Packaging with a sliding layer and method for pharmaceutical and cosmetic substances and preparation for the production thereof

Abstract

The present invention relates to a formulation for application on the inside of a hollow body to create a slip layer on a packaging for pharmaceutical or cosmetic products. The liquid formulation comprises the following ingredients: - a reactive silicone system for forming a silicone network of a slip layer, - a catalyst for catalyzing the crosslinking reaction of the reactive silicone system, - at least one non-reactive silicone oil, - and at least one diluent, wherein the diluent comprises a silicon-containing compound and wherein the content of the diluent in the formulation is at least 45 weight percent and at most 95 weight percent of the formulation. Furthermore, the present invention relates to a packaging for pharmaceutical or cosmetic products and to a method for producing a packaging for pharmaceutical or cosmetic products.

Description

[0001] This application is a divisional application of patent application 201910851365.8, filed on September 10, 2019. Technical Field

[0002] This invention generally relates to containers for containing pharmaceutical and cosmetic preparations. In particular, this invention relates to containers having a sliding layer that facilitates the sliding of a piston or stopper to empty the container. Background Technology

[0003] Plastic-based cosmetic and pharmaceutical encapsulations have been technology for decades, but they also present various challenges. When used as pharmaceutical encapsulations in syringes, the greatest challenge lies in moving the inserted stopper with minimal force. Low static and sliding friction of the stopper allows for complete and rapid ejection of the contents from the syringe and minimizes discomfort to the patient caused by uneven stopper movement or even stoppage.

[0004] From existing technologies, particularly as is well known, siliconized pharmaceutical packaging is used to address this challenge.

[0005] US4767414A describes applying silicone oil to the inner wall after plasma activation of the inner surface of a plastic. It is desirable in any case to be able to cancel the plasma activation step. Furthermore, chemically non-covalently bonded silicone oil may enter the patient's bloodstream, particularly the bloodstream.

[0006] EP0920879B1 describes a silicone-based mixture. The mixture, consisting of reactive and non-reactive silicone oils, achieves adhesion of the silicone layer to the substrate and good sliding properties of the stopper.

[0007] In addition, another challenge is maintaining the sliding performance of the sliding layer under various influences on the package. Summary of the Invention

[0008] Therefore, the objective of this invention is to provide a container for pharmaceuticals and cosmetics that has a sliding layer that is as insensitive as possible to external influences. This objective is achieved through the subject matter of the independent claims. Advantageous embodiments and extensions are given in the corresponding dependent claims.

[0009] Therefore, the present invention provides a formulation for application to the inside of a hollow body, which is used to create a sliding film or sliding layer on a pharmaceutical or cosmetic encapsulation. The liquid formulation includes: - A reactive organosilicon (Silikon) system used to form the organosilicon network of the sliding layer. -A catalyst for catalyzing the crosslinking reaction of the aforementioned reactive organosilicon system. - At least one non-reactive silicone oil (preferably polydimethylsiloxane). -At least one diluent, The diluent comprises a silicon-containing compound, and the diluent is present in a concentration of 45% by weight or more and 95% by weight or less in the formulation. According to one embodiment, the diluent is present in a concentration greater than 45% by weight and less than 95% by weight in the formulation.

[0010] In the context of this invention, non-reactive silicone oil is understood as a polysiloxane without crosslinkable or polymerizable groups. Specifically, non-reactive silicone oil is a polysiloxane containing aliphatic groups, such as polydimethylsiloxane.

[0011] It has been demonstrated that the slip layer becomes particularly resistant when the solvent ratio, i.e., the diluent ratio, is greater than 45 wt% of the formulation. Therefore, for hexamethyldisiloxane (HMDSO) as a diluent, a solvent ratio of at least 50 wt% is considered particularly advantageous. A gradual decrease in the solvent ratio results in a less cured layer. For a low solvent ratio, higher layer strength and better curing can be assumed, as this prevents solvent molecules from intercalating into the polymer chains. However, this is not the case.

[0012] According to the invention, the diluent or solvent comprises a silicon-containing compound, preferably an organosilicon compound. It has been surprisingly shown that the Si content of the diluent plays a decisive role in layer adhesion and curing. In this case, the use of siloxanes or polysiloxanes (e.g., HMDSO) has proven particularly advantageous. In this case, the corresponding layer has a uniform composition and good layer adhesion to the substrate. In particular, the good layer adhesion is surprising in this respect because the substrate comprises an organic plastic and generally does not have Si-O bonds; the diluent covalently interacts with the silicone oil present in the formulation and thus increases layer adhesion. Therefore, it can be envisioned, without being limited to this assumption, that the silicon-containing diluent also acts as an adhesion promoter between the generally non-silicone substrate and the silicone oil in the formulation.

[0013] Furthermore, siloxane-based silicon-containing diluents (such as HMDSO) have relatively low surface tension, which is advantageous in terms of wetting the substrate surface. Typically, without being limited to siloxane-based diluents, the silicon-containing diluent preferably has a surface tension of less than 19 mN / m.

[0014] Furthermore, it is speculated that the silicon or siloxane functionality of the diluent advantageously affects the solubility of the silicone oil in the diluent and thus also advantageously affects the uniform distribution of the silicone oil in the formulation, which in turn achieves high uniformity of the corresponding coating.

[0015] In contrast, formulations containing silicone-free solvents (such as toluene) as diluents cannot produce uniform layers. In such cases, increasing the diluent content cannot significantly improve layer performance.

[0016] On the other hand, in the formulations according to the invention, even higher proportions of diluent have proven advantageous in terms of the layer properties of the corresponding layers. Therefore, in the extended embodiment, the proportion of diluent in the formulation is at least 60% by weight, preferably greater than 70% by weight, particularly preferably greater than 80% by weight, and even more particularly preferably greater than 82% by weight. Thus, the diluent in the formulation can easily exceed 4 / 5 of the total weight, and the sliding layer prepared therefrom has very good performance.

