CN105218684B - A kind of long aliphatic chain modified cellulose derivative medicine covering material - Google Patents
A kind of long aliphatic chain modified cellulose derivative medicine covering material Download PDFInfo
- Publication number
- CN105218684B CN105218684B CN201510726068.2A CN201510726068A CN105218684B CN 105218684 B CN105218684 B CN 105218684B CN 201510726068 A CN201510726068 A CN 201510726068A CN 105218684 B CN105218684 B CN 105218684B
- Authority
- CN
- China
- Prior art keywords
- cellulose
- long
- acid
- chain
- chloride
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Landscapes
- Polysaccharides And Polysaccharide Derivatives (AREA)
Abstract
A kind of long aliphatic chain modified cellulose derivative medicine covering material that the present patent application is provided; it is that a kind of long aliphatic chain of cellulose acetate phthalate is material modified; reacted by fatty acylated reagent in homogeneous cellulose DMAc/LiCl solution and cellulose long-chain fatty acid ester is made, be made under room temperature environment with phthalic anhydride.This cellulose long-chain aliphatic acid phthalic acid ester substantially improves cellulose acetate phthalate (CAP) machinability, including thermoplasticity, mechanical property and molding processibility, especially plasticity and film forming, especially there is medicament slow release control ability, make a kind of newtype drug and release control material.
Description
Technical field
Present patent application refers to excipient substance, more particularly to polymer drug coating material, medicament slow release material
Material, particularly fiber derivative type polymer drug coating material, Thermosensitive Material Used for Controlled Releasing of Medicine.
Background technology
Cellulose is the most extensive in distributed in nature, and its derivative is widely used in chemical industry, oil, weaving, light industry, the energy
And biotechnology field.Wherein, cellulose acetate is one of which more important cellulose esters, also known as acetate fiber
Element, and industrial scale preparation has been obtained, and also it is modified being also easier to realization again to it, many cellulose derivatives are
Preparation is modified based on cellulose acetate, such as cellulose acetate phthalate CAP, it is more to be applied to medicine neck
Domain, is used as drug coating membrane material.
But, a key technology of cellulose acetate phthalate has the disadvantage that fragility is big, it is necessary to add appropriate plasticizer
To improve its film forming plasticity, such as Jiping Liu article " Properties of heat-humidity cured
cellulose acetate phthalate free films. European Journal of Pharmaceutical
Sciences 17 (2002) 31–41”.But the use of plasticizer has been found to that human body can be brought great potential side effect.
The content of the invention
The goal of the invention of the present patent application is to provide a kind of long aliphatic chain modified cellulose with superior moldability energy
Derivative medicine covering material, the covering material has good dissolubility in cushioning liquid, and the dissolubility is conducive to release,
And meet the higher release efficiency of the carrying medicament in certain time.The long fat of one kind that present patent application is provided is chain modified
Cellulose derivative medicine covering material technical scheme, its main technical content is：A kind of long aliphatic chain modified cellulose derives
Thing medicine covering material, is that the long aliphatic chain of cellulose acetate phthalate is material modified, is made by following preparation method：
Step one：Fatty acylated reagent is added in homogeneous cellulose DMAc/LiCl solution, in 50 DEG C of -80 DEG C of temperature conditionss
Under, react 2-12 hours, cellulose long-chain fatty acid ester is made；
Step 2: the reaction solution of step one is cooled into room temperature, phthalic anhydride and catalyst of triethylamine, room temperature are added
Obtained cellulose is dried in lower reaction 30 minutes, thereafter, aqueous hydrochloric acid solution acidifying, the scrubbed and neutral filter cake that is filtrated to get
Long chain fatty acids phthalic acid ester.
In the step of above-mentioned overall technical architecture one, described fatty acylated reagent is that mol ratio is 1：1 long-chain fat
Acid and paratoluensulfonyl chloride.Described long chain fatty acids are the long chain fatty acids that carbon number is not less than 6, including：Caproic acid, octanoic acid,
Capric acid, laurate, palmitic acid, myristic acid, stearic acid etc..
In above-mentioned overall technical architecture step one, described fatty acylated reagent is long-chain fat acyl chlorides, and homogeneous fine
Tie up the cellulose anhydroglucose unit of element DMAc/LiCl solution（AUG）Mol ratio with long-chain fat acyl chlorides is 1：1~4.Institute
The long-chain fat acyl chlorides stated is the long-chain fat acyl chlorides that carbon number is not less than 6, including：Caproyl chloride, caprylyl chloride, decanoyl chloride, bay
Acyl chlorides, palmitoyl chloride, myristyl chloride, stearyl chloride etc..
The long aliphatic chain modified cellulose derivative medicine covering material that the present patent application is provided, is a kind of novel cellulose
Derivative, the material component that the novel cellulose derivative is based on --- homogeneous cellulose DMAc/LiCl solution, is known public affairs
Open material, Chinese patent CN2010105753428 homogeneous cellulose DMAc/LiCl solution, and《Macromolecule is circulated a notice of》2010
" research and the application of cellulose/LiCl/DMAc solution systems " that 10th interim Lee's shape etc. is delivered has related detailed record.
