IP Library Granted Patent US 9,101,669
Granted Patent B2
US 9,101,669 · App. 13/362,205 · Granted Aug 11, 2015

Self-assembed conjugate and use thereof

Inventors: Sei Kwang Hahn (Pohang, KR); Kimoon Kim (Pohang, KR); Hyuntae Jung (Pohang, KR); Jeong-A Yang (Cheongju, KR); Kyeng Min Park (Pohang, KR)
Assignee: POSTECH ACADEMY-INDUSTRY FOUNDATION
A61K47/38A61K9/06A61K31/138A61K31/337A61K31/436A61K31/4745A61K31/513A61K31/555A61K31/65A61K31/704A61K31/7068A61K31/713A61K33/24A61K39/39A61K45/06A61K47/24A61K47/34A61K47/36A61K47/4823A61K47/48784A61K49/0043A61K49/0054C08B37/0072C08L5/08A61K8/11B82Y5/00
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Quick Facts
Patent No.
US 9,101,669
App. No.
13/362,205
Granted
Aug 11, 2015
Kind
B2
Abstract

Provided are a self-assembled conjugate of a host molecule containing compound and a guest molecule containing compound, a delivery composition of a bioactive material comprising the self-assembled conjugate and a bioactive material to be delivered, and a composition for tissue engineering containing the self-assembled conjugate and a cell.

Claims (25)

1. A self-assembled conjugate comprising a compound of chemical formula I and a compound of chemical formula II:

[B] m -[H] n,   (chemical formula I)

[B] m -[G] l;   (chemical formula II)

in chemical formula I and II,

H is a cucurbit[n]uril n=5-12 having a functional group selected from the group consisting of an amine group, a carboxyl group, a hydroxyl group, an aldehyde group, an allyloxy group, a vinyl group, an acryl group, a thiol group, and a combination thereof;

G is selected from the group consisting of a C1-C20 aminoalkyl group having at least one amine group and a C1-C20 aminoalkyl group having metallocene;

B is a monomer of a polymer having a functional group selected from the group consisting of an amine group, a carboxyl group, a hydroxyl group, an aldehyde group, an allyloxy group, a vinyl group, an acryl group, a thiol group, and a combination thereof, wherein the polymer is at least one selected from the group consisting of polyethylene glycol (PEG), poly lactic acid (PLA), poly glycolic acid (PGA), poly lactic-co-glycolic acid (PLGA), hyaluronic acid, chitosan, dextran, and cellulose;

m, which is the number of the monomer, is an integer from 1 to 10,000; and

n and l, which are the mole number of the host molecule or the guest molecule, respectively, are independently selected from integers from 1 to 10,000, wherein the ratio of m:n or 1 is 1:0.2 to 1:1, and the ratio of n: 1 is 1:0.1 to 1:10, and

wherein the equivalent ratio between the compound of chemical formula I and a compound of chemical formula II is 1:0.1 to 1:10 (equivalent of the compound of chemical formula I:equivalent of the compound of chemical formula II).

2. The self-assembled conjugate according to claim 1 , wherein H is a cucurbit[n]uril n=6 or 7 linked with a functional group selected from the group consisting of an amine group, a hydroxyl group, an allyloxy group, and a combination thereof.

3. The self-assembled conjugate according to claim 1 , wherein G is selected from the group consisting of spermine (SPM), diaminohexane (DAH), ferrocene methylamine, and a combination thereof.

4. The self-assembled conjugate according to claim 1 , wherein B is a hyaluronic acid liked with a functional group selected from the group consisting of an amine group, a carboxyl group, a hydroxyl group, an aldehyde group, an allyloxy group, a vinyl group, an acryl group, a thiol group, and a combination thereof.

5. The self-assembled conjugate according to claim 1 , which is in an aqueous solution form wherein the concentration of the self-assembled conjugate is 2 to 10%(w/v) to form a hydrogel.

6. A method for preparing a delivery composition of a bioactive material, comprising the step of:

providing a the self-assembled conjugate according to claim 1 and a bioactive material.

