CN109106695A - A kind of preparation method of the segmented intestine targeted sustained-release micro-spheres of brufen - Google Patents
A kind of preparation method of the segmented intestine targeted sustained-release micro-spheres of brufen Download PDFInfo
- Publication number
- CN109106695A CN109106695A CN201811197044.2A CN201811197044A CN109106695A CN 109106695 A CN109106695 A CN 109106695A CN 201811197044 A CN201811197044 A CN 201811197044A CN 109106695 A CN109106695 A CN 109106695A
- Authority
- CN
- China
- Prior art keywords
- brufen
- spheres
- preparation
- release micro
- mixed phase
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Abstract
The invention discloses a kind of preparation methods of the segmented intestine targeted sustained-release micro-spheres of brufen, using polyelectrolyte composite algorithm-ionic cross-linking joint technology, the water-soluble polysaccharide of chitosan and surface with anion is set to form the double-layered compound film of compact structure, insoluble drug brufen is wrapped in the capsule core of microballoon, processing is also coated to microballoon using acid resistant material simultaneously, to reduce the release of drug in the gastrointestinal tract, the colon targeting drug administration of brufen is realized.The present invention not only effectively reduces the side effect of brufen in the gastrointestinal tract, but also extends the half-life period of drug in vivo, it is made more fully to play a role.The advantages that present invention also has preparation process simple, mild condition, environmental protection, drug safety is high.
Description
Technical field
The invention belongs to pharmaceutical fields, and in particular to a kind of preparation method of the segmented intestine targeted sustained-release micro-spheres of brufen.
Background technique
Oral administration is to apply the main approach of drug, have many advantages, such as to be easy to be administered, flexibility height, compliance it is good,
But there is also fewer defects, such as have first pass effect and reduce the bioavilability of drug, for proteins and peptides class medicine
Object efficiently use drug cannot because being easily degraded in stomach and small intestine.
Oral colon specific targeting drug-delivery system (OCDDS) be by certain galenic pharmacy means, make drug by oral administration after do not exist
Upper gi tract release just starts to be disintegrated to colon site or erosion solution releases drug, not only can increase drug in target
To the concentration in site, locally or systemically therapeutic effect is played, higher drug bioavailability and effective rate of utilization are obtained, and
Many adverse reactions of the drug after systemic Absorption can also be reduced.The good characteristics such as targeting and sustained release based on OCDDS, it is not
Only can be used as proteins and peptides class drug administration route or targeted therapy ulcerative colitis, intestines worm, constipation and
The important channel of the colonic diseases such as colon cancer.
Brufen is a kind of alkylbenzene propionic non-steroid antiphlogistic, is widely used in anti-inflammatory, analgesia, antipyretic, antirheumatic etc..
But due to brufen poorly water-soluble, biological half-life is shorter, and maintenance therapy concentration needs frequent drug administration and increases its gastrointestinal tract
Adverse reaction, while also increasing the detrimental effect to kidney.Sustained release preparation such as, which is made, in brufen can reduce medicining times,
The compliance of patient's medication is improved, and mitigates the adverse reaction of drug.
The reported in literature of existing ibuprofen slow-release microballoon at present, but sodium alginate is mostly used, gelatin, chitosan etc. is capsule
Material, and microballoon is prepared using water-in-oil emulsion-solvent evaporated method, ionic cross-linking etc., prepared microballoon is mostly monofilm
Structure, micro-sphere structure is not fine and close enough, is easy to discharge under one's belt, is unable to colon targeting drug administration.And the present invention is with chitosan and surface
Water-soluble polysaccharide with anion is compound capsule material, and wherein surface band is cationic in acid condition for chitosan, can be with surface band
The water-soluble polysaccharide of anion occurs polyelectrolyte reaction and generates compound, then solidifies life under the action of small molecule crosslinking agent
At the microballoon of inside and outside double membrane structure, the micro-sphere structure is finer and close, and stability is more preferable under one's belt.In addition, polyeletrolyte is multiple
Closing object also has many advantages, such as low interfacial tension, good diffusion and plasticity, and good biocompatibility, thus
It is a kind of good biomaterial, has a wide range of applications and study in terms of pharmaceutical carrier.
Summary of the invention
The object of the present invention is to provide a kind of preparation methods of the segmented intestine targeted sustained-release micro-spheres of brufen, multiple using polyelectrolyte
Legal-ionic cross-linking joint technology makes the water-soluble polysaccharide of chitosan and surface with anion form the bilayer of compact structure
Brufen is wrapped in the capsule core of microballoon by composite membrane, while being also coated processing to microballoon using acid resistant material, into one
Step reduces the release of drug in the gastrointestinal tract, to realize the colon targeting drug administration of brufen.