[0017] Low layer strength typically leads to the failure of the sliding layer, as it is peeled off as the plug moves through the hollow body, or even separates from the inner wall without external force. Consequently, the desired coefficients of static and sliding friction (“HGR coefficients”) are often unattainable. For example, excessively low levels of HMDSO as a diluent indicate that polymerization of the reaction solution is reduced to such an extent that the reaction solution flows downwards from the upright sample in the hollow body and accumulates on the substrate.

[0018] In this context, the beneficial effect of high concentrations of diluent or solvent in the formulation on the layer strength of the crosslinked layer is quite surprising. Low concentrations of reactive groups typically result in lower degrees of polymerization and thus weakly crosslinked layers. However, in the crosslinking of the formulation according to the invention, surprisingly, despite high solvent or diluent ratios in the formulation, layers with high crosslinking degree and high layer strength are still obtained.

[0019] Furthermore, it can be observed that the wetting of the formulation with a high proportion of diluent is very uniform. Therefore, with the diluent content according to the invention, no islands of the formulation, such as the so-called lotus effect, occur on the substrate to be wetted. This results in uniform wetting of the surface. Therefore, according to one embodiment of the invention, at a temperature of 23°C, after one second, the contact angle of the formulation on clean borosilicate glass is less than 28°, more preferably less than 26°, more preferably less than 24°, more preferably less than 22°, more preferably less than 20°, more preferably less than 18°, more preferably less than 15°, more preferably less than 12°, more preferably less than 10°, and more particularly preferably less than 5°. In this case, the contact angle decreases with increasing diluent content.

[0020] Alternatively or additionally, according to another embodiment, a 10 µl (microliter) droplet of the formulation applied to a clean borosilicate glass surface at 23°C spreads in the range of 7.3 to 20 mm, preferably in the range of 7.5 to 18 mm, particularly in the range of 7.9 to 17 mm, more preferably in the range of 9 to 16 mm, even more preferably in the range of 9.5 to 15 mm, even more preferably in the range of 10 to 14 mm, even more preferably in the range of 11 to 13.5 mm, and particularly preferably in the range of 12 to 13 mm. In this case, the spreading is determined by measuring the droplet size using an optical microscope 5 seconds after the droplet is applied.

[0021] According to the present invention, a high proportion of diluent in the formulation also advantageously affects the wetting rate and the crosslinking rate. Therefore, the crosslinking rate increases with the concentration of diluent in the formulation, allowing the formulation to be applied more quickly.

[0022] The formulation has a diluent content that ensures rapid crosslinking and uniform application of the formulation on the substrate to be coated, as well as advantageous spread of the formulation on the substrate. Conversely, formulations with a diluent content greater than 95% by weight can no longer be applied uniformly. Furthermore, the corresponding formulation no longer exhibits any measurable spread. Moreover, the layers obtained after diluent evaporation have only a very small thickness, thus these layers only have insufficient sliding effect. Furthermore, from an economic point of view, it is disadvantageous to apply the correspondingly diluted formulation with an additional proportion of solvent, which does not positively affect the layer performance.

[0023] Furthermore, the formulation according to the invention is highly advantageous in terms of the amount of organosilicon it contains. Therefore, the concentration of the organosilicon mixture can be adjusted by the amount of diluent in the formulation, thereby giving the corresponding coating the minimum layer thickness required for the desired tribological properties. This prevents the application of excessive organosilicon mixture and excessively thin layers. In this case, such a formulation has proven particularly advantageous, wherein the proportion of diluent in the formulation is 45% by weight or more and 95% by weight or less, preferably greater than 45% by weight and less than 95% by weight, more preferably 50% by weight or more and less than 95% by weight, more preferably 55% by weight or more and less than 95% by weight, more preferably 60% by weight or more and less than 95% by weight, more preferably 65% ​​by weight or more and less than 95% by weight, more preferably 70% by weight or more and less than 95% by weight, more preferably 75% by weight or more and less than 95% by weight, more preferably 80% by weight or more and less than 90% by weight, and most preferably 83% by weight or more and 88% by weight or less.

[0024] According to one embodiment of the invention, the viscosity of the formulation at a temperature of 23°C is in the range of 0.5 to 200 mPas, preferably in the range of 1 to 50 mPas, and particularly preferably in the range of 1 to 10 mPas.

[0025] Alternatively or additionally, according to one embodiment of the invention, the viscosity of the formulation at a temperature of 23°C can be in the range of 1 to 50,000 cSt, preferably in the range of 10 to 35,000 cSt, more preferably in the range of 1,000 to 30,000 cSt, more preferably in the range of 2,500 to 22,000 cSt, more preferably in the range of 5,000 to 18,000 cSt, and even more particularly preferably in the range of 8,000 to 10,000 cSt.

[0026] In the context of this invention, the diluent can be a silicon-containing compound, preferably a Si-containing solvent, more preferably a Si-containing organic solvent in which reactive silicone systems and non-reactive silicone oils are soluble. To ensure good solubility of the silicone component in the formulation according to the invention, a non-polar solvent is preferably used as the diluent. In this case, it has proven particularly advantageous to use an organosilicon compound having at most six silicon atoms as the diluent.

[0027] A particularly suitable diluent is: Cyclic organosilicones, particularly: octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecylcyclohexasiloxane, tetramethylcyclotetrasiloxane, and pentamethylcyclopentasiloxane. Hexamethyldisiloxane (HMDSO) Octamethyltrisiloxane, Decamethyltetrasiloxane.

[0028] As a diluent, mixtures, especially mixtures containing one or more of the above substances, can also be used.

