I|||llIlllllllIlllllllIllllllllllllllllllillllllllllillillllllllllillllllll

US005357035A
United States Patent [19] [11] Patent Number: 5,357,035
Gruber et a1. [45] Date of Patent: * Oct. 18, 1994

[54] CONTINUOUS PROCESS FOR 3,839,297 10/1974 Wassermann et al. ............ .. 528/357
MANUFACTURE OF LACI‘IDE POLYMERS 3,887,699 6/1975 Yolles .. . . . . .. . . . . . . .. 424/19

WITH PURIFICATION BY DISTILLATION 3,912,692 10/1975 Casey et al. 528/354

4,045,418 8/ 1977 Sinclair ....... .. 328/357
[75] Inventors: Patrick R. Gruber, St. Paul; Eric S. 4,249,531 2/ 1981 Heller et a1. ...................... .. 128/260
Hall, Crystal; Jeffrey J. Kolstad, (List continued on next page.)
Wayzata; Matthew L. Iwen,
Minneapolis; Richard D. Benson, FOREIGN PATENT DOCUMENTS
Maple Plain; Ronald L. Borchardt, 808731 3/1969 Canada .
Eden Prairie, all of Minn.
(List continued on next page.)
[73] Assignee: Cargill, Incorporated, Minnetonka,
Minn.
OTHER PUBLICATIONS
Notice: The portion of the term of this patent W. Carothers, G. Dorough, and F. Van Natta (“Studies
subsequent to Aug. 25, 2009 has been of Polymerization and Ring Formation. X. The Revers
disclaimed. ible Polymerization of Six-Membered Cyclic Esters”,
[21] App]. No.: 122,145 1932, American Chemical Society Journal, v. 54, pp.
Sep. 16, 1993 761-772).
[22] Filed: (List continued on next page.)
Related US. Application Data
[63] Continuation of Ser. No. 926,901, Aug. 7, 1992, Pat.
Primary Examiner—.lohn Kight, III
No. 5,258,488, each and Ser. No. 927,149, is a continua
tion of Ser. No. 825,059, Jan. 24, 1992, Pat. No. Assistant Examiner—Shelley A. Dodson
5,142,023. Attorney, Agent, or Firm—Merchant, Gould, Smith,
Edell, Welter & Schmidt
[51] Int. Cl.5 ................... .. C08G 63/08; CO7D 319/12
[521 US. Cl. .................................. .. 528/354; 525/415;
526/67; 526/68; 528/ 357; 549/274 [57] ABSTRACT
[53] Field of Search ......................... .. 525/415, 67, 68; A process for the continuous production of polylactide
528/354, 357; 549/274 polymers from lactic acid which incorporates removal
[56] References Cited of water or a solvent carrier to concentrate the lactic
acid feed followed by polymerization to a low-molecu
U.S. PATENT DOCUMENTS lar-weight prepolymer. This prepolymer is fed to a
1,095,205 5/1914 Gruter et a1. .. .... .. 528/361 reactor in which a catalyst is added to facilitate genera
1,849,107 3/1932 Moss . ... ... .. . . . . . .. 528/354 tion of lactide, the depolymerization product of poly
1,995,970 4/ 1934 Dorough . . .. . . .. .. . . . . . .. 528/354
lactic acid. The lactide generated is continuously fed to
2,396,994 3/ 1946 Filachione et a1. .... .. 528/ 354
a distillation system as a liquid or vapor wherein water
2,703,316 3/1955 Schneider . ....... . . . . . . .. 528/357

2,758,987 8/1956 Salzberg . . . . . . . . . .. 528/357

and other impurities are removed. The resultant puri
2,951,828 9/1960 Zeile et a1. . .... .. 5.28/354 ?ed liquid lactide is fed directly to a polymerization
3,268,487 8/ 1966 Klootvijk .... .. 528/357 process.
3,322,791 5/1967 Selman .... .. 549/274
3,531,561 9/1970 Trehu . .. ... . . . . . . . .. 264/210

3,636,956 1/1972 Schneider .. .... .. 606/224

3,772,420 11/1973 Glick et a1. . . .. . . . . .. 264/102

3,773,919 ll/l973 Boswell et al. .................. .. 424/19 22 Claims, 8 Drawing Sheets

 5,357,035
Page 2

U.S. PATENT DOCUMENTS 0107591 2/1984 European Pat. Off. .

_ 0261572 3/ 1988 Euro can Pat. Off. .
4,273,920 Nevin ................................ -. 528/361 0275581 7/1988 Eurogean Pat .
4,279,249 7/1981 V6112 et a1. . .... .. 128/92 0299730 1/1989 European Pat. Of? _
4,595,713 6/1986 JOhIl 523/105 0314245 5/1989 European Pat. Off‘ .
4,643,734 2/1987 Lin .................... .. 623/16 0052510 3/1992 European Pa, 0ft '
4,677,191 Tanaka Ct a1 ..... .. 528/361 0481732 4/1992 European Pat Off
4,719,246
4,683,288 7/1987
l/1988 Murdoch
Tanaka...............
Ct Ctal.81. ... 521/134
528/361 0507554 10/1992 European Pat‘
Pat
Pat: Off. .

4,728,721 Yamamoto et a1. .............. n Fed Rep of (‘geniahy

Murdoch et a1. ................. .. Fed. Rep. of Gennany .
4,797,468 V1989 Hutchinson ..... .. c~0 528/254 3632103 3/1988 Fed. Rep. of Germany
Gennany .
4,800,219 1/1989 525/413 4_283227 of1992 Japan '
i’ 549/274 wo90/01521 2/1990 PCT Int’l App]. .
419501258 82990 231/22? wo91/02015 2/1991 PCT 1m Appl. .
1 1 / WO91/06601 5/1991 PCT 1m’1 Appl. .
4,960,866 10/1990 -- 528/499 wo92/00292 1/1992 PCT Int’l Appl. .
4,966,982 10/1990 549/274 wo92/00974 1/1992 PCT Int’l Appl. .
4,981,696 V1991 424/486 wo92/04410 3/1992 PCT Int’l App]. .
4,983,745 V1991 -- 549/274 WO92/O4412 3/1992 PCT Int’l Appl. .
4,990,222 2/1991 203/91 WO92/o44l3 3/1992 PCT Int’l APPL _
5,011,946 4/1991 549/274 WO92/05167 4/1992 PCT 1pm App]. .
5,023,349 6/1991 ~ 549/274 WO92/05168 4/1992 PCT Int’l Appl. .
$023,350 6/1991 . ~- 549/274 wo92/05311 4/1992 PCT 11101 App]. .
5,028,667 MCLaIII 618i. . -. wO92/l534O 9/1992 PCT lntil Appl' .
5,041,529 8/1991 Shinoda et a1. .. 528/354 WON/17155 11/1992. PCTIm’l APPL _
Bhatia .............. .. .. United i

Nieuwenhuis et 8.1. ........... .. United i

Muller ............................... .. United Kingdom ‘
5,076,983 Loomis 61 a1. .. 2145422 United Kingdom .
5,097,005 3/1992 Tietz ................. .. .. 528/272
5,108,399 4/ 1992 Eitenmuller et al. 606/77 OTHER PUBLICATIONS
5,132,397 7/1992 DeGuia .................... .. .. 528/ 354 . . . .

