Use of cyclodextrins as carriers for silicone materials and active substances

Abstract

The present invention relates to cyclodextrins as part of silicone compositions and their use to form articles for the absorption, encapsulation, and delivery of active substances and other compounds. Examples of such articles can be transdermal patches, PSAs, medical devices, membranes, gels, clothing, or other wearable materials. The cyclodextrins are compatible with silicone matrices without the need for additional compatibilizers. The present invention can be used in a variety of applications, including cosmetics, medical, home care, textiles, industrial, and other applications.

Description

Technical Field

[0001] The present invention relates to cyclodextrin as part of a silicone composition and its use for forming articles for the absorption, encapsulation and delivery of active substances and other compounds. Examples of such articles can be transdermal patches, pressure-sensitive adhesives, medical devices, membranes, gels, clothing or other wearable materials, etc. Cyclodextrin has compatibility with a silicone matrix without using additional compatibilizers. The present invention can be used in various applications including cosmetics, medicine, home care, textiles, industry and others.

[0002] The silicone-compatible cyclodextrin can be used in applications such as controlled release, delayed release or extended release, on-demand release and trigger release of active substances.

Background Art

[0003] In the prior art, the reaction between reactive rubber or silicone rubber and modified cyclodextrin has already been described.

[0004] US5,391,592 describes a silicone elastomer for contact lens applications, produced by reacting alkenyl-modified cyclodextrin (CD) with SiH-containing silicone via a hydrosilylation reaction to create a lipophilic CD-silicone polymer. This patent does not teach the encapsulation and release of active substances from the elastomer. Furthermore, the lipophilicity of CD does not necessarily mean compatibility with silicone. Therefore, forming an elastomer using only hydrophilic or lipophilic CD requires special conditions, such as the use of additional compatibility elements (e.g., solvent, high temperature). Thus, in the example of '592, toluene is used as a solvent to bring the different components (cyclodextrin and silicone) into the same phase for the hydrosilylation reaction necessary to produce the elastomer material for contact lenses. The use of an additional solvent results in additional manufacturing costs due to the required special handling, as well as environmental and health concerns.

[0005] US7,235,186B2 describes the bonding of cyclodextrins to silicones by condensation reactions. However, it requires the use of specific types of cyclodextrins, namely CDs functionalized with halotriazine, epoxy, amino, vinylsulfonyl, acryloyl, or methacryloyl groups. Specially functionalized cyclodextrins are expensive. The applicability of products obtained from this process is limited. For example, they are not suitable for RTV-2 type rubbers. The presence of certain functional groups, such as nitrogen-containing amines or triazine residues, may also interfere with certain curing methods, for example, with platinum catalysts used for curing some rubbers. US7,235,186B2 does not mention the compatibility of cyclodextrin-modified silicones with other silicones. The '186 patent also describes crosslinkable silicone compositions based on organosilicon compounds containing cyclodextrin radicals. The silicones described therein and cyclodextrin-modified silicones or silanes are not considered to be compatible and are not thought to react in a homogeneous phase. Therefore, crosslinking is preferably carried out in the form of an emulsion containing an additional emulsifier. The presence of an additional emulsifier can negatively affect desirable properties in many applications, in addition to increasing costs. Furthermore, various problems arise in many applications due to the leaching of the emulsifier. Crosslinking is based on a condensation reaction and requires temperatures above 100°C.

[0006] Materials Science and Engineering C 28(2008)705-715 describes the synthesis of silicone-containing β-cyclodextrin, but the synthesis involves multiple steps. The β-cyclodextrin is chemically grafted onto a poly(methylhydrosiloxane) polymer or poly(methylhydrosiloxane-co-dimethylsiloxane) copolymer by a hydrosilylation reaction. The multi-step synthesis includes regioselective bonding of a tosyl group to one of the primary hydroxyls, conversion to an allyl derivative, and then acetylation of the remaining hydroxyl group. The final step involves grafting the cyclodextrin derivative onto the silicone polymer by a hydrosilylation reaction. This process is too complex, potentially leading to high costs and lacking the simplicity required for industrial production. The monoallyl peracetylated β-cyclodextrin derivative used is incompatible with silicone. Large quantities of the flammable and toxic solvent toluene were required as a solvent to chemically bond this cyclodextrin derivative to the silicone polymer. This product is not cross-linked silicone rubber.

[0007] DE4324636 describes the modification of alkenyl-functionalized cyclodextrins with hydro-functionalized polysiloxanes via hydrosilylation, and their immobilization on support materials for application to chromatographic separation. Here again, since the cyclodextrins used are incompatible with silicone, a large amount of solvent, such as toluene, is required for the reaction between the CD and the hydro-functionalized silicone. The CD-modified silicones mentioned in this patent are not elastomers. The use of materials for controlled release of active substances is not taught.

[0008] CN102019171 describes a solid-phase microextraction coating characterized by containing a bonded β-cyclodextrin and polydimethylsiloxane. Compatibility of the materials for controlled release is not taught.

[0009] US9492549 suggests the possibility of using cyclodextrin as a hydrophilic component to facilitate the release of silver salts from an antimicrobial composition comprising an alkenyl and / or alkynyl-substituted polysiloxane, at least one polysiloxane containing a silicon-bonded hydrogen atom, and at least one hydrosilylation catalyst. Since cyclodextrin is not compatible with silicone and is not chemically bonded, phase separation is expected to occur even without the use of other compatibilizers. Phase separation may degrade the properties of the final product.

[0010] EP1206290B1 describes a pressure-sensitive adhesive composition containing cyclodextrin. While the adhesive is described as being silicone rubber-based (different from cross-linked silicone polymers), the cyclodextrin used is in hydrocolloidal form and is not compatible with silicone. If compatibility with silicone is required, additional compatibility elements will be necessary.

[0011] US6851462B2 describes rubber compositions comprising cyclodextrins or substituted or derivatized cyclodextrins that are compatible with rubber. Silicone rubber is not part of the rubbers described. Silicone offers advantages such as breathability, biocompatibility, and reduced trauma due to good skin adhesion. This patent does not teach the compatibility of cyclodextrins with silicone rubber, and therefore these rubbers do not have the beneficial advantages provided by silicone.

[0012] US4978532 describes hydroxypropyl-β-cyclodextrin as a medical-grade silicone pressure-sensitive adhesive, DHEA, and a penetration enhancer. Cyclodextrin is not compatible with silicone, and therefore heterogeneity is expected in the absence of other compatible elements.

[0013] Uniformity of rubber compositions is important before and / or after curing for ease of processing and proper retention of desired properties. Heterogeneous mixtures are difficult to process because not all components are uniformly distributed. Heterogeneously cured elastomers have defects arising from points or areas of heterogeneity, which adversely affect mechanical and other properties. Therefore, in the prior art, additional compatibilizers and solvents are used to homogenize the composition. However, this increases inconvenience, hazard, and cost. For example, when using organic solvents, which are often flammable, special handling environments must be ensured. Therefore, it is desirable to avoid this.

[0014] The conventional technologies described above, whether used individually or in combination, cannot solve the problem of easily and efficiently manufacturing silicone materials containing cyclodextrin.

[0015] Therefore, an object of the present invention is to provide products and processes for the encapsulation and controlled release of active substances from silicone matrices (e.g., silicone elastomers, silicone PSA (pressure-sensitive adhesives), etc.) incorporating cyclodextrins, wherein such cyclodextrins are compatible with silicone matrices, and cyclodextrin cavities can still be used for the encapsulation and delivery of various active substances.

[0016] The object of the present invention is a silicone-compatible cyclodextrin or its derivatives that are part of a silicone matrix, and the use of such cyclodextrins for encapsulating active substances within the cavity and for releasing the active substances as needed. Such cyclodextrin derivatives of the present invention are compatible with silicone matrices and therefore the amount of organic solvent can be minimized or avoided.

[0017] To avoid an excessive number of pages in the description of this invention, only preferred embodiments of each individual feature are shown for each component.

