RU2575348C2 - Hydrophilic gels, obtained from grafted photoinitiators - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to methods for obtaining hydrophilic gel precursor and gel. Method includes stage of hardening matrix composition, which includes polymer photoinitiator of general formula (I) polymer-[CR₂-CHR-spacer(PI)_n]_m (I), by its exposure to UV-radiation with obtaining hydrophilic gel precursor. In addition method includes obtaining hydrophilic gel by additional exposure of matrix composition to swelling-inducing medium. Additional exposure of matrix composition can be realised before or after its exposure to UV-radiation.

EFFECT: possibility of applying polymer photoinitiator as single matrix composition component makes it possible to exclude additives from composition components, thus reducing probability of leaching components with low molecular weight from cross-linked matrix composition.

20 cl, 2 dwg, 1 ex

Description

Field of Invention

The present invention relates to methods for producing a hydrophilic gel precursor and gel. The present invention also relates to gels and hydrophilic gel precursors obtained using the aforementioned method, as well as to medical devices including gels and hydrophilic gel precursors. The present invention also provides the use of a polymer photoinitiator in the preparation of a gel.

BACKGROUND OF THE INVENTION

Curing of coatings by means of ultraviolet (UV) radiation, thereby leading to the formation of a coating for use as a gel (for example, a hydrogel), requires effective methods of initiating a chemical reaction leading to the curing process. Crosslinking of the polymer material through the formation of radical particles when irradiated with UV light is widely used to obtain hydrogels for coating medical devices. Coating compositions with polyvinylpyrrolidone and a photoinitiator as the main components that cure with UV radiation are often used to produce hydrogels. The photoinitiators used in these methods can be either oligomeric or polymeric. Oligomeric photoinitiators have the ability to partially diffuse into the surface of the cured material, thereby bringing these substances into a state of exposure to the environment.

European patent No. 2060589 discloses arylketones with a Si-H functional group, in which the arylketone includes a photoinitiator moiety.

US patent No. 4477326 relates to polymer photoinitiators, including organosilane polymers.

The purpose of the invention

The aim of the present invention is to provide a method for producing hydrophilic gel precursors and gels, as well as hydrophilic gel precursors and gels resulting from these methods.

SUMMARY OF THE INVENTION

In a broad aspect, the present invention relates to a method for producing a hydrophilic gel, said method comprising the steps of:

but. providing a matrix composition comprising a polymer photoinitiator of the general formula I:

The polymer is [CR ₂ -CHR spacer (PI) _n ] _m (I)

b. curing the matrix composition obtained in step a. by exposing it to UV radiation and

c. exposing the matrix composition to a swelling medium.

Steps b. and c. can be done in any order. In the above polymer photoinitiator of formula (I), m is an integer from 1 to 5000, n is a real number greater than 0 and less than 5, PI is a photoinitiator moiety, and each R group is a substituent independently selected from hydrogen, C1- C25 linear alkyl, C3-C25 branched alkyl, C3-C25 cycloalkyl, aryl, heteroaryl, -OH, -CN, halogens, amines (e.g. -NR'R '', where R 'and R' 'are alkyl groups, predominantly C1-C25 alkyl groups) and amides (e.g., -CONR'R '' or R'CONR '' -, where R 'and R' 'are alkyl groups, preferably C1-C25 alkyl groups).

The present invention also relates to a method for producing a gel, said method comprising the steps of:

a. providing a matrix composition comprising a polymer photoinitiator of the general formula I:

The polymer is [CR ₂ -CHR spacer (PI) _n ] _m (I)

where m is an integer from 1 to 5000;

n is a real number greater than 0 and less than 5; and

PI is a photoinitiator fragment;

the polymer is selected from the group consisting of polyacrylates, polyalkyl ethers, polyurethanes, polyethylene vinyl acetate, polyvinyl pyrrolidone and their copolymers and mixtures thereof;

and where each R group is a substituent independently selected from hydrogen, C1-C25 linear alkyl, C3-C25 branched alkyl, C3-C25 cycloalkyl, aryl, heteroaryl, -OH, -CN, halogens, amines (e.g., -NR ' R ″, where R ″ and R ″ are alkyl groups, predominantly C1-C25 alkyl groups) and amides (for example, —CONR′R ″ or R′CONR ″ -, where R ″ and R ″ are are alkyl groups, preferably C1-C25 alkyl groups),

b. curing the matrix composition obtained in step a. by exposing it to UV radiation,

c. exposing the matrix composition to a swelling medium, thereby producing a hydrophilic gel,

where is stage c. may be performed before or after step b.

The present invention also provides a method for producing a gel, said method comprising the steps of:

a. providing a matrix composition comprising a polymer photoinitiator of the general formula I:

Polymer [CR ₂ -CHR-spacer _{(PI) n] m (I} ),

where m is an integer from 1 to 5000;

n is a real number greater than 0 and less than 5; and

PI is a photoinitiator fragment;

the polymer is selected from the group consisting of polyacrylates, polyalkyl ethers, polyurethanes, polyethylene vinyl acetates, polyvinyl pyrrolidone and their copolymers and mixtures thereof;

and where each R group is a substituent independently selected from hydrogen, C1-C25 linear alkyl, C3-C25 branched alkyl, C3-C25 cycloalkyl, aryl, heteroaryl, -OH, -CN, halogens, amines (e.g., -NR ' R ″, where R ″ and R ″ are alkyl groups, predominantly C1-C25 alkyl groups) and amides (for example, —CONR′R ″ or R′CONR ″ -, where R ″ and R ″ are are alkyl groups, preferably C1-C25 alkyl groups),

b. curing the matrix composition obtained in step a. by exposing it to UV radiation,

c. exposing the matrix composition to a swelling medium, thereby producing a hydrophilic gel,

where is stage c. may be performed before or after step b.

A number of photoinitiators falling within the total volume of the above formula (I) can be used in the method of the present invention, such as, for example, photoinitiators with the general formulas II, IIa, IIb, III, IV and V:

The polymer is [CR ₂ -CHR-C (= O) -spacer (PI) _n ] _m (II),

Polymer [CR ₂ -CHR-C (= O) -O - spacer _{(PI) n] m (IIa} ),

The polymer is [CR ₂ -CHR-C (= O) -NH-spacer (PI) _n ] _m (IIb),

The polymer is [CR ₂ -CHR-O-spacer (PI) _n ] _m (III),

The polymer is [CR ₂ —CHR-NR ¹ spacer (PI) _n ] _m (IV),

Polymer [CR ₂ -CHR-Ph-spacer _{(PI) n] m (V} ).

In the above formulas: m is an integer from 1 to 5000; n is a real number greater than 0 and less than 5; Ph is an optionally substituted phenyl group, each R group is a substituent independently selected from hydrogen, C1-C25 linear alkyl, C3-C25 branched alkyl, C3-C25 cycloalkyl, aryl, heteroaryl, -OH, -CN, halogens, amines (e.g., -NR'R '', where R 'and R''are alkyl groups, predominantly C1-C25 alkyl groups) and amides (e.g., -CONR'R''orR'CONR''-, where R 'and R''are alkyl groups, preferably C1-C25 alkyl groups); R ¹ is a substituent independently selected from hydrogen, C 1 -C 25 linear alkyl, C 3 -C 25 branched alkyl, C 3 -C 25 cycloalkyl, aryl, heteroaryl, —OH, —CN, and halogens, and PI is a photoinitiator moiety.

The matrix composition may further include one or more hydrophilic gelling polymers and / or hydrophilic gelling monomers. The matrix composition can alternatively consist of a polymer photoinitiator of the general formula I.

