CN103656606A - Polypeptide colon-targeted drug delivery preparation and preparation method thereof - Google Patents

Polypeptide colon-targeted drug delivery preparation and preparation method thereof Download PDF

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CN103656606A
CN103656606A CN201210351286.9A CN201210351286A CN103656606A CN 103656606 A CN103656606 A CN 103656606A CN 201210351286 A CN201210351286 A CN 201210351286A CN 103656606 A CN103656606 A CN 103656606A
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preparation
parts
polypeptide
weight
colon
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郭丽
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TIANJIN JIAHONG TECHNOLOGY Co Ltd
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TIANJIN JIAHONG TECHNOLOGY Co Ltd
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Abstract

The invention discloses a colon-targeted drug delivery preparation of hemalbumin polypeptide, which is an orally taken preparation for releasing the drug at a colon part, and prepared by coating a drug-containing pellet containing the hemalbumin polypeptide component with colon-targeted coating liquor or directly filling the drug-containing pellet into a colon-targeted capsule shell, wherein the drug-containing pellet consists of the following components in parts by weight: 60-92 parts of drug powder containing the hemalbumin polypeptide component, 5-25 parts of sucrose, 3-15 parts of povidone K30; and the drug powder comprises the following components in parts by weight: 10-100 parts of hemalbumin polypeptide and 0-90 parts of other drugs and/or nutrients. The preparation disclosed by the invention is a colon release drug with target zone drug concentration higher than that of other tissues, enters blood circulation through the colon, can effectively avoid metabolism destruction of peptide drugs of common orally-taken preparation in the stomach to bring treatment effect of the drug into full play, and is safe and convenient to take orally.

Description

One peptide species colon targeting drug administration preparation and preparation method thereof
Technical field
The invention belongs to and prepare biological medicament technical field, relate to a kind of colon targeting preparation, more particularly refer to colon targeting preparation of a kind of haemproteins polypeptide and preparation method thereof.
Background technology
Blood powder is divided into plasma powder and blood cell powder, and wherein blood cell accounts for 2/3.The blood powder resource of China is very abundant, if the blood of more than the 10 hundred million boss poultrys of butchering every year can, by efficient recovery, can be produced blood cell powder and surpass 200,000,000 kg every year.But at present, the blood after butchering is done edible or makes feedstuff or produce haemachrome, superoxide dismutase, thrombin for biochemical pharmacy except small part, very major part is used as garbage and directly discharges, contaminated environment.Therefore, how reasonably to utilize the animal blood in slaughterhouse, improve its use value, this is very important to the scientific development of Animal Product Processing Industry.In the developed country such as European, Japanese, the utilization rate of Sanguis sus domestica has reached more than 50%, and they are mainly exploitation peptide class reagent, peptide medicament and functional food and food additive.
Nowadays due to the developing rapidly of biological enzyme technology, utilize protease hydrolysis Sanguis sus domestica also more and more to improve the research of its utilization rate.Find after deliberation, the protein hydrolysate of Sanguis sus domestica has many different physiologically actives.At present, the protease kind of available hydrolysis Sanguis sus domestica is a lot, through enzyme, decomposes and porcine haemoglobin matter can be resolved into the mixture such as aminoacid, peptide, peptone, haemachrome with fragranced.Think that at present peptides from swine blood has following function: (1) immune-enhancing activity, has the function that significantly improves immunity of organism defence; (2) in stimulation bone marrow, grain is unicellular, strengthens the oxidative metabolism of ripe neutrophilic granulocyte, and strengthens its phagocytosis.(3) Scavenger of ROS and lipoid peroxidization resistant.Therefore peptides from swine blood can be used as enrich blood, medicine or the health product of hemopoietic, the auxiliary treatment while also can be used as tumor patient radiotherapy.But, oral protein polypeptide drug was often just lost activity by protease hydrolysis numerous in gastrointestinal tract before being absorbed, therefore, such medicine all adopts the administering mode of intramuscular injection or intravenous drip, but so, give patient, especially need the patient of long-term prescription, brought many troubles and misery.
