CN102441173A

CN102441173A - Preparation method of a drug release system with water-insoluble protein powder as drug carrier

Info

Publication number: CN102441173A
Application number: CN2010102999534A
Authority: CN
Inventors: 徐卫林; 杨红军; 王珍珍; 崔卫钢; 李文斌
Original assignee: Wuhan Textile University
Current assignee: Wuhan Textile University
Priority date: 2010-09-30
Filing date: 2010-09-30
Publication date: 2012-05-09

Abstract

The invention aims to provide a preparation method of a drug release system which depends on a water-insoluble protein powder as a drug carrier. According to the preparation method of the drug release system, the water-insoluble protein powder with good water absorption is used as a drug carrier, and simultaneously the water-insoluble protein powder forms a continuous water channel in a polymer so as to provide a channel for complete drug release and thoroughly solve the problem that drugs can not be released from the inside of the polymer. The preparation method has advantages of simple technology and fast preparation speed. As the water-insoluble protein powder has good biocompatibility and is nontoxic and harmless, the prepared drug release system also has good biocompatibility and is nontoxic and harmless. Through the water channel formed by the water-insoluble protein powder during the application process, the drug release speed can be effectively controlled, and the carried drug can be completely released, thus reaching better curative effects and avoiding drug waste.

Description

Water-insoluble protein powder body is the method for preparing of the drug delivery system of pharmaceutical carrier

Technical field

The present invention relates to a kind of method for preparing that relies on water-insoluble protein powder body as the drug delivery system of pharmaceutical carrier, belong to medicine and medical instruments field.

Background technology

Mostly bio-medical material is macromolecular material; These bioabsorbable polymer materials need directly to contact with blood; Therefore as bioabsorbable polymer material except that should possessing necessary mechanical property and biological function, also must possess good blood compatibility and histocompatibility.Therefore, biocompatibility, blood compatibility and anticoagulation function how to improve material are the key issues of basic research and material preparation.The main method that improves macromolecular material biocompatibility, blood compatibility and anticoagulation function at present has two kinds; One, utilize method some medicines on the surface grafting of macromolecular material of chemical graft, so that improve biocompatibility, blood compatibility and the anticoagulation function of macromolecular material; Two, the medicine of adding different cultivars forms drug delivery system in macromolecular material, improves biocompatibility, blood compatibility and the anticoagulation function of macromolecular material.

The method of utilizing chemical graft is grafted on the surface of macromolecular material with some medicines, can form for a long time, have the surface of good biocompatibility, blood compatibility and anticoagulant property on the surface of material, but there is a shortcoming in this method.The activity that is grafted on the medicine of polymer surface reduces greatly.In order to improve the anticoagulant property of polyurethane material, people such as Park are grafted on heparin sodium the surface of polyurethane through hydrophilic Polyethylene Glycol.The activity that they find heparin sodium after the grafting only has only 20% before the grafting.

Drug delivery system is that medicine was constantly discharged in the long time.The research of this system and application all are intended to improve the toxic and side effects and the minimizing administration number of times of curative effect, reduction and the minimizing medicine of medicine, to reduce patient's misery.In order under the situation of not destroying pharmaceutically active, to improve the various biological properties of macromolecular material, people are applied to drug delivery system in the macromolecule.The drug delivery system that is applied at present in the macromolecular material can't be used clinically, and main cause is that drug release maybe can't discharge too soon.In some drug delivery systems, drug release only can be kept several hrs, does not have due effect.Other drug delivery system is that medicine is directly mixed with polymer, is coated fully by polymer at the process Chinese medicine granule of molding, in use can't discharge, and causes the waste of medicine.In order to improve the anticoagulant property of polyurethane material, with polyurethane and heparin sodium dissolving and do film forming, experimental result is illustrated in only has 7% medicine from system, to discharge to people such as Qiang in 25 hours in the mixed solution of oxolane and water.While is along with the increase of time; Therefore drug release rate is almost 0.; Need a kind of new drug delivery system to be applied in the polymer at present, so that under the prerequisite of not destroying pharmaceutically active, improve biocompatibility, blood compatibility and the anticoagulant property of polymer.

Because natural bioprotein powder body has excellent biocompatibility, low inflammatory reaction property and favorable mechanical and physical and chemical performance receive biomaterial circle extensive studies in recent years.At artificial skin, prosthetic ligament, there is good prospects for application aspects such as artificial blood vessel, and can be used as the medicament slow release material, enzyme immobilization material etc.In organizational project, its excellent cell growth property also makes it be with a wide range of applications with slow degradability.

