KR101983653B1 - Pharmaceutical carrier compositions for intra-articular injection - Google Patents
Pharmaceutical carrier compositions for intra-articular injection Download PDFInfo
- Publication number
- KR101983653B1 KR101983653B1 KR1020150052264A KR20150052264A KR101983653B1 KR 101983653 B1 KR101983653 B1 KR 101983653B1 KR 1020150052264 A KR1020150052264 A KR 1020150052264A KR 20150052264 A KR20150052264 A KR 20150052264A KR 101983653 B1 KR101983653 B1 KR 101983653B1
- Authority
- KR
- South Korea
- Prior art keywords
- polymer
- carrier
- core
- glycolide
- drug
- Prior art date
Links
Images
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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
- A61K9/1647—Polyesters, e.g. poly(lactide-co-glycolide)
Abstract
The present invention relates to a carrier for an articular cavity-administered drug.
Description
The present invention relates to a carrier for an articular cavity-administered drug.
Clinical studies have been attempted to directly inject drugs such as NSAIDs, which have analgesic effects, into joints for the purpose of relieving the pain of patients with osteoarthritis as well as pain complaints after joint surgery.
However, it has been reported that when the drug solution is simply administered to joints as a method of treating osteoarthritis, the drug rapidly flows out from the joint synovial fluid to the blood, and the treatment effect is only a few hours. This is due to the very thin and discontinuous structure of the joint synovial fluid, and there is a wide gap between the synovial cells of 0.1 ~ 5.5 ㎛, which causes the problem that the drugs administered in the joints are easily disappeared.
Therefore, some pharmacological approaches have been attempted to prevent the rapid loss of drugs injected into joints and to improve the retention of joints. Among them, microparticle - based retention enhancement studies were carried out to minimize the outflow into synovial intercellular space and to control drug release by loading drugs in the size of 0.5 ~ 100 ㎛. However, it is known that such a method is recognized as an external substance by the immune system in the tissue, is predated and rapidly removed from the synovial fluid, and may cause a foreign body feeling and discomfort in the joint.
Another approach, nanoparticle-based studies, has the problem of failing to effectively control efflux through synovial spaces. In the case of a reversible gel forming system based on a gel or tissue environment, most of the biodegradable or biocompatible substances have not been identified, and the drug release control function is weak, so that the drug can not be released for a long time.
Existing studies have limitations in improving the retention of drugs through physical or immunological elimination mechanisms in the joints.
Accordingly, it is an object of the present invention to provide a carrier for drug-administered drugs, which is excellent in biocompatibility and biodegradability and is excellent in the control of drug release.
In order to accomplish the above object, the present invention provides a core polymer; A cationic polymer that is non-covalently mixed at one end with the core polymer and the opposite end provides positive charge to the surface of the carrier; And a coating polymer encapsulating a part or the whole of the surface of the core polymer. According to a preferred embodiment of the present invention, the carrier for articular projected drug is in the form of microspheres, and the average diameter may be 50 nm to 20 탆.
The carrier for a drug-administered drug according to the present invention exhibits a positive charge on the surface thereof, thereby forming an electrostatic binding aggregate with an anionic polymer in the joint cavity. Through this, it is possible to prevent physical leakage through synovial intercellular spaces, minimize recognition and capture from immune cells, and improve retention in joints.
Furthermore, it can be utilized as a differentiated intra-articular drug delivery system in the future.
Brief Description of the Drawings Fig. 1 (a) is an optical image of a microscope of an aggregate formed by an electrostatic reaction with a hyaluronic acid, an anionic polymer in vivo, of a carrier of Example 1, Fig. 1 (b) (C) is an image obtained by merging (a) and (b) of the carrier of Example 1, and FIG.
FIG. 2 (a) is an image of an optical microscope after mixing the carrier of Comparative Example 2 with hyaluronic acid which is an anionic polymer in vivo, and FIG. 2 (b) is an image of the carrier of Comparative Example 2 using a multi- (C) is an image obtained by merging (a) and (b).