Above-mentioned purpose is realized by using following technical scheme:
A kind of preparation method of the segmented intestine targeted sustained-release micro-spheres of brufen, it the following steps are included:
(1) chitosan is dissolved in the acid solution that pH is 3-6, adds brufen, be vortexed and ultrasonic treatment makes to disperse
Uniformly, it is configured to the interior mixed phase that chitosan concentration is 10-50mg/mL, ibuprofen concentration is 50-125mg/mL；
(2) it is dissolved after mixing on surface with crosslinking agent with the water-soluble polysaccharide of anion with water, is configured to water-soluble polysaccharide
The outer mixed phase that concentration is 5-12.5mg/mL, crosslinker concentration is 2.5-10mg/mL；
(3) interior mixed phase is added dropwise in outer mixed phase, the volume ratio of interior mixed phase and outer mixed phase is 1:5-20, is stirred
After mixing solidification, precipitating is washed with deionized, is freeze-dried, the drug bearing microsphere that partial size is 1.5-2mm is obtained；
(4) obtained drug bearing microsphere coating solution made of acid resisting material is coated, makes coating weight gain 10-
100% to get the segmented intestine targeted sustained-release micro-spheres of brufen.
Preferably, the pH of the acid solution is 3.5.
Preferably, in the interior mixed phase, chitosan concentration 30mg/mL, ibuprofen concentration 50mg/mL.
Preferably, in the outer mixed phase, Carboxymethyl Konjac Glucomannan concentration is 7.5mg/mL, crosslinker concentration is
2.5mg/mL。
Preferably, water-soluble polysaccharide of the surface with anion is selected from sodium alginate, cellulose sodium sulfate, chondroitin sulfate
Element, xanthan gum, Carboxymethyl Konjac Glucomannan, most preferably Carboxymethyl Konjac Glucomannan.
Preferably, the crosslinking agent is sodium tripolyphosphate.
Preferably, the volume ratio of the interior mixed phase and outer mixed phase is 1:10.
Preferably, the coating solution is by polyacrylic resinⅡ, polyacrylic resinⅢ, dehydrated alcohol, lemon triethylenetetraminehexaacetic acid
Ester composition, mass ratio are (1-3): (4-8): (15-25): (5-10).
It is further preferred that the polyacrylic resinⅡ, polyacrylic resinⅢ, dehydrated alcohol, triethyl citrate
Mass ratio be 2:6:21:8.25.
Preferably, the coating weight gain is 78%.
Compared with prior art, the present invention has the advantage that
1) by the water-soluble polysaccharide by the chitosan and surface of surface band cation with anion poly- electricity occurs for the present invention
Solve qualitative response generate compound, then crosslinking agent sodium tripolyphosphate effect under by electrostatic interaction formation compact structure,
Drug bearing microsphere with double membrane structure efficiently coats insoluble drug brufen wherein, while microsphere surface is through resistance to
The segmented intestine targeted controlled release that drug is realized after acid layer coating, effectively reduces the side effect of brufen in the gastrointestinal tract, and
Performance with enzyme degradation targeting drug release and sustained release in simulation colonic fluid, can extend the half-life period of drug in vivo, sufficiently send out
Wave drug effect.
2) use microballoon prepared by the present invention for macroscopic millimeter rank, encapsulation rate and drugloading rate with higher,
Curative effect of medication can not only be improved, taking dose is reduced, moreover it is possible to improve product yield, reduce production cost.
3) wall material used in the present invention is from a wealth of sources, cheap and easily-available, has good biocompatibility and degradability,
Catabolite is nontoxic in vivo, can be metabolized safely；And the mild condition of microballoon is prepared, method is easy, without using organic molten
Agent will not introduce noxious material, therefore product is more safe and environment-friendly.
Detailed description of the invention
Fig. 1 is the SEM image of brufen drug bearing microsphere.
Fig. 2 is release profiles of the segmented intestine targeted sustained-release micro-spheres of brufen in 1.2 simulate the gastric juice of pH (SGF).
Fig. 3 is the segmented intestine targeted sustained-release micro-spheres of brufen respectively in the phosphate buffer solution (PBS) of pH 6.8 and in pH 6.8
Simulation colonic fluid (SCF) in release profiles.
