Summary of the invention
For solving the deficiencies in the prior art, a kind of pharmaceutical excipient is the object of the present invention is to provide to prepare and application.
In order to realize above-mentioned target, the present invention adopts following technical scheme:
A pharmaceutical excipient preparation, comprises the steps:
S1, Mierocrystalline cellulose pulverized to be placed on mass concentration be in the sodium hydroxide solution of 1%-5%; bath raio 1:40-1:70; heated and boiled 40-80min; Mierocrystalline cellulose is placed in the sodium hydroxide solution that mass concentration is 5%-30% again after adopting plate-and-frame filter press press filtration; bath raio 1:40-1:70; 20-40 DEG C of standing 60-120min, takes out and clean oven dry and obtain alkali cellulose;
S2, the alkali cellulose obtained by step S1 are pulverized, add and fill in the etherification kettle of reaction medium, bath raio is 1:50-1:80, and adjust ph is 7-9, stir while slowly drip propylene oxide and methyl chloride wherein, 40-60 DEG C of reaction 3-6 hour, after reaction terminates, regulates the pH value of product to neutral with dilute hydrochloric acid or oxalic acid, leave standstill 1-3 hour, suction filtration also uses dehydrated alcohol, deionized water wash according to this, dries and grinds, and crosses 100 mesh sieves and obtains intermediate product;
S3, the intermediate product obtained by step S2 are added in crosslinker solution, stir and be warming up to 50-70 DEG C, adjust ph is 2-5, carry out crosslinking reaction, the reaction times is 1-5 hour, after naturally cooling to room temperature, filter and use deionized water and absolute ethanol washing to filtrate to be neutral, be dried to constant weight, grind rear mistake 100 mesh sieve, obtain pharmaceutical excipient.
Aforementioned fibers element is one or more in cotton fibre, Microcrystalline Cellulose, bamboo pulp fiber, paper pulp Hectometer, stalk.
Crosslinker solution in abovementioned steps S3 is the mixture of solvent and water, and solvent is one or more in dioxane, dimethyl formamide or dimethyl sulfoxide (DMSO).
The volume ratio of aforementioned solvents and water is 1:10-1:5.
Previous reaction medium is the one in deionized water, dehydrated alcohol, acetone, methyl alcohol.
Further, the application of a kind of pharmaceutical excipient of the present invention is as follows: by this pharmaceutical excipient infrared drying 1-2 hour at 120 DEG C, after 200 mesh sieves after grinding, direct compression after then mixing with other auxiliary materials and medicine.
Other auxiliary materials aforementioned are be selected from one or more mixtures in lactose, talcum powder, pre-paying starch.
Usefulness of the present invention is: (1), using natural Mierocrystalline cellulose as modification object, cheaper starting materials is easy to get, renewable, degradable, good biocompatibility, safety and environmental protection; (2) present invention process is simple and easy to realize, and reaction conditions is gentle, and the processing unit without the need to precision can realize, and the cross-linked hydroxypropyl methylcellulose pharmaceutical excipient obtained has good disintegration effect.
Embodiment
Do concrete introduction below in conjunction with specific embodiment to the present invention, but the present invention is not limited to following examples, the raw material that the present invention adopts is commercial.
embodiment 1
S1, paper pulp Hectometer pulverized to be placed on mass concentration be in the sodium hydroxide solution of 3%; bath raio 1:40; heated and boiled 80min; again paper pulp Hectometer is placed in the sodium hydroxide solution that mass concentration is 5% after adopting plate-and-frame filter press press filtration; bath raio 1:40; 20 DEG C of standing 60min, takes out and clean oven dry and obtain alkaline pulp Hectometer Mierocrystalline cellulose;
S2, the alkaline pulp Hectometer Mierocrystalline cellulose obtained by step S1 are pulverized, add and fill in the etherification kettle of dehydrated alcohol, bath raio is 1:50, and adjust ph is 7, stir while slowly drip propylene oxide and methyl chloride wherein, 50 DEG C are reacted 3 hours, after reaction terminates, regulate the pH value of product to neutral with dilute hydrochloric acid, leave standstill 2 hours, suction filtration also uses dehydrated alcohol, deionized water wash according to this, dries and grinds, and crosses 100 mesh sieves and obtains intermediate product;
S3, the intermediate product obtained by step S2 are added in the mixing solutions of dioxane and water, the volume ratio of dioxane and water is 1:10, stir and be warming up to 50 DEG C, adjust ph is 2, carries out crosslinking reaction, reaction times is 3 hours, after naturally cooling to room temperature, filter and use deionized water and absolute ethanol washing to filtrate to be neutral, being dried to constant weight, grind rear mistake 100 mesh sieve, obtain pharmaceutical excipient.