[0018] Those skilled in the art should expressly interpret this type of disclosure as expressly disclosing and expressly desiring any combination that is preferred to varying degrees; that is, any combination within a single component and between different components.

[0019] According to the present invention, A curable silicone rubber composition, wherein, in each case, relative to the total amount of the silicone rubber composition, -20 to 99.9% by weight of silicone matrix, and -0.1 to 80% by weight of cyclodextrin (CD) modified by a silylation reaction and containing a silyl group of formula (1) -(OSi(R 1 )3) x (1) [In the formula, R 1 These are, independently of each other, the same or different, and are alkyl groups, alkylene groups, aryl groups or alkyl-substituted aryl groups, and carbonyl groups. x is a number between 1 and 96. -0 to 50% by weight of at least one active molecule (guest molecule) Includes, However, the curable silicone rubber composition is provided in which the total amount of all components is always 100% by weight.

[0020] A preferred amount is 50-95% by weight of the silicone matrix and 0.1-60% by weight of at least one cyclodextrin (CD) modified as described above and containing the silyl group of formula (1). More preferably, the silicone matrix is ​​70-95% by weight and 0.1-50% by weight of at least one cyclodextrin (CD) containing the silyl group of formula (1) as described above.

[0021] If the silicone rubber composition contains any active substance, the amount is preferably 0.1 to 50% by weight, more preferably 0.1 to 30% by weight.

[0022] All of the above-mentioned preferred amounts are subject to the condition that the total amount of all components is always 100% by weight.

[0023] Silyl-modified cyclodextrin In formula (1), R as an alkyl group 1 is preferably a methyl group, an ethyl group, a propyl group, or an isobutyl group; more preferably a methyl group and an ethyl group; and most preferably a methyl group.

[0024] R as an alkylene group 1 is preferably a vinyl group, a propylene group, or an isobutylene group; more preferably a vinyl group.

[0025] R as an aryl group or an alkyl-substituted aryl group 1 is preferably a phenyl group and a toluene group; more preferably a phenyl group.

[0026] R 1 is preferably selected from methyl, ethyl, vinyl, and phenyl.

[0027] x is preferably a numerical value from 1 to 30, more preferably a numerical value from 1 to 24.

[0028] The advantage of the present invention is that the cyclodextrin of the present invention has compatibility with the silicone matrix, so that no significant inhomogeneity or phase separation occurs.

[0029] The cyclodextrin of the present invention is compatible with the silicone matrix by a very special modification of cyclodextrin (CD) with short silyl groups (e.g., trimethylsilyl, vinyldimethylsilyl, etc.) carried out by a silylation reaction. These modified CDs can be incorporated into the silicone composition at room temperature or, in some cases, by heating, using standard mixing techniques such as magnetic stirring, homogenization, high-speed mixing, etc.

[0030] In such silylation reactions, the alcohol group of CD is silylated. In this process, a proton is substituted with, for example, a trialkylsilyl group, typically trimethylsilyl (-SiMe3). In a typical process, the substrate is deprotonated with a suitable strong base such as butyllithium or a Grignard reagent, and then treated with a silyl chloride. Preferred silyl chlorides are chlorotrimethylsilane, chlorodimethylvinylsilane, and phenyldimethylchlorosilane. It is even more preferable to use bis(trimethylsilyl)amine (=hexamethyldisilazane=HMN) and bis(vinyldimethylsilyl)amine (VMN) instead of silyl chloride.

[0031] The following scheme illustrates a schematic example of a process for producing the silicone-compatible cyclodextrin of the present invention by silylation of a commercially available cyclodextrin (CD-OH) (such as CAVAMAX® W7 or W8 from Wacker Chemie AG, Germany) with a trimethylsilyl group or a vinyldimethylsilyl group in the presence of pyridine (Py). [ka]

[0032] Various silyl functional groups can be used for silylation. For example, silyl groups include alkyl, alkenyl, aryl, aralkyl, and carbonyl groups.

[0033] Silyl-modified cyclodextrins may exist as non-reactive components (e.g., trimethylsilyl-modified cyclodextrins) or they may be chemically bonded to the silicone matrix (e.g., vinyldimethylsilyl-modified cyclodextrins).

[0034] Silicone matrix Silicone matrices can be produced by standard chemistry of known prior art used in the manufacture of such materials, such as those produced by RTV-2, RTV-1, hydrosilylation, radical, anionic, cationic or condensation polymerization, UV or other high-energy radiation irradiation, thiolencric chemistry, etc.

[0035] Although these have long been known in the prior art, this specification briefly describes some of these suitable silicone compositions.

[0036] Addition crosslinked silicone composition Addition crosslinked silicone compositions have long been known to those skilled in the art. In its simplest form, an addition crosslinked silicone composition comprises at least one organopolysiloxane having at least two aliphatic unsaturated groups (e.g., Si-bonded vinyl groups) in its molecule, at least one organohydrogen-polysiloxane having two or more SiH groups in its molecule, and at least one catalyst, also called a hydrosilylation catalyst, that facilitates the addition of Si-bonded hydrogen to aliphatic multiple bonds. The viscosity of the addition crosslinked silicone composition can be adjusted to enable the production of HTV (high-temperature vulcanized), LSR (liquid silicone rubber), and RTV (room-temperature vulcanized) silicone elastomers. These can be one-component, two-component, or multi-component compositions.

[0037] Condensed crosslinked silicone composition Condensation-crosslinked silicone compositions have long been known to those skilled in the art. Common examples of condensation-crosslinked silicone compositions are referred to as RTV-1 (one-component) and RTV-2 (two-component). RTV-2 compounds typically include, as one of their components, at least one organopolysiloxane having terminal silanol groups, and further components such as fillers and plasticizers. The second component (curing agent) includes a crosslinking agent silane or siloxane combined with a catalyst to promote the condensation reaction, and optionally further components such as plasticizers. As the crosslinking agent silane or siloxane, silanes and siloxanes having at least three hydrolyzable residues are mainly used. This condensation-crosslinked RTV-1, which hardens upon intrusion of moisture from the atmosphere to produce a silicone elastomer from which hydrolysis products have been removed, is based on the possibility of terminal-blocking the terminal silanol organopolysiloxane with a crosslinking agent containing multiple hydrolyzable groups, while simultaneously preventing crosslinking. As a crosslinking agent, any silane or its partial hydrolysate having at least three hydrolyzable groups can be used. To achieve a sufficiently high crosslinking rate, most RTV-1 compounds include a condensation catalyst, such as organotin compounds and organotitanium compounds, or group I and II metal compounds.

[0038] Peroxide crosslinked silicone composition These compositions have also been known to those skilled in the art for a long time. In its simplest form, a peroxide-induced crosslinking silicone composition comprises at least one organopolysiloxane having at least two crosslinkable groups per molecule, such as methyl or vinyl groups, and at least one suitable organic peroxide catalyst. These are typically produced as HTV compounds.

[0039] Photo-induced crosslinked silicone composition These compositions have also been known to those skilled in the art for a long time. The photo-induced crosslinking silicone composition comprises at least one photoactivating initiator or catalyst, depending on the reaction mechanism.

[0040] Furthermore, all of the silicone compositions of the present invention described above may contain further additives (W) that are conventionally known to be used in their manufacture, such as reinforcing fillers, non-reinforcing fillers, bactericides, fragrances, rheological additives, corrosion inhibitors, antioxidants, light stabilizers, heat stabilizers, flame retardants, agents that affect electrical properties, dispersing additives, solvents, adhesion promoters, pigments, dyes, plasticizers, organic polymers, and the like.

[0041] An addition-curing silicone composition is preferred as the silicone matrix.

[0042] active substance The active substance is a guest molecule that can be encapsulated (compounded) within the cavity of the cyclodextrin molecule. Examples of guest molecules include drugs, pharmaceuticals, cosmetics or personal care or health active substances, biocides, insecticides, fungicides, herbicides, pheromones, fragrances, flavorings, pigments, pharmaceutically active compounds, natural oils or other oils, antigens, active compounds for antistatic or flame-retardant finishes, stabilizers (ultraviolet light), dyes, odor-generating molecules, etc., or combinations of two or more.

