June, 2010

Bioabsorbable Polymer

Poly(DL-Lactide-co-Glycolide)

Mitsui PLGA Series

INC. Each grade of PLGA has a different rate of decomposition process.What is Mitsui PLGA? USES PLGA is a unique base polymer for controlled release of drugs and medical implant materials. HEALTH CARE MATERIALS DIVISION . MITSUI CHEMICALS. PROPERTIES Standard grade of PLGA is an almost colorless or light tan solid manufactured in transparent pellet form. PLGA is easily decomposed into glycolic acid and lactic acid by reaction with water.

INC. HEALTH CARE MATERIALS DIVISION .Advantage of Mitsui PLGA for Medical Use ・ Least Residual Solvent ・ Molecular Weight is well Controlled ・ Drug Master File is registered with FDA ・ Manufactured under cGMP MITSUI CHEMICALS.

APPLICATIONS (Examples 1) Anti-Cancer Drug US 5304377 •Microcapsule of Leuprorelin acetate with PLGA and PLA Control of releasing time of the drug Prolong the anti-cancer effect US 5603961 •Microsphere of CDPP (Cisplatin) with PLGA and PLA Control of initial burst and releasing time of the drug Lower the toxicity and stabilize the anti-cancer effect MITSUI CHEMICALS. INC. HEALTH CARE MATERIALS DIVISION .

HEALTH CARE MATERIALS DIVISION . INC.APPLICATIONS (Examples 2) GnRH analogues for prostate cancer ZOLADEX(AstraZeneca) •Pellet of Goserelin acetate with PLGA Control of releasing time of the drug (interval : 28days ,12weeks) Prolong the anti-cancer effect DECAPEPTYL(Debiopharm) •Microsphere of triptorelin with PLGA and PLA Control of initial burst and releasing time of the drug (interval : 1week~6months) Prolong the anti-cancer effect MITSUI CHEMICALS.

INC. HEALTH CARE MATERIALS DIVISION .Structures of Release Controlled Drugs Microcapsule Microsphere MITSUI CHEMICALS.

HEALTH CARE MATERIALS DIVISION . Drug. INC. Water Solvent elimination Filtration Drying Polymer. Organic solvent O = Oil W = Water Solvent elimination Filtration Drying Microsphere Water O/W Emulsion (W/O/W) Drug. Solvent W/O/W Emulsion Microsphere MITSUI CHEMICALS.Formulation (1) Emulsion (O/W) Polymer.

HEALTH CARE MATERIALS DIVISION Spray Drying Microsphere . INC.Formulation (2) Fusion Polymer Heating Fusion Drug Mixing Strand Ground. Drying Microsphere Spray dry Polymer Heating Fusion Drug Mixing MITSUI CHEMICALS.

Hydrolysis of PLGA in vitro (Residual Weight) 100 100 80 60 40 20 Residual Weight (%) 80 60 40 20 0 0 20 0 Days 40 60 ;PLGA 5-50 ;PLGA 75-65 MITSUI CHEMICALS. HEALTH CARE MATERIALS DIVISION Hydrolysis conditions in phosphate buffer solution (pH = 7. INC.3) temp: 37 ℃ .

3) temp: 37 ℃ . INC. HEALTH CARE MATERIALS DIVISION Hydrolysis conditions in phosphate buffer solution (pH = 7.Hydrolysis of PLGA in vitro (Molecular Weight) 100 100 80 60 Mw Retention (%) 80 60 40 20 40 20 0 0 20 0 Days 40 60 ;PLGA 5-50 ;PLGA 75-65 MITSUI CHEMICALS.

Chemical Formula Color Odor Tm(Melting Point)/ºC Tg(Glass Transition)/ ºC Solubility 26202-08-4 PLGA 5 26780-50-7 PLGA 75 ( C4H4O4 )x light tan ( C4H4O4 )x ( C6H8O4 )y white to light tan Odorless 220-230 Odorless - 35-40 HFIP 45-55 CH2Cl2 CHCl3 DMF DMSO THF MITSUI CHEMICALS. INC. HEALTH CARE MATERIALS DIVISION .Physical Properties PGA CAS No.

60 – 0.90 – 1. PLGA 5.45 – 0. 25℃ **Molecular Weight : (Standard polymer-Solvent) (by GPC) PMMA-HFIP for PGA.5 g / dl (Chloroform).55 < 2.45 – 0.0 < 2.10 kDa (100) GLD < 1.70 0.0 LTD – ppm < 10 ppm < 10 % < 0. PS-THF for PLGA MITSUI CHEMICALS.80 (50 – 55) (78 – 85) (62 – 76) (50 – 60) < 2.0 < 2. INC. HEALTH CARE MATERIALS DIVISION . 30℃.1 *Inherent viscosity : PGA : 0. 4.1 20 – 30 70 – 80(DL) 0.0 < 50 < 10 < 0.72 – 0. 6-Trichlorophenol / Phenol = 7 / 10). PLGA 75: 0.60 0.5 g /dl (2.Properties Polymer Co-polymer ratio,mol% *Inherent Viscosity **Molecular Weight Residual monomer, % Sn content Heavy metals Sulphated ash GLD PGA 100 LTD( form) – dL/g 0.0 < 50 < 10 < 0.1 PLGA 5-50 PLGA 75-75 PLGA 75-65 PLGA 75-50 45 – 55 45 – 55(DL) 0.

and “PLGA 75-65” is a product decomposing in three months.GRADE Standard grade “PLGA 5-50” is a product with the decomposition rate of one month. One of the characteristics of our PLGA is that no solvent remaining in this product. INC. the products of which physical properties and inherent viscosity are partially altered. “PLGA 75-65” and “PLGA75-75” which decompose slower than “PLGA 5-50”. Upon request. are available as a special grade. HEALTH CARE MATERIALS DIVISION . This is due to our unique manufacturing method which does not contain solvent in the manufacturing and purifying processes. MITSUI CHEMICALS. “PLGA 75-50”.

GMP & DMF The PLGA series are manufactured at our cGMP plant in Nagoya Works . Drug Master File is filed to FDA and Medicine Control Agency of U. HEALTH CARE MATERIALS DIVISION . INC..K. Product Master File is filed to Canadian Authority in 5 and 75 type respectively. MITSUI CHEMICALS.

26202-08-4] Glycolic Acid PLGA [CAS No. INC. HEALTH CARE MATERIALS DIVISION . 2678050-7] H HO C CH3 O C OH O H3C O CH3 O Lactide (LTD) O Lactic Acid MITSUI CHEMICALS.Ring Opening Polymerization of Glycolide and (or) Lactide O O O O Glycolide (GLD) Catalyst Initiator HO H C H Hydrolysis O C OH PGA [CAS No.

HEALTH CARE MATERIALS DIVISION PLGA . INC.Manufacturing Process of PLGA O O O GLD GLD O H3C O O O CH3 O Catalyst Initiator Polymerization Removal of Monomers Pelletization or Crashing LTD O O O O CHCOCHCO CH3 CH3 l CHCOCHCO H H m n MITSUI CHEMICALS.

Sign up to vote on this title
UsefulNot useful