U.S. patent application number 09/523887 was filed with the patent office on 2002-10-24 for liquid crystalline polymers.
Invention is credited to Chickering, Donald E. III, Edwards, Edwin E., Jacob, Jules S., Jong, Yong S., Mathiowitz, Edith.
Application Number | 20020155146 09/523887 |
Document ID | / |
Family ID | 24086845 |
Filed Date | 2002-10-24 |
United States Patent
Application |
20020155146 |
Kind Code |
A1 |
Mathiowitz, Edith ; et
al. |
October 24, 2002 |
LIQUID CRYSTALLINE POLYMERS
Abstract
Methods for inducing a thermoplastic polymer, which can be
non-mesogenic, to exhibit liquid crystalline properties have been
developed. The method includes the steps of (a) heating the polymer
from an initial temperature below its glass transition temperature
(Tg) to a temperature greater than its Tg and below its melting
temperature (Tm); (b) exposing the polymer to a pressure greater
than about 2 metric tons/in.sup.2, preferably between about 2 and
10 metric tons/in.sup.2, preferably for at least about one minute,
while maintaining the temperature greater than its Tg; and (c)
cooling the polymer below the Tg while maintaining the elevated
pressure. Unlike many prior art transition processes which are
reversible, this process provides a liquid crystal state that can
be maintained for years at ambient conditions. In a preferred
embodiment, the plastics are bioerodible thermoplastic polymers,
such as polyanhydrides, some polyesters, polyamides, and
polyaromatics. The liquid crystalline polymers can be used in the
controlled release or retention of substances encapsulated in the
polymers. The polymer can be in a variety of forms including films,
film laminants, and microparticles. In a preferred embodiment, the
LC polymers are used to encapsulate therapeutic, diagnostic, or
prophylactic agents for use in medical or pharmaceutical
applications.
Inventors: |
Mathiowitz, Edith;
(Brookline, MA) ; Jacob, Jules S.; (Taunton,
MA) ; Chickering, Donald E. III; (Framingham, MA)
; Jong, Yong S.; (Providence, RI) ; Edwards, Edwin
E.; (Providence, RI) |
Correspondence
Address: |
PATREA L. PABST
HOLLAND & KNIGHT LLP
ONE ATLANTIC CENTER, SUITE 2000
1201 WEST PEACHTREE STREET
ATLANTA
GA
30309-3400
US
|
Family ID: |
24086845 |
Appl. No.: |
09/523887 |
Filed: |
March 13, 2000 |
Current U.S.
Class: |
424/426 ;
424/400 |
Current CPC
Class: |
C09K 19/38 20130101;
B29C 55/00 20130101; B29C 55/18 20130101; B29K 2105/0079
20130101 |
Class at
Publication: |
424/426 ;
424/400 |
International
Class: |
A61F 002/00; A61K
009/00 |
Claims
We claim:
1. A method for inducing a liquid crystalline state in a polymer
comprising the steps of: (a) heating the polymer from an initial
temperature below its glass transition temperature to a temperature
greater than its glass transition temperature and below its melting
temperature; and (b) applying pressure to the polymer until a
liquid crystalline state is induced in the polymer, while
maintaining the temperature at greater than the glass transition
temperature; and (c) cooling the polymer below the glass transition
temperature while maintaining the pressure.
2. The method of claim 1 wherein the pressure in step (b) and (c)
is between about 28 and 140 MPa.
3. The method of claim 1 wherein the polymer is pressed in step (b)
for greater than about one minute.
4. The method of claim 3 wherein the polymer is pressed in step (b)
for between about 1 and 10 minutes.
5. The method of claim 1 wherein the polymer is a non-mesogenic
polymer.
6. The method of claim 5 wherein the polymer is selected from the
group consisting of celluloses, poly(acrylic acid)s,
polyacrylonitriles, poly(L-analine)s, polyamides,
polybutylene-terephthalate, poly(.epsilon.-caprolactam),
poly(.epsilon.-caprolactone), polycarbonates, polyesters,
polyhydroxybutyrate, polyimides, polylactams, polylactones,
polymethacrylates, polynucleotides, polypropylenes, polystyrenes,
polytetrafluoroethylene, polyurethanes, and vinyl polymers.
7. The method of claim 1 wherein the polymer is a polyethylene.
8. The method of claim 1 wherein the polymer is bioerodible.
9. The method of claim 8 wherein the polymer is selected from the
group consisting of polycaprolactone, poly(fumaric acid-co-sebacic
acid), poly(carboxyphenoxypropane-co-sebacic acid), poly(maleic
acid), poly(hydroxy acids), copolymers of poly(hydroxy acids), and
blends thereof.
10. The method of claim 1 wherein the polymer is
non-bioerodible.
11. The method of claim 10 wherein the polymer is selected from the
group consisting of polyethylene, polystyrene, polyvinylphenol,
nylons, and polypropylene.
12. The method of claim 1 wherein the polymer is a mesogenic
polymer.
13. The method of claim 1 wherein the polymer is
water-insoluble.
14. The method of claim 13 wherein the polymer is selected from the
group consisting of polyolefins and polyesters.
15. The method of claim 1 wherein the polymer is water-soluble.
16. The method of claim 1 wherein the polymer is in a shaped form
selected from the group consisting of sheets, films, coatings,
pellets, beads, artificial organs, prosthetic devices, sutures, and
tissue engineering scaffolds.
17. A composition comprising a non-mesogenic polymer which exhibits
liquid crystalline properties at a temperature below the glass
transition temperature of the polymer.
18. The composition of claim 17 wherein the polymer is made by a
method comprising the steps of (a) heating the polymer from an
initial temperature below its glass transition temperature to a
temperature greater than its glass transition temperature and below
its melting temperature; and (b) applying pressure to the polymer
until a liquid crystalline state is induced in the polymer, while
maintaining the temperature at greater than the glass transition
temperature; and (c) cooling the polymer below the glass transition
temperature while maintaining the pressure.
19. The composition of claim 17 wherein the polymer is selected
from the group consisting of polyethylene, celluloses, poly(acrylic
acid)s, polyacrylonitriles, poly(L-analine)s, polyamides,
polybutylene-terephthal- ate, poly(.epsilon.-caprolactam),
poly(.epsilon.-caprolactone), polycarbonates, polyesters,
polyhydroxybutyrate, polyimides, polylactams, polylactones,
polymethacrylates, polynucleotides, polypropylenes, polystyrenes,
polytetrafluoroethylene, polyurethanes, vinyl polymers, poly(lactic
acid), polylactide-co-glycolide, copolymers thereof, and blends
thereof.
20. The composition of claim 17 further comprising an encapsulated
agent.
21. The composition of claim 20 wherein the encapsulated agent is
an active agent for use in medical or pharmaceutical
applications.
22. The composition of claim 20 wherein the encapsulated agent is
selected from the group consisting of perfumes, flavoring agents,
coloring agents, sunscreens, and pesticides.
23. A method for release of an encapsulated agent comprising
providing to a release site a composition comprising a) a polymer
which exhibits liquid crystalline properties at a temperature below
the glass transition temperature of the polymer, and b) an agent
encapsulated in the polymer.
24. The method of claim 23 wherein the agent is an active agent for
use in medical or pharmaceutical applications.
25. The method of claim 23 wherein the agent is selected from the
group consisting of scents, flavoring agents, coloring agents,
sunscreens, and pesticides.
26. An article for the release of an encapsulated agent comprising
a polymer which exhibits liquid crystalline properties at a
temperature below the glass transition temperature of the polymer,
and the agent encapsulated in the polymer, wherein the polymer is
in a form selected from the group consisting of films, laminants,
coatings, slabs, microparticles, containers for packaging of food
or drugs, and orthopedic or prosthetic devices.
27. A monolithic composition for controlled delivery of an active
agent comprising made using a process comprising providing a
polymer which contains substantially no liquid crystalline phase,
heating the polymer above its glass transition temperature and then
subjecting the polymer to a pressure sufficient to induce a liquid
crystalline phase in at least a portion of the polymer, and
combining the polymer with the active agent.
28. The composition of claim 27 wherein the polymer is
water-insoluble.
29. The composition of claim 27 wherein the polymer is
water-soluble.
30. The composition of claim 27 wherein the polymer is combined
with the active agent to form a mixture before the step of inducing
the liquid crystalline phase.
31. The composition of claim 27 wherein the polymer is combined
with the active agent after the step of inducing the liquid
crystalline phase.
32. The composition of claim 27 wherein the mixture of polymer and
active agent is heated above the melting temperature of the active
agent and then cooled before the step of inducing the liquid
crystalline phase.
33. A barrier composition for use in packaging comprising a
non-mesogenic polymer which exhibits liquid crystalline properties
at a temperature below the glass transition temperature of the
polymer, wherein the rate of diffusion of fluids through a layer of
the polymer is reduced relative to the rate of diffusion of fluids
through a layer of a form of the polymer which does not exhibit
liquid crystalline properties.
34. A packaging article comprising the barrier composition of
33.
35. The barrier composition of claim 33 wherein the fluid is
selected from oxygen, water vapor, liquid water, and carbon
dioxide.
Description
BACKGROUND OF THE INVENTION
[0001] This invention generally relates to liquid crystal
compositions, and more specifically to polymeric materials in a
liquid crystalline state.