Specific embodiment
The present invention is described in detail below by specific embodiment.
Embodiment 1
The preparation method of the segmented intestine targeted sustained-release micro-spheres of brufen, steps are as follows:
(1) chitosan is dissolved in 1% (v/v) acetic acid solution, adjusts pH to 3.5, adds brufen, be vortexed and surpass
Sound is uniformly dispersed, and is configured to the interior mixed phase that chitosan concentration is 30mg/mL, ibuprofen concentration is 50mg/mL.
(2) Carboxymethyl Konjac Glucomannan and sodium tripolyphosphate are dissolved with water, is configured to Carboxymethyl Konjac Glucomannan
The outer mixed phase that concentration is 7.5mg/mL, tripolyphosphate na concn is 2.5mg/mL.
(3) under magnetic stirring (500-600r/min), inner aqueous phase is added dropwise in outer aqueous phase with syringe, it is interior mixed
Closing mutually is 1:10 with the volume ratio of outer mixed phase, continues stirring solidification 15min, then with deionized water by washing of precipitate 3 times, then
It is freeze-dried the brufen drug bearing microsphere that 2h is 1.5-2mm to get partial size.
Be measured with partial size of the vernier caliper to drug bearing microsphere, measure made drug bearing microsphere average grain diameter be 1.79 ±
0.02mm.It is characterized using microstructure of the scanning electron microscope to drug bearing microsphere, from Fig. 1 (A) as can be seen that carrying medicine
The monnolithic case of microballoon compares rounding, the smooth densification of the membrane structure on surface；Fig. 1 (B-C) is respectively the section of drug bearing microsphere and cuts
Face hollows out figure, it is evident that microballoon has double membrane structure from figure, inside is in typical capsule core shape；Fig. 1 (D) is that load medicine is micro-
Ball internal bladder/nuclear structure sectional view, it is internal in fine and close reticular structure, mainly crosslinking agent sodium tripolyphosphate and chitosan
The result of entanglement；Fig. 1 (E) is internal bladder/nuclear structure enlarged section, it can be seen from the figure that also inlaying in reticular structure
Embedded with ibuprofen crystal, form is consistent with pure ibuprofen crystal (Fig. 1 F), shows that drug mainly exists in the form of crystal
In microballoon.
Using the determination of ibuprofen in ultraviolet specrophotometer measurement drug bearing microsphere, drug encapsulation is then calculated according to content
Rate and drugloading rate, wherein encapsulation rate refers to that the brufen total amount in drug bearing microsphere accounts for the percentage of brufen inventory, carries medicine
Amount refers to the brufen weight contained in every 1mg drug bearing microsphere.The entrapment efficiency for the drug bearing microsphere being calculated is
76.74%, drugloading rate is 510.23 μ g/mg, and yield and medicament contg have all reached higher level.
(4) by polyacrylic resinⅡ (L100), polyacrylic resinⅢ (S100), dehydrated alcohol and triethyl citrate
(TEC) stirring and dissolving is made into coating solution, mass ratio 2:6:21:8.25.Then drug bearing microsphere is wrapped with coating solution
Clothing makes drug bearing microsphere weight gain 78% to get the segmented intestine targeted sustained-release micro-spheres of brufen.
Acid resistance detection is carried out to the segmented intestine targeted sustained-release micro-spheres of brufen, Fig. 2 is simulate the gastric juice of the drug in pH 1.2
(SGF) release conditions of 2h in；Fig. 3 is drug in the phosphate buffer solution (PBS) of pH 6.8 and the simulation colonic fluid of pH 6.8
(SCF) release conditions in.
From figure 2 it can be seen that burst size of the 2h in the buffer of pH 1.2 illustrates this only 8% or so before drug
The sustained-release micro-spheres of invention preparation have good acid resistance, drug can be protected not to be decomposed in gastric acid.It can from 3
Out, drug slow release in PBS, 8h Cumulative release amount are that 74.68%, 23h reaches peak value 93.33%；And 8h is tired in SCF
Burst size 96.81% is counted, reaches peak value 99.94% for 24 hours.Two curve comparisons can be seen that drug and can sufficiently release in SCF
Put, and slow release effect is more preferable, this is because contain 'beta '-mannase in SCF, and Carboxymethyl Konjac Glucomannan have compared with
More enzyme binding sites in conjunction with 'beta '-mannase and can occur localized degradation, so that micro-sphere structure is become loose, be conducive to medicine
Object spreads and dissolves out from capsule/core-membrane structure, so that the Cumulative release amount of its unit time be made to increase, shows tool of the present invention
There is the performance of enzyme degradation drug release.And due to being free of enzyme in PBS, drug release is very slow, and cumulative release amount is not high, to guarantee
Drug can be targeted to colon.