The method of obtaining the native protein powder body has two kinds: the method for regeneration and physics behind the chemolysis.The method of chemolysis is that natural protein material is dissolved in salt or other solvents, obtains proteinic aqueous solution.Obtain regenerated protein powder body after the protein aqueous solution dialysis.The protein powder body that this method obtains generally is water-soluble material, causes loss in vivo easily, is difficult to use as biomaterial.The existing water-fast processing mode of protein powder body that makes is that protein material is immersed in methanol or other the organic solvent, and this method causes the harm problem of residual methanol to human body easily.Utilize the method for physics to obtain water-insoluble protein powder body and can overcome the difficult problem that the chemolysis method is brought.The water-insoluble protein powder body that utilizes physical method to prepare has kept physics, chemistry and the biological property of original protein fibre, has excellent biological compatibility, and is a kind of nontoxic, harmless native protein powder body.

Summary of the invention

Problem to above-mentioned existence; The object of the present invention is to provide a kind of method for preparing that relies on water-insoluble protein powder body as the drug delivery system of pharmaceutical carrier; The method for preparing of this drug delivery system is to rely on that to have good absorptive water-insoluble protein powder body be pharmaceutical carrier; Simultaneously water-insoluble protein powder body forms successive aquaporin in that polymer is inner, for the release fully of medicine provides path, thoroughly solves the difficult problem that medicine can't discharge from polymer inside.

Its concrete technical solution is:

1) preparation of pharmaceutical aqueous solution: medicine fully is dissolved in the distilled water, obtains pharmaceutical aqueous solution, and the mass percent of pharmaceutical aqueous solution Chinese medicine is between 5-50%;

Wherein, a kind of in the following material of said choice of drug: heparin sodium, Ahylysantinfarctase, aspirin, hirudin, rapamycin, dexamethasone, Anti-CD34 and paclitaxel;

2) take the preparation of the non-aqueous soluble protein matter of medicine powder body; The water-insoluble protein powder body of particle diameter less than 100 μ m is immersed in the pharmaceutical aqueous solution of above-mentioned preparation, stirs, soak time >=1 hour, the mixture with powder body and pharmaceutical aqueous solution is placed in the exsiccator dry then.After removing distilled water, surplus materials is placed in the high speed Universalpulverizer and pulverizes, and pulverizes time 2-8 minute, obtains to take medicated egg white matter medicament powder;

Wherein, described water-insoluble protein powder body is selected a kind of in the following material for use: fibroin protein powder body, wool protein powder body and eider down protein powder body;

The mass percent of described water-insoluble protein powder body and pharmaceutical aqueous solution is 1: 6;

The temperature of described exsiccator is between 30-60 degree centigrade;

3) preparation of polymer solution: polymer fully is dissolved in the solvent, obtains polymer solution, the mass percent of polymer is between 10-20% in the polymer solution;

Wherein, described polymer is selected a kind of in the following material for use: polyurethane, polylactic acid, gather Acetic acid, hydroxy-, bimol. cyclic ester and poly (glycolide-co-lactide);

Described solvent is selected a kind of in the following solvent for use: N ' dinethylformamide, oxolane, N ' N-dimethyl acetylamide, 1,4-dioxane, chloroform and hexafluoroisopropanol;

4) take the preparation of the water-insoluble protein powder body of medicine and polymer mixed solution: the water-insoluble protein powder body of medicine of taking of above-mentioned preparation mixes with polymer solution; The use rotating speed is that water-insoluble protein powder body of medicine and mixture of polymers are taken in 500 rev/mins-1000 rev/mins agitator stirring; Stirred 2-5 hour, and made and take the water-insoluble protein powder body of medicine and be dispersed in the polymer solution;

Wherein, saidly take the water-insoluble protein powder body of medicine and the blended mass percent of polymer solution is 1: 10～1: 20;

5) above-mentioned preparation take the water-insoluble protein powder body of medicine and polymer mixed solution be placed on vacuum for-0.1Mpa～-environment of 1Mpa in, deaeration 1-2 hour;

6) the mixture drying and moulding of taking water-insoluble protein powder body of medicine and polymer solution after the deaeration;

Wherein baking temperature is controlled at 30-60 degree centigrade.