[0002] Liquid Crystal Polymers
[0003] It has generally been thought that in order for normally
flexible polymers to display liquid crystalline characteristics,
rod-like or disk-like elements, i.e. mesogens, must be incorporated
into their chains. The placement of these mesogens typically
controls the type of liquid crystalline ("LC") polymer formed.
Polymer liquid crystals (PLCs) generally can be divided into two
types: main-chain PLCs and side-chain PLCs. Main-chain polymer
liquid crystals are formed when the mesogens are themselves part of
the main chain of a polymer. Conversely, side chain liquid crystal
polymers are formed when the mesogens are connected as side chains
to the polymer by a flexible bridge, or spacer.
[0004] Thermoplastic polymers combined with mesogens have been
extensively studied because the ordered fluid phases of liquid
crystals offer unique properties useful, for example, as precursors
to high performance polymeric films, fibers, and injection molded
articles. For example, U.S. Pat. No. 4,668,760 to Boudreaux Jr., et
al. describes a process that includes synthesizing a liquid crystal
polyester, devolatilizing the liquid crystal polyester, and then
shaping the devolatilized polyester into an article of manufacture,
such as fibers useful in tire cords. These polymers have mostly
been aromatic copolyesters, since many polymers, including some
aromatic homopolyesters, have melting points too high to form
thermotropic mesophases without decomposition.
[0005] Temperature and Pressure Induced Phase Changes
[0006] Elevated pressure is known to reversibly induce the
formation of a liquid crystalline state in mesogenic polymers. For
example, Hsiao, et al., Macromolecules 21:543-45 (1988) discloses a
process of heating a sample of HIQ-20 (a copolyester) above the
clearing temperature (342.degree. C.), applying a pressure of up to
6000 bar (0.6 GPa) to the sample, reducing the temperature to the
mesophase temperature, maintaining the temperature for 1 hr., and
then cooling the sample to room temperature at a rate of 3.degree.
C./min. It was found that cooling the mesophase into the solid
state under moderate pressure yielded a morphology that differed
from that in the solid cooled at ambient pressure. The study was
limited to the mesogenic polymer, HIQ-20.
[0007] Maeda, et al., Macromolecules 28:1661-67 (1995) describes a
study on the thermotropic polymer (4,4'-dihydroxybiphenyl)
tetradecanedioic acid polyester (PB-12), which is known to exhibit
liquid crystalline properties. The phase transition of PB-12 under
hydrostatic pressures up to 300 MPa was observed. The typical phase
transition of crystal (K)-smectic H (S.sub.H)-isotropic melt (I)
was observed under hydrostatic pressures up to 90-100 MPa and
elevated temperatures. A new smectic phase was formed irreversibly
from the usual S.sub.H phase by increasing pressure on a
quasi-isothermal process. After heating above the clearing
temperature, the sample was supercooled at high pressures, and the
glassy S.sub.B phase was found coexistent with the normal crystals
at room temperature under atmospheric pressure. Other thermotropic
polyesters studied include two homopolymers and the corresponding
copolymer based on 4,4'-biphenyldiol as the mesogen and aliphatic
dibasic acids containing 7 and 8 methylene groups as flexible
spacers (Maeda, et al., Makromol. Chem, 194:3123-34 (1993)).
[0008] Phase transitions as a function of temperature and pressure
have been studied on other select polymers. Rastogi, et al., Nature
353 (1991) examined poly(4-methyl-pentene-1), which is crystalline
under ambient conditions, and which was found to become reversibly
amorphous on increasing pressure in two widely separate temperature
regimes (approximately 20.degree. C. and 200.degree. C.). The
transformation occurred via liquid-crystal and amorphous phases as
pressure or temperature was varied. The liquid crystalline state
was not retained when returned to ambient conditions.
Polytetrafluoroethylene and polyethylene also have been examined
for structure of high pressure phases, as described in Tetuo
Takemura, "Structure and physical properties of high polymers under
high pressure" (Reprint of a paper read at November 1978 Meeting of
Polymer Science in Japan) and Plate & Shibaev, "Comb-Shaped
Polymers and Liquid Crystals" (Cowie, ed.) pp.207-09 (Plenum Press,
New York 1987). The references do not indicate retention of a
liquid crystalline state in these polymers at ambient temperature
after applying pressure.
[0009] Efforts to use liquid crystalline materials in controlled
release systems are described in U.S. Pat. No. 5,753,259 to
Engstrom, et al. These non-polymeric systems include a cubic liquid
crystalline phase and purportedly provide a highly reproducible
controlled drug release system, in contrast to solutions involving
polymers.
[0010] PCT WO 98/47487 discloses a drug delivery composition that
includes an active substance (e.g., drug) and a fatty acid ester
substance capable of forming a liquid crystalline phase in the
presence of a liquid medium. In these compositions, which can be
mixed with polycarbophiles, the lipid forms a liquid crystalline
state, but the polymer itself does not. Furthermore, the
requirement of a liquid medium, particularly water, significantly
limits the forms and uses of the compositions.
[0011] It is therefore an object of this invention to provide
non-mesogenic polymers that exhibit liquid crystalline properties
at ambient temperatures.
[0012] It is a further object of this invention to provide methods
for inducing a liquid crystalline state in any thermoplastic
polymer, preferably in the substantial absence of water.
[0013] It is a further object of this invention to provide methods
for inducing a liquid crystalline state in cross-linked
polymers.
[0014] It is another object of the present invention to provide a
liquid crystalline polymer that retains its liquid crystalline
state for an extended period of time, such as several hours or
years.
[0015] It is another object of this invention to provide
non-mesogenic polymer systems for the controlled release of a
variety of molecules, including therapeutic and diagnostic agents,
as well as cosmetics and fragrances.
[0016] It is still a further object of this invention to provide
methods for reducing the permeability of various polymers to
molecules, such as gases or fragrances, by inducing liquid
crystalline properties in the polymers.
[0017] It is another object of the present invention to provide
compositions including polymers such as high- and/or low-density
polyethylene having improved physical or mechanical properties
which are useful in various applications.
[0018] It is also an object of the present invention to provide
methods and articles for displaying information using polymers that
exhibit liquid crystalline properties at ambient temperatures.
[0019] It is another object of the present invention to provide a
method of inducing unique liquid crystalline states in mesogenic
polymers.
BRIEF SUMMARY OF THE INVENTION
[0020] Methods are provided for inducing a polymer, which can be
non-mesogenic or mesogenic, to exhibit liquid crystalline
properties. The method includes the steps of (a) heating the
polymer from an initial temperature below its glass transition
temperature (Tg) to a temperature greater than its Tg and below its
melting temperature (Tm); (b) exposing the polymer to a pressure
greater than about 28 MPa (2 metric tons/in.sup.2), preferably
between about 28 and 140 MPa (2 and 10 metric tons/in.sup.2),
typically for between about 30 seconds and 5 minutes, preferably
for at least about one minute, while maintaining the temperature
greater than its Tg; and (c) cooling the polymer below the Tg while
maintaining the elevated pressure, typically for between about 30
seconds and 5 minutes. Unlike many prior art transition processes
which are reversible at ambient conditions, this process produces a
liquid crystalline state, or another new state with similar
characteristics, that can be maintained for years at ambient
conditions, even after removing the pressure.
[0021] Methods for identifying polymers having liquid crystals
("LC") or non-LC ordered phases include those known in the art,
such as optical pattern or texture observations with a polarizing
microscope, differential scanning calorimetry, miscibility or
density comparisons, molecular orientations by either supporting
surface treatments or external fields, and classical x-ray and
x-ray diffraction techniques.
[0022] Polymer can be bioerodible or non-bioerodible.
Representative non-mesogenic, bioerodible polymers include
polylactic acid, polylactide-co-glycolide, polycaprolactones,
polyvaleric acid, polyorthoesters, polysaccharides, polypeptides,
and certain polyesters. Representative mesogenic, bioerodible
polymers include some polyanhydrides and polybutylene
terephthalate. Preferred non-mesogenic, non-erodible polymers
include polyethylene, polypropylene, polystyrene, and
polytherephthalic acid. The polymer can be water-soluble or
water-insoluble.
[0023] The liquid crystalline polymers described herein can be used
in the controlled release or retention of substances encapsulated
in the LC polymers. The polymer can be in a variety of forms
including films, film laminants, and microparticles. In a preferred
embodiment, the LC polymers are used to encapsulate therapeutic,
diagnostic, or prophylactic agents for use in medical or
pharmaceutical applications. Other substances which can be
encapsulated include scents such as perfumes, flavoring or coloring
agents, sunscreen, and pesticides.
[0024] The methods of inducing liquid crystalline properties in
polymer also can be used to improve the permeability of polymers in
numerous applications, such as packaging, particularly food and
pharmaceutical packaging. The methods similarly can be used to
enhance the structural performance of polymeric devices, such
prosthetics made of polyethylenes.
BRIEF DESCRIPTION OF THE DRAWINGS
[0025] FIG. 1 is a graph showing release rate (hours) of insulin
fabricated in polycaprolactone polymeric slabs prepared in three
different formulations: solvent cast (triangle), melt cast
(square), and liquid crystalline state (diamond).