The Proteolytic enzyme enzyme concentration at colon position is much smaller than other sections of digestive tract, and medicine is longer in this position time of staying, and the resistance that colon wall penetrates macromole is also little than small bowel, is conducive to drug absorption.Therefore the oral administration that, colon targeting drug administration system is protein and peptide drugs provides optimal absorption place.Because colonic segment motion is very slow, therefore can be regarded as the sealing " compartment " being formed by all unabsorbed nutrients, moisture, metabolite.Medicine can be in this formation " bank " of concentrating, and absorb thus human blood, thereby guarantee that medicine is absorbed (zero level absorption curve) with constant speed.This feature can guarantee that protein and peptide synchronizes absorption all the time at this position with short absorbent, make medicine in whole absorption phase in absorbing state stably.In sum, colon targeting drug administration is one of the most effective approach of albumen and peptide medicament oral application: 1. medicine in time of staying of colon long and colon surface amass and can partly improve greatly the shortcoming of its mucosa poor permeability; 2. absorption enhancer time of staying in colon long, can more effectively promote the large intestinal absorption of this class medicine; 3. the albumen at human body ileocecus or following position or peptide medicament are aided with suitable absorption enhancer again, with the administration of oral colon-target medicine-feeding technology, do not need to use the proteinase inhibitor just can oral application.On domestic market, there is not yet the colon targeting preparation of haemproteins polypeptide, also have no the research report of this preparation.Therefore developing this class preparation not only has important clinical meaning, but also has wide market prospect.
Summary of the invention
The first problem that the present invention need to solve is to provide that a kind for the treatment of comprises anemia, cancer radiation low leukocyte counts, immunity reduces and has the colon targeting preparation of the haemproteins polypeptide of anti-aging effects.
Another problem that the present invention need to solve is to provide a kind of preparation method of producing the colon targeting preparation of above-mentioned haemproteins polypeptide.
Disclosed by the invention theing contents are as follows:
One peptide species colon targeting drug administration preparation, adopt segmented intestine targeted coating solution to carry out coating or described pastille micropill is directly packed into the oral formulations in the release of colon position of making in segmented intestine targeted capsule shells the pastille micropill that contains haemproteins polypeptide composition, it is characterized in that: described pastille micropill is comprised of the medicated powder that contains haemproteins polypeptide composition, sucrose and PVP K30, and the ratio of weight and number of each component is: 60~92 parts, medicated powder, 5~25 parts of sucrose, 3~15 parts of PVP K30s; Described medicated powder is by weight: 0~90 part of 10~100 parts of haemproteins polypeptide, other medicines and/or nutrient.
Wherein said other medicines and/or nutrient are: one or two or more kinds of calcium, magnesium, vitamin A, vitamin B, vitamin C, vitamin D, vitamin E, Golden jujube, Mel, Radix Salviae Miltiorrhizae, Fructus Schisandrae Chinensis, Fructus Jujubae mixes.
The granularity of described pastille micropill is at 10~3000 μ m, and described coatings weight is 2~62% of pastille micropill weight.Preferred proportion is 12%.The granularity of finished product micropill is at 10~3000 μ m, preferred size 600~800 μ m.
The raw material that described segmented intestine targeted coating solution contains following parts by weight: Eudragit E UDRAGIT S100 and Eudragit E UDRAGIT are 5~25 parts of 60~90 parts, 1~15 part of triethyl citrate and Pulvis Talci; Wherein the ratio of weight and number of Eudragit E UDRAGIT S100 and Eudragit E UDRAGIT L100 is 1: 1.5.
The raw material that described segmented intestine targeted coatings contains following parts by weight: 4~25 parts of 65~95 parts of Opadries, 1~10 part of triethyl citrate and Pulvis Talci.
The raw material that described segmented intestine targeted coatings contains following parts by weight: 5~25 parts of hydroxypropyl emthylcellulose HPMC75~95 part and pectin.