5,134,171 7/1992 Hammel et a1. ......... .. 521/93 E- FlliichloPe’ E-_ C°§te1l°1 T‘ D1?” and C- Flsher
5,136,017 8/1992 Kharas et a1_ __ 528/354 (“Lactic Ac1d Denvanves as Plastlcizers Esters of Pol
5,l36,057 8/1992 Bhatia ........... .. 549/274 ymeric Lectic Acid”, 1951, Bur. Agric. Ind. Chem, v.
5,142,023 8/1992 Gruber et al. 528/354 11, pp_ 1-11)_
5,149,833 9/1992 HFSS ef al 549/274 D. Deane and E. Hammond (“Coagulation of Milk for
Sinclair ......... .. .. cheese_Making Ester Hydrolysis”, Journal of
5,210,296 5/1993 Cockrem et a1. .. 562/589 D . S . v 43 1421_l429)
5,229,528 7/1993 Brake et a1. 549/274 ‘W3’ cfence' ;, .’ PP‘ ‘ . .
5,236,560 8/1993 Drysdale 203/99 Kulkarni et a1. ( 131odegradable Po1y(1act1c ac1d) Poly
5,247,058 9/1993 Gruber er a1. ,, 52g/354 mers”, 1971, J. Blamed. Mater. Res., v. 5, pp. 169-181).
5,247,059 9/1993 Gruber et a1. .. .. 528/354 A. Schindler, R. Jeffcoat, G. Kimmel, C. Pitt, M. Wall
5,258,488 11/1993 Gruber et a1. .................... .. 528/354 and R. Zweidinnger (“Biodegradable Polymers for
Sustained Drug Delivery”, 1977, Contemporary Topics
FOREIGN PATENT DOCUMENTS in Polymer Science, v. 2, pp. 251-287).
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923245 3/1973 Canada . (List continued on next page.)
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Page 3
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G. Van Hummel and S. Harkema (“Structure of
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F. Kohn, J. Van Don Berg, G. Van De Ridder and J.
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A. Chavla and T. Chang (“In-Vivo Degradation of
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I. McNeill and H. Leiper (“Degradation Studies of
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(published on an unknown date in 1986 by Ciba-Geigy
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J. Leenslag and A. Pennings (“Synthesis of high
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Nakamura et al. (“Surgical Application of Biodegrad
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K. Jamshidi, S. Hyon and Y. Ikada (“Thermal Charac
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unknown date in 1989, by Stars Laboratory, Additives
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“GE Specialty Chemicals Product Guide CA -4001E”,
(published on an unknown date in 1989, by General
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WV 26102).
“Tinuvin @ 123 Hindered Aminoether Light Stabilizer
for Coatings”, (published on an unknown date in 1989,
by Ciba-Geigy Corporation, Three Skyline Drive,
Hawthorne, NY. 10532).
“Irganox® B-Blends Antioxidants and Process Stabi
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brochure published on or before May 1, 1990, by Uni
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06749).
“Ethanox® 398 Antioxidant, The First Fluorophos
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Florida Blvd., Baton Rouge, La. 70801).
“The Resomer ® Resorbable Polyesters” (published on
or before an unknown date in Feb., 1991 by Boehringer
Ingelheim KG, D-6507 Ingelheim, W. Germany).
P. Klemchuk, (“Introduction to Polymer Degrada
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Principles of Polymer Degradation and Stabilization in
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tute of Materials Science, State University of New York
at New Paltz).
R. Thomas, (“Degradation and Stabilization of Engi
neering Polymers ”, lecture notes distributed at a semi
nar entitled: Principles ofPolymer Degradation and Stabi
lization in Orlando, Fla., Oct. 28-30, 1991, sponsored by
The Institute of Materials Science, State University of
New York at New Paltz).
W. Enlow, (“Process Stabilization with Phosphite Anti
oxidants”, lecture notes distributed at a seminar entitled:
Principles of Polymer Degradation and Stabilization in
Orlando, Fla., Oct. 28-30, 1991, sponsored by The Insti
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at New Paltz).
“Naugard ® XL-l Specialty Chemicals”, (product
brochure published on an unknown date in Feb., 1992,
by Uniroyal Chemical Co., Inc., Middlebury, Conn.
06749). ' as Narcotic Antagonist Delivery Systems”, Life Sci
Sir John Meurig Thomas, (“Solid Acid Catalysts 38 ,
Apr. 1992, Scientific American, pp. 112-118).
“Argus Product Data, Argus ® Dimyristyl Thiodipro
pionate”, (published on or befor an unknown date in
Aug, 1992, by Argus Division, Witco Corporation, 633
Court Street, Brooklyn, N.Y. 11231-2193).
“Argus Thiochemical Product Data, Argus ® Thiodi
propionate” (published on or before an unknown date in
Aug., 1992, by Argus Division,” Witco Corporation,
633 Court Street, Brooklyn, N.Y. 11231-2193).
“Argus Product Data, Argus ® Distearyl Thiodipropi
onate”, (published on or before an unknown date in
Aug., 1992, by Argus Division, Witco Corporation, 633
Court Street, Brooklyn, N.Y. 11231-2193).
“Argus Product Data, Mark® 2140 Pentaerythrityl
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known date in Aug., 1992, by Argus Division, Witco
Corporation, 633 Court Street, Brooklyn, NY
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“Argus Thiochemical Product Data, Argus ® Dilauryl
Thiodipropionate”, (published on or before an un
known date in Aug., 1992, by Argus Division, Witco
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“Argus Product Data, Seenox ® 4125 Pentaerythritol
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before an unknown date in Aug., 1992, by Argus Divi
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“Irganox® MD 1024, Metal Deactivator/Antioxi
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US. Patent Oct. 18, 1994 Sheet 1 of 8 5,357,035