[0026] FIGS. 2A and 2B are graphs showing thermal analysis
(temperature, .degree. C. versus heat flow, mW) of a commercial
poly(tetrafluoroethylen- e) film, TEFLON.TM., before and after
heating above the glass transition temperature (20.degree. C.) and
pressing for 1 min. using a pressure of 890 MPa (10 metric tons per
cm.sup.2). FIG. 2A shows an LC sample (after heat treatment) and
FIG. 2B shows a non-LC sample (before heat treatment). The first
run of the Differential Scanning Calorimetry (DSC) revealed a glass
transition at 2.degree. C. and a broad peak between 129-150.degree.
C. which was attributed to the new phase which was probably in
equilibrium with the amorphous phase.
[0027] FIG. 3 is a graph showing thermal analysis (temperature,
.degree. C. versus heat flow, mW) of polystyrene films 2.5 kDa that
were first heated to the indicated temperatures, 23, 50, 70, 83,
90, and 100.degree. C., and pressed by holding for 3 minutes at
-20.degree. C., then heating for -20.degree. C. to 250.degree. C.
at 10.degree. C./min. at 890 MPa. There are two new transitions
before the glass transition for the samples processed at
temperatures of 70, 80, 90, and 120.degree. C.
[0028] FIGS. 4A-4B are graphs showing thermal analysis of
polystyrene films (45 kDa) that were heated to the indicated
temperatures, 23, 60, 80, 100, and 120.degree. C., pressed as
described in FIG. 3, cooled from 250.degree. C. to 20.degree. C. at
10.degree. C./min, and then heated from -20.degree. C. to
250.degree. C. at 10.degree. C./min. FIG. 4A shows the first
heating curves and FIG. 4B shows the second heating curves. Note
the disappearance of the thermal peaks after the second heat.
[0029] FIGS. 5A-5D are graphs showing Fourier Transform Infrared
Spectroscopy (FTIR) for polycaprolactone ("PCL") film cast (5A),
Fidji (5B), PCL-Fidji melt cast film that was pressed with high
pressure (5C), and the PCL-Fidji melt cast film after three
years.
[0030] FIG. 6 is a graph showing X-ray powder diffraction of PCL
(112kD) film pressed at 6 tons and heated to 50.degree. C. (a), PCL
solvent cast film (b), and background (c).
[0031] FIG. 7 is a graph showing thermal analysis by DSC of PCL
pressed films. Temperatures (-20.degree. C., 40.degree. C.,
50.degree. C., and 60.degree. C. ) on the graphs indicate the
heating temperature before pressure was applied.
[0032] FIGS. 8A-8C are graphs showing X-ray diffraction of
polylactic acid polymer (PLA) (130 kDa) for PLA with no LC state
(8A), PLA with dispersed LC state (8B), and PLA with LC state (8C).
Arrows indicate diffraction of the clay material on which the film
was supported.
[0033] FIGS. 9A-9C are graphs showing X-ray powder diffraction of
polystyrene film (2.5 kDa) for no LC (9A), LC (9B), and LC-crushed
sample (9C). Arrows indicate diffraction of the clay material on
which the film was supported.
[0034] FIGS. 10A-10D are graphs showing X-ray powder diffraction of
polystyrene film (120 kDa) for no LC (10A); pure polymer with
pressure only, no LC (10B); pure polymer heated with no pressure,
no LC (10C); and pure polymer treated with heat and 890 MPa
pressure, LC (10D). Arrows indicate diffraction of the clay
material on which the film was supported.
[0035] FIGS. 11A-11B are graphs showing X-ray powder diffraction of
polystyrene film (50 kDa) for pure polymer, no LC (11A); and pure
polymer treated with heat and pressure, LC (11B). Arrows indicate
diffraction of the clay material on which the film was supported.
Differentiate heat and pressure between FIGS. 11a & 11b.
[0036] FIGS. 12A-12B are graphs showing X-ray powder diffraction of
low density polyethylene film ("LDPE") (50 kDa) for pure polymer,
no LC pellet (12A); and pure polymer treated with heat and
pressure, LC (12B).
[0037] FIG. 13 is a graph showing X-ray powder diffraction of a
polyanhydride (polycarboxyphenoxy-propane-co-sebacic acid (20:80))
polymers heated to three different temperatures, 60, 70, and
75.degree. C., and pressed.
[0038] FIGS. 14A-14E are graphs showing X-ray powder diffraction of
high density polyethylene ("HDPE") films, untreated (14A) and
treated with pressure and different temperatures( 60.degree. C.
(14B), 80.degree. C. (14C), 100.degree. C. (14D), and 127.degree.
C. (14E)).
[0039] FIGS. 15A-15B are graphs showing X-ray powder diffraction of
HDPE films, showing total area under curve and total area under
amorphous region for treated HDPE samples. FIG. 16 is a bar graph
showing Full Width at Half Maximum Peak Height ("FWHM") for peaks
at 22.5 and 24.0 2.theta. of HDPE samples which have been treated
with pressure and different temperatures (60, 80, 100, and
127.degree. C.).
[0040] FIG. 17 is a bar graph showing percent crystallinity for
HDPE untreated samples and samples which have been treated with 890
MPa pressure and different temperatures (60, 80, 100, and
127.degree. C.).
[0041] FIG. 18 is a bar graph showing percent crystallinity for
polystyrene untreated samples and samples which have been treated
with pressure and different temperatures (25, 60, 80, 100, and
120.degree. C.).
[0042] FIGS. 19A-19B are graphs showing X-ray powder diffraction of
PCL films, untreated and treated with pressure and different
temperatures.
DETAILED DESCRIPTION OF THE INVENTION
[0043] It has been discovered that liquid crystals can be induced
in virtually any polymer, even those without mesogenic structures
which had been thought to be necessary for the exhibition of liquid
crystalline properties. The method of inducing the liquid crystals
includes the application of high pressure to the polymer, while
heating it above or near the glass transition temperature yet below
the melting point of the polymer. Unlike many prior art transition
processes which are reversible, this process induces a liquid
crystal state that can be maintained for years at ambient
conditions.
[0044] 1. Definitions
[0045] As used herein, the term "molecular weight" refers to weight
average molecular weight when that term is used to refer to the
molecular weight of polymers, and can be abbreviated by the symbol
"MW" or "Mw." The symbols "Da" and "kDa" refer to "Daltons" and
"kiloDaltons," respectively, both standard units of measure for
weight average molecular weight.
[0046] As used herein, the terms "liquid crystal" and "liquid
crystalline" are used as those terms are known in the art,
discussed in more detail below, and further include the phase
induced in non-mesogenic polymers which differs from the
crystalline phase of the polymers based on comparison of changes in
optical properties, x-ray diffraction, density, or thermal analysis
results.
[0047] The term "non-mesogenic polymer" is used herein to refer to
polymers without discotics and/or rigid, rod-shaped molecules,
which structures are known in the art to promote two-dimensional
columnar ordering and/or preferential alignment along one spatial
direction.
[0048] As used herein, the term "ambient" is used to refer to
normal, approximately average, environmental temperatures and
pressures, typically about 25.degree. C. and about 760 mm Hg.
[0049] As used herein, the term "bioerodible" is used to refer to
polymeric materials that will erode or degrade over time (usually
in vivo), preferably less than about one year due, at least in
part, to contact with a aqueous solution of pH 6-8 at a temperature
of between about 25 and 38.degree. C. and/or cellular action,
especially enzymatic cleavage. The term may include polymer that
erodes in vitro when exposed to water and/or enzyme. The term does
not include polymers that erode over two or more years due to
hydrolytic degradation.
[0050] As used herein, the term "water soluble polymer" refers to
polymers that have at least 1% solubility (w/w) at 25.degree. C.
and 760 mm Hg.
[0051] 2. Liquid Crystals
[0052] Liquid crystals are materials that exhibit long-range order
in only one or two dimensions, not all three. A distinguishing
characteristic of the liquid crystalline state is the tendency of
the molecules, or mesogens, to point along a common axis, known as
the director. This feature is in contrast to materials where the
molecules are in the liquid or amorphous phase, which have no
intrinsic order, and molecules in the solid state, which are highly
ordered and have little translational freedom. The characteristic
orientational order of the liquid crystal state falls between the
crystalline and liquid phases.
[0053] Liquid crystalline ("LC") structures typically are
categorized as nematic, smectic, or cholesteric. The nematic phase
is characterized by molecules that have no positional order, but
tend to point along the director. The smectic phase is a mesophase
in which molecules show a degree of translational order not present
in the nematic phase. In the smectic phase, the molecules maintain
the general orientational order of the nematic phase, and also
align themselves in layers or planes. Motion is restricted to
within these planes; however, separate planes can flow past one
another. Several smectic mesophases are known, such as smectic A
and smectic H. The cholesteric, or chiral nematic, phase typically
is composed of nematic mesogenic molecules containing a chiral
center, which produces intermolecular forces that cause alignment
between molecules at a slight angle to one another. The resulting
structure can be visualized as consisting of multiple, thin
nematic-like layers stacked such that the director in each layer is
twisted or offset with respect to those above and below so as to
form a helical pattern.
[0054] Liquid crystals also can be classified as thermotropic or
lyotropic. These types are distinguishable by the mechanisms, or
transitions, facilitating their organization structure.