This cellulose long-chain aliphatic acid phthalic acid ester is white, canescence, flaxen cake mass；According to length
The substitution value ratio change of chain fatty acyl group and phthalyl, it is tried in chloroform, acetone, dimethyl sulfoxide, cushioning liquid etc.
There are different dissolubility or swelling behavior in agent.Product is only cellulose long-chain fatty acid ester, and substitution value is more than 1.5, dissolved in
Chloroform and insoluble in acetone, and the cellulose long-chain aliphatic acid phthalic acid ester of the inventive method synthesis passes through and controls dehydration
Glucose unit（AGU）With the condition such as the mol ratio of acylating reagent, reaction time and reaction temperature, can be by long chain fatty acids ester group
Substitution value control between 0.8~2, to ensure to have sufficient amount of hydroxyl and phthalic anhydride to carry out esterification, control
The addition of phthalic anhydride processed is quality controllable to make its substitution value, by the control of phthalic acid ester group substitution value 0.5~0.9 it
Between, obtained product has good dissolubility in pH value is 7.4 cushioning liquid, and the dissolubility is conducive to carrying medicament
Release, disclosure satisfy that the release institute carrying medicament of the greater efficiency in certain time.
The presence of long chain fatty acyl in the cellulose long-chain aliphatic acid phthalic acid ester that the technical program is obtained, significantly
Cellulose acetate phthalate (CAP) machinability, including thermoplasticity, mechanical property and molding processibility are improved,
Especially plasticity and film forming, are easy to compressing, casting-volatilization shaping in the case of without plasticizer, in field of medicaments,
As medicine covering material, its medicament slow release control ability having makes a kind of newtype drug and releases control material.By fiber
Plain long chain fatty acids phthalic acid ester replaces existing cellulose acetate phthalate (CAP), overcomes existing fibre
Dependence of the plain cellulose acetate phthalate ester (CAP) of dimension in terms of processing characteristics to plasticizer, it is to avoid plasticizer is in medicine
Using to human body potential hazard, also with the technological merit that technique is simple, process conditions are easily realized.
Brief description of the drawings
Fig. 1 to Fig. 4 is experimental result curve map of the product to two kinds of insoluble drug release situations of embodiment 8 to 11 respectively, its
In cubic stain correspond to left side drug release rate ordinate, circle stain corresponds to that right side drug accumulation burst size is vertical to sit
Mark.
Embodiment
A kind of long aliphatic chain modified cellulose derivative medicine covering material of the present patent application, is the adjacent benzene of cellulose acetate
The long aliphatic chain of dicarboxylic acid esters is material modified, is made by following preparation method.
Embodiment 1
With the sad phthalic acid ester of the synthetically prepared cellulose of homogeneous cellulose DMAc/LiCl solution：
Step one, the synthesis of cellulose caprylate：
Mass concentration is 2% cellulose DMAc/LiCl solution 50g, is inserted in 100ml there-necked flasks, and starts stirring dress
Put；With cellulose anhydroglucose unit（AGU）With the mol ratio n (AGU) of caprylyl chloride：N (caprylyl chloride) is 1：2, add quantitative
Caprylyl chloride, add 5ml acid binding agent pyridines, the hydrochloric acid produced to reduce reaction influences on the degraded of cellulose, in 50 DEG C of temperature
Under the conditions of degree react 12 hours, after be cooled to room temperature, it is stand-by；
Step 2：Phthalic anhydride 2g and 5ml catalyst of triethylamine, room temperature bar are added after being reacted to step one in system
Stirring reaction 30 minutes under part, are thereafter 1 with water volume ratio by 35% hydrochloric acid of concentration:1 aqueous solution 100ml acidifyings, then take out
Filter, obtained filter cake is by distilled water cyclic washing to neutrality, and vacuum freeze-drying obtains the sad phthalic acid of cellulose to constant weight
Ester.Remaining, which collects filtrate, to reclaim wherein each component using the way of distillation.
Product acid number is 40mgKOH/g, and saponification number is 410 mgKOH/g, and sad ester group substitution value is 1.56, O-phthalic
Perester radical substitution value is 0.19, and it is 2 that product, which is dissolvable in water acetone and the volume ratio of ethanol,：In 1 mixed liquor, in cushioning liquid
It is insoluble.