3 is a graph showing the evaluation of retention in the joint cavity of Experimental Example 3;
Hereinafter, the present invention will be described in detail. The following detailed description is merely an example of the present invention, and therefore, the present invention is not limited thereto.
Existing studies have limitations in improving the retention of drugs through physical or immunological elimination mechanisms in the joints.
Therefore, the present inventors have made an effort to improve the biocompatibility and biodegradability and to control the release of the drug. A core polymer for controlling drug release, and a cationic polymer having one end thereof non-covalently mixed with the core polymer and the other end providing a positive charge on the surface of the carrier, whereby the anionic biopolymer present in the joint cavity and the electrostatic Thereby allowing crosslinking to be formed. In addition, since the carrier for drug-administered drugs of the present invention is nanoparticles and exhibits positive charge, it provides physical dispersion stability of particles through electrostatic repulsion.
Thus, it has been confirmed that the micro-aggregate formation can be induced and the retention of the nanoparticles in the joint cavity can be drastically improved through physical and immunological avoidance mechanisms. Thus, the present invention has been completed.
That is, the present invention relates to a core polymer; A cationic polymer, one end of which is mixed non-covalently with the core polymer and the other end of which is positively charged on the surface of the carrier; And a coating polymer encapsulating a part or the whole of the surface of the core polymer.
The characteristics and kinds of each component of the present invention will be described below.
Core polymer
The core polymer of the present invention is excellent in biocompatibility and biodegradability and can control and control the release of the loading material, and the polymer is in the form of a core. That is, the core polymer may contain drugs to be administered in the joint muscles.
And the core polymer is designed in a matrix form to substantially decompose from the site of administration within one to six months after the substantially loaded active ingredient is released.
According to a preferred embodiment of the present invention, the core polymer may comprise a linear polyester polymer. And the linear polyester polymer may comprise polylactide-co-glycolide (PLGA), polyglycolide (PGA), polylactide (PLA) and mixtures thereof. Specifically, the linear polyester may be prepared from an? -Hydroxycarboxylic acid such as lactic acid and glycolic acid by condensation of a lactone dimer. That is, the preferred chain in the linear polyester is a copolymer of lactic acid and glycolic acid or a lactone dimer, which is an alpha -carboxylic acid residue. The lactide: glycolide molar ratio of the polylactide-co-glycolide preferably used in accordance with the present invention is 100: 0 to 40:60, preferably 90:10 to 40:60, more preferably 85:15 To 65:35. Linear polyesters preferably used in accordance with the present invention are those having a linear polylactide (PLA) and / or a linear polylactide-co-glycolide (PLGA) of from about 10,000 to about 500,000 Da, And may have a weight average molecular weight (Mw) of about 50,000 Da. And may have a polydispersity Mw / Mn of, for example, from 1.2 to 2. Suitable examples include those known commercially as Resomers in Boehringer Ingelheim. According to a preferred embodiment of the present invention, the core polymer is in the form of a microparticle of nanoparticles.
Cationic Polymer
In the present invention, the cationic polymer serves to impart cationic property to the carrier for drug-administered drugs of the present invention. Specifically, the cationic polymer is composed of one end which non-covalently mixes with a part of the core polymer and the other end which shows a positive charge. Thus, the cationic polymer provides ionic cross-linking with the anionic polymer in the joint cavity by providing a positive charge on the surface of the carrier, which is a nanoparticle.
According to a preferred embodiment of the present invention, the cationic polymer is selected from the group consisting of Eudragit RL (copolymers of ethyl acrylate, methyl methacrylate and trimethylammonioethyl methacrylate chloride), chitosan, polyethylene imine (PEI) (3 '- [N', N'-dimethylaminoethane carbamoyl] cholesterol, DC-Chol) and cetyltrimethylammonium bromide (Cetyl trimethylammonium bromide (CTAB), and the like.