Thermotropic transitions, which occur in most liquid crystals, are
induced thermally by raising the temperature of a solid and/or
lowering the temperature of a liquid. Thermotropic liquid crystals
can be further classified as enantiotropic or monotropic.
Enantiotropic liquid crystals can be changed into the LC state both
by lowering the temperature of a liquid and raising of the
temperature of a solid, while monotropic liquid crystals can only
be changed into the LC state from either an increase in the
temperature of a solid or a decrease in the temperature of a
liquid, but not both. In contrast to thermotropic mesophases,
lyotropic transitions occur under the influence of solvents, not a
change in temperature. The solvent induces aggregation of the
constituent mesogens into micellar structures, since lyotropic
mesogens typically are amphophilic.
[0055] Numerous chemical compounds are known to exhibit one or more
liquid crystalline phases. The molecules of these compounds
typically include discotics and/or rod-shaped molecules. Discotics
are flat, plate-like molecules consisting of a core of adjacent
aromatic rings, which facilitate two-dimensional columnar ordering.
Rod-shaped molecules, in contrast, have an elongated rigid
anisotropic geometry, which promotes preferential alignment along
one spatial direction. For example, the interconnection of two
rigid cyclic units results in a compound having a linear planar
conformation. Linking units containing multiple bonds, such as
--(CH.dbd.N)--, --N.dbd.N--, --(CH.dbd.CH).sub.n--, and
--CH.dbd.N--N.dbd.CH--, also restrict the freedom of rotation.
These groups can conjugate with phenylene rings, enhancing the
anisotropic polarizability and increasing the molecular length,
while maintaining the rigidity of the structure.
[0056] 3. Identification of Liquid Crystals
[0057] At least two independent methods are used to verify that a
particular material includes a liquid crystal phase. The presence
of LCs in the polymers described herein can be measured using
essentially any technique known in the art. The methods can be used
to identify the ordered structures in materials considered liquid
crystalline or materials that include an ordered phase that is not
generally considered liquid crystalline. Useful methods include
optical pattern or texture observations with a polarizing
microscope, differential scanning calorimetry, miscibility or
density comparisons, molecular orientations by either supporting
surface treatments or external fields, and classical x-ray and
x-ray diffraction techniques, which are described in Noel,
"Identification of Mesophases Exhibited by Thermotropic Liquid
Crystalline Polymers" in Polymer Liquid Crystals (Blumstein, ed.)
pp.21-59 (Plenum Press, New York 1983).
[0058] 4. Polymers
[0059] The methods described herein can induce a LC state in a wide
variety of polymers, including non-mesogenic polymers. The polymers
useful in the methods described herein are referred to as "LC
polymers," which include both mesogenic (known in the prior art to
exhibit LC properties) and non-mesogenic (according to the prior
art, incapable of exhibiting LC properties). The selection of the
polymer in which it is desirable to induce liquid crystals depends
on a variety of factors, including physical and chemical properties
of the polymer, processing requirements, physical and chemical
specifications of the end product, and cost of the polymer.
Bioerodeability and water solubility are two such factors.
[0060] Mesogenic Polymers
[0061] Examples of mesogenic liquid crystalline polymers which can
be used in the methods described herein include
poly(.beta.-thioester) [from 1,6-hexane-bisthiol and
3-methyl-1,6-hexamethylene-p-phenylate p-phenylate diacrylate],
poly(1,2-dimethyl ethylene-p-terphenylate),
poly(tetraoxyethylene-p-terphenylate),
poly(ethylene-p-terphenylate),
poly(4'-cyanobiphenyl-4-oxyhexylacrylate), 2-hydroxypropyl
cellulose, poly(bis trifluoroethoxyphosphazene), poly(p-phenylene
benzobisthiazole), polybenzamide, polystyrene/polyisoprene block
copolymers, polystyrene/polyethylene oxide block copolymers,
polyanhydrides poly(hydroxybenzoate/hydroxynaphthalate),
poly(.gamma.-benzyl-L-glutamate- ), poly(phenylene
terephthalamide), poly(bromo-p-phenylene-1,10-diphenyl decanate),
and poly(.gamma.-benzyl-L-glutamate)s. The repeat unit structure
and type of LC structure for each of these polymers is provided,
for example, in Woodward, Atlas of Polymer Morphology, pp. 223-25
(Hanser Publishers, New York).
[0062] Non-Mesogenic Polymers
[0063] Examples of non-mesogenic liquid crystalline polymers which
can be used in the methods described herein include amyloses;
derivatized celluloses such as alkyl cellulose, hydroxyalkyl
celluloses, cellulose ethers, cellulose esters, nitro celluloses,
methyl cellulose, ethyl cellulose, hydroxypropyl cellulose,
hydroxy-propyl methyl cellulose, hydroxybutyl methyl cellulose,
cellulose acetate, cellulose propionate, cellulose acetate
butyrate, cellulose acetate phthalate, carboxylethyl cellulose,
cellulose triacetate, and cellulose sulphate sodium salt
(collectively referred to herein as "celluloses"); ladder polymers;
phenol-formaldehydes; polyacetals; polyacetylene; polyacrylamides;
poly(acrylic acid)s; polyacrylonitriles; poly(L-analine)s;
polyamides; polyanalines; polybenzimideazoles;
polybenzobisoxazoles; polybenzobisthiazoles; 1 ,2-polybutadienes;
cis-1 ,4-polybutadiene; trans-1,4-polybutadiene; poly(butene-1);
polybutylene-terephthalate; polycarbonate; cis,
trans-1-4-polychloroprene; polychlorotrifluoroethylen- e;
polydiethylsiloxane; polydimethylsiloxane; polydiphenylsiloxane;
some polyesters; polyetheretherketone; polyethylene and derivatives
thereof, such as poly(ethylene imine), poly(ethylene oxide),
poly(ethylene glycol), and polyethylene-terephthalate; polyglycine;
poly(hexamethylene adipamide); polyimide; poly(imino-1,3-phenylene
iminoisophthaloyl) (NOMEX.TM.); poly(imino-1,4-phenylene
iminoterephthaloyl) (KEVLAR.TM.); polyisobutylene; polyisocyanate;
polyisocyanide; cis-1,4-polyisoprene; trans-1,4-polyisoprene;
polylactam; polylactone; polystyrenes including poly(p-methyl
styrene); poly(methyl acrylate) and derivatives thereof, such as
poly(methyl methacrylate); poly(.alpha.-methyl styrene);
poly(methylene oxide); polymethylphenyl-siloxane; polynitrile;
polynucleotide; poly(n-pentene-2); poly(n-pentene-1); polypeptides
such as poly(.alpha.-amino acid); poly(p-phenylene oxide);
poly(p-phenylene sulfide); poly(p-phenylene vinylene);
poly(p-phenylene); some polyphosphates; some polyphosphazenes;
polyphosphonate; polyalkylenes such as polypropylene; polyakylene
oxide; poly(pyromellitimide-1,4-diphen- yl ether) (KAPTON.TM.);
polypyrrole; polysilane; polysilazane; polysiloxane; polysulfide;
polysulfur; polytetrafluoroethylene (TEFLON.TM.);
poly(tetramethylene oxide); polythiophene; polyurea; polyurethane;
poly(L-valine); poly(vinyl acetate); poly(vinyl alcohol);
poly(vinyl chloride); poly(vinyl fluoride); poly(2-vinyl pyridine);
poly(N-vinyl pyrrolidone); poly(vinylidene chloride);
poly(vinylidene fluoride); and vinyl polymer. The structure of the
repeat unit for each of these polymers is provided, for example, in
Physical Properties of Polymers Handbook (J. Mark, ed.), ch. 2, pp.
29-36 (AIP Press, Woodbury, N.Y. 1996).
[0064] Bioerodible LC Polymers
[0065] Representative bioerodible LC polymers include
polyanhydrides and some polyesters. Representative polyanhydrides
include poly(fumaric acid-co-sebacic acid),
poly(carboxyphenoxypropane-co-sebacic acid), and poly(maleic acid).
Preferred LC polymers include polyethylene, polystyrene,
polycaprolactone, poly(lactic acid), and
polylactide-co-glycolide.
[0066] Suitable bioerodible LC polymers include both mesogenic and
non-mesogenic polymers. Representative non-mesogenic, bioerodible
polymers include polylactic acid, polylactide-co-glycolide,
polycaprolactones, polyvaleric acid, polyorthoesters,
polyhydroxybutyrate, polysaccharides such as amylose and cellulose,
polypeptides (e.g., poly-L-alanine,
poly-.gamma.-benzyl-L-glutamate, polyglycine, and poly-L-valine),
poly(.epsilon.-caprolactam), poly(.epsilon.-caprolactone), and
certain polyesters. Representative mesogenic, bioerodible polymers
include polyanhydrides, polybutylene terephthalate, and
polycarbonate.
[0067] Non-bioerodible LC Polymers
[0068] Suitable non-bioerodible LC polymers also include both
mesogenic and non-mesogenic polymers. Preferred LC polymers include
polyesters, polypropylene, polystyrene, and polyterephthalic
acid.