Embodiment 2
With the synthetically prepared cellulose n-nonanoic acid phthalic acid ester of homogeneous cellulose DMAc/LiCl solution;
Step one：The synthetic reaction of cellulose pelargonate
Mass concentration is 2% cellulose DMAc/LiCl solution 50g, added in 100ml there-necked flasks, by the de- of cellulose
Water glucose unit：N-nonanoic acid：The mol ratio n (AGU) of paratoluensulfonyl chloride：N (n-nonanoic acid)：N (paratoluensulfonyl chloride) is 1：4：4 add
Enter n-nonanoic acid and paratoluensulfonyl chloride, paratoluensulfonyl chloride therein is the solution being dissolved in 5ml DMAc, add acid binding agent pyrrole
Pyridine 6ml, influences for reducing, weakening degraded of the hydrochloric acid produced in reaction on cellulose, stirs anti-under 50 DEG C of temperature conditionss
Answer 12 hours, after be cooled to room temperature, it is stand-by；
Step 2：Phthalic anhydride 2g and 5ml catalyst of triethylamine, room temperature bar are added after being reacted to step one in system
Stirring reaction 30 minutes under part, are thereafter 1 with water volume ratio by 35% hydrochloric acid of concentration:1 aqueous solution 100ml acidifyings, then take out
Filter, obtained filter cake is dried in vacuo 24 hours at room temperature by distilled water cyclic washing to neutrality, obtains the adjacent benzene two of cellulose n-nonanoic acid
Formic acid esters.Wherein each component can be reclaimed using the way of distillation by collecting filtrate.
Product acid number is 12mgKOH/g, and saponification number is 450 mgKOH/g, and n-nonanoic acid ester group substitution value is 2.85, O-phthalic
Perester radical substitution value is 0.08, and product is dissolved in chloroform, is not dissolved in cushioning liquid.
Embodiment 3
With the synthetically prepared cellulose capric acid phthalic acid ester of homogeneous cellulose DMAc/LiCl solution：
Step one：The synthesis of cellulose decylate：
Mass concentration is 2% cellulose DMAc/LiCl solution 50g, added in 100ml there-necked flasks, breakdown stirring dress
Put, by the dehydrated glucose unit of cellulose：Capric acid：The mol ratio n (AGU) of paratoluensulfonyl chloride：N (capric acid)：N is (to toluene
Sulfonic acid chloride) it is 1：4：4 add capric acid and paratoluensulfonyl chloride, and paratoluensulfonyl chloride therein is the solution for being dissolved in 5mlDMAc, then
6ml acid binding agent pyridines are added, is influenceed with reducing, weakening degraded of the hydrochloric acid produced in reaction on cellulose, is warming up to 50 DEG C simultaneously
Maintenance reaction 12 hours, is down to thereafter room temperature, pours into and is separated out in distilled water, suction filtration, filters out product and washs two by 50 DEG C of ethanol
To three times, cellulose decylate is obtained；
Step 2：Phthalic anhydride 2g and 5ml catalyst of triethylamine, room are added into the reacted system of step one
Stirring reaction 30 minutes under the conditions of temperature, by 35% hydrochloric acid of concentration with water volume ratio be 1:1 aqueous solution 100ml acidifyings, then suction filtration
Precipitation, filter cake is washed with distilled water to neutrality, is dried in vacuo 24 hours at room temperature, obtains cellulose capric acid phthalic acid ester.
Its each component can be reclaimed using the way of distillation by collecting filtrate.
Product acid number is 10mgKOH/g, and saponification number is 465 mgKOH/g, and capric acid ester group substitution value is 2.91, O-phthalic
Perester radical substitution value is 0.07, and product is dissolved in chloroform, is not dissolved in cushioning liquid.
Embodiment 4
With homogeneous cellulose DMAc/LiCl solution synthetic cellulose laurate phthalic acid ester：
Step one：The synthesis of cellulose laurate should：
Mass concentration is 2% cellulose DMAc/LiCl solution 50g, added in 100ml there-necked flasks, breakdown stirring dress
Put, by the dehydrated glucose unit n (AGU) of cellulose：N (bay isoxazolecarboxylic acid) is 1：3 mol ratio adds bay isoxazolecarboxylic acid, then
Acid binding agent pyridine 5ml is added, is influenceed with reducing, weakening degraded of the hydrochloric acid produced in reaction on cellulose, is warming up to 50 DEG C, dimension
Reaction 12 hours is held, room temperature is cooled to, it is standby；
Step 2：Phthalic anhydride 2g and 5ml catalyst of triethylamine, room temperature are added after to the reaction of step one in system
Under the conditions of stirring reaction 30 minutes, with water volume ratio be 1 by 35% hydrochloric acid of concentration:1 aqueous solution 100ml acidifyings, suction filtration sinks
Form sediment, filter cake is dried 24 hours by distillation water washing to neutrality, room temperature in vacuo, and cellulose laurate phthalic acid ester is made.Receive
Wherein each component can be reclaimed using the way of distillation by collecting filtrate.
Product acid number is 11mgKOH/g, and saponification number is 445 mgKOH/g, and laurate ester group substitution value is 2.87, adjacent benzene two
Formic acid ester group substitution value is 0.07, and product is dissolved in chloroform, is not dissolved in cushioning liquid.