[0029] Reactive organosilicon systems used to form organosilicon networks include polysiloxanes having crosslinkable groups. The reactive organosilicon system is preferably a multi-component system, and particularly preferably a two-component system. Not only high-temperature crosslinked organosilicon multi-component systems (HTV systems) but also low-temperature or room-temperature crosslinked organosilicon multi-component systems (RTV systems) have been tested and proven suitable. In this case, the reactive organosilicon system contains functional groups capable of undergoing crosslinking reactions.

[0030] In this configuration, the reactive organosilicon system preferably comprises a first component and a second component. The first component has at least one first functional group, and the second component has multiple second functional groups. The first and second functional groups react with each other to form common bonds. In this configuration, the first and second functional groups can have different or the same chemical forms. For example, both the first and second functional groups can be vinyl groups.

[0031] Preferably, the proportion of the first component in the reactive organosilicon system is higher than that of the second component. Preferably, the mass ratio of the first component to the second component is 10:1 to 30:1. Therefore, the first component forms the basis of the organosilicon network generated during crosslinking, while the second component acts as a crosslinking agent.

[0032] According to an improved embodiment, the first component comprises a vinyl-functionalized polysiloxane and the second component comprises a polysiloxane having Si-H groups. A preferred embodiment comprises a vinyl-functionalized polydimethylsiloxane as the first component and a copolymer having dimethylsiloxane and methylhydrosiloxane monomer units as the second component. In this case, it has proven particularly advantageous to use a copolymer having the following structure: .

[0033] The number of crosslinking points in the sliding layer can be adjusted by the ratio m / n and the arrangement of the two monomer units in the copolymer, and thus the degree of crosslinking can be adjusted.

[0034] Furthermore, the viscosity of the formulation is also affected by the viscosity of the silicone oil it contains. Therefore, according to one embodiment of the invention, the viscosity of the non-reactive silicone oil is in the range of 2,500 to 50,000 cSt, preferably in the range of 5,000 to 35,000 cSt, and particularly preferably in the range of 18,000 to 22,000 cSt.

[0035] The formulation also contains a catalyst for the crosslinking reaction of the components in the organosilicon multicomponent system. Particularly preferred is a soluble platinum-containing catalyst, such as chloroplatinic acid.

[0036] According to one embodiment of the invention, the catalyst is present in a proportion of 0.001-5% by weight of the reaction solution, preferably 0.01-1.5% by weight. It has proven particularly advantageous that the weight ratio of the catalyst to the reactive organosilicon system is in the range of 0.01 to 0.2, preferably in the range of 0.01 to 0.1. In this case, the degree of polymerization or crosslinking of the sliding layer can be adjusted by the catalyst proportion. When the amount of catalyst is too small, the polymerization or crosslinking reaction occurs very slowly. Conversely, when the amount of catalyst is very high, crosslinking occurs so rapidly that in some cases the heat of reaction released in the crosslinking reaction cannot be removed, and thus the diluent evaporates. Therefore, the amount of diluent decreases, thereby increasing the viscosity of the reaction solution. This, in turn, can lead to a low degree of crosslinking or polymerization due to the fixation of the polymer chains. In this case, the corresponding sliding layer has only low stability.

[0037] According to a particularly preferred embodiment, the formulation comprises at least one inhibitor for suppressing spontaneous reactions in the reactive organosilicon system. This is advantageous for controlling the formulation until the application of the sliding layer. Furthermore, the inhibitor has not been shown to be detrimental to the sliding properties and strength of the layer. In particular, organic compounds with triple bonds have been shown to be suitable inhibitors. In this case, the inhibitor can form a reversible complex with the catalyst, thereby suppressing spontaneous crosslinking reactions in the reactive organosilicon system.

[0038] The present invention also relates to a method for producing encapsulated components. According to this method, a formulation is applied as a layer to the inside of a hollow body, and then a reaction is initiated between the components of an organosilicon multicomponent system to form an organosilicon network and obtain a cured sliding layer.

[0039] In this case, the formulation can be applied using a simple application process, such as spraying or smearing it onto the inner wall of the container.

[0040] Curing, or crosslinking, is preferably performed by heating the applied layer to a temperature in the range of 150 to 280°C. Temperature treatment can be particularly performed by infrared radiation or convection current. Through temperature treatment, a crosslinking reaction occurs in the reactive silicone oil system. Simultaneously, the diluent evaporates at least partially. Alternatively, curing can be performed by plasma at significantly lower temperatures.

[0041] In particular, when the thickness of the sliding layer is less than 3 μm, a durable sliding layer or sliding film is obtained. A layer thickness of less than 1 μm is especially preferred. To ensure sufficient storage of silicone oil in the layer and continuous coverage of the intended sliding surface, it is advantageous to have a layer thickness of at least 0.4 μm, preferably at least 0.5 μm. In this case, the corresponding sliding layer exhibits high mechanical stability. Furthermore, the sliding layer displays high resistance to water and chemicals such as ethanol or detergents. High resistance in the context of this invention is specifically understood to mean that after treating the sliding layer with the aforementioned substances, sliding friction does not increase, or at least does not increase persistently.

[0042] It has been shown in a surprising way that, upon cleaning the sliding layer, the hollow body prepared by the method according to the invention can at least partially regenerate its static-sliding friction properties. Therefore, after cleaning the sliding layer, the original static-sliding friction can be at least partially regenerated through storage, for example, under the influence of heat, or directly before inserting the plug or filler. Thus, the encapsulation according to the invention has regenerative properties.

[0043] Therefore, when the surface of the sliding layer is cleaned, or when non-reactive organosilicon that contributes significantly to the sliding action is removed from the surface, the sliding layer prepared by the method according to the invention or by the formulation described herein has the special property of layer regenerability in terms of sliding action, in addition to very low static and sliding friction coefficients.

[0044] Regeneration performance can be assessed by cleaning the layer surface with ethyl acetate. The HGR value is determined before and after cleaning, and, if necessary, after regeneration treatment (e.g., storage, and, if necessary, at elevated temperatures).

[0045] Furthermore, the present invention also relates to a package for pharmaceuticals or cosmetics, the package comprising a cylindrical hollow body coated on its inner side with a sliding layer, wherein the sliding layer has an organosilicon network containing silicone oil. This design of the hollow body allows a plug to be inserted into the hollow body, and the static friction coefficient of the plug inserted into the hollow body on the sliding layer is up to 20%, preferably up to 10%, particularly preferably up to 5%, greater than the average sliding friction coefficient. Therefore, in these sliding layers, the static friction coefficient and the sliding friction coefficient are almost the same, whereas the prior art system has a significantly higher static friction coefficient relative to the sliding friction coefficient compared to the average sliding friction. This, for example, can cause the plug moving on the sliding layer to not experience uniform movement, but rather to be pushed in uncontrolled and rapidly after overcoming static friction. Conversely, the package according to the invention allows for very uniform and controlled movement of the plug through the hollow body.

[0046] The static and sliding friction coefficients are determined by moving a suitable stopper directly through a hollow body at a constant speed of 100 mm / min after insertion, and measuring the force required for this as a function of insertion depth. At the start of the stopper's movement, typical static and sliding friction graphs show a linear increase in force. Once the static friction force is overcome, the stopper will begin to move and slide through the cylinder, requiring a relatively constant thrust under good sliding conditions. The maximum value that typically appears on the static-sliding friction graph immediately before the start of the stopper's sliding motion represents the static friction coefficient. The relatively constant force during the sliding motion represents the sliding friction coefficient. Static-sliding friction graphs are typically measured using a stopper, which is also used as a stopper in primary pharmaceutical packaging to achieve the corresponding seal without requiring excessive force.

[0047] Preferably, a standard stopper is used. In the sense of this application, the standard stopper is made of an elastomer polymerized by cross-linking / vulcanization. The standard stopper may be coated with a very thin layer of silicone, as the stopper is typically vulcanized in a mold coated with an anti-stick coating, for example, made of silicone, for demolding. Furthermore, the standard stopper has an outer diameter slightly larger than the inner diameter of the sliding piston, so that it is under compression when inserted. Thus, in the case of a syringe with a typical inner diameter of 6.5 mm for a "1 ml long" syringe, the stopper may, for example, have an outer diameter of 6.9 + / - 0.1 mm.

[0048] According to an advantageous design of the invention, when the standard plug moves on the sliding layer at a speed of 100 mm / min, the static friction coefficient and / or sliding friction coefficient is less than 10 N, preferably less than 8 N or even less than 6 N.

[0049] The inventors have recognized that the encapsulation according to the invention has a surprisingly regenerative effect. Therefore, according to one embodiment of the invention, the sliding layer has a regenerative effect, such that the sliding action of the sliding layer is regenerated after the silicone oil is removed from its surface. It can be seen that such an encapsulation is highly advantageous if, for example, it is cleaned before being filled with pharmaceuticals or cosmetics. In this context, in the sense of the invention, particularly when the sliding friction is raised from an initial level to a higher level, determined within a period of less than 5 minutes after cleaning the silicone oil, and the sliding friction decreases significantly again after a regeneration period of more than 10 minutes after cleaning the silicone oil, the sliding layer is referred to as having a regenerative effect. If the sliding friction does not return to the initial level (i.e., the coefficient of friction before cleaning the silicone oil) after cleaning the silicone oil and the subsequent regeneration time, then in this case, the regenerative effect can also be understood as a decrease in sliding friction after cleaning.

[0050] Sliding layers are particularly suitable for containers made of plastics, especially those made of polyolefins (e.g., cyclic olefin copolymers (COC) or cyclic olefin polymers (COP)). Another suitable material is glass, particularly borosilicate glass, preferably glass of class 1b according to ISO 719. Another suitable class of glass is aluminosilicate glass. Silicate glasses having an Al₂O₃ content greater than 6% by weight are called aluminosilicate glasses.

[0051] Surprisingly, a durable sliding layer can also be applied to polyolefin substrates such as COC or COP, even though polyolefins do not contain silicon and therefore cannot covalently bond a silicone oil network on the substrate via Si-Si or Si-O bonds. Unwilling to be bound by this assumption, the inventors hypothesize that a silicon-containing diluent acts as an intermediary between the nonpolar silicon-free substrate and the silicone network. According to one embodiment of the invention, the container is thus made of a silicon-free material. Surprisingly, not only in the case of silicon-free materials but also in the case of silicon-containing container materials such as borosilicate glass or aluminosilicate glass, a primer is not required for applying the sliding layer and for durable curing. Therefore, according to another embodiment of the invention, the formulation is applied directly to the inside of the container without pretreatment with a primer and subsequently cured. Thus, the sliding layer can be applied directly to the inner surface of the container.

[0052] According to an extended embodiment of the invention, the roughness of a plastic surface can be reduced by using the layer according to the invention. In this case, the roughness of the sliding layer is less than 40 nm, preferably less than 20 nm.

[0053] Polydimethylsiloxane is particularly suitable for use as a non-reactive silicone oil. Generally, non-reactive silicone oils are advantageous if the chain length is not very large, as this has a favorable effect on the regeneration capability of the sliding layer. Polydimethylsiloxane has an average chain length, or correspondingly an average molar mass, that is so small that it still exists as an oil at room temperature (23°C), i.e., as a fluid.

[0054] A sliding surface may be specifically arranged in the syringe or capillary to facilitate the sliding of the stopper or piston for the extraction and / or delivery of pharmaceuticals or cosmetics. Therefore, according to one embodiment, the package is a syringe or capillary. In this case, the sliding layer preferably covers at least the area inside the hollow body on which the stopper can slide.

[0055] This characteristic is clearly produced by a specific formulation with a high proportion of diluent, and is unrelated to the regeneration ability of the sliding layer after the silicone oil is removed.

[0056] In a preferred embodiment, the sliding layer has a sliding friction coefficient µ. G and static friction coefficient µH ratio µ G / µ H， It is greater than 0.80. Preferably, the ratio µ G / µ H The static friction is at least greater than 0.9 or even 0.95. Therefore, in these sliding layers, the static friction and sliding friction are almost equal, whereas in the prior art, the static friction is much greater. This could, for example, cause a plug moving on the sliding layer to stop instead of experiencing uniform motion.

[0057] The invention will now be explained with reference to the embodiments and accompanying drawings. Attached Figure Description

[0058] Figure 1 The image shows a syringe-type package for pharmaceuticals or cosmetics.

[0059] Figure 2 A graph showing the coefficient of friction for the plug displacement of ten syringes is displayed.

[0060] Figure 3 The graph shows the coefficient of friction of the stopper displacement after the syringe has been treated in water with ultrasound for 60 seconds.

[0061] Figure 4 The graph shows the coefficient of friction of the stopper displacement after the syringe was treated in 0.1M NaOH aqueous solution for 60 seconds, with a storage time of 30 minutes before measurement.

[0062] Figure 5 A graph showing the coefficient of friction of the stopper displacement after the syringe has been treated with ultrasound in acetone for 60 seconds is displayed.

[0063] Figure 6 The graph shows the coefficient of friction of the plug displacement after removing the non-reactive silicone oil from the sliding layer (by ultrasonic treatment with ethyl acetate for more than 60 seconds).

[0064] Figure 7 The graph shows the coefficient of friction of the plug displacement after the non-reactive silicone oil was removed from the sliding layer and the plug was subsequently stored at room temperature for 24 hours.

[0065] Figure 8 The graph shows the coefficient of friction of the plug displacement after the non-reactive silicone oil was removed from the sliding layer and the plug was subsequently stored at 40°C for 24 hours. Detailed Implementation

[0066] Example 1 In the first embodiment, 10 g of vinyl-functionalized polydimethylsiloxane was placed in a reaction vessel and 65 g of decamethylcyclopentasiloxane was added. Under constant stirring at 800 rpm, 0.5 g of methylhydrosiloxane-dimethylsiloxane copolymer, 6.25 g of liquid polydimethylsiloxane, 0.01 g of isopropanol containing 10% hexachloroplatinic acid as a catalyst, and 0.05 g of 2,4,7,9-tetramethyl-5-decyn-4,7-diol as an inhibitor were added to the reaction mixture. After stirring for 60 seconds, the reaction solution was ready for use. In this case, the vinyl-functionalized polymethylsiloxane and the methylhydrosiloxane-dimethylsiloxane copolymer form a reactive organosilicon system, the polydimethylsiloxane forms a non-reactive silicone oil, and the decamethylcyclopentasiloxane forms a diluent.

[0067] The prepared formulation was applied to the inside of a hollow plastic body via a wiping process and cured by heating to 175°C for 20 seconds. In this case, a standard-sized 1ml COC syringe with an inner diameter of 6.5mm ("1ml long") was used as the substrate for depositing the sliding layer. Subsequently, the static and sliding friction coefficients of the cured sliding layer were determined. Here, a Datwyler Pharma Packaging V9361FM457 / 0FLNC2057 stopper with an outer diameter of 6.9+ / -0.1mm was pressed into the syringe at a speed of 100mm / min. The force required was recorded. Here, both the static and sliding friction coefficients were less than 10N. The measurement results were... Figure 2 As shown in the image.

[0068] Example 2 In the second embodiment, 80g of vinyl-functionalized polydimethylsiloxane was placed in a reaction vessel and 640g of hexamethyldisiloxane was added. Under constant stirring at 1000rpm, 2g of methylhydrosiloxane-dimethylsiloxane copolymer, 48g of liquid polydimethylsiloxane, 1.1g of 1,1,3,3-tetramethyl-1,3-divinyldisiloxane platinum complex, and 0.1g of butynediol as an inhibitor were added to the reaction mixture. After stirring for 60 seconds, the formulation was ready for use.

[0069] The formulation was applied to the inside of the hollow plastic body via a wiping process and cured by heating to 250°C for 3.5 seconds. In this case, a standard-sized 1ml COC syringe with an inner diameter of 6.5mm ("1ml long") was used as the substrate for depositing the sliding layer. Subsequently, the static and sliding friction coefficients of the cured sliding layer were determined. Here, a Datwyler Pharma Packaging V9361FM457 / 0FLNC2057 stopper with an outer diameter of 6.9+ / -0.1mm was inserted into the syringe at a speed of 100mm / min. The force required was recorded. Both the static and sliding friction coefficients were less than 10N.

[0070] Table 1 shows the surface roughness values ​​of the untreated syringe made of COC and the corresponding syringe surface roughness after the application of the sliding layer of the present invention.

[0071] Table 1: Comparison of roughness values Roughness values ​​are determined using a white light interferometer according to DIN EN ISO / IEC 17025.

[0072] Example 3 In the third embodiment, 80g of vinyl-functionalized polydimethylsiloxane was placed in a reaction vessel and 640g of decamethylcyclopentasiloxane was incorporated. Under constant stirring at 1000 rpm, 2g of methylhydrosiloxane-dimethylsiloxane copolymer, 48g of liquid polydimethylsiloxane, 1.1g of isopropanol containing 10% hexachloroplatinic acid as a catalyst, and 0.1g of butynediol as an inhibitor were added to the reaction mixture. After stirring for 60 seconds, the formulation was ready for use.

[0073] The formulation was applied to the inside of the hollow plastic body via a wiping process and cured by heating to 250°C for 3.5 seconds. In this case, a standard-sized 1ml COC syringe with an inner diameter of 6.5mm ("1ml long") was used as the substrate for depositing the sliding layer. Subsequently, the static and sliding friction coefficients of the cured sliding layer were determined. Here, a Datwyler Pharma Packaging V9361FM457 / 0FLNC2057 stopper with an outer diameter of 6.9+ / -0.1mm was inserted into the syringe at a speed of 100mm / min. The force required was recorded. Both the static and sliding friction coefficients were less than 10N.

[0074] The sliding layer according to the invention has a low roughness. Specifically, the roughness Rms of the sliding layer is at most 40 nm, preferably at most 30 nm, and particularly preferably at most 20 nm. Due to the low roughness, particularly low static and sliding friction coefficients can be achieved. Furthermore, according to an improvement of the invention, the roughness of the substrate used can be reduced by applying the sliding layer of the invention. This is particularly advantageous when using plastic substrates, such as COC substrates, which have a greater roughness than glass. According to one embodiment of this improvement, the roughness Rms of the substrate coated with the sliding layer of the invention is reduced by at least 20%, preferably at least 40%, and particularly preferably at least 40%, compared to a corresponding uncoated substrate.

[0075] The following comparative examples will illustrate the impact of each component on the performance of the formulation or the sliding layer.

[0076] Comparative Example 1: The Effect of Diluent Content 80g of vinyl-functionalized polydimethylsiloxane was placed in a reaction vessel and mixed with 80g of hexamethyldisiloxane. Under constant stirring at 400 rpm, 2g of methylhydrosiloxane-dimethylsiloxane copolymer, 48g of liquid polydimethylsiloxane, 1.1g of isopropanol, 10% hexachloroplatinic acid as a catalyst, and 0.1% butynediol as an inhibitor were added to the reaction mixture. After stirring for 60 seconds, the reaction solution was ready for use.

[0077] The reaction solution is applied to the inside of the hollow plastic body by wiping and then cured by heating to 250°C for 3.5 seconds.

[0078] However, when stored upright with the opening facing downwards, the reaction solution does not remain completely within the hollow plastic body, or, in the case of horizontal storage, it accumulates at the bottom of the hollow plastic body. Due to the height inhomogeneity of the layers within the hollow plastic body, measurements of the static or sliding friction coefficients are not possible.

[0079] Compare with Example 2 (the effect of diluent) In this comparative example, toluene was used as a diluent, standing out due to its nonpolarity and lack of Si atoms. Therefore, 80 g of vinyl-functionalized polydimethylsiloxane was placed in a reaction vessel and 640 g of toluene was added. Under constant stirring at 400 rpm, 2 g of methylhydrosiloxane-dimethylsiloxane copolymer, 48 g of liquid polydimethylsiloxane, 1.1 g of 1,1,3,3-tetramethyl-1,3-divinyldisiloxane platinum complex as a catalyst, and 0.1 g of butynol as an inhibitor were added to the reaction mixture. After 60 seconds of stirring, the reaction solution was ready for use.

[0080] The formulation was applied to the inside of the hollow plastic body by wiping and then attempted to be cured by heating to 250°C for 3.5 seconds.

[0081] The formulation exhibited severe wetting defects and failed to form any uniform film. Strong droplet formation was observed. The reaction solution did not fully solidify. Due to the high degree of inhomogeneity within the hollow plastic layer, measurements of the static or sliding friction coefficients were not possible. Therefore, it is clear that the diluent cannot be selected solely based on its compatibility (i.e., the solubility of the individual formulation components).

[0082] Compare with Example 3 (the effect of diluent) Comparable results were also obtained in the third comparative example.

[0083] 80g of vinyl-functionalized polydimethylsiloxane was placed in a reaction vessel and 640g of cyclohexane was added. Under constant stirring at 400rpm, 2g of methylhydrosiloxane-dimethylsiloxane copolymer, 48g of liquid polydimethylsiloxane, and 1.1g of 1,1,3,3-tetramethyl-1,3-divinyldisiloxane platinum complex were added as a catalyst.

[0084] The reaction solution was applied to the inside of the plastic hollow body by wiping and then attempted to be cured by heating to 250°C for 3.5 seconds.

[0085] The reaction solution exhibited severe wetting defects and failed to form any uniform film. Droplet and streak formation was observed. The reaction solution did not completely solidify. Due to the high degree of inhomogeneity within the hollow plastic layer, measurements of the static or sliding friction coefficients were not possible.

[0086] Compare with Example 4 (catalyst amount) 80 g of vinyl-functionalized polydimethylsiloxane was placed in a reaction vessel and 640 g of toluene was added. Under constant stirring at 400 rpm, 2 g of methylhydrosiloxane-dimethylsiloxane copolymer, 48 g of liquid polydimethylsiloxane, and 11 g of 1,1,3,3-tetramethyl-1,3-divinyldisiloxane platinum complex were added as a catalyst. In this comparative example, the catalyst proportion was 1.4% by weight. The catalyst weight to reactive organosilicon system weight ratio was 1:7.45.

[0087] Due to the significantly increased proportion of catalyst, the formulation exhibits a strong exothermic reaction while simultaneously forming a gas. In this case, it can be inferred that it is gaseous toluene. The formulation gels and it is impossible to apply a thin film.

[0088] The composition of other embodiments and comparative examples is listed in Table 2.

[0089] Table 2: Composition of Examples A to E Examples B to D are embodiments, while Example A is a comparative example, whose formulation has a lower diluent ratio (40% by weight) compared to the formulation according to the invention, and Example E is a comparative example, whose formulation has a higher diluent ratio (99% by weight) compared to the formulation according to the invention.

[0090] Table 3 shows the measurement results used to determine the spreading behavior of each example A to E. For this purpose, a 10 µl drop of the corresponding formulation was applied to a clean borosilicate glass plate at a temperature of 23 °C. The droplet size, i.e., the lateral dimension of the droplet on the glass surface, was measured using an optical microscope. In this case, the first measurement (t0) was taken as soon as possible after droplet formation, i.e., within 1 second after the droplet was applied to the glass surface.

[0091] Table 3: Spreading Behavior The times given in Table 3 represent the time interval between t0 and the determination of the droplet's spread on the glass surface. For example E, spread can no longer be determined after 60 seconds because most of the formulation has evaporated at that time.

[0092] Table 4 shows the results of the droplet morphology analysis used to determine the contact angle.

[0093] Table 4: Contact Angle To determine the contact angle, drop shape analysis (DSA) was used. This drop shape analysis is an image analysis method used to determine the contact angle from the shadowed image of a droplet located on a glass surface. In this case, a single drop of formulation was applied to a clean borosilicate glass plate at 23°C. Images of the droplets were captured using a camera and transmitted to the DSA software. Shape recognition was performed based on the analysis of the image's grayscale levels, and then a geometric model describing the droplet shape was fitted to the droplet shape. The angle between the droplet shape and the sample surface was thus determined as the contact angle.

[0094] Figure 1A package 1, representing a particularly preferred embodiment of the invention, is shown as a syringe 3 for administering pharmaceuticals or cosmetics. The syringe 3, made of, for example, glass or preferably plastic, is a hollow body 5 having a cylindrical portion 7 and a Luer conical connector 18 on which an injection needle can be placed. A stopper 12 is inserted into the cylindrical portion, which can be moved axially by pressure on a push rod 13. For operation, the cylindrical portion has a flange 15 at the end for the insertion opening of the stopper 12.

[0095] On the inner side of the package, particularly on the inner side of the cylindrical portion 7, a sliding layer 10 is provided. Thus, the sliding layer covers the area inside the hollow body 5, allowing the stopper 12 to slide in this area when the syringe is emptied or withdrawn.

[0096] The sliding layer 10 is formed as an organosilicon network, in which silicone oil is contained.

[0097] The sliding layer 10, which can be manufactured using the formulations and methods described herein, is typically characterized by a low and highly uniform coefficient of friction during stopper movement. This involves both variations in the coefficient of friction along the stopper's displacement path and differences between different encapsulation components.

[0098] Figure 2 The graphs demonstrate this. The graph shows the coefficient of friction during the movement of the stopper used in ten different syringes. Frictional forces were recorded for the entire possible displacement path. To measure the static-sliding friction curves, the stopper was inserted into the syringe, and the static-sliding friction curves were recorded. As shown, the maximum fluctuation between various test samples is approximately one Newton, where material tolerances and stopper dimensions also contribute significantly. Furthermore, from... Figure 2 It can also be clearly seen that the ratio of the friction coefficients of all measured syringes, µ G / µ H Greater than 0.95. The results are summarized in Table 5.

[0099] Table 5: In Figure 2 The measured static friction coefficient and sliding friction coefficient shown are... Here, the ratio µ G / µ H The friction coefficients can be directly read from the coefficients listed in Table 5. Therefore, the force measured at the beginning of the plug's displacement process can be directly attributed to static friction, and the average sliding friction can be distributed to the force measured during the displacement process. The force F listed in Table 5... 滑动摩擦This represents the average sliding friction coefficient obtained from all measurements taken during the displacement of the plug within the range of 3 to 30 mm. Therefore, the ratio µ can be determined by dividing the two force values. G / µ H .

[0100] When considering only a single syringe, the fluctuations along the displacement path are remarkably small. The fluctuation of sliding friction along the path is less than 0.5 Newtons in all cases. This is beneficial for ensuring uniform movement and force application when delivering the contents of the package. In the example shown, the sliding friction is between 4 and 5 Newtons. Although the absolute magnitude of the frictional force also depends on the size, the relative fluctuation is a quantity substantially independent of the size. Without being limited to the specific embodiment shown, for this purpose, according to one implementation, the fluctuation of friction along the movable path of the stopper is at most one-tenth of this average frictional value.

[0101] Also noteworthy is that, due to the increase in static friction, the curve does not actually show any superelevation at the start of the movement.

[0102] The sliding layer prepared using this formulation has also proven resistant to various treatments performed on the internal space of the hollow body. Figure 3 An example of this situation is shown in the image. Figure 2 Thus, the graph shows the measured frictional force as the stopper moves along the syringe on the sliding layer. Ten more samples were measured. The syringes were ultrasonically treated in water for 60 seconds before measurement. Figure 2 The comparison of the measured values ​​showed that friction was unaffected, especially after ultrasonic treatment, there was no significant increase in friction.

[0103] Figure 4 Similarly, the measured frictional force of the syringe stopper moving on the sliding layer after ultrasonic treatment in a 0.1M NaOH aqueous solution for 60 seconds is shown. Here, friction is also almost unaffected, indicating that the sliding layer has high stability even at high pH values.

[0104] exist Figure 5 The figure shows the measured frictional force as the stopper moves along the sliding layer after the corresponding syringe has been ultrasonically treated in acetone for 60 seconds. The friction is almost unaffected by the treatment, indicating that the sliding layer has high resistance to polar organic solvents.

[0105] Figures 6 to 8 The regeneration capability of the sliding layer according to the present invention is demonstrated. Here, the regeneration performance was tested by cleaning the layer surface with ethyl acetate (using ultrasonic cleaning for 60 seconds). After cleaning ( Figure 6 And, if necessary, after regeneration treatment (e.g., storage, and, if necessary, at elevated temperatures), Figure 7and 8 Determine the HGR value.

[0106] It has been surprisingly found that hollow plastic bodies produced by the method according to the invention can at least partially regenerate their static-sliding friction properties upon cleaning of the sliding layer. Although measurements were taken immediately after cleaning ( Figure 6 The HGR value showed a significant increase, but the original static-sliding friction could be at least partially restored by storage. This can be achieved by means of... Figure 7 To demonstrate. Therefore, the syringe has regenerative capabilities.

[0107] from Figure 8 As can be seen, a slightly higher temperature is particularly advantageous in this regard.

[0108] Conversely, if the silicone network is largely damaged by mechanical action, such as by cleaning with a pipe cleaner, then the regeneration effect can no longer be observed.

[0109] List of reference numerals

Claims

1. A formulation for application onto the inner side of a hollow body to create a sliding layer on a package for pharmaceuticals or cosmetics, wherein, The liquid formulation includes: - A reactive organosilicon system for forming the organosilicon network of the sliding layer. -A catalyst for catalyzing the crosslinking reaction of the aforementioned reactive organosilicon system. - At least one non-reactive silicone oil, - and at least one diluent, The diluent comprises a silicon-containing compound, and the content of the diluent in the formulation is more than 45% by weight and less than 95% by weight of the formulation.

2. The formulation according to claim 1, characterized in that, The reactive organosilicon system is a multi-component system, preferably a two-component system.

3. The formulation according to any one of the preceding claims, characterized in that, It has at least one of the following characteristics: -The diluent comprises a silicon-containing organic compound having up to 6 silicon atoms. -The diluent has a surface tension of less than 19 mN / m; Preferably, the formulation has at least one of the following diluents: - Cyclic organosilicones, particularly octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecylcyclohexasiloxane, tetramethylcyclotetrasiloxane, and pentamethylcyclopentasiloxane. - Hexamethyldisiloxane (HMDSO) -Octamethyltrisiloxane -Decamethyltetrasiloxane.

4. The formulation according to any one of the preceding claims, wherein, The viscosity of the formulation at 23°C is in the range of 1 to 50,000 cSt, preferably in the range of 10 to 35,000 cSt, and particularly preferably in the range of 2,500 to 22,000 cSt, and even more particularly preferably in the range of 8,000 to 10,000 cSt.

5. The formulation according to any one of the preceding claims, wherein, The viscosity of the formulation at a temperature of 23°C is in the range of 0.5 to 200 mPas, preferably in the range of 1 to 50 mPas, and particularly preferably in the range of 1 to 10 mPas.

6. The formulation according to any one of the preceding claims, wherein, At a temperature of 23°C, after 1 second, the contact angle of the formulation on the borosilicate glass surface is less than 28°, preferably less than 24°, particularly preferably less than 18°, and even more particularly preferably less than 5°.

7. The formulation according to any one of the preceding claims, wherein, At a temperature of 23°C, after 5 seconds, a droplet of the formulation with a volume of 10 µl spreads on a borosilicate glass surface in the range of 7.3 to 20 mm, preferably in the range of 7.9 to 17 mm, particularly preferably in the range of 9.5 to 15 mm, and even more particularly preferably in the range of 11 to 13.5 mm.

8. The formulation according to any one of the preceding claims, characterized in that, The formulation comprises an organometallic catalyst, preferably a platinum-containing catalyst, particularly preferably chloroplatinic acid; preferably, the catalyst is present in a proportion of 0.001-5% by weight, preferably 0.01-1.5% by weight, and / or the weight ratio of the catalyst to the reactive organosilicon system is in the range of 0.01 to 0.2, preferably in the range of 0.01 to 0.

1.

9. The formulation according to any one of the preceding claims, wherein, The formulation has an inhibitor for inhibiting spontaneous reactions in reactive organosilicon systems, and wherein the inhibitor is preferably an alkyne.

10. A method for producing a package for pharmaceuticals or cosmetics, wherein, The formulation according to any one of the preceding claims is applied as a layer to the inside of the hollow body of the encapsulation, and then the components of the organosilicon multi-component system are reacted to form an organosilicon network and obtain a cured sliding layer.

11. The method according to claim 10, characterized in that, The applied formulation is used to initiate the reaction of the components of the organosilicon multicomponent system by heating, preferably by heating to a temperature in the range of 150 to 280°C and / or by applying infrared radiation, convection or plasma.

12. The method according to any one of claims 10 or 11, characterized in that, Without pretreatment with a primer, the formulation is applied directly to the inside of the container and subsequently cured.

13. A package for pharmaceuticals or cosmetics, the package comprising a cylindrical hollow body (5) having a sliding layer (10) coated on its inner side, wherein the sliding layer (10) has an organosilicon network containing silicone oil, the hollow body being designed such that a plug can be inserted into the hollow body, and the static coefficient of friction of the plug inserted into the hollow body on the sliding layer is up to 20% greater than the average sliding coefficient of friction.

14. The package according to claim 13, wherein, The static friction coefficient of the plug inserted into the hollow body on the sliding layer is up to 10% greater than the average sliding friction coefficient, preferably up to 5%.

15. The package according to any one of claims 13 or 14, wherein, When the standard plug moves on the sliding layer at a speed of 100 mm / min, the static friction coefficient and / or sliding friction coefficient of the plug inserted into the hollow body is less than 10 N, preferably less than 8 N, and particularly preferably less than 6 N.

16. The package according to any one of claims 13 to 15, wherein, After the silicone oil is removed from the surface of the sliding layer, the sliding effect of the sliding layer is regenerated.

17. The package according to any one of claims 13 to 16, characterized in that, The thickness of the sliding layer is less than 3µm, preferably less than 1µm, and at least 0.4µm, preferably at least 0.5µm.

18. The package according to any one of claims 16 and 17, characterized in that, The container comprises at least one of the following materials: - Polyolefins, preferably COC or COP. - Glass, especially borosilicate glass or aluminosilicate glass. - Silicon-free materials.

19. The package according to any one of claims 13 to 18, wherein, The sliding layer is applied directly to the inside of the hollow body.

20. The package according to any one of claims 13 to 19, characterized in that, The encapsulation is a syringe or a capillary tube, and the sliding layer preferably covers at least the area inside the hollow body, on which the stopper of the syringe or capillary tube can slide.

21. The package according to any one of claims 13 to 20, wherein, sliding friction coefficient µ G and static friction coefficient µ H ratio µ G / µ H It is greater than 0.80, preferably greater than 0.9, and particularly preferably greater than 0.95.

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