Coating polymer
The coating polymer of the present invention is a biocompatible material that covers part or all of the surface of the core polymer. The coating polymer component that encapsulates the core polymer includes at least one water-soluble polymer selected from the group consisting of gelatin, polyvinyl alcohol, agarose, poly (N-isopropylacrylamide), and alginate . The water-soluble polymer may vary depending on the polymer, but may be contained in water as a solvent in an amount of about 0.01 to 10% by weight. Among them, polyvinyl alcohol may be contained in water as a solvent in an amount of 0.01 to 5% by weight.
Meanwhile, the carrier for drug-administered drugs of the present invention is in the form of microparticles, and the average diameter of the carrier may be 50 nm to 20 um, preferably 100 nm to 10 um.
The thickness of the cationic polymer and the coating polymer may be smaller than the average diameter of the core polymer. Thus, the average diameter of the core polymer and the average diameter of the carrier may be substantially the same.
The method for preparing a drug-containing drug carrier of the present invention is as follows.
First, the microparticles may be prepared by an oil-in-water single emulsion method. More specifically, the drug is dissolved in an organic solvent in which a core-forming polymer, which is a water-insoluble polymer, and a positive charge polymer are dissolved. Then, a coating polymer solution which is a solution of a core stabilizer is added and homogenized by ultrasonic treatment to form an oil / water emulsion. Thereafter, an emulsifier solution is added to the emulsion and homogenized, and the remaining solvent is removed by using a rotary evaporator or the like to obtain particles of the drug carrier of the present invention. The average diameter of the particles obtained through the above process may be 50 nm to 20 m, preferably 100 nm to 10 m.
Alternatively, the microparticles may be prepared by a water / oil / water double emulsion method. More specifically, a drug aqueous solution is added to an organic solvent containing a core-forming polymer and a positively charged polymer, which are water-insoluble polymers, to prepare a water / oil emulsion by ultrasonic pulverization and homogenization, Water / oil / water emulsion is prepared through ultrasonic pulverization and homogenization. Thereafter, the solvent is removed using a rotary evaporator to obtain a microparticle that is a carrier for a drug of the present invention. The average diameter of the particles obtained through the above process may be 50 nm to 20 um, preferably 100 nm to 10 um.
The organic solvent to be used in the oil / water single emulsion method and the water / oil / water emulsion may be any generally usable ones, but preferably includes at least one selected from ethyl acetate, dichloromethane, acetone and triacetin .
When the drug contained in the preparation is a water-soluble macromolecule, that is, a protein, a peptide, a nucleic acid or the like, it is preferably prepared by a water / oil / water double emulsification method. When the drug contained in the microspheres is insoluble Is preferably produced by an oil / water single emulsion method.
In addition, any drug that can be contained in the carrier for drug-administered drug of the present invention may be used as long as it is generally used. That is, drugs that can be delivered into the joints include all biological and chemical substances used for the prevention, treatment, alleviation or alleviation of the disease. More specifically, the drug includes various forms such as proteins, peptides, compounds, extracts and / or nucleic acids, and the nucleic acid includes, but is not limited to, DNA, RNA, oligonucleotides and / or vectors. The drugs that can be used in the present invention are not limited by specific drugs or classifications, and may be, for example, antioxidants, antibiotics, anticancer agents, antiinflammatory agents, antiinflammatory agents, antiviral agents, antimicrobial agents and / or hormones. Agents may optionally contain various excipients in the art such as diluents, release retardants, inert oils and / or binders. Examples of the above protein drug include superoxide, catalase or glutathione. Examples of the compound drug include pentoxifyline, dexamethasone, ibuprofen Ibuprofen, Naproxen, Indomethacin, Celecoxib, Piroxicam, Diclofenac, Tocopherol, Tocotrienol, Resveratol, , Ascorbic acid, lycopene or naringenin, and the like, but are not limited thereto.
