THERMOPLASTIC POLY(URETHANE-UREA) POLYADDUCTS

Abstract

A thermoplastic poly(urethane-urea) polyadduct with sterically hindered urea groups of the following Formula (I):

—[I-M-(I—C.sub.1).sub.a—(I-M).sub.b-(I—C.sub.2).sub.c].sub.n-  (I)

I, M, C.sub.1 and C.sub.2 each representing bivalent residues linked to each other via a urethane or urea moiety. In the residues I, C.sub.1 and C.sub.2, when more than four carbon atoms are present, optionally at least one of them is substituted by a heteroatom selected from oxygen and nitrogen. Optionally at least one of the residues I, M, C.sub.1 and C.sub.2 includes one or more ester moieties. a, b and c each independently represent an integer from 0 to 10, and n is a number ≥3 representing the number of blocks in the polyadduct. Within each separate block a+c≥1, and in all blocks together at least one a≥1 and at least one c≥1.

Claims

1. A thermoplastic poly(urethane-urea) polyadduct with sterically hindered urea groups of the following Formula (I):
—[I-M-(I—C.sub.1).sub.a—(I-M).sub.b-(I—C.sub.2).sub.c].sub.n-  (I) wherein I, M, C.sub.1 and C.sub.2 each represent bivalent residues that are linked to each other via a urethane or urea moiety, whereof each I independently represents a bivalent, saturated or unsaturated, aliphatic, alicyclic or aromatic residue with 1 to 20 carbon atoms derived from a diisocyanate; each M independently represents a bivalent residue of an aliphatic polyether, polyester or polycarbonate derived from a macrodiol having a number average molecular weight M.sub.n≥500; each C.sub.1 independently represents a bivalent, saturated or unsaturated, aliphatic or alicyclic residue with 1 to 30 carbon atoms derived from a diamine or amino alcohol with at least one sterically hindered secondary amino group through removal of one N-linked hydrogen atom each of the diamine or one N-linked and the O-linked hydrogen atoms of the amino alcohol; each C.sub.2 independently represents a bivalent, saturated or unsaturated, aliphatic, alicyclic or aromatic residue with 1 to 20 carbon atoms derived from a diol, diamine or amino alcohol; wherein, in the residues I, C.sub.1 and C.sub.2, when more than four carbon atoms are present, optionally at least one of them is substituted by a heteroatom selected from oxygen and nitrogen; wherein optionally at least one of the residues I, M, C.sub.1 and C.sub.2 comprises one or more ester moieties; and a, b and c each independently represent an integer from 0 to 10, and n is a number ≥3 representing the number of blocks in the polyadduct; provided that within each separate block a+c≥1 and in all blocks together at least one a≥1 and at least one c≥1.

2. The thermoplastic poly(urethane-urea) polyadduct according to claim 1, wherein: a and c are each independently ≤5 or ≤3; and/or a and c are each independently ≥1; and/or b≥1; and/or b=c or b=a or b+1=a+c; and/or n≥5 or n≥10 or n≥50.

3. The thermoplastic poly(urethane-urea) polyadduct according to claim 1, wherein at least one of the residues I, M, C.sub.1 and C.sub.2 comprises one or more ester moieties cleavable under physiological conditions, and that the residues I, M, C.sub.1 and C.sub.2 as well as any cleavage products thereof are biocompatible and physiologically acceptable.

4. The thermoplastic poly(urethane-urea) polyadduct according to claim 1, wherein the residues I are each independently derived from a diisocyanate selected from the following group: 1,6-hexamethylene diisocyanate, 4,4′-diisocyanatodicyclohexylmethane, isophorone diisocyanate, 1,3-bis(isocyanatomethyl)cyclohexane, diphenylmethane-4,4′-diisocyanate, L-lysine ethyl ester diisocyanate.

5. The thermoplastic poly(urethane-urea) polyadduct according to claim 1, wherein the residues M are each independently derived from a polyether, polyester or polycarbonate selected from the following group: polytetrahydrofuran, polyethylene glycol, polypropylene glycol, polycaprolactone, polylactide, polyglycolide, poly(lactide-co-glycolide), polyhexamethylene carbonate.

6. The thermoplastic poly(urethane-urea) polyadduct according to claim 1, wherein the residues C.sub.1 are each independently derived from a diamine and selected from residues of the following Formula (II): ##STR00029## wherein the bonds marked with asterisks each show the linkage to the carbonyl group of a urethane or urea moiety linking the residues I, M, C.sub.1 and C.sub.2, R.sub.1 is selected form bivalent, saturated or unsaturated, aliphatic or alicyclic residues with 1 to 20 carbon atoms; and the R.sub.2 are each independently selected from hydrogen and monovalent, bulky, saturated or unsaturated, aliphatic or alicyclic residues with 1 to 10 carbon atoms, provided that not both R.sub.2 are simultaneously hydrogen, wherein the two residues R.sub.2 are optionally linked to each other and form a ring comprising the two nitrogen atoms, R.sub.1, and at least one carbon atoms of the two residues R.sub.2; provided that the ring is not piperazine, 2-methylpiperazine or 2,5-dimethylpiperazine.

7. The thermoplastic poly(urethane-urea) polyadduct according to claim 6, wherein R.sub.1 is selected from C.sub.1-C.sub.10-alkylene or C.sub.4-C.sub.10-cycloalkylene residues; and/or the R.sub.2 are each independently selected from 1,1-dimethyl-substituted, saturated or unsaturated C.sub.1-C.sub.6-alkyl residues or 1-methyl-substituted C.sub.3-C.sub.6-cycloalkyl residues.

8. The thermoplastic poly(urethane-urea) polyadduct according to claim 7, wherein R.sub.1 is selected from C.sub.2-C.sub.6-alkylene or C.sub.5-C.sub.6-cycloalkylene residues; and/or the R.sub.2 are each independently selected from isopropyl, tert-butyl, 1,1-dimethylpropyl or 1-methylcyclohexyl.

9. The thermoplastic poly(urethane-urea) polyadduct according to claim 1, wherein at least one of the residues C.sub.2 comprises one or more ester moieties.

10. The thermoplastic poly(urethane-urea) polyadduct according to claim 9, wherein the residues C.sub.2 are each independently derived from a diol from the following group: bis(hydroxyethyl) terephthalate, 1,4-butanediol, bis(3-hydroxypropyl) carbonate, 2-hydroxyethyl lactate, neopentyl glycol hydroxypivalate, 2-hydroxyethyl glycolate.

11. The thermoplastic poly(urethane-urea) polyadduct according to claim 1, wherein b+1=a+c and the polyadduct corresponds to the following Formula (IV):
—[(I-M-I—C.sub.1).sub.a—(I-M-I—C.sub.2).sub.c].sub.n-  (IV) wherein a and c are each independently selected from 1 to 3 or a and c are each 1; and n≥5 or n≥10 or n≥20.

12. A method of performing thermomechanical or solvent-based processes with polymers self-reinforcing on contact with water, the method comprising using the thermoplastic poly(urethane-urea) polyadduct according to claim 1.