FEED CRUDE LACTIC ACID TO

AN EVAPORATOR CONTINUOUSLY

REMOVE WATER OR SOLVENT ___ DISCARD OR RECYCLE

FROM CRUDE LACTIC ACID REMOVED WATER. SOLVENT OR
* CONDENSATION BY-PRODUCT
FEED CONCENTRATED LACTIC ACID
TO A PRE-POLYMER REACTOR
I RECYCLE 0R DISCARD
POLYMERIZE CONCENTRATED
LACTIC ACID TO FORM A _.. REMOVED WATER. SOLVENT OR
CONDENSATION BY-PRODUCT
PRE-POLYMER BY-REMOVING WATER coNm‘mM-ED wn-H me no
FEED PRE-POLYMER TO __ SIMULTANEOUSLY FEED CATALYST
A LACTIDE REACTOR TO A LACTIDE REACTOR
L

REMOVE CRUDE LAC-"DE As REMOVE AND RECYCLE OR DISCARD

HIGH BOIUNG UNREAC'I'ED POLYMER
A VAPOR FROM LACTIDE REACTOR As UQUID FRO" W m
I
PARTIALLY CONDENSE CRUDE F__J RDIOVE WATER AND
LACTIDE IN A CONDENSER LACTIDE IMPURI'IY AS A VAPOR
i AND REC’YCLE OR DISCARD
FEED CONDENSED ‘CRUDE LACTIDE
TO A DISTILLATION SYSTEM
I
PURIFY LACTIDE IN THE REMOVE WATER AND ucnc
msnumou SYSTEM -" ACID IMPURITIES AS A
i DISTILLATE / OVERHEAD STREAM,
REMOVE PURIFIED LACTIDE AS RECYCLE 0" D'SCARD
A HIGH BOILING BOTTOMS STREAM
FROM THE DISTILLATION SYSTEM
I
FEED PURIFIED LACTIDE AS
A UQUID DIRECTLY TO A
POLYMERIZATION SYSTEM
I
POLYMERIZE LACTIDE
TO POLYLACTIDE FIG. 1
US. Patent 0a. 18, 1994 Sheet 2 of 8 5,357,035

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US. Patent Oct. 18, 1994 Sheet 5 of 8 5,357,035

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US. Patent Oct. 18, 1994 Sheet 7 of 8 5,357,035

0u
noI

z5oE.mz3ou
\.6:@n8882o6r .9\068:gHE1MBE -
-
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US. Patent Oct. 18, 1994 Sheet 8 of 8 5,357,035

ONN

_
_

c2 .2.“
m

our

mRar-.05 ._.< ZDEQSOM

 5,357,035
1 2
by evaporation or other means. The overall polymeriza
CONTINUOUS PROCESS FOR MANUFACTURE tion reaction is represented by:
OF LACI‘IDE POLYMERS WITH PURIFICATION
BY DISTILLATION

CROSS-REFERENCE TO RELATED
APPLICATION CH3
The present application is a continuation application Lactic Acid
of both U.S. applications Ser. No. 07/926,901, ?led
Aug. 7, 1992, and U.S. Ser. No. 07/927,149 also ?led 0 0
Aug. 7, 1992. U.S. Ser. No. 07/926,901 issued as U.S. ll ll ll
Pat. No. 5,258,488 on Nov. 2, 1993. U.S. Ser. No.
07/ 927,149 issued as U.S. Pat. No. 5,247,058 on Sep. 21,
HO—(IZH—C
CH3
O-(fH-C
CH3
O-(fH-C-OH
CH3
+
n-2
1993. Each of U.S. Ser. No. 07/927,149 and U.S. Ser.
No. 07/926,901 is a continuation of U.S. Ser. No. n-1 H2O
07/ 825,059 ?led Jan. 24, 1992 and now issued as U.S.
Water
Pat. No. 5,142,023.
BACKGROUND OF THE INVENTION While step 11 of said polymerization reaction is repre
1. Field of the Invention 20 sented by:
The present invention relates to processes for the
continuous production of lactide polymers from crude
lactic acid in the ?eld of biodegradable polymers.
2. Description of the Prior Art
The continued depletion of land?ll space and the 25
problems associated with incineration of waste have led
to the need for development of truly biodegradable
polymers to be utilized as substitutes for non-biodegrad
able or partially biodegradable, petrochemical-based
polymers. The use of lactic acid and lactide to manufac
ture a biodegradable polymer is well known in the med
ical industry. As disclosed by Nieuwenhuis et a1. (U.8.
Pat. No. 5,053,485), such polymers have been used for
making biodegradable sutures, clamps, bone plates and
biologically active controlled release devices. It will be
appreciated that processes developed for the manufac
ture of polymers to be utilized in the medical industry
have incorporated techniques which respond to the Water
need for high purity and biocompatibility in the ?nal
' polymer product. Furthermore, the processes were As Dorough (U.S. Pat. No. 1,995,970) recognized
designed to produce small volumes of high dollar-value and disclosed, the resulting polylactic acid is limited to
products, with less emphasis on manufacturing cost and a low molecular weight polymer of limited value, based
yield. It is believed that prior to Applicants’ develop on physical properties, due to a competing depolymeri
ment, viable, cost-competitive processes for the contin zation reaction in which the cyclic dimer of lactic acid,
uous manufacture of lactide polymers from lactic acid 45 lactide, is generated. As the polylactic acid chain
having physical properties suitable for replacing present lengthens, the polymerization reaction rate decelerates
petrochemical-based polymers in packaging, paper until it reaches the rate of the depolymerization reac
coating and other non-medical industry applications tion, which effectively, limits the molecular weight of
were unknown. the resulting polymers. An example of this equilibrium
50 reaction is represented below.
It is known that lactic acid undergoes a condensation
reaction to form polylactic acid when water is removed