[0043] Guest molecules (=active substances) can be incorporated into the cyclodextrin before, during, or after the formation of the silicone matrix and released whenever needed for the final application. The CD of this invention can also be used to absorb molecules such as odor-causing compounds, if necessary.

[0044] Because the cavity size and / or shape of CD can change, it is unclear whether CD can be used for encapsulation after silyl modification. However, it has been shown that the complexation and release of guest molecules can still be achieved from curable silicone elastomers incorporating silylated CD.

[0045] The present invention further provides a method for producing the curable silicone rubber composition of the present invention by mixing all the compounds at room temperature or under heating using standard mixing techniques such as magnetic stirring, homogenization, and high-speed mixing.

[0046] The present invention further provides a silicone product obtained by filling a mold with a curable silicone rubber composition or by applying it to a surface and then curing it.

[0047] When such silicone products of the present invention contain active substances, they can be used for controlled, delayed, or induced release of such active substances in applications such as pharmaceuticals, cosmetics, personal care, wellness, room fragrances, biocides, insecticides, fungicides, herbicides, and textiles.

[0048] The silicone product of the present invention as a transdermal controlled release device: Transdermal patches containing therapeutic components are constructed by mixing the therapeutic component with silylated CD to form a complex, adding the therapeutic component-CD complex to an adhesive elastomer cured silicone matrix, stretching and curing the film of the composition to form a curable adhesive film, and combining this film with various other layers commonly found in transdermal adhesive patches, such as a backing layer and a release liner. The combination of the various layers of the patch can be done by standard methods used to produce such types of patches, such as lamination. For the end user to use the patch, after removing the release liner, the patch is applied to the skin and pressure is applied until the patch adheres. The therapeutic component penetrates from the skin into the bloodstream in a controlled manner over a long period of time. Appropriate skin penetration enhancers can be used. Such enhancers are already known.

[0049] The silicone product of the present invention as an insect repellent band: A complex can be formed by mixing a suitable silylated CD with an insect repellent component (e.g., DEET). This complex is incorporated into a curable silicone matrix used in the manufacture of wearable insect repellent bands. After the band is manufactured, the insect repellent component is released from the band over a long period, providing longer-lasting protection for the wearer.

[0050] The silicone product of the present invention as a wearable cosmetic face mask: A wearable anti-aging facelift mask can be constructed by forming a complex of silylated CD and an anti-aging active substance (e.g., retinol, glycolic acid, etc.), mixing the complex with an RTV-2 type curable silicone matrix, and molding the formulation into a face mask. While the consumer uses the face mask, the complex slowly releases the anti-aging active substance over a long period, thus enhancing the potency of the active substance. Such a method can also be used to create under-eye patches for wrinkle removal.

[0051] Silicone product of the present invention with trigger release: The active substance can be complexed with silyl-modified CD. This complex can be incorporated into a silicone matrix, and a device (e.g., a transdermal patch or topical patch) can be manufactured using the silicone material. The silicone material can, for example, be part of the adhesive component of the patch. By applying an appropriate trigger, the CD-active complex degrades and releases the active substance. Triggers can be, for example, body heat (normal or high body temperature), bodily fluid exudates such as sweat, moisture, pH, mechanical forces (e.g., abrasion, chemicals), other external stimuli (e.g., light, hair dryer), water, heat, electricity, chemicals, and combinations thereof.

[0052] One example of triggered release is when heat generated by using a supercooled solution within a patch induces release. The supercooled solution begins to solidify, generating heat. The solidification process can be initiated by an activating element, such as using an activated crystal, as described in US6,103,139. ​​The heat thus generated causes dissociation of the silyl CD active complex, releasing the active ingredient. Another example of triggered release is the use of a chemical that binds more strongly to silyl CD and replaces the original guest molecule that causes the release.

[0053] The silicone product of the present invention whose release is induced by a chemical heating method: An air-activated chemical heating mechanism based on the oxidation of a substance can be used for the decomposition of silyl CD-activated complexes and the release of active components. Such a heating mechanism is described in US2013 / 0006337A1. A mixture of iron powder, salt, water, activated carbon, and an absorbent material is used, and oxygen reacts with the iron powder, releasing heat through this oxidation reaction. While the heat generated by the oxidation of iron powder is used in many commercially available hand warmers, this principle can be used in the present invention to release active components from silyl CD-activated complexes.

[0054] The silicone product of the present invention whose release is induced by an external heating device: One example of a triggered release is when the release is induced by heat generated by an external heating device, such as a battery-operated or electrically powered handheld heater, as described in US2006 / 0142750A1.

[0055] Such silicone products of the present invention, when they do not contain active substances, can be used for applications to capture unwanted substances.

[0056] The silicone product of the present invention that captures unwanted substances with silyl CD: Silicone-compatible cyclodextrins (CDs) can be used to capture undesirable chemicals. For example, silyl CDs can be incorporated into a silicone elastomer matrix. During processing or use of elastomers in devices, the cyclodextrin component can capture unwanted chemicals. For example, during the curing of elastomers, silyl CDs may form complexes with catalytic toxins that adversely affect the curing process. Another example is that during the use of a cured silicone material (e.g., a film), odor-causing molecules can bind to the initially empty silyl CD cavities.

[0057] The following embodiments illustrate a principled implementation of the present invention, but the present invention is not limited to what is disclosed herein.

[0058] In the following examples, all quantities and percentages are by weight unless otherwise specified. Unless otherwise specified, the following examples are carried out at ambient atmospheric pressure, i.e., about 1000 hPa, room temperature, i.e., about 20°C, or at a temperature established by mixing the reactants at room temperature without additional heating or cooling. [Examples]

[0059] General conditions for the preparation of silicone-compatible cyclodextrins: To synthesize silylated cyclodextrins, a four-necked round-bottom flask equipped with a mechanical stirrer, thermocouple, dropping funnel, water cooler, nitrogen gas inlet and outlet, and a bypass adapter with various neck adapters and stopcocks to accommodate a rubber diaphragm was used. A heating mantle was used to heat the flask. All glassware was pre-dried in an oven at 125°C for at least 4 hours and cooled to room temperature before use. An electronic thermostat was used in combination with a thermocouple to control the heating of the flask and its contents. Preparation was carried out under a gentle flow of dry nitrogen gas. Vacuum distillation was performed in a rotary evaporator equipped with a dry ice cooler. Filtration was performed by either standard gravity filtration or vacuum filtration using a Buchner funnel.

[0060] The cyclodextrin (either β-cyclodextrin (WACKER CAVAMAX® W7) or γ-cyclodextrin (WACKER CAVAMAX® W8)) was pre-dried as follows to remove absorbed water from the solid powder. The cyclodextrin was placed in a crystallization dish and left to stand in an oven heated to 100°C for 16 hours. The dish was then removed from the oven and placed in a desiccator lined with phosphorus pentoxide (P2O5) powder, and cooled to room temperature.

[0061] Synthesis of trimethylsilyl β-cyclodextrin CH62: β-cyclodextrin (60.0 g, 0.0529 mol) was gradually added to a 1 L four-necked glass flask containing 600 g (7.59 mol) of anhydrous pyridine while continuously stirring at 200 rpm. The mixture was then stirred for 30 minutes to uniformly disperse the cyclodextrin. A slightly yellowish, translucent dispersion without large, identifiable solid particles was obtained. Next, 71.7 g (0.444 mol) of bis(trimethylsilyl)amine (also known as hexamethyldisilazane or HMN) was added to the dispersion, generating an off-white, cloudy, gelatinous slurry. Chlorotrimethylsilane (48.2 g, 0.444 mol) was added dropwise to this slurry using a glass dropping funnel. After the addition of chlorotrimethylsilane, the slurry changed to an opaque white dispersion. Exothermic reaction was observed immediately after the addition of chlorotrimethylsilane. The reactor atmosphere was continuously replaced with a nitrogen blanket to remove any ammonia that may be generated by passing a 3.7 wt% hydrochloric acid aqueous solution through the foaming process, thereby completing the reaction.