The present invention further discloses the preparation method of polypeptide colon targeting drug administration preparation, it is characterized in that being undertaken by following step:
The first step, the medicated powder that preparation contains haemproteins polypeptide composition;
Second step, is placed in medicated powder in centrifugal coating granulator, and spray mass concentration (g/mL) is 40~60% sucrose syrup moistening medicated powder, controls whitewashing flow, and 40~70 ℃ of forced air dryings, make 60~80 order ball cores;
The 3rd step, the mass concentration (g/mL) of take is that the alcoholic solution of 1~5% dimension polyketone K30 is adhesive, for powder machine, to ball core, sprays medicated powder, control the feed ratio of adhesive and medicated powder, make ball core be increased to the micropill of 10~3000 μ m, oven dry is sieved, and obtains pastille micropill;
The 4th step, prepares segmented intestine targeted coating solution;
The 5th step, the pastille micropill that the 3rd step is obtained is placed in centrifugal coating granulator, to micropill, sprays segmented intestine targeted coating solution; 40~70 ℃ of forced air dryings; coatings weight be pastille micropill weight 2~62% time stop whitewashing, oven dry is sieved, and obtains the segmented intestine targeted type preparation of haemproteins polypeptide.
Wherein the 4th step is prepared the concrete steps of segmented intestine targeted coating solution and is: by each component as claimed in claim 5, drop into successively in 80% ethanol and to dissolve the alcoholic solution that is mixed with the acrylic resin that mass concentration (g/mL) is 10%, stir, cross 80 mesh sieves, obtain the segmented intestine targeted coating solution of pH dependent form.
The concrete steps that the 4th step is prepared segmented intestine targeted coating solution are: by each component as claimed in claim 5, drop into successively in 80% ethanol and to dissolve the alcoholic solution that is mixed with the Opadry that mass concentration (g/mL) is 8%, stir, cross 80 mesh sieves, obtain the segmented intestine targeted coating solution of pH dependent form.
The concrete steps that the 4th step is prepared segmented intestine targeted coating solution are: by each component as claimed in claim 6, successively in dissolved water, stir, cross 80 mesh sieves, be mixed with the aqueous solution of the hydroxypropyl emthylcellulose that mass concentration (g/mL) is 30%, obtain the segmented intestine targeted coating solution of enzyme dependent form.
The preferred version of the preparation method of the colon targeting drug administration preparation of haemproteins polypeptide of the present invention is:
The acrylic resin that is 60~95% by percentage by weight, 1~15% triethyl citrate, 5%~25% talcous solid material, drop into successively in 80% ethanol and to dissolve the alcoholic solution that is mixed with the acrylic resin that mass concentration (g/mL) is 10%, stir, cross 80 mesh sieves, obtain the segmented intestine targeted coating solution of pH dependent form, wherein the weight ratio of acrylic resin S100 and acrylic resin L100 is 1: 1.5.
Another preferred version as the preparation method of the colon targeting drug administration preparation of haemproteins polypeptide of the present invention is:
The Opadry that is 65~95% by percentage by weight, 1~10% triethyl citrate, 5~25% talcous solid material, drop into successively in 80% ethanol and to dissolve the alcoholic solution that is mixed with the Opadry that mass concentration (g/mL) is 8%, stir, cross 80 mesh sieves, obtain the segmented intestine targeted coating solution of pH dependent form.
The 3rd preferred version as the preparation method of the colon targeting drug administration preparation of haemproteins polypeptide of the present invention is:
The hydroxypropyl emthylcellulose that is 75~95% by percentage by weight, during 5~25% pectin dissolves successively, in water, stir, cross 80 mesh sieves, be mixed with the aqueous solution of the hydroxypropyl emthylcellulose that mass concentration (g/mL) is 30%, obtain the segmented intestine targeted coating solution of enzyme dependent form.
The good effect that utilizes polypeptide colon targeting drug administration preparation compared with prior art to have disclosed by the invention is:
1, preparation of the present invention adopts oral administration, avoids the misery of the long-term acupuncture injection of patient, improves compliance, the safer convenience of oral administration.