ll
no-cpn-c-o-prvc
CH3 CH3 CH3

i/CHST .4
 5,357,035
-continued

CH3

Given this understanding, Dorough was convinced

that high molecular weight polymers could not be gen ing improved biodegradability. However, no commer
erated directly from lactic acid. He was, however, suc cially viable process for the large-scale manufacture of
cessful in generating high molecular weight polymers such lactide polymers is believed to have been disclosed
from lactide, through the lactic acid dimer generated 15 to date.
from the low molecular weight polymers of lactic acid. Lactic acid is commercially available and manufac
Because these polymers are generated from lactide, tured from several known processes. Representative
they are known as polylactides. examples of such processes are disclosed by Glassner et
It is well known that lactic acid exists in two forms a1. (European Patent Application, EP 393818, Oct. 24,
which are optical enantiomers, designated as D-lactic 20 1990), G. Machell, “Production and Applications of
acid and L-lactic acid. Either D-lactic acid, L-lactic Lactic Acid”, Industrial Chemist and Chemical Manu
acid or mixtures thereof may be polymerized to form an facturer, v. 35, pp. 283-90 (1959) and Kirk Othmer,
intermediate molecular weight polylactic acid which, Encyclopedia of Chemical Technology, “Lactic Acid”, v.
upon further polymerization, generates lactide as earlier 12, pp. 177-78 (2nd ed. 1963).
disclosed. The lactide, or the cyclic dimer of lactic acid, 25 The optical activity of either lactic acid or lactide is
may have one of three types of optical activity depend known to alter under certain conditions, with a ten
ing on whether it consists of two L-lactic acid mole dency toward equilibrium at optical inactivity, where
cules, two D-lactic acid molecules or an L-lactic acid equal amounts of the D and L enantiomers are present.
molecule and a D-lactic acid molecule combined to Relative concentrations of D and L in the starting mate
form the dimer. These three dimers are designated L 30 rials, the presence of impurities or catalysts and time at
lactide, D-lactide and meso-lactide, respectively. In varying temperatures and pressures are known to affect
addition, a 50/50 mixture of L~lactide and D-lactide the rate of such racemization.
with a melting point of about 126° C. is often referred to Muller (U.S. Pat. No. 5,053,522) discloses that the
in the literature as D,L-lactide. preparation of optically pure lactide from an optically
DeVries (U .8. Pat. No. 4,797,468) recently disclosed 35 pure lactic acid feed is possible when utilizing appropri
a process for the manufacture of lactide polymers utiliz ate conditions and catalysts. However, there is no
ing a solvent extraction process to purify lactide prior to teaching of a process which controls the optical purity
polymerization. With DeVries’ disclosure, the inventor of the resulting lactide to desired degrees or minimizes
recognized that existing literature recommends puri? overall costs and maximizes yield of the lactide product.
cation of lactide by several recrystallization steps. It is Furthermore, there is no disclosure of a commercially
believed that processes prior to DeVries solvent extrac viable lactide puri?cation system, which allows produc
tion method, have generally utilized a recrystallization tion of polymer grade lactide, from crude lactic acid,
step to purify the crude lactide in order to obtain a which may subsequently be polymerized to produce a
source of lactide suitable for polymerization. However, variety of non-medical-related polylactide polymers
processes utilizing such recrystallization steps are 45 suitable for replacing existing petrochemical-based pol
known to have relatively poor yields due to signi?cant ymers.
losses of lactide during the recrystallization steps. It is Accordingly, a need exists for a continuous manufac
believed that producers of medical-related biodegrad turing process which utilizes commercially-available
able products have not been concerned with such low lactic acid to produce polylactide polymers suitable as a
yields because of the high margin generally expected 50 cost-competitive replacement for petrochemical-based
for sales of such products and the lack of competitive polymers. The present invention addresses this need as
alternatives. It will be appreciated, however, that in well as other problems associated with the production
developing a process for the large-scale, commercial of lactide polymers. The present invention also offers
manufacture of biodegradable polymers, such as poly further advantages over the prior art, and solves other
lactides, for use in nonmedical-products-oriented appli 55 problems associated therewith.
cations where such polymers will necessarily compete
with low-cost polymers made from petrochemicals, it SUMMARY OF THE INVENTION
will be important to maximize yield and minimize other The present invention provides a continuous process
overall cost factors to produce a biodegradable polymer for the production of lactide polymers from a crude
which is cost-competitive. 60 lactic acid feed source. The crude lactic acid feed may
The biogradable polylactide polymers must also pos be any available combination of the optical enantiomers
sess physical properties suitable for application in non D-lactic acid and L-lactic acid in solution with a hy
medical products presently utilizing petrochemical droxylic medium such as water or other solvent such as
based polymers such as packaging materials, paper coat methanol, ethanol, propanol, butanol, isopropanol, iso
ings and any other disposable articles. Nieuwenhuis et 65 butanol, or the like, or mixtures thereof. The source of
a1. disclose that lactide polymers derived from polymer lactic acid could also be an ester of lactic acid, such as
ization of mixtures of the three lactides result in poly methyl lactate, ethyl lactate, propyl lactate, butyl lac
mers with a variety of useful physical properties, includ tate, isopropyl lactate, isobutyl lactate or the like, or
 5,357,035
5 6
mixtures thereof. It is, however, recognized that the metal compounds derived from carboxylic acids or the
composition of the lactic acid feed source and the de like. It is believed, any such catalyst may be utilized in
sign and operating conditions of the process disclosed the process disclosed herein. Polymer properties will,
herein will affect the optical purity of the ?nal polylac however, vary. In a preferred embodiment, the pre
tide polymer product. The process disclosed herein 5 polymer and catalyst are mixed together in a static
provides for the control of racemization to advanta mixer to facilitate an even distribution of catalyst within
geously produce a polymer grade lactide of selected the prepolymer. The solution within the lactide reactor
optical purity and composition. Because racemization would quickly come to an equilibrium distribution of
can be controlled, it is possible to project the optical lactide and polylactic acid with the temperature and
purity and composition of the resulting product based catalyst employed. Heat is added to vaporize the crude
on that of the starting material. When polymerized, the lactide which is continuously removed from the lactide
resulting polylactide can have desirable physical prop reactor, thus driving the depolymerization reaction,
erties for a wide variety of non-medical related applica resulting in the net production of lactide as the contents