Embodiment 5
With homogeneous cellulose DMAc/LiCl solution synthetic cellulose laurate phthalic acid ester：
Step one：The synthesis of cellulose laurate：
Mass concentration 2% is cellulose DMAc/LiCl50g solution, added in 100ml there-necked flasks, breakdown agitating device,
By the dehydrated glucose unit n (AGU) of cellulose：N (bay isoxazolecarboxylic acid) mol ratio is 1：2 add quantitative bay isoxazolecarboxylic acid,
Again plus acid binding agent pyridine 5ml, degraded of the hydrochloric acid produced to reduce, in reduction reaction on cellulose influences, and is warming up to 80 DEG C, and
Maintenance reaction 5 hours, is cooled to room temperature, standby；
Step 2：Phthalic anhydride 2g and 5ml catalyst of triethylamine, room temperature are added into the reacted system of step one
Stirring 30 minutes, by 35% hydrochloric acid of concentration with water volume ratio be 1:1 aqueous solution 100ml acidifyings, suction filtration precipitation, filter cake is by steaming
Distilled water is washed to neutrality, is dried in vacuo 24 hours at room temperature, cellulose laurate phthalic acid ester is made.Collecting filtrate can
Wherein each component is reclaimed using the way of distillation.
Product acid number is 81mgKOH/g, and saponification number is 415 mgKOH/g, and laurate ester group substitution value is 1.71, adjacent benzene two
Formic acid ester group substitution value is 0.37, and it is 2 that product, which is dissolved in acetone and the volume ratio of ethanol,：It is molten in cushioning liquid in 1 mixed liquor
It is swollen.
Embodiment 6
With homogeneous cellulose DMAc/LiCl solution synthetic cellulose laurate phthalic acid ester：
Step one：The synthesis of cellulose laurate：
Mass concentration 2% is cellulose DMAc/LiCl solution 50g, added in 100ml there-necked flasks, opens agitating device,
By the dehydrated glucose unit n (AGU) of cellulose：N (bay isoxazolecarboxylic acid) mol ratio is 1：3 add quantitative bay isoxazolecarboxylic acid, then
Plus acid binding agent pyridine 5ml, influenceed with reducing, weakening degraded of the hydrochloric acid produced in reaction on cellulose, be warming up to 80 DEG C, and tie up
Reaction 2 hours is held, room temperature is cooled to, it is standby；
Step 2：Phthalic anhydride 2g and 5ml catalyst of triethylamine, room temperature are added into the reacted system of step one
Stirring 30 minutes, by 35% hydrochloric acid of concentration with water volume ratio be 1:1 aqueous solution 100ml acidifyings, suction filtration precipitation, obtained filter
Cake is dried in vacuo 24 hours at room temperature by distillation water washing to neutrality, and cellulose laurate phthalic acid ester is made.Collect
Filtrate can reclaim wherein each component using the way of distillation.
Product acid number is 80mgKOH/g, and saponification number is 315 mgKOH/g, and laurate ester group substitution value is 1.68, adjacent benzene two
Formic acid ester group substitution value is 0.87, and it is 2 that product, which dissolves in cushioning liquid, acetone, volume ratio,：1 acetone and alcohol mixeding liquid.
Embodiment 7
With homogeneous cellulose DMAc/LiCl solution synthetic cellulose laurate phthalic acid ester：
Step one：The synthesis of cellulose laurate：
Mass concentration 2% is cellulose DMAc/LiCl solution 50g, added in 100ml there-necked flasks, opens agitating device,
By the dehydrated glucose unit n (AGU) of cellulose：N (bay isoxazolecarboxylic acid) mol ratio is 1：4 add quantitative bay isoxazolecarboxylic acid,
Pyridine 5ml is added, is influenceed with reducing, weakening degraded of the hydrochloric acid produced in reaction on cellulose, is warming up to 80 DEG C, and maintain
Reaction 2 hours, is cooled to room temperature, standby；
Step 2：Phthalic anhydride 2g and 5ml catalyst of triethylamine, room temperature are added into the reacted system of step one
Stirring 30 minutes, by 35% hydrochloric acid of concentration with water volume ratio be 1:1 aqueous solution 100ml is acidified, suction filtration precipitation, obtained filter
Cake is dried in vacuo 24 hours at room temperature by distillation water washing to neutrality, and cellulose laurate phthalic acid ester is made.Collect
Filtrate can reclaim wherein each component using the way of distillation.
Product acid number is 8mgKOH/g, and saponification number is 515 mgKOH/g, and laurate ester group substitution value is 2.68, adjacent benzene two
Formic acid ester group substitution value is 0.17, and product dissolves in dimethyl sulfoxide DMSO.
