Sungkyunkwan University

Samsung Life Public Welfare Foundation

Doo Sung Lee

Bong Sup Kim

Min Sang Kim

Minh Khanh Nguyen

Je Sun You

Huynh Dai Phu

Yi Li

Jung Hee Lee

You Han Bae

Sang Hee Ahn

Hye Young Kim

Hee Chul Park

Young Yih Han

Moon Soo Gil

Kiattikhun Manokruang

Cong Truc Huynh

Guanghui Gao

Kasala Dayananda

Jae Myoung Noh

Woo Sun Shim

The present disclosure relates to a polypeptide based block copolymer having biodegradability due to peptidase, and a process for the preparation thereof, and polymer micelles using the same. The block copolymer according to the present disclosure is a block copolymer of a polyethylene glycol-based compound having properties such that the solubility for water is different depending on the pH, but cannot form micelles due to a self-assembly phenomenon; and a polyglutamic acid-based compound formed using an aminolysis reaction of glutamic acid and tertiary amine in which the end of one alkyl group is substituted with NH, or using an aminolysis reaction of glutamic acid and triamine. The block copolymer of the present disclosure has advantages in that the block polymer has both pH sensitivity and biodegradability due to peptidase in the body, and thereby a degradation rate related to a drug release cycle is controlled. Therefore, the block copolymer according to the present disclosure is effective in that the block copolymer can be used as a target-oriented drug delivery agent depending on the pH changes in the body, and as a drug delivery agent that can control the rate of degradation.

Polypeptide based block copolymer and the process for the preparation thereof, and the polymer micelles using the same

The present invention relates to a conjugate of albumin and a temperature- and pH-sensitive multi-block copolymer, a method of preparation thereof, and a sustained-release drug carrier comprising the same, and more specifically, to a conjugate in which polyethylene glycol-poly(amino urethane) (PEG-PAU) or polyethylene glycol-poly(amino ester urethane) (PEG-PAEU) multi-block copolymer is conjugated to albumin, a method of preparing the same, and a long-term sustained-release drug carrier comprising the same, capable of reducing an initial burst release of drugs and improving an affinity to drugs.

Albumin conjugated temperature and pH-sensitive multi-block copolymer, a method of preparation thereof and drug delivery system using the same

The present invention relates to a fiducial marker comprising barium sulfate (BaSO), a solvent, and a polyethylene glycol-poly(aminourethaneurea) multi-block copolymer, as active ingredients. The fiducial marker of the present invention has an effect of significantly remedying disadvantages of image distortion and dose distortion, which are involved in the gold inner marker used in the conventional art. The fiducial marker of the present invention has very limited in vivo mobility, and thus the fiducial marker is maintained at the position at which it has been initially injected. Since the fiducial marker of the present invention is maintained in a sol or liquid state before in vivo injection, and transited into a gel or solid phase after in vivo injection, the injectability of the fiducial marker by an injector syringe is favorable, and the state of the fiducial marker can be controlled into a phase suitable to each site of the therapeutic target.

Biocompatible fiducial marker using multi-block copolymers

Disclosed herein are pH- and temperature-sensitive block copolymer with excellent safety and a method for preparing the same and a hydrogel and a drug carrier using the block copolymer. According to the present invention, the pH- and temperature-sensitive block copolymer comprises: obtained by copolymerization of: (a) polyethylene glycol-based compound (A); and (b) poly (&#x3b2;-amino ester)-based oligomer (B) or poly (amido amine)-based oligomer (C) or coupling of mixture (D) thereof. In order to control biodegradation rate, the block copolymer is mixed with poly (amido amine)-based oligomer instead of the poly (&#x3b2;-amino ester)-based oligomer and then coupling them.

Temperature and pH-sensitive block copolymer having excellent safty in vivo and hydrogel and drug delivery system using thereof

A polypeptide based block copolymer having biodegradability due to peptidase, a process for the preparation thereof, and polymer micelles using the same are provided. The block copolymer is a block copolymer of a polyethylene glycol-based compound having properties such that the solubility for water is different depending on the pH, but cannot form micelles due to a self-assembly phenomenon; and a polyglutamic acid-based compound formed using an aminolysis reaction of glutamic acid and tertiary amine in which the end of one alkyl group is substituted with NH, or using an aminolysis reaction of glutamic acid and triamine.

The present document relates to a manufacturing method for pH-sensitive graft polymer micelles and a polymer micelle-type pharmaceutical composition containing the graft copolymer. The pH-sensitive graft copolymer micelles are usable as various markers and contrast agents for various molecular images for the diagnosis and treatment of diseases and a carrier for delivery of various medicines according to disease. The pH-sensitive graft copolymer forms micelles that can be used in target-oriented diagnosis and medicine release according to changes in the pH of a body. The polymer micelles are provided by inducing a graft copolymer of poly (&#x3b2;-amino ester) compounds which has a solubility in water depending on pH but is incapable of forming the micelles due to a self-assembly phenomenon, and hydrophilic poly(ethylene glycol) compounds.