Owing to adopted above technical scheme; The method for preparing that water-insoluble protein powder body of the present invention is the drug delivery system of pharmaceutical carrier is to adopt to have good absorptive water-insoluble protein powder body as pharmaceutical carrier; Water-insoluble protein powder body is immersed in the distilled water that contains medicine; Powder body is expanded, rely on the drug level difference that drug conveying is entered into powder body.In dry run, cause medicine to lose activity in order to prevent medicine because of baking temperature is too high, therefore adopt 30-60 degree centigrade cold drying.In the dry run, most of medicine is fixed in the powder body, and remaining medicine sticks on the surface of powder body.After taking the water-insoluble protein powder body and polymer mixed behind the medicine, use agitator to stir, will take the water-insoluble protein powder body of medicine and be dispersed in the polymer solution, after vacuum defoamation, can carry out processing and forming.This method for preparing can be accomplished in 24 hours, and is rapidly convenient.In the drug delivery system after the preparation, take the water-insoluble protein powder body of medicine and be dispersed in the polymer, adjacent water-insoluble protein powder bulk phase connects, and forms successive aquaporin.The medicine that carries in the powder body outwards discharges through aquaporin.In whole dispose procedure, therefore the release of medicine need can effectively control the rate of release of medicine through the distance of whole aquaporin through the length of control water-insoluble medicine formation aquaporin, reach the purpose of effective treatment.The medicine that carries in the powder body can reach release completely under the help of aquaporin, can not cause the waste of medicine.To the concentration that needs medicament in different use field, service time and the therapeutic process, the present invention can reach the drug delivery system that preparation contains different pharmaceutical quantities through changing the concentration of pharmaceutical aqueous solution.Long or treatment needed in the therapeutic process of high concentration medicament the time between the drug delivery system of high pharmaceutical quantities can use in use.The drug delivery system of low pharmaceutical quantities needs in the therapeutic process of low concentration medicament in the time of can using in treatment time short or treatment.

Preparation technology of the present invention is simple, preparation speed fast, because water-insoluble protein powder body has excellent biological compatibility, nontoxic, harmless; Therefore the drug delivery system after the preparation also has excellent biological compatibility; Nontoxic, harmless, in use rely on effectively control drug release speed of aquaporin that water-insoluble protein powder body forms, the medicine that carries is discharged fully; Reach better therapeutic effect, avoid the waste of medicine.

Description of drawings

Accompanying drawing is the structural principle sketch map of the water-insoluble protein powder body of the present invention drug delivery system that is pharmaceutical carrier.

The specific embodiment

Below in conjunction with accompanying drawing and embodiment method for preparing of the present invention is done further explain.

The method for preparing concrete steps of the drug delivery system of water-insoluble protein powder body key medicine thing carrier are following:

The preparation of the preparation of the preparation → pharmaceutical aqueous solution of water-insoluble protein powder body → the take preparation → polymer solution of the water-insoluble protein powder body of medicine → take preparation → vacuum defoamation, the molding of water-insoluble protein powder body of medicine and polymer solution mixture.

At first, selected protein fibre material is cut into 3-5mm with disintegrating apparatus, use super-refinement powder body equipment particle diameter to be processed into the water-insoluble protein powder body of mean diameter≤100 μ m as the granule of 3-5mm then.The protein fibre of selecting for use is a kind of in following three kinds of fibers: fibroin protein fiber, wool protein fiber and eider down protein fibre.

The preparation of pharmaceutical aqueous solution.Take by weighing the medicine that need carry and be dissolved in fully in the distilled water, obtain the pharmaceutical aqueous solution of certain concentration.Its Chinese medicine is a kind of in the following drug material: heparin sodium, Ahylysantinfarctase, aspirin, hirudin, rapamycin, dexamethasone, Anti-CD34 and paclitaxel.Drug concentrations is controlled at 5-50%.

Take the preparation of the water-insoluble protein powder body of medicine.Take by weighing the water-insoluble protein powder body of particle diameter below 100 μ m, be immersed in the pharmaceutical aqueous solution of above-mentioned preparation, the mass ratio of powder body and pharmaceutical aqueous solution is 1: 6, powder body soak time >=1 hour.Then the mixture of water-insoluble protein powder body and pharmaceutical aqueous solution is placed in the exsiccator of temperature between 30-60 degree centigrade and carries out drying.After removing distilled water, surplus materials is placed in the high speed Universalpulverizer and pulverized 2-8 minute, obtains to take the water-insoluble protein powder body of medicine.

Prepare polymer solution then: take by weighing polymer and be dissolved in fully in the solvent, obtain the polymer solution of polymer concentration between 10-20%.The polymer that uses is a kind of in the following material: polyurethane, polylactic acid, gather Acetic acid, hydroxy-, bimol. cyclic ester and poly (glycolide-co-lactide).Solvent is selected a kind of in the following solvent for use: N ' dinethylformamide, oxolane, N ' N-dimethyl acetylamide, 1,4-dioxane, chloroform and hexafluoroisopropanol.