If the medium causing the swelling is water, a hydrogel is obtained.

In another embodiment, the present invention provides a method for producing a hydrophilic gel precursor, said method comprising the steps of:

a. providing a matrix composition consisting of a polymer photoinitiator of the general formula I:

The polymer is [CR ₂ -CHR spacer (PI) _n ] _m (I),

where m is an integer from 1 to 5000;

n is a real number greater than 0 and less than 5; and

PI is a photoinitiator fragment;

the polymer is selected from the group consisting of polyacrylates, polyalkyl ethers, polyurethanes, polyethylene vinyl acetates, polyvinyl pyrrolidone and their copolymers and mixtures thereof;

and where each R group is a substituent independently selected from hydrogen, C1-C25 linear alkyl, C3-C25 branched alkyl, C3-C25 cycloalkyl, aryl, heteroaryl, -OH, -CN, halogens, amines (e.g., -NR ' R ″, where R ″ and R ″ are alkyl groups, predominantly C1-C25 alkyl groups) and amides (for example, —CONR′R ″ or R′CONR ″ -, where R ″ and R ″ are are alkyl groups, preferably C1-C25 alkyl groups),

b. curing the matrix composition obtained in step a. by exposing it to UV radiation.

The present invention relates to a hydrophilic gel precursor prepared in this way.

The present invention also relates to a gel obtained by the methods of the present invention. Since the photoinitiator remains bound in the matrix composition after curing, these gels can be distinguished from known gels by analyzing their chemical composition.

Also provided is a medical device that includes the gel or hydrophilic gel precursor of the present invention.

In addition, the present invention provides the use of a polymer photoinitiator of the general formula I, II, IIa, IIb, III, IV or V in the preparation of a gel.

Additional details of the present invention are presented in the following description and dependent claims.

List of legend symbols

Figure 1 illustrates a common motif of polymer photoinitiators, with photoinitiator fragments in the side chain on the polymer skeleton.

Figure 2 is a schematic illustration of the method (s) of the present invention.

Detailed Disclosure of Invention

Definitions

“Optional substituted” means optionally substituted with one or more substituents selected from the group consisting of C1-C25 linear, branched or cyclic alkyls, aryls, —OH, —CN, halogens, amines, amides, alcohols, esters, thioethers, sulfones and their derivatives, sulfonic acid and its derivatives, sulfoxides and their derivatives, carbonates, isocyanates, nitrates, acrylates. Preferably, one or more substituents are selected from the group consisting of —OH, —CN, halogens, amines, amides, alcohols, esters, thioethers, sulfones and their derivatives, sulfonic acid and its derivatives, sulfoxides and their derivatives, carbonates, isocyanates, nitrates, acrylates. Most preferably, the substituent is selected from the group consisting of —OH, —CN, halogens, amines, amides, alcohols, esters, thioethers, sulfones and their derivatives, sulfonic acid and its derivatives and sulfoxides and their derivatives.

Hydrophilic

A material is described as hydrophilic if it has a natural affinity for water. Hydrophilic materials are defined as materials that have a contact angle with water of less than 90 °, preferably less than 80 °, more preferably less than 75 ° and most preferably less than 50 ° (see ASTM D7334-08), measured by measuring dynamic wetting angle. Briefly, a method for measuring the dynamic angle of wetting of a drop of water on a surface is carried out by applying a drop of water (~ 5-20 μl) with a controlled size within 0.1 μl using a hypodermic syringe. Then the goniometer is adjusted so that it is possible to determine the internal angle of each of the two points of contact of the drop. Two angle measurements are taken (one at each drop edge) of three drops on the sample, and the wetting angle for the sample is the average of these six angle measurements.

The hydrophilic polymer probably contains atoms with high values of electronegativity, such as oxygen and nitrogen. Materials that are hydrophilic as defined above will also have affinity for short chain alcohols (e.g. C1-C8) and glycerin. Specific examples of hydrophilic polymers are polyethylene oxides, polyvinyl acetates, polyvinyl pyrrolidones, polymers with an amine functional group, for example poly (2-ethyl-2-oxazoline), acryloplasts, polyesters, polyalkyl ether sulfonates and polyvinyl alcohols.

Hydrophilic gels

The gel is an interconnected rigid mesh structure with pores of submicron sizes and polymer chains, the average length of which is more than a micrometer. The expression "gel" is discussed in detail in Flory, P. J. Principles of Polymer Chemistry; Cornell University Press: Ithaca, NY, 1953; Chapter IX.

The definition of the gel is given in Polymer Gels and Networks, 1 (1993), 5-17: The gel is a soft, hard or solid material of two or more components, one of which is a liquid present in significant quantities. Solid gels are characterized by the absence of an equilibrium modulus, the storage modulus G '(ω), which exhibits a distinct plateau with a length of at least an order of seconds, and the loss modulus G' '(ω), which is much smaller than the accumulation modulus in the plateau region.

In the interest of characterizing the effectiveness of the photoinitiator in crosslinkable polymer matrices, the transition from liquid to solid material is important. Liquids are characterized as having G '' (ω)> G '(ω) and, accordingly, solids are characterized by G' '(ω) <G' (ω). The transition from a liquid to a solid, often called a gel point, is determined at G '' (ω) = G '(ω). The curing time, defined as the time from the initiation of the curing process to the moment when G ″ (ω) = G ′ (ω) or tan δ = 1, is a characteristic indicator of the effectiveness of the photoinitiator in a particular matrix composition.

Specific Embodiments of the Present Invention

The present invention provides gels, including hydrophilic gels, hydrophilic gel precursors and methods for their preparation.

As set forth generally in FIG. 2, the present invention provides a method for producing a hydrophilic gel, said method comprising the steps of:

a. providing a matrix composition comprising a polymer photoinitiator of the general formula I:

The polymer is [CR ₂ -CHR spacer (PI) _n ] _m (I),

b. curing the matrix composition obtained in step a. by exposing it to UV radiation, and

c. exposing the matrix composition to a swelling medium, thereby producing a hydrophilic gel,

where is stage c. may be performed before or after step b.

Since photoinitiators are bound within the matrix composition after curing, the likelihood of leaching low molecular weight photoinitiators from the surface of the cured material is reduced.

Each R group is a substituent independently selected from hydrogen, C1-C25 linear alkyl, C3-C25 branched alkyl, C3-C25 cycloalkyl, aryl, heteroaryl, -OH, -CN, halogens, amines (e.g., -NR'R ' ', where R' and R '' are alkyl groups, predominantly C1-C25 alkyl groups) and amides (e.g. -CONR'R '' or R'CONR '' -, where R 'and R' 'are alkyl groups, preferably C1-C25 alkyl groups). Preferably, R is independently selected from hydrogen, C1-C25 linear alkyl, C3-C25 branched alkyl, C3-C25 cycloalkyl, preferably hydrogen.

Advantageously, the polymer is thermoplastic. Advantageously, the polymer is selected from the group consisting of polyolefins, polyacrylates, polyesters, polyurethanes, polyamides, polyalkyl oxides, polydialkylsiloxanes or various copolymers containing blocks or repeating units of these polymers. Preferably, the polymer is selected from the group consisting of polyolefins, polyacrylates, polyesters, polyurethanes, polyamides, polyalkyl oxides and polydialkyl siloxanes. Most preferably, the polymer is a polyolefin or polyalkyl oxide, preferably polyalkyl oxide. The polymer preferably has a molecular weight in the range of 50 to 500,000 Da.

