DESCRIPTION
Title of the Invention:
LOW-CHARGING FIBER AND METHOD FOR PRODUCING THE SAME
Technical Field
The present invention relates to a low-charging fiber
having an average surface porosity of less than 3% and made
of a biodegradable polymer that contains a specific amount of
a specific phospholipid.
Background Art
Various medical devices formed from biodegradable
polymers, particularly aliphatic polyesters such as
polylactic acid, polyglycolic acid, andpolycaprolactone, and
copolymers thereof, are known. For example, a formed article
in the form of a fiber has been applied to a suture thread or
a bioabsorbable sheet.
Electrospinning (also referred to as an electric field
spinning method) allows for the easy production of a fiber
having a small fiber diameter. According to this production
method, the surface area of a fibrous formed article can be
increased to enhance adhesion to cells. Therefore, its
applications to carriers for cell culture, scaffoldmaterials
for regenerative medicine, and the like have been studied.
Generally, it is knownthatapolyesteris easilycharged
and that the half-life of the built-up charge is long.
Accordingly, a fibrous formed article obtained by processing
an aliphatic polyester into a fiber is likely to be charged
and thus is not easy to use. Thus, a polyester fiber having
excellent antistatic properties has been demanded.
However, biodegradable low-charging polyester fibers
for in vivo use are heretofore unknown.
JP-A-9-157954 describes an antistatic fiber made of an
antistatic polymer and a polyester copolymer. This fiber is
naturallydegradable andaimedtopreventpollution, andthere
is no description about in vivo use or use of a
low-molecular-weight compound as an antistatic agent.
JP-A-8-231837 describes an antistatic polylactic acid
obtainedbyaddingapolyalkyleneetherandanantistaticagent
made of an aliphatic polyester other than polylactic acid to
polylactic acid. However, there is no description about in
vivo use or use of a low-molecular-weight compound as the
antistatic agent.
W006/022430 describes a fiber obtained by adding a
phospholipidtopolylactic acid, but nowhere describes a fiber
having antistatic properties.
Disclosure of the Invention
An object to be achieved by the invention is to provide
a biodegradable low-charging fiber.
The prevent inventors have conductedextensive research
to achieve the object. As a result, they have found that
surprisingly, when a specific amount of a specific
phospholipid that is not known to have antistatic properties
is addedto abiodegradablepolymer, and the resultingmixture
is formed into a fiber having a smooth surface, low-charging
properties are developed. The invention has thus been
accomplished.
That is, the invention is a fiber containing a
biodegradable polymer that contains a phospholipid andhaving
anaverage surfaceporosityof less than 3%. The phospholipid
is one of the following: dilauroylphosphatidylcholine in an
amount of 0.2 wt% to 5 wt%; dimyristoylphosphatidylcholine in
an amount of 0.4 wt% to 5 wt%; dipalmitoylphosphatidylcholine
in an amount of 1 wt% to 5 wt%; dioleoylphosphatidylcholine
in an amount of 1 wt% to 5 wt%;
dioleoylphosphatidylethanolamine in an amount of 1 wt% to 5
wt%; and two or more of the phospholipids in a total amount
of 5 wt% or less, the twoormore phospholipids being inatotal
amount of 1 wt% or more, containing at least
dilauroylphosphatidylcholine in an amount of 0.2 wt% or more,
or containing at least dimyristoylphosphatidylcholine in an
amount of 0.4 wt% or more.
The fiber ofthe invention is biodegradable andalso has
@
excellent antistatic properties.
Best Mode for Carrying Out the Invention
The fiberoftheinventioncontainsone ofthe following,
relative to the biodegradable polymer:
a) dilauroylphosphatidylcholine in an amount of 0.2 wt%
to 5 wt%,
b) dimyristoylphosphatidylcholine in an amount of 0.4
wt% to 5 wt%,
c) dipalmitoylphosphatidylcholine in an amount of 1 wt%
to 5 wt%,
d) dioleoylphosphatidylcholine in an amount of 1 wt% to
5 wt%, and
e) dioleoylphosphatidylethanolamine in an amount of 1
wt% to 5 wt%, or
f) two or more of the phospholipids a) to e) .
In the case of f), it is necessary to meet both the
requirement 1: the total amount of the phospholipids is 5 wt%
or less, and the requirement 2: the total amount is 1 wt% or
more, at least dilauroylphosphatidylcholine is contained in
an amount of 0.2 wt% or more, or at least
dimyristoylphosphatidylcholine is contained in an amount of
0.4 wt% or more.
Here, when the phospholipid content is more than 5 wt%,
although an antistatic effect is exhibited, the durability or
CI
spinning properties of the fiber itself deteriorate.