7. The method according to claim 6 , wherein the bioactive material is at least one selected from the group consisting of a drug, a fluorescent material, a radioisotope, a target-oriented material, an imaging material, a cell, a protein drug, an antibody, and an aptamer.

8. The method according to claim 7 , wherein the drug is at least one selected from the group consisting of paclitaxel, doxorubicin, docetaxel, 5-fluoreuracil, oxaliplatin, cisplatin, carboplatin, berberine, epirubicin, doxycycline, gemcitabine, rapamycin, tamoxifen, herceptin, avastin, tysabri, erbitux, campath, zevalin, humira, mylotarg, xolair, bexxar, raptiva, remicade, siRNA, aptamer, interferon, insulin, reopro, rituxan, zenapax, simulect, orthoclone, synagis, erythropoietin, epidermal growth factor (EGF), human growth hormone (hGH), thioredoxin, Fel d1, Bee Venom Phospholipase A2 (Api m1), myelin basic protein, Hsp60, and Chaperone DnaJ (Hsp 40).

9. The method according to claim 7 , wherein the fluorescent material is at least one selected from the group consisting of fluorescein, rodamine, Dansyl, Cyanine dye (Cy), and antracene.

10. The method according to claim 7 , wherein the radioisotope is at least one selected from the group consisting of 3 H, 14 C, 22 Na, 35 S, 33 P, 32 P, and 125 I.

11. The method according to claim 7 , wherein the target-oriented material is a peptide comprising at least one selected from the group consisting of RGD (arginine-leucine-aspartic acid), TAT (threonine-alanine-threonine), and MVm (methionine-valine-D-methionine); a peptide recognizing a specific cell; an antigen; an antibody; folic acid; nucleic acid; an aptamer; and a carbohydrate.

12. The method according to claim 7 , wherein the imaging material is at least one selected from the group consisting of a gadolinium (Ga)-complex selected from gadolinium-diethylenetriamine penta-acetic acid (Ga-DTPA), gadolinium-diethylenetriamine penta-acetic acid-BMA (Ga-DTPA-BMA), gadolinium-tetraazacyclododecanetetraacetic acid (Ga-DOT), and Gadolinium-(1,4,8,11-tetraazacyclotetradecane) (Ga-cyclam); a nanoparticle of a metal selected from gold, silver, manganese, cadmium, selenium, tellurium, zinc, which has an average diameter of 1 to 200 nm; and a carbon nano-material selected from a single-walled carbon nanotube, a multi-walled carbon nanotube, fullerene, and graphene.

13. The method according to claim 7 , wherein the cell is at least one selected from the group consisting of cancer cells, bone cells, skin cells, stomach cells, intestinal cells, lung cells, liver cells, brain cells, blood endothelial cells, immune cells, eythrocytes, leukocytes, lymphocytes, preosteoblasts, osteoblast, mesenchymal stem cell, and induced pluripotent stem cell.

14. A composition for tissue engineering containing the self-assembled conjugate according to claim 1 and one or more selected from the group consisting of a cell, a cell-differentiation inducer, a cell-proliferation accelerator, a cell-growth factor, and a cell-adsorption inducer.

15. The composition for tissue engineering according to claim 14 , wherein the cell is at least one selected from the group consisting of cancer cells, bone cells, skin cells, stomach cells, intestinal cells, lung cells, liver cells, brain cells, blood endothelial cells, immune cells, eythrocytes, leukocytes, lymphocytes, preosteoblasts, osteoblast, mesenchymal stem cell, and induced pluripotent stem cell.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 2, 2018
From: POSTECH ACADEMY-INDUSTRY FOUNDATION
To: PHI BIOMED CO., LTD.
Reel/Frame 047183/0053 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 31, 2012
From: HAHN, SEI KWANG; KIM, KIMOON; JUNG, HYUNTAE; YANG, JEONG-A; PARK, KYENG MIN
To: POSTECH ACADEMY-INDUSTRY FOUNDATION
Reel/Frame 027624/0097 →
Continuity (1)
Related Publication 20130195751A1 · Aug 1, 2013