Note: Descriptions are shown in the official language in which they were submitted.
2 9 ~
Transparent thermoplastic polyetherester amidimide
elastomars and their use for the production of articles
of medical use
This invention relates to transparent thermoplastic
polyetherester amidimide elastomers and their use for the
production of articles of medical use.
:
Many thermoplastic elastomers (TPE) are ~lsed in medicine,
especially polyure-thanes. Such a TPE for medical purposes
is not only required to have the general basic character-
istics ~elasticity, dimensional stability, flexibility,
resistance to sterilization) but for many uses it is also
required to be transparent. Such materials must also be
non-toxic.
Thermoplastic polyurethanes of aliphatic 1- ~ -dihydroxy-
polyethers and aromatic diisocyanates fulfil most of the
criteria mentioned above but they have low thermal
stability. Aromatic polyurethanes already begin to undergo
thermal degradation at processing temperatures and the
degradation is accelerated by traces of moisture and by
impurities (see, for example, M. Szycher, V.L. Poirier and
D.J. Dempsey in Journal Elastomer Plasts, Vol.15, page 83,
Le A 27 833 - ~ C 2
metabolites such as arom~tic dlamines Which are cl~ssi~ied
as highly toxic in animal experiments. Further, the
transparency of these matsrials is not optimal.
It was an object of the present invention to develop
thermoplastically processible transparent polymers for
medical uses which would resemble polyurethanes in having
the required elastomeric properties but have greater
tharmal stability.
It has now surprisingly been found that the new polymer
class of polyesterether amidimides are comparable in
their elastic properties to elastomeric polyurethanes and
are in addition distinguished by excellent transparency.
The present invention there~ore relates to thermoplastic,
elastomeric and transparent polyetherester amidimides
(PEEAI) ccrresponding to the following formula
... . .
O - E - O ) ~ ( - O - D - O ) ~ ] - OC~N - A - N~
O O
m
NH-A-N~-CO-S-C
~n
wherein
A denotes a divalent group of an aliphatic or
cycloaliphatic diamine having 1 to 25 carbon atoms,
Le A 27 833 3
20~ 9~
E denotes a divalent group of an aliphatic 1,~
dihydroxypolyether having a molecular weight of
from 400 to 2500 g/mol,
D denotes a divalent group of an aliphatic or cyclo-
aliphatic 1,~-dihydroxy compound having 2 to 15
carbon atoms, and
S denotes a divalent group of an aliphatic, cycloali-
phatic or aromatic dicarboxylic acid having 5 to 43
carbon atoms, under the condition that x is in the
range of from 0.1 to 0.9, pre~erably from 0.3 to
0.7, that the molar ratio of imide structure to
amide structure (m:n~ is greater than 2:1 and that
the weight avera~e molecular weight (Mw) determined
absolutely by light scattering has values from
~ 15 20,000 to 200,000.
;
Transparent elastic polyetherester amidimides correspond-
ing to the present invention are obtained when the molar
ratio of imide structure to amide structure ~m:n) is
greater than 2:1, preferably from 2:1 to 20:1. Polymers
having a molar ratio of imide structural units to amide
structural units (m:n) less than 2:1 or greater than 25:1
no longer fulfil the requirement for transparency.
Suitable diamines, which may ~e used alone or in combina-
tion for the preparation of the divalent A group, are
primary aliphatic or cycloaliphat.ic diamines having 1 to
25, preferably 2 to 15 carbon atoms, such as 1,4-diamino-
butane, 1,6-diaminohexane, 1,4-diaminocyclohexane,
5-amino-1-amino-methyl-1,3,3-trimethylcyclohexane, bis-
(4-aminocyclohexyl)-methane and bis-(4-amino-3-methyl-
cyclohexyl)-methane. 1,6-Diaminohexane, 5-amino-1-
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` ` 2~59~
cyclohexyl)-methane axe preferred diamines.
The following are examples of l,~-dihydroxypolyethers
having a molecular weight of from 400 to 2500 g/mol,
preferably from 650 to 2000 g/mol, which may be used alone
or in combination with various types or identical types
having differing molecular weights for producing the
divalent E group~ dihydroxypoly(ethylene oxide),
~ dihydroxy-poly-(1,3~propylene oxide), 1,~-dihydroxy-
poly-~tetramethylene oxide), randomly structured or block
copolymers of ethylene oxide and 1,2-propylene oxide and
randomly structured and block copol~mers of tetra-
hydrofuran with ethylene oxide or propylene oxide.
