MXPA00008950A - Silicone contact adhesive with reduced cold flow - Google Patents

Abstract

The invention relates to a method for producing polysiloxane contact adhesive coatings with reduced cold flow. According to said method, a suitable flat base is coated with a single-component polysiloxane contact adhesive solution and the coating dried. A complex consisting of a metal ion from the following group:calcium, magnesium, zinc, aluminium, titanium, zirconium or hafnium, with a low-molecular organic complexing agent is added to the organic adhesive coating solution. Said metal ion is not freed from its bond with the complexing agent until the adhesive solution is heated and/or dried.

Description

Low-fusing, cold-flow silicone contact adhesive The invention relates to crosslinking reagents in contact adhesive formulations based on silicone polymers. Among other possible technical applications, these contact adhesive formulations find their main application in the manufacture of medicinal dressings. The new crosslinked silicone contact adhesives are especially suitable for manufacturing medicinal dressings containing active ingredients, the so-called transdermal therapeutic systems (STT). The crosslinking reagents described are used in the coating and drying in an organic solvent medium of silicone-based contact adhesive formulations. Only under these conditions do the reactants display their crosslinking activity, which leads to the formation of a three-dimensional polymeric reticle. The resultant contact adhesive layers thus lose their fluidity, the so-called "cold creep." Cold creep is an undesirable phenomenon, since two surfaces joined by a layer of contact adhesive can be displaced due to their own force of gravity when said creep occurs, so that it is not possible to guarantee a reliable union of said surfaces as far as the relative position of the same is concerned In the case of STTs, this problem especially affects the adhesion of the system On the point of application in people and animals In addition, during STT storage, due to the effect of gravity and cohesion and adhesion forces, it is possible that undesirable deformation or previous displacement occurs within the system when it is presented the cold creep in the silicone adhesive layer of the system.

It has surprisingly been found that the reagents used in the crosslinking of polyacrylate-based contact adhesives can also be used successfully in silicone polymers, in spite of the basically different chemistry of both types of polymer. The organometallic complexes of certain metal cations have been found to be particularly effective. According to the invention, among all of them it is preferable to use complexes of metals such as aluminum, titanium, zirconium or zinc. Acetylacetone is especially suitable as an organic complex for use in medicine. The crosslinking reagents are added to the silicone contact adhesive solution and only develop their crosslinking activity once the solvents, or the stabilizing additives, are removed during the drying process. The contact adhesives based on silicone polymers are of special importance in their application in medicine. This is due to its excellent compatibility with the skin in relation to the production of dermatitis (irritations) and immunological reactions (sensitization, allergen). On the other hand, silicone contact adhesives have been shown to behave reliably and sustainably on human skin for several days. This is also influenced by its strongly hydrophobic character. Silicone contact adhesives in the field of STTs are characterized by their high chemical compatibility with the active ingredients and pharmaceutical auxiliary materials, which improve the chemical stability and storage capacity of the products based on them. On the other hand, the extraordinarhigh permeability (diffusibility) of silicone polymers, which facilitates the transfer of active ingredients and auxiliary materials from the system, plays a special role. Apart from the mentioned advantages, in the contact adhesives for application in medicine that are on the market (for example, the series of products Bio-PS A Q7 of the Dow Corning Company), there is a notable absence of rheological properties. These are polymers based on polysiloxane, which do not present three-dimensional cross-linking, or have a three-dimensional cross-linking limited to only one microscopic area. They have a basically linear structure, very little branched in the best of cases. This is necessary in order to dissolve the products in organic solvents, for example short chain alkanes (heptane, gasoline) or ethyl acetate and to be able to add them to a formulation in a solvent medium. On the other hand, these polymers, which correspond to the state of the art, are one-component polymer solutions. This means that the polymers contained in the solution are not intended to react as two components at a later stage of the processing, such as the typical resin with a hardener. However, a component does not mean that there can not be in the solution different types of polysiloxane polymers, even mixed with other polymers of different chemical character (for example, polyacrylates) depending on the case. The processes for making the one-component solutions of contact adhesives of polysiloxanes described below should not be confused with those processes and catalysts, which have been described in multiple ways for the two-component silicone adhesives. The one-component systems contain at least two different types of polysiloxanes, which are intended to react within the framework of a further stage of processing to form a three-dimensional polymeric lattice, in a manner similar to a resin with a hardener. The polysiloxane concept also comprises copolymers of the polysiloxane, in whose polymer chains there are incorporated, or are bound to them, segments of different chemical character, for example, based on polyethylene oxide, polypropylene oxide, polyvinylpyrrolidone or poly (meth) acrylate. The preparation of polysiloxane contact adhesive solutions in the STT manufacturing sector comprises the application and drying to achieve contact adhesive polymer films. The lack of three-dimensional crosslinking in the finished product constitutes a disadvantage, since the linear polymer chains retain a certain fluidity, even if it is extremely slow. This is called in the technique "cold creep", since it occurs even at room temperature.The forces that favor such creep are: 1. The force of gravity 2. All the mechanical forces that can act on the product during the manufacturing or storage 3. Adhesion forces between the contact adhesive polymer and the surfaces covered by it (resulting in shrinkage or extension) 4. Cohesion forces in the polymer itself (shrinkage) Cold flow almost always negative in the STT storage period, which is usually two years or more.The cold creep can cause the products, for example, to stick to their packaging.This effect also appears after the application of the apositos on the skin of people or animals, favored especially by the body temperature.In applications of several hours or several days can get to slip the dressing on the foot l, due to an authentic STT flow over this. On the other hand, the silicone adhesive can flow slowly on the skin extending beyond the original surface of the dressing. This often leaves residues on the skin at the periphery of the system once it is removed. These residues are considered very annoying by the user. The problem of cold creep in silicone contact adhesives is known. US Patent 5,232,702 describes a large number of possible solutions. Numerous fillers and additives are mentioned in said patent, but none is described as a crosslinking reagent. The cross-linking reactions in relation to the support systems of the active ingredients are explicitly qualified as problematic or impossible, due to the excessive temperatures required or the insufficient biological compatibility of the reagents (column 5, lines 3-10). Instead, many other beneficial measures for cohesion are described. Since in practice these measures do not always make it possible to control the problem, the purpose of the invention is to develop novel and more effective methods of suppressing the cold creep of silicone-based contact adhesives. This purpose is achieved surprisingly by adding reagents, which are applied for the suppression of cold flow in a type of chemically completely different contact adhesion polymers, polyacrylates.