Embodiment 8
With the adjacent acid esters of benzene first two of homogeneous cellulose DMAc/LiCl solution synthetic celluloses capric acid：
Step one：Mass concentration 2% is cellulose DMAc/LiCl solution 50g, and added in 100ml there-necked flasks, unlatching is stirred
Device is mixed, by the dehydrated glucose unit n (AGU) of cellulose：N (decanoyl chloride) mol ratio is 1：2 add quantitative decanoyl chloride, then add
Acid binding agent pyridine 5ml, is influenceed with reducing, weakening degraded of the hydrochloric acid produced in reaction on cellulose, is warming up to 80 DEG C, and maintain
Reaction 2 hours, is cooled to room temperature, standby；
Step 2：Phthalic anhydride 1g and 5ml catalyst of triethylamine, room temperature are added into the reacted system of step one
Stirring 30 minutes, by 35% hydrochloric acid of concentration with water volume ratio be 1:1 aqueous solution 100ml acidifyings, suction filtration precipitation, obtained filter
Cake is dried in vacuo 24 hours at room temperature by distillation water washing to neutrality, and cellulose capric acid phthalic acid ester is made.The filter of collection
Liquid can reclaim wherein each component using the way of distillation.
Its product is determined using saponification method：Its capric acid ester group substitution value is 1.52, and phthalic acid ester group substitution value is
0.12, it is 2 that product, which dissolves in acetone, volume ratio,：Do not dissolved in 1 acetone and alcohol mixeding liquid, cushioning liquid.
Medicament slow release is tested：Precise retens 16.5mg, takes the adjacent benzene of the plain capric acid of the present embodiment sample fiber
The acid esters 208.6mg of first two, is inserted through in high-temperature sterilization, the mortar of drying, after grinding 20min, being carried out with powder compressing machine jointly
Tabletting, numbering is No. 1, No. 2, No. 3, and the sample mass of carrying medicament is followed successively by 62.2mg, 60.9mg, 76.5mg, drug loading
Amount is respectively 4.9mg, 4.8mg, 6.1mg.
The test of sustained release performance is carried out to press sheet compression：In the Na that pH value is 7.42 HPO4/NaH2PO4Enter in cushioning liquid
OK, shaking bath temperature is set as 37 DEG C, and 5ml cushioning liquid is added in conical flask, and clear liquid was poured out at interval of 1 hour,
The buffer solution for being supplemented same volume continues to vibrate, and takes out clear liquid and selects dilution or directly testing drug to contain according to concentration
Amount, ultraviolet-uisible spectrophotometer sets wavelength as 350nm, measures its absorbance.Parallel test is averaged, such as curve map 1.
In preceding 4 hours, the medication amount discharged per hour is substantially suitable, very small to the 8th hour burst size, explanation
The material has certain control release ability, and total burst size reaches the 35-40% of carrying medicament amount.
Embodiment 9
With the adjacent acid esters of benzene first two of homogeneous cellulose DMAc/LiCl solution synthetic celluloses n-nonanoic acid：
Step one：Mass concentration 2% is cellulose DMAc/LiCl solution 50g, and added in 100ml there-necked flasks, unlatching is stirred
Device is mixed, by the dehydrated glucose unit n (AGU) of cellulose：N (pelargonyl chloride) mol ratio is 1：2 add quantitative pelargonyl chloride, then add
Acid binding agent pyridine 5ml, is influenceed with reducing, weakening degraded of the hydrochloric acid produced in reaction on cellulose, is warming up to 80 DEG C, and maintain
Reaction 2 hours, is cooled to room temperature, standby；
Step 2：Phthalic anhydride 1.5g and 5ml catalyst of triethylamine, room are added into the reacted system of step one
Temperature stirring 30 minutes, by 35% hydrochloric acid of concentration with water volume ratio be 1:1 aqueous solution 100ml acidifyings, suction filtration precipitation is obtained
Filter cake is dried in vacuo 24 hours at room temperature by distillation water washing to neutrality, and cellulose n-nonanoic acid phthalic acid ester is made.Collect
Filtrate can reclaim wherein each component using the way of distillation.
Its product is determined using saponification method：Its n-nonanoic acid ester group substitution value is 1.38, and phthalic acid ester group substitution value is
0.32, product is swelled in cushioning liquid, and it is 2 to be dissolved in acetone, volume ratio：1 acetone and alcohol mixeding liquid.
Medicament slow release is tested：Precise retens 10.0mg, takes the adjacent benzene first of cellulose n-nonanoic acid of the present embodiment
Two acid esters sample 108.0mg, are added through in high-temperature sterilization, the mortar of drying, after grinding 20min, being carried out with powder compressing machine
Tabletting, numbering be tabletting 1, No. 2, the sample mass of carrying medicament is followed successively by 56.0mg, 62.0mg, and drug loading is respectively
4.7mg, 5.3mg.