Therefore, this is undesirable.
The phospholipids may be extracted from animal tissue
and may also be artificially synthesized.
Examples of biodegradable polymers for use in the
inventionincludealiphaticpolyesters suchaspolylacticacid,
polyglycolic acid, polycaprolactone, polydioxanone, lactic
acid-glycolic acid copolymers, lactic acid-caprolactone
copolymers, polyglycerol sebacic acid, polyhydroxyalkanoic
acid, and polybutylene succinate; aliphatic polycarbonates
such as polymethylene carbonate; polysaccharide derivatives
such as cellulose diacetate, cellulose triacetate, methyl
cellulose, propyl cellulose, benzyl cellulose, and
carboxymethylcellulose; proteins such as fibroin, gelatin,
and collagen; and derivatives thereof. Aliphatic polyesters
such as polylactic acid, polyglycolic acid, and lactic
acid-glycolic acid copolymers are preferable, and polylactic
acid and lactic acid-glycolic acid copolymers are more
preferable .
In the case where polylactic acid is used,
polymer-forming monomers include, but are not particularly
limited to, L-lactic acidandD-lactic acid. In addition, the
optical purity or molecular weight of the polymer, the
proportions of L- and D-forms, or their arrangement is not
particularly limited, but a polymer having a high L-form
content is preferable. It is also possible to use a
stereocomplexofpoly(L-lactic acid) andpoly(D-lactic acid).
It is preferable that the biodegradable polymer used in
the invention has high purity. In particular, with respect
to residues contained in the polymer, such as additives,
plasticizers, residual catalysts, residual monomers, and
residual solvents usedin formingorpost-processing, the less
residues the better. Particularly in the case of medical
applications, the amount of residues needs to be controlled
below the safety standard.
In addition, the molecular weight of the biodegradable
polymer used in the invention is preferably from 1 x lo3 to
5 x lo6, more preferably from 1 x lo4 to 1 x lo6, and still more
preferably from 5 x lo4 to 5 x lo5. In addition, the terminal
structure of the polymer and the catalyst for polymer
polymerization can be arbitrarily selected.
As long as the desired object is not impaired, other
polymers or other compounds may also be mixed into the fiber
of the invention. For example, polymer copolymerization,
polymer blending, and compound mixing may be performed.
It is preferable that the fiber of the invention has an
average fiber diameter of from 0.1 pm to 10 pm. In the case
where the average fiber diameter is less than 0.1 pm or more
than 10 pm, when such a fiber is formed into a fibrous formed
article and used as a medical supply, excellent
d
characteristics are not obtained. The average fiber diameter
is more preferably from 1.0 pm to 8.0 pm, and still more
preferablyfrom2.0 pmto 7.0 pm. Incidentally, fiber diameter
refers to the diameter of a fiber cross-section. The
cross-sectional shape of a fiber is not limited to a circular
shape, and may also be an elliptical or modified shape. As
the fiber diameter in the case of an elliptical shape, the
average of the lengths of the major axis and minor axis is
calculatedas the fiber diameter. In addition, when the fiber
cross-section is not either circular or elliptical, the
cross-sectional shape is approximated to a circle or ellipse
to calculate the fiber diameter.
The average porosity of the fiber of the invention is
less than 3%, more preferably less than 2.5%, and still more
preferably less than 2%. The average porosity herein refers
to the percentage of the pore area relative to the area of the
entire fiber surface, and is determined by the binarization
processing of a scanning electron microscope photograph of a
fiber structure (~20,000)u sing image processing software
(next NewQube). However, it is alsopossibletousedifferent
image processing software equivalent to the above image
processing software.
As an example of a spinning method for providing a fiber
with an average porosity of less than 3%, it is possible to
reduce the relative humidity during electrospinning.
IB
Specifically, the relative humidityis preferably25% or less,
and more preferably 20% or less.
Electrospinning is a method in which a high voltage is
appliedtoa solutionof apolymerina solvent, thereby giving
a fibrous formed article on the electrode. Electrospinning
usually includes a step of dissolving a polymer in a solvent
to produce a solution, a step of applying a high voltage to
the solution, a step of discharging the solution, a step of
evaporating the solvent from the discharged solution to
produce a fibrous formed article, an optional step of
dissipatingthe charge on the produced fibrous formedarticle,
anda stepof accumulatingthe fibrous formedarticlebycharge
dissipation (see, e.g.,W006/022430). However, aslongasthe
fiber of the invention canbe obtained, other spinningmethods
such as spunbonding and melt-blowing may also be used.