[0062] After the addition of chlorotrimethylsilane, the dispersion was stirred for a further 65 minutes. The solvent was distilled under vacuum until an off-white paste was obtained. The paste and 375 mL of n-heptane were then mixed using a magnetic stirrer for at least 30 minutes. The solid was filtered from the mixture, and the colorless, clear filtrate was distilled under vacuum to remove the solvent until solid foam was formed. The solid foam was then cooled in a freezer set to -30°C, ground into fine particles, and dried in a vacuum oven at 55°C. The particles were cooled to room temperature and then ground into a fine powder using a mortar and pestle to obtain 112.7 g of a fine white powder. By 1H NMR, mass spectrometry, and SEC, the product was confirmed to be a substituted cyclodextrin having an average of 17.5 trimethylsilyl (TMS) groups and 3.5 OH groups.

[0063] Synthesis of trimethylsilyl-cyclodextrin CH48-2: γ-cyclodextrin (60.0 g, 0.0463 mol) was gradually added to a 1 L four-necked glass flask containing 600 g (7.59 mol) of anhydrous pyridine while continuously stirring at 200 rpm. The mixture was then stirred for 30 minutes to uniformly disperse the cyclodextrin. A slightly yellowish, translucent dispersion without large, identifiable solid particles was obtained. Next, 70.9 g (0.439 mol) of WACKER SILAZANE HMN, bis(trimethylsilyl)amine, was added to the dispersion to increase its turbidity. To this dispersion, 50.3 g (0.463 mol) of chlorotrimethylsilane was added dropwise using a glass dropping funnel. Upon addition of chlorotrimethylsilane, an opaque white dispersion was formed. An exothermic reaction of approximately 20-25°C was observed immediately after the addition of chlorotrimethylsilane. The reactor atmosphere was continuously replaced with a nitrogen blanket to remove any ammonia that may be generated by passing a 3.7 wt% hydrochloric acid aqueous solution through the foaming process, thereby completing the reaction.

[0064] After the addition of chlorotrimethylsilane, the dispersion was stirred for a further 65 minutes. The solvent was distilled under vacuum until an off-white paste was obtained. The paste and 375 mL of n-heptane were then mixed using a magnetic stirrer for at least 30 minutes. The solid was filtered from the mixture, and the colorless, clear filtrate was distilled under vacuum until solid bubbles formed. The solid bubbles were then cooled in a freezer set to -30°C, ground into fine particles, and dried in a vacuum oven at 55°C for 16 hours. The particles were cooled to room temperature and then ground into a fine powder using a mortar and pestle to obtain 125.8 g of a fine white powder. By 1H NMR, mass spectrometry, and SEC, the product was confirmed to be a substituted cyclodextrin having an average of 21.5 TMS groups and 2.5 OH groups.

[0065] Synthesis of vinyldimethylsilyl β-cyclodextrin CH70-2: β-cyclodextrin (35.0 g, 0.0308 mol) was gradually added to a 1 L four-necked glass flask containing 375 g (4.74 mol) of anhydrous pyridine while continuously stirring at 200 rpm. The mixture was then stirred for 30 minutes to homogeneously disperse the cyclodextrin. A slightly yellowish, translucent dispersion without large, identifiable solid particles was obtained. Next, 42.0 g (0.227 mol) of WACKER SILAZANE VMN, bis(dimethylvinylsilyl)amine (also known as 1,1,3,3-tetramethyl-1,3-divinyldisilazane or VMN), and 27.3 g (0.226 mol) of chlorodimethylvinylsilane were placed in a separate dropping funnel. Then, approximately 10-15% of bis(dimethylvinylsilyl)amine was added dropwise (for about 1 minute), at which point the addition of chlorodimethylvinylsilane was started. The addition of both reagents was continued simultaneously until completion. Exothermic reaction was observed immediately after the addition of chlorodimethylvinylsilane. The addition of the silylating agent formed an opaque off-white dispersion. The reactor atmosphere was continuously replaced with a nitrogen blanket to remove any ammonia that may be produced and complete the reaction, passing through a 3.7 wt% aqueous hydrochloric acid solution.

[0066] After the addition of the silylation agent, the dispersion was stirred for a further 65 minutes. The solvent was distilled under vacuum until an off-white paste was obtained. The paste and 375 mL of n-heptane were then mixed using a magnetic stirrer for at least 30 minutes. The solid was filtered from the mixture, and the colorless, clear filtrate was distilled under vacuum to form solid foam. The solid foam was cooled in a freezer set to -30°C, ground into fine particles, and dried in a vacuum oven at 60°C for 16 hours. The particles were cooled to room temperature and ground into a fine powder using a mortar and pestle to obtain 68.0 g of a fine white powder. By 1H NMR, mass spectrometry, and SEC, the product was confirmed to be a substituted cyclodextrin having an average of 17.3 VDMS and 3.7 OH groups.

[0067] Synthesis of dimethylvinylsilyl γ-cyclodextrin CH61: γ-cyclodextrin (60.0 g, 0.0463 mol) was gradually added to a 1 L four-necked glass flask containing 600 g (7.59 mol) of anhydrous pyridine while continuously stirring at 200 rpm. The mixture was then stirred for 30 minutes to uniformly disperse the cyclodextrin. A slightly yellowish, translucent dispersion without large, identifiable solid particles was obtained. Next, 81.5 g (0.440 mol) of WACKER SILAZANE VMN, bis(dimethylvinylsilyl)amine, was added to the dispersion to increase its turbidity. To this dispersion, 55.8 g (0.462 mol) of chlorodimethylvinylsilane was added dropwise using a glass dropping funnel. Upon addition of chlorodimethylvinylsilane, an opaque white dispersion was formed. Exothermic reaction was observed immediately after the addition of chlorodimethylvinylsilane. The reactor atmosphere was continuously replaced with a nitrogen blanket to remove any ammonia that may be generated by passing a 3.7 wt% hydrochloric acid aqueous solution through the foaming process, thereby completing the reaction.

[0068] After the addition of the silylation agent, the dispersion was stirred for a further 65 minutes. The solvent was distilled under vacuum until an off-white paste was obtained. The paste and 375 mL of n-heptane were then mixed using a magnetic stirrer for at least 30 minutes. The solid was filtered from the mixture, and the colorless, clear filtrate was distilled under vacuum to form solid foam. The solid foam was cooled in a freezer set to -30°C, ground into fine particles, and dried in a vacuum oven at 55°C for 16 hours. The particles were cooled to room temperature and ground into a fine powder using a mortar and pestle to obtain 149.0 g of a fine white powder. By 1H NMR, mass spectrometry, and SEC, the product was confirmed to be a substituted cyclodextrin having an average of 21.8 VDMS groups and 2.2 OH groups.

[0069] Synthesis of trimethylsilylvinyldimethylsilyl β-cyclodextrin CH74: β-cyclodextrin (20.0 g, 0.0176 mol) was gradually added to a 500 mL four-necked glass flask containing 250 g (3.16 mol) of anhydrous pyridine while continuously stirring at 200 rpm. The mixture was then stirred for 30 minutes to homogeneously disperse the cyclodextrin. A slightly yellowish, translucent dispersion without large, identifiable solid particles was obtained. WACKER SILAZANE HMN, 20.9 g (0.129 mol) of bis(trimethylsilyl)amine was placed in a glass addition funnel, and 4.46 g (0.0370 mol) of chlorodimethylvinylsilane and 10.1 g (0.0930 mol) of chlorotrimethylsilane were placed in another glass addition funnel. Bis(trimethylsilyl)amine was added dropwise for approximately 2 minutes, and then the dropwise addition of the two chlorosilanes was started. The dropwise addition of the silylation agents was continued simultaneously until both supplies were complete. Exothermic reaction was observed immediately after the addition of chlorosilane. The reactor atmosphere was continuously replaced with a nitrogen blanket to remove any ammonia that may be produced by bubbling through a 3.7 wt% hydrochloric acid aqueous solution and to complete the reaction.