[0069] 5. Process For Inducing The LC State In Polymers
[0070] The process for inducing a liquid crystal state in a polymer
includes the following steps: (a) heating the polymer from an
initial temperature below its glass transition temperature (Tg) to
a temperature greater than its Tg and below its melting temperature
(Tm); (b) subjecting the polymer to a pressure greater than about
28 MPa (2 metric tons/in.sup.2), preferably between about 28 and
140 MPa (2 and 10 metric tons/in.sup.2), preferably for at least
about one minute, while maintaining the temperature greater than
its Tg; and (c) cooling the polymer below the Tg while maintaining
the elevated pressure. Preferably, the polymer is heated and cooled
at a rate between about 1 and 30.degree. C./min. The pressure is
not required to be maintained for long periods of time at the
elevated temperature prior to quenching the polymer, in order to
induce the liquid crystalline phase in the polymer. Durations of
between about 1 and 10 minutes are preferred.
[0071] The method of inducing an LC state is believed to occur by
the polymer chains become more fluid at temperatures between Tg and
Tm, and are thus more susceptible to alignment under pressure.
Above Tm, however, the polymer chains are completely in the liquid
phase.
[0072] 6. Applications For The LC Polymers
[0073] The LC polymer can be made in a variety of forms including
films, film laminants, coatings, membranes, microparticles, slabs,
extruded forms, and molded forms. Several types of delivery
devices, such as thin films, pellets, cylinders, discs, and
microparticles can be prepared from the LC polymers, using methods
well known to those of skill in the art. As used herein,
microparticles are particles having a diameter of less than about
one millimeter that include an incorporated agent. The
microparticles can have a spherical, non-spherical, or irregular
shape. Preferably, the microparticles are spherical. The LC
polymers can be combined with each other, with non-LC polymers, or
with other materials such as metals, ceramics, glasses, or
semiconductors, the latter typically in the form of coatings. The
polymers can be fabricated into articles and then treated to induce
the LC state, or the LC state can be induced and then articles
formed from the LC polymer.
[0074] The advantage of LC polymer films over other polymer films
is that the films generally are more dense, thus providing greater
mechanical strength and delayed diffusion through the film. These
advantages are particularly useful in packaging applications.
[0075] Compositions that include the LC polymers can be monolithic
or layered. The term "monolithic" is used herein to describe a
continuous phase having imbedded structures, rather than layers.
The LC polymers can be prepared separately and then mixed with
other materials in a process that does not change the transition
temperature.
[0076] The applications for these polymers are numerous.
Bioerodible LC polymers, for example, can be used in delivery
systems for therapeutic, diagnostic, and prophylactic agents,
particularly as implantable devices. Non-erodible LC polymers, for
example, can be used in display systems, such as for computers, and
in message systems wherein a message can be displayed or hidden
from view based on changes in the opacity/transparence of the LC
polymer which occur with changes in the crystal structure of the
material. LC polymers also can be used in product packaging. For
example, LC polymers can be adapted to form membranes or films that
are less permeable to gases, such as oxygen, as compared to non-LC
polymer films. The LC polymers also may be adapted for use as a
shape memory material, capitalizing on the state change of the
polymers to provide a particular effect.
[0077] The methods of inducing liquid crystalline properties in
polymer also can be used to improve the permeability of polymers in
numerous applications, such as packaging, particularly food and
pharmaceutical packaging. The methods similarly can be used to
enhance the structural performance of polymeric prosthetic devices,
such artificial knees made of polyethylenes.
[0078] The unique physical properties of the LC polymers described
herein can be highly useful in the release of substances
encapsulated in the LC polymers. Representative substances for
encapsulation include scents such as perfumes or pheromones,
flavoring agents (e.g., edible oils), dyes or other coloring
agents, nutrients (e.g., minerals such as calcium, zinc, vitamins
A, E, C, and D, and the B vitamins), sunscreen, and pesticides.
Encapsulation of substances in LC polymers generally requires that
the substance be mixed into the polymer prior to the induction of
the LC state. This mixing typically is done by adding the substance
to the polymer while in solution or while above the Tm of the
polymer before treating the polymer as described herein to induce
an LC state.
[0079] In a preferred embodiment, the LC polymers are used to
encapsulate therapeutic, diagnostic, or prophylactic agents
(referred to collectively herein as "active agents"), for various
medical and pharmaceutical applications. Examples of suitable
therapeutic and/or prophylactic agents include proteins, such as
hormones, antigens, and growth factors; nucleic acids, such as
antisense molecules; and small molecules, such as antibiotics,
steroids, decongestants, neuroactive agents, vasoactive agents,
analgesics, anesthetics, and sedatives. Examples of suitable
diagnostic agents include radioactive isotopes and radiopaque
agents. The polymeric matrices can include more than one
incorporated agent. A therapeutically, prophylactically, or
diagnostically effective amount of the agents are incorporated into
the LC polymer matrices. An effective amount of these agents can be
readily determined by a person of ordinary skill in the art taking
into consideration factors such as body weight; age; physical
condition; therapeutic, prophylactic, or diagnostic goal desired;
type of agent used; type of polymer used; initial burst and
subsequent release levels desired; and desired release rate.
Typically, the polymeric matrices will include between about 0.01%
(w/w) and 80% (w/w) of incorporated agent.
[0080] The incorporated agent may be in the form of particles, for
example, crystalline particles, non-crystalline particles, freeze
dried particles, or lyophilized particles. LC polymer particles
preferably are less than about 20 .mu.m in size, and more
preferably less than about 5 .mu.m, for parenteral or pulmonary
administration to a patient, but may be substantially larger for
internal or subcutaneous administration. The particles also may
include a stabilizing agent and/or other excipient.
[0081] Another application for the polymers is as a barrier
material, for example, in packaging. That is, the polymer,
typically in the form of a film coating on a packaging article, can
serve as a barrier to prevent or delay fluids, such as water,
oxygen, or carbon dioxide, from diffusing into or out of a closed
packaging container, such as those containers used for food or
drugs. The polymer can be formed and applied by adapting the
methods disclosed herein to known techniques for making and coating
packaging articles.
[0082] Other applications for the LC polymers include the
production of high-strength materials and optical devices. The LC
polymers can be used in the production of high strength fibers and
products requiring strong, lightweight materials of construction.
The LC polymers can also be used in liquid crystal displays,
capitalizing on the unique optical properties of LC materials. The
utilization of LC polymers in optically nonlinear devices,
including optical waveguides and electro-optic modulators, as well
as in optical recording and imaging, is also envisioned. Another
application for the LC polymers is in temperature sensing devices,
for example. In one medical application, the sensor is attached to
the skin to provide a temperature map indicating local temperature
variations. Such devices are useful, for example, in the diagnosis
of certain medical ailments, such as tumors, or areas of infection
or inflammation or poor circulation which have a temperature
different from the surrounding healthy tissue.
[0083] High density polyethylene (HDPE) has enormous application in
prosthetics, for example, hip bone replacement. However, HDPE in
load bearing applications exhibits wear debris over time. It has
been hypothesized that reducing crystallinity (spherulites
structures) can reduce this wear debris. Therefore, the use of a
liquid crystal form of HDPE is one means of reducing HDPE
crystallinity while retaining a high degree of order in the
"crystalline" polymer. The same techniques are applicable to a
variety of other crystalline polymers.
[0084] The compositions and methods of preparation and use thereof
described herein are further described by the following
non-limiting examples.
Example 1
Study of Induction and Retention of LC State in Polymers
[0085] A series of studies were conducted on a several polymers,
which are listed below in Table 1. A 0.5 g sample of each polymer
was heated above the glass transition temperature (Tg), usually 5
to 10.degree. C. for the amorphous materials and 10 to 20.degree.
C. for the crystalline polymers. Crystalline materials, such as
PCL, were heated up to 2 to 5.degree. C. below the melting point.
The polymer sample was then placed on rectangular plates and
pressed at a pressure ranging from 28 and 140 MPa (2 to 10 metric
tons/in.sup.2) using a brass pin dye with a Wabash Press. The
sample was allowed to cool under pressure from 0.5 to 10 minutes.
All samples exhibited typical Schlieren, or liquid crystalline,
structure under polarizing optical microscopy. Rotation of the
polarizer's analyzer indicated that the structure is retained at
all angles. Most samples that were left at room temperature
retained the liquid crystalline structure for at least 3 years as
determined by optical microscopy.
1TABLE 1 Induction and Retention of LC State in Various Polymers LC
State Amorphous Molecular Observed By Duration of or Semi- Weight
Polarized Tg Tm LC State Polymer Type crystalline? (MW) Light?
(.degree. C.) (.degree. C.) (yrs.) Polycaprolactone C 110 K Yes --
60 2 Polycaprolactone C 32 K Yes -- -- 2 Polystyrene A .sup. 2.3 K
Yes .about.120 -- 2 Polystyrene A 45 K Yes .about.120 -- 2
Polystyrene A 120 K Yes .about.120 -- 2 Polylactide-co- A -- Yes
30-40 -- 3 glycolide 50:50 Polylactide-co- A -- Yes 30-40 -- 3
glycolide 25:75 Polylactide C 2 K Yes 45 120 3 Polytetrafluoro- C
-- Yes -- -- 2 ethylene
Example 2
Release of Insulin from Polycaprolactone: Melt, Liquid Crystal, and
Solvent Cast Slabs
[0086] Polycaprolactone (PCL) (MW=110 kDa) containing insulin was
formed into cylindrical slabs, each of approximately the same
dimensions, using one of the following techniques: (1) solvent
casting of a 10% (w/v) solution, (2) melt casting in a custom mold
at 80.degree. C., and (3) heat compression at 60.degree. C. (hot
melt) with application of 890 MPa (10,000 metric tons/cm.sup.2)
using a brass pin dye with a Wabash Press. The hot melt process
provided the liquid crystal formulation.