tions. Furthermore, impurities such as color bodies, of the lactide reactor seek equilibrium. It is believed that
carbohydrates, proteins, amino acids, salts, metal ions, 15 concentrations of unreactive high-boiling polylactic
and other carboxylic acids and organic acids, may be acid and other non-volatile impurities will concentrate
present in the crude lactic acid feed. Applicant’s process in the solution within the lactide reactor. It is believed
disclosed herein overcomes problems associated with this will require a purge stream to remove such impuri
producing a polymer grade lactide when such contami ties.
nants are present. 20 In a preferred embodiment of the present invention, a
Referring now brie?y to FIG. 1, which provides a portion of the purge stream of unreactive high boiling
preferred ?owchart of the overall process disclosed polylactic acid or other non-volatile impurities in the
herein, the crude lactic acid is ?rst fed to an evaporator, solution within the lactide reactor may be recycled to a
continuously. Within the evaporator a portion of the point prior to the lactide reactor system or fed to poly
water or solvent or any condensation reaction by-pro 25 merization. Based on experimental data which will fol
duct is removed from the crude lactic acid. The water low hereinbelow, it is believed that any long chain
or solvent or any condensation reaction by-product is lactic acid polymers will undergo transesteri?cation to
removed as a vapor from the evaporator and discarded form lower molecular weight polylactic acids which
or recycled. The evaporator thus concentrates the lac may be utilized as a feed source to the lactide reactor.
tic acid in the crude feed. It is believed there will be This allows further maximization of yield due to re
some condensation reaction occurring and the lactic duced loss of valuable feed material.
acid may start to form oligomers and low molecular The crude lactide vapor is composed of a mixture of
weight polymers during the evaporation step, produc all three possible lactides: L-lactide, D-lactide, and
ing a condensation reaction by-product. This concen meso-lactide, in various combinations. Along with the
trated lactic acid is next fed to a prepolymer reactor, 35 lactide, there is residual water, lactic acid and condensa
which in reality is a further evaporator. tion reaction byproducts. This crude lactide may be fed
It is well known in the art that as water or solvent are directly to a distillation system as a vapor for puri?ca
removed from a solution of lactic acid, the remaining tion In a preferred embodiment, this stream is fed to a
lactic acid will begin to polymerize. In the prepolymer partial condenser in which the lactide condenses and
reactor, suf?cient water or solvent and condensation 40 the majority of the water and other impurities remain as
byproducts such as water, ethanol, methanol, propanol, vapors and are recycled back to the lactide reactor or
butanol, isopropanol, isobutanol and the like are re other upstream process equipment such as the evapora
moved to cause the lactic acid to polymerize to form tor or prepolymer reactor. Preferably, the condensed
lactic acid polymers having an average molecular crude lactide is fed directly to a distillation system for
weight of about 100 to about 5000, preferably about 200 45 puri?cation. Within this distillation system residual
to about 3000, and more preferably about 400 to about water and lactic acid are preferably removed as a distil
2500. The water or solvent removed is recycled or late product and recycled back to the lactide reactor or
discarded. In preferred embodiments, the water or sol other upstream process equipment such as the evapora
vent is recycled back to the evaporation process, be tor or prepolymer reactor. In addition, provision may
cause it may be contaminated with lactic acid. In this be made to remove low molecular weight oligomers
preferred embodiment, loss of feed material is pre which may be present in the crude lactide or formed
vented and the overall yield is increased. during distillation. The puri?ed lactide is preferably fed
It is recognized by Applicants that the evaporation to a polymerization reactor of conventional design.
and prepolymerization stages may be combined into one The preferred overall process disclosed herein allows
step. However, Applicants have discovered the bene?t 55 for the continuous manufacture of lactide polymers
of utilizing two steps that allow ?rst removing uncon from a crude lactic acid with little or no waste of raw
taminated water or solvent in the evaporation step material lactic acid feed. This is accomplished by main
which is readily discarded or reused without treatment. taining the crude lactide which waste generated in the
The vapor stream from the prepolymerization reactor is lactide reactor as a liquid or vapor and avoiding the
greatly reduced in volume, yet contains some lactic yield loss associated with the recrystallization step tra
acid. Recycling back through the initial evaporation ditionally used to purify the lactide. The puri?ed lactide
step allows recovery of any lactic acid carryover, thus leaving the distillation system is further maintained as a
preventing loss of any valuable feed material. liquid and fed into a polymerization process. Other
The prepolymer product from the prepolymer reac monomers may be added to this puri?ed liquid lactide
tor, polylactic acid or PLA, is fed to a lactide reactor. A 65 prior to polymerization to achieve production of co
catalyst is simultaneously and continuously fed to the polymers of polylactide. Representative co-polymers
lactide reactor. Many suitable catalysts are known, such are disclosed by P. Dave, N. Ashar, R. Gross, S. Mc
as metal oxides, metal halides, metal dusts and organic Carthy, Survey of Polymer Blends Containing Poly
 5,357,035
7 8
(3-hydroxybutyrate-co-16% hydroxyvalerate), Polymer and high boiling impurities prior to distillation of the
Preparation, American Chemical Society, v. 31 (1), pp. crude lactide stream which is subsequently polymer
442-3 (1990); B. Riedl and R. Prud’homme, “Thermo ized. The prior art fails to disclose a process with such
dynamic Study of Poly(vinyl chloride)-Polyester advantages. Further, Applicants have found that impu~
Blends-by Inverse Gas Phase Chromatography” J Poly rities may prevent catalyst activation. In a preferred
mer Science, Part B, vol 24(1 1), pp. 2565-82 (1986); H. embodiment, this problem is overcome by first activat
Younes and D. Cohn, Phase Separation in Poly(ethy ing the catalyst by heating a mixture of the catalyst and
lene glycol)/Poly(lactic acid) Blends, European Polymer puri?ed lactic acid or lactide, then feeding such acti
.I., v. 24(8), pp. 765-73 (1988); Smith et al. (European vated catalyst with the crude lactic acid feed. It is be
Patent Application, EP 209371, Jan. 21, 1987); Pines et H 0 lieved the prior art contains no such teaching.
al. (European Patent Application EP 109197, May 23, These and various other advantages and features of
1984); J. Zhu, Y. Shao, W. Sui, S. Zhang, H. Xiao and novelty which characterize the present invention are
X. Tao, “Homopolymers and Copolymers of Glycolide pointed out with particularity in the claims annexed
and Lactide”, C-MRS Int. Symp. Proc. Meeting Date hereto and forming a part hereof. However, for a better