Embodiment 2
(1) chitosan is dissolved in the acetic acid solution that pH is 4.5, adds brufen, be vortexed and ultrasonic, be uniformly dispersed,
It is configured to the interior mixed phase that chitosan concentration is 20mg/mL, ibuprofen concentration is 75mg/mL.
(2) sodium alginate is dissolved with water respectively with sodium tripolyphosphate, be configured to sodium alginate concentration be 12.5mg/mL,
Tripolyphosphate na concn is the outer mixed phase of 5mg/mL.
(3) under magnetic stirring, inner aqueous phase is added dropwise in outer aqueous phase with syringe, interior mixed phase and outer mixed phase
Volume ratio be 1:8, continue stirring solidification 30min, then with deionized water by washing of precipitate 3 times, be then freeze-dried 3h to get
Brufen drug bearing microsphere.
The entrapment efficiency of drug bearing microsphere is 64.24%, and drugloading rate is 432.15 μ g/mg.
(4) by polyacrylic resinⅡ (L100), polyacrylic resinⅢ (S100), dehydrated alcohol and triethyl citrate
(TEC) stirring and dissolving is made into coating solution, mass ratio 3:4:25:5.Then drug bearing microsphere is coated with coating solution, is made
Drug bearing microsphere weight gain 100% is to get the segmented intestine targeted sustained-release micro-spheres of brufen.
Through detecting, in the simulation colonic fluid of pH 6.8,8h Cumulative release amount is that 88.14%, 18h reaches peak value.
Embodiment 3
(1) chitosan is dissolved in the acetic acid solution that pH is 5.5, adds brufen, be vortexed and ultrasonic, be uniformly dispersed,
It is configured to the interior mixed phase that chitosan concentration is 45mg/mL, ibuprofen concentration is 125mg/mL.
(2) chondroitin sulfate is dissolved with water respectively with sodium tripolyphosphate, be configured to chondroitin sulfate concentration be 5mg/mL,
Tripolyphosphate na concn is the outer mixed phase of 10mg/mL.
(3) under magnetic stirring, interior mixed phase is added dropwise in outer mixed phase with syringe, interior mixed phase is mixed with outer
The volume ratio for closing phase is 1:20, continues stirring solidification 15min, then be then freeze-dried washing of precipitate 3 times with deionized water
2h is to get brufen drug bearing microsphere.
The entrapment efficiency of drug bearing microsphere is 53.12%, and drugloading rate is 407.14 μ g/mg.
(4) by polyacrylic resinⅡ (L100), polyacrylic resinⅢ (S100), dehydrated alcohol and triethyl citrate
(TEC) stirring and dissolving is made into coating solution, mass ratio 1:8:15:10.Then drug bearing microsphere is coated with coating solution,
Make drug bearing microsphere weight gain 20% to get the segmented intestine targeted sustained-release micro-spheres of brufen.
It through detecting, is discharged in the simulation colonic fluid of pH 6.8,8h Cumulative release amount is that 91.34%, 20h reaches peak value.
Embodiment 4
(1) chitosan is dissolved in the acetic acid solution that pH is 3, adds brufen, be vortexed and ultrasonic, be uniformly dispersed, match
The interior mixed phase that chitosan concentration is 10mg/mL, ibuprofen concentration is 60mg/mL is made.
(2) cellulose sodium sulfate is dissolved with water respectively with sodium tripolyphosphate, being configured to cellulose sulfate na concn is
6mg/mL, the outer mixed phase that tripolyphosphate na concn is 3mg/mL.
(3) under magnetic stirring, inner aqueous phase is added dropwise in outer aqueous phase with syringe, interior mixed phase and outer mixed phase
Volume ratio be 1:5, continue stirring solidification 15min, then drug-loaded biological microballoon wash 3 times with deionized water, then freezing is done
Dry 2h is to get brufen drug bearing microsphere.
The entrapment efficiency of drug bearing microsphere is 54.25%, and drugloading rate is 424.13 μ g/mg.