[0070] After the addition of the silylation agent, the dispersion was stirred for a further 65 minutes. The solvent was distilled under vacuum until an off-white paste was obtained. The paste and 375 mL of n-heptane were then mixed using a magnetic stirrer for at least 30 minutes. The solid was filtered from the mixture, and the colorless, clear filtrate was distilled under vacuum until a waxy solid was obtained. The waxy solid was dried in a vacuum oven at 70°C for 16 hours to produce a solid mass, which was then ground into fine particles and dried for a further 6 hours under the same conditions. The particles were cooled to room temperature and ground in a mortar and pestle to obtain 37.8 g of a fine white powder. By 1H NMR, mass spectrometry, and SEC, the product was confirmed to be a substituted cyclodextrin having an average of 15.2 TMS, 1.4 VDMS, and 4.4 OH groups.

[0071] Synthesis of trimethylsilylvinyldimethylsilylγ-cyclodextrin CH85 γ-cyclodextrin (20.0 g, 0.0154 mol) was gradually added to a 500 mL four-necked glass flask containing 200 g (2.53 mol) of anhydrous pyridine while continuously stirring at 200 rpm. The mixture was then stirred for 30 minutes to uniformly disperse the cyclodextrin. A slightly yellowish, translucent dispersion was obtained, free from large, identifiable solid particles.

[0072] 20.9 g (0.129 mol) of WACKER SILAZANE HMN, bis(trimethylsilyl)amine, was placed in a glass addition funnel, and 3.91 g (0.0324 mol) of chlorodimethylvinylsilane and 10.6 g (0.0976 mol) of chlorotrimethylsilane were placed in a separate glass addition funnel. Bis(trimethylsilyl)amine was added dropwise for approximately 2 minutes, and then the addition of chlorosilane was started. The addition of the silylation agents was continued simultaneously until both supplies were complete. Exothermic reaction was observed immediately after the addition of chlorosilane. The atmosphere in the reactor was passed through a 3.7 wt% hydrochloric acid aqueous solution, and the reaction was continuously purged with a nitrogen blanket to remove any ammonia that may be produced and allowed to complete.

[0073] After the addition of the silylation agent, the dispersion was stirred for a further 65 minutes. The solvent was distilled under vacuum until an off-white paste was obtained. The paste and 150 mL of n-heptane were then mixed using a magnetic stirrer for at least 30 minutes. The solid was filtered from the mixture, and the colorless, clear filtrate was distilled under vacuum to form solid foam. The solid foam was then ground into fine particles and dried in a vacuum oven at 65°C for 16 hours. The particles were cooled to room temperature and ground into a fine powder using a mortar and pestle to obtain 38.5 g of a fine white powder. By 1H NMR, mass spectrometry, and SEC, the product was confirmed to be a substituted cyclodextrin having an average of 18.5 TMS, 1.34 VDMS, and 4.16 OH groups.

[0074] Synthesis of trimethylsilyl-vinyldimethylsilyl γ-cyclodextrin CH60 γ-cyclodextrin (20.0 g, 0.0154 mol) was gradually added to a 500 mL four-necked glass flask containing 200 g (2.53 mol) of anhydrous pyridine while continuously stirring at 200 rpm. The mixture was then stirred for 30 minutes to uniformly disperse the cyclodextrin. A slightly yellowish, translucent dispersion without large, identifiable solid particles was obtained. The mixture was cooled in an ice bath.

[0075] Using a glass dropping funnel, 23.7 g (0.146 mol) of WACKER SILAZANE HMN, bis(trimethylsilyl)amine, was slowly added to the cooled, stirred mixture. Then, using a dropping funnel, 18.93 g (0.157 mol) of chlorodimethylvinylsilane was added dropwise. Exothermic reaction was observed immediately after the addition of chlorosilane. The reactor atmosphere was passed through a 3.7 wt% hydrochloric acid aqueous solution, and the reaction was continuously purged with a nitrogen blanket to remove any ammonia that may be generated and allowed to complete.

[0076] After the addition of the silylation agent was complete, the ice bath was removed and the dispersion was stirred for a further 65 minutes. The solvent was distilled under vacuum until an off-white paste was obtained. The paste and 100 mL of n-heptane were then mixed using a magnetic stirrer for at least 30 minutes. The solid was filtered from the mixture, and the colorless, clear filtrate was distilled under vacuum to form a solid. The solid was pulverized and dried in a vacuum oven at 55°C for 16 hours to obtain 39.0 g of a white, brittle solid. By 1H NMR, mass spectrometry, and SEC, the product was confirmed to be a substituted γ-cyclodextrin having an average of 14.9 TMS, 8.1 VDMS, and 1.0 OH group.

[0077] Synthesis of trimethylsilyl-phenyldimethylsilyl β-cyclodextrin CH86 Silyl-modified cyclodextrin (CD) was synthesized using the same procedure as for CH74, with 18.0 g of β-CD, 233.5 g of pyridine, 9.4 g of bis(trimethylsilyl)amine (HMN), and 39.8 g of phenyldimethylchlorosilane. The purification procedure differed slightly from that of CH74. After distillation of the solvent under vacuum, the residue was extracted with n-heptane and filtered. Using a separatory funnel, the heptane solution of the filtrate was washed three times with an equal volume of methanol containing a few drops of brine. The heptane layer was collected from the bottom of the separatory funnel, the heptane was evaporated using a rotary evaporator, and the residue was dried in a vacuum oven to obtain a solid, which was then pulverized to obtain a white dry powder (38.0 g). By 1H NMR, mass spectrometry, and SEC, the product was confirmed to be a substituted cyclodextrin having an average of 7.9 TMS, 9.5 PhDMS (phenyldimethylsilyl), and 3.6 OH groups.

[0078] Synthesis of vinyldimethylsilyl-phenyldimethylsilyl β-cyclodextrin CH87 Silyl-modified cyclodextrin (CD) was synthesized using the same procedure as for CH86, with 20.1 g of β-CD, 234.0 g of pyridine, 24.1 g of bis(vinyldimethylsilyl)amine (VMN), and 22.1 g of phenyldimethylchlorosilane. The product was obtained as 33.0 g of a white, dry powder. By 1H NMR, mass spectrometry, and SEC, the product was confirmed to be a substituted cyclodextrin having an average of 11.2 VDMS, 5.1 PhDMS, and 4.7 OH groups.

[0079] Synthesis of trimethylsilylphenylpropyldimethylsilyl β-cyclodextrin CH88 Silyl-modified CD was synthesized using the same procedure as for CH86, with 18.1 g of β-CD, 233.2 g of pyridine, 9.4 g of bis(trimethylsilyl)amine (HMN), and 49.7 g of (3-phenylpropyl)dimethylchlorosilane. The product was obtained as 45.6 g of a colorless viscous liquid. By 1H NMR, mass spectrometry, and SEC, the product was confirmed to be a substituted cyclodextrin having an average of 8.4 TMS, 7.8 PhPrDMS (dimethyl(3-phenylpropyl)silyl), and 4.8 OH groups.

[0080] Synthesis of trimethylsilyl-vinyldimethylsilyl β-cyclodextrin CH77 with a low degree of silyl substitution: Silyl-modified cyclodextrin (CD) was synthesized using the same procedure as for CH74, with 25.0 g of β-CD, 300.7 g of pyridine, 18.7 g of bis(trimethylsilyl)amine (HMN), and 11.2 g of chlorodimethylvinylsilane. The product was obtained as 41.0 g of a white, brittle powder. By 1H NMR, mass spectrometry, and SEC, the product was confirmed to be a substituted cyclodextrin with an average of 8.0 TMS, 3.2 VDMS, and 9.8 OH groups. Therefore, in this silylated CD, approximately 53% of the total OH groups were derivatized, while an average of 47% of the OH groups remained underivative. In this case, the relative amount of silylating agent used was small, resulting in a relatively low degree of silylation.

[0081] Table 1 shows an overview of various silylated CD examples. [Table 1]

[0082] Although the examples shown are for β- and γ-cyclodextrins only, similar silylated cyclodextrins can also be prepared based on α-cyclodextrin.