As described above, the carrier for drug administration according to the preferred embodiment of the present invention binds to the anionic biopolymer in the joint cavity through electrostatic crosslinking to form an aggregate. The average diameter of the aggregates formed may be 0.1 μm or more, preferably 0.1 to 100 μm, more preferably 5 to 50 μm. Thus, the aggregates formed from the carrier of the present invention can increase the retention time in the joints.
Hereinafter, the present invention will be described in more detail with reference to examples. However, the embodiments of the present invention described below are illustrative only and the scope of the present invention is not limited to these embodiments. The scope of the present invention is indicated in the claims, and moreover, includes all changes within the meaning and range of equivalency of the claims. In the following Examples and Comparative Examples, "%" and " part " representing the content are based on weight unless otherwise specified.
Example 1 to 6: oil / water Single emulsification method The use of lipophilic fluorescent material Enclosed For joints Carrier Produce
A carrier for injecting a joint of the present invention encapsulated with a fluorescent substance was prepared according to the composition and manufacturing conditions shown in Table 1 below.
The organic solvent dichloromethane and ethyl acetate (ethyl acetate) were weighed out in a weight ratio of 3: 7 by mixing Eudragit RL (Evonik) and PLGA (Resomer 504, L / G ratio = 50:50, MW 38,000 to 54,000) acetate) and dissolved by stirring for 10 minutes. DiR (DiIC 18 (7), 1,1'-dioctadecyl-3,3,3 ', 3'-tetramethylindotricarbocyanine iodide) was added to the polymer (PLGA, Eudragi RL, polyvinyl alcohol) / 50 ratio. An aqueous solution of polyvinyl alcohol dissolved in distilled water was added to the organic solvent in which the polymer and the fluorescent material were dissolved, and the mixture was stirred for 10 minutes to prepare an emulsion. The emulsion was nano-emulsified using a bath-type sonicator (Branson 2210, output power 90W). The nanoemulsion was placed in a heating magnetic stirrer and agitated for about 5 hours to blow off the internal organic solvent (solvent evaporation) to prepare a carrier for injection of fluorescent material.
Example 7 to 10: water / oil / water Single emulsification method The water-soluble fluorescent material used Enclosed For joints Carrier Produce
A support for injection of jointed-steel mineral containing encapsulated minerals was prepared according to the composition and manufacturing conditions shown in Table 2 below.
The organic solvent dichloromethane and ethyl acetate (ethyl acetate) were weighed out in a weight ratio of 3: 7 by mixing Eudragit RL (Evonik) and PLGA (Resomer 504, L / G ratio = 50:50, MW 38,000 to 54,000) acetate) and dissolved by stirring for 10 minutes. After distilled water having a concentration of 2 mg / ml of Rhodamine B isothiocyanate was prepared, the mixture was mixed with the organic solvent and stirred at 13000 rpm for 10 minutes with a homogenizer. The water / oil emulsion thus formed was added to an aqueous solution prepared by dissolving polyvinyl alcohol in distilled water and subjected to nanoemulsification using a bath-type sonicator (Branson 2210, output power: 90 W). The nanoemulsion was placed in a heating magnetic stirrer and agitated for about 5 hours to blow up the internal organic solvent (solvent evaporation) to prepare a carrier for injection of the fluorescent material.
Comparative Example One: Dir Fluorescent material solution
DiR was added to 10 mM phosphate buffered saline (PBS) solution containing 1% (w / v) of sodium lauryl sulfate in the same amount as in Example 1, and the mixture was stirred for 30 minutes.