One of the applications of the fiber of the invention
is a fibrous formed article. Such a fibrous formed article
ispreferablyproducedwithoutperforminga fiber-cutting step
during the steps from spinning to processing into a fibrous
formed article.
The entire thickness of the fibrous formed article of
the invention is not particularly limited, but is preferably
from 25 pm to 200 pm, and more preferably from 50 to 100 pm.
As long as the desired object is not impaired, it is
possible to perform optional processing. For example, a
flocculent fiber structure may be further stacked on the
surface of the fibrous formed article of the invention, or a
flocculent structure may be inserted between the fibrous
formed articles of the invention to form a sandwich structure.
The fiber or fiber structure of the invention may be
surface-treatedwitha chemical suchas a surfactant tomodify
its surface hydrophilicity or hydrophobicity. In medical
applications, it is also possible to optionally perform a
coating treatment to impart antithrombogenicity or coat the
surface with a physiologically active substance such as an
antibody. In this case, the coating method, treatment
conditions, and chemical drugs used for the treatment may be
arbitrarily selected as long as the structure of the fiber is
not extremely destroyed and the object of the invention is not
impaired.
In addition, the fiber or fibrous formed article of the
inventionmay also optionallycontaina drug inside the fiber.
In the case where electrospinning is used for the formation,
drugs to be used are not particularly limited as long as they
are soluble in a volatile solvent and their physiological
activities are not lost upon dissolution. Specific examples
of such drugs include tacrolimus and analogs thereof, statin
drugs, and taxane anticancer drugs. In addition, protein
preparations and nucleic acid medicines may also be used as
longastheiractivitiescanbemaintainedinavolatilesolvent.
1,
In addition to drugs, further, metals, polysaccharides, fatty
acids, surfactants, and volatile-solvent-resistant
microorganisms may also be contained.
The fiber and fibrous formed article of the invention
are suitable for use as medical supplies, such as materials
for the protection of the surface of organs or wound sites,
covering materials, sealing materials, artificial dura mater,
adhesion barriers, and hemostatic materials.
Examples
1. Average Fiber Diameter:
The surface of an obtained fibrous formed article was
photographed with a scanning electron microscope (Keyence
Corporation: tradename "VE 8800") atamagnificationof ~2,000.
In the obtained photograph, 20 points were selected at random
and measured for fiber diameter. The average of all the fiber
diameters was calculated as the average fiber diameter (n =
20).
2. Average Thickness:
Using a high-accuracy digital length gauge (Mitutoyo
Corporation: trade name "Litematic VL-50") , the thickness of
a fibrous formed article (n = 10) was measured with a
length-measuring force of 0.01 N, and the average was
calculated. Incidentally, themeasurement was performedwith
the minimum measuring force required to use the measuring
*
instrument.
3. Average Apparent Density:
The mass of a fibrous formed article was measured, and
the average apparent density was calculated based on the area
and the average thickness determined by the above methods.
4. Average Porosity:
Average porosity was determined by the binarization
processing of a scanning electron microscope photograph of an
obtained fiber structure (~20,000)u sing image processing
software (next New Qube) .
5. Charge Test :
Measurementwasperformedbya charge test inaccordance
with the medical nonwoven fabric test method of JIS L 1912
(half -1if e measurement) . That is, a specimen was charged in
a corona discharge field, and the resulting initial charge
amount and the time until the charged voltage was attenuated
by half (half-life) were measured.
[Example 11
10 parts by weight of polylactic acid (molecular weight:
137,000, manufactured by Taki Chemical) having added thereto
1% dilauroylphosphatidylcholine was dissolved in 80 parts by
weight of dichloromethane and 10 parts by weight of ethanol
to give a uniform solution. Using the solution,
electrospinning was performedtoprepare a sheet-like fibrous
formed article. The inner diameter of the discharge nozzle
*
was 0.8 mm, thevoltage was 8 kV, the distance fromthe discharge
nozzle to the flat cathode plate was 15 cm, and the humidity
was 19%. The obtained fibrous formed article had an average
fiber diameter of 3.7 pm, a thickness of 80 pm, an average
apparent density of 138 kg/m3, and an average porosity of 0%.
The initial charge amount was 0.07 kV, and the half-life was
0.5 second.
[Example 21
A fibrous formedarticle was prepared in the same manner
as in Example 1, except for using 10 parts by weight of
polylactic acid (molecular weight: 137,000, manufactured by
Taki Chemical) having added thereto 5%
dioleoylphosphatidylethanolamine. The obtained fibrous
formed article had an average fiber diameter of 4.0 pm, a
thickness of 99 pm, an average apparent density of 165 kg/m3,
and an average porosity of 0%. The initial charge amount was
0.188 kV, and the half-life was 0.5 second.
