Emulsion composition for chemoembolization and method for producing same

1. An emulsion composition for chemoembolization, comprising

a polymer nanoparticle comprising a water-soluble anticancer agent, a water-insoluble anticancer agent, or a combination thereof as active ingredients, and an amphiphilic block copolymer comprising a hydrophilic (A) block and a hydrophobic (B) block;

a water-soluble contrast agent; and

a water-insoluble contrast agent,

wherein the hydrophilic (A) block is one or more selected from the group consisting of monomethoxypolyethylene glycol, monoacetoxypolyethylene glycol, polyethylene glycol, copolymer of polyethylene and propylene glycol, and polyvinyl pyrrolidone, and

the hydrophobic (B) block is one or more selected from the group consisting of polylactide, polyglycolide, polycaprolactone, polydioxan-2-one, copolymer of polylactide and glycolide, copolymer of polylactide and polydioxan-2-one, copolymer of polylactide and polycaprolactone and copolymer of polyglycolide and polycaprolactone; and

the water-soluble contrast agent is iopamidol, and the water-insoluble contrast agent is one or more selected from the group consisting of poppy fruit-derived iodized oil, soybean-derived iodized oil and ethiodol,

wherein the diameter of the polymer nanoparticle is 10 nm to 60 nm.

2. The emulsion composition for chemoembolization according to claim 1 , wherein the number average molecular weight of hydrophilic (A) block or hydrophobic (B) block is 500 to 50,000 Da.

3. The emulsion composition for chemoembolization according to claim 1 , wherein the weight ratio of the hydrophilic (A) block and hydrophobic (B) block is 2:8 to 8:2.

4. The emulsion composition for chemoembolization according to claim 1 , wherein the polymer nanoparticle further comprises a polylactic acid derivative containing a terminal group of a carboxylic acid.

5. The emulsion composition for chemoembolization according to claim 4 , wherein the polylactic acid derivative containing a terminal group of carboxylic acid is one or more selected from the group consisting of the compounds of Formulas 1 to 6:

RO—CHZ-[A] n -[B] m —COOM  [Formula 1]

in the Formula 1,

A is —COO—CHZ—; and

B is —COO—CHY—, —COO—CH 2 CH 2 CH 2 CH 2 CH 2 — or —COO—CH 2 CH 2 OCH 2 ; and

R is a hydrogen atom, acetyl, benzoyl, decanoyl, palmitoyl, methyl or ethyl group; and

Z and Y are independently a hydrogen atom, methyl or phenyl group; and

M is Na, K, or Li; and n is an integer from 1 to 30; and m is an integer from 0 to 20;

RO—CHZ—[COO—CHX] p —[COO—CHY′] q —COO—CHZ—COOM  [Formula 2]

in the Formula 2,

X is a methyl group; and

Y′ is a hydrogen atom or phenyl group; and

p is an integer from 0 to 25, and q is an integer from 0 to 25, on the proviso that sum of p and q is an integer from 5 to 25; and

R is a hydrogen atom, acetyl, benzoyl, decanoyl, palmitoyl, methyl or ethyl group; and

M is Na, K, or Li; and

Z is a hydrogen atom, methyl or phenyl group;

RO-PAD-COO—W-M′  [Formula 3]

in the Formula 3,

W-M′ is

and

PAD is selected from the group consisting of D,L-polylactic acid, D-polylactic acid, polymandelic acid, copolymer of D,L-lactic acid and glycolic acid, copolymer of D,L-lactic acid and mandelic acid, copolymer of D,L-lactic acid and caprolactone and copolymer of D,L-lactic acid and 1,4-dioxan-2-one; and

R is a hydrogen atom, acetyl, benzoyl, decanoyl, palmitoyl, methyl or ethyl group; and

M is independently Na, K, or Li;

S—O-PAD-COO-Q  [Formula 4]

in the Formula 4,

S is

and L is -NR1- or -0-, wherein R1 is a hydrogen atom or C 1-10 alkyl; and Q is CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 , CH 2 CH 2 CH 2 CH 3 , or CH 2 C 6 H 5 ; and a is an integer from 0 to 4; and b is an integer from 1 to 10; and M is Na, K, or Li; and

PAD is selected from the group consisting of D,L-polylactic acid, D-polylactic acid, polymandelic acid, copolymer of D,L-lactic acid and glycolic acid, copolymer of D,L-lactic acid and mandelic acid, copolymer of D,L-lactic acid and caprolactone and copolymer of D,L-lactic acid and 1,4-dioxan-2-one.

in the Formula 5, R′ is -PAD-O—C(O)—CH 2 CH 2 —C(O)—OM,

wherein PAD is selected from the group consisting of D,L-polylactic acid, D-polylactic acid, polymandelic acid, copolymer of D,L-lactic acid and glycolic acid, copolymer of D,L-lactic acid and mandelic acid, copolymer of D,L-lactic acid and caprolactone and copolymer of D,L-lactic acid and 1,4-dioxan-2-one, and M is Na, K, or Li; and a is an integer from 1 to 4.

YO—[—C(O)—(CHX) a —O—] m —C(O)—R—C(O)—[—O—(CHX′) b —C(O)—] n —OZ  [Formula 6]

in the Formula 6,

X and X′ are independently a hydrogen, alkyl having 1 to 10 carbon atoms or aryl having 6 to 20 carbon atoms; and

Y and Z are independently Na, K, or Li; and

m and n are independently an integer from 0 to 95 to meet 5<m+n<100; and

a and b are independently an integer from 1 to 6; and

R is —(CH2)k—, divalent alkenyl having 2 to 10 carbon atoms, divalent aryl having 6 to 20 carbon atoms or combination thereof, wherein k is an integer from 0 to 10.

6. The emulsion composition for chemoembolization according to claim 4 , wherein the terminal group of carboxylic acid in the polylactic acid derivative is fixed with a divalent or trivalent metal ion.

7. The emulsion composition for chemoembolization according to claim 6 , wherein the divalent or trivalent metal ion is selected from the group consisting of calcium (Ca 2+ ), magnesium (Mg 2+ ), barium (Ba 2+ ), chrome (Cr 3+ ), iron (Fe 3+ ), manganese (Mn 2+ ), nickel (Ni 2+ ), copper (Cu 2+ ), zinc (Zn 2+ ) and aluminum (Al 3+ ).

8. The emulsion composition for chemoembolization according to claim 1 , wherein the viscosity of the water-soluble contrast agent or water-insoluble contrast agent is 10 to 40 mPa at 37° C.

9. The emulsion composition for chemoembolization according to claim 1 , wherein the polymer nanoparticle is dissolved in the water-soluble contrast agent so that the concentration of anticancer agent is 1 to 40 mg/ml based on the total emulsion composition.

10. The emulsion composition for chemoembolization according to claim 9 , wherein the volume ratio of the water-soluble contrast agent in which the polymer nanoparticle is dissolved and water-insoluble contrast agent is 1:2 to 1:10.

11. The emulsion composition for chemoembolization according to claim 1 , wherein the viscosity of the emulsion composition is 20 to 50 mPa at 37° C.