2, preparation of the present invention is that colon discharges medicine, and target area drug level is higher than its hetero-organization, and per rectum enters blood circulation, can effectively avoid the peptide medicament of common oral preparation to destroy in the metabolism of stomach, gives full play to the therapeutical effect of medicine.
3, the drug molecule in colon targeting preparation of the present invention does not discharge at stomach; thereby protection drug molecule is not destroyed by gastric acid and gastric enzyme, arrives behind colon position, and the drug coating layer of pH dependent form or enzyme dependent form is destroyed; disintegrate discharges medicine, and drug molecule is absorbed and enters blood circulation.Haemproteins polypeptide has the function that significantly improves immunity of organism defence; Can also stimulate in bone marrow grain unicellular, strengthen the oxidative metabolism of ripe neutrophilic granulocyte, and strengthen its phagocytosis, and without obvious adverse reaction; Can be used as enrich blood, medicine or the health product of hemopoietic, the auxiliary treatment while also can be used as tumor patient radiotherapy.
The specific embodiment
Below in conjunction with embodiment, the present invention is described, the scheme of embodiment described here, do not limit the present invention, one of skill in the art can make improvements and change according to spirit of the present invention, these described improvement and variation all should be considered as within the scope of the invention, and scope of the present invention and essence are limited by claim.The present invention's various reagent used all has commercially available.Contained haemproteins polypeptide raw material wide material sources in the present invention, have a variety of production methods, and the method for producing haemproteins polypeptide does not belong to the scope that the present invention protects, therefore repeat no more.
The colon targeting preparation of haemproteins polypeptide of the present invention, adopt segmented intestine targeted coating solution to carry out coating or described pastille micropill is directly packed into the oral formulations in the release of colon position of making in segmented intestine targeted capsule shells the pastille micropill that contains haemproteins polypeptide composition, it is characterized in that: described pastille micropill is comprised of the medicated powder that contains haemproteins polypeptide composition, sucrose and PVP K30, and the weight ratio of each component is: medicated powder 60~92%, sucrose 5~25%, PVP K30 3~15%; Described medicated powder is by weight: haemproteins polypeptide 10~100%, other medicines and/or nutrient 0~90%.Other medicines and/or nutrient are that one or two or more kinds of calcium, magnesium, vitamin A, vitamin B, vitamin C, vitamin D, vitamin E, Golden jujube, Mel, Radix Salviae Miltiorrhizae, Fructus Schisandrae Chinensis, Fructus Jujubae etc. mixes.
The granularity of described pastille micropill is at 10~3000 μ m, and described coatings weight is 2~62% of pastille micropill weight.
The preparation method of preparing the colon targeting drug administration preparation of haemproteins polypeptide of the present invention, the steps include:
The first step, the medicated powder that preparation contains haemproteins polypeptide composition;
Second step, is placed in medicated powder in centrifugal coating granulator, and spray mass concentration (g/mL) is 40~60% sucrose syrup moistening medicated powder, controls whitewashing flow, and 40~70 ℃ of forced air dryings, make 60~80 order ball cores;
The 3rd step, the mass concentration (g/mL) of take is that the alcoholic solution of 1~5% dimension polyketone K30 is adhesive, for powder machine, to ball core, sprays medicated powder, control the feed ratio of adhesive and medicated powder, make ball core be increased to the micropill of 10~3000 μ m, oven dry is sieved, and obtains pastille micropill;
The 4th step, prepares segmented intestine targeted coating solution;
The 5th step, the pastille micropill that the 3rd step is obtained is placed in centrifugal coating granulator, to micropill, sprays segmented intestine targeted coating solution; 40~70 ℃ of forced air dryings; coatings weight be pastille micropill weight 2~62% time stop whitewashing, oven dry is sieved, and obtains the segmented intestine targeted type preparation of haemproteins polypeptide.