Preferred l,~-dihydroxypolyethers include l,~-dihydroxy-
poly-~tetramethylene oxide) having molecular weights of
from 650 to 2000 g/mol and copolymers of ethylene oxide
and tetrahydrofuran having molecular weights of up to 1500
g/mol and an ethylene oxide content below 20%.
-
The following are examples of 1,~-aliphatic or cyclo-
aliphatic 1,~-dihydroxy compounds having 2 to 15 carbon
atoms which are suitable for generating the divalent D
group: 1,2-Dihydroxyethane, 1,3-dihydroxypropane, 1,4-
dihydroxybutane, 1,4-dihydroxy-but-2-ene, 1,6-dihydroxy-
hexane, 1,4-dihydroxycyclohexane and/or 1,4-bis-(hydroxy-
methyl)-cyclohexane. 1,3-Dihydroxypropane, 1,4-dihydroxy-
butane and 1,4-bis-(hydroxymethyl)-cyclohexane, used
singly or as mixtures with one another, are preferred
l,~-dihydroxy compowlds.
Aliphatic dicarboxylic acids suitable for producing the
divalent S group having 4 to 43, preferably 6 to 30 carbon
atoms, include, for example, succinic acid and/or adipic
acid, and a cycloaliphatic dicarboxylic acid suitable for
this purpose is hexahydroterephthalic acid. The aromatic
Le A 27 833 5
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dicarboxylic acids used may ~e compounds corresponding to
the following formulae:
COOH
~IIa)
COOH
wherein
R denotes hydrogen, SO3H, NO2 or OH or
O o
HOoc~ N-A-N~ X3~ (Il,b).
o O
wherein
A has the meaning. indicated for the above general
formula.
The quantity of dicarboxylic acid added depends on the
desired proportion of amide structures in the polymers
according -to the invention. Dicarboxylic acids are
normally used in quantities of from 0.05 to 0.5 mol per 2
mol of trimellitic acid imide units.
The above-mentioned divalent groups may be partially
Le A 27 833 6
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. ' ,
'
.
2 ~ 9c5
replaced by trivalent or multivalent groups as chain
branching agents. The chain branching agents are normally
used in quantities of from 0.01 to 5.0~ by weight. The
following are examples of suitable chain branching agents:
Trimellitic acid, trimesic acid, pentaerythritol and
trimethylolpropane.
The transparent, elastic polyetherester amidimides of the
present invention may be adjusted to a weight average
molecular weight Mw of from 20,000 to 200,000 g/mol,
preferably from 20,000 to 150,000 g/mol (determined by light
scattering) by the addition of a chain terminator.
Examples of suitable chain terminators include mono~unc-
tional low molecular weight alcohols, amines and car-
boxylic acids having a boiling point above 200~C, such as
nonanol, decanol, dodecanol, stearyl alcohol or nonyl-
amine, decylamine, dodecylamine, stearylamine, nonane
carboxylic acid, decane carboxylic acid, dodecane
carboxylic acid and/or stearic acid.
The polymers of the present invention may easily be
prepared by solvent-frse condensation processes. In one
typical process of preparation, a diimide dicarboxylic
acid corresponding to formula (IIb) or the corresponding
precursors (trimellitic acid anhydride and diamine in
proportions of 2:1) are brought together with the desired
proportion of 1, ~~dihydroxypolyether, an equimolar
quantity of another dicarboxylic acid (or of the same
diimide dicarboxylic acid) and diamine and a 2 to 20 times
molar excess of l,(~-dihydroxy compound in the presence
of a metal catalyst at room temperature in a nitrogen
atmosphere. The reaction mixture becomes homogeneous and
stirrable at temperatures of about 180 to 220~C. The tem-
perature is then slowly raised to about 240-2809C, at
which stage polymerisation begins and volatile products
Le A 27 833 7
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which stage polymerisation begins and volatile products
distil off. When the major proportion of ~ater of reaction
and excess l,~-dihydroxy compound has distilled off, the
pressure is gradually reduced to about :L0 mbar. At this
stage, the stirrable, highly fluid reaction mixture
becomes progressively more viscous and the energy expended
by the stirrer increases.