Comparative Example 2: Neutral charge PLGA Nanoparticle carrier Produce
PLGA (Resomer 504, L / G ratio = 50: 50, MW 38,000 ~ 54,000) was dissolved in dichloromethane and ethyl acetate by stirring for 10 minutes. DiR was added at a ratio of 1/50 compared with the polymer for later fluorescence tracing after injection into the body. An aqueous solution of polyvinyl alcohol dissolved in distilled water was added to the organic solvent in which the polymer and the fluorescent material were dissolved, and the mixture was stirred for 10 minutes to prepare an emulsion. The emulsion was nano-emulsified using a bath-type sonicator (Branson 2210, output power 90W). The nanoemulsion was placed in a heating magnetic stirrer and agitated for about 5 hours for solvent evaporation to prepare a neutral carrier PLGA nanoparticle carrier containing the fluorescent substance.
Experimental Example 1: Physical and chemical properties evaluation
The particle uniformity, surface charge, and loading amount of the fluorescent materials of Examples 1 to 6 and Comparative Examples 1 and 2 were evaluated. The particle size distribution and the surface charge of the nanoparticle carrier were measured by dynamic light scattering method using a Zetasizer Nano-ZS (Malvern Instrument, Worcestershire, UK) after diluting the prepared nanoparticle carrier with 10 mM phosphate buffered saline . The loading amount of the fluorescent substance was determined by taking 1 mL of the suspension in which the carrier was suspended in PBS in a microtube, performing an ultracentrifuge at 20,000 xg for 60 minutes, and then submerging 0.9 mL of the submerged particles and supernatant The solution was dissolved in 0.9 mL of dimethylsulfoxide (DMSO) and quantitated with a Flexstation 3 Microplate Reader. The results of physical and chemical properties evaluation are shown in Table 3 below.
(nm)
± 0.8
± 1.3
± 1.2
± 3.4
± 2.6
± 1.9
± 1.3
(PDI)
(μg / mg)
Experimental Example 2: With hyaluronic acid ion Crosslinkability evaluation
Whether or not the carrier of Example 1 and Comparative Example 2 was crosslinked with hyaluronic acid, which is an anionic polymer in vivo, was evaluated in vitro. The ratio of hyaluronic acid (2.2 mg / mL) to osteoarthritis (1: 2 ratio) was measured by Hyperspectral Imaging System (HSI). Example 1 is shown in Fig. 1, and Comparative Example 2 is shown in Fig. FIGS. 1 and 2 (a) are optical images of a microscope, (b) are mapping images using a super multi-image spectroscopy system, and (c) are images in which a mapping image is superimposed on an optical image.
As shown in FIG. 1, it was confirmed that the carrier of Example 1 forms a micrometer-sized agglomerate through electrostatic crosslinking with hyaluronic acid. On the contrary, it can be seen that the carrier of Comparative Example 2 in FIG. 2 is uniformly dispersed in the anionic polymer solution without forming ionic crosslinking.
As a result, it can be seen that the retention time in the articular cavity can be greatly increased compared to Comparative Example 2 because the micro-aggregate formation of Example 1 is larger than the synovial cell gap around the joint cavity.
Experimental Example 3: intra-articular in mouse Residence property evaluation
The fluorescence of Comparative Example 1 and the carriers of Example 1 and Comparative Example 2 were injected into the knee joint muscles of a hairless mouse, and the retention of the particles in the joints was evaluated by intra-articular fluorescence intensity tracking. DiR contained in the carrier of Example 1 and Comparative Example 2 was not leaked to the outside, but a substantial amount was retained in the carrier for at least one month.
The fluorescent material of Comparative Example 1 and the carriers of Example 1 and Comparative Example 2 were mixed in a 10 mM PBS (Phosphate buffered saline) solution at a ratio of 1: 1 and then injected into the right articular cavity of the hairless mouse using an insulin syringe at 10 microliters mu] L). The fluorescence intensities of the joints were measured 7 days, 14 days, and 21 days after the injection using the IVIS spectrum (Pre-clinical In Vivo Imaging System). The results are shown in Fig.
