DE2625761A1 - MACROMOLECULAR SUBSTANCES FOR MANUFACTURING ARTIFICIAL BODY PARTS AND METHOD FOR THEIR MANUFACTURING - Google Patents

Description

PATENT AGENCY OFFICE
D-4 DÜSSELDORF · SCHUMANNSTE. 97

i

PATENT LAWYERS:
Dipl.-Ing. W. COHAUSZ Dipl.-Ing. W. FLORACK Dipl.-Ing. R. KNAUF ■ Dr.-Ing, Dipl.-Wirtsch.-Ing. A. GERBER Dipl.-Ing. HB COHAUSZ

Paolo Ferruti June 8th 1976

24, Viale Cassiodoro
Milan / Italy

Ezio Martuscelli
8, vico Monteroduni
Naples / Italy

Fernando Riva
2, Via Tritergola
Arco Feiice
Naples / Italy

and

Luciano Provençale
2, piazza dei Servili
Rome / Italy

Macromolecular substances for the manufacture of artificial body parts and processes for their manufacture

The invention relates to macromolecular substances for the production of artificial body parts and a method for their production.

The use of polymeric materials in the manufacture of prostheses and other artificial body parts is becoming the main one at present limited by the thrombogenic effect that this

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Exercise substances to a greater or lesser extent when they come into contact with blood. On the other hand, heparin is as one Substance known to have excellent anticoagulant properties.

In recent years, attempts have therefore been made to inhibit the surface of plastics by the deposition of heparin Grant properties. In practice, however, it always had to be determined that the plastics with heparin or only form a very weak chemical bond. It has therefore already been proposed to use an indirect connection between the plastic surface and the heparin through previous absorption of quaternary ammonium salts on the surface of the plastics, for example after a graphitization treatment, and then the heparin on those pretreated in this way Tie plastic. In practice, this method has not proven itself, because on the one hand the ammonium salts after some time desorbed and on the other hand because of the hemolytic effect exerted by compounds with quaternary ammonium groups, as they damage the platelets. This method has also proven to be inapplicable to flexible plastics.

In US * -PS 3,865,723 a group of macromolecular Described substances that have the nature of polyamide amines with tertiary amino groups that are highly selective in heparin absorb from the blood and other biological fluids and thus form stable complexes without affecting the plasma proteins or the blood cells have an effect. However, these polymers are used as materials for prostheses and artificial body parts not suitable because their mechanical properties are unsatisfactory and - unless crosslinked - they work well in water are soluble.

It is therefore the task of macromolecular substances to

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To provide that are suitable for the production of artificial body parts and have no thrombogenic effect, as well as a process for the production of these macromolecular substances
to specify.

According to the invention, this object is achieved in that the macromolecular substances consist of block polymers consisting of
Polyamidamine blocks and blocks from conventional polyaddition and polycondensation polymers are built up.

The process for the preparation of the macromolecular substances consists in that

a) Polyamidamine prepolymers by polyaddition of amines of the formulas

NH-R ⁵ -NH or R ₁ -NH ₀

Ii IZ

R ₁ R ₂

to Bis-Acry! amides of the formula

O O

CH ₀ = CH-ON-R ⁵ -NC-CH = CH ₀

Z ₁₁ Z

R ₃ R ₄

wherein .R ₂ and R _{2 are} alkyl or hydroxyalkyl radicals with 1 <-6
Carbon atoms, R ₃ and R _{4 are} alkyl radicals with 1-6 carbon atoms, R is an alkylene radical with 1-12 carbon atoms or together with R-. and R ₂ or R ₃ and R ₄ as well as with the nitrogen attached to it forms an unsubstituted or substituted piperazine ring, produced and

b) a monomer or a mixture of monomers, the thermoplastic Forms polyaddition or polycondensation polymers, polymerized in the presence of the polyamidamine prepolymer will.

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Advantageous further developments of the invention are set out in the subclaims specified.

The new polymers can be shaped excellently by the processes known for thermoplastics and, surprisingly, have physical and mechanical properties similar to those of addition and condensation polymers with blocks known structure are the same, while their chemical properties enable the direct formation of stable complexes with heparin. This ability is due to the polyamidamine blocks traced back. The new polymers are insoluble in water and behave like thermoplastics, so that they are after conventional Methods of injection molding, extrusion and compression molding or the like can be processed. The objects thus obtained absorb heparin on their surface from aqueous or aqueous-alcoholic solutions with a pH value between 0 and 9 with the formation of a firm bond, whereby they permanently acquire anti-coagulant properties.