Water-insoluble protein powder body of medicine and polymer solution mixture are taken in preparation: the water-insoluble protein powder body of medicine of taking of above-mentioned preparation mixes with polymer solution; The use rotating speed is that 500 rev/mins-1000 rev/mins agitator stirs the mixture of taking water-insoluble protein powder body of medicine and polymer solution; Mixing time 2-5 hour, make and take the water-insoluble protein powder body of medicine and be dispersed in the polymer solution.Taking water-insoluble protein powder body of medicine and the blended mass percent of polymer solution in the mixed process is 1: 10～1: 20.The mass ratio of taking water-insoluble protein powder body of medicine and polymer solution was controlled at 1: 10～1: 20, can guarantees that the drug delivery system for preparing has good intensity, prevent to cause in the use phenomenon of breaking or tearing.Under this ratio, take the water-insoluble protein powder body of medicine and well coated simultaneously, serious sudden and violent mistake phenomenon can not occur, so that obtain to discharge for a long time the drug delivery system of medicine by polymer.

At last, the mixture after the above-mentioned preparation is carried out deaeration.With above-mentioned preparation take the water-insoluble protein powder body of medicine and polymeric blends be placed on vacuum for-0.1Mpa～-environment of 1Mpa in deaeration, 1-2 hour deaeration time.Mixture after the deaeration is placed on temperature and in 30-60 degree centigrade baking oven, carries out drying and moulding.Under the 30-60 degrees celsius, carry out drying and can guarantee that the medicine in the mixture keeps original activity, reaches the effect of effective treatment.

Specific embodiment 1

It is 1% that the silkworm silk that obtains is placed on mass fraction, and bath raio is to boil 3 hours in 1: 20 the Na2CO3 solution, and the back of coming unstuck fully is clean with 50 ℃ of distilled water washs, dries to obtain fibroin fiber.

At first with fibroin fiber at the short flannel that breaks on the rotating blade about 3mm, grind again.Obtain the water-insoluble fibroin powder body of particle diameter below 100 μ m after the grinding.

The 1g heparin sodium is dissolved in the 19g distilled water, and the drug quality percentage ratio that obtains drug level is 5%.After stirring the water-insoluble fibroin powder body of 3.3g is disperseed wherein, the mass ratio of wherein water-insoluble fibroin powder body and heparin sodium pharmaceutical aqueous solution is 1: 6.The mixture of fibroin powder body and medicine soaked 1 hour in 25 degrees celsius held.Mixture to fibroin powder body and pharmaceutical aqueous solution carries out drying then, is placed in 30 ℃ the baking oven to heat, until wherein whole distilled water is all got rid of.Dried water-insoluble fibroin powder body is packed into and is pulverized in the omnipotent high speed disintegrator, and the pulverizing time is 2 minutes.

The 10g medical polyurethane is dissolved in the 90g N ' dinethylformamide, and the mass percent concentration of polymer is 10% in the polymer solution of acquisition.Water-insoluble fibroin powder body after the 4g heparin sodium is compound joins in the 40g polyurethane solutions; Utilize the reinforcement motor stirrer under 500 rev/mins condition, to stir 2 hours; The mixture that acquisition stirs, wherein carrying the water-insoluble fibroin powder body of heparin sodium medicine and the mass ratio of polyurethane solutions is 1: 10.Utilize medical vacuum cycle water pump that the vacuum in the mixture container is adjusted into-0.1MPa, sealing was placed 1 hour, so that remove the steam bubble in the blend.Mixture after the deaeration places 30 degrees centigrade baking oven to carry out drying and moulding.

Specific embodiment 2

The 2g heparin sodium is dissolved in the 18g distilled water, and the drug quality percentage ratio that obtains drug level is 10%.After stirring the water-insoluble fibroin powder body of 3.3g is disperseed wherein, the mass ratio of wherein water-insoluble fibroin powder body and heparin sodium pharmaceutical aqueous solution is 1: 6.The mixture of fibroin powder body and medicine soaked 2 hours 25 ℃ of condition held.Mixture to fibroin powder body and pharmaceutical aqueous solution carries out drying then, is placed in 40 degrees centigrade the baking oven to heat, until wherein whole distilled water is all got rid of.Dried water-insoluble fibroin powder body is packed into and is pulverized in the omnipotent high speed disintegrator, and the pulverizing time is 5 minutes.

The medical polylactic acid of 12g is dissolved in 88g 1, and in the 4-dioxane, the mass percent concentration of polymer is 12% in the polymer solution of acquisition.Water-insoluble fibroin powder body after the 4g heparin sodium is compound joins in the 44g polyurethane solutions; Utilize the reinforcement motor stirrer under 800 rev/mins condition, to stir 3 hours; The mixture that acquisition stirs, wherein carrying the water-insoluble fibroin powder body of heparin sodium medicine and the mass ratio of polyurethane solutions is 1: 11.Utilize medical vacuum cycle water pump that the vacuum in the mixture container is adjusted into-0.3MPa, sealing was placed 1.5 hours, so that remove the steam bubble in the blend.Mixture after the deaeration places 40 degrees centigrade baking oven to carry out drying and moulding.