Comparative Example 1 After the injection, the fluorescent substance solution was easily escaped from the inside of the articular cavity and rapidly disappear after the whole body was inflowed. The fluorescent material of Comparative Example 2 was found to have a higher value than the fluorescent material of Comparative Example 1, that is, it could stay longer than the articular cavity. However, the fluorescent material of Comparative Example 2 is lower than that of Example 1. On the other hand, as demonstrated in Experimental Example 2, Example 1 demonstrates that the retention of articular muscles is significantly improved by improving the physical and biological retentiveness of joints by forming anionic polymers and ionic agents in joints after implantation have.
Claims (6)
A cationic polymer, one end of which is mixed non-covalently with the core polymer and the other end of which is positively charged on the surface of the carrier; And
And a coating polymer that surrounds part or all of the surface of the core polymer,
Wherein the core polymer comprises a linear polyester polymer,
Wherein the linear polyester polymer is a linear polylactide-co-glycolide, the molar ratio of lactide to glycolide of the linear polylactide-co-glycolide is 85:15 to 65:35,
The linear polylactide-co-glycolide has a weight average molecular weight (Mw) of 10,000 to 50,000 Da and a Mw / Mn of 1.2 to 2,
The cationic polymer may be selected from the group consisting of Eudragit RL (copolymers of ethyl acrylate, methyl methacrylate and trimethylammonioethyl methacrylate chloride), chitosan, polyethylene imine (PEI), 3? - [N- Cholesterol, DC-Chol) and cetyl trimethylammonium bromide (CTAB), which are selected from the group consisting of 3'-dimethylaminoethanol, 3β- [N ', N'-dimethylaminoethane carbamoyl] ≪ / RTI >
Wherein the coating polymer comprises at least one water-soluble polymer selected from the group consisting of gelatin, polyvinyl alcohol, agarose, poly (N-isopropylacrylamide) and alginate, ,
The carrier for an articular cavity-administered drug is in the form of a microparticle,
The average diameter is 50 nm to 20 mu m,
Wherein the carrier for articular cavity-administered drug is bound to an anionic bioactive polymer in the joint cavity to form an aggregate having an average diameter of 0.1 mu m or more.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020150052264A KR101983653B1 (en) | 2015-04-14 | 2015-04-14 | Pharmaceutical carrier compositions for intra-articular injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020150052264A KR101983653B1 (en) | 2015-04-14 | 2015-04-14 | Pharmaceutical carrier compositions for intra-articular injection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20160122877A KR20160122877A (en) | 2016-10-25 |
| KR101983653B1 true KR101983653B1 (en) | 2019-05-29 |
Family
ID=57446489
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020150052264A KR101983653B1 (en) | 2015-04-14 | 2015-04-14 | Pharmaceutical carrier compositions for intra-articular injection |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR101983653B1 (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006014444A1 (en) | 2004-07-06 | 2006-02-09 | Zymogenetics, Inc. | Pharmaceutical composition comprising fgf18 and il-1 antagonist and method of use |
| US20120289469A1 (en) | 2011-05-10 | 2012-11-15 | Bend Research, Inc. | Methods and compositions for maintaining active agents in intra-articular spaces |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100709015B1 (en) * | 2002-11-13 | 2007-04-18 | (주)아모레퍼시픽 | Polymeric microparticulates for sustained release of drug and their preparation methods |
| KR100834733B1 (en) * | 2006-09-14 | 2008-06-09 | 광주과학기술원 | Drug Delivery System for Controlled Release of Angiogenesis-Promoting Protein Drugs |
| ITMI20070527A1 (en) * | 2007-03-16 | 2008-09-17 | Sadepan Chimica S R L | SEED DRILLS AND CONTAINERS IN ORGANIC FIBER FOR PANTAS AND PLANTS AND PROCEDURE FOR THEIR MANUFACTURE |