The spacer is preferably selected from the group consisting of a single bond, C1-C25 linear alkylene, C3-C25 branched alkylene, C3-C25 cycloalkylene, arylene, heteroarylene, amines, amides, alcohols, esters, esters, thioethers, sulfones and their derivatives, sulfonic esters and their derivatives, sulfoxides and their derivatives, as well as carbonates, ketones and esters. Preferably, the spacer is selected from the group consisting of C1-C25 linear alkylene, C3-C25 branched alkylene, C3-C25 cycloalkylene and esters.

The spacer may be a polymer structural unit. The spacer can be selected from the group consisting of polyolefins, polyacrylates, polyurethanes, polyesters, polyamides, polydialkylsiloxanes, polyalkyl oxides or various copolymers containing blocks or repeating units of said polymers. In the case of a polymer, the spacer may have a molecular weight in the range of 50 to 500,000 Da.

In formula (I), PI is a photoinitiator fragment.

In the polymer photoinitiator of formula (I), m is an integer from 1 to 5000, preferably from 1 to 3000, more preferably from 1 to 1000. n is a real number greater than 0 and less than 5.

Index n refers to the statistical average, and m represents the total number of fragments containing photoinitiators attached to the polymer skeleton. Thus, all (n x m) photoinitiator fragments are present in the polymer photoinitiator. An example of the designation is presented in figure 1.

Scheme 1: An example of a polymer type photoinitiator illustrating the statistical significance of indices. The final formula thus reads C ₂₀ H ₄₀ - (CH ₂ -CH ₂ -CO (PhCOPh)) ₂

In the present invention, M _w (weight average molecular weight) is used to characterize polymer photoinitiators. The effectiveness of the polymer photoinitiator is, inter alia, related to how well the photoinitiator is mixed with the gelling polymer (s) or monomer (s). Among the parameters important in this respect is the molecular weight of the photoinitiator. Too high molecular weight does not provide good miscibility of the polymer photoinitiator with other components of the matrix composition. With respect to the present invention, when considering a two-component system, the miscibility of the polymer photoinitiator with other components in the matrix composition is important. In particular, if the chemical nature and molecular weight of the polymer photoinitiator and the gelling polymer (s) (s) are significantly different, low miscibility is obtained, which in turn leads to a matrix composition that is difficult to cure.

Substructures

The present invention provides polymer photoinitiators with substructures falling within the scope of the above formula (I).

The polymer photoinitiator may have the general formula II:

Polymer- [CR ₂ -CHR-C (= O) -spacer (PI) _n ] _m (II)

where m is an integer from 1 to 5000;

n is a real number greater than 0 and less than 5;

each R group is a substituent independently selected from hydrogen, C1-C25 linear alkyl, C3-C25 branched alkyl, C3-C25 cycloalkyl, aryl, heteroaryl, -OH, -CN, halogens, amines (e.g., -NR'R ' ', where R' and R '' are alkyl groups, predominantly C1-C25 alkyl groups) and amides (e.g. -CONR'R '' or R'CONR '' -, where R 'and R' 'are alkyl groups, preferably C1-C25 alkyl groups);

and PI is a photoinitiator fragment.

Another substructure with respect to the polymer photoinitiator has the general formula IIa:

Polymer- [CR ₂ -CHR-C (= O) -O-spacer (PI) _n ] _m (IIa)

where m is an integer from 1 to 5000;

n is a real number greater than 0 and less than 5;

each R group is a substituent independently selected from hydrogen, C1-C25 linear alkyl, C3-C25 branched alkyl, C3-C25 cycloalkyl, aryl, heteroaryl, -OH, -CN, halogens, amines (e.g., -NR'R '', where R' and R '' are alkyl groups, mainly C1-C25 alkyl groups) and amides (e.g.
—CONR′R ″ or R′CONR ″ -, where R ′ and R ″ are alkyl groups, preferably C1-C25 alkyl groups);

and PI is a photoinitiator fragment.

An additional substructure with respect to the polymer photoinitiator has the general formula IIb:

Polymer [CR ₂ -CHR-C (= O) -NH - spacer _{(PI) n] m (IIb} )

where m is an integer from 1 to 5000;

n is a real number greater than 0 and less than 5;

each R group is a substituent independently selected from hydrogen, C1-C25 linear alkyl, C3-C25 branched alkyl, C3-C25 cycloalkyl, aryl, heteroaryl, -OH, -CN, halogens, amines (e.g., -NR'R ' ', where R' and R '' are alkyl groups, predominantly C1-C25 alkyl groups) and amides (e.g. -CONR'R '' or R'CONR '' -, where R 'and R' 'are alkyl groups, preferably C1-C25 alkyl groups);

and PI is a photoinitiator fragment.

The polymer photoinitiator may have the general formula III:

Polymer- [CR ₂ -CHR-O-spacer (PI) _n ] _m (III)

where m is an integer from 1 to 5000;

n is a real number greater than 0 and less than 5;

each R group is a substituent independently selected from hydrogen, C1-C25 linear alkyl, C3-C25 branched alkyl, C3-C25 cycloalkyl, aryl, heteroaryl, -OH, -CN, halogens, amines (e.g., -NR'R ' ', where R' and R '' are alkyl groups, predominantly C1-C25 alkyl groups) and amides (e.g. -CONR'R '' or R'CONR '' -, where R 'and R' 'are alkyl groups, preferably C1-C25 alkyl groups);

and PI is a photoinitiator fragment.

The polymer photoinitiator may also have the general formula IV:

The polymer is [CR ₂ -CHR-NR ¹ spacer (PI) _n ] _m (IV)

where m is an integer from 1 to 5000;

n is a real number greater than 0 and less than 5;

each R group is a substituent independently selected from hydrogen, C1-C25 linear alkyl, C3-C25 branched alkyl, C3-C25 cycloalkyl, aryl, heteroaryl, -OH, -CN, halogens, amines (e.g., -NR'R '', where R' and R '' are alkyl groups, mainly C1-C25 alkyl groups) and amides (e.g.
—CONR′R ″ or R′CONR ″ -, where R ′ and R ″ are alkyl groups, preferably C1-C25 alkyl groups);

R ¹ represents a substituent independently selected from hydrogen, C1-C25 linear alkyl, C3-C25 branched alkyl, C3-C25 cycloalkyl, aryl, heteroaryl, —OH, —CN and halogens;

and PI is a photoinitiator fragment.

The polymer photoinitiator may have the general formula V

Polymer- [CR ₂ -CHR-Ph-spacer (PI) _n ] _m (V)

where m is an integer from 1 to 5000;

n is a real number greater than 0 and less than 5;

Ph is an optionally substituted phenyl group

each R group is a substituent independently selected from hydrogen, C1-C25 linear alkyl, C3-C25 branched alkyl, C3-C25 cycloalkyl, aryl, heteroaryl, -OH, -CN, halogens, amines (e.g., -NR'R '', where R' and R '' are alkyl groups, mainly C1-C25 alkyl groups) and amides (e.g.
—CONR′R ″ or R′CONR ″ -, where R ′ and R ″ are alkyl groups, preferably C1-C25 alkyl groups);

and PI is a photoinitiator fragment.

According to substructure (V), the Ph group is substituted with one or more substituents independently selected from C1-C25 linear alkyl, C3-C25 branched alkyl, C3-C25 cycloalkyl, aryl, heteroaryl, -OH, -CN, halogens, amines (e.g. , —NR′R ″, where R ′ and R ″ are alkyl groups, preferably C1-C25 alkyl groups) and amides (for example, —CONR′R ″ or R'CONR ″ -, where R ’and R ″ are alkyl groups, preferably C1-C25 alkyl groups). Preferably, the phenyl group is unsubstituted.