The test of sustained release performance is carried out to press sheet compression：In the Na that pH value is 7.42 HPO4/NaH2PO4Enter in cushioning liquid
OK, shaking bath temperature is set as 37 DEG C, and 5ml buffer solutions are added in conical flask, and clear liquid was poured out at interval of 1 hour, mends
The buffer solution for filling same volume continues to vibrate, and takes out clear liquid and selects dilution or directly testing drug content according to concentration,
Ultraviolet-uisible spectrophotometer sets wavelength as 350nm, measures its absorbance.Parallel test is averaged, referring to Fig. 2.
In first 3 hours, quite, burst size is obviously reduced the medication amount discharged per hour within the 12nd hour, illustrates the material
With certain control release ability, total burst size reaches the 45-56% of carrying medicament amount.
Embodiment 10
With the adjacent acid esters of benzene first two of homogeneous cellulose DMAc/LiCl solution synthetic celluloses n-nonanoic acid：
Step one：Mass concentration 2% is cellulose DMAc/LiCl solution 50g, and added in 100ml there-necked flasks, unlatching is stirred
Device is mixed, by the dehydrated glucose unit n (AGU) of cellulose：N (pelargonyl chloride) mol ratio is 1：2.5 quantitative pelargonyl chloride is added, then
Plus acid binding agent pyridine 5ml, influenceed with reducing, weakening degraded of the hydrochloric acid produced in reaction on cellulose, be warming up to 80 DEG C, and tie up
Reaction 2 hours is held, room temperature is cooled to, it is standby；
Step 2：Phthalic anhydride 3g and 5ml catalyst of triethylamine, room temperature are added into the reacted system of step one
Stirring 30 minutes, by 35% hydrochloric acid of concentration with water volume ratio be 1:1 aqueous solution 100ml acidifyings, suction filtration precipitation, obtained filter
Cake is dried in vacuo 24 hours at room temperature by distillation water washing to neutrality, and cellulose n-nonanoic acid phthalic acid ester is made.The filter of collection
Liquid can reclaim wherein each component using the way of distillation.
Its product is determined using saponification method：Its n-nonanoic acid ester group substitution value is 1.62, and phthalic acid ester group substitution value is
0.75, it is 2 that product, which dissolves in cushioning liquid, acetone, volume ratio,：1 acetone and alcohol mixeding liquid.
Medicament slow release is tested：Precise retens 10.0mg, takes the adjacent benzene first of cellulose n-nonanoic acid of the present embodiment
Two acid esters sample 100.0mg, it is common to add through in high-temperature sterilization, the mortar of drying, after grinding 20min, using powder compressing machine
Carry out tabletting, numbering be tabletting 1, No. 2, the sample mass of carrying medicament is followed successively by 56.0mg, 52.0mg, drug loading point
Wei not 5.1mg, 4.7mg.
The test of sustained release performance is carried out to press sheet compression：In the Na that pH value is 7.42 HPO4/NaH2PO4Enter in cushioning liquid
OK, shaking bath temperature is set as 37 DEG C, and 5ml buffer solutions are added in conical flask, and clear liquid was poured out at interval of 1 hour, mends
The buffer solution for filling same volume continues to vibrate, and takes out clear liquid and selects dilution or directly testing drug content according to concentration,
Ultraviolet-uisible spectrophotometer sets wavelength as 350nm, measures its absorbance.Average value is removed in parallel test, referring to Fig. 3.
There is peak value in the medication amount of release in the 3rd hour, burst size is obviously reduced within the 15th hour, illustrate that the material has one
Fixed control release ability, the total burst size of medicine reaches the 85% of carrying medicament total amount within 48 hours.
Embodiment 11
The adjacent acid esters sample 100.0mg of benzene first two of the cellulose n-nonanoic acid of precise embodiment 10, be dissolved in 10ml acetone with
In alcohol mixed solution, the volume ratio of acetone and ethanol（V/V）For 2：1, precise retens 5.0mg is added it
In, ultrasonic vibration under ice-water bath, untill complete drug dissolution, in the culture dish that this solution is poured into diameter 35mm, room
Treat that solvent volatilizees completely under temperature, form translucent sheet material, weigh weight for 102.0mg, point take numbering be sheet material 1, No. 2, bear
The sample mass for carrying medicine is followed successively by 50.0mg, 52.0mg, and drug loading is respectively 2.5mg, 2.5mg.
The test of sustained release performance is carried out to samples of sheets：In the Na that pH value is 7.42 HPO4/NaH2PO4Enter in cushioning liquid
OK, shaking bath temperature is set as 37 DEG C, and 5ml buffer solutions are added in conical flask, and clear liquid was poured out at interval of 1 hour, mends
The buffer solution for filling same volume continues to vibrate, and takes out clear liquid and selects dilution or directly testing drug content according to concentration,
Ultraviolet-uisible spectrophotometer sets wavelength as 350nm, measures its absorbance.Parallel test is averaged, unit interval medicine
Burst size and Cumulative release amount are referring to Fig. 4.