Specific embodiment 3

At first with clean wool fiber at the short flannel that breaks on the rotating blade about 3mm, grind again.Obtain the water-insoluble Pilus Caprae seu Ovis powder body of particle diameter below 100 μ m after the grinding.

The 4g heparin sodium is dissolved in the 16g distilled water, and the drug quality percentage ratio that obtains drug level is 20%.After stirring the water-insoluble Pilus Caprae seu Ovis powder body of 3.3g is disperseed wherein, the mass ratio of wherein water-insoluble Pilus Caprae seu Ovis powder body and heparin sodium pharmaceutical aqueous solution is 1: 6.The mixture of Pilus Caprae seu Ovis powder body and medicine soaked 2.5 hours in 25 degrees celsius held.Mixture to Pilus Caprae seu Ovis powder body and pharmaceutical aqueous solution carries out drying then, is placed in 40 degrees centigrade the baking oven to heat, until wherein whole distilled water is all got rid of.Dried water-insoluble Pilus Caprae seu Ovis powder body is packed into and is pulverized in the omnipotent high speed disintegrator, and the pulverizing time is 6 minutes.

The medical Acetic acid, hydroxy-, bimol. cyclic ester that gathers of 15g is dissolved in the 85g chloroform, and the mass percent concentration of polymer is 15% in the polymer solution of acquisition.Water-insoluble Pilus Caprae seu Ovis powder body after the 4g heparin sodium is compound joins in the 60g polyurethane solutions; Utilize the reinforcement motor stirrer under 900 rev/mins condition, to stir 4 hours; The mixture that acquisition stirs, wherein carrying the water-insoluble fibroin powder body of heparin sodium medicine and the mass ratio of polyurethane solutions is 1: 15.Utilize medical vacuum cycle water pump that the vacuum in the mixture container is adjusted into-0.5MPa, sealing was placed 1.5 hours, so that remove the steam bubble in the blend.Mixture after the deaeration places 50 degrees centigrade baking oven to carry out drying and moulding.

Specific embodiment 4

At first with clean down fiber at the short flannel that breaks on the rotating blade about 3mm, grind again.Obtain the water-insoluble down-powder of particle diameter below 100 μ m after the grinding.

The 10g heparin sodium is dissolved in the 10g distilled water, and the drug quality percentage ratio that obtains drug level is 50%.After stirring the water-insoluble down-powder of 3.3g is disperseed wherein, the mass ratio of wherein water-insoluble down-powder and heparin sodium pharmaceutical aqueous solution is 1: 6.The mixture of down-powder and medicine soaked 2.5 hours in 25 degrees celsius held.Mixture to down-powder and pharmaceutical aqueous solution carries out drying then, is placed in 60 degrees centigrade the baking oven to heat, until wherein whole distilled water is all got rid of.Dried water-insoluble down-powder is packed into and is pulverized in the omnipotent high speed disintegrator, and the pulverizing time is 8 minutes.

The medical poly (glycolide-co-lactide) of 20g is dissolved in the 80g hexafluoroisopropanol, and the mass percent concentration of polymer is 20% in the polymer solution of acquisition.Water-insoluble down-powder after the 4g heparin sodium is compound joins in the 80g polyurethane solutions; Utilize the reinforcement motor stirrer under 1000 rev/mins condition, to stir 5 hours; The mixture that acquisition stirs, wherein carrying the water-insoluble down-powder of heparin sodium medicine and the mass ratio of polyurethane solutions is 1: 20.Utilize medical vacuum cycle water pump that the vacuum in the mixture container is adjusted into-1MPa, sealing was placed 2 hours, so that remove the steam bubble in the blend.Mixture after the deaeration places 60 degrees centigrade baking oven to carry out drying and moulding.

Specific embodiment 5

It is 1% that the silkworm silk that obtains is placed on mass fraction, and bath raio is to boil 3 hours in 1: 20 the Na2CO3 solution, and the back of coming unstuck fully is clean with 50 degrees centigrade of distilled water washs, dries to obtain fibroin fiber.

The 1g Ahylysantinfarctase is dissolved in the 19g distilled water, and the drug quality percentage ratio that obtains drug level is 5%.After stirring the water-insoluble fibroin powder body of 3.3g is disperseed wherein, the mass ratio of wherein water-insoluble fibroin powder body and heparin sodium pharmaceutical aqueous solution is 1: 6.The mixture of fibroin powder body and medicine soaked 1 hour in 25 degrees celsius held.Mixture to fibroin powder body and pharmaceutical aqueous solution carries out drying then, is placed in 30 degrees centigrade the baking oven to heat, until wherein whole distilled water is all got rid of.Dried water-insoluble fibroin powder body is packed into and is pulverized in the omnipotent high speed disintegrator, and the pulverizing time is 2 minutes.