Of the above substructures of the general formulas II, IIa, IIb, III, IV and V, substructures of the formula II (including IIa and IIb) are preferred. The reason is that the alkene conjugated to the carbonyl group is more reactive in the graft copolymerization process. Substructures of the general formula IIa are most preferred since they have the added benefit of compatibility with acrylate matrix compositions and are relatively simple to synthesize.

Photoinitiator and photoinitiator fragments

As described above, PI is a photoinitiator fragment. In the present invention, a photoinitiator is defined as a fragment which, upon absorption of light, forms reactive particles (ions or radicals) and initiates one or more chemical reactions or transformations. One preferred property of the photoinitiator is a good overlap between the spectrum of the UV light source and the absorption spectrum of the photoinitiator. Another desirable property is a slight overlap or lack of overlap between the absorption spectrum of the photoinitiator and the spectrum of the total intrinsic absorption of the other components in the matrix composition.

Mostly, photoinitiator fragments are located in the side chain of the polymer. This means that they are attached to the polymer at points other than the ends of the polymer chain. This arrangement is easily achieved by the method used for the synthesis of photoinitiators of formula I. If m is greater than 1, the unit units - [CR ₂ —CHR spacer (PI) _n ] _{m are} preferably uniformly distributed throughout the polymer.

The photoinitiator fragments of the present invention can independently be cleavable (Norrish type I) or non-cleavable (Norrish type II). Advantageously, all photoinitiator fragments of the present invention are non-cleavable (Norrisch Type II). For reference, see, for example, A. Gilbert, J. Baggott: “Essentials of Molecular Photochemistry”, Blackwell, London, 1991). Upon excitation, cleavable photoinitiator fragments spontaneously decay into two radicals, at least one of which is sufficiently reactive to take a hydrogen atom from most substrates. Benzoin esters (including benzyldialkyl ketals), phenylhydroxyalkyl ketones, and phenylaminoalkyl ketones are important examples of cleavable photoinitiator moieties. Non-cleavable photoinitiator fragments do not decay upon excitation, thus providing fewer opportunities for leaching small molecules from the matrix composition. The photoinitiator fragments of the present invention are effective in converting light from a UV or visible light source into reactive radicals that can pick up hydrogen atoms and other mobile atoms from polymers and therefore affect covalent crosslinking. Optionally, amines, thiols, and other electron donors can either be covalently linked to a polymer photoinitiator, or added individually, or both. The addition of electron donors is not necessary, but can increase the overall efficiency of the splittable photoinitiators in accordance with a mechanism similar to that described below for non-splittable photoinitiators.

Excited non-cleavable photoinitiators do not decay into radicals upon excitation, but take a hydrogen atom from an organic molecule or, more efficiently, take an electron from an electron donor (such as an amine or thiol). Electron transfer forms a radical anion on a photoinitiator and a radical cation on an electron donor. This is followed by proton transfer from the radical cation to the radical anion to produce two uncharged radicals; among them, the radical on the electron donor is sufficiently reactive to take away the hydrogen atom from most substrates. Benzophenones and related ketones such as thioxanthones, xanthones, anthraquinones, fluorenones, dibenzosuberones, benzyls and phenylketocoumarins are important examples of non-degradable photoinitiators. Most amines with a C-H bond in the α position with respect to the nitrogen atom and many thiols will function as electron donors. The photoinitiator fragments of the present invention are preferably non-cleavable.

Self-initiating photoinitiator fragments are included in the scope of the present invention. When excited by UV or visible light, such photoinitiators are mainly cleaved by the Norrish type I mechanism and, moreover, crosslink in the absence of any conventional photoinitiator, providing curing of thick layers. Not so long ago, a new class of photoinitiators based on complex β-ketoesters was introduced by M.L Gould, S. Narayan-Sarathy, T.E. Hammond and R.B. Fechter from Ashland Specialty Chemical, USA (2005): “Novel Self-Initiating UV-Curable Resins: Generation Three”, Proceedings from RadTech Europe 05, Barcelona, Spain, October 18-20, 2005, vol. 1, p. 245-251, Vincentz. After Michael ester catalyzed by base addition to polyfunctional acrylates, a network forms with a series of Quaternary carbon atoms, each with two adjacent carbonyl groups.

Another maleimide-based self-initiating system was also discovered by C.K. Nguyen, W. Kuang, and C.A. Brady from Albemarle Corporation and Brady Associates LLC, both USA (2003): “Maleimide Reactive Oligomers”, Proceedings from RadTech Europe 03, Berlin, Germany, November 3-5, 2003, vol. 1, p. 589-94, Vincentz. Maleimides initiate radical polymerization, acting mainly as non-cleavable photoinitiators and, at the same time, spontaneously polymerize by attaching a radical via a maleimide double bond. In addition, strong UV absorption by maleimide disappears in the polymer, i.e. maleimide is a photo-initiator bleached in the light; this makes it possible to cure thick layers.

Thus, in an embodiment of the present invention, photoinitiator fragments include at least two different types of photoinitiator fragments. Preferably, the absorption peaks of various photoinitiators are at different wavelengths, thus increasing the total amount of light absorbed by the system. The various photoinitiators may all be cleavable, all non-cleavable, or a mixture of cleavable and non-cleavable. A mixture of several photoinitiator fragments may exhibit synergistic properties, as described, for example, by J.P. Fouassier: “Excited-State Reactivity in Radical Polymerization Photoinitiators”, Ch. 1, pp. 1-61, in “Radiation curing in Polymer Science and technology”, Vol. II (“Photo-initiating Systems”), ed. by J.P. Fouassier and J.F. Rabek, Elsevier, London, 1993. Briefly, the transfer of effective energy or electron transfer is carried out from one photoinitiator fragment to another in pairs [4,4'-bis (dimethylamino) benzophenone + benzophenone], [benzophenone + 2,4,6 trimethylbenzophenone], [thioxantone + methylthiophenylmorpholinoalkyl ketone].

Moreover, not so long ago, it was found that covalently linked 2-hydroxy-1- (4- (2-hydroxyethoxy) phenyl) -2-methylpropan-1-one, which is commercially available under the trade name Irgacure 2959, and benzophenone in the molecule 4- (4-benzoylphenoxyethoxy) phenyl 2-hydroxy-2-propylketone give a significantly higher radical polymerization initiation efficiency than a simple mixture of two separate compounds, see S. Kopeinig and R. Liska from Vienna University of Technology, Austria (2005): “Further Covalently Bonded Photoinitiators”, Proceedings from RadTech Europe 05, Barcelona, Spain, October 18-20 2005, vol. 2, p. 375-81, Vincentz. This shows that different photoinitiator fragments can exhibit significant synergistic effects if they are present in the same oligomer or polymer.

Each and all of the above types of photoinitiators and photoinitiator fragments can be used as photoinitiator fragments in the polymer photoinitiators of the present invention.

In accordance with the present invention, the photoinitiator fragments are independently selected from the group consisting of benzoin esters, phenylhydroxyalkyl ketones, phenylaminoalkyl ketones, benzophenones, thioxantones, xanthones, acridones, anthraquinones, fluorenones, dibenzosuberone-hydroxyalkeno-α-hydroxyalkeno-alkylene-alkylene-alkylene-alkylene-alkylene-α-di-alkylene-alkylene-α-di-alkylene-alkylene-α-di-alkylene-alkylene-α-di-alkylene-alkylene-alkylene-alkylene-α-alkylene-alkylene-alkylene-α-alkylene-alkylene-alkylene-alkylene-alkylene-alkylene-alkylene-alkylene-alkylene-alkylene-α-alkylene-alkylene-alkylene-alkylene-alkylene-alkylene-alkylene-alkylene-alkylene-alkylene-alkylene-alkylene-alkylene-alkylene-alkylene-alkylene-alkylene-alkylene-alkylene-alkylene-alkylene-alkylene-Alkyl-alkylene-Alkenyl-Acid , acylphosphine oxides, phenylketocoumarins, silanes, maleimides and their derivatives. Advantageously, the photoinitiator fragments are optionally substituted benzophenones or thioxanthones. Benzophenones or thioxanthones may be “optionally substituted” with one or more moieties defined as R above.

