrated hydrochloric acid and analytical pure epoxy chloropropane; By massfraction be 36% concentrated hydrochloric acid be added drop-wise to that to add massfraction be in another reactor of 30% trimethylamine aqueous solution, stir 10 ~ 15 minutes to evenly; Add analytical pure epoxy chloropropane again, control temperature of reaction 25 ~ 35 DEG C, in 1 ~ 2 hour reaction times, obtain liquid cation etherifying agent 3-chloro-2-hydroxypropyl-trimethyl ammonium chloride and 3-chloro-2-hydroxypropyl trimethyl ammonium chloride, be called for short CHTAC;

(6) step (5) gained CHTAC is slowly added drop-wise in step (4) products therefrom, at temperature of reaction 50 ~ 60 DEG C, controls to dropwise for 2 ~ 3 hours, continue reaction 6 ~ 9 hours;

(7) with 30 ~ 50mL dehydrated alcohol settling step (6) gained solution, suction filtration, obtains filter cake; Use 20 ~ 30mL distilled water, 15 ~ 25mL absolute ethanol washing filter cake successively respectively each 2 ~ 3 times, detect the filtrate after washing without white precipitate to the silver nitrate solution by concentration being 0.05mol/L;

(8) the washed filter cake of step (7) gained is put into glass dish, the vacuum drying oven being placed in 50 DEG C is dried to constant weight and namely obtains the quaternized bagasse xylan of both sexes carboxymethylation-CHTAC.