The diimide dicarboxylic acid is prepared particularly
easily by reacting 2 mol of trimellitic acid per mol of
diamine under reflux in a suitable solvent such as
dimethylformaide or acetic acid.
Synthesis of the polyether ester amidimides according to
the invention is particularly simple when the diimide
dicarboxylic acids are prepared in situ in the process of
solvent-free polycondensation. For the preparation o~ the
polyetherester amidimides according to the invention,
trimellitic acid anhydride and ~he one or more than one
aliphatic diamine are used in a ratio of 2:1 wi.th the
addition of equimolar quantities of additional dicar-
boxylic acid and alipha-tic diamine optionally differing in
structure, together with the other ingredients. When
diimide dicarboxylic acid units are used for the synthesis
of the amide structures, the maximum ratio of trimellitic
acid anhydride to aliphatic diamine is 2:1.5. The
subsequent course of solvent-free condensation proceeds as
described above.
The esterification catalyst may also be added directly to
the reactive starting materials. When the precursors are
used as starting materials it may be advisable to carry
3n out a precondensation before the catalyst is added. Many
esterification catalysts are known but for the preparation
of the polyetherester amidimides according to the
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2 ~ S
titanates such as tetrabutyltitanate, magnesium acetate,
calcium stearata and/or dibutyl tin oxide. The quantities
of catalysts used range from about 0.005 to 1% by weight.
Antioxidants may be used in the reaction process, such as
the known systems based on sterically hindered phenols,
e.g. N,N'-hexamethylene-bis-(3,5-di-tert.-butyl-4-hydroxy-
hydrocinnamic acid amide~.
The thermoplastic elastomers according to the invention
may be worked up by typical extrusion or blow moulding
- 10 processes to produce medical articles of use such as blood
bags, catheters and intravenous tubes. The materials
according to th~ invention have excellent stress/strain
properties combined with low rigidity and excellent trans-
parency.
Le A 27 833 9
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2~'~L~S
Examples
All the solution viscosities indicated were determined in
methylene chloride at a concentration of 0.5 g of
polymer/lO0 ml. The thermogravimetric analyses (TGA) for
determining the thermal stability were carried out with a
PGS 2 instrument of Perkin Elmer. The rate of heating up
was always 20 K/min and the given temperature indicated a
weight loss of 1% of the sample mass. The weight average
molecular weight Mw was determined absolutely by light
scattexing.
Example 1
Preparation of the diimide dicarboxylic acids
1 Mol of 4,4'-diamino-dicyclohexylmethane (trans, trans
content >80~) and 2 mol of trimellitic acid anhydride are
carefully heated to 160C in l litre of dimethyl~ormamide,
and 2 mol o~ acetic acid anh~dride-are added when the exo-
thermic reaction has died down. The reaction mixture is
then heated under reflux at 160C for 4 hours, cooled to
60QC and poured into 5 times its volume of water. The pre-
cipitated diimide dicarboxylic acid is suction filtered,washed with water until neutral and then dried at lloqC.
Method of polymerisation
The reaction apparatus, consisting of a 250 ml single
necked flask with condensation attachment, metal stirrer
and guide and a receiver equipped to be cooled, is
evacuated three times and ventilated with hiyhly pure
nitrogen. 27.93 g (0.05 mol) of the diimide dicarboxylic
acid described above, 29.28 g (0.03 mol) of a polytetrahy-
dro-furan having an average molecular weight of lO00,
0.526 g ~2.5 mmol) of 4,4'-diamino-dicyclohexylmethane and
18 g (0.2 mol) of 1,4-butanediol are then introduced. 10
I.e A 27 833 10
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mg of butyl titanate dissolved in 1, 4-butanediol are added
as catalyst. The reaction flask i5 then placed in a metal
bath heated to 200aC and the stirrer is put into opera-
tion. When the solution, which is initially claudy, has
become homogeneous, the bath temperature is raised to
250 9 C within 2 hours, small quantities of a waterJdiol
mixture already distilling off at this stage. The pressure
is then reduced to 0.4 mbar within 30 minutes and the
temperature is kept constant at 250~C for 3 hours.
To complete the reaction, the temperature is raised to
260~C for 30 minutes and the pressure is lowered to 0.25
mbar. A transparent, soluble polyetherester imidamide
having a molar ratio of imide structure to amide structure
of 20:1 and a relative solution viscosity of ~rel = 1.336
is obtained. The average molecular weiyht Mw is 45,300.