Polymeric photoinitiators of the present invention

The polymer photoinitiators of the present invention can be synthesized by graft copolymerization of photoinitiator fragments on a polymer skeleton.

The graft copolymerization process begins with a polymer having an X-H bond and photoinitiator fragments (PI) containing at least one activated alkene functional group. The radical attachment of the X-H bond in the polymer is carried out via the C = C double bond of the activated (s) alkene (s) functional (s) groups (s) present on the photoinitiator fragment. X-H is a single bond present in a polymer that can form a radical, typically C-H or N-H. For this reason, in the graft copolymerization product, a hydrogen atom H is always present on the second carbon atom of the polymer, which has the formula —CHR—.

To simplify, each photoinitiator PI fragment preferably contains one activated alkene functional group per PI fragment.

By “activated alkene” is meant an alkene, which, through its substituents, has an increased reactivity with respect to radical addition reactions as compared to an alkene substituted with a hydrogen atom (H-). Substituents on alkene can act as electron-withdrawing or electron-donating substituents, thereby changing the electron density distribution of activated alkene. Electron acceptance or donation from an alkene can be via π bonds (i.e., delocalization of electrons) or σ bonds.

Advantageously, the activated alkene functional group is selected from the group consisting of acrylate, vinyl ester, vinylamine, acrylamide and styrene functional groups. Preferably, the activated alkene functional group is selected from the group consisting of acrylate, vinyl ester, vinylamine and styrene functional groups. Most preferably, the activated alkene is acrylate.

The method of the present invention described above, provides for the production of various polymer photoinitiators, namely those of the general formula I, II, IIa, IIb, III, IV, or V.

In one aspect, the activated alkene is an acrylate functional group. By “acrylate functional group” is meant the functional group C = CC (= O) -. In other words, a photoinitiator fragment (PI) containing an ethylene functional group from which the polymer photoinitiators of formula (I) are synthesized, contains a functional group: CR ₂ = CR-C (= O) -. The reaction products of the grafted copolymerization of these photoinitiator fragments with polymers have the general formula II:

Polymer- [CR ₂ -CHR-C (= O) -spacer (PI) _n ] _m (II)

During graft copolymerization, the acrylate functional group is converted to a CR ₂ -CHR fragment in formula (II).

Advantageously, the acrylate functional group is an acrylate ester, in which case the elementary units - [CR ₂ -CHR-C (= O) -spacer (PI) _n ] _m in formula II contain the CR ₂ -CHR-C (= O ) -O- (i.e., the spacer group contains an oxygen atom O adjacent to the carbonyl fragment (C = O)). This subclass of photoinitiators has the general formula IIa:

Polymer- [CR ₂ -CHR-C (= O) -O-spacer (PI) _n ] _m (IIa)

This formula is illustrated in Scheme 2.

Scheme 2: grafted copolymerization of 4-benzoylphenylacrylate on polyethylene oxide.

Additionally, the acrylate functional group may be acrylamide, in which case the elementary units - [CR ₂ -CHR-C (= O) -spacer (PI) _n ] _m in formula II contain the fragment CR ₂ -CHR-C (= O) - NH- (i.e., the spacer group contains a nitrogen atom N adjacent to the carbonyl fragment (C = O)). This subclass of photoinitiators has the general formula IIb:

Polymer [CR ₂ -CHR-C (= O) -NH - spacer _{(PI) n] m (IIb} )

This formula is illustrated in diagram 3.

Scheme 3: grafted copolymerization of N- (4-benzoylphenyl) acrylamide on polyethylene oxide.

In addition, a photoinitiator of the general formula II is preferred in which the spacer moiety contains an aromatic ring, preferably an optionally substituted phenyl ring adjacent to the carbonyl moiety (C = O).

The photoinitiator fragment (PI) of the present invention may be a mono-, di- or triacrylate (i.e. containing one, two or three fragments C = C-C (= O) -, respectively). Preferably, the photoinitiator fragment (PI) monomer is monoacrylate.

In another aspect, the activated alkene functional group is a vinyl ester functional group. By "vinyl ester functional group" means a functional group CR ₂ = CR-O-. This gives photoinitiators with the general formula III:

Polymer- [CR ₂ -CHR-O-spacer (PI) _n ] _m (III)

This formula is illustrated in diagram 4.

Scheme 4: grafted copolymerization of phenyl (4- (vinyloxy) phenyl) methanone on polyethylene oxide.

In a further aspect, the activated alkene functional group is a vinyl amide functional group, i.e. functional group CR ₂ = CR-NR ¹ -. This gives photoinitiators with the general formula IV:

The polymer is [CR ₂ -CHR-NR ¹ spacer (PI) _n ] _m (IV)

This formula is illustrated in diagram 5.

Scheme 5: grafted copolymerization of phenyl (4- (vinylamino) phenyl) methanone on polyethylene oxide.

In yet a further aspect, the activated alkene functional group is a styrene group, i.e. functional group CR ₂ = CR-Ph-. Thus, a photoinitiator with the general formula V is obtained:

Polymer- [CR ₂ -CHR-Ph-spacer (PI) _n ] _m (V)

This formula is illustrated in diagram 6.

Scheme 6: grafted copolymerization of phenyl (4-vinylphenyl) methanone on polyethylene oxide.

In all structures I, II, IIa, IIb, III, IV, and V above, R can be independently selected from hydrogen, C1-C25 linear alkyl, C3-C25 branched alkyl, and C3-C25 cycloalkyl.

Preferably, in all structures I, II, IIa, IIb, III, IV and V, all R groups are hydrogen. Since the R groups are “independently selected”, they can be the same or different in all cases and, preferably, are the same.

Polymeric photoinitiators can be synthesized using an extruder as a reactor in a method known as reaction mixing; the technique is well known among methods where vinylsilanes are grafted onto polyolefins. Photoinitiator fragments have an activated alkene functional group that can react with radicals formed on the polymer skeleton by reaction with a radical initiator. Therefore, graft copolymerization of photoinitiator fragments (PI) on the polymer can be activated using a radical initiator.

This is illustrated in Scheme 7, where benzoyl peroxide is used as a radical initiator. All methods are carried out in an extruder.

Scheme 7: grafted copolymerization of 3-acryloyl-9H-thioxanthen-9-one on polyethylene using benzoyl peroxide as a radical initiator.

Instead of using a radical initiator, it can be assumed that the shear forces present during extrusion are sufficient to cause chain breaking with the release of free radicals that can react with activated alkene-containing photoinitiator fragments. One of skill in the art can adjust the extruder screw set, if necessary, and optimize process parameters with respect to the extrusion process. Therefore, in accordance with the present invention, a method is provided where the graft copolymerization of photoinitiator fragments (PI) on a polymer is carried out in an extruder.

