CN101700240A - Preparation method of captopril bioadhesive sustained-release capsule - Google Patents
Preparation method of captopril bioadhesive sustained-release capsule Download PDFInfo
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- CN101700240A CN101700240A CN200910132794A CN200910132794A CN101700240A CN 101700240 A CN101700240 A CN 101700240A CN 200910132794 A CN200910132794 A CN 200910132794A CN 200910132794 A CN200910132794 A CN 200910132794A CN 101700240 A CN101700240 A CN 101700240A
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- captopril
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- aminopolysaccharide
- release capsule
- sustained
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- 239000002775 capsule Substances 0.000 title claims abstract description 25
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 title claims abstract description 20
- 229960000830 captopril Drugs 0.000 title claims abstract description 20
- 238000013268 sustained release Methods 0.000 title claims abstract description 16
- 239000012730 sustained-release form Substances 0.000 title claims abstract description 16
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 239000000227 bioadhesive Substances 0.000 title claims abstract description 13
- 239000003814 drug Substances 0.000 claims abstract description 29
- 238000001694 spray drying Methods 0.000 claims abstract description 13
- 239000000463 material Substances 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims abstract description 10
- 239000000843 powder Substances 0.000 claims abstract description 8
- -1 carboxymethylamino Chemical group 0.000 claims description 12
- 230000035587 bioadhesion Effects 0.000 claims description 8
- 230000009977 dual effect Effects 0.000 claims description 8
- 239000004005 microsphere Substances 0.000 claims description 7
- 229920002101 Chitin Polymers 0.000 claims description 5
- 239000001856 Ethyl cellulose Substances 0.000 claims description 5
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 5
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 5
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 5
- 230000006196 deacetylation Effects 0.000 claims description 5
- 238000003381 deacetylation reaction Methods 0.000 claims description 5
- 229920001249 ethyl cellulose Polymers 0.000 claims description 5
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 5
- 229940071826 hydroxyethyl cellulose Drugs 0.000 claims description 5
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 5
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 claims description 5
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 claims description 5
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 4
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 4
- 229920001282 polysaccharide Polymers 0.000 claims description 4
- 239000005017 polysaccharide Substances 0.000 claims description 4
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 4
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 3
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 3
- 239000012876 carrier material Substances 0.000 claims description 2
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 2
- 229940079593 drug Drugs 0.000 abstract description 12
- 230000000694 effects Effects 0.000 abstract description 8
- 239000008187 granular material Substances 0.000 abstract description 7
- 239000000203 mixture Substances 0.000 abstract description 7
- 238000001291 vacuum drying Methods 0.000 abstract description 7
- 239000011230 binding agent Substances 0.000 abstract description 5
- 239000002994 raw material Substances 0.000 abstract description 5
- 230000008901 benefit Effects 0.000 abstract description 4
- 239000003995 emulsifying agent Substances 0.000 abstract description 4
- 230000008569 process Effects 0.000 abstract description 3
- 238000012827 research and development Methods 0.000 abstract description 2
- 230000002349 favourable effect Effects 0.000 abstract 2
- 239000006185 dispersion Substances 0.000 abstract 1
- 238000005469 granulation Methods 0.000 abstract 1
- 230000003179 granulation Effects 0.000 abstract 1
- 238000004806 packaging method and process Methods 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 238000012856 packing Methods 0.000 description 12
- 241001597008 Nomeidae Species 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000000080 wetting agent Substances 0.000 description 6
- 210000001035 gastrointestinal tract Anatomy 0.000 description 5
- 230000008676 import Effects 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 102000003886 Glycoproteins Human genes 0.000 description 4
- 108090000288 Glycoproteins Proteins 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000002496 gastric effect Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000000853 adhesive Substances 0.000 description 3
- 230000001070 adhesive effect Effects 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000000265 homogenisation Methods 0.000 description 3
- 230000000968 intestinal effect Effects 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- XBBVURRQGJPTHH-UHFFFAOYSA-N 2-hydroxyacetic acid;2-hydroxypropanoic acid Chemical compound OCC(O)=O.CC(O)C(O)=O XBBVURRQGJPTHH-UHFFFAOYSA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 229920001661 Chitosan Polymers 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- 150000001720 carbohydrates Chemical group 0.000 description 2
- 229960001631 carbomer Drugs 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000001804 emulsifying effect Effects 0.000 description 2
- 210000001156 gastric mucosa Anatomy 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 210000003097 mucus Anatomy 0.000 description 2
- 229920001542 oligosaccharide Polymers 0.000 description 2