[0083] Examples of the solubility of silylated cyclodextrin in silicone: Silylated cyclodextrin CH60 (0.5 g) was mixed with 4.5 g of BELSIL® DM5 (trimethylsilyl-terminated linear polydimethylsiloxane, viscosity 5 mPa·s) using a vortex mixer to produce a 10% by weight mixture. A clear, homogeneous solution was produced. Such a homogeneous mixture can also be produced using a porcelain stirrer, overhead stirrer, Speedmixer®, or similar mixing techniques.

[0084] Similar experiments using silylated cyclodextrin CH70 have shown that the solubility of CD in DM5 is 25% by weight. A clear, homogeneous solution was formed.

[0085] Comparative example 1 of solubility: The experiments described above were repeated using CAVAMAX® W8, a natural γ-CD that has not been modified by silylation. The resulting mixture was heterogeneous and opaque, and showed significant phase separation.

[0086] Comparative Example 2 of Solubility (Solubility of Permethylated β-Cyclodextrin): We purchased permethylated β-cyclodextrin from Sigma Aldrich, in which all OH groups are derivatized to OMe groups but not silyl-modified. 0.5 g of permethylated β-CD and 4.5 g of DM5 were mixed in a vortex mixer to produce a 10 wt% mixture. The mixture was heterogeneous and opaque. This comparative example demonstrates that hydrocarbon (methyl in this case) substitution alone is insufficient to make CD compatible with silicone, and that the resulting mixture is heterogeneous, opaque, and exhibits significant phase separation.

[0087] Comparative Example 3 of Solubility (Solubility of Silylated Cyclodextrin with Low Silylation Degree): Silylated β-cyclodextrin CH77, which has a low number of silyl groups (average 7.95 TMS groups and 3.23 VDMS groups), was evaluated, and its solubility in DM5 at 10% by weight was confirmed. This cyclodextrin was found to be insoluble in DM5.

[0088] Experimental example of the production of silicone elastomers using silylated cyclodextrins: Experimental example of elastomer CH95-70 0.802 g (0.304 mmol) of CH70, dimethylvinylsilyl-β-cyclodextrin, and 52.0 g of silicon hydride-terminated polydimethylsiloxane fluid with a viscosity of approximately 1000 mPa·s were placed in a suitable plastic cup with a lid, along with a magnetic stirring bar. The cup was covered with nitrogen gas and then sealed to maintain an inert atmosphere during stirring. The materials were stirred until the cyclodextrin was completely dissolved. To this solution, 22.9 g of vinyl-terminated polydimethylsiloxane fluid with a viscosity of approximately 100,000 mPa·s was added, and the contents of the plastic cup were mixed by hand using the stirring rod. 0.0757 g of platinum catalyst solution, i.e., divinyltetramethyldisiloxane platinum composite (Pt content 1% w / w) diluted with vinyl-terminated polysiloxane, was added to the mixture and mixed by hand. Subsequently, the mixture was further mixed for 1 minute at 1250 rpm under vacuum (pressure of 95 mbar to degas the mixture) using a Speedmixer™ model DAC1100.2VAC manufactured by FlackTek, Inc.

[0089] Next, the composition was placed in a "plate and frame" mold lined with a suitable release liner. The composition and mold were cured in an oven preheated to 80°C for 1 hour to produce a rubber sheet approximately 6 inches x 6 inches x 0.072 inches in size. The cured elastomer sample was transparent and colorless.

[0090] Experimental example of elastomer CH95-60 Elastomer slabs were produced using a platinum catalyst solution from trimethylsilyl-vinyldimethylsilyl γ-cyclodextrin CH60, a silicon hydride-terminated polydimethylsiloxane fluid with a viscosity of approximately 1000 mPa·s, and a vinyl-terminated polydimethylsiloxane fluid with a viscosity of approximately 100,000 mPa·s. The procedure was the same as for CH95-70. The slabs were transparent and colorless.

[0091] Experimental examples of elastomer CH95-85 Elastomer slabs were produced using a platinum catalyst solution from trimethylsilyl-vinyldimethylsilyl γ-cyclodextrin CH85, a silicon hydride-terminated polydimethylsiloxane fluid with a viscosity of approximately 1000 mPa·s, and a vinyl-terminated polydimethylsiloxane fluid with a viscosity of approximately 100,000 mPa·s. The procedure was the same as for CH95-70. Table 2 shows examples of elastomer curing using silylated cyclodextrin.

[0092] [Table 2]

[0093] Comparison of cured elastomers incorporating silylated CD and cured elastomers incorporating unsilylated CD: Cured elastomer samples were prepared using dimethylvinylsilyl-trimethylsilyl-β-cyclodextrin CH68, which has an average of 11.2 TMS, 5.4 VDMS, and 4.4 OH groups, a silicon hydride-terminated polydimethylsiloxane fluid with a viscosity of approximately 1000 mPa·s, and a vinyl-terminated polydimethylsiloxane fluid with a viscosity of approximately 100,000 mPa·s, together with a platinum catalyst solution. The procedure was the same as for CH95-70. Another elastomer sample was prepared using the same recipe, but with silyl β-cyclodextrin CH68 replaced by native β-cyclodextrin CAVAMAX® W7. A third sample was prepared in the same manner, but with silyl β-cyclodextrin CH68 replaced by permethylated β-cyclodextrin. The sample containing silylated CDCH68 was clear and homogeneous, while the two comparison samples were heterogeneous and opaque, with greater domain separation.

[0094] Examples of complex formation of guest molecules by silyl cyclodextrins Silyl CD is suitable for binding many guest molecules within its cavity. CD guest complexes can be formed by various methods commonly used in the production of cyclodextrin complexes, such as grinding, kneading, precipitation, solvent evaporation, and freeze-drying. The formation of guest molecule complexes can be confirmed by standard methods described in the literature, such as visual changes in appearance, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), nuclear magnetic resonance (NMR), infrared spectroscopy (IR), and X-ray diffraction.

[0095] Complex formation of adamantane by silyl CD: The ability of silylated CD to complex with adamantane as a guest molecule was demonstrated by differential scanning calorimetry (DSC). Uncomplexed adamantane typically exhibits a thermal event corresponding to the solid-solid (polymorph) transition enthalpy from face-centered cubic to body-centered tetragonal lattices. This event occurs in crystalline solid samples of adamantane but not when individual adamantane molecules are individually bound to the CD cavity and separated from each other. Therefore, the absence of this thermal event indicates that adamantane is present in the CD cavity.

[0096] Adamantane complex formation by CD itself: A complex was formed by mixing silyl β-CD VP31-2, which has an average of 15.3 vinylsilyl groups, and adamantane in a 1:1 molar ratio in a 50 wt% toluene solution at 60°C for 1 hour. The complex (MG3) was isolated by removing the toluene using a vacuum oven.

[0097] Composite formation between silyl CD and adamantane in silicone elastomers: Silyl-CD VP31-2 and adamantane were dissolved in 50% by weight toluene in a 1:1 molar ratio (the ratio of the total mass of CD and adamantane to the mass of toluene was 1:1), and the mixture was stirred at 60°C for 1 hour to form a complex. This solution was then added to SiH-terminated linear PDMS with an average viscosity of approximately 1000 mPa·s (SiH:vinyl molar ratio 1:1) and mixed using a Speedmixer (2000 rpm, 2 min). Next, a platinum catalyst solution (the same as described in Table 1, 0.1% of the total mass of the mixture) was added to the mixture and mixed again with a Speedmixer (2000 rpm, 2 min). The mixture was then poured into an aluminum Petri dish and left to stand in an oven at 80°C for 1 hour. A colorless, transparent, and homogeneous elastomer (MG3-1) was obtained.