1990, v. 3, pp. 387-90 (1990); Jarrett et al. (US. Pat. No. understanding of the invention, its advantages, and the
4,788,979); and, T. Nakamura et al., Surgical Applica objects attained by its use, reference should be made to
tion of Biodegradable Films Prepared from Lactide the drawings which form a further part hereof, and to
Epsilon-Caprolactone Copolymers, Advanced Bioma the accompanying descriptive matter, in which there
terials, 7 (Biomater. Clin. Appl.) pp. 759-64 (1987). are illustrated and described preferred embodiments of
Applicants believe any monomer capable of co 20 the present invention.
polymerizing with lactide may be used with the process
disclosed herein. BRIEF DESCRIPTION OF THE DRAWINGS
In particular, this system allows recovery of any In the drawings, in which like referenced numerals
meso-lactide which may be present or formed within indicate corresponding parts or elements of preferred
the disclosed process and which is normally lost in a 25 embodiments of the present invention throughout the
recrystallization process. Further, the problems associ several views;
ated with handling solid materials are eliminated. These FIG. 1 is a flow diagram of the preferred overall
problems are well-documented by D. D. Deane and E. process steps of the present invention;
G. Hammond in “Coagulation of Milk for Cheese-Mak FIG. 2 is a detailed schematic representation of a
ing by Ester Hydrolysis”, J. Dairy Science, v. 43, pp. 30 preferred polylactide polymer production system in
1421-1429 (1960) and Nieuwenhuis et al. (US. Pat. No. accordance with the present invention;
5,053,485) which are incorporated herein by reference. FIG. 3 is a graph showing the effects of sodium on
The problems of storing such solids for any time period lactide production rate and optical purity;
are also disclosed by Deprospero et al. (U.S. Pat. No. FIG. 4 is a graph which represents the relationship
3,597,449) and F. E. Kohn et al. in J. ofApplied Polymer between the optical purity of generated lactide in rela
Science, Vol. 29, 4265-4277 (1984) which are incorpo tion to the molecular weight of the feed to the lactide
rated herein by reference. These problems include con reactor;
tamination by water vapor which would lead to ring FIG. 5 is a graph showing the relationship between
opening side reactions causing the lactide to convert to catalyst concentration and optical purity of the result
lactic acid. The presence of lactic acid in the feed to the 40 ing lactide;
?nal polymerization step will result in polymers of lirn FIG. 6 is a graph showing the effect of hydroxyl
ited molecular weight. impurities on polymer molecular weight at different
It is believed that the prior art does not teach use of temperatures;
distillation to purify crude lactide streams. Applicants FIG. 7 is a graph showing the effect of hydroxyl
believe that one would not turn to utilization of distilla 45 impurities on polymer molecular weight at different
tion due to the narrow differences between melting catalyst concentrations; and,
point and boiling point of lactide streams, which poten FIG. 8 is a graph showing the equilibrium lactide
tially could cause solid plugging problems within a concentration as a function of temperature.
distillation system. Furthermore, side reactions in
which the lactide ring is opened and polymers of lactic DETAILED DESCRIPTION OF THE
acid are formed may occur during distillation. It is be PREFERRED EMBODIMENTS
lieved, the prmence of such side reaction products As required, detailed embodiments of the present
would lead to undesirable molecular weight limitations invention are disclosed herein. However, it is to be
in the ?nal polymer product. Applicants have discov understood that the disclosed embodiments are merely
ered that proper design and control of a distillation 55 exemplary of the present invention which may be em
system coupled with direct feed of a crude lactide vapor bodied in various systems. Therefore, specific details
stream or a liquid crude lactide stream after partial disclosed herein are not to be interpreted as limiting, but
condensation to remove water and lactic acid vapor rather as a basis for the claims and as a representative
allows puri?cation of crude lactide in a conventional basis for teaching one skilled in the art to variously
distillation system. Previous to this disclosure, appli practice the present invention.
cants believe, any polymer made from non-optically Referring now to the ?gures, FIG. 2 represents an
pure lactide relied on blending the various lactide com overall schematic ?owchart encompassing the pre
ponents, each of which had been puri?ed separately ferred process disclosed herein. A crude lactic acid feed
using recrystallization of a crude lactide produced by (2) is provided. The crude lactic acid feed may be of
other techniques. 65 various grades. This could include USP, food grade, or
The present system also allows use of crude lactic any other solution in a hydroxylic medium. A hydrox
acid streams which contain impurities. As designed, the ylic medium is a medium which contains molecules
present system allows for removal of both low boiling having a hydroxyl group, mediums such as water, meth
 5,357,035
10
anol, ethanol, propanol, butanol, isopropanol, isobuta bly from about 75% to about 99% and more preferably
nol and the like, preferably having a number of carbon from about 85% to about 99%. In a preferred embodi
atoms in a range from 0-4, more preferably in a range ment, the evaporator system (22) is utilized to concen
from 0—2. The crude lactic acid can include from about trate the crude lactic acid feed from about 15% lactic
1% to about 99% by weight lactic acid, preferably, acid up to about 85% lactic acid.
from about 1% to about 85%, more preferably from The concentrated lactic acid is transferred via a ?uid
about 5% to about 50%. In a preferred embodiment, the transfer mechanism (24) through a pipeline (26) to a
crude lactic acid feed is a solution of about 15% lactic prepolymer reactor (38). The prepolymer reactor (38) is
acid and about 85% water which is commercially pro essentially a second evaporator system of any conven
duced. Many manufacturing processes for producing tional type which is utilized to further remove water or
crude lactic acid are known in the art, such as Glassner solvent from the crude lactic acid feed. A portion of the
et al., (European Patent Application, EP 393818, Oct. water or solvent vapor now also includes such water or
24, 1990); G. Machell, “Production and Applications of solvent produced from the lactic acid polymerization
Lactic Acid”, Industrial Chemist and Chemical Manu reaction previously disclosed, the condensation reac
facturer, v. 35, pp. 283-90 (1959) and Kirk Othrner, 15 tion by-product. The water or solvent vapor leaves the
Encyclopedia of Chemical Technology, “Lactic Acid”, v. prepolymer reactor (38) via line (32) and is condensed in
12, pp. 177-78 (2nd ed. 1963), which are incorporated a condenser (30). The condensed liquid is transferred
herein by reference. In an alternative embodiment, the via pipeline (36) to a transfer mechanism (34), with the
source of crude lactic acid (2) could be in the form of transferred liquid comprising water or solvent with
the ester of lactic acid such as methyl lactate, ethyl 20 small amounts of lactic acid and other impurities pres
lactate, and the like. These esters are known intermedi ent. This liquid may be discarded through line (28) or