The thermal stability determined according to dynamic PGA
was found to be 385RC.
Mechanical data:
Tensile strength 100~ (MPA) 5.2
20 Tensile stress 300% (MPA) 6.1
Tensile strength (MPA) 15.0
El~ngation at break (%) 750
Shore A 80
Exam~le 2
Method of polymerisation
The reaction apparatus, consisting of a 250 ml single
necked flask with condensation attachment, metal stirrer
and guide and a receiver e~uipped to be cooled is
evacuated three times and ventilated with pure nitrogen.
11.03 y (0.0525 mol) of 4,4'-diamino-dicyclohexylmethane,
19.2 g (0.1 mol) of trimellitic acid anhydride, 29.28 g
(0.03 mol) of a polytetrahydrofuran having an average
Le A 27 833 11
2 a ~
molecular weight of lO00 and 18 g ~0.2 mol) of l,4-
butanediol are then introduced. lO mg of butyl titanate
dissolved in 1,4-butanediol are added as catalyst. The
reaction flask i5 then introduced into a metal bath heated
to 200~C and the stirrer is put into operation~ When the
solution, which is initially cloudy, has become homogen-
eous, the bath temperature is raised to 250~C within 2hours, during which time small quantities of a water/diol
mixture already distil off. The pressure i~ then reduced
to 0.4 mbar within 30 minutes and the temperature is kept
constant at 250QC for 3 hours. To complete the reaction,
the temperature is raised to 260~C for 30 minutes and the
pressure is lowered to 0.25 mbar. A transparent, soluble
polyether ester imidamide having a molar ratio of imide
structures to amide structures of 20:1 and a relative
solution viscosity of ~rel = 1.621 is obtained. The
average molecular weight Mw is 91,300. llhe thermal
stability, determined according to dynamic TGA was found
to be 385~C.
20 Mechanical data:
Tensile stress 100% (MPA) 5.2
Tensile stress 300% tMPA) 6.2
Tensile strength (MPa) 15.3
Elongation at break (%) 82S
25 Shore A 85.
Example 3
Preparation of the diimide dicarboxylic acid (see
Example 1)
Method of polymerisation
The diimide dicarboxylic acid described in Example 1,
1.46 g (0.01 mol) of adipic acid, 0.58 g (0.005 mol) of
hexamethylene diamine, 9.25 g (0.02 mol) of a polytetra-
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hydrofuran having an average molecular weight of 1000 and18 g ~0.2 mol) of 1,4-butanediol are introduced into the
reaction apparatus described in Example 1 after the latter
has been flushed with highly pure nitrogen. 10 mg of butyl
titanate dissolved in 1,4-butanediol are added as
catalyst. The reaction flask is then introduced into a
metal bath heated to 200QC and the stirrer is put into
operation. When the solution, which is initially cloudy,
ha~ become homogeneous, the bath temperature is raised to
250QC within 2 hours, during which time small quantities
of a water/diol mixture already distil off. The pressure
is then reduced to 0.4 mbar within 30 minutes and the
temperature is kept constant at 250QC for 3 hours. To
complete the reaction, the temperature is raised to 260~C
for 30 minutes and the pressure is lowered to 0.25 mbar.
A transparent soluhle polyetherester imidamide having a
molar ratio of imide structures to amide structures oP 9:1
and a relative solution viscosity of ~rel = 1.664 is
obtained. The average molecular weight Mw is 116,700.
The thermal stability determined according to dynamic TGA
; is found to be 379QC.
Example 4
Preparation of the diimide dicarboxylic acids
1 Mol of Hexamethylene diamine and 2 mol of trimellitic
acid anhydride are carefully heated to 1609C in 1 litre of
dimethylformamide. 2 Mol of acetic acid anhydride are
added when the exothermic reaction has died down. The
reaction mixture is then heated under reflux at 160QC for
4 hours, cooled to 609C and poured into 5 times its volume
of water. The precipitated diimide dicarboxylic acid is
suction filtered, washed with water until neutral and then
dried at 110 Q C .
Le A 27 833 13
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Method of polymerisation
23.22 g (0.05 mol) of the diimide dicarboxylic acid
described above, 24.40 g ~0.025 mol) of polytetrahydro-
furan having an average molecular weight of 1000, 0.22 g5 (2.5 mmol) of hexamethylenediamine and 15.22 g (0.2 mol)
of 1,3-propanediol are introduced into the reaction
apparatus described in Example 1 after the apparatus has
been flushed with highly pure nitrogen. 10 mg of butyl
titanate dissolved in 0.42 ml of 1,4-butanediol are added
` 10 as catalyst.