PH-sensitive graft copolymer, manufacturing method for same, and polymer micelles using method

Disclosed is a dual-transition polymeric hydrogel. Also, provided is the use of the dual-transition polymeric hydrogel as a carrier for drug delivery and disease diagnosis, or in the preparation of a polymeric hydrogel-type pharmaceutical composition comprising the physiologically active agent loadable into the block copolymer. Being sensitive to pH as well as temperature, the block copolymer can form a more stable hydrogel at suitable temperatures and pH values. In addition, the block copolymer exhibits a dual transition behavior with pH values so that it can carry ionic drugs, proteins, DNA, and markers, whether positively or negatively charged, simultaneously. Therefore, it can be applied to a sustained drug delivery system for sparingly soluble, hydrophobic drugs, and hydrophilic drugs. Further, it is safe to and stable within the body, and is expected to find various applications in the medical field.

PH-sensitive polymer hydrogel with dual ionic transition and use thereof

Disclosed is a pH-sensitive block copolymer that forms polyionic complex micelles. The block copolymer is prepared by copolymerization of (a) a polyethylene glycol compound, (b) a poly(amino acid) compound, and (c) a heterocyclic alkyl amine compound having the ability to induce the formation of ionic complexes. Further disclosed is a drug or protein carrier using the block copolymer.

pH-sensitive block copolymer forming polyionic complex micelles and drug or protein carrier using the same

Disclosed is a block copolymer formed by coupling the following components with each other: (a) a copolymer (A) of a polyethylene glycol (PEG) type compound with a biodegradable polymer; and (b) at least one oligomer (B) selected from the group consisting of poly(&#x3b2;-amino ester) and poly(amido amine). A method for preparing the same block copolymer, and a polymeric hydrogel type drug composition comprising the temperature and pH-sensitive block copolymer and a physiologically active substance that can be encapsulated with the block copolymer are also disclosed. The multiblock copolymer is obtained by copolymerization of a pH-sensitive poly(&#x3b2;-amino ester) and/or poly(amido amine) type oligomer, a hydrophilic and temperature-sensitive polyethylene glycol type compound and a hydrophobic and biodegradable polymer. Therefore, the block copolymer can form a polymeric hydrogel structure due to its amphiphilicity resulting from the combination of a hydrophilic group and a hydrophobic group in the copolymer and ionization characteristics depending on pH variations, and thus can be used as a drug carrier for target-directed drug delivery depending on pH variations in the body.

Temperature and pH sensitive block copolymer and polymeric hydrogels using the same

An amphiphilic pentablock copolymer that is temperature- and pH-sensitive and has superior and sustained gel strength, includes (a) a hydrophilic triblock copolymer that is temperature-sensitive and that is a copolymer of a poly(ethylene glycol)-based compound and a biodegradable polymer that is one or more polymer selected from the group consisting of polylactide, polyglycolide, polycaprolactone, poly(caprolactone-lactide) random copolymer, poly(caprolactone-glycolide) random copolymer, poly(lactide-glycolide) random copolymer, and mixtures thereof; coupled with (b) a polyurethane-based oligomer (PU) that is pH sensitive and that includes a diisocyanate compound represented by a Formula as follows: OCN&#x2014;(CH)&#x2014;NCO, where n is an integer of 4 to 10, polymerized with a diol compound having a tertiary amine on a main chain thereof that is one or more of 1,3-bis{1-(2-hydroxyethyl) -4-pyridyl}propane and 1,4-bis(2-hydroxyethyl)piperazine, and is represented by Formulae as follows: where R and R' are alkyl groups of 1 to 8 carbon atoms, respectively.

Temperature and pH-sensitive block copolymer having excellent gel strength

Disclosed is a temperature- and pH-sensitive hydrogel composed of a poly(amidoamine) oligomer only. The hydrogel is prepared in a simple manner and is readily released from the body. Further disclosed are a method for preparing the hydrogel and a drug carrier using the hydrogel.

Poly(amidoamine) oligomer hydrogel for drug delivery and drug carrier using the same

Disclosed is a pH-sensitive block copolymer obtained by copolymerization of: (a) a polyethylene glycol compound (A); and (b) at least one poly(amino acid) compound selected from the group consisting of a poly(&#x3b2;-amino ester) and poly(amido amine) or a copolymer thereof (B). A method for preparing the same block copolymer, and a polymer micelle type drug composition comprising the pH-sensitive block copolymer and a physiologically active substance that can be encapsulated with the block copolymer are also disclosed. The pH-sensitive block copolymer is obtained by polymerization of a hydrophilic polyethylene glycol compound with a pH-sensitive biodegradable poly(amino acid) compound. Therefore, the pH-sensitive block copolymer can form a micelle structure due to its amphiphilicity and ionization characteristics depending on pH variations, and thus can be used as drug carrier for target-directed drug delivery depending on pH variations in the body.

pH sensitive block copolymer and polymeric micelle using the same

The present invention relates to a block copolymer formed by coupling the following components with each other, as well as a hydrogel composition comprising the block copolymer and a hydrogel formed from the composition: (a) a copolymer of a polyethylene glycol (PEG)-based compound with a biodegradable polymer; and (b) a sulfonamide-based oligomer. The inventive block copolymer shows the sol-gel transition behavior sensitive to changes in not only temperature but also pH. Thus, the inventive block copolymer overcomes the shortcomings of temperature-sensitive copolymers, form a more strong and stable hydrogel, and is stable in vivo. Accordingly, the inventive block copolymer can be used in various applications in the medical and drug delivery fields.

Growing community of inventors

Gwacheon-si, South Korea

Doo Sung Lee