Basic linear release in first 18 hours, burst size is obviously reduced after the 18th hour, illustrates that the material has necessarily
Control release ability, the total burst size of medicine reaches the 96% of carrying medicament total amount within 48 hours.
Claims (7)
1. a kind of long aliphatic chain modified cellulose derivative medicine covering material, it is characterised in that be cellulose phthalate
Long aliphatic chain it is material modified, be made by following preparation method：
Step one：Fatty acylated reagent is added in homogeneous cellulose DMAc/LiCl solution, under 80 DEG C of temperature conditionss, and reaction 2~
5 hours, it is made cellulose long-chain fatty acid ester, the substitution value of long chain fatty acids ester group is between 1.38~2；
Step 2: the reaction solution of step one is cooled into room temperature, phthalic anhydride and catalyst of triethylamine are added, at room temperature instead
Answer 30 minutes, thereafter, aqueous hydrochloric acid solution acidifying, the scrubbed and neutral filter cake that is filtrated to get dries obtained cellulose long-chain
Aliphatic acid phthalic acid ester, the substitution value of phthalic acid ester group is between 0.5~0.9.
2. according to a kind of long aliphatic chain modified cellulose derivative medicine covering material described in claim 1, it is characterised in that
Described fatty acylated reagent is that mol ratio is 1：1 long chain fatty acids and paratoluensulfonyl chloride, described long chain fatty acids are
Carbon number is not less than 6 long chain fatty acids.
3. according to a kind of long aliphatic chain modified cellulose derivative medicine covering material described in claim 2, it is characterised in that
Described long chain fatty acids are that caproic acid, octanoic acid, capric acid, laurate, palmitic acid, myristic acid, stearic acid are one of any.
4. according to a kind of long aliphatic chain modified cellulose derivative medicine covering material described in claim 1, it is characterised in that
Described fatty acylated reagent is long-chain fat acyl chlorides, and the cellulose anhydroglucose of homogeneous cellulose DMAc/LiCl solution
The mol ratio of unit and long-chain fat acyl chlorides is 1：1~4, described long-chain fat acyl chlorides is not less than 6 long-chain fat for carbon number
Fat acyl chlorides.
5. according to a kind of long aliphatic chain modified cellulose derivative medicine covering material described in claim 4, it is characterised in that
Described long-chain fat acyl chlorides includes caproyl chloride, caprylyl chloride, decanoyl chloride, lauroyl chloride, palmitoyl chloride, myristyl chloride, tristearin
Acyl chlorides is one of any.
6. according to a kind of long aliphatic chain modified cellulose derivative medicine covering material described in claim 1 or 4, its feature exists
In with homogeneous cellulose DMAc/LiCl solution synthetic cellulose laurate phthalic acid ester, its method is：
Step one：The synthesis of cellulose laurate：
Mass concentration is 2% cellulose DMAc/LiCl solution 50g, added in 100ml there-necked flasks, opens agitating device, presses
The dehydrated glucose unit of cellulose：Bay isoxazolecarboxylic acid mol ratio is 1：3 add quantitative bay isoxazolecarboxylic acid, then add acid binding agent pyridine
5ml, is warming up to 80 DEG C, maintenance reaction 2 hours is cooled to room temperature, standby；
Step 2：Phthalic anhydride 2g and 5ml catalyst of triethylamine is added into the reacted system of step one, is stirred at room temperature
30 minutes, by 35% hydrochloric acid of concentration with water volume ratio be 1:1 the aqueous solution 100ml acidifying, suction filtration precipitation, obtained filter cake by
Water washing is distilled to neutrality, and vacuum drying is made.