Several works describe in detail graft copolymerization of acrylates on polyethylene using reaction extrusion / blending, where, for example, graft copolymerization of 2- (dimethylamino) ethyl methacrylate is described in K. E. Oliphant, K. E. Russel, W. E. Baker Polymer, 36 (1995), 1597-1603. The radical initiator 1,1-di- (tert-butylperoxy) -3,3,5-trimethylcyclohexane was used in this method.

Similarly, Y. M. Krivoguz, S. S. Pesetskii, B. Jurkowski, T. Tomczyk J. Appl. Polym. Sci., 102 (2006), 1746-1754 describes how grafted copolymerization of itaconic acid is carried out on polypropylene and polyethylene, also using peroxide as a radical initiator in the mixing step.

The grafted copolymerization of photoinitiators on polymeric materials using activated alkenes as a starting material provides the following advantages: (a) Photoinitiators substituted with activated alkenes (e.g. acrylates) are readily available, namely 1- (4-benzoylphenyl) prop-2-en- 1-one (obtained from Chemos GmbH). (b) Residual activated alkenes in the form of starting material or pure polymers obtained by reacting the activated alkene with itself are generally more soluble than, for example, photo-initiator grafted onto a polyolefin. This facilitates the cleaning of the grafted photoinitiator.

An example within the scope of the present invention is shown in Scheme 8, wherein 1- (4-benzoylphenyl) prop-2-en-1-one is grafted onto polyethylene.

Scheme 8: treatment of 1- (4-benzoylphenyl) prop-2-en-1-one and polyethylene with the formation of a polymer photoinitiator.

A radical initiator, for example, may be 2,5-dimethyl-2,5-di- (tert-butylperoxy) hexane (trade name L-101, manufactured by Elf-Atokem France). Other suitable initiators may be dicumyl peroxide (trade name DCP, manufactured by AO Kazanorgsintez), 2,2-di- (tert-butyl peroxy) -5,5,6-trimethylbiscyclo- [2,2,1] -heptane (trade name D- 1, produced by the Chemical-Technological Center of the Academy of Sciences of the Republic of Belarus), 2,2-di (3-methyl-1-butyn-3-peroxy) -5,5,6-trimethylbiscyclo [2,2,1] -heptane (commercial name D2, produced by the Chemical-Technological Center of the Academy of Sciences of the Republic of Belarus) or 2,5-dimethyl-2-hydroxy-5-tert-butylperoxy-3-hexine (trade name OP-2, produced by Chemical-technolo Center of the Academy of Sciences of the Republic of Belarus), benzoyl peroxide, lauroyl peroxide, t-butyl-α-cumyl peroxide, di-t-butyl peroxide, di-t-amyl peroxide, t-butyl peroxybenzoate, t-amyl peroxybenzoate, 1,1-bis (t-butyl peroxy) -3,3,5-trimethylcyclohexane, α, α'-bis (t-butylperoxy) -1,3-diisopropylbenzene, α, α'-bis (t-butylperoxy) -1,4-diisopropylbenzene, 2,5-bis (t-butylperoxy) -2,5-dimethylhexane; 2,5-bis (t-butylperoxy) -2,5-dimethyl-3-hexine.

In a previous paper (Y.-J. Sun, G.-H. Hu, M. Lambla Angew. Makrom. Chem. 3982 (1995), 1-13), the addition of styrene improves the efficiency of graft copolymerization, in particular when polypropylene is decorated with acrylates, for example glycidyl methacrylate.

Of particular importance is grafted copolymerization on polyethylene oxide, as illustrated in Scheme 9, where 4-acryloylbenzophenone is grafted onto a PEO chain using a radical initiator.

Scheme 9: Grafted copolymerization of 4-acryloylbenzophenone on PEO.

Radical initiators suitable for the reaction depicted in Scheme 9, for example, can be selected from the initiators listed above.

Matrix composition

The polymer photoinitiators of formula (I) are combined with one or more gelling polymers and / or gelling monomers in a matrix composition. Gelling polymers are polymers that — due to their hydrophilic nature — hold a swelling medium, such as water, within the polymer structure, providing a hydrophilic gel after curing the matrix composition.

In particular, the gelling polymer may be a hydrogel forming polymer. The hydrogel forming polymer is selected from the group consisting of polyacrylates, polyalkyl esters such as polyethylene oxide, polyurethanes, polyamides, polyethylene vinyl acetates, polyvinyl pyrrolidone and their copolymers and mixtures thereof. Preferably, the hydrogel forming polymer is selected from the group consisting of polyalkyl ethers, polyurethanes, polyethylene vinyl acetate.

A gelling monomer is a monomer which, upon polymerization, forms a gelling polymer. The hydrogel forming monomer is one which forms hydrophilic polymers as described above. Suitable hydrogel-forming monomers can be selected from the group consisting of acrylate monomers, N-vinyl pyrrolidone, and epoxy monomers, and, for example, monomers with two or more functional hydroxyl and / or amino groups, such as diethanol and aminoethanol.

To obtain the gel after the curing step, polymerization of the monomer units is carried out, presumably with crosslinking. After the curing step, the crosslinked composition is then swelled using a swelling medium such as water, C1-C5 alcohols, glycerin and polyethylene glycol (PEG), preferably PEG-2000.

Other possible components in the matrix composition include antioxidants such as BHT (2,6-bis (1,1-dimethylethyl) -4-methylphenol), Irganox 1010 (from Ciba) and similar structures. Therapeutic additives are also possible components in the matrix composition. If such additional components are present in the matrix composition, they can be added directly at the same time that the matrix composition is formed, at any time prior to curing, or as a component of the swelling medium. The latter is most preferred.

Hardening

The matrix composition of the present invention is cured by exposing it to UV radiation.

Curing can be carried out either in a melt state or in solution. The latter includes the steps where the matrix composition is dissolved in a suitable solvent and, for example, sprayed onto a tube, and subsequently exposed to UV radiation. After this, the solvent can either be evaporated or left in the coating, and it functions as a swelling medium to form the desired gel.

The ultraviolet spectrum is divided into sections A, B and C, where UV A extends from 400 nm to 315 nm, UV B from 315 to 280 nm, and UV C from 280 to 100 nm. By using a light source that produces light with wavelengths in the visible region (400 to 800 nm), some advantages are obtained with respect to the curing depth, provided that the photoinitiator can successfully cure the material at such wavelengths. In particular, the scattering phenomenon is less pronounced at a longer wavelength, thereby providing a greater penetration depth into the material. Thus, photoinitiators that absorb and can cause curing at a longer wavelength are of interest. By a reasonable choice of substituents on aromatic fragments, the absorption spectrum of the polymer photoinitiator can be shifted to some extent in the red part of the spectrum, which can then facilitate curing at relatively large depths.

Multiphoton absorption can also be used to cure samples using light sources that emit at wavelengths twice or even several times the wavelength of light required for curing in a single-photon process. For example, a composition containing a photoinitiator with an absorption maximum at ~ 250 nm can probably be cured using a light source emitting at ~ 500 nm using a two-photon absorption process, provided that the two-photon absorption cross section is sufficiently high. A multiphoton initiated curing process can also contribute to greater spatial resolution with respect to the curable region, as illustrated in Nature 412 (2001), 697, where a 3D structure is formed using a two-photon curing process.

In the present invention, curing is initially initiated by exposing the matrix composition to high energy radiation, preferably UV light. The photo-initiated process is carried out by the methods described above, which are known per se, by irradiation with light or UV irradiation in the wavelength range from 250 to 500 nm. Sources of radiation that can be used are sunlight or artificial light, or lasers. Preferred are, for example, high-pressure, medium-pressure or low-pressure mercury lamps and xenon and incandescent lamps. Similarly, excimer, solid-state and diode-based lasers are preferred. Even pulsed laser systems can be considered as applicable to the present invention. In general, with respect to the initiation of chemical reactions, diode-based light sources are preferred.