[Example 31
A fibrous formedarticle was prepared in the same manner
as in Example 1, except that 11 parts by weight of polylactic
acid (molecularweight: 266,000, manufacturedby PURAC) having
addedthereto 0.2% dilauroylphosphatidylcholinewas dissolved
in 79 parts by weight of dichloromethane and 10 parts by weight
ofethanol. Theobtainedfibrous formedarticlehadanaverage
fiber diameter of 4.4 pm, a thickness of 79 pm, an average
e
apparent density of 139 kg/m3, and an average porosity of 0%.
The i n i t i a l amount of charge was 0 . 5 8 kV, and the h a l f - l i f e
was 7 . 6 seconds.
[Example 41
A fibrous formedarticle was prepared in the same manner
as in Example 1, except that 11 parts by weight of polylactic
acid (molecularweight: 133,000, manufacturedbyPURAC) having
added thereto 0.4% dimyristoylphosphatidylcholine was
dissolvedin 79partsbyweightof dichloromethaneand10parts
byweightofethanol. Theobtainedfibrous formedarticlehad
an average fiber diameter of 4 . 4 ym, a thickness of 91 pm, an
average apparent density of 142 kg/m3, and an average porosity
of 0%. The i n i t i a l chargeamountwas 0.44 kV, a n d t h e h a l f - l i f e
was 1.5 seconds.
[Example 51
A fibrous formed a r t i c l e was prepared in the same manner
as in Example 1, except that 11 parts by weight of polylactic
acid (molecularweight: 133,000, manufacturedby PURAC) having
addedtheretol% dipalmitoylphosphatidylcholinewas dissolved
in 79parts byweight of dichloromethane and10 parts byweight
ofethanol. Theobtainedfibrous formedarticlehadanaverage
fiber diameter of 6.2 pm, a thickness of 100 pm, an average
apparent density of 137 kg/m3, and an average porosity of 0%.
The i n i t i a l charge amount was 0 . 4 9 kV, and the h a l f - l i f e was
4 . 5 seconds.
[Example 61
A fibrous formedarticle was prepared in the same manner
as in Example 1, except that 11 parts by weight of polylactic
acid (molecularweight: 133,000, manufacturedby PURAC) having
added thereto 5% dilauroylphosphatidylcholine was dissolved
in 79parts byweight of dichloromethane and10 parts byweight
ofethanol. Theobtainedfibrous formedarticlehadanaverage
fiber diameter of 4.0 pm, a thickness of 79 pm, an average
apparent density of 116 kg/m3, and an average porosity of 0%.
The initial charge amount was 0.02 kV, and the half-life was
0.2 second.
[Example 71
A fibrous formedarticle was prepared in the same manner
as in Example 1, except that 11 parts by weight of a lactic
acid-glycolic acid copolymer (molecular weight: 115,000,
manufactured by PURAC) having added thereto 0.4%
dilauroylphosphatidylcholine was dissolved in 79 parts by
weight of dichloromethane and 10 parts by weight of ethanol.
The obtained fibrous formed article had an average fiber
diameter of 3.7 pm, a thickness of 78 pm, an average apparent
density of 163 kg/m3, and an average porosity of 0%. The
initial charge amount was 0.058 kV, and the half-life was 1.4
seconds.
[Example 81
A fibrous formedarticle was prepared in the samemanner
*
as in Example 1, except that 11 parts by weight of polylactic
acid (molecular weight: 133,000, manufacturedby PURAC) having
addedthereto 1% dioleoylphosphatidylcholine was dissolvedin
79 parts by weight of dichloromethane and 10 parts by weight
ofethanol. Theobtainedfibrous formedarticlehadanaverage
fiber diameter of 4 . 5 pm, a thickness of 79 pm, an average
apparent density of 141 kg/m3, and an average porosity of 0%.
The i n i t i a l charge amount was 0.36 kV, and the half - l i f e was
1 second.
[Example 91
A fibrous formedarticle was prepared in the same manner
as in Example 1, except that 11 parts by weight of polylactic
acid (molecularweight: 133,000, manufacturedby PURAC) having
addedthereto 0.4% dilauroylphosphatidylcholine was dissolved
in 79parts byweight of dichloromethane and10 parts byweight
ofethanol. Theobtainedfibrous formedarticlehadanaverage
fiber diameter of 4.0 pm, a thickness of 78 pm, an average
apparent density of 144 kg/m3, and an average porosity of 0%.
The i n i t i a l charge amount was 0.338 kV, and the h a l f - l i f e was
1 second.