The 10g medical polyurethane is dissolved in 90g N ' the N-dimethyl acetylamide, and the mass percent concentration of polymer is 10% in the polymer solution of acquisition.Water-insoluble fibroin powder body after the 4g heparin sodium is compound joins in the 40g polyurethane solutions; Utilize the reinforcement motor stirrer under 500 rev/mins condition, to stir 2 hours; The mixture that acquisition stirs, wherein carrying the water-insoluble fibroin powder body of heparin sodium medicine and the mass ratio of polyurethane solutions is 1: 10.Utilize medical vacuum cycle water pump that the vacuum in the mixture container is adjusted into-0.1MPa, 1h is placed in sealing, so that remove the steam bubble in the blend.Mixture after the deaeration places 30 degrees centigrade baking oven to carry out drying and moulding.

Specific embodiment 6

1.5g Ahylysantinfarctase is dissolved in the 18.5g distilled water, the drug quality percentage ratio that obtains drug level is 7.5%.After stirring the water-insoluble fibroin powder body of 3.3g is disperseed wherein, the mass ratio of wherein water-insoluble fibroin powder body and heparin sodium pharmaceutical aqueous solution is 1: 6.The mixture of fibroin powder body and medicine soaked 2 hours in 25 degrees celsius held.Mixture to fibroin powder body and pharmaceutical aqueous solution carries out drying then, is placed in 40 degrees centigrade the baking oven to heat, until wherein whole distilled water is all got rid of.Dried water-insoluble fibroin powder body is packed into and is pulverized in the omnipotent high speed disintegrator, and the pulverizing time is 5 minutes.

The medical polylactic acid of 12g is dissolved in the 88g N ' dinethylformamide, and the mass percent concentration of polymer is 12% in the polymer solution of acquisition.Water-insoluble fibroin powder body after the 4g heparin sodium is compound joins in the 44g polyurethane solutions; Utilize the reinforcement motor stirrer under 800 rev/mins condition, to stir 3 hours; The mixture that acquisition stirs, wherein carrying the water-insoluble fibroin powder body of heparin sodium medicine and the mass ratio of polyurethane solutions is 1: 11.Utilize medical vacuum cycle water pump that the vacuum in the mixture container is adjusted into-0.3MPa, sealing was placed 1.5 hours, so that remove the steam bubble in the blend.Mixture after the deaeration places 40 degrees centigrade baking oven to carry out drying and moulding.

Specific embodiment 7

The 2g heparin sodium is dissolved in the 18g distilled water, and the drug quality percentage ratio that obtains drug level is 10%.After stirring the water-insoluble Pilus Caprae seu Ovis powder body of 3.3g is disperseed wherein, the mass ratio of wherein water-insoluble Pilus Caprae seu Ovis powder body and heparin sodium pharmaceutical aqueous solution is 1: 6.The mixture of Pilus Caprae seu Ovis powder body and medicine soaked 2.5 hours in 25 degrees celsius held.Mixture to Pilus Caprae seu Ovis powder body and pharmaceutical aqueous solution carries out drying then, is placed in 40 degrees centigrade the baking oven to heat, until wherein whole distilled water is all got rid of.Dried water-insoluble Pilus Caprae seu Ovis powder body is packed into and is pulverized in the omnipotent high speed disintegrator, and the pulverizing time is 6 minutes.

Specific embodiment 8

The 3g heparin sodium is dissolved in the 17g distilled water, and the drug quality percentage ratio that obtains drug level is 15%.After stirring the water-insoluble down-powder of 3.3g is disperseed wherein, the mass ratio of wherein water-insoluble down-powder and heparin sodium pharmaceutical aqueous solution is 1: 6.The mixture of down-powder and medicine soaked 2.5 hours in 25 degrees celsius held.Mixture to down-powder and pharmaceutical aqueous solution carries out drying then, is placed in 60 degrees centigrade the baking oven to heat, until wherein whole distilled water is all got rid of.Dried water-insoluble down-powder is packed into and is pulverized in the omnipotent high speed disintegrator, and the pulverizing time is 8 minutes.

Specific embodiment 9

The 10g medical polyurethane is dissolved in the 90g oxolane, and the mass percent concentration of polymer is 10% in the polymer solution of acquisition.Water-insoluble fibroin powder body after the 4g heparin sodium is compound joins in the 40g polyurethane solutions; Utilize the reinforcement motor stirrer under 500 rev/mins condition, to stir 2 hours; The mixture that acquisition stirs, wherein carrying the water-insoluble fibroin powder body of heparin sodium medicine and the mass ratio of polyurethane solutions is 1: 10.Utilize medical vacuum cycle water pump that the vacuum in the mixture container is adjusted into-0.1MPa, 1h is placed in sealing, so that remove the steam bubble in the blend.Mixture after the deaeration places 30 degrees centigrade baking oven to carry out drying and moulding.