During the curing process, the polymer photoinitiator converts the matrix composition in a chemical process induced by light into a hydrophilic gel precursor.

Self curing

The polymeric photoinitiators described herein can also facilitate the curing of the surrounding matrix, but since the photoinitiators themselves are polymers, they can also “self-cure”, which means that the polymer photoinitiators alone can form a matrix composition that cures with UV exposure. This is especially important if the polymer in formula I is a polyolefin or polyalkyl oxide, preferably polyalkyl oxide.

In one aspect, therefore, the present invention provides a method for producing a hydrophilic gel precursor, said method comprising the steps of:

but. providing a matrix composition consisting of a polymer photoinitiator of the general formula I:

Polymer [CR ₂ -CHR-spacer _{(PI) n] m (I} ),

where m is an integer from 1 to 5000;

n is a real number greater than 0 and less than 5; and

PI is a photoinitiator fragment;

the polymer is selected from the group consisting of polyacrylates, polyalkyl ethers, polyurethanes, polyethylene vinyl acetates, polyvinyl pyrrolidone and their copolymers and mixtures thereof;

and where each R group is a substituent independently selected from hydrogen, C1-C25 linear alkyl, C3-C25 branched alkyl, C3-C25 cycloalkyl, aryl, heteroaryl, -OH, -CN, halogens, amines (e.g., -NR ' R ″, where R ″ and R ″ are alkyl groups, predominantly C1-C25 alkyl groups) and amides (for example, —CONR′R ″ or R′CONR ″ -, where R ″ and R ″ are are alkyl groups, preferably C1-C25 alkyl groups),

b. curing the matrix composition obtained in step a. by exposure to UV radiation.

The method of "self-curing" is mainly carried out using steps a. and b., carried out in alphabetical order, directly one after the other (i.e. without intermediate steps). In one aspect of this “self-curing” method, this method consists only of steps a. and b.

The one-component system — which is obtained using the “self-hardening” method — provides advantages in that the polymer photoinitiators are thermoplastic. For this reason, they become less viscous with a higher shear rate gradient, which simplifies their processing during extrusion. On the contrary, for example, polyvinylpyrrolidone cannot be extruded. All the details and structural modifications of the polymer photoinitiator given in this document are intended to produce photoinitiators suitable for use in the “self-curing” method.

In addition, the polymeric photoinitiators of the self-curing method may contain a single component of the matrix composition; those. the matrix composition may consist of polymer photoinitiators. This provides an advantage in that additives (e.g., plasticizers, viscosity modifiers) can be avoided, thereby reducing the likelihood of leaching low molecular weight components from a crosslinked matrix composition.

Gel state

To obtain the hydrophilic gel of the present invention, the matrix composition is exposed to a swelling medium such as water, C1-C5 alcohols, glycerol and polyethylene glycol (PEG), preferably PEG-2000 (referred to as step c. In this document). The composition is thus swollen to form a gel. Contact with the swelling medium may occur before or after curing of the matrix composition. The swelling medium may be in its original state or present in combination with other substances, for example, in saline or body fluid. Particles present in a gaseous state in equilibrium with a significant part, presented in its liquid form, also constitute a swelling medium.

The matrix composition can be cured by exposure to UV before or after exposure to a swelling medium. If cured first, a “dry” cured matrix composition (= gel precursor) is obtained. If the medium is first exposed to swelling, then the hydrophilic gel can be obtained in a one-step process, since the curing step is carried out in the presence of the medium that causes swelling. In other words, the swelling medium with respect to the hydrophilic gel is a solvent for the curing step. Regarding the steps of the method, step c. may be performed before or after step b. Advantageously, step c. carried out before step b.

In the “self-curing” process, the polymer photoinitiator can be cured by exposure to UV before or after exposure to a swelling medium. If cured first, a “dry” cured polymer photoinitiator (= hydrophilic gel precursor) is obtained. If the medium is first exposed to the swelling medium, then the hydrophilic gel can be obtained in a one-step process, since the curing step is carried out in the presence of the medium causing the swelling. In other words, the swelling medium with respect to the hydrophilic gel is a solvent for the curing step. Advantageously, step c. carried out before step b.

The gel is characterized as a swellable material, however, insoluble in the swelling medium. By hydrogel is meant a material having in its composition mainly a water-soluble or water-swellable material. The gel-like material is characterized on the basis of its rheological properties and in its dry state. In particular, the accumulation and loss modulus is used to characterize the mechanical properties of materials (T. G. Mezger: “The Rheology Handbook”, Vincentz Network, Hannover, 2006). As described above, curing the matrix composition is followed by tracking changes in G ′ (ω) and G ″ (ω) as a function of UV exposure time. In the examples used to describe the present invention, a frequency of 1 Hz was used to study the rheological properties, and the samples were heated to 120 ° C during testing.

The present invention also relates to a hydrophilic gel obtained by the methods described herein.

Medical device

One aspect of the present invention provides a medical device comprising a gel precursor or hydrophilic gel resulting from the methods of the present invention. The expression "medical device" should be interpreted in a fairly broad sense. Suitable examples of medical devices (including equipment) are catheters (such as urinary catheters), endoscopes, laryngoscopes, power tubes, drainage tubes, endotracheal tubes, catheter guide wires, surgical sutures, cannulas, needles, thermometers, condoms, uropreserves, protective coatings, for example, for gloves, stents and other implants, contact lenses, tubes for extracorporeal circulation, membranes, for example, for dialysis, blood filters, devices for auxiliary about blood circulation, dressings for wound care and colostomy. The most significant are catheters, endoscopes, laryngoscopes, power tubes, drainage tubes, catheter guide wires, surgical sutures and stents and other implants. Of particular interest to medical devices in the context of the present invention are catheters, such as urinary catheters.

A medical device can be coated, at least on its surface, with the gel precursor or hydrophilic gel of the present invention. In some embodiments, the hydrophilic gel covers the entire (external) surface of the medical device, and in some other embodiments, only a portion of its surface. In the most significant embodiments, the hydrophilic gel covers at least a portion of the surface (preferably the entire surface) of the medical device, which, when used properly, comes in direct contact with the body parts for which the medical device is intended. It is possible that the medical device is coated with a gel precursor, and a hydrophilic gel is formed in contact with the liquid — either with the patient’s biological fluids or with an activating solution containing water.

The present invention thus provides a catheter obtained by the method of the present invention, in particular a catheter where at least its surface portion is coated with a hydrophilic gel.

The present invention also relates to the use of a photoinitiator of the general formula I, II, IIa, IIb, III, IV or V, where m, n, PI, R, R ¹ , the spacer and the polymer are as defined herein, upon receipt of a hydrophilic gel, in particular hydrogel.

Example 1

A number of grafted polyethylene oxide polymers are prepared by loading a 60 g Brabender mixer PEO NF1 (Sumitomo) at 150 ° C. To this mixture, various amounts of 4-acryloylbenzophenone (1-10 g) and 2,5-bis (tert-butylperoxy) -2,5-dimethylhexane in various amounts (0.5-5 g) are added. This mixture was stirred for 20 minutes at 150 ° C and subsequently taken from a Brabender mixer. The isolated material was analyzed using FT-IR to confirm complete conversion of the added acrylate.

The effect of water on this material results in the formation of a hydrogel as a swellable material, however, insoluble in water. Moreover, the hydrogel is a solid or solid material of two or more components, one of which is a liquid present in significant quantities. Solid gels are characterized by the absence of an equilibrium modulus, the storage modulus G '(ω), which exhibits a distinct plateau with a length of at least an order of seconds, and the loss modulus G' '(ω), which is much smaller than the accumulation modulus in the plateau region.