[Comparative Example 11
A fibrous formedarticle was prepared in the same manner
as in Example 1, except that 10 parts by weight of polylactic
acid (molecular weight: 137,000, manufactured by Taki
Chemical) was dissolved in 90 parts by weight of a
d
dichloromethane solution. The obtained fibrous formed
article had an average fiber diameter of 6.2 pm, a thickness
of 107 pm, an average apparent density of 148 kg/m3, and an
average porosity of 30%. The initial charge amount was 0.528
kV, and no half-life was observed.
[Comparative Example 21
A fibrous formedarticle was prepared in the same manner
as in Example 1, except that 11 parts by weight of polylactic
acid (molecularweight: 133,000, manufacturedby PURAC) having
added thereto 0.5% dioleoylphosphatidylcholine was dissolved
in 89 parts by weight of dichloromethane, and that spinning
was performed at high humidity (36%). The obtained fibrous
formed article had an average fiber diameter of 3.9 pm, a
thickness of 71 pm, an average apparent density of 147 kg/m3,
and an average porosity of 27%. The initial charge amount was
0.38 kV, and no half-life was observed.
[Comparative Example 31
A fibrous formedarticle was prepared in the samemanner
as in Example 1, except that 11 parts by weight of polylactic
acid (molecularweight: 133,000, manufacturedby PURAC) having
added thereto 0.1% dioleoylphosphatidylethanolamine was
dissolved in 89 parts by weight of dichloromethane, and that
spinning was performed at high humidity (36%) . The obtained
fibrous formed article had an average fiber diameter of 4.2
pm, a thickness of 74 pm, an average apparent density of 160
(I
kg/m3, and an average porosity of 3 6.2%. The initial charge
amount was 0.32 kV, and no half-life was observed.
[Comparative Example 41
A fibrous formed article was prepared in the same manner
as in Example 1, except that 11 parts by weight of polylactic
acid (molecularweight: 133,000, manufacturedbyPURAC) having
added thereto 0.5% dioleoylphosphatidylethanolamine was
dissolved in 89 parts by weight of dichloromethane, and that
spinning was performed at high humidity (36%) . The obtained
fibrous formed article had an average fiber diameter of 3.9
pm, a thickness of 84 pm, an average apparent density of 156
kg/m3, and an average porosity of 37%. The initial charge
amount was 0.42 kV, and no half-life was observed.
[Comparative Example 51
A fibrous formedarticle was prepared in the samemanner
as in Example 1, except that 11 parts by weight of polylactic
acid (molecularweight: 133,000, manufacturedby PURAC) having
addedthereto 0.4% dilauroylphosphatidylcholinewas dissolved
in 89 parts by weight of dichloromethane, and that spinning
was performed at high humidity (31%). The obtained fibrous
formed article had an average fiber diameter of 5.5 pm, a
thickness of 77 pm, an average apparent density of 135 kg/m3,
and an average porosity of 30%. The initial charge amount was
0.3 kV, and no half-life was observed.
Industrial Applicability
The fiber ofthe invention is biodegradable andalso low
charging, and further has excellenthandleability. Therefore,
fiber formed articles made thereof are useful as medical
supplies, for example, especially as materials for the
protection of the surface of organs or wound sites, covering
materials, sealingmaterials, artificialduramater, adhesion
barriers, and hemostatic materials.

t
CLAIMS
1. A fiber comprising a biodegradable polymer that contains
a phospholipid and having an average surface porosity of less
than 3%,
wherein the phospholipid is one of the following:
dilauroylphosphatidylcholine in an amount of 0.2 wt% to
5 wt%;
dimyristoylphosphatidylcholine in an amount of 0.4 wt%
to 5 wt%;
dipalmitoylphosphatidylcholine in an amount of 1 wt% to
5 wt%;
dioleoylphosphatidylcholine in an amount of 1 wt% to 5
wt%; and
dioleoylphosphatidylethanolamine in an amount of 1 wt%
to 5 wt%; or is
two or more of the phospholipids in a total amount of
5 wt% or less, and in a total amount of 1 wt% or more, or contains
at least dilauroylphosphatidylcholine in an amount of 0.2 wt%
or more, or contains at least dimyristoylphosphatidylcholine
in an amount of 0.4 wt% or more.
2 . The fiber according to claim 1, wherein the biodegradable
polymer is an aliphatic polyester.
19
3 . The fiber according to claim 1, wherein the biodegradable
polymer is polylactic acid and/or a polylactic acid copolymer.
4 . The fiber according to claim 1, wherein the biodegradable
polymer is polylactic acid.
5. The fiber according to any one of claims 1 to 4, produced
by electrospinning.
6 . A fibrous formed article comprising the fiber of any one
of claims 1 to 5.