As the anti-coagulant articles do not contain any other compounds and especially no quaternary ammonium groups contain, they do not have the above-mentioned disadvantages that hitherto the use of macromolecular substances with heparinized surfaces in the biological-medical field.

The polyamide amines according to the invention are essentially obtained by polyaddition of disecondary bis-amines or primary monoamines to bis-acrylamides according to the following reactions:

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-CNR ⁵ -NC

X HN-R-NH + χ CH = CH-C-N-R -N-C-CH = CH,

i> R R

Yyy

-CH-CH-C-N-R-N-C-CH-CH

R "D

(I)

or

χ R-NH + χ CH = CH

C- N

- C

- CH = CH,

i?

NrtTT ft ττ / -ι XT TD- ^ * τ ρ r * TJ PTJ M

- LH -OJrI -L-JjJ-R -JNI-L-On -OH -N-

R R ^ R

2

where R and R are alkyl or hydroxyalkyl radicals with 1--6 carbon atoms, R and R are alkyl radicals with 1 ^ -6 carbon atoms atoms, R is an alkylene radical with 1-12 carbon atoms

12 3 4 or together with R and R or R and R and with the nitrogen attached to it forms an unsubstituted or substituted piperazine ring.

The average degree of polymerisation of these products can be determined from the ratio of the two chemical substances occurring in them

"~ 6 ■ * ■

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Functions (vinyl and amine function) in the starting monomer mixture according to the formula

χ - ^{1 +} A
η ~ T ^ Ä

under the assumption, which in this case must be considered to be correct, that the polyaddition reaction proceeds to completion.

When working with an excess of bis-acrylamides or amines it is possible to use polyamide amines with vinyl end groups or amino end groups to obtain.

It has been found that the polyamideamines with vinyl end groups for the preparation of new block polymers according to the invention are useful in which the blocks formed by conventional polymers are made of polyvinyl or polyvinylidene polymers exist.

If this type of polyamide amines with vinyl or vinylidene monomers, such as styrene, ring-substituted styrenes, alkyl acrylates, Alkyl methacrylates, acrylamide or substituted acrylamides, vinyl acetate, acrylonitrile od. Like., Among for the If the latter monomers are mixed under suitable polymerization conditions, they take part in the reaction with their end groups part and form the new block polymers.

It has also been found that polyamideamines with secondary amine ^ end groups when mixed with mixtures of monomers, the Polyamides, polyesters, polyureas, polyurethanes or the like. form, under suitable reaction conditions for the formation of the latter polymers with their amine end groups on the Participate polyaddition or polycondensation reaction and form the new block polymers according to the invention.

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Above it was indicated that the for the production of the macromolecular Fabrics according to the invention used polyamide amines "essentially" by polyaddition of disecondary bis-amines or primary monoamines obtained to bis-acrylamides will. This should be expressed that the main monomers also have other monomers with other chemical May contain functions, provided that these monomers contain the groups necessary for a polyaddition (amine and acrylyl groups) available. Examples of such monomers are: piperazine mono- and dicarboxylic acids, aliphatic amino acids with 1-6 Carbon atoms, allylamine and primary diamines with 2-12 Carbon atoms.

However, the addition of the aforementioned or similar monomers to the polymerization mixture does not lead to particular advantages with regard to the binding capacity of the end polymers for heparin, so that the complication of the structure of the polyamideamines and thus the end polymer in most cases offers no advantages.

To prepare the polyamidamines, the selected monomers are dissolved in water or an organic solvent containing hydroxyl groups, preferably an alcohol, and ^{polymerized at a temperature in the range from 10 to 50 °} C., the reaction time depending on the monomers used being a few hours (3 to 4 Hours) to a few days (3 to 5 days). Details of the manufacturing process can be found in the examples described below.

As already mentioned, for the production of the new block copolymers essentially the same procedures as for polymerizing the monomers to make known block copolymers used and therefore always in accordance with the

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Monomers or the monomer mixture selected with the previously prepared polyamide amines to be polymerized. These processes are also described in the examples below.

The accumulation of heparin on the surfaces of the macromolecular Articles made of fabrics, such as hoses, tubes, foils, yarns, fibers, etc., are made in a simple manner by bringing the objects into contact with an alcoholic, water-alcoholic one for a period of 2-100 minutes or an aqueous solution of heparin with a heparin content of 0.1 to 20% and a pH of 0-9. Once in a while It is advisable to pretreat the objects with an aqueous-alcoholic or aqueous solution of an acid, such as hydrochloric acid, Acetic acid, etc., at a concentration between 0.1 and 20%.