ate products of the lactic acid process disclosed above may be recycled through line (29) back to a static mixer
and incorporated herein by reference. or other mixing mechanism and fed once again through
It is well known in the art that lactic acid includes line (8) to the evaporator (22). The remaining liquid in
two optical isomers, the L and D enantiomers. Either 25 the prepolymer reactor is continuously transferred via
optical isomer or any combination thereof may be uti transfer mechanism (40) through line (42) to a hold tank
lized as a crude lactic acid feed to the present reactor (44).
system. Furthermore, Applicants recognize that the As previously disclosed, it is well recognized in the
crude lactic acid feed (2) may contain other impurities, art that lactic acid undergoes a condensation reaction to
such as color bodies, carbohydrates, proteins, amino form polylactic acid, the polymer of lactic acid, as
acids, salts, metal ions, and other carboxylic acids or water is removed. In a preferred embodiment of the
organic acids. As will be explained in greater detail present system, the prepolymer reactor (38) is utilized
below, and in Example 1, the overall system incorpo to remove adequate water or solvent and condensation
rated in the present invention includes outlets for such reaction by~product from the lactic acid to cause poly
impurities so that their impact on ?nal polymer prod merization up to a molecular weight of about 100 to
ucts is limited. These outlets are designated as (10), (28), about 5000, preferably about 200 to about 3000, and
(99), (71) and (66) of FIG. 2. Each will be discussed in more preferably about 400 to about 2500. As will be
greater detail below. Thus, in preferred embodiments detailed in Example 2, which follows, in preferred em
the need for a more costly puri?ed crude lactic acid bodiments the molecular weight of the polylactic acid
feed is eliminated. leaving the prepolymer reactor impacts the chemical
A fluid transfer mechanism (4) is provided to trans purity as well as the optical purity of the crude lactide.
port the crude lactic acid feed (2) through an optional This in turn will affect the distillation and the properties
in-line mixer (6) in a pipeline (8) to an evaporator system of the ?nal polymer product.
(22). The evaporator system (22) is utilized to concen Applicants recognize that the evaporator system (22)
trate the crude lactic acid feed (2) by removing water or 45 and the prepolymer reactor (38) could be combined into
any other solvent or hydroxylic medium which is used a single system which provided removal of water or
as a carrier for the lactic acid, such as methanol, ethanol solvent suf?cient to concentrate the lactic acid feed and
or the like and any condensation reaction by-products. also to polymerize such lactic acid. In the preferred
The evaporator system (22) may be of any conventional embodiment, as discussed above, the systems are sepa
type known in the art, such as a multiple effect evapora rate to take advantage of recognized differences in the
tor, a wiped ?lm evaporator, a falling ?lm evaporator, composition of the vapor leaving the evaporator (22) at
or any other conventional system. It is appreciated that line (18) and the vapor leaving the prepolymer reactor
such systems may be operated at pressures below atmo (38) in line (32). The ?rst step of concentrating the
spheric pressure, at atmospheric pressure or above at crude lactic acid in the evaporator (22) from 15% lactic
mospheric pressure with commensurate changes in heat 55 acid to 85% lactic acid results in substantially pure
load and operating temperatures. In a preferred embodi water or solvent leaving the evaporator in line (18),
ment, vacuum evaporation is utilized to reduce racemi which may be readily discarded without treatment. The
zation. Water vapor or solvent vapor, in reference to vapor in line (32) leaving the prepolymer reactor (38)
the hydroxylic medium or condensation reaction by will necessarily contain lactic acid and other impurities
product, is removed from the evaporator via a transfer 60 which are carried over in the evaporation process.
line (18), and condensed in a condenser (16). The con These impurities will preferably need to be recycled or
densed liquid is transferred in a pipeline (14) to a fluid treated before discarded. Thus, in the preferred embodi
transfer mechanism (12), such as a pump or the like. The ment, Applicants take advantage of the economic bene
?uid transfer mechanism (12) transports the condensed ?ts of removing nearly pure water (or solvent) in the
water or solvent via pipeline (10) as a waste stream and 65 evaporator (22) and reduced recycle or waste treatment
is discarded. of the vapor leaving the prepolymer reactor (38).
The lactic acid may be concentrated to a weight Applicants also recognize that the evaporator system
percent lactic acid of about 50% to about 99%, prefera (22) and pre-polymer reactor (38) may be replaced by a
 5,357,035
11 12
series of batch evaporators that concentrate the lactic the purge stream may be fed to the polymerization
acid and produce pre-polymer. The series of batch sys reactor (110) via line (68), if such polymer is desired. A
tems may be operated to provide a net continuous sup transfer mechanism (64) is provided to transport the
ply of pre-polymer. purge stream optionally to a point prior to the evapora
The hold tank (44) is maintained at a temperature 5 tor (22) such as the static mixer (6) or to the feed line
suf?cient to keep the polylactic acid in a ?owable liquid (26) to the prepolymer reactor (38) or to waste through
state. The hold tank (44) is, however, only a feature of line (66) or to a static mixer (104) for polymerization in
the preferred embodiment, recognizing the control a polymerization reactor (110).
problems which may result from direct feed to the lac The lactide vapor leaving the lactide reactor (60) in
tide reactor (60). This liquid is transferred via transfer 10 line (58) is partially condensed in a condenser (72). The
mechanism (46) through a pipeline (48) to a static in-line uncondensed vapor consists of residual lactic acid and
mixer or other mixing mechanism (50). Within the mix water or solvent, along with some lactide which re
ing mechanism (50) a catalyst is added to the polylactic mains uncondensed. This vapor stream leaves the sys
acid. Applicants recognize that any means of adding the tem through line (90) and is condensed in a condenser
catalyst to the polylactic acid would be appropriate; 15 (92), the liquid thus being transferred by transfer mecha
however, the static mixer (50) utilized in the preferred nism (96) through line (94). This liquid may optionally
embodiment allows more even distribution of the cata be discarded through line (99) or recycled through line
lyst within the liquid. The catalyzed polylactic acid is (98) back to the crude lactic acid static mixer (6). In the
transferred via transfer line (54) to the lactide reactor preferred embodiment, this stream is recycled in order
(60). It is well recognized in the art that polylactic acid 20 to recover and utilize any lactic acid or lactide which is
maintains a dynamic equilibrium with its depolymeriza not condensed in partial condenser (72).
tion product, lactide, as represented by the reaction The condensed crude lactide leaving condenser (72)
below: via line (74) is transferred via ?uid transfer mechanism