Specific embodiment 10

1.2g Ahylysantinfarctase is dissolved in the 18.8g distilled water, the drug quality percentage ratio that obtains drug level is 6%.After stirring the water-insoluble fibroin powder body of 3.3g is disperseed wherein, the mass ratio of wherein water-insoluble fibroin powder body and heparin sodium pharmaceutical aqueous solution is 1: 6.The mixture of fibroin powder body and medicine soaked 2 hours in 25 degrees celsius held.Mixture to fibroin powder body and pharmaceutical aqueous solution carries out drying then, is placed in 40 degrees centigrade the baking oven to heat, until wherein whole distilled water is all got rid of.Dried water-insoluble fibroin powder body is packed into and is pulverized in the omnipotent high speed disintegrator, and the pulverizing time is 5 minutes.

Specific embodiment 11

1.4g heparin sodium is dissolved in the 18.6g distilled water, the drug quality percentage ratio that obtains drug level is 7%.After stirring the water-insoluble Pilus Caprae seu Ovis powder body of 3.3g is disperseed wherein, the mass ratio of wherein water-insoluble Pilus Caprae seu Ovis powder body and heparin sodium pharmaceutical aqueous solution is 1: 6.The mixture of Pilus Caprae seu Ovis powder body and medicine soaked 2.5 hours in 25 degrees celsius held.Mixture to Pilus Caprae seu Ovis powder body and pharmaceutical aqueous solution carries out drying then, is placed in 40 degrees centigrade the baking oven to heat, until wherein whole distilled water is all got rid of.Dried water-insoluble Pilus Caprae seu Ovis powder body is packed into and is pulverized in the omnipotent high speed disintegrator, and the pulverizing time is 6 minutes.

Specific embodiment 12

1.6g heparin sodium is dissolved in the 18.4g distilled water, the drug quality percentage ratio that obtains drug level is 8%.After stirring the water-insoluble down-powder of 3.3g is disperseed wherein, the mass ratio of wherein water-insoluble down-powder and heparin sodium pharmaceutical aqueous solution is 1: 6.The mixture of down-powder and medicine soaked 2.5 hours in 25 degrees celsius held.Mixture to down-powder and pharmaceutical aqueous solution carries out drying then, is placed in 60 degrees centigrade the baking oven to heat, until wherein whole distilled water is all got rid of.Dried water-insoluble down-powder is packed into and is pulverized in the omnipotent high speed disintegrator, and the pulverizing time is 8 minutes.

Specific embodiment 13

Specific embodiment 14

Specific embodiment 15

Specific embodiment 16

Specific embodiment 17

The 10g medical polyurethane is dissolved in the 90g N ' dinethylformamide, and the mass percent concentration of polymer is 10% in the polymer solution of acquisition.Water-insoluble fibroin powder body after the 4g heparin sodium is compound joins in the 40g polyurethane solutions; Utilize the reinforcement motor stirrer under 500 rev/mins condition, to stir 2 hours; The mixture that acquisition stirs, wherein carrying the water-insoluble fibroin powder body of heparin sodium medicine and the mass ratio of polyurethane solutions is 1: 10.Utilize medical vacuum cycle water pump that the vacuum in the mixture container is adjusted into-0.1MPa, 1h is placed in sealing, so that remove the steam bubble in the blend.Mixture after the deaeration places 30 degrees centigrade baking oven to carry out drying and moulding.

Specific embodiment 18

The 2g Ahylysantinfarctase is dissolved in the 18g distilled water, and the drug quality percentage ratio that obtains drug level is 10%.After stirring the water-insoluble fibroin powder body of 3.3g is disperseed wherein, the mass ratio of wherein water-insoluble fibroin powder body and heparin sodium pharmaceutical aqueous solution is 1: 6.The mixture of fibroin powder body and medicine soaked 2 hours in 25 degrees celsius held.Mixture to fibroin powder body and pharmaceutical aqueous solution carries out drying then, is placed in 40 degrees centigrade the baking oven to heat, until wherein whole distilled water is all got rid of.Dried water-insoluble fibroin powder body is packed into and is pulverized in the omnipotent high speed disintegrator, and the pulverizing time is 5 minutes.

Specific embodiment 19

Specific embodiment 20

The 6g heparin sodium is dissolved in the 14g distilled water, and the drug quality percentage ratio that obtains drug level is 30%.After stirring the water-insoluble down-powder of 3.3g is disperseed wherein, the mass ratio of wherein water-insoluble down-powder and heparin sodium pharmaceutical aqueous solution is 1: 6.The mixture of down-powder and medicine soaked 2.5 hours in 25 degrees celsius held.Mixture to down-powder and pharmaceutical aqueous solution carries out drying then, is placed in 60 degrees centigrade the baking oven to heat, until wherein whole distilled water is all got rid of.Dried water-insoluble down-powder is packed into and is pulverized in the omnipotent high speed disintegrator, and the pulverizing time is 8 minutes.