The attached heparin can be crosslinked with glutaraldehyde or other aldehydes in order to remove the heparin from the To complicate the surface of the objects under the conditions prevailing in a biological environment.

The invention is described in more detail with the aid of the following examples.

EXAMPLE 1

A) 19.4238 g of 1,4-bis-acrylylpiperazine were dissolved in 48.75 ml of a 1'-molar aqueous solution of Ν, Ν'-dimethylenediamine, which had been titrated acidimetrically. The molar ratio ( Jt- ) of the two reagents was 0.975. Theoretically, a product should therefore have an average degree of polymerization

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of X equal to 79 can be obtained. The mixture was at room temperature Left for 4 days. Thereafter, the mixture was poured into an excess of acetone and several hours ditched. The product crystallized out and was separated by filtration. A polyamidoamine (yield 95%) with the formula

-CH ₂ -CH ₂ CO-N

-CO-CH-CH-N-CH-CH-N-

N-'2 "2 T" * 2 "~ * 2 j

CH.

CH.

and the end groups of the following kind

CH "= CH-CO-

-CO-

obtain. In osmotic measurements, an average Degree of polymerization found which agreed well with the theoretical expected value.

Using exactly the same procedure, polyamide amines with vinyl end groups and an average degree of polymerization between 10 and 300 (by changing the molar ratio ^ 1 of the bis-acrylamides to the amines in the monomer mixture in the range from 0.818 to 0.993) were prepared, with one of the following Until Acry! Amides was assumed: -

-CO-CH = CH ₂

CH = CH-CO-N11-CH ₂ -NH-CO-CII

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-ίο-

= CH-CO-NII (CH ₀ ) NII-CO-CH = CIl

CH SCH-CO-NH (CIl) NH-CO-CH = CH ₂ CH ₂ = CH-CO-NH (CH ₂ ) ₄ NIl-CO-CII = CH ₂ CH = CH-C0-NH (CH) NH- CO-CH = CH CH = CH-CO-N-Ch -CH ₂ -N-CO-CH = CH ₂

:H

ch

CH = CH-CO-N-CH -CH ₂ -N-COCH =

-N-CH ₂ -CH ₂ -N-

^C 2 ^H 5

: CH-CO-N-CH "-CH ₂ -N-CO-CH = CH ₂

-N-CH ₂ -CH ₂ -N-

The following amines were also used: CH ₃ NH ₂ , C ₂ H ₅ NH ₂ , C ₃ H ₇ NH ₂ , (CH ₃ J ₂ CH-

[NH

/ Λ ³ r <

üi TiH, mi NH

COOK

HN-CH _

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Instead of pure bis-acrylamides and pure amines, mixtures were also used used by bis-acrylamides and mixtures of amines; Likewise, the bis-acrylamides and amines with other monomers of the type specified (piperazine mono- and dicarboxylic acids, aliphatic amino acids with 1-6 carbon atoms, allylamines, primary diamines with 2-12 carbon atoms) are used. In each case, however, the ratio of bis-acrylamide monomers was to the amine monomers kept in the range given above.

B) 20 g of a polyamidamine of the formula

-CH _n -CH _n -CO-N N-CC-CH ₀ -CH-N-CH ₀ CH-N-

22 \ / 22 | 2- 2

Ν—— J ΠΗ

, CH, 3 3

with an average degree of polymerization of X = 79 and vinyl end groups according to that described under (A) Procedure was prepared in 60 ml of an 8: 2 dioxane / ethanol mixture dissolved, and 14 g of styrene per gram of polyamidamine and 1.5 g of azodiisobutyronitrile were added. The mixture was heated to 60 ° C. in a thermostatic bath for 24 hours. Then the mixture was in a Poured a 1: 1 mixture of ether and heptane and separated the precipitate. There were 145 g of a block copolymer of predominantly the following structure

obtained, in which the middle block has the poly-

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amidamine structure, while the side blocks had the polystyrene structure