13. The method according to claim 12, wherein the thermoplastic poly(urethane-urea) polyadduct is processed to a solid product that is exposed to water or an aqueous environment during or after processing in order to improve one or more of its thermomechanical properties.

14. The method according to claim 12, wherein the residues I, M, C.sub.1 and C.sub.2 of the thermoplastic poly(urethane-urea) polyadduct as well as any cleavage products thereof are biocompatible and physiologically acceptable; and the thermoplastic poly(urethane-urea) polyadduct or the solid product obtained therefrom are usable as biomaterials in biomedical applications.

15. The method according to claim 14, wherein at least one of the residues I, M, C.sub.1 and C.sub.2 comprises one or more ester moieties cleavable under physiological conditions; and the thermoplastic poly(urethane-urea) polyadduct is used for producing temporary body implants or the solid product obtained therefrom is usable as temporary body implant.

Description

SHORT DESCRIPTION OF THE DRAWINGS

[0084] Below, the present invention will be described in more detail by means of illustrative, non-limiting exemplary embodiments and with reference to the accompanying drawings, showing the following:

[0085] FIG. 1 shows a graphic comparison of the tensile elongations of foils drawn from TPUU produced in Example 1 after 24 hours of storage in a dry state and in water;

[0086] FIG. 2 shows a graphic comparison of the tensile strengths of foils drawn from TPUU produced in Examples 1 to 3 according to the present invention and from known TPUs after 7 hours of storage in a dry state and in water;

[0087] FIGS. 3 to 5 show the results of an experiment for examining degradability of the inventive TPUUs under simulated physiological conditions; and

[0088] FIGS. 6 to 10 show comparisons of NMR spectra of model substances recorded daily for one week to evaluate sterical hindrance of various secondary diamines.

EXAMPLES

[0089] As representative examples for especially preferred embodiments of the present invention, multiple TPUUs were prepared using the beforementioned preferred reactive process, i.e. by sequentially reacting the individual components while initially preparing prepolymers or intermediates, respectively, with isocyanates on both sides having the chain structure I-M-I, which were sequentially reacted with both the reactants introducing the chain extenders C.sub.2 and subsequently C.sub.1. The reactants were used in varying molar ratios, wherein each sum of the molar quantities corresponded to the molar quantity of macrodiol.

[0090] In this way, multiple preferred TPUUs of the invention of Formula (I) were obtained:

—[I-M-(I—C.sub.1).sub.a—(I-M).sub.b-(I—C.sub.2).sub.c].sub.n-  (I)

wherein b+1=a+c, more specifically TPUUs of Formula (IV):

—[(I-M-I—C.sub.1).sub.a—(I-M-I—C.sub.2).sub.c].sub.n-  (IV)

wherein a and c are each selected from 1 and 3, and wherein n≥10 or n≥20.

Example 1

[0091] By using the standard Schlenk line with argon as the inert gas, first, pre-dried poly-(tetrahydrofuran) (pTHF) (M.sub.n≈1 kDa, 6.059 g, 6.1 mmol, 1.00 eq., 19 ppm H.sub.2O) as the macrodiol was weighed into a reaction flask and dried at 60° C. under high vacuum for 1 hour. Subsequently, 5 ml abs. dimethylformamide (DMF), followed by hexamethylene diisocyanate (HMDI) (2.111 g, 12.6 mmol, 2.07 eq.) in 5 ml abs. DMF were added to the dried, melted pTHF. After adding 2 drops (about 0.04 ml) of tin(II) 2-ethyl-hexanoate as a catalyst, the reaction mixture was magnetically stirred at 60° C. under protective argon atmosphere for 3 hours. Then, bis(hydroxyethyl) terephthalate (BHET) (0.770 g, 3.03 mmol, 0.5 eq.) was added as the diol for introducing C.sub.2 as a solution in 5 ml abs. DMF. After further stirring at 60° C. for 3 hours, the reaction mixture was cooled to room temperature, after which N,N′-di-tert-butylethylenediamine (TBEDA) (0.522 g, 3.03 mmol, 0.5 eq.) was added as a secondary diamine for introducing C.sub.1 that was sterically hindered on both sides. After each addition, the transfer vessels or syringes, respectively, were each flushed with 5 ml abs. DMF. The reaction solution was stirred overnight. To recover and purify the prepared TPUU, the reaction mixture was diluted with DMF and added dropwise to ten times the volume of diethyl ether, whereby a colorless precipitate was precipitated which was subsequently dried.

[0092] By reacting these reactants at a ratio of C.sub.1:C.sub.2:M:I=1:1:2:4 (or 4.14, respectively), an especially preferred TPUU of the invention of Formula (IV) above was obtained, wherein a=b=c=1, i.e. a TPUU of Formula (V):

—[I-M-I—C.sub.1—I-M-I—C.sub.2].sub.n-  (V)

[0093] The value n was calculated from the weight average molecular weight (M.sub.w), as determined using gel permeation chromatography (GPC), and the molar mass of the blocks. The M.sub.w of the obtained TPUU was determined to be about 65.6 kDa, and the molar mass of one block was about 3.1 kDa, resulting in a value for the number of blocks n of about 21.

[0094] The precise structure of this TPUU of Formula (V) obtained in Example 1 is depicted overleaf. The average value m of the units M of polyTHF with a number average molecular weight M.sub.n of about 1 kDa is thus about 14. Furthermore, the portions corresponding to the units C.sub.1, C.sub.2, M and I as well as their detailed structures are depicted below, wherein each bond denoted by an asterisk indicates the attachment to the carbonyl group of the urethane moieties or the urea moieties, respectively, that connect the individual units.

##STR00011##

Example 2

[0095] To prepare another embodiment of the TPUUs of the invention, Example 1 was substantially repeated, wherein the molar ratio of the chain extender units C.sub.2 and C.sub.1 that were sequentially incorporated into the polymer chains was changed from 1:1 to 3:1. That is, at first, instead of 0.5 equivalents bis(hydroxyethyl) terephthalate 0.75 equivalents were reacted, and then instead of 0.5 equivalents N,N′-di-tert-butylethylenediamine only 0.25 equivalents were reacted.

[0096] By reacting the four reactants at a ratio of C.sub.1:C.sub.2:M:I=0.5:1.5:2:4 (or 4.14, respectively), a TPUU of Formula (IV) was obtained:

—[(I-M-I—C.sub.1).sub.a—(I-M-I—C.sub.2).sub.c].sub.n—  (IV)

wherein a=1 and c=3. The four portions that each contain one of the two chain extenders are randomly distributed within a block.

[0097] Using GPC, the M.sub.w of the TPUU thus obtained was determined to be about 62.8 kDa, and the molar mass of a block was about 6.3 kDa, resulting in a value for the number of blocks n of about 10.

Example 3

[0098] To prepare another preferred embodiment of a TPUU of the invention, Example 2 was substantially repeated, wherein in this case, the molar ratio between C.sub.2 and C.sub.1 was reversed. That is, at first, instead of 0.5 equivalents bis(hydroxyethyl) terephthalate only 0.25 equivalents were reacted, and then instead of 0.5 equivalents N,N′-di-tert-butylethylenediamine 0.75 equivalents were reacted.