Such transfer possibility was not expected, since the polysiloxanes that form the basic structure of silicone polymers have a chemical character totally different from that of polyacrylates, based exclusively on the chemistry of hydrocarbons.

In the case of polyacrylate-based contact adhesives, which have carboxyl or hydroxyl groups attached to the polymer, the technical possibility of achieving a three-dimensional crosslinking of the polymer chains by the addition of multivalent ions, for example, calcium, magnesium or zinc, but above all aluminum and the elements of the 4th subgroup, titanium, zirconium and hafhio, is known. Aluminum only appears as a trivalent ion, while the stable phase of oxidation +4 is used in the elements of subgroup 4o. By this way it is possible to transform the set of linear polymer chains into a non-fluid three-dimensional grid from a solution during drying, and not before. In order to be able to add the metal ions to the solvents, generally organic, and to inhibit a premature crosslinking reaction in the polymer solution, low molecular weight complexers are used, to which the metal ions are bound. Among these complexes, acetylacetone should be mentioned in the field of medicine, since it is relatively non-toxic and, on the other hand, it is easy to separate it from the product in the drying processes. In its enol chemical form, acetylacetone is a vinyl acid and forms the corresponding acetylacetone complexes with the metal ions. These complexes have a particularly stable chemical character, and can not be compared with the usual salts of organic acids with the corresponding metals. Aluminum acetylacetonate and titanium acetylacetonate are used for the crosslinking of polyacrylate-based contact adhesives in the drying phase of organic solvent solutions. During the cross-linking, metal ions transfer from the complexing agent to the functional groups of the acrylate polymer, several functional groups of various polymer chains joining together. It has been discovered that said acetylacetonates, widely used as crosslinking reagents in polyacrylates, surprisingly have a phenomenological effect practically identical in polysiloxanes, despite being both types of polymer completely different from the chemical point of view: The fluidity of the adhesives silicone contact is significantly reduced. The characteristic of this modification in polysiloxanes is similar to that which occurs in polyacrylates, which can be based on a three-dimensional crosslinking through a mechanism whose details are unknown. The novel crosslinking was tested on two groups of silicone-based contact adhesives that are very important in the field of medicine. These are contact adhesives based on polydimethylsiloxane in a form incompatible with amines and a form compatible with amines. The form incompatible with amines is characterized by remaining during the polymerization a residue of silanol groups (hydroxyl groups attached to silicon) in the polymer. This is the standard type, capable of reacting through the silanol groups with primary, secondary or tertiary amino groups, reactions that are not desirable. Since many active pharmaceutical ingredients contain amino groups, it is counted especially with compatible types with amines for its use in STT. In these, what is called an end-capping is performed: the silanol groups are blocked by suitable reagents, for example, by attachment of a trimethylsilyl group. As a standard, a contact adhesive based on a polyacrylate with a small percentage of free carboxyl groups was used. The ability of three-dimensional crosslinking of such acrylates with the crosslinking agents object of the present discussion is well known in the world of the art. The following formulations were studied: Al = aluminum; Ti = titanyl The crosslinker concentration data refers to the dry mass of adhesive. Bio-PSA Q7-4602, from the manufacturer Dow Corning, is the solution of a silicone content adhesive incompatible with amines in ethyl acetate. The product 4301 differs in that it is compatible with amines. The solvent in this case is heptane. Durotak 387-2051, from the manufacturer National Starch, is the solution of a polyacrylate contact adhesive in a mixture of ethyl acetate and heptane without the addition of a crosslinking agent.