[0098] Complex formation was confirmed by DSC experiments. DSC was performed on natural adamantane, the product from a 1:1 CD:adamantane complex formation protocol (MG3), and the product from a silicone elastomer product from a complex formation protocol with silyl CD and adamantane (MG3-1). The results are shown in Figure 1 along with DSC thermograms of (a) silyl CD VP31-2, (b) adamantane, (c) elastomer MG3-1 containing the silyl CD-adamantane complex, (d) a 1:1 mixture of VP31-2 and adamantane without a complex formation protocol, and (e) the product from a 1:1 VP31-2 and adamantane complex formation protocol (MG3).

[0099] In the experiment, a solid-solid transition of adamantane was observed at approximately -59°C (thermogram b). This thermal event of adamantane is not present in thermogram e (product from a 1:1 composite formation experiment with CD:adamantane) or thermogram c (elastomer incorporating the product MG3 from CD and the adamantane composite formation protocol). Since MG3 is the starting material for elastomer MG3-1, the results indicate that adamantane was successfully composited after the composite formation protocol, and this composite remains intact within the elastomer.

[0100] To confirm that uncompounded adamantane can be detected using this method, a physical mixture of silyl CD VP31-2 and adamantane in a 1:1 ratio (without the compounding procedure) was prepared (DSC results are shown in thermogram d). From Figure 4, it is clear that the amount of uncompounded adamantane can be detected using this method (characteristic peak observed in thermogram d).

[0101] Examples of complex formation between silyl CD and geraniol Trimethylsilyl-β-cyclodextrin CH62 (1.416 g, 0.59 mmol) was weighed out and placed in a mortar. Then, geraniol (0.09100 g, 0.59 mmol) was added to TMS-β-CD, and the mixture was ground with a pestle for 15 minutes. The mixture was checked for solid lumps, and grinding was continued until no lumps remained. Complex formation was confirmed by DSC analysis (Figure 2).

[0102] The endothermic peak at approximately 240°C for pure geraniol indicates its boiling point. The disappearance of this peak confirms the formation of a complex of the CD-geraniol combination.

[0103] Similar experiments were conducted using other active substances, and the formation of the complex was confirmed by DSC.

[0104] Figure 3 shows the DSC thermograms of α-tocopherol in a 2:1 combination with VDMS-TMS-β-CDMG15 and VDMS-TMS-γ-CDCH60.

[0105] The plot for pure α-tocopherol shows a glass transition temperature (Tg) of approximately -61°C. The complete disappearance of this peak in both combinations with TMS-β-CDMG15 and TMS-γ-CD CH60 confirms that both CDs form a complex with α-tocopherol.

[0106] Examples of complex formation between silyl CD and salicylic acid: Trimethylsilyl-β-cyclodextrin CH62 (1.415 g, 0.59 mmol) was weighed out and placed in a mortar. Then, salicylic acid (0.0815 g, 0.59 mmol) was added to TMS-β-CD, and the mixture was ground with a pestle for 15 minutes. Approximately 5-7 mL of ethanol was added to the mixture, and grinding was continued for another 15 minutes. The mixture was placed in a small flask and the ethanol was evaporated in a 90°C oven. Composite formation was confirmed by optical microscopy analysis.

[0107] Microscopic images reveal a distinct crystalline phase in the complex, which is different from the original crystalline phase of salicylic acid or the amorphous powder mixture of the physical blend.

[0108] Table 3 shows various examples of complex formation between silyl CD and various guest molecules. [Table 3]

[0109] Complex formation offers advantages for the practical application of guest molecules, many of which are active ingredients in pharmaceuticals and cosmetics. For example, complex formation slows the evaporation of the active ingredient, extending its duration of action. This has been confirmed by thermogravimetric analysis (TGA). Figure 4 shows the thermogravimetric analysis results of a 1:1 complex of pure geraniol and trimethylsilyl-β-cyclodextrin CH62.

[0110] The complex with TMS-β-CD CH62 contained approximately 6% by weight of geraniol. Pure geraniol began to evaporate at approximately 75°C and completely evaporated at approximately 225°C. In the complex, evaporation did not begin until approximately 110°C and continued slowly until approximately 300°C. Therefore, complex formation with silyl CD slowed the loss of geraniol.

[0111] The TGA thermogram in Figure 5 shows similar observations regarding the 1:1 complex formation of silyl CD MG15 and α-pinene compared to pure α-pinene.

[0112] As the TGA results show, weight loss of pure pinene by evaporation began at almost room temperature (<30°C). This starting temperature increased significantly to about 135°C for the pinene-CD combination. Pure pinene completely evaporated at 140°C, but it took about 200°C for pinene to completely evaporate from the complex.

[0113] The complexes formed between silylated CD and various guest molecules were incorporated into an elastomer, resulting in transparent and / or homogeneous formulations for the silicone rubber composition and cured silicone products of the present invention.

[0114] It is not clear that a cured silicone elastomer product other than the present invention incorporates a complex of unsilylated natural β-CD and geraniol.

[0115] In some cases, incorporating silyl CD into an elastomer curing composition offers the practical advantage of achieving good curing. Some active substances may inhibit the catalyst used for curing (e.g., platinum). Encapsulating the active substance in silyl CD prevents the active substance from contaminating the catalyst. An example using salicylic acid as the active substance is shown below.

[0116] A cured elastomer / CD / salicylic acid sample (VP178-3) containing salicylic acid and silyl CD in a 1:1 molar ratio was prepared according to the following procedure.

[0117] SiH-terminated linear silicone (1.449 g) with an approximate formula MHD220MH and a viscosity of approximately 1000 mPa·s and SiH-terminated pendant SiH-containing silicone (0.045 g) with an approximate formula MHD95.5DH9.6MH and a viscosity of approximately 165 mPa·s were mixed using a Speedmixer (trademark). A silyl CD CH62 inclusion complex (1.057 g, CD:salicylic acid molar ratio 1:1) prepared according to the procedure described above was added and further mixed with the silicone components until the complex was sufficiently dispersed. Vinyl-terminated linear silicone (1.981 g) with a viscosity of approximately 1000 mPa·s was added and further mixed. Platinum catalyst solution (containing 1% platinum) (0.078 g) was added and further mixed. The mixture was left to stand in an oven at 120°C for 1 hour to obtain a cured elastomer.

[0118] A control sample (VP178-2) without silylated CD was prepared using the following procedure. A SiH-terminated linear silicone with approximate formula MHD220MH and viscosity approximately 1000 mPa·s (2.900 g) and a SiH-terminated pendant SiH-containing silicone with approximate formula MHD95.5DH9.6MH and viscosity approximately 165 mPa·s (0.090 g) were mixed using a Speedmixer™. Salicylic acid (0.088 g) was added and mixed further until well dispersed. Vinyl-terminated linear silicone with viscosity approximately 1000 mPa·s (3.963 g) was added and mixed further. Platinum catalyst solution (containing 1% platinum) (0.078 g) was added and the mixture was mixed further. The mixture was left to stand in an oven at 120°C for 1 hour, but the mixture remained liquid and no hardening occurred.

[0119] Examples of using silyl-modified CD for controlled release of geraniol from elastomers: A cured elastomer / CD / geraniol sample (VP141-2-1) with a molar ratio of geraniol to CD of 10:1 was prepared by the following procedure: Trimethylsilyl-β-cyclodextrin CH62 (1.41 g, 0.59 mmol) and geraniol (0.90 g, 5.9 mmol) were placed in a plastic cup and mixed using a Speedmixer® at 2000 rpm for 2 minutes (the mixing was repeated 2-3 times). The mixture had a nearly homogeneous appearance. 13.95 g of SiH-terminated linear silicone with an approximate formula MHD220MH and a viscosity of approximately 1000 mPa·s, 0.71 g of SiH-terminated pendant SiH-containing silicone with an approximate formula MHD95.5DH9.6MH and a viscosity of approximately 165 mPa·s, 22.31 g of vinyl-terminated linear silicone with a viscosity of approximately 1000 mPa·s, and 0.078 g of platinum catalyst solution were placed in a cup and mixed using a Speedmixer™ at 2000 rpm for 2 minutes (3-4 times). The resulting colorless and transparent mixture was placed in a sealed cup and allowed to cure at room temperature for 24-36 hours to obtain a cured elastomer sample.

[0120] A control sample (VP141-2-0) without silylated CD was prepared using the following procedure. 14.13 g of SiH-terminated linear silicone with approximate formula MHD220 MH and viscosity approximately 1000 mPa·s, 0.77 g of SiH-terminated pendant SiH-containing silicone with approximate formula MHD95.5DH9.6 MH and viscosity approximately 165 mPa·s, and 0.93 g of geraniol were weighed out and placed in a plastic cup. The mixture was then mixed using a Speedmixer® at 2000 rpm for 2 minutes (the mixing was repeated twice). Next, 23.09 g of vinyl-terminated linear silicone with viscosity approximately 1000 mPa·s and a platinum catalyst solution (0.075 g) were placed in the cup and mixed using a Speedmixer® at 2000 rpm for 2 minutes (the mixing was repeated 2-3 times). The resulting colorless, transparent mixture was placed in a sealed cup and left at room temperature for 24-36 hours to cure, obtaining a cured elastomer sample.

[0121] The release of geraniol from both samples (sample containing silylated CD = present invention, control = not present invention) was confirmed by heating the samples at 60°C for 150 hours using a Thermo Scientific Heratherm oven and measuring the weight loss. The release profiles of residual geraniol are shown in Figure 6.

[0122] First, rapid release of geraniol was observed from both samples due to the loss of excess uncomplexed geraniol. Note that pure geraniol completely evaporates in just a few hours. The control elastomer sample (VP141-2-0) released all of its geraniol in 72 hours, while the elastomer / CD sample still had about 6% of geraniol remaining at that point. The amount of remaining geraniol corresponds to the amount present in the 1:1 complex with CD, after which much slower release was observed.

[0123] Geraniol was completely released from the elastomer / CD sample after 140 hours. Therefore, the release of geraniol / CD in sample VP141-2-1 was extended up to 140 hours.

[0124] Examples of using silyl-modified CD for controlled release of α-tocopherol from elastomers: First, an inclusion complex of trimethylsilyl-vinyldimethylsilyl-β-cyclodextrin CH74 and α-tocopherol was prepared. Excess tocopherol (molar ratio of tocopherol to CD 20:1) was used. Trimethylsilyl-vinyldimethylsilyl-β-cyclodextrin (CH74, 0.608 g, 0.259 mmol) was weighed out and placed in a mortar, then thoroughly ground before adding tocopherol. Tocopherol (2.229 g, 5.176 mmol) was added to silyl-CD (CH74) and ground with a pestle for 15 minutes. The mixture was a yellowish semi-solid. The mixture was checked for solid lumps and ground until no lumps remained.

[0125] An elastomer / CD / tocopherol (tocopherol:CD molar ratio 20:1) matrix (VP142-1) was prepared using the following procedure.

[0126] 2.837 g of a prepared tocopherol-CD combination containing the composite and excess tocopherol (tocopherol:CD molar ratio 20:1) was placed in a plastic cup, and 12.00 g of SiH-terminated linear silicone with approximate formula MHD220 MH and viscosity of approximately 1000 mPa·s was added. The cup containing the mixture was mixed using a Speedmixer (trademark) at 2000 rpm (x3 times) for 2 minutes to form a homogeneous mixture. 8.194 g of vinyl-terminated linear silicone with viscosity of approximately 1000 mPa·s and 0.0230 g of platinum catalyst solution were added, and the mixture was mixed using a Speedmixer (trademark) at 2000 rpm (x2 times) for 2 minutes. Using the obtained mixture, a drawdown film (thickness 15 mil) was prepared on a MYLARTM sheet. The film was left to cure in a preheated oven (80°C) for 2 hours to obtain a cured elastomer film.

[0127] A control elastomer sample (VP142-0) without silylated CD was prepared by the following procedure. 10.00 g of SiH-terminated linear silicone with approximate formula MHD220 MH and viscosity approximately 1000 mPa·s, 0.200 g of SiH-terminated pendant SiH-containing silicone with approximate formula MHD95.5DH9.6 MH and viscosity approximately 165 mPa·s, and 2.409 g of α-tocopherol were weighed out and placed in a plastic cup. The mixture was then mixed using a Speedmixer™ at 2000 rpm for 2 minutes (x4). Next, 12.27 g of vinyl-terminated linear silicone with viscosity approximately 1000 mPa·s and a platinum catalyst solution (0.0249 g) were added to the cup and rapidly stirred at 2000 rpm for 2 minutes (x4). As a result, a viscous, milky, yellowish mixture was obtained. Using the resulting mixture, a drawdown film (15 mil) was prepared on a MYLARTM sheet. The film was placed in a preheated oven (80°C) and cured for 2 hours.

[0128] Tocopherol release from two samples, elastomer / CD (VP142-1) and control (VP142-0), was confirmed using the following procedure.

[0129] Samples were punched out from the cured film using a 1 cm diameter biopsy punch, weighed, and their exact mass was recorded. Each sample was placed in a sealed glass vial, and 16.00 g of isopropanol (IPA) was filled into the vial. The vials (each containing the sample and IPA) were placed in an orbital shaker. The tocopherol concentration in the IPA solution was measured by HPLC analysis of aliquots taken at different time intervals. Subsequently, the weight percentage of tocopherol remaining in each sample was calculated.

[0130] Figure 7 shows the release profiles of α-tocopherol from a silicone matrix, illustrating the residual amount of tocopherol at different time intervals, with elastomer-CD-tocopherol sample VP142-1 (solid line) representing the present invention and control VP-142-0 (dotted line) representing a non-present invention.

[0131] An initial, rapid release of excess tocopherol was observed in both samples. Subsequent release was much faster in the control sample (only about 6% of tocopherol remained after 95 hours). In the elastomer sample containing silyl CD, tocopherol release was observed more slowly (for a longer period) (approximately 35% of tocopherol still remained after 150 hours). [Brief explanation of the drawing]

[0132]

Claims

1. A curable silicone rubber composition, in which case, in relation to the total amount of the silicone rubber composition -20 to 99.9% by weight of a silicone matrix, and - At least one cyclodextrin (CD) modified by a silylation reaction in an amount of 0.1 to 80% by weight, containing a silyl group of formula (1) -(OYes(R １ ) ３ ) ｘ (1) [In the formula, R １ These are, independently of each other, the same or different, and are alkyl groups, aryl groups or alkyl-substituted aryl groups, and carbonyl groups. x is a number between 1 and 96. - 0 to 50% by weight of at least one active molecule (= guest molecule) Includes, The curable silicone rubber composition wherein the total amount of all components is always 100% by weight.

2. The curable silicone rubber composition according to claim 1, which is an addition-curable silicone composition.

3. R １ The curable silicone rubber composition according to claim 1, wherein is selected from methyl, ethyl, vinyl, and phenyl.

4. The curable silicone rubber composition according to claim 1, wherein x is a value between 1 and 30.

5. The curable silicone rubber composition according to claim 1, wherein the guest molecule is selected from the group consisting of drugs, pharmaceuticals, cosmetics or personal care or health active substances, biocides, insecticides, fungicides, herbicides, pheromones, fragrances, flavorings, pigments, pharmaceutically active compounds, natural oils or other oils, antigens, active compounds for antistatic or flame-retardant finishes, stabilizers (ultraviolet light), dyes, and odor-generating molecules, or a combination of two or more such molecules.

6. A method for producing the curable silicone rubber composition described in claim 1, comprising the step of mixing all the compounds by standard mixing techniques at room temperature or by heating.

7. A silicone product obtained by filling a mold with the curable silicone rubber composition described in claim 1, or by applying it to a surface and then curing it.

8. Use of the silicone product according to claim 7, in which it contains an active substance, for controlled release, delayed release, or induced release of the active substance.

9. Use of the silicone product according to claim 8 in any one application selected from the group consisting of pharmaceutical applications, cosmetic applications, personal care applications, wellness applications, room fragrance applications, biocides, insecticides, fungicides, herbicides, and textile applications.

10. Use of the silicone product according to claim 7 for the purpose of capturing unwanted substances when it does not contain an active substance.

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