- 150000002482 oligosaccharides Chemical class 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 230000009056 active transport Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000005354 coacervation Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- GHVNFZFCNZKVNT-UHFFFAOYSA-M decanoate Chemical compound CCCCCCCCCC([O-])=O GHVNFZFCNZKVNT-UHFFFAOYSA-M 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 235000019832 sodium triphosphate Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 208000018556 stomach disease Diseases 0.000 description 1
- 108010021724 tonin Proteins 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a method for preparing captopril bioadhesive sustained-release capsule, including: aminopolysaccharide is dissolved and then mixed with captopril bulk drug, the mixture is poured into dispersion phase, and emulsifier solution is added in, high pressure homogenizing and spray drying are carried out, pH, in and out air temperature, charging flow and the like of system are controlled, so as to obtain powder microballoon, the microballoon is sieved and then evenly mixed with binding agent, granulation and vacuum drying are carried out, the granules are placed into empty capsules, and packaging is carried out, thus obtaining product of the invention. The invention has the prominent characteristics that the technique has the advantages of simple and stable operation process and available raw materials; the invention also has the great importance that auxiliary material with adhesion and sustained release functions is adopted in preparation of the sustained-release capsule, so that property of capsule is more stable and burst effect is avoided; the material adopted by the invention has favourable biocompatibility and degradability; and the invention is hopeful to develop an ideal medicine for preventing and treating angiocardiopathy and has favourable research and development application prospect.
Description
Technical field: the preparation method that the invention belongs to a kind of captopril bioadhesive sustained-release capsule in new drug development field.
Background technology: captopril (captopril, Cap) be the tonin inhibitor, be widely used in the treatment of hypertension and congestive heart failure clinically. at present, clinical commonly used be coated tablet or the ordinary tablet of water solublity Cap, because its biological half-life only is 1.9h, need day clothes 3-4 time, only can keep 6～8h when taking in to act on when total amount reaches 37.5～75.0mg, single dose po 50mg, peak concentration can reach more than the 600ug/L, and its treatment concentration be this bigger Wave crest and wave trough difference of 50 μ g/L. may be cause dizzy, headache, the main cause of untoward reaction such as intestines and stomach disorder, therefore, for alleviating the Cap untoward reaction, improve the curative effect that Cap prevents and treats cardiovascular disease, press for the slow releasing preparation of developing Cap as early as possible.
In recent years, attempted number of research projects abroad, some has also applied for patent, but only limit in vitro study mostly, clinical data is insufficient, practical application effect does not still have final conclusion, the research of domestic this respect concentrates on the release characteristics research of Cap under traditional slow-release material substantially, but because Cap is soluble in water, discharge than difficult blocked, being prone in the slow releasing agent application process of making dashes forward releases phenomenon, and the minor alteration of pH value will cause tangible pseudo-first-order decomposition reaction, Cap is unstable in the slight alkali environment of small intestinal, easily resolve into different metabolite,, and show different absorption types in gastrointestinal target region location difficulty, some position is an Active transport, some position then needs carrier protein to assist, and absorbs the declined bioavailability of oral administration that is subject to the influence of food and makes medicine, is difficult for making slow releasing agent, therefore, develop ideal Cap slow-released system so far and be still one of modern medicinal agents focus.
There is bibliographical information to utilize microcrystalline Cellulose acetate, polyvinylpyrrolidone, sodium tripolyphosphate prepares the film coating slow releasing tablet, utilize hydrogel to prepare the pulse controlled release system and adopt complex coacervation to prepare microcapsule medicine-releasing system etc. with the ethyl cellulose of different viscosities, but owing to exist the gastrointestinal tract holdup time shorter, can not carry out long medicine location in the gastrointestinal absorption zone discharges, high amount of drug discharges in the gastrointestinal tract bottom, drug absorption is insufficient, and medicine is unstable under the alkaline environment of small intestinal bottom, easily decompose, cause bioavailability to reduce, degradation under the curative effect, so far do not see the clinical application research report. in addition, still the slow-release material that has bibliographical information to use insoluble polymer to add some hydrophobic implants prepares the Cap slow releasing agent, a kind of mobile equilibrium system of floating in gastrointestinal tract of bibliographical information is also arranged, the Cap Atrigel of also with good grounds adhesive systems hypothesis preparation, its purpose is the holdup time of raising system at the effective absorption site of gastrointestinal tract, to increase the bioavailability of Cap, improve curative effect, but because result of the test is mainly still disputable based on practical application effect in its body of in vitro tests.