The manufacture of the adhesive masses was carried out by adding the equivalent amount of a solution of acetylacetonate of 2% Ti in ethenol, or of a solution of 4% Al acetylacetonate in ethyl acetate, to the solution of the adhesive and subsequent mixing.

The viscous adhesive solutions were applied in thin layer on a sheet of polyethylene terephthalate (PET) (Hostephan RN 100 from Hoechst) with the aid of a suitable film extender frame and dried for 10 minutes at 80 ° C in an oven with extraction of fumes The layer thickness was adjusted in all the formulations to obtain a weight per unit area of dry film of 60 g / m2 D 5%. This corresponds to 6 mg / cm2 and a layer thickness of approximately 60 D Dm. In all the contact adhesives tested, the coating on PET produces a bond that is almost impossible to separate by mechanical means. Alternatively, the contact adhesive films were also prepared under the same conditions on a repellent support sheet by coating with a fluorinated polymer (ScotchPak 1022 of 3M). Under these conditions, the adhesive film of the support sheet can easily be detached mechanically and further processed. The effects of the addition of crosslinker on the manufactured adhesive adhesive layers were studied with the aid of apparatuses according to two measurement methods: The "tack" or "stickiness" of a contact adhesive describes its ability to spontaneously fix on a surface. This stickiness that appears spontaneously, even after a minimum contact time without hardly applying pressure, basically depends on the fluidity of the contact adhesive. A high fluidity allows a rapid contact, which covers the entire surface of the microscopic structure of a substrate surface, ie a high tack. Fluency is not the only characteristic associated with stickiness, but it is the most important. The "Rolling Ball" method is used to measure stickiness. This method consists of rolling a ball of a suitable material on the thin layer of the contact adhesive stuck to a flat support, the ball having an initial velocity at the moment of beginning to roll. The distance the ball makes to stand can be measured, due to the brake effect exerted by the stickiness of the contact adhesive, or the time it takes the ball to travel a given path without stopping in that path. The results of this last variant are not conditioned by the erratic itinerary that the ball usually follows when "it is trapped". The passage time of the ball was measured on an inclined plane (glass plate 1 cm thick) with adjustable inclination angle and a path of 59 cm. For this measurement the ball was rolled over the contact adhesive film stuck on a PET sheet after traveling a specified preliminary course of 17.5 cm. The measurement of the passage time was made between two modulated infrared light barriers through a connected electronic timer, which records thousandths of a second.

For an angle of inclination of 35 ° C using a special steel bearing of 18 nm in diameter the average passage times of 6 tests indicated in Fig. 1 were obtained. The measurements indicate a correlation of the decrease in the passage time with the increase in the concentration of crosslinker for the three types of adhesive. So, as the crosslinking agent increases in the silicone content adhesives, the tackiness decreases, as expected in accordance with the theory of crosslinking and consequent reduction of the fluidity of the polymer, and as can be appreciated, in the same way, in the known example of the crosslinking of polyacrylate (Al 1-A14). This is especially true for the silicone adhesive incompatible with amines (SI 1 -SI 4), but also clearly for the amine compatible variant (S21-S24).

On the other hand, it has been found that the crosslinking produces especially noteworthy effects in a range of aluminum concentration of 0.05%, and also between 0.05% and 0.1%.