Although the present invention has been described with reference to a number of embodiments and preferred features, the most comprehensive scope should not be construed as being limited specifically to these embodiments. The scope of the present invention is defined by the attached claims. Compatible features from various embodiments and aspects of the present invention can be combined at the discretion of a person skilled in the art, while remaining within the scope of the present invention.

Claims (20)

1. A method of obtaining a hydrophilic gel, where the specified method includes the steps of:
but. for obtaining a matrix composition comprising a polymer photoinitiator of the general formula I:
$$P\mathrm{about}l\mathrm{and}meR-{[C{R}_2-CHR-\mathrm{from}Pe\mathrm{th}\mathrm{from}eR{(PI)}_n]}_m\left(\text{I}\right)$$

,
where m is an integer from 1 to 5000;
n is a real number greater than 0 and less than 5; and
PI is a photoinitiator moiety independently selected from the group consisting of benzoin esters, phenylhydroxyalkyl ketones, phenylaminoalkyl ketones, benzophenones, thioxanthones, xanthones, acridones, anthraquinones, fluorenones, dibenzosuberones, benzyls, benzylketals, α-hydroxyalkenoalkenoalkenoalkenoalkenalkenoalkenalkenalkenoalkenalkenalkenoalkenalkenalkenoalkenalkenalkenoalkenalkenalkenoalkenalkenalkenoalkenalkenalkenoalkenalkenoalkenalkenoalkenalkenalkenalkenoalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenon acylphosphine oxides, phenylketocoumarins, silanes, maleimides and their derivatives;
the polymer is selected from the group consisting of polyacrylates, polyalkyl ethers, polyurethanes, polyethylene vinyl acetates, polyvinyl pyrrolidone and their copolymers and mixtures thereof;
the spacer is selected from the group consisting of a single bond, C1-C25 linear alkylene, C3-C25 branched alkylene, C3-C25 cycloalkylene, arylene, heteroarylene, amines, amides, alcohols, esters, esters, thioethers, sulfones and their derivatives, complex sulfonic esters and their derivatives, sulfoxides and their derivatives and carbonates, ketones and esters;
and where each R group is a substituent independently selected from hydrogen, C1-C25 linear alkyl, C3-C25 branched alkyl, C3-C25 cycloalkyl, aryl, heteroaryl, —OH, —CN, halogens, amines and amides,
and one or more gelling polymers selected from the group consisting of polyacrylates, polyalkyl ethers such as polyethylene oxide, polyurethanes, polyamides, polyethylene vinyl acetates, polyvinyl pyrrolidone and their copolymers and mixtures thereof, and / or gelling monomers selected from the group consisting of acrylate monomers, N-vinylpyrrolidone, epoxy monomers and monomers with two or more functional hydroxyl and / or amino groups, such as diethanol and aminoethanol;
b. curing the matrix composition obtained in step a. by exposing it to UV radiation,
c. exposing the matrix composition to a swelling medium, thereby producing a gel,
where is stage c. may be performed before or after step b. 2. The method of claim 1, wherein the gelling polymer is selected from the group consisting of polyacrylates, polyalkyl ethers, polyurethanes, polyethylene vinyl acetates, polyvinyl pyrrolidone and their copolymers and mixtures thereof. 3. The method of claim 1, wherein the gelling monomer is selected from the group consisting of acrylate monomers, N-vinylpyrrolidone and epoxy monomers. 4. The method according to p. 1, where the polymer in formula I has a molecular weight in the range from 50 to 500,000 Da. 5. The method according to claim 1, where the spacer is a polymer structural unit. 6. The method of claim 1, wherein the spacer has a molecular weight in the range of 50 to 500,000 Da. 7. The method according to p. 1, where m is an integer from 1 to 3000. 8. The method of claim 1, wherein the polymer photoinitiator of formula I is synthesized by graft copolymerization of photoinitiator fragments (PI) on a polymer in the presence of a radical initiator. 9. The method of claim 1, wherein the grafted copolymerization of photoinitiator fragments (PI) on the polymer is carried out in an extruder. 10. The method according to p. 1, where the photoinitiator elementary units are in the side chain of the polymer. 11. The method of claim 1, wherein the matrix composition further comprises an antioxidant. 12. The method of claim 1, wherein R is independently selected from hydrogen, C1-C25 linear alkyl, C3-C25 branched alkyl, C3-C25 cycloalkyl, preferably R is hydrogen. 13. The method of claim 1, wherein the swelling medium is selected from the group consisting of water, C1-C5 alcohols, glycerol and polyethylene glycol (PEG), preferably it is PEG-2000. 14. The method of claim 1, wherein the swelling medium comprises water, and the gel thus obtained is a hydrogel. 15. The method according to p. 1, where step c. carried out before step b. 16. A method of obtaining a hydrophilic gel precursor, wherein said method comprises the steps of:
but. for obtaining a matrix composition consisting of a polymer photoinitiator of the general formula I:
$$P\mathrm{about}l\mathrm{and}meR-{[C{R}_2-CHR-\mathrm{from}Pe\mathrm{th}\mathrm{from}eR{(PI)}_n]}_m\left(\text{I}\right)$$

,
where m is an integer from 1 to 5000;
n is a real number greater than 0 and less than 5; and
PI is a photoinitiator moiety independently selected from the group consisting of benzoin esters, phenylhydroxyalkyl ketones, phenylaminoalkyl ketones, benzophenones, thioxanthones, xanthones, acridones, anthraquinones, fluorenones, dibenzosuberones, benzyls, benzylketals, α-hydroxyalkenoalkenoalkenoalkenoalkenalkenoalkenalkenalkenoalkenalkenalkenoalkenalkenalkenoalkenalkenalkenoalkenalkenalkenoalkenalkenalkenoalkenalkenalkenoalkenalkenoalkenalkenoalkenalkenalkenalkenoalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenalkenon acylphosphine oxides, phenylketocoumarins, silanes, maleimides and their derivatives;
the polymer is selected from the group consisting of polyacrylates, polyalkyl ethers, polyurethanes, polyethylene vinyl acetates, polyvinyl pyrrolidone and their copolymers and mixtures thereof;
the spacer is selected from the group consisting of a single bond, C1-C25 linear alkylene, C3-C25 branched alkylene, C3-C25 cycloalkylene, arylene, heteroarylene, amines, amides, alcohols, esters, esters, thioethers, sulfones and their derivatives, complex sulfonic esters and their derivatives, sulfoxides and their derivatives and carbonates, ketones and esters;
and where each R group is a substituent independently selected from hydrogen, C1-C25 linear alkyl, C3-C25 branched alkyl, C3-C25 cycloalkyl, aryl, heteroaryl, —OH, —CN, halogens, amines and amides,
b. curing the matrix composition obtained in step a. by exposing it to UV radiation. 17. A method of obtaining a hydrophilic gel, where the specified method includes the steps a. and b., as defined in paragraph 16, wherein said method includes an additional step:
c. exposing the matrix composition to a swelling medium, thereby producing a hydrophilic gel,
where is stage c. may be performed before or after step b. 18. The method of claim 17, wherein the swelling medium is selected from the group consisting of water, C1-C5 alcohols, glycerol, and polyethylene glycol (PEG). 19. The method of claim 17, wherein the swelling medium comprises water, and the gel thus obtained is a hydrogel. 20. The gel obtained by the method according to any one of paragraphs. 1-15.

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