[0087] First, the starting material was prepared from 24.63 mg of
insulin suspended in 2.0 g of PCL in methylene chloride and
thoroughly mixed in a Virtis rotor-stator in 100 ml methylene
chloride. The loading was 12.3 .mu.g of micronized insulin/mg
polymer, or 1.23% (w/w). The dispersed drug-polymer mix was cast
into a film, allowed to dry, cut into pieces, and ground to make a
uniform starting material. Before grinding, an aliquot of the film
material was used for solvent casting of films. The ground starting
material was melted at 80.degree. C. in a mold to make melt cast
samples. For the heat-compressed series, the ground starting
material was compressed under a pressure of 890 MPa (10 metric
tons/cm.sup.2) at 60.degree. C., and had liquid crystalline
morphology when observed with crossed polarizers in a light
microscope. A physical description of the samples is provided in
Table 2 below.
2TABLE 2 Polymer Sample Specifications Sample Slab Diameter Slab
Thickness Slab Weight Slab Type No. (cm) (mm) (mg) Heat Compr. 1
9.14 500 43.3 Heat Compr. 2 9.0 148 10.2 Heat Compr. 3 9.0 296 29.0
Heat Compr. 4 9.0 385 28.9 Heat Compr. 5 9.0 1212 66.5 Melt Cast 1
7.7 1643 63.1 Melt Cast 2 7.7 1801 63.0 Melt Cast 3 7.7 1626 60.5
Melt Cast 4 7.7 1761 58.8 Melt Cast 5 7.7 1606 61.6 Solvent Cast 1
10.3 155 8.7 Solvent Cast 2 10.3 242 12.4 Solvent Cast 3 10.3 278
20.1 Solvent Cast 4 10.3 324 14.1 Solvent Cast 5 10.3 263 18.1
[0088] Aliquots of films were incubated in 1 ml of physiological
saline at pH 7.4 at 37.degree. C. The release fluids periodically
were collected and replaced with fresh saline. Insulin release was
determined with BCA Protein Assay.
[0089] Release kinetics observed for the different samples are
shown in FIG. 1. One can see that the insulin is released by
diffusion, since the polymer had no time to degrade during the 80
hr. time period observed. Additionally, due to the low
concentration of the insulin, it is clear that different
formulations exhibit different release rates based on the nature of
the polymer fabrication. Liquid crystalline material released the
drug at a rate that is between the rate of release of the solvent
cast (the fastest) and the melt cast (the slowest) release
curves.
[0090] The release must be dependent on polymer microstructure,
since the insulin loading was low, which reduces the opportunity
for formation of interconnected pores or channels, which would
facilitate release of insulin or any other loaded agent. In
contrast, when loading is high, e.g. above about 30%, some of the
drug can diffuse out of the polymer through channels created as
drug particles in close proximity to one another diffuse out,
leaving pores that are interconnected and creating a path for
further diffusion. This conclusion is further supported by the fact
that the polymer does not degrade within the time scale of the
study (80 hrs). Therefore, the liquid crystal formulation
necessarily has different physical properties than the solvent or
melt cast formulations.
Example 3
Density of Liquid Crystal Samples Compared to Untreated Polymer
[0091] The densities of the polymers that were induced to enter the
liquid crystal state in Example 1 were compared with the densities
of the native (untreated) polymers, using flotation in either
sucrose or sodium bromide step gradients. Density gradients were
prepared by overlaying 2 ml steps of concentrated sucrose solutions
ranging from 12 to 60% (w/v), or concentrated sodium bromide
solutions ranging from 10 to 60% (w/v), in 15 ml centrifuge tubes.
All solutions contained 0.1% (w/v) PLURONIC.TM. F127 (made by BASF)
to reduce hydrophobic interactions and facilitate wetting of the
polymer surface. Samples were introduced onto the uppermost layer,
the tubes were centrifuged at 2,000 rpm for 10 min., and the final
position of the sample within the gradient was recorded. For each
sample, the liquid crystalline (LC) state was first determined by
polarized light. Phases referred to herein as "LC" are phases that
reveal typical LC morphology with optical microscopy.
[0092] Polystyrene
[0093] The native sample of polystyrene (PS) (2.5 kDa) floated at
the interface between the 12 and 20% (w/v) sucrose solutions,
corresponding to a density of between 1.0465 and 1.0810 g/ml. The
liquid crystal sample of PS floated near the top of the 12% sucrose
(w/v) layer corresponding to a density of between 1.0 and 1.0465
g/ml. This value demonstrates that a physical change had occurred
in the polymer structure which was not due to "densification" of
the glass transition. (In many experiments detailed in the prior
art, the application of pressure for long periods of time has the
effect of increasing the density of polystyrene.) Here, the exact
opposite phenomenon was observed: a decrease in polymer density.
This corresponds well with additional experiments in which the
degree of crystallinity was decreased in samples induced to have an
LC state.
[0094] Polycaprolactone
[0095] The native sample of polycaprolactone (PCL) (32 kDa) floated
at the interface between the 40 and 60% (w/v) sucrose solutions,
corresponding to a density of between 1.1764 and 1.2865 g/ml. The
liquid crystal sample of PCL floated in the middle of the 40%
sucrose (w/v) layer, corresponding to a density of 1.1764 g/ml. A
lower polymer density was observed in the LC state, similar to the
effect seen in the PS study.
[0096] Polylactic Acid
[0097] Both the native and liquid crystal samples of polylactic
acid (PLA) (2 kDa) floated in the middle of the 40% (w/v) sodium
bromide layer, corresponding to a density of 1.410 g/ml.
[0098] Polylactide-co-glycolide
[0099] The native sample of polylactide-co-glycolide (PLG) (50:50
RG503H) floated on top of the 20% (w/v) sodium bromide layer
corresponding to a density of less than 1.410 g/ml ,while the
liquid crystal PLG floated at the interface between the 50 and 60%
(w/v) sodium bromide. The densities of the 50 and 60% sodium
bromide solutions are not given in Table 5 below, but are greater
than 1.410 g/ml.
[0100] While the changes in density are specific for each polymer,
it is clear that the LC phase induced in each case changed the
polymer properties. The specific type of LC state induced, however,
was not determined. In the case of PLG, which is an amorphous
polymer, inducing an LC state increased the density. This contrasts
with the other polymers tested in this Example in which the
polymers are semicrystalline.
Example 4
Thermal Analysis of Liquid Crystalline Polymers and TEFLON.TM.
[0101] Samples that were pressed with heat as described in Example
1 and found to have LC properties (as determined by polarized
light) were studied using Differential Scanning Calorimetry (DSC).
The results are shown in FIGS. 2A and 2B. The studies were
performed with a Perkin-Elmer Model DSC 7 connected to a controller
model TAC 7/DX. Samples were heated from -20 to 250.degree. C. at a
rate of 20 or 10.degree. C./min., cooled back to -20.degree. C. at
the same rate, and heated again to 250.degree. C. Identification of
the LC first order transition was always found on the first run
only.
[0102] FIG. 2A depicts a thermal analysis of a commercial
TEFLON.TM. film, poly(tetrafluoroethylene), that was heated above
the glass transition temperature (above 20.degree. C.) and pressed
for 1 min. using a pressure of 890 MPa (10 ton/cm.sup.2). The first
run of the DSC revealed a glass transition at 2.degree. C., a broad
peak between 129 and 150.degree. C., which was attributed to the
new phase which was probably in equilibrium with the amorphous
phase. Additionally, a well-defined melt at 348.degree. C. was
observed. These results, taken in combination with the polarized
light observation, indicate that it is possible to induce LC
properties in TEFLON.TM. and that the phase is stable for long
periods of time. FIG. 2B illustrates thermal analysis of amorphous
TEFLON.TM..
Example 5
Temperature as a Factor in LC Formation in Polystyrene
[0103] A series of polystyrene (PS) (MW =2.5 kDa) samples was
prepared, and each sample heated to 23, 50, 70, 83, or 90.degree.
C. The samples were pressed for one minute with a pressure of 890
MPa (10 ton/cm.sup.2). Optical observation indicated that samples
pressed at the glass transition temperature (Tg) (approximately
70.degree. C.) and lower resulted in LC structures with "fan" type
morphology, while samples that were pressed at higher temperatures
displayed Schlieren structures under optical polarized microscopy.
While it is difficult to determine if the final configuration is
nematic or smectic, the structures are assumed to be either
type.
[0104] DSC was conducted as described in Example 4. The DSC
results, which are presented in FIG. 3 and Table 3, show a glass
transition temperature at 67 .degree. C. for the untreated sample.
For some treated samples, the Tg is reduced to 48 .degree. C.,
depending on the temperature at which the pressure was applied.
Treatment of the polymer above 70.degree. C. reveals a well defined
thermal peak, attributable to the induction of the new phase.