The use of aluminum-based crosslinkers (S31 + S32) instead of titanium (SI 1 + 812) in silicone adhesive adhesives proves to be equally effective (Fig. 2). On the other hand, the shear strength of the manufactured contact adhesive films was studied. In linear, fluid, non-crosslinked polymers, a slow flow of the film occurs when a shear force is applied. Provided that said force is not applied too quickly, which would cause the film to break, the constant action of a shearing force makes it possible to observe a practically consistent flow velocity. On the contrary, during a three-dimensional transverse crosslinking of the polymer chains, the viscous portion is practically lost, and only elastic deformation is possible. By increasing the shearing force, the structure of the polymer and the entire film are mechanically torn. Therefore, in relation to shearing, crosslinked and non-crosslinked adhesives have very different characteristics. To study the behavior during shearing, 12-mm-diameter circular die-cut specimens were taken from the manufactured contact adhesive films. These round pieces of film were fixed between two strips of a PET sheet (Hostaphan RN 100 of Hoechst) as shown in Fig. 3. After imprisoning this set in a conventional tensile testing machine (universal testing machine 81803 from Frank, Weinheim), the necessary shear force was recorded graphically over time to reach a constant shear rate of 2.5 mm / min. The force / time diagrams corresponding to 6 individual measurements are shown in Figs. 4 to 7. In the case of the polyacrylate taken as a reference, a constant shear force is produced in a short time, when the polymer is not crosslinked, which has to be used for the maintenance of the previously specified constant shear rate: the polymer flows (Fig. 4). On the other hand, when the polymer is crosslinked, there is a rapid increase in the shearing force, accompanied by an elastic deformation, until finally the elastic extensibility of the film is exceeded and this is torn, whereby the force of shear falls rapidly to zero (Fig. 5). The silicone film without addition of crosslinker shows a behavior very similar to that of the non-crosslinked polyacrylate film, since for a given shearing force the specified shear rate corresponding to a given shearing force is also maintained by the flow. The necessary forces move only at a higher level, and the "peak energy" to move from the resting state to a flow movement is more marked than in the case of non-crosslinked polyacrylate (Fig. 6). related to different chain lengths and different interaction forces between the molecules of both types of polymer, however, the most important thing is the characteristic change of the fluidity in a silicone film with crosslinking agent, very similar to the case of the crosslinked polyacrylate transversally, in this case a shearing force is created accompanied by elastic deformation, which finally falls to zero when the film is torn (Fig. 7).

This clearly demonstrates that the silicone-based contact adhesive film ceases to be fluid after the addition of the titanyl acetylacetonate crosslinker.

Claims (11)

R E I V I N D I C A C I O N S

1. Process for manufacturing cold-fused low-flow polysiloxane-based adhesive adhesives by coating and drying a one-component polysiloxane contact adhesive solution on an appropriate flat substrate, characterized by adding to the organic solution of the adhesive intended for coating a complex consisting of a metal ion from the group of calcium, magnesium, zinc, aluminum, titanium, zirconium or hafhion and an organic compound of low molecular weight, leaving the metal ion free from its union with the complexer only under the conditions of heating and / or drying of the adhesive solution. Process according to claim 1, characterized in that the metal addition is at least 0.005% by weight, based on the mass of dry adhesive. Process according to claim 1, characterized by using amounts of metal ranging from 0.005 to 0.5% by weight, based on the mass of dry adhesive. Process according to one or more of the preceding claims, characterized in that basically all the organic complexing agent is removed during drying. Process according to one or more of the preceding claims, characterized in that drying takes place at a temperature between 20 and 120 ° C. Process according to one or more of the preceding claims, characterized in that the weight per unit area of the film is placed. dry between 10 and 300 g / m

2. Process according to one or more of the preceding claims, characterized in that the organic complexing agent consists of acetylacetone or the acetylacetone participates in the formation of the complex. Process according to one or more of the preceding claims, characterized in that the metal constituting the complex is aluminum or titanium. Process according to one or more of the preceding claims, characterized in that the polysiloxane used is basically polydimethylsiloxane. 10. Process according to claim 9, characterized in that the free silanol groups of the polydimethylsiloxane are chemically blocked by a suitable end-capping and, therefore, are resistant to the amines. 11. Medicinal dressing, characterized by having at least one layer of contact adhesive based on polysiloxane in its stratiform structure, manufactured by a process according to one of the preceding claims. SUMMARY In a process of manufacturing layers of low cold flow polysiloxane contact adhesive by coating and drying a one component polysiloxane content adhesive solution on a suitable smooth substrate, it is added to the organic solution of the coating adhesive a complex consisting of a metal ion of the group of calcium, magnesium, zinc, aluminum, titanium, zirconium or hafnium and an organic compound of low molecular weight, the metal ion being released from its binding to the complex only under heating conditions and / or drying of the adhesive solution.