By this pharmaceutical excipient in 120 DEG C of infrared dryings 1 hour, after 200 mesh sieves after grinding, compressing tablet after mixing with lactose, talcum powder, pre-paying starch and medicine, compressibility can be good, and disintegration is respond well.
embodiment 2
S1, cotton fibre pulverized to be placed on mass concentration be in the sodium hydroxide solution of 5%; bath raio 1:70; heated and boiled 40min; cotton fibre is placed in the sodium hydroxide solution that mass concentration is 15% again after adopting plate-and-frame filter press press filtration; bath raio 1:60; 30 DEG C of standing 120min, takes out and clean oven dry and obtain alkaline cotton fibre;
S2, the alkaline cotton fibre obtained by step S1 are pulverized, add and fill in the etherification kettle of deionized water, bath raio is 1:80, and adjust ph is 9, stir while slowly drip propylene oxide and methyl chloride wherein, 40 DEG C are reacted 6 hours, after reaction terminates, regulate the pH value of product to neutral with dilute hydrochloric acid, leave standstill 1 hour, suction filtration also uses dehydrated alcohol, deionized water wash according to this, dries and grinds, and crosses 100 mesh sieves and obtains intermediate product;
S3, the intermediate product obtained by step S2 are added in the mixing solutions of dimethyl sulfoxide (DMSO) and water, the volume ratio of dimethyl sulfoxide (DMSO) and water is 1:8, stir and be warming up to 70 DEG C, adjust ph is 5, carries out crosslinking reaction, reaction times is 5 hours, after naturally cooling to room temperature, filter and use deionized water and absolute ethanol washing to filtrate to be neutral, being dried to constant weight, grind rear mistake 100 mesh sieve, obtain pharmaceutical excipient.
By this pharmaceutical excipient in 120 DEG C of infrared dryings 2 hours, after 200 mesh sieves after grinding, compressing tablet after mixing with lactose, talcum powder and medicine, compressibility can be good, and disintegration is respond well.
embodiment 3
S1, Microcrystalline Cellulose pulverized to be placed on mass concentration be in the sodium hydroxide solution of 1%; bath raio 1:60; heated and boiled 40min; Microcrystalline Cellulose is placed in the sodium hydroxide solution that mass concentration is 20% again after adopting plate-and-frame filter press press filtration; bath raio 1:50; 40 DEG C of standing 90min, takes out and clean oven dry and obtain alkaline Microcrystalline Cellulose;
S2, the alkaline Microcrystalline Cellulose obtained by step S1 are pulverized, add and fill in the etherification kettle of acetone, bath raio is 1:70, and adjust ph is 8, stir while slowly drip propylene oxide and methyl chloride wherein, 60 DEG C are reacted 6 hours, after reaction terminates, regulate the pH value of product to neutral with oxalic acid, leave standstill 2 hours, suction filtration also uses dehydrated alcohol, deionized water wash according to this, dries and grinds, and crosses 100 mesh sieves and obtains intermediate product;
S3, the intermediate product obtained by step S2 are added in the mixing solutions of dimethyl formamide and water, the volume ratio of dimethyl formamide and water is 1:5, stir and be warming up to 70 DEG C, adjust ph is 2, carries out crosslinking reaction, reaction times is 5 hours, after naturally cooling to room temperature, filter and use deionized water and absolute ethanol washing to filtrate to be neutral, being dried to constant weight, grind rear mistake 100 mesh sieve, obtain pharmaceutical excipient.
By this pharmaceutical excipient in 120 DEG C of infrared dryings 1 hour, after 200 mesh sieves after grinding, compressing tablet after mixing with lactose, talcum powder, pre-paying starch and medicine, compressibility can be good, and disintegration is respond well.
embodiment 4
S1, crushed stalk is placed on mass concentration is in the sodium hydroxide solution of 5%; bath raio 1:40; heated and boiled 80min; again paper pulp Hectometer is placed in the sodium hydroxide solution that mass concentration is 30% after adopting plate-and-frame filter press press filtration; bath raio 1:70; 20 DEG C of standing 120min, takes out to clean oven dry and obtain alkaline stalk cellulose;
S2, the alkaline stalk cellulose obtained by step S1 are pulverized, add and fill in the etherification kettle of dehydrated alcohol, bath raio is 1:80, and adjust ph is 7, stir while slowly drip propylene oxide and methyl chloride wherein, 60 DEG C are reacted 5 hours, after reaction terminates, regulate the pH value of product to neutral with oxalic acid, leave standstill 3 hours, suction filtration also uses dehydrated alcohol, deionized water wash according to this, dries and grinds, and crosses 100 mesh sieves and obtains intermediate product;
S3, the intermediate product obtained by step S2 are added in the mixing solutions of dioxane and water, the volume ratio of dioxane and water is 1:6, stir and be warming up to 70 DEG C, adjust ph is 4, carries out crosslinking reaction, reaction times is 5 hours, after naturally cooling to room temperature, filter and use deionized water and absolute ethanol washing to filtrate to be neutral, being dried to constant weight, grind rear mistake 100 mesh sieve, obtain pharmaceutical excipient.
By this pharmaceutical excipient in 120 DEG C of infrared dryings 2 hours, after 200 mesh sieves after grinding, compressing tablet after mixing with lactose, talcum powder and medicine, compressibility can be good, and disintegration is respond well.
More than show and describe ultimate principle of the present invention, principal character and advantage.The technician of the industry should understand, and above-described embodiment does not limit the present invention in any form, the technical scheme that the mode that all employings are equal to replacement or equivalent transformation obtains, and all drops in protection scope of the present invention.