The slow release medicine-releasing system that the very difficult imagination can not be kept enough gastrointestinal tract holdup times and stability can produce satisfied bioavailability, the prominent slow release medicine-releasing system of releasing problem of water soluble drug that can not solve really more hard to imagine has gratifying vivo effect. therefore, we think development Cap Atrigel, at effective control Cap rate of release, overcome that water soluble drug is prominent and release tendency in, must guarantee that Cap is in the operating stability of intestinal and enough gastrointestinal holdup times.
In view of above consideration the present invention adopts Study of New Method to prepare captopril bioadhesive sustained-release capsule, this invention prevents and treats the cardiovascular disease effect, reduces untoward reaction, overcomes to dash forward and release phenomenon and provide new manufacturing technology for developing ideal water-soluble drug sustained release system for improving Cap, has huge social benefit and economic benefit.
Summary of the invention: it is the method that main carrier auxiliary material prepares bioadhesive sustained-release capsule with the aminopolysaccharide derivant that the purpose of this invention provides a kind of, to remedy the deficiency of prior art.
It is raw material that the present invention mainly adopts aminopolysaccharide (chitosan) derivant and Cap; its concrete grammar is earlier the aminopolysaccharide derivant to be dissolved; after under stirring condition, aminopolysaccharide derivative solution and Cap crude drug being mixed; be poured in the decentralized photo solution; and to wherein adding solution such as emulsifying agent; high pressure homogenize is fully emulsified; vacuum defoamation; import spray-drying pelleting machine; pass through control reaction temperature; the system acid-base value; homogenization pressure and emulsifying and deaeration time and spray-drying pelleting machine inlet temperature; leaving air temp; feed rate; sample introduction temperature etc.; promptly obtain captopril slow release powder microsphere; sieve after with have bioadhesion and medicament slow release dual function carrier auxiliary material; the binding agent mix homogeneously; reuse 75% ethanol is made granule as wetting agent; through low-temperature vacuum drying; the Capsules of packing into No. 1, packing promptly gets product of the present invention.
The present invention has easy to operate, the easy advantage such as stable and cheap for manufacturing cost of preparing technique process. the present invention has extensive applicability to raw material, all chitin derivants with free amine group all can be suitable for. therefore, raw material sources of the present invention are very extensive. and significance of the present invention also is to have adopted in the captopril bioadhesive sustained-release capsule preparation saccharide residue that has bioadhesion and medicament slow release dual function and be easy on the glycoprotein oligosaccharide connection to form hydrogen bond, produce stronger mucus gel networks, with the stronger adhesive attraction of gastric mucosa glycoprotein tool. carrier auxiliary material, the result makes the capsule performance of preparation more stable, the stomach adhesiveness is stronger, reaching gastric Cap location discharges, having overcome the prominent phenomenon of releasing that the water-soluble drug sustained-release preparation is prone to. the material safety that the present invention adopts has no side effect, has excellent biological compatibility, biodegradability, characteristics such as filming performance is good. the present invention is expected to develop the ideal medicament of a kind of treatment and angiocardiopathy preventing, have good research and development application prospect. therefore, this invention technology has fine economic development potentiality.
The specific embodiment: it is raw material that the present invention adopts aminopolysaccharide (chitosan) derivant; dissolving earlier obtains the solution of aminopolysaccharide derivant; the concentration of aminopolysaccharide derivative solution is 4%-12%; can use the deacetylation scope is 50%-98%; molecular weight is 20; 000Da-2; 000; the aminopolysaccharide of 00Da and derivant thereof; the addition of Cap is 0.1-6 a times of aminopolysaccharide; under stirring condition, aminopolysaccharide derivative solution and aspirin crude drug are mixed; be poured in the decentralized photo; mixeding liquid volume can be the 1/6-1/24 of decentralized photo; to wherein adding emulsifying agent; high pressure homogenize is fully emulsified; vacuum defoamation; import spray-drying pelleting machine; pass through control reaction temperature; the system acid-base value; mixing speed and emulsifying and deaeration time and spray-drying pelleting machine sample introduction temperature; the sample introduction flow; inlet temperature; leaving air temp; promptly obtain captopril slow release powder microsphere; sieve after with have bioadhesion and medicament slow release dual function carrier auxiliary material; the binding agent mix homogeneously, reuse 75% ethanol is made granule as wetting agent, through low-temperature vacuum drying; the Capsules of packing into No. 1, packing promptly gets product of the present invention.