Embodiment 1
Take 20 grams of standby haemproteins polypeptide lyophilized powder and 10 grams of Fructus Jujubaes, 0.2 gram of vitamin B; be mixed into compound recipe medicated powder; put in centrifugal coating granulator, then spray 50% sucrose syrup moistening, 40~70 ℃ of forced air dryings 4 hours; make 60~80 order ball cores; the alcoholic solution of 3% PVP K30 of take is adhesive, by for powder machine to ball core spray medicated powder, make ball core be increased to the micropill of 500~800 μ m; oven dry is sieved, and obtains pastille micropill.Controlling the wherein percentage by weight of each component is: compound recipe medicated powder 60 %, sucrose 25%, PVP K30 15%.
Take 60 grams of acrylic resin S100, join in 800 milliliter of 80% alcoholic solution stirring and dissolving, add successively again 7 grams of triethyl citrates and 12 grams of Pulvis Talci, stirring and evenly mixing, crosses the solution of gained after 80 order steel sieves, makes the segmented intestine targeted coating solution of pH dependent form.
Prepared pastille micropill is put in centrifugal coating granulator, to micropill, sprayed the coating solution that said method makes, 40~70 ℃ of forced air dryings 1~3 hour, stop whitewashing when coatings increases weight 12% time, and oven dry is sieved, and obtains segmented intestine targeted type preparation.
Embodiment 2
Take 25 grams of standby haemproteins polypeptide lyophilized powder, 4 grams of Fructus Lycii crude drug; 1.2 grams of vitamin Bs, are mixed into compound recipe medicated powder, put in centrifugal coating granulator; spray again 50% sucrose syrup moistening; 40~70 ℃ of forced air dryings 4 hours, make 60~80 order ball cores, and the alcoholic solution of 3% PVP K30 of take is adhesive; by spraying medicated powder for powder machine to ball core; make ball core be increased to the micropill of 100~500 μ m, oven dry is sieved, and obtains pastille micropill.Controlling the wherein percentage by weight of each component is: compound recipe medicated powder 92 %, sucrose 5%, PVP K30 3%.
Take 60 grams of acrylic resins, wherein the weight ratio of acrylic resin S100 and acrylic resin L100 is 1: 1.5, join in 800 milliliter of 80% alcoholic solution, stirring and dissolving, add successively again 11 grams of triethyl citrates and 4 grams of Pulvis Talci, stirring and evenly mixing, crosses the solution of gained after 80 order steel sieves, makes the segmented intestine targeted coating solution of pH dependent form.
Prepared pastille micropill is put in centrifugal coating granulator, to micropill, sprayed the coating solution that said method makes, 40~70 ℃ of forced air dryings 1~3 hour, coatings increases weight 15% time and stops whitewashing, and oven dry is sieved, and obtains segmented intestine targeted type preparation.
Embodiment 3
Take standby 160 grams of haemproteins polypeptide lyophilized powder and 160 grams of Fructus Schisandrae Chinensis; pulverizing is mixed into compound recipe medicated powder; put in centrifugal coating granulator, then spray 50% sucrose syrup moistening, 40~70 ℃ of forced air dryings 4 hours; make 60~80 order ball cores; the alcoholic solution of 3% PVP K30 of take is adhesive, by for powder machine to ball core spray medicated powder, make ball core be increased to the micropill of 800~1000 μ m; oven dry is sieved, and obtains pastille micropill.Controlling the wherein percentage by weight of each component is: compound recipe medicated powder 80%, sucrose 15%, PVP K30 5%.
Take 600 grams of acrylic resins, wherein the weight ratio of acrylic resin S100 and acrylic resin L100 is 1: 1.5, join in 10000 milliliter of 80% alcoholic solution, stirring and dissolving, add successively again 70 grams of triethyl citrates and 120 grams of Pulvis Talci, stirring and evenly mixing, the solution of gained is crossed 80 order steel sieves and is made the segmented intestine targeted coating solution of pH dependent form.
Prepared pastille micropill is put in centrifugal coating granulator, to micropill, sprayed the coating solution make as stated above, 40~70 ℃ of forced air dryings 1~3 hour, coatings increases weight 18% time and stops whitewashing, and oven dry is sieved, and obtains segmented intestine targeted type preparation.