3TABLE 3 DSC Results for Polystyrene (MW = 2.5 kDa) Films
Temperature Treated (.degree. C.) Tg (.degree. C.) Cp (J/g.degree.
C.) Peak @ (.degree. C.) H (J/g) untreated 67.34 .195 -- -- 23
65.73 .342 -- -- 50 60.65 .289 -- -- 70 59.19 .279 -- -- 83 48.07
.070 69.83 2.539 90 49.80 .141 69.03 4.746 100 54.68 .315 68.200
1.713
[0105] FIGS. 4A and 4B and Table 4 provide the DSC results for a
similar treatment on a higher molecular weight polystyrene polymer
(45 kDa). The first run of the thermal heating (FIG. 4A) revealed
the same trend as shown with the lower molecular weight
polystyrene. A thermal peak arises when the sample is heated above
the glass transition temperature (60.degree. C.). This transition
disappeared after heating the sample to 250.degree. C., as
illustrated in FIG. 4B and Table 4. Although the glass transition
lowers as the pressure was applied, the glass transition returned
to its original value after the second heat., further indicating
that the phase transition is induced with the application of
pressure.
4TABLE 4 DSC Results for Polystyrene (MW = 45 kDa) Films Temp.
Treated (.degree. C.)* Tg (.degree. C.) Cp (J/g.degree. C.) Temp.
Peak (.degree. C.) H (J/g) Untreated (1) 65.85 .265 -- -- Untreated
(2) 59.30 .303 -- -- 23 (1) 64.65 .211 -- -- 23 (2) 60.63 .284 --
-- 60 (1) 61.995 .262 -- -- 60 (2) 61.310 .242 -- -- 80 (1) 52.427
.151 68.866 2.67 80 (2) 59.749 .234 -- -- 100 (1) 54.223 .226
76.700 3.188 100 (2) 59.848 .239 -- -- 120 (1) 54.626 .175 78.866
1.988 120 (2) 60.882 .231 -- -- *(1) denotes first thermal run; (2)
denotes second thermal run
Example 6
Encapsulation of Perfume in Polycaprolactone Film
[0106] Formulation #1
[0107] A polymer blend was prepared by mixing 11.0 g of PCL (MW=72
kDa) (Aldrich Chemical Co, Lot 03218AF, Cat.#18160-9) and 4.0 g PCL
(MW=32 kDa) (Scientific Polymers, Inc., Lot 7, Cat.#047) in a
crucible while molten at 60 .degree. C. Fidji essence (0.2 ml) then
was added to the polymer blend to give a perfume loading of 1.33%
(w/w).
[0108] A portion (4.44 g) of the polymer mixture then was pressed
between steel plates in a 4.2 cm.times.2.7 cm.times.0.4 mm mold at
a pressure of 710 to 890 MPa (8 to 10 metric tons/cm.sup.2) and
allowed to cool for four minutes under pressure to form a film.
Disks 8 mm in diameter were punched from the film with a borer, and
a 0.1 mm center hole was drilled into each disk. Using polarizing
light microscopy, the films appeared to be liquid crystalline.
[0109] Formulation #2
[0110] The remaining portion (10.56 g) of the polymer mixture from
Formulation #1 was remelted and an additional 1.2 ml of Fidji
essence was added to produce a loading of 12.7% (w/w). The
melt-press-quench procedure described above for Formulation #1 was
repeated with this formulation to yield a film, from which 8 mm
disks with center holes were punched. Using polarizing light
microscopy, the films appeared to be liquid crystalline.
[0111] Formulation #3
[0112] A third formulation was prepared by melting 10.0 g of PCL
(MW=72 kDa) (Aldrich Chemical Co, Lot 03218AF, Cat. #18160-9) at
60.degree. C. and adding 3.0 ml of Fidji essence to the polymer, to
give a perfume loading of 29.1% (w/w). The melt-press-quench and
punch procedure described above was repeated. The resulting films
appeared to be liquid crystalline, using polarizing light
microscopy.
[0113] Formulation #4
[0114] A fourth formulation was prepared by melting 2.0 g of PCL
(MW=72 kDa) (Aldrich Chemical Co, Lot 03218AF, Cat. #18160-9) at
60.degree. C. and adding 0.2 ml of Fidji essence to the polymer, to
yield a perfume loading of 9.1% (w/w). The melt-press-quench
procedure described above for Formulation #1 was repeated. A
"blank" (no perfume) polymer film was also prepared using the same
procedure. A "laminated film" was prepared by spreading 0.3 ml of
Fidji essence between the blank and perfume-loaded films,
subjecting the films to a pressure of 4 metric tons/cm.sup.2 for
one minute using a 0.8 mm thick mold. The laminants were then
cooled under pressure for one minute, and 8 mm disks with center
holes were punched out. Using polarizing light microscopy, the
films appeared to be liquid crystalline.
[0115] Field Test of Perfume Devices
[0116] Formulations 1 through 4 were all field-tested as
scent-releasing devices. Several women were asked to wear the
perfume-loaded disks either on earrings or attached to necklaces.
The disks were intended to release more perfume scent when heated
from contact with the body. The scent of Formulations 2, 3, and 4
were evident even after three weeks and could be detected at a
distance of two feet from the wearer. The devices maintained their
scent after storage in a sealed container for more than 3
years.
[0117] FTIR Analysis of Perfume Formulations
[0118] Formulation samples were prepared by solvent casting and
analyzed three approximately three years later. Each sample
contained the Fidji perfume even after 3 years, as confirmed by
Fourier-Transform Infrared Spectroscopy (FTIR). FIGS. 5A-5D show
the results of FTIR spectroscopy using a Perkin Elmer spectrometer
model 1725x. The following four sample were analyzed: pure PCL
(FIG. 5A), pure Fidji (FIG. 5B), PCL-Fifji melt cast and compressed
(FIG. 5C), and a sample of PCL-Fidji kept at room temperature for
three years (FIG. 5D). The last sample still retained the aroma of
the perfume.
Example 7
Effect of Pressure on PCL Film--X-ray Analysis
[0119] X-ray analysis was performed on PCL film samples to assess
the effect of pressure on the structure of the polymer. Two PCL
film samples were prepared by dissolving PCL (MW=112 kDa) in
methylene chloride and allowing the solvent to evaporate at room
temperature (solvent cast). One of the sample was heated to
50.degree. C. and compressed with 83 MPa (6 metric tons/cm2) for a
minute. Both samples were X-rayed using a Siemens Diffraktometer
D5000. FIG. 6 shows the X-ray diffraction patterns for the two PCL
films, one solvent cast only, and one solvent cast and
heat/pressure treated. A comparison of the two patterns
demonstrates that a more ordered structure was induced by the
pressure and heating.
Example 8
Effect of Pressure on PCL Film--Thermal Analysis
[0120] DSC analysis, as described in Example 4, was performed on
PCL (MW =72 kDa) film samples to assess the effect of pressure on
the structure of the polymer. Film samples were produced; heated to
20, 40, 50, or 60.degree. C.; and then subjected to a pressure of
10 metric tons/cm.sup.2 for one minute. The samples were then
analyzed by DSC, producing the results presented in FIG. 7 and
Table 5. The major change in the thermal peak is shown to be the
increase in the heat of fusion of the peak at about 60.degree. C.
These results demonstrate that the order in the polymer systems is
increased as result of applying the pressure, i.e. a more ordered
structure was induced by the pressure and heating.
5TABLE 5 DSC Results for PCL (MW = 2.5 kDa) Films Treatment
Temperature (.degree. C.) Peak at .degree. C. H (J/g) Untreated
62.366 64.057 20 59.53 75.95 40 59.66 75.616 50 60.033 72.568 60
59.700 75.618
Example 9
Effect of Pressure on PLA Film--X-ray Analysis
[0121] X-ray analysis was performed on PLA film samples to assess
the effect of pressure on the structure of the polymer. Three PLA
(MW=130 kDa) film samples were prepared as described above. The
first PLA sample was heated to 100.degree. C. and cooled room
temperature at atmospheric pressure. No LC morphology was observed
when the first sample was analyzed using polarized light. X-ray
diffraction analysis was performed as described in Example 7. The
diffraction pattern for the first sample is shown in FIG. 8A.
[0122] The second and third samples were heated to 100.degree. C.
and compressed with 890 MPa (10 metric tons/cm.sup.2) for two
minutes. Optical microscopy revealed dispersed LC properties in the
second sample, and LC in the entire field of the third sample.
X-ray diffraction patterns for samples two and three are shown in
FIGS. 8B and 8C. A new diffraction peak appeared at about
17.degree. in the samples that had LC morphology. Additional
diffraction peaks also were observed, which appear to be a result
of structural changes occurring after application of pressure. The
morphology of these samples were retained for at least three
years.
Example 10
Effect of Pressure on Polystyrene Films--X-ray Analysis
[0123] X-ray analysis was performed on polystyrene (PS) film
samples to assess the effect of pressure on the structure of the
polymer. Three PS films were prepared by heating each sample to
about 80.degree. C. and applying 890 MPa (10 tons/cm.sup.2) of
pressure for 2 minutes. Each film had a different molecular weight:
2.5 kDa, 50 kDa, or 250 kDa. X-ray analysis was performed as
described in Example 7.
[0124] FIGS. 9A-9C show the X-ray diffraction patterns for the 2.5
kDa PS sample. FIG. 9A shows the X-ray diffraction pattern for a
sample that was heated to 90.degree. C. and subjected to a light
pressure of 0.5 metric tons per 2 cm.sup.2 for 2 minutes. No LC
structure was observed. FIG. 9B shows the x-ray diffraction pattern
for a 2.5 kDa sample that was heated to 80.degree. C. and subjected
to a pressure of 10 metric tons per 2 cm.sup.2 for 2 minutes. The
X-ray diffraction patterns showed LC structure and new broad peaks
between 10 to 25.degree.. The same sample then was crushed with a
mortar and pestle and re-analyzed, as shown in FIG. 9C. A new
diffraction is observed at 10.degree., providing strong evidence
that a new phase is being created under these conditions. The
morphology was maintained for approximately four years at room
temperature, since the crushed sample polarized light showed the
specific Schlieren structure during that period of time.
[0125] FIGS. 10A-10D show the X-ray diffraction patterns for the
250 kDa PS sample. The diffraction pattern for the untreated sample
revealed only an amorphous hump (FIG. 10A). The diffraction pattern
for the sample subjected only to elevated pressure (FIG. 10B) was
substantially identical to that for the untreated sample. The
diffraction pattern for the sample subjected only to elevated
temperature at atmospheric pressure (FIG. 10C) also was
substantially identical to that for the untreated sample. The
diffraction pattern for the sample subjected to both elevated
temperature and pressure (FIG. 10D), however, revealed a more
ordered structure, indicative of LC properties. The Figures
collectively demonstrate that both heat and pressure are necessary
to induce the LC phase in the polymer.
[0126] FIGS. 11A and 11B show the X-ray diffraction patterns for
the 50 kDa PS samples that were prepared by heating to 20.degree.
C. and applying a pressure of 10 metric tons per 2 cm.sup.2 for 2
seconds. The diffraction pattern in FIG. 11B shows two broad peaks
at 10 to 20.degree..
Example 11
Effect of Pressure on Polyethylene Films: X-ray Analysis
[0127] FIGS. 12A and 12B show X-ray diffraction patterns for low
density polyethylene (50 kDa) in the form of am untreated pellet
(as supplied by the manufacturer) and as a (heat and pressure)
treated film in the LC state, respectively. The morphology of the
LC sample is substantially different from that of the original
polymer.
Example 12
Effect of Pressure on Polyanhydride Films: X-ray Analysis
[0128] FIG. 13 shows X-ray diffraction patterns for a sample made
of polyanhydride poly(carboxy-methoxy-propane-co-sebacic) anhydride
20:80. This polymer has a glass transition temperature of about
45.degree. C. and melting temperature of about 86.degree. C. One
sample was untreated. Other samples were heated to 60, 70, or
75.degree. C., and pressed as described in Example 10. The
untreated polymer (no applied pressure) has four typical peaks in
the region of 19 to 28.degree.. The 75.degree. C. sample
demonstrated the same peaks but with lower intensity. The 70 and
75.degree. C. samples showed the same four peaks but the lateral
orientation became more pronounced. These patterns and the LC
nature of those sample support the conclusion that an LC structure
is produced.
Example 13
Crystallinity Reduction in High Density Polyethylene
[0129] HDPE Film Preparation
[0130] High density polyethylene (HDPE) (Scientific Polymers Cat.
#141, Lot 15) in the form of pellets was used for this study. Eight
pellets of HDPE were assembled on a glass slide in a pattern of
concentric circles with each pellet about 0.3 cm in any direction
from neighboring pellets. This assembly, along with another free
glass slide, was placed on a programmable hot plate set at 150
.degree. C. When the pellets began to melt, they were sintered
together by pressing down on them with the free glass slide. The
resulting flat, transparent film was removed immediately from the
hot plate and allowed to cool between the glass slides. Upon
cooling, the HDPE film regained its original opaque color, and the
circular film was removed from between the glass slides.
[0131] Four additional films were similarly prepared. The films had
a diameter of about 2 cm. Four films subsequently were treated to
induce an LC state, and one film (control) was left untreated.
[0132] LC Induction Treatment
[0133] Four of the HDPE film were each placed on a thin aluminum
sheet, and the resulting HDPE/Al assembly then was placed onto a
programmable hotplate, along with a second, empty aluminum sheet.
The programmable hot plate was set at 60, 80, 100, and 127.degree.
C., respectively, for each of the films. The assembly was allowed
to equilibrate at the set temperature for about half a minute, and
then the HDPE film was sandwiched between the aluminum sheets and
the assembly pressurized at 890 MPa (10 tons/cm.sup.2) for one
minute using a Wabash Hydraulic Press set at room temperature.
[0134] Determination of Crystallinity
[0135] All of the films (untreated and processed at 60, 80, 100,
and 127.degree. C.) were analyzed using a D5000 Powder
Defractometer X-ray machine with the settings shown in Table 6
below.
6TABLE 6 Powder X-ray Diffraction Settings for HDPE Series Step
drive: Normal, coupled Step mode: Continuous scan Step time: 2.0 s
Step size: 0.02.degree. 2.theta. Sample Start position: 0.00 0.00
Stop position: 70.00 35.00 Tube current: 30 .about. 35 mA Tube
voltage: 40 kV Measurement channel: 1 Detector voltage: 875 V
Amplifier: 2 Base level: 0.50 V Upper level: 2.50 V Adjustment:
Automatic x scale: 0.00 .degree./cm y scale: 1000. Cps/cm
[0136] The diffraction spectra that were obtained are shown in
FIGS. 14A-E. The two largest peaks, occurring at 2.theta.=21.5 and
24.0, respectively, were selected to determine Full Width at Half
Maximum Peak Height ("FWHM") using the x-ray machine. The results
are shown in the graphs in FIGS. 15A-B and in the bar graph in FIG.
16. FIG. 15a demonstrates the total area under the curve and FIG.
15b demonstrates the amorphous area.
[0137] The data obtained from the x-ray analysis was converted to a
computer spreadsheet and graphs were constructed from the
spreadsheet. The graphs were then copied in to PhotoShop on a
Macintosh computer (Microsoft Paint on IBM) and saved as a PICT
file (256 Color Bitmap for Microsoft Paint). This file was then
opened in the program NIH Image (Scion in IBM) and the following
areas (as shown in FIGS. 15A-B) were calculated in pixels:
[0138] 1. Total area under curve (A.sub.T);
[0139] 2. Total area under amorphous region (A.sub.A); and
[0140] 3. Total area under baseline of curve (A.sub.B). Percent
crystallinity was then determined using the following formula: 1
Area of crystalline region Total area under curve = ( A T - A A )
.times. 100 A T - A A (EQ.1)
[0141] FIG. 17 shows that percent crystallinity increased from the
untreated film to the film processed at 80.degree. C. A decrease in
the percent crystallinity was observed at 100.degree. C. It is
believed that 100.degree. C. is the ideal (or near ideal)
temperature for inducing the LC phase in HDPE, based on earlier DSC
data collected. The results here show that the treated HDPE film
has a lower percent crystallinity, confirming the hypothesis that
inducing the LC phase by the method described herein can reduce the
crystallinity of a polymer.
Example 14
Crystallinity Reduction in Polystyrene
[0142] A series of thin films were prepared from Polystyrene 45K
(MW=45 kDa) (Scientific Products Inc. Cat 400, Flakes CAS3
90003-53-6), using the methods described in Example 13. The raw
material was in the form of yellowish flakes about 2 mm thick and
about 102 cm.sup.2 in area, but in an irregular shape. The
temperature series was created by heating the polymer samples on a
Cole Parmer, 0446444-series Digital Hot Plate.
[0143] Polystyrene (PS) samples were heated to 25, 60, 80, 100, or
120.degree. C. and immediately pressurized at 890 MPa (10
tons/cm.sup.2) for one minute using a Wabash Hydraulic Press. The
percent crystallinity was determined as described in Example 13.
FIG. 18 shows that the crystallinity of the polymer samples was
decreased when the LC state was induced in the polymer above its
Tg, which is about 100.degree. C. The lowest crystallinity was
obtained for the sample heated to 120.degree. C.
Example 15
Crystallinity in PCL as Function of Process Temperature
[0144] Five pieces of PCL film were made by melting the PCL polymer
on a hotplate and then flattening the melted polymer under pressure
between two glass plates. Upon cooling, four of the films were
reheated to 20, 40, 50, and 60 .degree. C., respectively, and
immediately pressurized to 10 metric tons/cm.sup.2 using a Wabash
floor press for one minute. The remaining film was pressurized
without reheating (i.e. unprocessed). The resulting five films were
then analyzed on a powder X-ray Defractometer. The spectra were
used to calculate percent crystallinity of each film using the
ratio of the crystalline and total areas as shown in FIGS. 19A-19B.
From the data, there appears to be a decrease in percent
crystallinity for film processed at 40.degree. C., which is below
the melt temperature of 60.degree. C. and suggests that the liquid
crystal phase of this polymer can be induced optimally at about
40.degree. C.
[0145] Those skilled in the art will recognize, or be able to
ascertain using no more than routine experimentation, many
equivalents to the specific embodiments of the invention described
herein. Such equivalents are intended to be encompassed by the
following claims.
* * * * *