-CH -CH-

had. The product was analyzed and a nitrogen content of 1.70% was found, which corresponds to a content of
8.57% by weight of polyamidamine blocks. It was found that the behavior of the new polymer (hereinafter referred to as PAA-1) towards solvents practically with
corresponds to that of polystyrene, while it differs considerably from that of polyamidamine. Comparative tests were carried out in which the polymers were reprecipitated from solutions in a common solvent with alcohols and cyclohexane, which are specific precipitants for polystyrene or polyamidoamine. A 2.5%
Solution of PAA-1 in methylene chloride was poured into 5 times the amount of isobutyl alcohol and n-octyl alcohol, respectively. Intense opalescence was obtained in both cases, but by itself
no flocculation observed after standing for seven days. Under the same conditions, a 2.5% solution gave one
10: 1 mixture of polystyrene (M = 34,000) and the previously used polyamidoamine in methylene chloride produced a flaky precipitate which completely settled after standing for 8 hours. On the other hand, the same PAA-1 solution gave
Pour into 5 times the amount of cyclohexane a completely clear mixture, while the same solution of polystyrene and polyamidamine when pouring into 5 times the amount of cyclohexane one
Resulted precipitate, which can be separated by decantation

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could. From these dissolution and precipitation experiments it can be concluded that there is no free product in the PAA-1 product Polyamide amine was present. However, the presence of traces of free polystyrene could not be completely ruled out.

In terms of mechanical properties, the PAA-1 product was found to be a thermoplastic material, its injection molding was somewhat more difficult than that of polystyrene, but essentially carried out under the same conditions could be.

C) With the help of a special mold made of chrome-plated brass, the were manufactured according to the procedure of the previous paragraph PAA-1 polymers produced some raw cylindrical test specimens. The test specimens had a length of 25 mm, one Inside diameter of 15 mm and an outside diameter of 20 mm. They were pretreated with a 5% alcoholic Acetic acid solution (to ionize the amine groups), a treatment with a 1: 1 water / ethanol solution that Contained 10% heparin, and a treatment with a 2.5% aqueous solution of glutaraldehyde (to fix the heparin by partial crosslinking) and then washed repeatedly and carefully with distilled water. The test specimens then became more thrombotic by methods widely accepted in the field of biology for testing absence Properties (in this context, refer to the work of Vincent L. Gott and Akira Furuse "Antithrombogenic surfaces, classification and in vivo evaluation ", Federation Proceedings, Volume 30, No. 5, September / October 1971) into the inferior vena cava of an experimental animal (dog) implanted. After 2 weeks, the test specimens were removed and inspected; they only showed slight, uneven traces of a thrombosis at the junctures, while the interior completely

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remained consistent. Polystyrene control bodies were massively thrombosed and their interior was clogged. From it the conclusion can be drawn that the test specimens made of PAA-1 were permanently antithrombogenic after heparinization.

The other copolymers listed in Table I were prepared by the same procedure, one of which is described Polyamidamine assumed, but a molar ratio of 0.983 between bis-amine and bis-acrylamide was used. The following Operation was carried out as in the case of PAA-1, but different amounts were added to the polyamidoamine solution Styrene and azodiisobutyronitrile added.

Table I.

Mn the poly N Wt% Block- amidamine blocks % Polyamide amine blocks Copolymers 10,000 1, 70 8.57 PAA-1 16000 1, 78 8.97 PAA-2 . Il 3.20 16.10 PAA-3 Il 4.22 21.27 PAA-4 Il 5.07 25.55 PAA-5 II 6.65 33.52 PAA-6 Il 9.84 49.60 PAA-7 Il 12.78 64.35 PAA-8 Il 12.85 64.85 PAA-9 Il 15.90 80.00 PAA-10 Il 16.46 82.80 PAA-11

In the following Table II is the solubility data of the block Copolymers PAA ~ 1, of the polyamidamine used for its production and given by polystyrene.

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Table II

PAA-1 ⁺⁺ behavior Polystyrene U Polyamide amine U L. U L. n-heptane U U U benzene L. U L. Diethyl ether L. Ls L. Dioxane L. L. L. chloroform L. L. L. Dichloromethane Ls Ls L. Chlorobenzene U U U Ethyl acetate Ls U L. acetone U U U 2-butanone U L. U Methanol U L. U 95% ethanol Ls L. Ls Isobutanol L. Ls L. 1-octanol Ls Dimethylformamide

L = soluble; LS = soluble near the boiling point; U = insoluble

50 mg of polymer in 2 ml of solvent. The polyamide amine was in crystalline form.

Literature data for all solvents with the exception of the
1-octanols.

The same results in terms of physical properties, the workability and the antithrombogenic properties

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Shanks of the objects made from it were also included obtained all other polymers of this example prepared from the specified monomers (bis-acrylamides and amines) had been.