l
o
|
C-H + HO-CH-C
l’ O-CH-C
l’ O-CH- C-OH
l
\ / \ | | l
C CH3 CH3 CH3 CH3
|| "-4
O

It is further recognized that this reaction is catalyzed

by such compounds as tin dust, tin halide, tin oxide, and (76) through line (78) to a distillation system (80) for
organic tin compounds derived from C1—C20 carboxylic puri?cation of the lactide. Applicants recognize that
acids, as disclosed by Muller in U.S. Pat. No. 5,053,522, 45 partial condensation may not be necessary and the
which is incorporated herein by reference. Other met crude lactide vapor may be fed directly to the distilla
als, such as zinc, and their halides, oxides and organic tion system (80). The distillate leaving the distillation
compounds thereof, have been recognized by the art as system (80) in line (82) is composed of water or solvent,
possible catalysts for the lactide reaction. It is believed some residual lactic acid, and some lactide carryover.
any metals of Groups IV, V or VIII of the Periodic 50 This stream is condensed in condenser (84) and trans
Table and compounds thereof, are possible catalysts for ferred via ?uid transfer mechanism (88), in line (86), and
generating lactide. In a preferred embodiment tin oxide may be discarded or recycled back to a point prior to
is utilized as catalyst. In a most preferred embodiment the evaporator (22), such as the static mixer (6) or the
the catalyst is activated prior to feed. feed line (26) to the prepolymer reactor (38) through
As lactide is generated within the lactide reactor (60), 55 line (71), or more preferably recycled in line (70) back
it is removed as a vapor continuously through line (58). to the static mixer (50) to be recatalyzed and re-fed to
The removal of lactide further drives the depolymeriza the lactide reactor (60). This preferred embodiment
tion reaction. It is believed that some high-boiling or allows minimization of waste by preventing loss of
non-volatile contaminants present in the feed to the lactic acid or converted lactic acid to lactide from the
entire system will concentrate in the lactide reactor and 60 feedstock.
necessitate inclusion of a purge stream (62). Example 1 The re?ned lactide is removed from the distillation
below details the effect of cationic impurities and Exam system (80) via transfer mechanism (100) in line (102)
ple 11, the detrimental effects of concentrating metal and fed to a polymerization reactor (110). Applicants
ions in the lactide reactor (60). It is believed other impu recognize that the distillation system (80) may include
rities would have a similar effect and necessitate the 65 more than one distillation column or a ?ash drum. The
purge stream (62). A portion of this purge stream (56) polymerization process may be of any conventional
may be recycled back to the static mixer (50) and recat design known to the art, such as that disclosed by J.
alyzed and fed to the lactide reactor (60). Alternatively, Leenslag and A. Pennings, “Synthesis of High Molecu
 5,357,035
13 14
lar Weight Poly (L-lactide) Initiated with Tin 2-Ethyl
hexanoate”, Makromol. Chem, v. 188, pp. 1809-14 degree of racemization (%) =
(1987) and F. Kohn et al., The Ring-Opening Polymeri
zation of D,L-Lactide in the Melt Initiated with Tet
raphenyltin, J. Applied Polymer Science, v. 29, pp. 100% [ % of malority 85188111101116!‘ — 50 :IX 100
4265-77 (1984), which are incorporated herein by refer
ence.
Applicants recognize that in a preferred embodiment Thus, an initial composition of 75% L and 25% D
one may choose to add a non-lactide monomer to the which results after racemization to a 50% L, 50% D
puri?ed lactide leaving the distillation system (80). This mixture would equate to a degree of racemization of
co-monomer may be added via line (101). The comono 100%. In all instances, no matter what initial composi
mers are fed to the polymerization reactor (110) and tion, a 100% degree of racemization coincides with a
polymerized to form a co-polymer. Many co-polymers composition of 50% each enantiomer, or optical inac
of polylactide are known to the art. These include P. tivity- This recognizes the tendency toward equilibrium
Dave, N. Ashar, R. Gross, S. McCarthy, Survey of at a 50% concentration of each enantiomer, corre
Polymer Blends Containing Poly (3-hydroxybutyrate sponding to optical inactivity. In the most preferred
co-16% hydroxyvalerate), Polymer Preparation, Ameri embodiment of the system, each unit operation is con
can Chemical Society, v. 31 (1), pp. 442-3 (1990); B. trolled to a degree that allows production of a puri?ed
Riedl and R. Prud’homme, “Thermodynamic Study of lactide mixture with selected chemical and optical com
Poly(vinyl chloride)-Polyester Blends by Inverse Gas position. The optical composition of the lactide mixture
Phase Chromatography”, J. Polymer Science, Part B, is determined by the relative abundance of D- and L
vol. 24(11), pp. 2565-82 (1986); H. Younes and D. lactic acid sub~units in the polylactic acid within the
Cohn, Phase Separation in Poly(ethylene glycol) lactide reactor. As recognized by Nieuwenhuis et al. in
/Poly(lactic acid) Blends, European Polymer J., v. 24(8), US. Pat. No. 5,053,485, the disclosure of which is in
‘ pp. 765-73 (1988); Smith et al. (European Patent Appli 25 corporated herein by reference, the blend of lactide
cation, EP 209371, Jan. 21, 1987); Pines et al. (European isomers used to produce the polymer affects the physi
Patent Application EP 109197, May 23, 1984); J. Zhu, cal properties of the polymer, including the biodegrad
Y.-Shao, W. Sui, S. Zhang, H. Xiao and X. Tao, “Ho ability.
mopolymers and Copolymers of Glycolide and Lac In a preferred embodiment, the evaporator (22) is
tide”, C-MRS Int. Symp. Proc. Meeting Date 1990, v. 3, operated to minimize residence time so that there is
; pp. 387-90 (1990); Jarrett et a1. (U.S. Pat. No. little or no effect on optical purity. The prepolymer
4,788,979); and, T. Nakamura et al., Surgical Applica reactor (38) is also operated to minimize racemization.
tion of Biodegradable Films Prepared from Lactide This includes reducing the residence time within the
Epsilon-Caprolactone Copolymers, Advanced Bioma reactor.
terials, 7 (Biomater. Clin. Appl.) pp. 759-64 (1987), The crude lactide produced in the lactide reactor (60)
which disclosures are incorporated herein by reference.will be a mixture of the three possible lactides which
Applicants believe any co-polymers of polylactide may may be generated from L- and D-lactic acid. These
be produced from the process disclosed herein. include an L-lactide, a D-lactide, and meso-lactide.
Fluid transfer mechanisms disclosed throughout this
As detailed in Example 3 hereinbelow, the concentra
detailed description would normally be a pump. How 40 tion of catalyst added to static mixer (50) also affects the
ever, Applicants recognize that through design choices degree of racemization and composition of the crude
other mechanisms for transfer, such as gravitational
flow, may also be utilized.
lactide product. In a preferred embodiment, the catalyst
Applicants further recognize that the preferred over concentration level is adjusted based on desired proper
all system described herein is a complex combination of ties of the ?nal polymer product.
many known chemical engineering unit operations. So Applicants have discovered, and detailed in Example
that the bene?t of the overall combination may be rec 12, that the quality of the crude lactide charged to the
ognized, Applicants herein disclose in further detail the distillation system has a signi?cant effect on the opera
selection, operation, and bene?ts of selecting such unit tion of said system. In particular, acidic impurities such
operations, along with actual laboratory experimental 50 as lactic acid and low molecular weight oligomers,
results exemplifying the disclosed advantages. which are formed by ring opening reactions of lactic
As previously stated, the crude lactic acids fed to this acid or water with lactide, can cause premature poly
process (2) may be made up of L-lactic acid or D-lactic merization in the distillation system. In a preferred em
acid, or combinations thereof. The composition of the bodiment, applicants believe such side reactions may be
feed, however, does not translate directly through the controlled by partially condensing the crude vapor
entire process to de?ne the composition of the polymer prior to feeding to distillation to remove impurities.
product leaving the polymerization reactor (110) The distillation system (80) may also be operated to
through line (108). Applicants recognize that racemiza control racemization of the lactide and other side reac
tion, or conversion of one optical enantiomer to the tions. In a preferred embodiment, this system is de
other, may occur. It is believed that such racemization 60 signed to minimize racemization by utilizing a packed
is driven by such factors as temperature, pressure, time column distillation system which minimizes liquid
at a given temperature or pressure, the presence of holdup, along with a thermal-siphon reboiler which
catalysts or impurities, and relative concentrations of limits residence time of the bottom liquids, and utilizing
the two enantiomers at any given time. The degree of a minimum re?ux ratio to further reduce holdup time in
racemization is de?ned herein by the percent conver 65 the column. It is, however, recognized that other distil
sion of the optical enantiomer that is present in excess of lation systems may be utilized with varying impact on
50%. As an equation, this calculation would be de?ned the optical purity of the puri?ed lactide and resultant
as: polymer product.