Embodiment 4
Take standby 200 grams of haemproteins polypeptide lyophilized powder and 120 grams of Radix Salviae Miltiorrhizaes; pulverizing is mixed into compound recipe medicated powder; put in centrifugal coating granulator, then spray 50% sucrose syrup moistening, 40~70 ℃ of forced air dryings 4 hours; make 60~80 order ball cores; the alcoholic solution of 3% PVP K30 of take is adhesive, by for powder machine to ball core spray medicated powder, make ball core be increased to the micropill of 1000~1200 μ m; oven dry is sieved, and obtains pastille micropill.Controlling the wherein percentage by weight of each component is: compound recipe medicated powder 75%, sucrose 25%, PVP K30 5%.
Take 600 grams of Opadries, join in 10000 milliliter of 80% alcoholic solution, stirring and dissolving, then add successively 85 grams of triethyl citrates and 171 grams of Pulvis Talci, stirring and evenly mixing, the solution of gained to cross 80 order steel sieves to make the segmented intestine targeted coating solution of pH dependent form.
Prepared pastille micropill is put in centrifugal coating granulator, to micropill, sprayed the coating solution make as stated above, 40~70 ℃ of forced air dryings 1~3 hour, coatings increases weight 12% time and stops whitewashing, and oven dry is sieved, and obtains segmented intestine targeted type preparation.
Embodiment 5
Take 80 grams of haemproteins polypeptide lyophilized powder; put in centrifugal coating granulator; spray again 50% sucrose syrup moistening medicated powder; 40~70 ℃ of forced air dryings 4 hours, make 60~80 order ball cores, and the alcoholic solution of 3% PVP K30 of take is adhesive; by spraying medicated powder for powder machine to ball core; make ball core be increased to the micropill of 600~900 μ m, oven dry is sieved, and obtains pastille micropill.Controlling the wherein percentage by weight of each component is: lyophilizing medicated powder 90%, sucrose 6%, PVP K30 4%.
Take 200 grams of hydroxypropyl emthylcelluloses, join in 700 ml waters, stirring and dissolving, then add 10 grams of pectin, stirring and evenly mixing, solution to cross 80 order steel sieves to make the segmented intestine targeted coating solution of enzyme dependent form.
Prepared pastille micropill is put in centrifugal coating granulator, to micropill, sprayed the coating solution make as stated above, 40~70 ℃ of forced air dryings 1~3 hour, coatings increases weight 12% time and stops whitewashing, and oven dry is sieved, and obtains segmented intestine targeted type preparation.
Embodiment 6
Use the method for preparing pastille micropill in above-described embodiment to make pastille micropill, then by this pastille micropill fill in segmented intestine targeted capsule shells, fill specification be every containing 50~300 milligrams of haemproteins polypeptide, obtain the capsule of segmented intestine targeted type preparation.

Claims (10)

1. a peptide species colon targeting drug administration preparation, adopt segmented intestine targeted coating solution to carry out coating or described pastille micropill is directly packed into the oral formulations in the release of colon position of making in segmented intestine targeted capsule shells the pastille micropill that contains haemproteins polypeptide composition, it is characterized in that: described pastille micropill is comprised of the medicated powder that contains haemproteins polypeptide composition, sucrose and PVP K30, and the ratio of weight and number of each component is: 60~92 parts, medicated powder, 5~25 parts of sucrose, 3~15 parts of PVP K30s; Described medicated powder is by weight: 0~90 part of 10~100 parts of haemproteins polypeptide, other medicines and/or nutrient.
2. polypeptide colon targeting drug administration preparation claimed in claim 1, is characterized in that: described other medicines and/or nutrient are: one or two or more kinds of calcium, magnesium, vitamin A, vitamin B, vitamin C, vitamin D, vitamin E, Golden jujube, Mel, Radix Salviae Miltiorrhizae, Fructus Schisandrae Chinensis, Fructus Jujubae mixes.
3. polypeptide colon targeting drug administration preparation described in claim 2, is characterized in that: the granularity of described pastille micropill is at 10~3000 μ m, and described coatings weight is 2~62% of pastille micropill weight.