EXAMPLE 2

A) Following the procedure described in the first part of Example 1, a polyamidoamine was prepared which essentially had the same structure as that of Example 1 except that it was replaced by vinyl end groups secondary amine type

-CH ₂ -CH ₂ -UH

-NI

CH ₃

would have. This polyamidoamine was made from 19.4238 grams of 1,4-bis-acrylylpiperazine and 51.28 ml of a 2 molar aqueous solution of N, N'-dimethylene ethylenediamine. The molar ratio (A) between the two reagents was 0.975; but was different than in Example 1- - an excess of amine in relation to the bis-acrylamide is present. The polyamidamine obtained had nevertheless an average degree of polymerization of X ~ 79, but, as already mentioned, secondary amine end groups. Polyamidamines with amine end groups and degrees of polymerisation between 10 and 300 were produced by the same process, starting from the compounds given in Example 1 and the amine excess depending on the desired average degree of polymerization was changed.

B) To a solution of 17.51 g of 2,4-tolylene diisocyanate in 40 ml of anhydrous cyclohexanone were added dropwise with stirring 10.61 g of anhydrous diethylene glycol and 5'g of the after

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The polyamidamine obtained in the above paragraph and having an average degree of polymerization of X _n * 79 and amine end groups, which was dissolved in 40 ml of anhydrous dimethyl sulfoxide, was added. After the addition had ended, the reaction mixture was ^{heated to 115 °} C. in an oil bath and kept at this temperature for 21/2 hours. The reaction mixture was then poured into about 2 liters of ether, the precipitate was separated off, washed with ether, suspended in distilled water, washed several times by decanting with water, filtered off and ^{dried at 50 °} C. under a pressure of 0.1 torr. Thus, there was obtained 25 g of a block copolymer having, in its molecular structure, polyamidamine blocks of the above structure and polyurethane blocks of the structure

NH-C-O-

were included. Elemental analysis of the copolymer gave the presence of 15 wt% polyamidamine blocks.

Following the same procedure and using the polyamideamines prepared by the procedure of Example 1-A, produced a whole range of amine-terminated polymers. The resulting polymers had different physical properties than the polyamide amines and largely resembled the polyurethanes in terms of their physical properties.

Some test specimens produced by extrusion from the

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The aforementioned polymers were implanted in the inferior vena cava of test animals and were found to be permanent antithrombogenic;

EXAMPLE 3

1,4-bis-acrylylpiperazine (19.424 g, 0.1 mol) was added with 49.00 ml of a 2 molar aqueous solution of methylamine treated, which had been titrated against a standard acid solution. The molar ratio between amine and bis-acrylamide was 0.98.

After stirring until a homogeneous solution was obtained, the reaction mixture was left to stand at room temperature (18-20 ° C.) for 2 days under an inert gas atmosphere. The very viscous solution was then poured into 500 ml of acetone. A gummy precipitate was obtained, which was separated by decantation, washed twice with 250 ml of acetone and then dried at room temperature under a pressure of 0.1 torr. The polyamide amine thus obtained had an intrinsic viscosity of 0.37 dl / g, measured in chloroform at 30 ⁰ C. To a solution that had been prepared by heating 10 g of the polyamide amine in 90 ml of pure Dimenthylformamid obtained was added 140 g of thoroughly purified Styrene and 1.4 g of azodiisobutyronitrile were added. After purging with nitrogen, the mixture was left to stand for 2 days at 60 ^° C. under an inert gas atmosphere; then the product was isolated by treating the reaction mixture with excess ether. The copolymer was washed by trituration under ether and extracted with water at room temperature for 2 hours. No water-soluble basic products were found in the aqueous phase (the free polyamidoamine is easily soluble in water). After drying in vacuo, the copolymer was dissolved in chloroform and with an excess of one

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aliphatic hydrocarbon (pentane, hexane or heptane) precipitated again and dried. The yield was about 105 g. The nitrogen content of the product was determined to be 1.68%, which corresponds to a polyamidamine content of about 9% by weight. As the physical properties of the new block copolymers essentially correspond to those of the polymers that form the blocks of conventional polymers, it appears that the latter are chosen depending on the physical properties of rigidity or flexibility, hardness or softness that are required for the special prostheses or artificial body parts to be produced.