[0099] By reacting the four reactants at a ratio of C.sub.1:C.sub.2:M:I=1.5:0.5:2:4 (or 4.14, respectively) a TPUU of Formula (IV) was obtained:

—[(I-M-I—C.sub.1).sub.a—(I-M-I—C.sub.2).sub.c].sub.n—  (IV)

wherein a=3 and c=1, and the four portions containing the chain extenders are randomly distributed within a block.

[0100] Using GPC, the M.sub.w of the TPUU thus obtained was determined to be about 74.4 kDa, and the molar mass of a block was about 6.1 kDa, resulting in a value for the number of blocks n of about 12.

[0101] In the following examples 4 to 13, by reacting the reactants anew at a ratio of C.sub.1:C.sub.2:M:I=1:1:2:4, similarly to the abovementioned Example 1—but by varying the components—other especially preferred TPUUs of the invention of Formula (V) were obtained, wherein a=b=c=1, i.e. TPUUs of Formula (V):

—[I-M-I—C.sub.1—I-M-I—C.sub.2].sub.n-  (V)

Example 4

[0102] Example 1 was substantially repeated, wherein instead of poly(tetrahydrofuran) (pTHF) (M.sub.n≈1 kDa) as the macrodiol a poly(hexamethylene carbonate)diol (pHMC) having a number average molecular weight M.sub.n of about 1.2 kDa in abs. DMF was reacted with HMDI, BHET, and finally TBEDA as the secondary diamine sterically hindered on both sides, wherein by precipitating with diethyl ether the desired polyadduct was obtained as a flaky, colorless precipitate that was removed by filtration and dried.

[0103] Consequently, the structure of this TPUU corresponds to the depicted structure for the TPUU of Example 1 of Formula (V) —[I-M-I—C.sub.1—I-M-I—C.sub.2].sub.n— above, wherein the macrodiol radical derived from pTHF is replaced by the corresponding radical M derived from pHMC of the formula below, wherein the value for m is about 9.

##STR00012##

[0104] Using GPC, the M.sub.w of the TPUU thus obtained was determined to be about 128 kDa, and the molar mass of a block was about 3.6 kDa, resulting in a value for the number of blocks n of about 36.

Example 5

[0105] Example 1 was substantially repeated, wherein instead of poly(tetrahydrofuran) (pTHF) as the macrodiol a poly(caprolactone) diol, more precisely poly(caprolactone) diol-540 (pCL540) having a number average molecular weight M.sub.n of about 540 Da was reacted with HMDI, BHET, and finally TBEDA as the secondary diamine sterically hindered on both sides, wherein by precipitating with diethyl ether the desired polyadduct was obtained as a flaky, colorless precipitate that was removed by filtration and dried.

[0106] Consequently, the structure of this TPUU corresponds to the depicted structure for the TPUU of Example 1 of Formula (V) —[I-M-I—C.sub.1—I-M-I—C.sub.2].sub.n— above, wherein the macrodiol radical derived from pTHF is replaced by the corresponding radical M derived from pCL540 of the formula below, wherein the value for each m≈2.

##STR00013##

[0107] Using GPC, the M.sub.w of the TPUU thus obtained was determined to be about 62.4 kDa, and the molar mass of a block was about 2.2 kDa, resulting in a value for the number of blocks n of about 28.

Example 6

[0108] Example 5 was substantially repeated, wherein instead of poly(tetrahydrofuran) (pTHF) as the macrodiol, again, a poly(caprolactone) diol, but in this case poly-(caprolactone) diol-2000 (pCL2000) having a number average molecular weight M.sub.n of about 2.2 kDa was reacted with HMDI, BHET, and TBEDA, wherein by precipitating with diethyl ether the desired polyadduct was obtained as a sticky, colorless precipitate that was removed from the reaction vessel with a spatula and dried.

[0109] The structure of this TPUU corresponds to that of the TPUU of Example 5, but having accordingly higher values for the degree of polymerization m of the radical M derived from pCL2000, namely about 9 each.

[0110] Using GPC, the M.sub.w of the TPUU thus obtained was determined to be about 56.4 kDa, and the molar mass of a block was about 5.4 kDa, resulting in a value for the number of blocks n of about 10.

Example 7

[0111] Example 4 was substantially repeated, wherein instead of hexamethylene diisocyanate (HMDI) 4,4′-diisocyanato dicyclohexylmethane (H12MDI) as the diisocyanate was reacted with pHMC, BHET, and finally TBEDA as the secondary diamine sterically hindered on both sides, wherein by precipitating with diethyl ether the desired polyadduct was obtained as a flaky, colorless precipitate that was removed by filtration and dried.

[0112] Consequently, the structure of this TPUU corresponds to the depicted structure for the TPUU of Example 1 of Formula (V) —[I-M-I—C.sub.1—I-M-I—C.sub.2].sub.n— above, wherein radical M derived from pTHF is replaced by radical M derived from pHMC (m=9) and radical I derived from HMDI is replaced by radical I derived from H12MDI of the following formulae.

##STR00014##

[0113] Using GPC, the M.sub.w of the TPUU thus obtained was determined to be about 46.2 kDa, and the molar mass of a block was about 3.5 kDa, resulting in a value for the number of blocks n of about 13.

Example 8

[0114] Example 1 was substantially repeated, wherein instead of bis(hydroxyethyl) terephthalate (BHET) 1,4-butanediol (BDO) as the chain extender for introducing C.sub.2 was reacted with pTHF, HMDI, and TBEDA as the secondary diamine sterically hindered on both sides, wherein by precipitating with diethyl ether the desired polyadduct was obtained as a sticky, colorless precipitate that was removed from the reaction vessel with a spatula and dried.

[0115] Consequently, the structure of this TPUU corresponds to the depicted structure for the TPUU of Example 1 of Formula (V) —[I-M-I—C.sub.1—I-M-I—C.sub.2].sub.n— above, wherein the radical derived from BHET is replaced by the radical C.sub.2 derived from BDO of the following formula.

##STR00015##

[0116] Using GPC, the M.sub.w of the TPUU thus obtained was determined to be about 54.7 kDa, and the molar mass of a block was about 3.0 kDa, resulting in a value for the number of blocks n of about 18.

Example 9

[0117] Example 1 was substantially repeated, wherein instead of BHET bis(3-hydroxypropyl) carbonate (BHPC) as the chain extender for introducing C.sub.2 was reacted with pTHF, HMDI, and TBEDA as the secondary diamine sterically hindered on both sides, wherein by precipitating with diethyl ether the desired polyadduct was obtained as a sticky, colorless precipitate that was removed from the reaction vessel with a spatula and dried.

[0118] Consequently, the structure of this TPUU corresponds to the depicted structure for the TPUU of Example 1 of Formula (V) —[I-M-I—C.sub.1—I-M-I—C.sub.2].sub.n— above, wherein the radical derived from BHET is replaced by the corresponding radical C.sub.2 derived from BHPC of the following formula.

##STR00016##

[0119] Using GPC, the M.sub.w of the TPUU thus obtained was determined to be about 163 kDa, and the molar mass of a block was about 3.1 kDa, resulting in a value for the number of blocks n of about 53.

Example 10

[0120] Example 1 was substantially repeated, wherein instead of BHET 2-hydroxyethyl lactate (ethylene glycol lactate, EGLA) as the chain extender for introducing C.sub.2 was reacted with pTHF, HMDI, and TBEDA as the secondary diamine sterically hindered on both sides, wherein by precipitating with diethyl ether the desired polyadduct was obtained as a sticky, colorless precipitate that was removed from the reaction vessel with a spatula and dried.

[0121] Consequently, the structure of this TPUU corresponds to the depicted structure for the TPUU of Example 1 of Formula (V) —[I-M-I—C.sub.1—I-M-I—C.sub.2].sub.n—above, wherein the radical derived from BHET is replaced by the corresponding radical C.sub.2 derived from EGLA of the following formula.

##STR00017##

[0122] Using GPC, the M.sub.w of the TPUU thus obtained was determined to be about 58.9 kDa, and the molar mass of a block was about 3.0 kDa, resulting in a value for the number of blocks n of about 19.

Example 11

[0123] Example 1 was substantially repeated, wherein instead of N,N′-di-tert-butylethylenediamine (TBEDA) N-tert-butylaminoethanol (TBAE) as the chain extender for introducing C.sub.1, i.e. an amino alcohol with only one sterically hindered secondary amino group, was reacted with pTHF, HMDI, and BHET, wherein by precipitating with diethyl ether the desired polyadduct was obtained as a flaky, colorless precipitate that was removed by filtration and dried.

[0124] Consequently, the structure of this TPUU corresponds to the depicted structure for the TPUU of Example 1 of Formula (V) —[I-M-I—C.sub.1—I-M-I—C.sub.2].sub.n— above, wherein the radical derived from TBEDA is replaced by the corresponding radical C.sub.1 derived from TBAE of the following formula.

##STR00018##

[0125] Using GPC, the M.sub.w of the TPUU thus obtained was determined to be about 103 kDa, and the molar mass of a block was about 3.1 kDa, resulting in a value for the number of blocks n of about 33.

Example 12

[0126] Example 1 was substantially repeated, wherein instead of N,N′-di-tert-butylethylenediamine (TBEDA) N,N′-diisopropylethylenediamine (IPEDA) as a chain extender for introducing C.sub.1, i.e. a diamine with a slightly weaker sterically hindered secondary amino group, was reacted with pTHF, HMDI, and BHET, wherein by precipitating with diethyl ether the desired polyadduct was obtained as a flaky colorless precipitate that was removed by filtration and dried.

[0127] Consequently, the structure of this TPUU corresponds to the depicted structure for the TPUU of Example 1 of Formula (V) —[I-M-I—C.sub.1—I-M-I—C.sub.2].sub.n—above, wherein the radical derived from TBEDA is replaced by the corresponding radical C.sub.1 derived from IPEDA of the following formula.

##STR00019##

[0128] Using GPC, the M.sub.w of the TPUU thus obtained was determined to be about 85.3 kDa, and the molar mass of a block was about 3.1 kDa, resulting in a value for the number of blocks n of about 28.

Example 13

[0129] Example 1 was substantially repeated, wherein instead of N,N′-di-tert-butylethylenediamine (TBEDA) 2,6-dimethylpiperazine (2,6-DMP) as a chain extender for introducing C.sub.1, i.e. a cyclic diamine with only one sterically hindered secondary amino group (the second amino group is also secondary, but not sterically hindered according to the invention as shown in Example 14 for Comparison Example 3) was reacted with pTHF, HMDI, and BHET, wherein by precipitating with diethyl ether the desired polyadduct was obtained as a solid, colorless precipitate that was removed by filtration and dried.

[0130] Consequently, the structure of this TPUU corresponds to the depicted structure for the TPUU of Example 1 of Formula (V) —[I-M-I—C.sub.1—I-M-I—C.sub.2].sub.n—above, wherein the radical derived from TBEDA is replaced by the corresponding radical C.sub.1 derived from 2,6-DMP of the following formula.

##STR00020##

[0131] Using GPC, the M.sub.w of the TPUU thus obtained was determined to be about 153.4 kDa, and the molar mass of a block was about 3.1 kDa, resulting in a value for the number of blocks n of about 49.

Comparison Example 1

[0132] Similarly to Example 1, a comparison polymer was prepared by reacting pTHF, HMDI, and BHET, wherein no sterically hindered secondary diamine for introducing C.sub.1 was added, but an amount of BHET equimolar to the amount of pTHF was used. As a result, the ratio of radicals in the polyadduct was C.sub.2:M:I=1:1:2, which is thus a thermoplastic poly(urethane) (TPU; without urea moieties) of the following Formula (VI):

—[I-M-I—C.sub.2].sub.n-  (VI)

[0133] Using GPC, the M.sub.w of the TPUU thus obtained was determined to be 46 kDa, and the molar mass of a block was about 1.6 kDa, resulting in a value n of about 29.

[0134] Due to the cleavable ester bonds in C.sub.2, this TPU is degradable under physiological conditions, but, does not have any self-enhancing properties.

Comparison Example 2

[0135] To compare the TPUUs above with a commercially available TPU, a thermoplastic poly(urethane) without urea moieties, Pellethane® 2363-80A was acquired from Lubrizol LifeSciences. This is a non-biodegradable TPU made from methylene di(phenyl-isocyanate) (MDI), poly(tetrahydrofuran) (pTHF) and 1,4-butanediol, having a molecular weight M.sub.n of about 37 kDa and a M.sub.w of about 63 kDa which was subjected to the same tests as the polyadducts of the Examples of the invention and the other Comparison Examples.

Comparison Example 3

[0136] Example 1 was substantially repeated, wherein instead of N,N′-di-tert-butylethylenediamine (TBEDA), piperazine (Pip) as the chain extender for introducing C.sub.1, i.e. a cyclic diamine with two secondary amino groups, but not sterically hindered according to the invention, as shown in Example 14, was reacted with pTHF, HMDI, and BHET, wherein by precipitating with diethyl ether the desired polyadduct was obtained as a solid, colorless precipitate that was removed by filtration and dried.

[0137] Consequently, the structure of this TPUU corresponds to the depicted structure for the TPUU of Example 1 of Formula (V) —[I-M-I—C.sub.1—I-M-I—C.sub.2].sub.n— above, wherein the radical derived from TBEDA is replaced by the corresponding radical C.sub.1 derived from Pip of the following formula.

##STR00021##

[0138] Using GPC, the M.sub.w of the TPUU thus obtained was determined to be about 325.5 kDa, and the molar mass of a block was about 3.1 kDa, resulting in a value for the number of blocks n of about 105.

Comparison Example 4

[0139] Example 1 was substantially repeated, wherein instead of N,N′-di-tert-butylethylenediamine (TBEDA), 2,5-dimethylpiperazine (2,5-DMP) as the chain extender for introducing C.sub.1, i.e. again a cyclic diamine with two secondary amino groups, neither of which sterically hindered according to the invention, as shown in Example 14, was reacted with pTHF, HMDI, and BHET, wherein by precipitating with diethyl ether the desired polyadduct was obtained as a solid, colorless precipitate that was removed by filtration and dried.

[0140] Consequently, the structure of this TPUU corresponds to the depicted structure for the TPUU of Example 1 of Formula (V) —[I-M-I—C.sub.1—I-M-I—C.sub.2].sub.n—above, wherein the radical derived from TBEDA is replaced by the corresponding radical C.sub.1 derived from 2,5-DMP of the following formula.

##STR00022##

[0141] Using GPC, the M.sub.w of the TPUU thus obtained was determined to be about 51.8 kDa, and the molar mass of a block was about 3.1 kDa, resulting in a value for the number of blocks n of about 17.

Example 14

[0142] Foil Preparation and Testing

[0143] The TPUUs of the invention obtained in Examples 1 to 13 and the TPUs of Comparison Examples 1 to 4 were dissolved in abs. DMF at a concentration of 10% by weight. These solutions were poured into Teflon molds, sized 60×40×2 mm, and the solvent was removed by evaporation at room temperature. After 24 h, the foils thus obtained were dried for further 3 d in the desiccator under vacuum, after which their thickness was measured using an electronic external measuring gauge K110T from Kroeplin which was about 100 μm in every case. Then one half of the foils was immersed in deionized water and, like the other half that was left in a dry state, stored for up to 28 d at room temperature. Before conducting any tests, any wet-stored samples were dried in a desiccator at 80° C. and 120 mbar for 24 h.

[0144] Tensile Testing

[0145] After dry or wet storage (and drying) of the foils, respectively, for the indicated duration of time, three parts of the TPUU foils each were die-cut as type 5B tensile testing samples and subjected to tensile testing according to ISO 527-1 using a Zwick Z050 tensile tester, wherein the samples that had been chucked in the tensile tester were pulled apart at a speed of 50 mm/min until they broke. Each sample was tested in triplicate, the results were averaged, and the thus measured elongation at break (as a percentage of the initial length) was used as a measure for the foil tear strength and the ultimate tensile strength (in MPa) as a measure for tensile strength. Table 1 below shows direct comparisons of the mean values thus obtained for every time as difference between mean values that were calculated for the wet-stored samples and the dry-stored samples, Δ.sub.wet-dry, each indicated as a percentage of the value for the dry sample.

[0146] Furthermore, FIG. 1 graphically depicts the results of first tests after only 24 h of storage for the TPUU of Example 1. In this case, a comparison between each tolerated maxi-mum standard force between the dry and the wet samples serves as a measure for the self-enhancement of the TPUUs of the invention due to the abovementioned recombination reactions when contacted with water. It is apparent from FIG. 1 that the dry-stored foil broke at an elongation of about 800%, i.e. about 9 times its initial length, whereas the foil that had been stored for 24 h in water even withstood an elongation of over 1000%, i.e. 11 times its initial length.

[0147] FIG. 2 graphically depicts the results (each averaged from triplicates) of tensile tests with a first series of foils of Examples 1 to 3 and Comparison Examples 1 and 2 that were dry or wet-stored (and dried), respectively, for 7 d. It is apparent that all three TPUUs of the invention experienced an enhancement of their tensile strength when stored in water. The TPUU of Example 2 that contained the smallest number of unstable urea compounds of the chain extender moieties C.sub.1, and consequently, created new polymers with the greatest chain lengths through the recombination reactions when contacted with water (analogously to Scheme D) showed the strongest tensile strength, whereas the TPUUs of Examples 1 and 3 that contained twice or three times the amount of C.sub.1 units, respectively, experienced a respective smaller degree of improvement. Nevertheless, even the TPUU of Example 3 having 3 times the amount of unstable urea compounds than that of Example 2 and therefore had had to experience the biggest amount of recombination reactions within the original polymer chain showed an improved tensile strength of about 50% compared to the corresponding dry-stored polymer.

[0148] In contrast, the TPU of Comparison Example 1 without unstable urea compounds had basically the same tensile strength after dry and wet storage, whereas the tensile strength of the TPU of Comparison Example 2 that was multiple times the one of the other tested polymers in a dry state had decreased by about a third when stored in water. While not wishing to be bound by theory, the inventors attribute this to the breaking of hydrogen bonds between urethane moieties of adjacent polymer chains due to swelling during the storage in an aqueous environment. As a result, the decreased tensile strength of the TPUs of Comparison Example 2 was in the range of the tensile strength of the TPUUs of the invention of Example 2 that was improved due to the wet storage.

[0149] After these first tests with TPUUs of the invention of Examples 1 to 3 and the TPUs of the Comparison Examples 1 and 2 those five polymers as well as TPUUs of Examples 4 to 13 and the Comparison Examples 3 and 4 were tested in a further test series. To this end, foil samples that had been wet-stored or dry-stored, respectively, for 24 h, 7 d and 28 d at room temperature were tested in triplicate.

[0150] Table 1 overleaf lists, as mentioned before, the differences of the mean values of the values that were measured for all samples of Examples 1 to 13 and the Comparison Examples 1 to 4 after their respective storage times (24 h, 7 d, or 28 d) at room temperature. Since, in most cases, the values that were determined after 7 d were already representative, only the value after 7 d was determined for some later Examples and Comparison Examples.

[0151] Due to the fact that the amount of sterical hindrance of the secondary diamines that were employed as chain extenders for introducing the radical C.sub.1 was small to non-existent, those four TPUUs were subjected another test series at 60° C. to enhance their reactivity. The respective differences of the mean values after a storage time of 24 h as well as 7 d are indicated in Table 2 below.

TABLE-US-00001 TABLE 1 Results of tensile testing with three foils each, wet-stored or dry-stored, respectively, at room temperature Tear strength, [%] Tensile strength, [MPa] Δ.sub.wet-dry [%] Δ.sub.wet-dry [%] Example 24 h 7 d 28 d 24 h 7 d 28 d Example 1  −6  30  −14  −3  67  30 Example 2  −4  10  43  −1  48  17 Example 3  4 1147  425  0 331 107 Example 4  −9 .sup.1)  −9 .sup.1)  12 .sup.1)  15 .sup.1)  23  82 Example 5  74  176  625  45  16  52 Example 6  −1 .sup.1)   5 .sup.1)  24  35  51  81 Example 7 −80  −30  −28 .sup.1)  55  33  22 .sup.1) Example 8 136  288  367 133 297 286 Example 9 317  818 1688  38  75 552 Example 10  0 .sup.1)   0  44 .sup.1)  0 .sup.1)   0 .sup.1)  32 Example 11 226  306  548 105  85 103 Example 12 −14 .sup.1)  −1 .sup.1)   1 .sup.1)  0 .sup.1)  11 .sup.1)   4 .sup.1) Example 13  −4  54 Comparison  −1 .sup.1)  22 .sup.1)   9 .sup.1)  7 .sup.1)  −1 .sup.1)   4 .sup.1) Example 1 Comparison  −3 .sup.1)   1 .sup.1)   7 .sup.1)  2 .sup.1)  14 .sup.1)   1 .sup.1) Example 2 Comparison  −7 .sup.1)  10 .sup.1) Example 3 Comparison  −5 .sup.1)   9 .sup.1) Example 4 .sup.1) statistically not significant, since the standard deviations of the mean values overlap

TABLE-US-00002 TABLE 2 Results of tensile testing with three foils each, wet-stored or dry-stored, respectively, at 60° C. Tear strength, [%] Tensile strength, [MPa] Δ.sub.wet-dry [%] Δ.sub.wet-dry [%] Example 24 h 7 d 24 h 7 d Example 12 5 .sup.1)  9 .sup.1) 52 146  Example 13 −13   76 Comparison Example 3 −30 .sup.1)  −21 .sup.1)  −18 .sup.1) −52 .sup.1) Comparison Example 4 2 .sup.1) −15 .sup.1)  28 .sup.1)  3 .sup.1) .sup.1) statistically not significant, since the standard deviations of the mean values overlap

[0152] It is clear from Table 1 that for the Examples of the invention for the majority of the measured values a contact with water at room temperature led to an improvement of the tear strength or tensile strength, respectively, by a double-digit percentage range (highlighted in bold). In the Comparison Examples, this is only the case with three measured values which also show overlapping standard deviations of mean values and are therefore not statistically significant. Therefore, as expected, no significant change in mechanical properties after a wet storage was measurable in any samples of the Comparison Examples.

[0153] As a measure for “self-enhancement” of the solid samples prepared from the TPUUs of the invention due to recombination reactions when contacted with water, as shown in Scheme D (or for the chain extender only sterically hindered on one side of Example 11 in Scheme E, respectively), especially the tensile strength improvements are relevant. Here, six out of twelve examples of the invention already show an improvement in a double-digit percentage range after 24 h and even eleven out of thirteen examples after 7 d or 28 d of wet storage, respectively. Furthermore, for four examples all measured values were substantially improved after a wet storage compared to a dry storage, among them also Example 11 having only one unstable urea group per C.sub.1 unit.

[0154] Consequently, the occurrence of the above mentioned recombination reactions was demonstrated for almost all examples of the present invention—representing various components of the TPUUs of the invention and different proportions of sterically hindered urea groups per molecule. The only exception being the TPUU of Example 12 with nitrogen atoms substituted with isopropyl that caused a relatively low sterical hindrance.

[0155] Therefore, the polymer of Example 12 as well as the TPUU of Example 13, using 2,6-dimethylpiperazine as the diamine sterically hindered on one side, together with both piperazine-containing TPUUs of Comparison Examples 3 and 4, i.e. with piperazine or 2,5-dimethylpiperazine, respectively, as C.sub.1 units, were subjected to another test at 60° C., to determine whether the reactivity of the urea group could be increased with higher temperatures.

[0156] As apparent from Table 2, this was the case for both examples of the invention, especially since the tensile strength for the isopropyl-containing TPUU of Example 12 was already increased after 24 h by more than 50% and after 7 d by almost 150%. The 2,6-dimethylpiperazine-containing TPUU of Example 13 also showed an increased tensile strength by over 75% after already 24 h at 60° C. In contrast, the increase in temperature in the Comparison Examples 3 and 4 containing piperazine or 2,5-dimethylpiperazine, respectively, did not have the desired effect—on the contrary: in this case, the values at 60° C. were even worse than after storage at room temperature.

[0157] This dearly shows that the piperazine-containing or 2,5-dimethylpiperazine-containing TPUUs, respectively, from the literature cited in the beginning are not sterically hindered according to the invention, whereas TPUUs substituted with isopropyl certainly are.

[0158] Comparatively bad were also the results at room temperature for the TPUU of Example 7 in which the tear strength compared to dry storage even decreased and a clear improvement of the tensile strength after only 24 h weakened in the course of further wet storage, as well as for Example 10 in which a clear improvement was observed only after 28 d. While not wishing to be bound by theory, the inventors attribute this to the following circumstances.

[0159] The self-enhancing effect caused by the recombination reactions is not only influenced by the type and position of the unstable urea groups in the molecule, but also strongly by the structure of the polymer, i.e. the relative self-enhancement depends on the storage time as well as on the building blocks of the TPUU. Specifically, the stable urea groups formed by the recombination reactions result in a stiffening of the polymer matrix as a whole. At a certain concentration of these urea groups, this leads to the self-enhancing effect being “saturated”. Consequently, sterically hindered, unstable urea groups that still exist at this point cannot undergo a recombination reaction according to the principle of Schemes D and E since the primary amines and isocyanates formed in situ in the matrix are no longer mobile enough to bond with each other. As a result, from this point on, they no longer serve as self-enhancing groups, but rather as degradable groups, as shown in Scheme F. Because of this, especially when stored in water for a longer period of time and/or in case of a high number of sterically hindered urea groups, the self-enhancing effect can be weakened or even turn into a degradation effect.

[0160] This effect is especially pronounced for the TPUU of Example 7 that has a very rigid matrix due to the presence of H12MDI and pHMC. Even though a pronounced self-enhancement was observed after only 24 h it had already decreased in test samples that were wet-stored for 7 d. After 28 d of wet storage no significant self-enhancing effect caused by newly formed stable urea groups was observed since it was compensated for by the degradation of still existing sterically hindered urea groups.

[0161] The reason why in Example 10 improvements could only be observed after 28 d could be attributed to the fact that a hydrolysis of part of the lactic acid ester bonds compensated for the self-enhancing effect achieved by recombination, i.e. again degradation reactions. When using the TPUUs of the invention as temporary body implants such a hydrolysis may be desirable, though.

[0162] In any case, this self-enhancement's dependence on the matrix stiffness induced by the remaining components (macrodiol, diisocyanate, chain extenders) and on simultaneously occurring degradation reactions shows that the ideal wet storage time for achieving the respective desired effect obviously varies for differently composed TPUUs.

[0163] Melting Point Determination

[0164] Furthermore, the melting points of the TPUUs of the invention contained in the foils of the TPUUs of Examples 1 to 3 from the first test series were determined using DSC. Table 3 below shows the values measured.

TABLE-US-00003 TABLE 3 Ratio Tmax-dry Tmax-wet ΔT Example C.sub.1:C.sub.2 (° C.) (° C.) (° C.) 1 1:1 80.41 85.81 5.40 2 1:3 87.44 92.26 4.82 3 3:1 75.38 84.41 9.03

[0165] These values show that an increase of the peak melting temperatures was observed for all polymers “recombined” by reaction with water, wherein the TPUU of Example 3 with the highest proportion of unstable urea compounds in C.sub.1 had the lowest melting point, but experienced the greatest increase through the recombination reactions with water. Accordingly, the TPUU of Example 2 having the fewest C.sub.1 units within the polymer chain showed the highest melting point that experienced the smallest increase due to the smallest number of recombination reactions in water.

Example 15

[0166] Degradability

[0167] To evaluate if the new polyadducts of the present invention are degradable under physiological conditions a foil was prepared from the TPUU prepared in Example 1 with a chain extender unit ratio of C.sub.1:C.sub.2=1:1 similarly to Example 12, but in this case with an average thickness of 800 μm. 15 circular disks with a diameter of 5 mm were die-cut form the foil, the weights of which were determined more precisely, but were each between 15 and 20 mg.

[0168] Then, to simulate physiological conditions, every disk was placed in a test tube in 20 ml PBS (1×, pH 7.4) after which the test tubes were heated in an autoclave to 90° C. After 7, 14, 25, 35, and 41 d three each were taken. The disks therein contained were placed in deionized water three times for 15 min to remove the contained salts. Subsequently, the drained net weight as well as—after drying to constant weight (24 h at 80° C. and 120 mbar) —the dry weight was determined, and a molecular weight determination using gel permeation chromatography was performed. From the values thus obtained loss of mass, decrease of molecular weight and swelling of the individual samples were calculated according to the equations 1 to 3 below.

[00001]$\begin{array}{cc}{m}_{\mathrm{eros}}\left(t\right)=\frac{m_t-m_0}{m_0}.Math.100& \mathrm{Equation}1\end{array}$$\begin{array}{cc}\%{\stackrel{\_}{M}}_w\left(t\right)=\frac{{\stackrel{\_}{M}}_w\left(t\right)}{{\stackrel{\_}{M}}_w\left(0\right)}.Math.100& \mathrm{Equation}2\end{array}$$\begin{array}{cc}s\left(t\right)=\frac{m_t^w-m_t}{m_t}.Math.100& \mathrm{Equation}3\end{array}$ [0169] m.sub.eros(t) Loss of mass after t days of degradation [0170] t Degradation time in d [0171] m.sub.t Sample weight after t days of degradation in mg [0172] m.sub.0 Sample weight before degradation in mg [0173] % M.sub.w(t) Decrease of molecular weight after t days of degradation in % [0174] M.sub.w(t) Molecular weight after t days of degradation in kDa [0175] M.sub.w(0) Molecular weight before degradation in kDa [0176] s(t) Swelling of sample after t days of degradation in % [0177] m.sub.t.sup.w Drained net weight of sample after t days of degradation in mg

[0178] The results of these calculations are graphically illustrated in FIGS. 3 to 5. Primarily, they show that already after 7 d the molecular weight had decreased by about ¾ of the molecular initial weight—with about 10% loss of mass and barely increased swellability, and after 41 d, by the end of the degradation study, it had decreased by about 90%—just like the loss of mass. From an extrapolation of the graphs of FIGS. 3 and 4, it can be deducted that the degradation would have been complete after about another week at 90° C. in PBS, i.e. after about a total of 7 weeks.

[0179] By comparing the proportions of the chain extender units C.sub.1 and C.sub.2 of the TPUU of Example 1 tested in this example with those of both polyadducts of Examples 2 and 3 in which the proportion of cleavable ester moieties in C.sub.2 is twice or half as high, respectively, it can be deducted that the TPUU of Example 2 would have degraded much faster and that of Example 3 much slower. Furthermore, it is expected that it should not make much of a difference if these cleavable ester moieties are contained in the units C.sub.2 or in the isocyanate units I, in the macrodiol units M, or within the units C.sub.1 derived from sterically hindered amines. Corresponding investigations are object of the current research of the inventors.

[0180] In summary, the explanations above show that the TPUUs of the present invention are completely degradable under simulated physiological conditions and that the rate of degradation can be controlled through the proportions of cleavable ester moieties.

Reference Examples 1 to 4—NMR Tests

[0181] NMR has been identified as a method for determining with less effort which secondary amines are sterically hindered amines according to the invention that, upon reaction with isocyanates, form unstable bonds with the carbonyl group of the resulting urea moieties. But since identifying individual signals in a polymer matrix using NMR with sufficient accuracy is not possible, multiple model molecules were synthesized according to Scheme G below, by reacting each secondary diamine R.sub.2—NH—R.sub.1—NH—R.sub.2 on both sides with monofunctional hexyl isocyanate.

##STR00023##

[0182] This results in two urea groups that would also be the part of the chain that is relevant for the self-enhancing effect in the TPUUs of the invention, but that can be examined in the model molecules without interfering signals by means of NMR.

[0183] The reactivity of these urea groups was tested in solution in deuterochloroform by adding propylamine. If they are sterically hindered, unstable urea compounds that open reversibly in solution while forming free amino groups and isocyanates and close when returning to their original urea group, it is possible for the intermediarily formed isocyanates to react with propylamine while forming one or two non sterically hindered and therefore stable urea groups; see Scheme H below. Since, in this way, new signals can be detected using NMR, a clear identification of the reactivity of each secondary amine can be made.

##STR00024##

[0184] For reasons of comparison, the test series was conducted with those diamines that had performed especially well or badly, respectively, in the preceding foil storage tests of Example 14, i.e. N,N′-di-tert-butylethylenediamine (TBEDA), the chain extender of the TPUUs of Examples 1 to 10, N,N′-diisopropylethylenediamine (IPEDA), that of the TPUU of Example 12, and both diamines piperazine (Pip) and 2,5-dimethylpiperazine (2,5-DMP) known in the art. The syntheses of the corresponding diurea model molecules are described below.

Reference Example 1—TBEDA

[0185] ##STR00025##

[0186] N,N′-Bis(tert-butyl)ethylenediamine was added dropwise to 2.5 equivalents hexyl diisocyanate, dissolved in 5 ml abs. THF, and stirred at room temperature for 24 h. The solvent and the excess reactant were distilled off to quantitatively obtain the respective diurea as pure substance.

[0187] .sup.1H NMR (400 MHz, acetonitrile-d.sub.3) δ [ppm]: 6.18 (s, 2H, NH), 3.25 (s, 4H, N(CH.sub.3)—CH.sub.2—), 3.12 (d, J=5.4 Hz, 4H, N—CH.sub.2), 1.47 (m, 4H, N—CH.sub.2—CH.sub.2), 1.36 (s, 18H, C(CH.sub.3).sub.3), 1.29 (m, 12H, CH.sub.2), 0.88 (t, 6H, CH.sub.3).

Reference Example 2—IPEDA

[0188] ##STR00026##

[0189] 2.5 equivalents of hexyl isocyanate (1 ml, 6.9 mmol) was dissolved in 10 ml abs. THF under argon atmosphere, after which 1 equivalent of N,N′-diisopropylethylenediamine (0.5 ml, 2.8 mmol) was slowly added through a septum using a syringe at room temperature, wherein a slight heat generation was observed. The reaction mixture was stirred at room temperature for 24 h, after which the solvent and excess isocyanate were distilled off to quantitatively obtain 1.07 g (98%) of the desired diurea as pure, slightly yellowish solid.

[0190] mp: 97.0-99.5° C.

[0191] .sup.1H NMR (400 MHz, CDCl.sub.3) δ [ppm]: 5.64 (bs, 2H), 4.15 (bs, 2H), 3.25 (q, 4H), 3.09 (s, 4H), 1.54 (qn, 4H), 1.31 (m, 12H), 1.13 (d, 12H), 0.88 (t, 6H).

Reference Example 3—Pip

[0192] ##STR00027##

[0193] 1.00 g piperazine (1 eq.) was weighed in and dried at 0.06 mbar and at room temperature for 1 hour. 50 ml abs. THF was added under argon to dissolve the solid. Then, 4.20 ml (2.5 eq.) hexyl isocyanate was slowly added dropwise, after which the temperature of the reaction mixture increased and a white precipitate was formed. After stirring for 24 h, the solid was removed by filtration, washed with a small amount of dry THF and dried, resulting in 3.18 g (80%) of a white, crystalline solid.

[0194] mp: 178.6-181.2° C.

[0195] .sup.1H NMR (400 MHz, CDCl.sub.3) δ [ppm]: 0.88 ppm (t, 6H), 1.29 (m, 12H), 1.50 (qn, 4H), 3.23 (q, 4H), 3.42 (s, 8H), 4.39 (t, 2H).

Reference Example 4—2,5-DMP

[0196] ##STR00028##

[0197] 0.50 g dry 2,5-dimethylpiperazine (1 eq.) was dissolved in 25 ml abs. THF under argon atmosphere. Subsequently, 1.6 ml hexyl isocyanate was added dropwise to the stirred solution at room temperature, wherein the solution was heated and a precipitate was formed. After stirring at room temperature for 24 h, the precipitate was removed by filtration, washed with a small amount of dry THF and dried, resulting in 1.16 g (72%) of a white crystalline solid.

[0198] mp: 166.1-168.4° C.

[0199] .sup.1H NMR (400 MHz, CDCl.sub.3): δ [ppm]: 4.37 (t, 2H), 4.11 (m, 2H), 3.53-3.16 (8H), 1.50 (m, 4H), 1.30 (m, 12H), 1.18 (d, 6H), 0.89 (t, 6H).

[0200] 10 to 15 mg of each of these diureas were dissolved in a NMR tube in 0.5 ml CDCl.sub.3 and first measured as a pure substance. Subsequently, each volume of a solution of 10.5 μl propylamine in 1 ml CDCl.sub.3 was added, so that the molar ratio between diurea and propylamine was 1:1 (±0.1). An initial .sup.1H NMR measurement of the mixtures was performed immediately after the preparation (0 d), and further measurements were performed at an interval of 24 h (1 d to 7 d). Between the measurements each NMR tube was stored at room temperature.

Reference Example 1

[0201] FIG. 6 shows the sequence of the NMR spectra for the TBEDA diurea for the days 0 to 7 from bottom to top. It is apparent that, in the course of 7 days, several new peaks formed in the ppm range between about 2.5 and 3.4 that continuously increased in intensity.

[0202] Therefore, FIG. 7 is a magnified depiction of this spectral range and shows the positions of the relevant hydrogen atoms on the newly formed molecules in four pictures. [0203] Picture 1 shows the intact diurea in which the hydrogen atoms of the hexyl radicals appear in an α position relative to the urea groups at 3.12 ppm and those of the central ethylene radical of the diamine appear at 3.25 ppm on the spectrum. [0204] Picture 2 shows the molecule that is formed when, in Scheme H above, an unstable urea bond is eliminated upon reaction of the intermediarily formed isocyanate with propylamine, so only one nitrogen atom of the N,N′-bis(tert-butyl)ethylenediamine is bonded in a urea group and the other one is present as a secondary tert-butylamino group. As a result, the position of the α hydrogens in the hexyl radical shifts from 3.12 to 3.03 ppm, and the position of the hydrogen atoms of the ethylene group shifts from consistent 3.25 ppm to 3.38 ppm in an α position relative to urea or 2.78 ppm in an α position relative to the secondary free amine. [0205] Picture 3a shows the free N,N′-bis(tert-butyl)ethylenediamine that is released upon reaction of the unstable urea group, remaining in the newly formed urea molecule above with another propylamine, the hydrogen atoms of which appear at 2.87 ppm on the spectrum. [0206] Finally, picture 3b shows the position of the hydrogen atoms of propylamine in an α position relative to the amino group at 2.50 ppm.

[0207] It is apparent from the .sup.1H NMR spectrum on the very bottom that, immediately after mixing the solvent of the diurea model molecule with propylamine, two peaks appeared at 2.78 ppm and 3.03 ppm on day 0 and a third one at 3.38 ppm on day 1 that could be attributed to the mono urea of picture 2. All these peaks gained in intensity in the course of the following days, and from day 2 on, the peak of the hydrogen atoms of the free N,N′-bis(tert-butyl)ethylenediamine can be seen at 2.87 ppm, the intensity of which is constantly increasing afterwards. Accordingly, both reactions with propylamine shown in Scheme H occurred continuously, resulting in the diurea model molecule degrading progressively.

Reference Examples 2 to 4

[0208] No analogous reactions could be observed for the IPEDA diurea of Reference Example 12, containing the N,N′-diisopropylethylenediamine used in the TPUU of the present invention of Example 12 which—as demonstrated in Table 2 above—only forms unstable urea groups at higher temperatures, or for both piperazine-containing diureas of Reference Examples 3 and 4, i.e. piperazine and 2,5-dimethylpiperazine. FIGS. 8 to 10 clearly show that, in the course of 7 d, the compositions of the three reaction mixtures did not change at all.

[0209] Therefore, the results of the Reference Examples 3 and 4 prove once again along with those in Table 2 that piperazine and 2,5-dimethylpiperazine—and with near certainty also the 2-methylpiperazine also known in the art—are not sterically hindered amines according to the present invention.

[0210] By using the methodology employed in the present Reference Examples, a person of ordinary skill in the art can relatively easily determine if a particular secondary diamine or a secondary amino alcohol is suited as a chain extender for introducing the radical C.sub.1 in a TPUU according to the present invention in advance—without having to prepare the corresponding polyadducts, turn them into foils and test them according to Example 14. In case a certain compound turns out to be unsuitable after having been stored for several days at room temperature another test series can be conducted in which the NMR tube is stored in between measurements at a higher temperature that is primarily limited by the boiling point of the solvent used.

[0211] Consequently, it was clearly demonstrated herein that the new thermoplastic poly(urethane-urea) polyadducts according to the invention, having sterically hindered urea groups of formula (I) in a solid state can, by treating them with water, be converted to new polymers, the physical characteristics of which are improved in many ways compared to those of the starting polymers. Therefore, the TPUUs of the invention are ideal for preparing solid products for various applications. Due to their physiological degradability they are especially suited to be used as temporary body implants.