Specific embodiment 21

Specific embodiment 22

Specific embodiment 23

2 heparin sodiums are dissolved in the 18g distilled water, and the drug quality percentage ratio that obtains drug level is 10%.After stirring the water-insoluble Pilus Caprae seu Ovis powder body of 3.3g is disperseed wherein, the mass ratio of wherein water-insoluble Pilus Caprae seu Ovis powder body and heparin sodium pharmaceutical aqueous solution is 1: 6.The mixture of Pilus Caprae seu Ovis powder body and medicine soaked 2.5 hours in 25 degrees celsius held.Mixture to Pilus Caprae seu Ovis powder body and pharmaceutical aqueous solution carries out drying then, is placed in 40 degrees centigrade the baking oven to heat, until wherein whole distilled water is all got rid of.Dried water-insoluble Pilus Caprae seu Ovis powder body is packed into and is pulverized in the omnipotent high speed disintegrator, and the pulverizing time is 6 minutes.

Specific embodiment 24

Specific embodiment 25

Specific embodiment 26

Specific embodiment 27

Specific embodiment 28

The 3g heparin sodium is dissolved in the 7g distilled water, and the drug quality percentage ratio that obtains drug level is 15%.After stirring the water-insoluble down-powder of 3.3g is disperseed wherein, the mass ratio of wherein water-insoluble down-powder and heparin sodium pharmaceutical aqueous solution is 1: 6.The mixture of down-powder and medicine soaked 2.5 hours in 25 degrees celsius held.Mixture to down-powder and pharmaceutical aqueous solution carries out drying then, is placed in 60 degrees centigrade the baking oven to heat, until wherein whole distilled water is all got rid of.Dried water-insoluble down-powder is packed into and is pulverized in the omnipotent high speed disintegrator, and the pulverizing time is 8 minutes.

Specific embodiment 29

Specific embodiment 30

Specific embodiment 31

Specific embodiment 32

Claims

1. water-insoluble protein powder body is the method for preparing of the drug delivery system of pharmaceutical carrier, it is characterized in that the preparation that water-insoluble protein powder body is the drug delivery system of pharmaceutical carrier may further comprise the steps:

A) preparation of pharmaceutical aqueous solution: medicine fully is dissolved in the distilled water, obtains pharmaceutical aqueous solution, and the mass percent of pharmaceutical aqueous solution Chinese medicine is between 5-50%;

B) take the preparation of the non-aqueous soluble protein matter of medicine powder body: the water-insoluble protein powder body of particle diameter less than 100 μ m is immersed in the pharmaceutical aqueous solution of above-mentioned preparation; Stir; Soak time >=1 hour, the mixture with powder body and pharmaceutical aqueous solution is placed in the exsiccator dry then.After removing distilled water, surplus materials is placed in the high speed Universalpulverizer and pulverizes, and pulverizes time 2-8 minute, obtains to take medicated egg white matter medicament powder;

Wherein, described water-insoluble protein powder body is wherein a kind of of following material: fibroin protein powder body, wool protein powder body and eider down protein powder body;

The temperature of described exsiccator is between 30-60 degree centigrade;

C) preparation of polymer solution: polymer fully is dissolved in the solvent, obtains polymer solution, the mass percent of polymer is between 10-20% in the polymer solution;

Wherein, described polymer is wherein a kind of of following material: polyurethane, polylactic acid, gather Acetic acid, hydroxy-, bimol. cyclic ester and poly (glycolide-co-lactide);

Described solvent is wherein a kind of of following solvent: N ' dinethylformamide, oxolane, N ' N-dimethyl acetylamide, 1,4-dioxane, chloroform and hexafluoroisopropanol;

D) take the preparation of the water-insoluble protein powder body of medicine and polymer mixed solution: the water-insoluble protein powder body of medicine of taking of above-mentioned preparation mixes with polymer solution; The use rotating speed is that water-insoluble protein powder body of medicine and mixture of polymers are taken in 500 rev/mins-1000 rev/mins agitator stirring; Stirred 2-5 hour, and made and take the water-insoluble protein powder body of medicine and be dispersed in the polymer solution;

E) above-mentioned preparation take the water-insoluble protein powder body of medicine and polymer mixed solution be placed on vacuum for-0.1Mpa～-environment of 1Mpa in, deaeration 1-2 hour;

F) the mixture drying and moulding of taking water-insoluble protein powder body of medicine and polymer solution after the deaeration;

Wherein baking temperature is controlled at 30-60 degree centigrade.