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Claims (1)

Expectations 1. Macromolecular substances for the production of artificial body parts, characterized in that
that they consist of block polymers, which consist of polyamidamine blocks and blocks of conventional polyaddition
and polycondensation polymers. 2. Macromolecular substances according to claim 1, characterized
characterized in that the polyamidamine ^ blocks the structure -NR -'- N-CH -CH _o -ö-NR ^D -N-ft-CH -CH - have, in which R ₁ and R «are alkyl or hydroxyalkyl radicals
with 1-6 carbon atoms, R ₃ and R. are alkyl radicals with 1-6 carbon atoms, R _{5 is} an alkylene radical with 1-12 carbon atoms or together with R ₁ and R ₉ or R., and R4 and the nitrogen attached to it forms an unsubstituted or substituted piperazine ring. 3. Macromolecular substances according to claim 1, characterized characterized in that the polyamidamine blocks the structure -N- -N-R-N- C-CH -CH - - 21 - 609853/1069 in which R ₁ , R 1 and R _{4 are} alkyl radicals with 1-6 carbon atoms, R _{5 is} an alkylene radical with 1-12 carbon atoms or, together with R and R, and the nitrogen attached to it, an unsubstituted or substituted one Piperazine ring forms. 4. Macromolecular substances according to one of claims 1 to 3, characterized in that the polyamidamine blocks also contain other monomers, preferably made of of the group piperazine mono- and dicarboxylic acids, aliphatic amino acids with 1-6 carbon atoms, allylamines and primary Diamines with 2-12 carbon atoms. 5. Macromolecular substances according to one of claims 1 to 4, characterized in that the polyamidamine blocks contain end groups of the following type: 0
-CH ₂ -CH-C- * 6. Macromolecular substances according to one of claims 1 to 4, characterized in that the Polyamidamine blocks contain end groups of the following types: -NR ⁵ - *1
wherein R., and R are as defined above. 7. Macromolecular substances according to one of claims 1 to 6, characterized in that the blocks of conventional polymers are polyvinyl or polyvinylidene addition polymers, preferably from the group of polystyrenes, polyacrylates, polymethacrylates, polyacrylamides, Polyacrylonitrile and polyvinyl acetate. - 22 - 609853/1069 8. Macromolecular substances according to one of claims 1 to 6, characterized in that the blocks of - conventional polymers condensation polymers, preferably from the group consisting of polyamides, polyureas, polyurethanes and polyesters. J Process for the production of macromolecular substances according to one of Claims 1 to 8, characterized in that draws that a) Polyamidamine prepolymers by polyaddition of Amines of the formulas NH-R ⁵ -NH to bis-acr-ylamides of the formula 0 0
CH _O = CH-CNR ⁵ -NC-CH = CH ₂ wherein R ₁ and R _{2 are} alkyl or hydroxyalkyl radicals with 1-6 carbon atoms, R-. and R _{A is} alkyl radicals with 5
1-6 carbon atoms, R is an alkylene radical with 1-12 carbon atoms or together with R .. and R ₂ or R-. and R- as well as with the nitrogen attached to it forms an unsubstituted or substituted piperazine ring, produced and b) a monomer or a mixture of monomers, the thermoplastic Forms polyaddition or polycondensation polymers in the presence of the polyamidamine prepolymer is polymerized. 10, method according to claim 9, characterized - 23 - 609853/1069 draws that a vinyl-terminated Polyamidamine prepolymer with vinyl or vinylidene monomers is copolymerized. 11. The method according to claim 9, characterized in that that a polyamidamine prepolymer containing amine end groups with a mixture of monomers is polymerized, which forms condensation or addition polymers. 12. The method according to claim 9, characterized in that the process step (a) is carried out in water or an organic solvent containing hydroxyl groups at temperatures in the range of 10-50 ⁰ C and the reaction time is a few hours to a few days. 13. The method according to claim 9, characterized that process step (b) is among those for the polymerization of monomers or monomers is carried out under suitable conditions for thermoplastic addition or condensation polymers. 14. Use of the macromolecular substances according to one of the claims 1 to 8 for the manufacture of objects for biomedical purposes. 15. Use according to claim 14, characterized in that that is attached to the surface of the objects with heparin. 16. A method for producing the articles according to claim 15, characterized in that the - 24 - 609853/1 069 -2A- Objects in a known manner by extrusion, injection molding, pressing or the like. Shaped and in an aqueous, alcoholic or aqueous-alcoholic solution of heparin can be immersed. 17. The method according to claim 16, characterized in that that the heparin solution contains 0.1-20% heparin and has a pH of 0-9. S09853 / 1063