7. according to a kind of long aliphatic chain modified cellulose derivative medicine covering material described in claim 1 or 4, its feature exists
In with the adjacent acid esters of benzene first two of homogeneous cellulose DMAc/LiCl solution synthetic celluloses n-nonanoic acid, its method is：
Step one：Mass concentration is 2% cellulose DMAc/LiCl solution 50g, added in 100ml there-necked flasks, opens stirring
Device, by the dehydrated glucose unit of cellulose：Nonanoyl cl molar ratio is 1：2.5 add quantitative pelargonyl chloride, then add acid binding agent pyrrole
Pyridine 5ml, is warming up to 80 DEG C, maintenance reaction 2 hours is cooled to room temperature, standby；
Step 2：Phthalic anhydride 3g and 5ml catalyst of triethylamine is added into the reacted system of step one, is stirred at room temperature
30 minutes, by 35% hydrochloric acid of concentration with water volume ratio be 1:1 aqueous solution 100ml acidifyings, suction filtration precipitation, obtained filter cake is washed
Wash to neutrality, vacuum drying is made.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510726068.2A CN105218684B (en) | 2015-10-30 | 2015-10-30 | A kind of long aliphatic chain modified cellulose derivative medicine covering material |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510726068.2A CN105218684B (en) | 2015-10-30 | 2015-10-30 | A kind of long aliphatic chain modified cellulose derivative medicine covering material |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105218684A CN105218684A (en) | 2016-01-06 |
| CN105218684B true CN105218684B (en) | 2017-10-24 |
Family
ID=54988008
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510726068.2A Active CN105218684B (en) | 2015-10-30 | 2015-10-30 | A kind of long aliphatic chain modified cellulose derivative medicine covering material |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105218684B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113621182A (en) * | 2021-09-07 | 2021-11-09 | 山东友成生物科技有限公司 | Preparation process and equipment of cellulose lactate phthalate sustained-release material |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100387126B1 (en) * | 2001-04-19 | 2003-06-12 | 삼성정밀화학 주식회사 | A purification method of hydroxypropylmethyl cellulose phthalate |
| KR101436170B1 (en) * | 2007-06-26 | 2014-09-01 | 후지필름 가부시키가이샤 | Cellulose acylate composition, cellulose acylate film, and its applications |
| US20090203900A1 (en) * | 2008-02-13 | 2009-08-13 | Eastman Chemical Comapany | Production of cellulose esters in the presence of a cosolvent |
| MY157672A (en) * | 2012-05-31 | 2016-07-15 | Otsuka Pharma Co Ltd | Multilayer film and bag formed of multilayer film |
-
2015
- 2015-10-30 CN CN201510726068.2A patent/CN105218684B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN105218684A (en) | 2016-01-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Guaresti et al. | Synthesis of stimuli–responsive chitosan–based hydrogels by Diels–Alder cross–linkingclick reaction as potential carriers for drug administration | |
| Maharjan et al. | Regenerated cellulose nanofiber reinforced chitosan hydrogel scaffolds for bone tissue engineering | |
| Soorbaghi et al. | Bioaerogels: Synthesis approaches, cellular uptake, and the biomedical applications | |
| Nagahama et al. | Preparation of biodegradable chitin/gelatin membranes with GlcNAc for tissue engineering applications | |
| Ghahremanzadeh et al. | Investigation and comparison of new galactosylation methods on PCL/chitosan scaffolds for enhanced liver tissue engineering | |
| Muhd Julkapli et al. | Preparation, properties and applications of chitosan-based biocomposites/blend materials: a review | |
| Liu et al. | On importance of impurities, potential leachables and extractables in algal nanocellulose for biomedical use | |
| JP5968447B2 (en) | Chitosan and / or chitin complex with enhanced physical properties and uses thereof | |
| Yin et al. | Glucose-responsive insulin delivery microhydrogels from methacrylated dextran/concanavalin A: preparation and in vitro release study | |
| US20070053987A1 (en) | Cross-linked polysacharide and protein matrices and methods for their preparation | |
| CN102276732A (en) | Cellulose interpolymers and methods of oxidation | |
| WO2002060971A1 (en) | Crosslinked polysaccharide sponge | |
| Garcia-Fuentes et al. | The effect of hyaluronic acid on silk fibroin conformation | |
| Liu et al. | Potentially immunogenic contaminants in wood-based and bacterial nanocellulose: assessment of endotoxin and (1, 3)-β-d-glucan levels | |
| Nouri-Felekori et al. | Bioorthogonal hydroxyethyl cellulose-based scaffold crosslinked via click chemistry for cartilage tissue engineering applications | |
| Wang et al. | Click synthesis by Diels-Alder reaction and characterisation of hydroxypropyl methylcellulose-based hydrogels | |
| CN105218684B (en) | A kind of long aliphatic chain modified cellulose derivative medicine covering material | |
| Norouzi et al. | Electrospun nanofibers using β-cyclodextrin grafted chitosan macromolecules loaded with indomethacin as an innovative drug delivery system | |
| CN103804528A (en) | New method for preparing cyclodextrin (meth)acrylate | |
| Oprea et al. | Nanocomposites from functionalized bacterial cellulose and poly (3-hydroxybutyrate-co-3-hydroxyvalerate) | |
| Virtanen et al. | Synthesis and melt processing of cellulose esters for preparation of thermoforming materials and extended drug release tablets | |
| CN112494463A (en) | Berberine/mineralized collagen composite membrane and preparation method and application thereof | |
| DE4404840A1 (en) | Thermoplastic biodegradable polysaccharide derivatives, process for their preparation and their use | |
| CN101225115A (en) | Precipitation modifying method for cellulose type solid enteric coatings | |
| Arulmoorthy et al. | Biosynthesis and characterization of chitosan based hydrogel: A potential in vitro wound healing agent |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB03 | Change of inventor or designer information |
Inventor after: Huang Fengyuan Inventor after: Yu Yan Inventor after: Wu Xiaojie Inventor after: Liu Bo Inventor before: Yu Yan Inventor before: Huang Fengyuan Inventor before: Wu Xiaojie Inventor before: Liu Bo |
|
| CB03 | Change of inventor or designer information | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |