• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    In the method of coating a one-component pressure-sensitive polysiloxane adhesive solution on a carrier of a suitable flat shape and dried to produce a pressure-sensitive polysiloxane adhesive layer, A complex of a metal ion of one of the group consisting of calcium, magnesium, zinc, aluminum, titanium, zirconium or hafnium and a low molecular weight organic complex former is added to the organic adhesive solution to be coated, and the adhesive solution is heated and / or Only when dried, the metal ions are released from the bond with the complex forming agent.
    公开号:KR20010041429A
    申请号:KR1020007009565
    申请日:1999-02-26
    公开日:2001-05-15
    发明作者:슈미쓰크리스토프；브라크트슈테판
    申请人:보도 아스무센；엘티에스 로만 테라피-시스템 악티엔게젤샤프트；
    IPC主号:
    专利说明:

    Pressure sensitive silicone adhesive with reduced low temperature fluidity {SILICONE CONTACT ADHESIVE WITH REDUCED COLD FLOW}
    Apart from other technical applications, the pressure sensitive adhesive formulations are mainly used in the manufacture of medical patches. Silicone pressure sensitive adhesives crosslinked by these novel methods are particularly suitable for the manufacture of medical patches, ie, transdermal absorption therapy systems (TTS), containing the active substance in medical patches.
    In coating and drying the solvent-containing pressure-sensitive silicone-based adhesive formulation, the above-mentioned crosslinking agent is used according to the present invention.
    Only under these conditions, the crosslinking agent causes a crosslinking reaction to form a three-dimensional polymer network structure.
    The pressure sensitive adhesive layer thus produced loses fluidity, the so-called cold flow.
    When flowed at a low temperature, both sides joined to each other by the pressure-sensitive adhesive layer can be displaced from each other even by their own weight, and as a result, low-temperature fluidity is not preferable because the positionless bonding between these surfaces can not be reliably achieved. It is not a phenomenon.
    In the case of TTS, this problem is of particular concern when adhesively bonding this system to the site of application for humans or animals. In addition, when a low temperature flow occurs in the silicone adhesive layer included in the TTS, deformation or dislocation may undesirably occur in the system even during storage due to the influence of self weight, cohesion and adhesion.
    Although silicone-based polymers and polyacrylates have fundamentally different chemical properties, it has surprisingly been found that the crosslinking agents used for crosslinking polyacrylate-based pressure-sensitive adhesives can be successfully used for silicone-based polymers.
    It has also been found that organometallic complexes of certain metal cations are particularly effective. Among them, complex compounds of metals such as aluminum, titanium, zirconium or zinc are particularly preferred in the present invention. As the organic complex former, acetylacetone is particularly suitable for medical use.
    When the crosslinking agent is added to the solution of the pressure-sensitive silicone adhesive, the crosslinking reaction occurs only after the solvent or stabilizer is removed by drying.
    Silicone-based polymer pressure sensitive adhesives are particularly important for medical applications. This is because the compatibility with the skin against the induction of skin inflammation and immune response (sensory, allergic) is excellent. In addition, pressure-sensitive silicone-based adhesives are products that adhere to human skin reliably and for a long time, that is, for several days. Their strong water repellent nature also plays an important role in this situation.
    In the field of TTS, the pressure-sensitive silicone-based adhesive is excellent in chemical compatibility with the pharmaceutically active agent and adjuvant, and improves the chemical stability and storage of the adhesive-based product. It is particularly important in view of facilitating the release of the active agent and the adjuvant, which also contains the high permeability (diffusion) of the silicone polymer.
    In addition to these advantages, the pressure-sensitive silicone-based adhesives (Dow Corning, Bio-PSA Q7 family) available on medical devices show significant deficiencies in rheological properties.
    These products are polysiloxane-based polymers which do not undergo three-dimensional crosslinking or exhibit crosslinking only in very limited microregions. They are actually threadlike and have a structure that branches only within a small range or does not branch at all.
    This product is required to be dissolved in organic solvents such as short-chain alkanes (heptane, petrol) or ethyl acetate, and therefore be able to apply them to solvent containing processes.
    Moreover, these conventional polymers are monocomponent polymer solutions.
    One-component means that the polymer contained in the solution does not become a two-component reaction between the usual resin and the curing agent in the next step.
    However, the meaning of one component does not mean that the solution does not contain at least one polyoxysiloxane polymer, and if necessary, the solution contains a mixture with chemically different polymers such as polyacrylates.
    The process for preparing a one-component pressure-sensitive polysiloxane solution, which will be described below, should not be confused with the production process and catalysts described variously for a two-component silicone adhesive. The system contains at least two different polysiloxanes to form a three-dimensional polymer network with conventional resins and hardeners in the following process.
    The polysiloxanes also include mixed polymers of polysiloxanes incorporating or adding chemically different polymer chains with polysiloxanes such as, for example, polyethylene oxide, polypropylene oxide, polyvinylpyrrolidone or poly (meth) acrylates.
    The TTS manufacturing field includes a process of coating and drying the pressure-sensitive polysiloxane adhesive solution to form a thin pressure-sensitive polymer film.
    In this process, the lack of three-dimensional crosslinking is disadvantageous in that the linear polymer chains are very slowly but have a constant flowability. The lack of three-dimensional crosslinking is referred to as low temperature fluidity because the lack of three-dimensional crosslinking occurs at room temperature.
    All of the following forces can promote fluidity:
    Self-weight
    2. Any mechanical force that may affect the product during the manufacturing process or storage.
    3. Adhesion between the pressure-sensitive polymer and the surface they cover, resulting in shrinkage or spreading
    4. Cohesion of the polymer itself (resulting in shrinkage)
    Low temperature fluidity has a substantially uncomfortable effect during storage of TTS (which may be more than two years). For example, it may result in adhesion between the product and the packaging material.
    This phenomenon undesirably occurs even when applied to human or animal skin, especially promoted by warm body temperature. When the TTS adheres for hours or days, displacement of the TTS can occur as the TTS substantially flows over the skin. In addition, the pressure sensitive silicone-based adhesive can spread on the skin by slowly flowing past the area where the original adhesive was applied. This often leaves residue on the skin along the edge region of the system after removal of the system. This residue is very annoying for the user.
    The problem of low temperature fluidity in pressure sensitive silicone based adhesives is known. US 5,232,702 discloses a number of possible measures. Various fillers and additives are described here, but no crosslinking agents are described.
    In addition, with respect to the active material system, the crosslinking reaction is described as problematic or impossible because the temperature required for the crosslinking reaction is too high or the biological compatibility of the crosslinking agent is insufficient (5 columns, 3 to 10 lines).
    Instead, many other means of improving cohesion have been described.
    Indeed, since these means may not always control the above problems, it is an object of the present invention to provide a new and more effective method for suppressing low temperature fluidity in pressure sensitive silicone based adhesives.
    The present invention relates to a crosslinking agent for crosslinking a pressure-sensitive silicone based polymer adhesive formulation.
    1 is a graph of cloud time versus titanium content when using titanyl acetylacetonate as crosslinking agent.
    FIG. 2 is a graph of cloud time versus aluminum content when aluminum acetylacetone is used as the crosslinking agent. FIG.
    3 is a schematic diagram of a method for measuring shear force of a film.
    4-7 is a graph of shear force / time
    This object is surprisingly achieved by adding chemicals which are used to inhibit low temperature fluidity in chemically completely different pressure sensitive adhesive polymer groups, ie polyacrylates.
    This conversion application was not foreseen because polysiloxanes, the skeletal structure of silicone-based polymers, had chemically different properties from those of pure hydrocarbon polyacrylates.
    For pressure-sensitive polyacrylate-based adhesives in which a polymer has a free carboxyl group or a free hydroxyl group, multivalent ions (e.g., calcium, magnesium or zinc, in particular aluminum and group 4B such as titanium, zirconium and hafnium) It is known that the three-dimensional crosslinking of polymer chains can be formed by the addition of an element). Only aluminum acts as a trivalent ion, and elements of group 4B are used in a stable oxidation state (+4).
    In this way, the transformation of the linear polymer chain layer into a fluidized three-dimensional network structure can be delayed until drying from solution is performed.
    On the one hand, in order to be able to use the metal ions in most organic solvents and to prevent premature crosslinking reactions in the polymer solution, on the other hand, low molecular weight complexing formers are used in which the metal ions are initially bound. Among these complex formers, acetylacetone plays an important role in the pharmaceutical field because it is relatively low toxicity and can be easily removed from the product during the drying process.
    Acetyl acetone is chemically a vinyl logic acid (vinylogous acid) in the form of an enol to form a complex with a metal ion (corresponding compound: acetylacetonate). Since these complex compounds have particularly stable chemical properties, they cannot be compared with organic acids and common salts of each metal.
    Aluminum acetylacetonate and titanyl acetylacetonate are used to crosslink a pressure-sensitive polyacrylate-based adhesive during drying from an organic solvent.
    In the crosslinking process, the metal ions are transferred from the complex former to the functional group of the acrylate polymer, whereby several functional groups of different polymer chains are crosslinked.
    It has been found that aluminum acetylacetonate and titanyl acetylacetonate, which are frequently used in polyacrylates as crosslinking agents, have surprisingly substantially the same effect when used in completely different polysiloxanes. That is, the fluidity | liquidity of a pressure-sensitive silicone type adhesive agent falls very much.
    Changes in the case of polysiloxanes are thought to occur, as in the case of polyacrylates, in which three-dimensional crosslinking occurs where the mechanism is unclear.
    The novel crosslinking method was tested with two groups in a pressure sensitive silicone based adhesive, which are of particular importance for medical use, amine incompatible and amine compatible on reduced pressure polydimethylsiloxane based adhesive.
    The amine non-compatible type is characterized in that the residue of silanol groups (hydroxyl groups bonded to silicon) remains in the polymer during polymerization. This is the standard form that can cause undesirable reactions between primary, secondary or tertiary amine groups and silanol groups.
    Since many pharmaceutically active substances contain amine groups, amine compatible forms can be used especially for TTS applications. They are so-called end capping (addition of suitable additives such as trimethylsilyl groups to inactivate silanol groups).
    A pressure-sensitive polyacrylate adhesive having a low proportion of free carboxyl groups was used as a control. It is conventionally known to three-dimensionally crosslink the acrylate with the crosslinking agent described herein.
    The following combinations were tested:
    Crosslinking agent: Al-acetylacetonate (% Al 3+ (W / W)) --- 0.01 0.025 0.05 Pressure Sensitive Polyacrylate AdhesiveDurotak 387-2051 A11 A12 A13 A14 Pressure Sensitive Silicone AdhesiveBio-PSA Q7-4602 S31 --- --- S32 Crosslinking agent: Ti-acetylacetonate (% Ti 4+ (W / W)) --- 0.05 0.1 0.2 Pressure Sensitive Silicone AdhesiveBio-PSA Q7-4602 S11 S12 S13 S14 Pressure Sensitive Silicone Adhesive Bio-PSA Q7-4301 S21 S22 S23 S24 Al: aluminum; Ti: Titanium
    The crosslinker concentrations indicated above are relative to the dry adhesive weight.
    Bio-PSA Q7-4602 (Dow corning agent) is a solution of an amine-incompatible pressure-sensitive silicone adhesive whose solvent is ethyl acetate. Product 4301 is amine compatible and differs from product 4602 in that the solvent is heptane. Durotak 387-2051 (manufactured by National Starch) is a solution of a pressure-sensitive polyacrylate adhesive in which no crosslinking agent is added and the solvent is a mixture of ethyl acetate and heptane.
    An adhesive is prepared by adding 2% solution of titanyl acetylacetonate (solvent: ethanol) or 4% solution of aluminum acetylacetonate (solvent: ethyl acetate) to the adhesive solution and then mixing.
    The viscous adhesive solution was applied in a thin layer onto a polyethylene terephthalate film (Hostaphan RN100, manufactured by Hoechst) using a suitable film stripping frame and dried in an 80 ° C. exhaust oven for 10 minutes. For all formulations the layer thickness was adjusted such that the weight per unit area of the dry film was 60 g / m 2 ± 5%. This corresponds to 6 mg / cm 2 and the layer thickness is about 60 μm.
    When all the pressure-sensitive adhesives tested were coated on polyethylene terephthalate, a mechanically almost inseparable bond was achieved. Further, a pressure-sensitive adhesive film was prepared under the same conditions on a non-tacky finish supported film by coating with a fluoropolymer (ScotchPak 1022, manufactured by 3M). Under this condition, the pressure-sensitive adhesive film could be easily removed from the supporting film mechanically and applied to the next step.
    The effect of the crosslinker in the pressure sensitive adhesive thus produced was examined by two measurement methods.
    Describe the spontaneous tack of the pressure sensitive adhesive with the surface.
    The spontaneous tack that appears after very short contact without excessive pressure is highly dependent on the flowability of the pressure sensitive adhesive. High fluidity allows for rapid contact and covers the detailed structure of the substrate surface over the entire substrate, resulting in high tack. Flowability is not the only property that determines stickiness, but most importantly.
    The rolling ball method is a suitable measuring method for showing adhesiveness. In this method, after a ball having a suitable material and having an initial velocity, the ball is rolled over the pressure-sensitive adhesive attached to the flat carrier as a thin film layer.
    By the braking effect of this pressure sensitive adhesive, which depends on the adhesiveness of the pressure sensitive adhesive, the distance can be calculated after the ball stops, or the time required for the ball to cover the distance without stopping can be measured. This second result is not distorted by the unusual process of ball sticking.
    The run time of the ball was measured on an inclined surface (glass plate having an intensity of 1 cm) having a proper inclination angle and a distance of 59 cm. The ball was rolled on a pressure-sensitive adhesive film fixed to a polyethylene terephthalate film, previously limited to a distance of 17.5 cm.
    The cloud time was measured between two modularized infrared barriers using an electronic clock with a display capability of 1/1000 second.
    The rolling time shown in FIG. 1 was measured 6 times using the bearing ball of the high quality steel rolling element of diameter 18mm, and was calculated | required as the intermediate value at the inclination angle of 35 degrees.
    For all three types of adhesives, an increase in crosslinker concentration resulted in a decrease in cloud time. Therefore, the tackiness of the pressure-sensitive silicone adhesive is reduced by addition of a crosslinking agent, as expected, due to crosslinking, i.e., lowering the fluidity of the polymer, which is clearly seen in the known examples for the crosslinking of polyacrylate adhesives (A11-A14). have.
    This phenomenon is particularly maintained precisely in the amine non-conforming silicone adhesives (S11-S14), but limitedly in the amine non-conforming silicone adhesives (S21-S24).
    In addition, the crosslinking is particularly effective at an aluminum concentration of 0.05% or less, and is also effective at 0.05% to 0.1%.
    The same effect was obtained when an aluminum crosslinking agent was used instead of a titanium crosslinking agent as a crosslinking agent for the pressure-sensitive silicone adhesive (FIG. 2).
    In addition, the shear strength of the prepared pressure-sensitive adhesive film was tested.
    When a shear force is applied to the non-crosslinked linear flowable polymer, the flow of the film occurs slowly. If the shear is not too fast and the film does not tear, then a nearly constant flow rate appears when a constant shear force is applied.
    On the other hand, when the polymer chain is three-dimensionally crosslinked, the viscous portion is almost lost, and only elastic deformation may occur. Increasing the shear force causes mechanical tearing of the polymer structure resulting in tearing of the entire film.
    Therefore, the crosslinked pressure-sensitive adhesive film and the non-crosslinked pressure-sensitive adhesive film exhibit very different properties in terms of action on shear force.
    In order to test this action, the round piece of diameter 12mm was cut out and cut out from the pressure-sensitive adhesive film produced above. As shown in Fig. 3, round pieces of these films were fixed between stripes of two polyethylene terephthalate films (Hostaphan RN 100, manufactured by Hoechst).
    This arrangement was clamped in a conventional tensile tester (Universal Tester 81803, manufactured by Frank, Weinheim), and then the shear force per hour was measured under a constant shear rate of 2.5 mm / minute.
    The graphs of shear force / time of six individual measurements thus obtained are shown in FIGS. 4 to 7, respectively.
    In the case of polyacrylate as a reference example, in a non-crosslinked state, after a short time shear force is applied to maintain a predetermined constant shear rate, a constant shear force is maintained: that is, the polymer flows (Fig. 4).
    On the other hand, in the crosslinked state, the film finally exceeds the elastic expansion, and the shear force rapidly increases until the film tears and the shear force rapidly drops to zero, i.e., under elastic deformation (Fig. 5).
    Silicone films without crosslinkers exhibit a very similar appearance to uncrosslinked polyacrylate films: under constant shear forces, a certain shear rate is maintained. Only the required shear force is located at a higher level than the non-crosslinked polyacrylate, and the energy barrier for the transition from the resting state to the flow motion is also clearer (Fig. 6). This is due to the different chain lengths of the two polymers and the interaction forces between the internal molecules.
    However, what is decisive is due to the characteristic change of the crosslinker-containing silicone film. Much like the crosslinked polyacrylate film, the tearing of the film maintains the shearing force under elastic strain where the shearing force finally drops to zero (FIG. 7).
    This is evidence that the pressure sensitive silicone based adhesive film no longer flows after addition of the crosslinker titanyl acetylacetone.
    权利要求:
    Claims (11)
    [1" claim-type="Currently amended] In preparing a pressure-sensitive polysiloxane adhesive solution of one component on a flat carrier and dried to prepare a pressure-sensitive polysiloxane adhesive layer,
    A complex of a metal ion of one of the group consisting of calcium, magnesium, zinc, aluminum, titanium, zirconium or hafnium and a low molecular weight organic complex former is added to the organic adhesive solution to be coated and the adhesive And only when the solution is heated and / or dried, the metal ions are released from the bond with the complex forming agent.
    [2" claim-type="Currently amended] The method of claim 1,
    Wherein said metal addition amount is at least 0.005% by weight relative to the weight of said dried adhesive.
    [3" claim-type="Currently amended] The method of claim 1,
    The metal addition amount is 0.005 to 0.5% by weight relative to the weight of the dried adhesive, low temperature fluidity reduced polysiloxane adhesive layer production method.
    [4" claim-type="Currently amended] The method according to any one of claims 1 to 3,
    Characterized in that the organic complex former is removed during substantially drying, low temperature fluidity reduced pressure polysiloxane adhesive layer.
    [5" claim-type="Currently amended] The method according to any one of claims 1 to 4,
    The said drying is performed at 20-120 degreeC, The manufacturing method of the pressure-sensitive polysiloxane adhesive layer by which the low temperature fluidity | liquidity was reduced.
    [6" claim-type="Currently amended] The method according to any one of claims 1 to 5,
    A method for producing a reduced pressure polysiloxane adhesive layer, the low temperature fluidity, characterized in that the weight per unit area of the dried film is 10 ~ 300g / ㎡.
    [7" claim-type="Currently amended] The method according to any one of claims 1 to 6,
    Wherein said organic complex former is acetylacetone or acetylacetone participates in the formation of said complex, low temperature fluidity reduced polysiloxane adhesive layer production method.
    [8" claim-type="Currently amended] The method according to any one of claims 1 to 7,
    The metal participating in the complex is aluminum or titanium, characterized in that the low-temperature fluidity reduced pressure polysiloxane adhesive layer production method.
    [9" claim-type="Currently amended] The method according to any one of claims 1 to 8,
    Characterized in that the polysiloxane is substantially polydimethylsiloxane, wherein the low temperature fluidity reduced pressure polysiloxane adhesive layer is produced.
    [10" claim-type="Currently amended] The method of claim 9,
    And wherein the free silanol groups present in the polydimethylsiloxane are chemically inert through suitable end capping to be amine resistant, thereby reducing the low temperature fluidity of the reduced pressure polysiloxane adhesive layer.
    [11" claim-type="Currently amended] A medical patch comprising a layered structure having at least one pressure-sensitive polysiloxane adhesive layer produced by the method of any one of claims 1 to 10.
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    同族专利:
    公开号 | 公开日
    US6706390B1|2004-03-16|
    KR100566724B1|2006-04-03|
    JP2002506916A|2002-03-05|
    HU0100993A3|2001-11-28|
    PL343153A1|2001-07-30|
    JP4886929B2|2012-02-29|
    ID26345A|2000-12-14|
    WO1999047619A1|1999-09-23|
    EP1070104B1|2003-10-22|
    TR200002474T2|2000-12-21|
    ZA9902021B|1999-09-27|
    CA2322273A1|1999-09-23|
    SK13482000A3|2001-02-12|
    ZA992021B|1999-09-27|
    IL138415A|2005-12-18|
    AU742104B2|2001-12-20|
    JP2009144164A|2009-07-02|
    HU0100993A2|2001-06-28|
    MY133129A|2007-10-31|
    AT252623T|2003-11-15|
    NO20004564D0|2000-09-13|
    EP1070104A1|2001-01-24|
    AU3030499A|1999-10-11|
    JP4887383B2|2012-02-29|
    NZ505907A|2002-06-28|
    IL138415D0|2001-10-31|
    DE19811218A1|1999-09-16|
    ES2212543T3|2004-07-16|
    CA2322273C|2008-12-16|
    DK1070104T3|2004-02-16|
    NO20004564L|2000-09-13|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    法律状态:
    1998-03-14|Priority to DE19811218.1
    1998-03-14|Priority to DE1998111218
    1999-02-26|Application filed by 보도 아스무센, 엘티에스 로만 테라피-시스템 악티엔게젤샤프트
    2001-05-15|Publication of KR20010041429A
    2006-04-03|Application granted
    2006-04-03|Publication of KR100566724B1
    优先权:
    申请号 | 申请日 | 专利标题
    DE19811218.1|1998-03-14|
    DE1998111218|DE19811218A1|1998-03-14|1998-03-14|Preparation of polysiloxane adhesive laminates|
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