The reaction flask is then introduced into a metal bath
heated to 200~C and the stirrer is put into operation.
When the initially cloudy solution has become homogeneous,
the bath temperature is raised to 250UC within 2 hours,
during which time small quantities of a water/diol mixture
already distil off. The pressure is then reduced to 0.4
mbar within 30 minutes and the temperature is kept
constant at 250QC ~or 3 hours. To complete the reaction,
the temperature is raised to 260QC for 30 minutes and the
pressure is lowered to 0.25 mbar. A transparent, soluble
polyetherester imidamide having a molar ratio of imide
structures to amide structures of 20:1 and a relative
solution viscosity o~ ~rel = 1.380 is obtained. The
average molecular weight Mw is 37,900. The thermal
stability according to TGA is 365~C.
Mechanical data:
Tensile stress 100% (MPa) 5.8
Tensile stress 300% (MPa) 6.6
Tensile strength (MPa) 13.0
30 Elonyation at break (%) 67S
Shore A go
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Method of polymerisation
11.03 g (0.0525 mol) of 4,4'-diamino-dicyclohexylmethane,
19.2 g (0.1 mol) of trimellitic aci~ anhydride, 24.25 g
(0.025 mol) of a polytetrahydro~uran having an average
molecular weight of 1000, 18 g (0.2 mol) of 1,4-butanediol
and 0.269 g ~0.01 mol) o~ stearylamine are introduced into
the reaction apparatus described in Example 1 after the
apparatu~ has been fl~lshed with highly pure nitrogen. 10
mg of butyl titanate dissolved in 1,4-butanediol are added
as catalyst. The reaction flask is then introduced into a
metal bath heated to 200~C and the stirrer is put into
operation. When the initially cloudy solution has become
homogeneous, the bath temperature is raised to 250~C
within 2 hours, during which time small quantities of
water/diol mixture already distil off. The pressure is
then reduced to 0.4 ~bar within 30 minutes and the
temperature is kept constant at 250~C for 3 hours.
To complete the reaction, the temperature is raised to
2609C for 30 minutes and the pressure is lowered to 0.25
mbar. A transparent, soluble polyetherester imidamide
having a molar ratio of imide structures to amide
structures of 20 : 1 and a relative solution viscosity of
~rel = 1.320 is obtained. The average molecular weight Mw
is 41,000. The thermal stability according to TGA is 385-
~C .
Mechanical data:
Tensile stress 100~ (MPa) 5.2
Tensile stress 300% (MPa) 6.5
30 Tensile strength (mPa) 13.5
Elongation at break (~) 740
Shore A 88
Le A 27 833 15
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Example 6Method of polymerisation
1.163 kg (5.54 mol) of 4,4'-diamino-dicyclohexylmethane,
0.470 kg (2.77 mol) of 5-amino-1-aminomethyl-1,3,3-
trimethylcyclohexane, 3.043 kg (15.83 mol) of trimelliticacid anhydride, 2.884 kg (2 91 mol) of a polytetrahydro-
furan having an average molecular weight of 1000, 1.661 kg
(0.83 mol) of a polytetrahydrofuran having an average
molecular weight of 2000 and 0.598 kg (4.15 mol) of 1,4-
cyclohexane dimethanol together with a solution of 1.662 gof butyltitanate in 70 ml of 1,4-butanediol as catalyst
are introduced into a 20 1 autoclave which has been
flushed with nitrogen. The reaction mixture is stirred
under its own pressure at the rate of 100 revs/min at
200QC for 2 hours. The reaction mixture is then heated to
250~C and stirred at 50 revs/min for 2 hours. A vacuum is
applied within one hour and the temperature is raised to
260QC. As soon as the speed of stirring- has fallen to
below 40 revs/min, the product is expelled from the auto-,
clave by means of nitrogen and is spun and granulated.
A transparent, soluble polyetherester imidamide having a
molar ratio of imide structures to amide structures of
20:1 and a relative solution viscosity of ~rel = 1.260 is
obtained. The average molecular weight Mw is 28,500 and
the thermal stability according to TGA is 395QC.
Le A 27 833 16
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