(4) by polyacrylic resinⅡ (L100), polyacrylic resinⅢ (S100), dehydrated alcohol and triethyl citrate
(TEC) stirring and dissolving is made into coating solution, mass ratio 2:5:18:6.Then drug bearing microsphere is coated with coating solution, is made
Drug bearing microsphere weight gain 60% is to get the segmented intestine targeted sustained-release micro-spheres of brufen.
It through detecting, is discharged in the simulation colonic fluid of pH 6.8,8h Cumulative release amount is that 91.68%, 16h reaches peak value.
Claims (10)
1. a kind of preparation method of the segmented intestine targeted sustained-release micro-spheres of brufen, it is characterised in that the following steps are included:
(1) chitosan is dissolved in the acid solution that pH is 3-6, adds brufen, be vortexed and ultrasonic treatment makes to be uniformly dispersed,
It is configured to the interior mixed phase that chitosan concentration is 10-50mg/mL, ibuprofen concentration is 50-125mg/mL；
(2) it is dissolved after mixing on surface with crosslinking agent with the water-soluble polysaccharide of anion with water, is configured to water-soluble polysaccharide concentration
The outer mixed phase for being 2.5-10mg/mL for 5-12.5mg/mL, crosslinker concentration；
(3) interior mixed phase is added dropwise in outer mixed phase, the volume ratio of interior mixed phase and outer mixed phase is 1:5-20, and stirring is solid
After change, precipitating is washed with deionized, is freeze-dried, the drug bearing microsphere that partial size is 1.5-2mm is obtained；
(4) obtained drug bearing microsphere coating solution made of acid resisting material is coated, makes coating weight gain 10-100%, i.e.,
Obtain the segmented intestine targeted sustained-release micro-spheres of brufen.
2. the preparation method of the segmented intestine targeted sustained-release micro-spheres of brufen as described in claim 1, it is characterised in that: the acid solution
PH be 3.5.
3. the preparation method of the segmented intestine targeted sustained-release micro-spheres of brufen as described in claim 1, it is characterised in that: the interior mixed phase
In, chitosan concentration 30mg/mL, ibuprofen concentration 50mg/mL.
4. the preparation method of the segmented intestine targeted sustained-release micro-spheres of brufen as described in claim 1, it is characterised in that: the outer mixed phase
In, Carboxymethyl Konjac Glucomannan concentration is 7.5mg/mL, crosslinker concentration 2.5mg/mL.
5. the preparation method of the segmented intestine targeted sustained-release micro-spheres of brufen as described in claim 1, it is characterised in that: the surface band yin
The water-soluble polysaccharide of ion is sweet poly- selected from sodium alginate, cellulose sodium sulfate, chondroitin sulfate, xanthan gum, carboxy methyl konjaku Portugal
Sugar, preferably Carboxymethyl Konjac Glucomannan.
6. the preparation method of the segmented intestine targeted sustained-release micro-spheres of brufen as described in claim 1, it is characterised in that: the crosslinking agent is
Sodium tripolyphosphate.
7. the preparation method of the segmented intestine targeted sustained-release micro-spheres of brufen as described in claim 1, it is characterised in that: the interior mixed phase
Volume ratio with outer mixed phase is 1:10.
8. the preparation method of the segmented intestine targeted sustained-release micro-spheres of brufen as described in claim 1, it is characterised in that the coating solution by
Polyacrylic resinⅡ, polyacrylic resinⅢ, dehydrated alcohol, triethyl citrate composition, mass ratio is (1-3): (4-8):
(15-25):(5-10)。
9. the preparation method of the segmented intestine targeted sustained-release micro-spheres of brufen as claimed in claim 8, it is characterised in that: the polyacrylic acid
Resin II, polyacrylic resinⅢ, dehydrated alcohol, triethyl citrate mass ratio be 2:6:21:8.25.