The acid-base value of aminopolysaccharide, Cap mixed solution can be pH 1-12, homogenization pressure can be 10-50MPa, homogenizing time can be 30-120s, in order to make mixed solution fully emulsified, homogenization pressure can be 40-70mpa, and homogenizing time can be 90-180s, reaction temperature can be 5-60 ℃, deaeration time 5-10min, in order to make the abundant deaeration of solution, the deaeration time can extend to 8-15min.
Consider that Cap meets easily oxidation of heat, water solublity is higher, slow release capsule preparation is easy to occur the prominent phenomenon of releasing of medicine, adopted the saccharide residue that has bioadhesion and medicament slow release dual function and be easy on the glycoprotein oligosaccharide connection to form hydrogen bond, produce stronger mucus gel networks, with the stronger adhesive attraction of gastric mucosa glycoprotein tool. carrier auxiliary material, make the capsule performance more stable, has bioadhesion and medicament slow release dual function carrier material can be a microcrystalline Cellulose, hydroxypropyl emthylcellulose (HPMC), carboxymethyl cellulose (CMC), hydroxypropylmethyl cellulose phthalate (HPMCP), ethyl cellulose (EC), hydroxyethyl-cellulose (HEC), addition can be 1: 3-1: 5; The reagent of employed adjusting pH can be 10% ammonium bicarbonate, also can be sodium hydroxide, ammonia, potassium hydroxide, hydrochloric acid, acetic acid; Employed decentralized photo can be a dilute hydrochloric acid solution, also can be acetum; Employed emulsifying agent can be a Tween 80, also can be span, sodium lauryl sulphate. employed binding agent can be PVPK30, carbomer, carboxymethyl cellulose.
Spray condition: the sample introduction temperature can be 10-70 ℃, and the sample introduction flow can be 50-500ml/min, and inlet temperature can be 100-300 ℃, and leaving air temp can be 10-100 ℃.
The slow release powder microsphere that the spray drying mode obtains sieve after with have bioadhesion and medicament slow release dual function carrier auxiliary material, binding agent mix homogeneously, reuse 75% ethanol is made granule as wetting agent, through low-temperature vacuum drying, the Capsules of packing into No. 1, packing promptly gets product of the present invention.
Aminopolysaccharide derivant of the present invention can comprise part deacetylation chitin, whole deacetylation chitin (being aminopolysaccharide), carboxymethylamino polyose, hydroxyethylamino polysaccharide, hydroxypropyl aminopolysaccharide, aminopolysaccharide doped quaternary ammonium salt, polyvinyl alcohol graft copolymerized aminopolysaccharide etc.
The specific embodiment is given an example:
Embodiment 1
Carboxymethylamino polyose is dissolved; after under stirring condition, carboxymethylamino polyose solution and Cap crude drug being mixed; be poured in the dilute hydrochloric acid solution; and to wherein adding a certain amount of Tween 80 solution; regulate pH; the 10MPa homogenizing is fully emulsified; vacuum defoamation 8min imports spray-drying pelleting machine, regulates the spray drying parameter to be: 10 ℃ of sample introduction temperature; sample introduction flow 50ml/min; 100 ℃ of inlet temperature; 10 ℃ of leaving air temps; promptly obtain captopril slow release powder microsphere; sieve after and HPMCP; the carbomer mix homogeneously, reuse 75% ethanol is made granule as wetting agent, through low-temperature vacuum drying; the Capsules of packing into No. 1, packing promptly gets product of the present invention.
Embodiment 2
With polyvinyl alcohol graft copolymerized aminopolysaccharide dissolving; after under stirring condition, polyvinyl alcohol graft copolymerized aminopolysaccharide solution and Cap crude drug being mixed; be poured in 5% acetum; and to wherein adding a certain amount of span solution; regulate pH; the 30MPa homogenizing is fully emulsified; vacuum defoamation 10min; import spray-drying pelleting machine; regulating the spray drying parameter is: 50 ℃ of sample introduction temperature; sample introduction flow 200ml/min; 200 ℃ of inlet temperature; 50 ℃ of leaving air temps; promptly obtain captopril slow release powder microsphere; sieve after and HPMC; the PVPK30 mix homogeneously, reuse 75% ethanol is made granule as wetting agent, through low-temperature vacuum drying; the Capsules of packing into No. 1, packing promptly gets product of the present invention.
Embodiment 3
The hydroxyethylamino polysaccharide is dissolved; after under stirring condition, hydroxyethylamino polysaccharide solution and Cap crude drug being mixed; be poured in 20% acetum; and to wherein adding a certain amount of sodium dodecyl sulfate solution; regulate pH; the 50MPa homogenizing is fully emulsified; vacuum defoamation 15min; import spray-drying pelleting machine; regulating the spray drying parameter is: 70 ℃ of sample introduction temperature; sample introduction flow 500ml/min; 300 ℃ of inlet temperature; 100 ℃ of leaving air temps; promptly obtain captopril slow release powder microsphere; sieve after and HEC; the carboxymethyl cellulose mix homogeneously, reuse 75% ethanol is made granule as wetting agent, through low-temperature vacuum drying; the Capsules of packing into No. 1, packing promptly gets product of the present invention.
Claims (5)
1. the preparation method of a captopril bioadhesive sustained-release capsule.
2. the preparation method of a kind of captopril bioadhesive sustained-release capsule according to claim 1, what its captopril slow release powder method for preparing microsphere adopted is spray drying method.
3. the preparation method of a kind of captopril bioadhesive sustained-release capsule according to claim 1 has added in its bioadhesive sustained-release capsule preparation and has had bioadhesion and medicament slow release dual function carrier auxiliary material.
4. the preparation method of a kind of captopril bioadhesive sustained-release capsule according to claim 1, its described aminopolysaccharide comprise part deacetylation chitin, all deacetylation chitin (being aminopolysaccharide), carboxymethylamino polyose, hydroxyethylamino polysaccharide, hydroxypropyl aminopolysaccharide, aminopolysaccharide doped quaternary ammonium salt, polyvinyl alcohol graft copolymerized aminopolysaccharide etc.
5. added in the preparation of a kind of captopril bioadhesive sustained-release capsule according to claim 3 and had bioadhesion and medicament slow release dual function carrier material comprises microcrystalline Cellulose, hydroxypropyl emthylcellulose (HPMC), carboxymethyl cellulose (CMC), hydroxypropylmethyl cellulose phthalate (HPMCP), ethyl cellulose (EC), hydroxyethyl-cellulose (HEC).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910132794A CN101700240A (en) | 2009-04-14 | 2009-04-14 | Preparation method of captopril bioadhesive sustained-release capsule |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910132794A CN101700240A (en) | 2009-04-14 | 2009-04-14 | Preparation method of captopril bioadhesive sustained-release capsule |
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| Publication Number | Publication Date |
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| CN101700240A true CN101700240A (en) | 2010-05-05 |
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| CN200910132794A Pending CN101700240A (en) | 2009-04-14 | 2009-04-14 | Preparation method of captopril bioadhesive sustained-release capsule |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105560212A (en) * | 2016-03-24 | 2016-05-11 | 长沙佰顺生物科技有限公司 | Method for preparing captopril microcapsule |
| CN108743565A (en) * | 2018-07-04 | 2018-11-06 | 青岛科技大学 | A kind of preparation method of acetylsalicylic acid site specific DDS for colon bioadhesive sustained-release capsule |
-
2009
- 2009-04-14 CN CN200910132794A patent/CN101700240A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105560212A (en) * | 2016-03-24 | 2016-05-11 | 长沙佰顺生物科技有限公司 | Method for preparing captopril microcapsule |
| CN108743565A (en) * | 2018-07-04 | 2018-11-06 | 青岛科技大学 | A kind of preparation method of acetylsalicylic acid site specific DDS for colon bioadhesive sustained-release capsule |
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