| KR101277658B1 (en) * | 2011-07-11 | 2013-06-21 | 조선대학교산학협력단 | Method of preparing biomedical ceramic materials comprising multi-drug delivery system |
-
2015
- 2015-04-14 KR KR1020150052264A patent/KR101983653B1/en active IP Right Grant
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006014444A1 (en) | 2004-07-06 | 2006-02-09 | Zymogenetics, Inc. | Pharmaceutical composition comprising fgf18 and il-1 antagonist and method of use |
| US20120289469A1 (en) | 2011-05-10 | 2012-11-15 | Bend Research, Inc. | Methods and compositions for maintaining active agents in intra-articular spaces |
Non-Patent Citations (3)
| Title |
|---|
| Journal of Controlled Release 2002, 82, 105-114* |
| 논문(DRUG DES DEVEL THER.,2016) |
| 미국공개특허공보 제2008-0289469호(2012. 11. 15.)* |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20160122877A (en) | 2016-10-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| McCall et al. | PLGA nanoparticles formed by single-or double-emulsion with vitamin E-TPGS | |
| Lee et al. | PLA micro-and nano-particles | |
| Lai et al. | Overview of the preparation of organic polymeric nanoparticles for drug delivery based on gelatine, chitosan, poly (d, l-lactide-co-glycolic acid) and polyalkylcyanoacrylate | |
| Gagliardi et al. | Sodium deoxycholate-decorated zein nanoparticles for a stable colloidal drug delivery system | |
| Natarajan et al. | Sustained-release from nanocarriers: a review | |
| Vrignaud et al. | Strategies for the nanoencapsulation of hydrophilic molecules in polymer-based nanoparticles | |
| Mehanny et al. | Studying the effect of physically‐adsorbed coating polymers on the cytotoxic activity of optimized bisdemethoxycurcumin loaded‐PLGA nanoparticles | |
| Trivedi et al. | Nanomicellar formulations for sustained drug delivery: strategies and underlying principles | |
| Gaber et al. | Protein-polysaccharide nanohybrids: Hybridization techniques and drug delivery applications | |
| Graf et al. | Poly (alkycyanoacrylate) nanoparticles for enhanced delivery of therapeutics–is there real potential? | |
| Jose et al. | Carboplatin loaded Surface modified PLGA nanoparticles: Optimization, characterization, and in vivo brain targeting studies | |
| Jose et al. | Polymeric lipid hybrid nanoparticles: properties and therapeutic applications | |
| JP2006514698A5 (en) | ||
| Azizi et al. | Fabrication of protein-loaded PLGA nanoparticles: effect of selected formulation variables on particle size and release profile | |
| Wang et al. | Novel PEG-graft-PLA nanoparticles with the potential for encapsulation and controlled release of hydrophobic and hydrophilic medications in aqueous medium | |
| Zhuang et al. | Preparation of particulate polymeric therapeutics for medical applications | |
| Rong et al. | Applications of polymeric nanocapsules in field of drug delivery systems | |
| Tomeh et al. | Stiffness-tuneable nanocarriers for controlled delivery of ASC-J9 into colorectal cancer cells | |
| He et al. | Sequence-controlled delivery of peptides from hierarchically structured Nanomaterials | |
| Ribeiro et al. | Biodegradable nanoparticles as nanomedicines: are drug-loading content and release mechanism dictated by particle density? | |
| CN107157953A (en) | A kind of psoralen polymer nanoparticle preparation and preparation method | |
| Manimaran et al. | Nanogels as novel drug nanocarriers for CNS drug delivery | |
| Lee et al. | Photoreactive-proton-generating hyaluronidase/albumin nanoparticles-loaded PEG-hydrogel enhances antitumor efficacy and disruption of the hyaluronic acid extracellular matrix in AsPC-1 tumors | |
| Panta et al. | Protein drug-loaded polymeric nanoparticles | |
| JP7465876B2 (en) | Multicompartment systems of nanocapsule-in-nanocapsule type for the encapsulation of lipophilic and hydrophilic compounds and related manufacturing methods |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| E902 | Notification of reason for refusal | ||
| E90F | Notification of reason for final refusal | ||
| E701 | Decision to grant or registration of patent right | ||
| GRNT | Written decision to grant |