4. polypeptide colon targeting drug administration preparation claimed in claim 3, is characterized in that the raw material that described segmented intestine targeted coating solution contains following parts by weight:
Eudragit E UDRAGIT S100 and Eudragit E UDRAGIT are 5~25 parts of 60~90 parts, 1~15 part of triethyl citrate and Pulvis Talci; Wherein the ratio of weight and number of Eudragit E UDRAGIT S100 and Eudragit E UDRAGIT L100 is 1: 1.5.
5. polypeptide colon targeting drug administration preparation described in claim 3, is characterized in that the raw material that described segmented intestine targeted coatings contains following parts by weight: 4~25 parts of 65~95 parts of Opadries, 1~10 part of triethyl citrate and Pulvis Talci.
6. polypeptide colon targeting drug administration preparation claimed in claim 3, is characterized in that the raw material that described segmented intestine targeted coatings contains following parts by weight: 5~25 parts of hydroxypropyl emthylcellulose HPMC75~95 part and pectin.
7. the preparation method of a peptide species colon targeting drug administration preparation, is characterized in that being undertaken by following step:
(1) medicated powder that preparation contains haemproteins polypeptide composition;
(2) medicated powder is placed in centrifugal coating granulator, spray mass concentration (g/mL) is 40~60% sucrose syrup moistening medicated powder, controls whitewashing flow, and 40~70 ℃ of forced air dryings, make 60~80 order ball cores;
(3) take mass concentration (g/mL) is that the alcoholic solution of 1~5% dimension polyketone K30 is adhesive, for powder machine, to ball core spray medicated powder, control the feed ratio of adhesive and medicated powder, make ball core be increased to the micropill of 10~3000 μ m, oven dry is sieved, and obtains pastille micropill;
(4) prepare segmented intestine targeted coating solution;
(5) the pastille micropill the 3rd step being obtained is placed in centrifugal coating granulator; to micropill, spray segmented intestine targeted coating solution, 40~70 ℃ of forced air dryings, coatings weight be pastille micropill weight 2~62% time stop whitewashing; oven dry is sieved, and obtains the segmented intestine targeted type preparation of haemproteins polypeptide.
8. preparation method claimed in claim 7, it is characterized in that step (4) prepares the concrete steps of segmented intestine targeted coating solution and be: by each component as claimed in claim 5, drop into successively in 80% ethanol and to dissolve the alcoholic solution that is mixed with the acrylic resin that mass concentration (g/mL) is 10%, stir, cross 80 mesh sieves, obtain the segmented intestine targeted coating solution of pH dependent form.
9. preparation method claimed in claim 7, the concrete steps that it is characterized in that the segmented intestine targeted coating solution of step (4) are: by each component as claimed in claim 5, drop into successively in 80% ethanol and to dissolve the alcoholic solution that is mixed with the Opadry that mass concentration (g/mL) is 8%, stir, cross 80 mesh sieves, obtain the segmented intestine targeted coating solution of pH dependent form.
10. preparation method claimed in claim 7, it is characterized in that: the concrete steps that step (4) is prepared segmented intestine targeted coating solution are: by each component as claimed in claim 6, successively in dissolved water, stir, cross 80 mesh sieves, be mixed with the aqueous solution of the hydroxypropyl emthylcellulose that mass concentration (g/mL) is 30%, obtain the segmented intestine targeted coating solution of enzyme dependent form.
CN201210351286.9A 2012-09-20 2012-09-20 Polypeptide colon-targeted drug delivery preparation and preparation method thereof Pending CN103656606A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110200147A (en) * 2019-06-20 2019-09-06 重庆凡特施特生物科技有限公司 A kind of sustained release composite polymineral and its processing technology
CN110974943A (en) * 2019-12-09 2020-04-10 广东药科大学 Oral insulin pharmaceutical preparation and preparation method thereof

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110200147A (en) * 2019-06-20 2019-09-06 重庆凡特施特生物科技有限公司 A kind of sustained release composite polymineral and its processing technology
CN110974943A (en) * 2019-12-09 2020-04-10 广东药科大学 Oral insulin pharmaceutical preparation and preparation method thereof

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Application publication date: 20140326