10. the preparation method of the segmented intestine targeted sustained-release micro-spheres of brufen as described in claim 1, it is characterised in that: the coating increases
Weight is 78%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811197044.2A CN109106695B (en) | 2018-10-15 | 2018-10-15 | Preparation method of ibuprofen colon-targeted sustained-release microspheres |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811197044.2A CN109106695B (en) | 2018-10-15 | 2018-10-15 | Preparation method of ibuprofen colon-targeted sustained-release microspheres |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109106695A true CN109106695A (en) | 2019-01-01 |
| CN109106695B CN109106695B (en) | 2020-09-22 |
Family
ID=64854274
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811197044.2A Active CN109106695B (en) | 2018-10-15 | 2018-10-15 | Preparation method of ibuprofen colon-targeted sustained-release microspheres |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109106695B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111195232A (en) * | 2020-01-15 | 2020-05-26 | 浙江工业大学 | double-pH-sensitive mesalazine colon-targeted sustained-release solid dispersion and preparation method thereof |
| CN112245409A (en) * | 2020-10-23 | 2021-01-22 | 安徽大学 | Vegetable protein-ursodesoxycholic acid sustained-release nanoparticle composite microcapsule and preparation method thereof |
| CN114288272A (en) * | 2021-12-29 | 2022-04-08 | 佛山职业技术学院 | Preparation method of colon-targeted microcapsule |
-
2018
- 2018-10-15 CN CN201811197044.2A patent/CN109106695B/en active Active
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111195232A (en) * | 2020-01-15 | 2020-05-26 | 浙江工业大学 | double-pH-sensitive mesalazine colon-targeted sustained-release solid dispersion and preparation method thereof |
| CN111195232B (en) * | 2020-01-15 | 2022-03-18 | 浙江工业大学 | double-pH-sensitive mesalazine colon-targeted sustained-release solid dispersion and preparation method thereof |
| CN112245409A (en) * | 2020-10-23 | 2021-01-22 | 安徽大学 | Vegetable protein-ursodesoxycholic acid sustained-release nanoparticle composite microcapsule and preparation method thereof |
| CN112245409B (en) * | 2020-10-23 | 2022-03-15 | 安徽大学 | Vegetable protein-ursodesoxycholic acid sustained-release nanoparticle composite microcapsule and preparation method thereof |
| CN114288272A (en) * | 2021-12-29 | 2022-04-08 | 佛山职业技术学院 | Preparation method of colon-targeted microcapsule |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109106695B (en) | 2020-09-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Prasher et al. | Current-status and applications of polysaccharides in drug delivery systems | |
| EP2630955B1 (en) | Immediate release and sustained release ibuprofen dosing regimen | |
| EP1916995B2 (en) | Ph-controlled pulsatile delivery system, methods for preparation and use thereof | |
| JPS61501151A (en) | Diffusion coated multiple unit dose | |
| JP2008511611A (en) | Therapeutic 4-phenylbutyric acid controlled release formulation | |
| CN109106695A (en) | A kind of preparation method of the segmented intestine targeted sustained-release micro-spheres of brufen | |
| CN103417515B (en) | Biodegradable nanoparticle-entrapped oral colon-targeted micro-capsule and preparation method thereof | |
| WO2002064148A2 (en) | Oral formulations containing mucopolysaccharide for small intestine delivery and their use in the treatment circulatory disorders | |
| JP2008513383A (en) | Oral pharmaceutical composition for the targeted delivery of platinum complexes to the colorectal region, process for its preparation and its use as a medicament | |
| Shashni et al. | Design of enzyme-responsive short-chain fatty acid-based self-assembling drug for alleviation of type 2 diabetes mellitus | |
| Zhu et al. | Recent advances on drug delivery nanoplatforms for the treatment of autoimmune inflammatory diseases | |
| Xu et al. | Microparticles based on alginate/chitosan/casein three‐dimensional system for oral insulin delivery | |
| Ramana | Preparation and In-vitro characterization of ethylcellulose coated pectin alginate microspheres of 5-fluorouracil for colon targeting | |
| Sabra et al. | Gastrointestinal delivery of APIs from chitosan nanoparticles | |
| US20080305174A1 (en) | Polymeric nanocapsules for use in drug delivery | |
| EP2632428B1 (en) | Modified starch derivative-based matrix for colon targeting | |
| Assifaoui et al. | Pectin as drug-release vehicle | |
| Singh et al. | Harmonious biomaterials for development of in situ approaches for locoregional delivery of anti-cancer drugs: current trends | |
| CN101181273A (en) | Method for preparing chitosan-polyasparagic acid-5efudix nano particle | |
| AU2019334434A1 (en) | Controlled drug release formulation | |
| CA3060026A1 (en) | Polymer based formulation for release of drugs and bioactives at specific git sites | |
| El-Sherbiny et al. | Hydrogels for pulmonary drug delivery | |
| WO1998024412A2 (en) | Compounds useful against diseases of the colon and methods for orally administering same | |
| Ahmari et al. | A green approach for preparation of chitosan/hydroxyapatite/graphitic carbon nitride hydrogel nanocomposite for improved 5-FU delivery | |
| Jana et al. | Alginate-Based Gastrointestinal Tract Drug Delivery Systems |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |