In-situ curing silicone foam for wound care

Abstract

The present invention provides a multiphase silicone composition comprising a. a first phase comprising silicone, wherein said silicone comprises a vinyl- functionalized silicone polymer, and optionally a catalyst, b. a second phase comprising silicone, wherein said silicone comprises a cross linker, c. optionally a third phase, wherein at least one of said phases in the composition comprises an acid, and wherein at least one of said phases in the composition comprises a base, wherein said base is a carbonate or a bicarbonate, and wherein said acid and said base is present in difference phases in the composition, and wherein at least one of said phases in the composition comprises glycerol, and wherein at least one of said phases in the composition is an emulsion.

Description

[0001] P471393EP00 ln-situ curing silicone foam for wound care

[0002] Technical field of the invention

[0003] The invention relates to a composition and method to produce an in-situ forming foam dressing for cavity wounds. In particular, the invention related to a multiphase silicone composition comprising a first phase comprising silicone, wherein said silicone comprises a vinyl-functionalized silicone polymer; a second phase comprising silicone, wherein said silicone comprises a cross linker; and optionally a third phase. Additionally, the invention relates to a method of producing said silicone composition, and use of said composition.

[0004] Background

[0005] Close to 50 million people are suffering from chronic wounds worldwide, and the number is steadily increasing, primarily driven by ageing populations and growing incidence of obesity, diabetes and cardiovascular diseases. The socio-economic impact of chronic wounds is significant. Treatment and care of chronic wounds account for more than 3% of the total healthcare expenditure in developed countries, and the hard-to-heal chronic wounds often lead to decreased quality of life for patients due to prolonged hospitalization, loss of function and mobility, distress, anxiety, and social isolation.

[0006] WO2016 / 189117 appear to disclose an elastomeric composition comprising a silicone rubber, glycerol, and at least one crosslinking agent, wherein said glycerol is present as discrete droplets in the silicone rubber, obtainable through the application of high shear forces.

[0007] Mazurek, P.; Ekbrant, B. E. F.; Madsen, F. B.; Yu, L.; Skov, A. L. Glycerol-Silicone Foams - Tunable 3-Phase Elastomeric Porous Materials. European Polymer Journal 2019, 113, 107-114, appear to disclose Glycerol-silicone foams.

[0008] Jun, S.; Yu, L.; Skov, A. L. Remarkable Improvement of the Electro-Mechanical Properties of Polydimethylsiloxane Elastomers through the Combined Usage of Glycerol and Pyridinium-Based Ionic Liquids. Polymer-Plastics Technology and Materials 2019, 59, 3, 271-81, appear to describe electro-mechanical properties of polydimethylsiloxane elastomers through the combined usage of glycerol and pyridinium-based ionic liquids.P471393EP00 Mazurek, P.; Brook, M. A.; Skov, A. L. Glycerol-Silicone Elastomers as Active Matrices with Controllable Release Profiles. Langmuir 2018, 34, 11559-11566, appear to describe glycerolsilicone elastomers as active matrices with controllable release profiles.

[0009] Mazurek, P.; Frederiksen, N. S.; Silau, H.; Yuusuf, N. A.; Mordhorst, H.; Pamp, S. J.; Skov, A. L. Glycerol-Silicone Membranes for Sustained and Controlled Topical Delivery of Antimicrobial and Pain-Relief Drugs. Advanced Materials Interfaces 2021, 8, 2001873, appear to describe glycerol-silicone membranes for sustained and controlled topical delivery of antimicrobial and pain-relief drugs. Mazurek, P.; Yuusuf, N. A.; Silau, H.; Mordhorst, H.; Pamp, S. J.; Brook, M. A.; Skov, A. L. Simultaneous Delivery of Several Antimicrobial Drugs from Multi-Compartment Glycerol-Silicone Membranes. Journal of Applied Polymer Science 2021, 138, 50780, appear to describe simultaneous delivery of several antimicrobial drugs from multi-compartment glycerol-silicone membranes.

[0010] Summary of the invention

[0011] The present invention relates to a composition and method to produce an in-situ forming foam dressing for chronic cavity wounds. The foam dressing may deliver an undisturbed wound healing by providing an optimal healing environment inside the wound bed.

[0012] The invention is based on a reactive glycerol-in-silicone emulsion technology. The composition of the invention may be injected into the wound, and the silicone reacts to form a crosslinked matrix where the porous structure results from the reaction of organic acid and base (carbonate or bicarbonate), overall causing the formation of a foam. The buffer system ensures a favourable acidic environment in the wound. The buffer system may be combined with a pH indicator that serves as an indicator for proper mixing and for required change of dressing. Alkaline conditions in the wound bed are a clear indication of infection, and this causes the pH indicator to change color. According to an embodiment, the invention includes a two / three-phase formulation, where the phases are stored separately in a two / three / four-cartilage syringe attached with a mixing head. The formulation may contain two foaming agents, an organic acid and an inorganic base, stored separately in the syringe, which upon mixing form the build-in buffer system. During the application, the phases may be mixed, and the content may be injected into the wound, the mixing resulting in a soft and flexible foam with the exact shape of the wound bed. According to anP471393EP00 embodiment, when the phases of the formulation get in contact, the reaction between the vinyl terminated silicone and the silicone hydrides forms the silicone matrix and the reaction between the base and the acid generates the gas for foaming.

[0013] According to an embodiment, the invention relates to a multiphase composition, having a vinyl functionalized silicone (for example, a silicone part A to use the nomenclature of commercial products) in one phase and a silicone comprising a cross linker (for example silicone part B) in another phase, and having acid in one phase and base in another phase, where the phases when mixed together creates a foam. A technical effect of such a difference is that when the phases of the formulation get in contact, the reaction between the vinyl functionalised silicone polymer (for example a vinyl terminated silicone) and the cross linker (for example silicone hydrides) forms the silicone matrix and the reaction between the base and the acid generates the gas for foaming. The current products on the market fail to solve three main challenges within wound healing: - Antimicrobial efficacy: Current antimicrobial foams contain disputed silver with no proven antibacterial efficacy inside the wound, only in the foam. Toxic effects on keratinocytes and fibroblasts have been reported, impairing the wound healing.

[0014] -Too frequent dressing change: Every dressing change results in up to 12 hours set-back in healing, thereby prolonging the wound healing process.

[0015] - Lack of multifaceted wound dressings: Chronic wounds are complex due to a multifactorial dynamic tissue healing process, i.e., several dressing features are required to address this complexity. No existing product fulfils all these criteria.

[0016] There is a need for a wound dressing, addressing the limitations listed above.

[0017] Additionally, there is a need for a non-toxic wound dressing, that does not adhere to a granulating wound, while providing a seal that prevents bacteria to reach the wound.

[0018] Both constituents (glycerol and silicone) of the composition according to the invention are biocompatible and non-toxic. Additionally, silicone does not adhere strongly or fixedly to granulating wounds while providing an excellent seal that prevents bacterial ingress.

[0019] A wound dressing should provide an effective management of wound exudate combined with antimicrobial activity to deliver an optimal healing environment.P471393EP00 The composition, according to the invention, provides the benefit that it conforms to the contour of the wound bed, leaving no gap between the dressing and wound bed and, thereby, hindering internal pressure sores. The composition according to the invention is soft and based on silicone that helps to promote tissue growth. Additionally, the composition according to the invention secures a moist wound bed by the presence of glycerol. Due to the ability to keep the pH low, the composition according to the invention may inhibit microbial growth. The composition absorbs and retains wound exudate both during wear and upon removal, resulting in trauma free use. According to an embodiment, the invention may also signal unhealthy conditions in the wound via a colour change from a pH indicator.

[0020] According to a first aspect, the invention concerns a multiphase silicone composition comprising a. a first phase comprising silicone, wherein said silicone comprises a vinyl- functionalized silicone polymer, and optionally a catalyst,

[0021] b. a second phase comprising silicone, wherein said silicone comprises a cross linker, c. optionally a third phase,

[0022] wherein at least one of said phases in the composition comprises an acid, and wherein at least one of said phases in the composition comprises a base, wherein said base is a carbonate or a bicarbonate, and wherein said acid and said base is present in difference phases in the composition, and wherein at least one of said phases in the composition comprises glycerol, and wherein at least one of said phases in the composition is an emulsion.

[0023] According to a second aspect, the invention concerns a method of producing the composition, wherein said method comprises the steps of:

[0024] a. Providing a first silicone material comprising a vinyl-functionalized silicone polymer and optionally comprising a catalyst,

[0025] b. Providing a second silicone material comprising a cross linker, c. Providing glycerol, an acid and a base,

[0026] d. Mixing said first silicone material, and optionally said glycerol and optionally said acid / or base, to provide a first phase, e. Mixing said second silicone material, and optionally said glycerol and optionally said acid and / or base, to provide a second phase, andP471393EP00 f. Loading said first phase and said second phase into separate compartments in a compartment syringe,

[0027] wherein at least one of said phases comprises glycerol and wherein at least one of said phases is an emulsion.

[0028] According to a third aspect, the invention concerns a multiphase silicone composition comprising a. a first phase comprising silicone, wherein said silicone comprises a vinyl- functionalized silicone polymer, and optionally a catalyst,

[0029] b. a second phase comprising silicone, wherein said silicone comprises a cross linker, c. optionally a third phase,

[0030] wherein at least one of said phases in the composition comprises an acid, and wherein at least one of said phases in the composition comprises a base, wherein said base is a carbonate or a bicarbonate, and wherein said acid and said base is present in difference phases in the composition, and wherein at least one of said phases in the composition comprises glycerol, and wherein at least one of said phases of said composition is an emulsion,

[0031] wherein said base is potassium bicarbonate (KHCO3), sodium bicarbonate (NaHCO3), potassium carbonate (K2CO3) or sodium carbonate (Na2CO3), and

[0032] wherein said glycerol is in an amount of above 60 phr.

[0033] Detailed description of the invention

[0034] The invention relates to an in-situ forming silicone-glycerol emulsion, which via a curing reaction in the wound is tailormade resulting in a foam with the exact shape of the wound bed, thereby optimal for treating cavity wounds.

[0035] The formulation can contain an organic acid and an inorganic base, providing a built-in buffer system, which upon mixing ensure a favourable acidic environment in the wound. The buffer system controls the pH and keeps the pH low which is unfavourable for infected wounds. The organic acid acts as an antimicrobial and keeps the conditions of the wound ideal for healing.P471393EP00 The formulation can include a pH indicator, that serves as a visual indicator for proper mixing and as a wound health indicator, that tracks the pH in the wound indicating when the dressing needs to change.

[0036] The system may be a two-component system (Phase I and Phase II) or a three-component system (Phase I, Phase II, and Phase III), the system may comprise a medical grade silicone elastomer emulsified with glycerol, an organic acid, and an inorganic base, serving as foaming system, into storage-stable compositions that are mixed upon injection into the wound. The two foaming agents may be stored in the phases separately. The reaction between the base and the acid upon mixing generates the gas for foaming.

[0037] The invention will hereafter be described by way of the following non-limiting items.

[0038] According to an embodiment, the invention concerns a multiphase silicone composition comprising a. a first phase comprising silicone, wherein said silicone comprises a vinyl- functionalized silicone polymer, and optionally a catalyst,

[0039] b. a second phase comprising silicone, wherein said silicone comprises a cross linker, c. optionally a third phase,

[0040] wherein at least one of said phases in the composition comprises an acid, and wherein at least one of said phases in the composition comprises a base, wherein said base is a carbonate or a bicarbonate, and wherein said acid and said base is present in difference phases in the composition, and wherein at least one of said phases in the composition comprises glycerol, and wherein at least one of said phases in the composition is an emulsion.

[0041] A vinyl terminated chain is a polymer with vinyl groups at the chain ends. The position of the vinyl group is specified but the polymer is not specified. The term "telechelic polymer" is also commonly used.

[0042] A vinyl functionalized silicone (polysiloxane) is a silicone polymer with vinyl groups at either the chain ends or as a side group on the main polysiloxane chain. The polymer is specified to silicone, but the positions of the vinyl groups are unspecified.

[0043] A vinyl terminated silicone is a silicone polymer with vinyl groups at the chain ends. Both the polymer and the position of the vinyl group are specified.P471393EP00 An emulsion may be defined as a mixture of two or more liquids that are normally immiscible. Assuming two liquids present, then one of the liquids will be dispersed as small droplets in the other liquid, creating a stable mixture of the two immiscible liquids, denoted an emulsion.

[0044] According to an embodiment, the invention concerns the composition, wherein said first phase comprises a vinyl functionalized silicone, wherein said vinyl functionalized silicone is a vinyl-terminated polydimethylsiloxane. According to an embodiment, the invention concerns the composition, wherein said first phase comprises a vinyl functionalized silicone, wherein said vinyl functionalized silicone is a vinyl-functionalized polydimethylsiloxane.

[0045] According to an embodiment, said vinyl-functionalized silicone polymer may be a vinyl terminated chain, a vinyl functionalized silicone or vinyl terminated silicone.

[0046] A cross linker may be defined as a molecule that facilitates the formation of a three-dimensional network. For example, in addition curing systems the vinyl group in a vinyl functionalized polydimethylsiloxane reacts with a cross linker containing Si-H bonds in the presence of a catalyst. The cross linker needs an average functionality of more than two to form a network. The cross linker may be a methylhydrosiloxane-dimethylsiloxane copolymer.

[0047] According to an embodiment, said cross linker may be a silicone polymer or oligomer comprising more than two hydride groups, such as 3 hydride groups, 2 -30 hydride groups, 3 - 25, 4 - 20, 5 -15, or about 10 hydride groups. According to an embodiment, said cross linker may be a hydride functionalised silicone. According to an embodiment, said cross linker may be a methylhydrosiloxane-dimethylsiloxane copolymer.

[0048] Silicone hydrides are a silicone polymer chain with hydride at either the chain ends or as side groups on the silicone backbone. According to an embodiment, the silicone hydrides are used as crosslinkers.

[0049] According to an embodiment, the invention concerns the composition, wherein said catalyst is a Pt (platinum) catalyst.

[0050] Examples of commercially available Pt catalysts and the producers thereof are described below:

[0051] Catalyst 511: 1% Pt, Evonik

[0052] Catalyst 512: 2% Pt, EvonikP471393EP00 Catalyst 517: 2% Pt, Evonik

[0053] SIP6831.2: 2% Pt in xylene, Gelest

[0054] SIP6832.2: PLATINUM-CYCLOVINYLMETHYLSILOXANE COMPLEX, Gelest

[0055] SIP6830.3: 3% Pt in vinyl terminated PDMS, Gelest

[0056] The catalysts vary in e.g. ligand, solvent, platinum content, viscosity, and vinyl content for those complexed with telechelic PDMS oligomers.

[0057] According to an embodiment, the invention concerns the composition, wherein said phases in the composition when mixed together create a foam, and wherein said liquid foam formulation is an emulsion.

[0058] According to an embodiment, the invention concerns the composition, wherein said silicone of said second phase additionally comprises a vinyl-functionalized silicone polymer.

[0059] According to an embodiment, the invention concerns the composition, wherein said acid and said base forms a buffer system upon mixing.

[0060] According to an embodiment, the invention concerns the composition, wherein in at least one phase, said silicone comprises glycerol droplets.

[0061] According to an embodiment, the invention concerns the composition, wherein said glycerol droplets has a size of about 0.1. - 20 pm, 1 - 10 pm, 2-9 pm, 3 -8 pm, 4- 7 pm, 5 -6 pm or about 5 pm.

[0062] According to an embodiment, the invention concerns the composition, wherein in at least one phase, said silicone comprises uniformly distributed glycerol droplets.

[0063] According to an embodiment, the invention concerns the composition, wherein said glycerol is glycerol droplets.

[0064] According to an embodiment, the invention concerns the composition, wherein said acid and / or said base is dissolved in said glycerol. According to an embodiment, the invention concerns the composition wherein said glycerol is emulsified in said silicone.P471393EP00 According to an embodiment, the invention concerns the composition, wherein said acid and / or said base is dissolved, dispersed, or emulsified in said glycerol, and thereafter said glycerol is emulsified in said silicone.

[0065] According to an embodiment, the invention concerns the composition, wherein said acid is an organic acid.

[0066] According to an embodiment, the invention concerns the composition, wherein at least one phase comprises a pt-catalysed silicone.

[0067] According to an embodiment, the invention concerns the composition, wherein said glycerol is in an amount of 1 - 120 parts per hundred rubber, 5 - 115 parts per hundred rubber or preferably, 20 - 110 parts per hundred rubber (phr). The unit of phr is used for ease when formulating.

[0068] According to an embodiment, the invention concerns the composition, wherein said glycerol is in an amount of about 20 phr, about 40 phr, about 60 phr, about 80 phr or about 100 phr.

[0069] According to an embodiment, the invention concerns the composition, wherein said glycerol is in an amount of 20 - 110 phr, 20 - 100 phr, 25-110 phr, 35 - 95 phr, 40 - 90 phr, 45 - 85 phr, 50 - 90 phr, 50 - 80 phr, 55 - 75 phr, 40 - 90 phr, or 60 - 70 phr.

[0070] According to an embodiment, the invention concerns the composition, wherein said composition comprises at least one acid, at least two acids or at least three acids.

[0071] According to an embodiment, the invention concerns the composition, wherein said acid is a citric acid, acetic acid, a hyaluronic acid or a lactic acid, preferably L-lactic acid (C3H6O3).

[0072] According to an embodiment, the invention concerns the composition, wherein at least one of said phases in the composition comprises at least two different acids, preferably lactic acid and citric acid.

[0073] According to an embodiment, the invention concerns the composition, wherein said acid is in an amount of 0.5 - 50 parts per hundred glycerol, 0.5 - 33 parts per hundred glycerol, 1 -32 parts per hundred glycerol, 1-20 parts per hundred glycerol, 0.9 - 21 parts per hundred glycerol, 1 - 15 parts per hundred glycerol, 5-15 parts per hundred glycerol, or preferably 5-20 parts per hundred glycerol (phg).

[0074] Parts per hundred glycerol of a given component "x" were calculated by:P471393EP00 m(x)

[0075] * 100

[0076]

[0077] m(glycerol')

[0078] Where m(x) is the mass of a given component and m(glycerol) is the mass of glycerol in the formulation. For example, 5 phg lactic acid indicates that 5 g of lactic acid is added to the formulation containing 100 g of glycerol the 5 g of lactic acid and the 100 g of glycerol can be split into the different phases.

[0079] According to an embodiment, the invention concerns the composition, wherein said base is potassium bicarbonate (KHCO3), sodium bicarbonate (NaHCO3) or potassium carbonate (K2CO3). According to an embodiment, the invention concerns the composition, wherein said base is K2CO3. According to an embodiment of the invention, said base is KHCO3.

[0080] According to an embodiment, the invention concerns the composition, wherein at least one of said phases in the composition comprises at least two different bases.

[0081] According to an embodiment, the invention concerns the composition, wherein said base is in an amount of 0.1 - 15 parts per hundred glycerol, 0.5-15 parts per hundred glycerol, 0.5 - 10 parts per hundred glycerol, or preferably 0.5 - 5 parts per hundred glycerol (phg).

[0082] According to an embodiment, the invention concerns the composition, wherein said composition comprises a resin, preferably SQO-229Q. resin, such as SQO-229Q. resin from Gelest Inc, US.

[0083] SQO-229Q. resin is to be understood as si la n ol-tri met hylsi ly I modified Q. resin.

[0084] According to an embodiment, the invention concerns the composition, wherein said resin is in an amount of 0.1 - 10 parts per hundred rubber, 0.1 - 5 parts per hundred rubber or preferably 0.2 -1 parts per hundred rubber (phr).

[0085] According to an embodiment, the invention concerns the composition, wherein said composition comprises an emulsifier, preferably DBE-821, Span80, Tween80, PPG1000, PPG2000, PEG200, PEG400, or PEG600.

[0086] According to an embodiment, the invention concerns the composition, wherein the emulsifier can be added to any or all phases of the composition to stabilise the system. According to an embodiment, the invention concerns the composition, wherein the emulsifier is added to a phase that is an emulsion.P471393EP00 According to an embodiment, the invention concerns the composition, wherein said composition comprises an emulsifier in an amount of 0.1 - 40 parts per hundred rubber, 0.2 - 30 parts per hundred rubber, 0.2 - 20 parts per hundred rubber, 0.2 - 10 parts peer hundred rubber, 0.2 - 5 parts per hundred rubber, or preferably 0.4 - 20 parts per hundred rubber (phr).

[0087] According to an embodiment, the invention concerns the composition, wherein said composition comprises a pH indicator.

[0088] According to an embodiment, the invention concerns the composition, wherein the composition comprises a pH indicator, wherein said pH indicator in one of the phases.

[0089] According to an embodiment, the invention concerns the composition, wherein said pH indicator is selected among a red cabbage extract, Anthocyanin, Bromothymol blue, Bromophenol blue, and Bromocresol purple.

[0090] When a pH indicator is present in one of the phases, the phases will have different colours, proper mixing can therefore be confirmed visually by observing uniform colour of the mixture when applied. The colour will depend on the pH indicator. As an example, phase I could comprise no pH indicator and therefore be white, and phase II could comprise the base and bromothymol blue and therefore being blue. When mixed, the resulting solution, the foam will be yellow since the mixed formulation is acidic. The foam will change colour back to blue / green, indicating the need for change of a wound dressing.

[0091] According to an embodiment, the invention concerns the composition, wherein said pH indicator is in an amount of 0.001 - 1.5 parts per hundred rubber, 0.1 - 1 parts per hundred rubber or preferably 0.1 - 0.5 parts per hundred rubber (phr).

[0092] According to an embodiment, the invention concerns the composition, wherein said composition additionally comprises a silicone oil, preferably DMS-T31.

[0093] A silicone oil may be defined as a non-reactive oil. A silicone oil may be used to adjust the softness of the resulting foam and / or to decrease the viscosity of the composition according to the invention.

[0094] According to an embodiment, the invention concerns the composition, wherein the viscosity in the first phase and the second phase is about the same, for example, about 1-300 Pa s, 20-300 Pa s, 40-P471393EP00 250 Pa s, and optionally, wherein the viscosity in the third phase is about the same as in the first phase and / or the second phase.

[0095] According to an embodiment, the invention concerns the composition, wherein said silicone oil is in an amount of 0.001 - 25 parts per hundred rubber, 0.1 - 20 parts per hundred rubber, or preferably 1 - 15 parts per hundred rubber (phr).

[0096] According to an embodiment, the invention concerns the composition, wherein said composition comprises water, preferably in an amount of 0.1 - 50 parts per hundred rubber, 0.1 - 30 parts per hundred rubber, 1 -30 parts per hundred rubber, or preferably 10 - 20 parts per hundred glycerol (phr). According to an embodiment, the invention concerns the composition, wherein said composition comprises water in said first phase.

[0097] According to an embodiment, the invention concerns the composition, wherein the composition does not comprise one or more of the following: silicone oil, water, a ph indicator or an emulsifier. According to an embodiment, the invention concerns a multiphase silicone composition comprising a. a first phase comprising silicone, wherein said silicone comprises a vinyl- functionalized silicone polymer, a catalyst, glycerol and lactic acid, and b. a second phase comprising silicone, wherein said silicone comprises a cross linker, glycerol and KHCO3,

[0098] wherein said first and said second phase are emulsions.

[0099] According to an embodiment, the invention concerns a multiphase silicone composition comprising a. a first phase comprising silicone, wherein said silicone comprises a vinyl- functionalized silicone polymer, a catalyst, glycerol and citric acid, and b. a second phase comprising silicone, wherein said silicone comprises a cross linker, glycerol and KHCO3,

[0100] wherein said first and said second phase are emulsions.

[0101] According to an embodiment, the invention concerns a multiphase silicone composition comprising a. a first phase comprising silicone, wherein said silicone comprises a vinyl- functionalized silicone polymer, a catalyst, glycerol and NaHCO3, andP471393EP00 b. a second phase comprising silicone, wherein said silicone comprises a cross linker, glycerol and lactic acid,

[0102] wherein said first and said second phase are emulsions.

[0103] According to an embodiment, the invention concerns a multiphase silicone composition comprising a. a first phase comprising silicone, wherein said silicone comprises a vinyl- functionalized silicone polymer, a catalyst, glycerol and KHCO3, and b. a second phase comprising silicone, wherein said silicone comprises a cross linker, glycerol and lactic acid.

[0104] wherein said first and said second phase are emulsions.

[0105] According to an embodiment, the invention concerns a multiphase silicone composition comprising a. a first phase comprising silicone, wherein said silicone comprises a vinyl- functionalized silicone polymer, a catalyst, glycerol and lactic acid, and b. a second phase comprising silicone, wherein said silicone comprises a cross linker, glycerol and K2CO3,

[0106] wherein said first and said second phase are emulsions.

[0107] According to an embodiment, the invention concerns a multiphase silicone composition comprising a. a first phase comprising silicone, wherein said silicone comprises a vinyl- functionalized silicone polymer, a catalyst, glycerol and K2CO3, and b. a second phase comprising silicone, wherein said silicone comprises a cross linker, glycerol and lactic acid,

[0108] wherein said first and said second phase are emulsions.

[0109] According to an embodiment, the invention concerns a multiphase silicone composition comprising a. a first phase comprising silicone, wherein said silicone comprises a vinyl- functionalized silicone polymer, a catalyst, and lactic acid, and

[0110] b. a second phase comprising silicone, wherein said silicone comprises a cross linker, and glycerol, and

[0111] c. a third phase comprising glycerol and K2CO3

[0112] wherein said second phase is an emulsion.P471393EP00 According to an embodiment, the invention concerns a multiphase silicone composition comprising a. a first phase comprising silicone, wherein said silicone comprises a vinyl- functionalized silicone polymer, a catalyst, glycerol and lactic acid, and b. a second phase comprising silicone, wherein said silicone comprises a cross linker, and

[0113] c. a third phase comprising glycerol and K2CO3,

[0114] wherein said first phase is an emulsion.

[0115] According to an embodiment, the invention concerns a multiphase silicone composition comprising a. a first phase comprising silicone, wherein said silicone comprises a vinyl- functionalized silicone polymer, a catalyst, glycerol and lactic acid, and b. a second phase comprising silicone, wherein said silicone comprises a cross linker, and glycerol and

[0116] c. a third phase comprising a vinyl-functionalized silicone polymer, glycerol and KHCO3, and optionally a catalyst,

[0117] wherein said first phase and said second phase and said third phase are emulsions.

[0118] According to an embodiment, the invention concerns a multiphase silicone composition comprising a. a first phase comprising silicone, wherein said silicone comprises a vinyl- functionalized silicone polymer, a catalyst, and lactic acid, and

[0119] b. a second phase comprising silicone, wherein said silicone comprises a cross linker, and glycerol and

[0120] c. a third phase comprising a vinyl-functionalized silicone polymer, glycerol and KHCO3, and optionally a catalyst,

[0121] wherein said second phase and said third phase are emulsions.

[0122] According to an embodiment, the invention concerns a multiphase silicone composition comprising a. a first phase comprising silicone, wherein said silicone comprises a vinyl- functionalized silicone polymer, a catalyst, glycerol, lactic acid, and citric acid andP471393EP00 b. a second phase comprising silicone, wherein said silicone comprises a cross linker, and glycerol and

[0123] c. a third phase comprising a vinyl-functionalized silicone polymer, glycerol and KHCO3, and optionally a catalyst,

[0124] wherein said first phase and said second phase and said third phase are emulsions. According to an embodiment, the invention concerns a multiphase silicone composition comprising a. a first phase comprising silicone, wherein said silicone comprises a vinyl- functionalized silicone polymer, a catalyst, water, lactic acid, and acetic acid and b. a second phase comprising silicone, wherein said silicone comprises a cross linker, and glycerol and

[0125] c. a third phase comprising a vinyl-functionalized silicone polymer, glycerol and KHCO3, and optionally a catalyst,

[0126] wherein said first phase and said second phase and said third phase are emulsions. According to an embodiment, the invention concerns a multiphase silicone composition comprising a. a first phase comprising silicone, wherein said silicone comprises a vinyl- functionalized silicone polymer, a catalyst, water, and acetic acid and b. a second phase comprising silicone, wherein said silicone comprises a cross linker, and glycerol and

[0127] c. a third phase comprising a vinyl-functionalized silicone polymer, glycerol and KHCO3, and optionally a catalyst.

[0128] wherein said first phase and said second phase and said third phase are emulsions.

[0129] According to an embodiment, the invention concerns a multiphase silicone composition comprising a. a first phase comprising silicone, wherein said silicone comprises a vinyl- functionalized silicone polymer, a catalyst, lactic acid, and citric acid and b. a second phase comprising silicone, wherein said silicone comprises a cross linker, glycerol and citric acid, and

[0130] c. a third phase comprising a vinyl-functionalized silicone polymer, glycerol and KHCO3, and optionally a catalyst,

[0131] wherein said second phase and said third phase are emulsions.P471393EP00 According to an embodiment, the invention concerns a multiphase silicone composition comprising a. a first phase comprising silicone, wherein said silicone comprises a vinyl functionalized silicone polymer, a catalyst, lactic acid, and water and b. a second phase comprising silicone, wherein said silicone comprises a cross linker, glycerol, and

[0132] c. a third phase comprising a vinyl-functionalized silicone polymer, glycerol and KHCO3, and optionally a catalyst.

[0133] wherein said first phase and said second phase and said third phase are emulsions. According to an embodiment, the invention concerns a multiphase silicone composition comprising a. a first phase comprising silicone, wherein said silicone comprises vinyl functionalized silicone polymer, a catalyst, lactic acid, citric acid and water and b. a second phase comprising silicone, wherein said silicone comprises a cross linker, glycerol and citric acid, and

[0134] c. a third phase comprising a vinyl-functionalized silicone polymer, glycerol and KHCO3, and optionally a catalyst.

[0135] wherein said first phase and said second phase and said third phase are emulsions. According to an embodiment, the invention concerns a multiphase silicone composition comprising a. a first phase comprising silicone, wherein said silicone comprises a vinyl functionalized silicone polymer, a catalyst, lactic acid, citric acid, glycerol and water and

[0136] b. a second phase comprising silicone, wherein said silicone comprises a cross linker and glycerol, and

[0137] c. a third phase comprising a vinyl-functionalized silicone polymer, glycerol and KHCO3, and optionally a catalyst.

[0138] wherein said first phase and said second phase and said third phase are emulsions. According to an embodiment, the invention concerns a multiphase silicone composition comprising a. a first phase comprising silicone, wherein said silicone comprises a vinyl- functionalized silicone polymer, a catalyst, water, lactic acid, and citric acid andP471393EP00 b. a second phase comprising silicone, wherein said silicone comprises a cross linker, and glycerol

[0139] c. a third phase comprising a vinyl-functionalized silicone polymer, glycerol and KHCO3, and optionally a catalyst,

[0140] wherein said first said second phase and said third phase are emulsions.

[0141] According to an embodiment, the invention concerns a multiphase silicone composition comprising a. a first phase comprising silicone, wherein said silicone comprises a vinyl- functionalized silicone polymer, a catalyst, glycerol, and citric acid and b. a second phase comprising silicone, wherein said silicone comprises a cross linker, and glycerol

[0142] c. a third phase comprising a vinyl-functionalized silicone polymer, glycerol and KHCO3, and optionally a catalyst,

[0143] wherein said first said second phase and said third phase are emulsions.

[0144] According to an embodiment, the invention concerns a kit of parts comprising

[0145] a. The multiphase composition according to the invention, and

[0146] b. at least one syringe having a mixing head.

[0147] According to an embodiment, the invention concerns a method of producing the composition according to the invention, wherein said method comprises the steps of:

[0148] a. Providing a first silicone material comprising a vinyl-functionalized silicone polymer, and optionally comprising a catalyst,

[0149] b. Providing a second silicone material comprising a cross linker, c. Providing glycerol, an acid and a base,

[0150] d. Mixing said first silicone material, and optionally said glycerol and optionally said acid / or base, to provide a first phase, e. Mixing said second silicone material, and optionally said glycerol and optionally said acid and / or base, to provide a second phase, and f. Loading said first phase and said second phase into separate compartments in a compartment syringe,

[0151] wherein at least one of said phases is an emulsion, andP471393EP00 wherein at least one of said phases comprises glycerol.

[0152] According to an embodiment, the invention concerns a method of producing the composition according to the invention, wherein said method comprises the steps of:

[0153] a. Providing a first silicone material comprising a vinyl-functionalized silicone polymer, and optionally comprising a catalyst,

[0154] b. Providing a second silicone material comprising a cross linker, c. Providing glycerol, an acid and a base,

[0155] d. Mixing said first silicone material, and optionally said glycerol and said acid, to provide a first phase,

[0156] e. Mixing said second silicone material, and optionally said glycerol and said base, to provide a second phase, and

[0157] f. Loading said first phase and said second phase into separate compartments in a compartment syringe,

[0158] wherein at least one of said phases is an emulsion, and

[0159] wherein at least one of said phases comprises glycerol.

[0160] According to an embodiment, the invention concerns a method of producing the composition according to the invention, wherein said method comprises the steps of:

[0161] a. Providing a first silicone material comprising a vinyl-functionalized silicone polymer, and optionally comprising a catalyst,

[0162] b. Providing a second silicone material comprising a cross linker, c. Providing glycerol, an acid and a base,

[0163] d. Mixing said first silicone material, and optionally said glycerol and said base, to provide a first phase,

[0164] e. Mixing said second silicone material, and optionally said glycerol and said acid, to provide a second phase, and

[0165] f. Loading said first phase and said second phase into separate compartments in a compartment syringe,

[0166] wherein at least one of said phases is an emulsion, and

[0167] wherein at least one of said phases comprises glycerol.P471393EP00

[0168] According to an embodiment, the invention concerns a method of producing the composition according to the invention, wherein said method comprises the steps of:

[0169] a. Providing a first silicone material comprising a vinyl-functionalized silicone polymer, and optionally comprising a catalyst,

[0170] b. Providing a second silicone material comprising a cross linker, c. Providing glycerol, an acid and a base,

[0171] d. Dissolving said acid or said base in said glycerol,

[0172] e. Mixing

[0173] a. said first silicone material, and

[0174] b. optionally said glycerol with dissolved acid or base, and c. optionally said acid or base,

[0175] to provide a first phase,

[0176] f. Mixing

[0177] a. said second silicone material, and

[0178] b. optionally said glycerol with dissolved acid or base, and c. optionally said acid and / or base,

[0179] to provide a second phase, and

[0180] g. Loading said first phase and said second phase into separate compartments in a compartment syringe,

[0181] wherein at least one of said phases comprises glycerol.

[0182] According to an embodiment, the invention concerns the method, wherein said method comprises a step of mixing a silicone, a base, an acid and / or glycerol, to provide a third phase.

[0183] According to an embodiment, the invention concerns the method, wherein said method comprises a step of mixing a) a silicone material, b) a glycerol with dissolved acid or base, c) a base, d) an acid and / or e) glycerol.P471393EP00 According to an embodiment, the invention concerns the method, wherein said compartment syringe is a dual compartment syringe, a three-compartment syringe, or a four-compartment syringe.

[0184] According to an embodiment, the invention concerns the method, wherein said first phase and said second phase is loaded into said separate compartments in said compartment syringe in a volumetric ratio of 1:1.

[0185] According to an embodiment, the invention concerns the method, wherein said first phase, said second phase and said third phase is loaded into said separate compartments in said compartment syringe in a volumetric ratio of 1:1:1:1, with one phase being loaded into two compartments. According to an embodiment, the invention concerns the method, wherein said mixing is performed at a level of about 500 - 5000 rpm, about 700 - 4000 rpm, or preferably about 800 -3800 rpm.

[0186] According to an embodiment, the invention concerns the method, wherein said mixing speed is performed at a level of 500 rpm, 1500 rpm, 2500 rpm or 3500 rpm.

[0187] According to an embodiment, the invention concerns the method, wherein said mixing speed is performed at 3500 rpm and said glycerol content is 80 phr.

[0188] According to an embodiment, the invention concerns the method, wherein said method comprises a step of mixing at a level of less than 1000 rpm.

[0189] In the examples contained herein, mixing is performed by a dual asymmetric centrifuge, SpeedMixer DAC 330-100 SE from FlackTek, unless otherwise stated.

[0190] It is recognized that rotational speed, expressed in rotations per minute (rpm), does not constitute a reliable or comparable measure of shear applied to a composition across different instruments and compositions, rpm is a kinematic parameter that reflects the angular velocity of a rotating element but does not inherently account for the shear forces imparted to the material. Shear is a dynamic property dependent on multiple system-specific factors, and, therefore, rpm alone cannot be used as a universal metric.

[0191] Geometric dependenciesP471393EP00 The shear rate experienced by a composition is a function of the linear velocity at the interface between the rotating element and the material, which is defined by the relationship:

[0192] v = a> • r

[0193] where to represents angular velocity and r denotes the radius of rotation. Consequently, instruments operating at identical rpm values but differing in diameter will generate substantially different tangential velocities and shear conditions. A Speedmixer has two axes of rotation, and thus, it becomes close to impossible to describe the shear forces experienced in the composition, as this will depend on several coordinates.

[0194] Material properties

[0195] Shear stress is governed by the equation:

[0196] T

[0197]

[0198] = - y =?7(y) - y

[0199] where is the viscosity of the composition and y is the shear rate, y is the shear.

[0200] Variations in viscosity, particularly in non-Newtonian systems exhibiting shear-thinning or shearthickening behavior, result in non-linear correlations between rpm and effective shear, even in the simplest of mixers. Thus, identical rpm values can produce markedly different shear environments depending on the composition's rheological characteristics.

[0201] Operational conditions

[0202] Additional factors, such as container fill level, temperature, and system geometry, further influence shear distribution. Higher container fill level will for example lead to increased temperatures inside the formulation. Temperature changes will modify the viscosity and thereby alter the shear stress at a given rpm.

[0203] Conclusion

[0204] Due to these dependencies, rpm cannot serve as a standardized or comparable measure of shear across instruments. Accurate characterization of shear requires consideration of geometric parameters, fluid rheology, and operational conditions. It is preferably expressed in terms of calculated shear rate or shear stress rather than rotational speed. However, such calculations are not available across instruments.P471393EP00 According to an embodiment, the invention concerns the method, wherein said method comprises a step of providing one or more excipients and / or additives.

[0205] According to an embodiment, the invention concerns a method of producing the composition according to the invention, wherein said method comprises the steps of:

[0206] a. Providing a first silicone material comprising a vinyl-functionalized silicone polymer, and optionally comprising a catalyst,

[0207] b. Providing a second silicone material comprising a cross linker, c. Providing glycerol, an acid and a base,

[0208] d. Optionally, providing one or more excipients and / or additives, e. Mixing said first silicone material, and optionally said glycerol and / or said acid or base at a level of at least 1000 rpm, to provide a first phase, f. Mixing said second silicone material, and optionally said glycerol and / or said acid or base at a level of at least 1000 rpm, to provide a second phase, g. Loading said first phase and said second phase into separate compartments in a compartment syringe,

[0209] wherein at least one of said phases is an emulsion, and

[0210] wherein at least one of said phases comprises glycerol.

[0211] According to an embodiment, the invention concerns a method of producing the composition of the invention, by any of the methods described in the examples. According to an embodiment, the composition according to the invention comprises the content described in any of the examples. According to an embodiment, the invention concerns a use of the composition according to the invention for the treatment of a wound, preferably a chronic cavity wound.

[0212] According to an embodiment, the invention concerns a method comprising:

[0213] a. Identifying a subject having a wound, preferably a cavity wound, b. Treating said subject with the composition according to the invention. According to an embodiment, the invention concerns the method, wherein said subject is human. According to an embodiment, the invention concerns a method of diagnosing an infection in a wound, which method comprises:P471393EP00 a. Providing a composition according to the invention, wherein said composition has been applied to a wound of a subject,

[0214] b. Detecting the colour of said composition,

[0215] c. Comparing said colour with a reference colour,

[0216] d. Determining if the colour of said composition correspond to said reference colour and evaluating the wound likely to be infected with a bacteria; or determining if the colour of said composition does not correspond to said reference colour and evaluating the subject unlikely to be infected with bacteria.

[0217] According to an embodiment, the invention concerns a method of diagnosing the need for changing a wound dressing, which method comprises:

[0218] a. Providing a composition according to the invention, wherein said composition has been applied to a subject,

[0219] b. Detecting the colour of said composition,

[0220] c. Comparing said colour with a reference colour,

[0221] d. Determining if the colour of said composition corresponds to said reference colour and evaluating the subject likely to benefit from a change of a wound dressing; or determining if the colour of said composition does not correspond to said reference colour and evaluating the subject unlikely to benefit from a change of a wound dressing.

[0222] According to an embodiment, the invention concerns a multiphase silicone composition comprising a. A first phase comprising an acid,

[0223] b. A second phase comprising a base, wherein said base is a carbonate or a bicarbonate, and

[0224] c. Optionally a third phase,

[0225] wherein said first and / or said second phase additionally comprises silicone, and

[0226] wherein said first and / or said second phase additionally comprises glycerol, and

[0227] wherein said phases when mixed together creates a foam.P471393EP00 An example of a cross-linking reaction is provided below. This is an example of the addition curing reaction of telechelic vinyl silicone polymer with a hydride functional crosslinker into a silicone elastomer / rubber:

[0228]

[0229] Cross-linker

[0230] A silicone product may comprise two parts, part A and part B. Part A may comprise a vinyl-functionalized silicone polymer, and part B may comprise a cross-linker. More specifically Part A may comprise vinyl terminated chains and a catalyst, part B may comprise hydride functionalized silicone and vinyl terminated silicone. When part A and part B are mixed they shift from liquid to solid. When the hydrides and vinyls meet in the presence of a catalyst, they form a solid network. According to an embodiment of the invention, said first phase comprises part A of a silicone product, and said second phase comprises part B of a silicone product. According to an embodiment said silicone product is " Silbione RTV 4410 QC A / B from Elkem, France".

[0231] The commercial silicone product " Silbione RTV 4410 QC A / B from Elkem, France", comprises a part A, comprising vinyl terminated chains and Pt catalyst, and a part B comprising hydride functionalized silicone and vinyl functionalized silicone.

[0232] According to an embodiment, the invention concerns the composition wherein said base is a water-or glycerol-soluble carbonate.P471393EP00 According to an embodiment, the invention concerns the composition, wherein said base is potassium bicarbonate (KHCO3), sodium bicarbonate (NaHCO3), potassium carbonate (K2CO3) or sodium carbonate (Na2CO3).

[0233] According to an embodiment, the invention concerns the composition, wherein said base is a bicarbonate, such as potassium bicarbonate (KHCO3) or sodium bicarbonate (NaHCO3).

[0234] According to an embodiment, the invention concerns the composition, wherein said glycerol is in an amount of about 80 phr or about 100 phr.

[0235] According to an embodiment, the invention concerns the composition, wherein said glycerol is in an amount of above 60 phr.

[0236] According to an embodiment, the invention concerns the composition, wherein said glycerol is in an amount of 60 - 140 phr, 65 - 135 phr, 70-130 phr, 75 - 125 phr, 80- 120 phr, 85 - 115 phr, 90 - 110 phr, 95 - 105, or about 100 phr.

[0237] According to an embodiment, the invention concerns the composition, wherein said mixing is performed at a level of about 500 - 5000 rpm, about 700 - 4000 rpm, or preferably about 800 -3800 rpm.

[0238] According to an embodiment, the invention concerns the composition, wherein said mixing speed is performed at a level of 500 rpm, 1500 rpm, 2500 rpm or 3500 rpm.

[0239] According to an embodiment, the invention concerns the composition, wherein said mixing speed is performed by a dual asymmetric centrifuge, such as a dual asymmetric centrifuge SpeedMixer DAC 330-100 SE.

[0240] According to an embodiment, the invention concerns the method, wherein said mixing is performed at a level of about 500 - 5000 rpm, about 700 - 4000 rpm, or preferably about 800 -3800 rpm.

[0241] According to an embodiment, the invention concerns the method, wherein said mixing speed is performed at a level of 500 rpm, 1500 rpm, 2500 rpm or 3500 rpm.P471393EP00 According to an embodiment, the invention concerns the method, wherein said mixing speed is performed by a dual asymmetric centrifuge, such as a dual asymmetric centrifuge SpeedMixer DAC 330-100 SE.

[0242] The description herein of any aspect or embodiment of the invention using terms such as "comprising", "having," "including," or "containing" with reference to an element or elements is intended to provide support for a similar aspect or embodiment of the invention that "consists of', "consists essentially of", or "substantially comprises" that particular element or elements, unless otherwise stated or clearly contradicted by context, e.g. a composition described herein as comprising a particular element should be understood as also describing a composition consisting of that element, unless otherwise stated or clearly contradicted by context. It will be further understood that the terms "comprises," "comprising," "includes" and / or "including," when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and / or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or groups thereof.

[0243] As used herein, the singular forms "a," "an," and "the" are intended to include the plural forms, including "at least one," unless the content clearly indicates otherwise. " At least one" is not to be construed as limiting "a" or "an."

[0244] Unless otherwise defined, all terms used herein (including technical and scientific terms) have the same meaning as commonly understood by those skilled in the art to which this invention pertains. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and will not be interpreted in an idealized or overly formal sense unless expressly so defined in the present specification.

[0245] Description of the figures

[0246] Figure 1: Schematic illustration of the U-column setup used for investigation of the generated pressure during foaming.

[0247] Figure 2: Absorption and buffer system setup. Left: drawing of the setup in CAD software. Right: schematic 2D representation of the absorption setup.

[0248] Figure 3: Droplet size of the emulsions depending on the glycerol content.P471393EP00 Figure 4: Density of foams depending on glycerol content.

[0249] Figure 5: Displacement under a force of 50 N depending on glycerol content.

[0250] Figure 6: Droplet size of the emulsions depending on the mixing speed when forming the emulsions. Figure 7: Density of foams related to the mixing speed when forming the emulsions.

[0251] Figure 8: Displacement of foams under a force of 50 N depending on the mixing speed when forming the emulsions.

[0252] Figure 9: Foam application and removal from shallow and deep cavities cut in a pork belly.

[0253] Figure 10: pH over time in an artificial wound model with the foam applied in a cavity.

[0254] Figure 11: Absorption in the foam and evaporation through the foam in an artificial wound model. Figure 12: pH over time in an artificial wound model wound with the foam under compression applied in the cavity.

[0255] Figure 13: Absorption in the foam and evaporation through the foam in an artificial wound model under compression.

[0256] Figure 14: Fluid retention after 25% compression.

[0257] Figure 15: Strain at break of the foam after 0, 1, 3, or 5 days of absorption.

[0258] Figure 16: Tensile strength at break of the foam after 0, 1, 3, or 5 days of absorption.

[0259] Figure 17: Curing profiles of formulation fabricated as described in Example 9.

[0260] Figure 18: Cross-section of foams from formulation described in Example 9 before and after preheating the formulation for 3 days at 55°C.

[0261] Figure 19: Curing profile of formulation fabricated as described in Example 10.

[0262] Figure 20: Curing profile of formulation fabricated as described in Example 11.

[0263] Figure 21: Curing profile of foams fabricated as described in Example 12 before and after heat treatment of the formulation.

[0264] Figure 22: Curing profile of foam made as in Example 19 with PEG200: Water = 1:0 before and after heat treatment of the formulation.P471393EP00 Figure 23: Curing profile of foam made as in Example 19 with PEG200: Water = 1:1 before and after heat treatment of the formulation.

[0265] Figure 24: Curing profile of foam made as in Example 19 with PEG200: Water = 1:2 before and after heat treatment of the formulation.

[0266] Figure 25: Curing profile of foam made as in Example 19 with PEG200: Water = 0:1 before and after heat treatment of the formulation.

[0267] Figure 26: Cross-section of foams with varying KHCO3 content

[0268] Figure 27: Foam with additional crosslinker (HMS-301) and lactic acid (LA_HMS), or acetic acid (AA_HMS), or lactic acid-acetic acid combination (LA_AA_HMS)

[0269] Figure 28: Optical density (OD) as a function of time for a bacterial solution starting at OD 0.05 with and without foam described in Example 26.

[0270] Figure 29: Optical density (OD) as a function of time for a bacterial solution starting at OD 0.05 with and without foam described in Example 27.

[0271] Figure 30: Phase separation samples with 150 phr glycerol.

[0272] Figures 31-34: Change in droplet size (pm) over time (days) for different mixing speeds (rpm) and glycerol content (phr). Figures 31 and 33 are formulated using S4410 and figures 32 and 34 are formulated using S184.

[0273] Figure 35: Cross-section of foams at different time points for two compartment formulation with 90 phr glycerol.

[0274] The accompanying Figure and Examples are provided to explain rather than limit the present invention.

[0275] When describing the embodiments of the present invention, the combinations of all possible embodiments have not been explicitly described. Nevertheless, the mere fact that certain measures are recited in mutually different dependent claims or described in different embodiments does not indicate that a combination of these measures cannot be used to advantage. The present invention envisages all possible combinations and permutations of the described embodiments.

[0276] Unless specifically defined herein, all technical and scientific terms used have the same meaning as commonly understood by a skilled artisan in the field.P471393EP00 All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will prevail.

[0277] Further, the materials, methods, and examples are illustrative only and are not intended to be limiting, unless otherwise specified.

[0278] Examples

[0279] Materials

[0280] The two-component silicone elastomer was the Silbione RTV 4410 QC A / B from Elkem, France. The recommended mixing ratio from the manufacturer is part A: part B 1:1. 99% pure glycerol was obtained from VWR, Denmark. The liquid glass used was " Thinking Putty - Falling Water" and obtained from Crazy Aarons, US. Silanol-trimethylsilyl modified Q. resin (SQO 229Q), polydimethylsiloxane trimethylsiloxy terminated (DMS-T46), and (25-35% methylhydrosiloxane) -dimethylsiloxane copolymer, trimethylsiloxane terminated, 25-35 cSt, (HMS-301) were obtained from Gelest, USA. 85% pure L-lactic acid was obtained from TCI, Switzerland. Polyethylene glycol with average molecular weight of 200 g / mol (PEG200), polyethylene glycol with average molecular weight of 400 g / mol (PEG400), polypropylene glycol with average molecular weight of 1000 g / mol (PPG1000), polypropylene glycol with average molecular weight of 2000 g / mol (PPG2000), bromothymol blue 95% dye content, sodium chloride 99% purity, calcium chloride 93% purity, and sodium bicarbonate (NaHCO3) 99.5% purity were obtained from Sigma Aldrich, Germany. Polyethylene glycol with an average molecular weight of 600 g / mol (PEG600) was obtained from Merck-Schuehardt, Germany. Potassium hydrogen carbonate (KHCO3) was obtained from Fluka, Germany, and potassium carbonate (K2CO3) was obtained from Merck, Germany. Emulsifier DBE-821 was obtained from ABCR GmbH, Germany. 10 mL inject syringes were from B Braun, Denmark. PET (polyethylene terephthalate) support (190 pm thick, HOSTAPHAN®, Mitsubishi Polyester Film) was purchased from Putz GmbH + Co. Folien KG, Germany. PETG basic filament was obtained from Bambu Lab, EU. Dual syringes in a volume of 50 mL (AD451000-2) and 100 mL (100011) dual cartridge sets ratio 1:1 were obtained from adhesive dispensing Ltd, UK. Static mixing heads B system mixer nozzle twist lock with an inner diameter of 4.3 and 12 mixing elements, B system mixer nozzle twist lock with an inner diameter of 5.4 and 12 mixing elements, B system mixer nozzle twist lock with an inner diameter of 7.5 and 11 mixing elements, or A-system mixer nozzle bayonet with e.g. 17 elements and an inner diameter of 5.4mm, were obtained from Adhesive DispensingP471393EP00 Ltd, UK. Tesa double-sided tape 50 mm x 2 m was obtained from LavprisVaerktpj, Denmark. An RS-8861 infrared thermometer was obtained from RS Pro, China. LB medium (Lennox, batch number 180434) was obtained from Chemsolute, Germany. Escherichia coli BL21(DE3) modified with pET21a+ for green fluorescent protein (GFP) was used. Conical falcon tubes 50 mL (Sterile) were obtained from Fisher Scientific, Denmark. Polystyrene cuvettes (with dimensions 10 x 4 x 45 mm) were obtained from Sarstedt, Germany.

[0281] Fabrication

[0282] EXAMPLES 1-10 deal with TWO-COMPARTMENT SYSTEMS and EXAMPLES 11-27 deal with THREE-COMPARTMENTS SYSTEMS.

[0283] For the dual-compartment formulations, two phases were loaded into separate compartments in a dual-compartment syringe.

[0284] For the three-compartment systems, three phases were loaded into a four-compartment syringe with a volumetric ratio of 1:1:1:1, with two identical phases.

[0285] The formulation could then be injected into a container / cavity through a mixing head for both the two-compartment and three-compartment systems. The total volumes for the formulations were 40 mL, 50 mL, or 100 mL. The mixing head was, e.g., a B system mixer nozzle twist lock with an inner diameter of 4.3 and 12 mixing elements, a B system mixer nozzle twist lock with an inner diameter of 5.4 and 12 mixing elements, a B system mixer nozzle twist lock with an inner diameter of 7.5 and 11 mixing elements, or an A-system mixer nozzle. After application through the mixing head, the foam will start to form. Mixing through the mixing heads were evaluated visually by including a pH indicator, bromothymol blue, in one phase and assessing the color change through the mixing head. Transporting the formulations through the mixing heads resulted in a uniform color halfway through for all mixing heads.

[0286] The formulation was cured into solid foams at 35 °C for 30 minutes in a laboratory oven: Memmert UF110, with forced convection, 108 liters from Buch Holm, Denmark, with 20% air circulation, unless otherwise specified.

[0287] A typical formulation consists of 2-3 emulsions (phases) containing:

[0288] A two-component silicone formulation (with its two parts annotated part A and part B)P471393EP00 Glycerol

[0289] Organic acid, e.g., lactic acid or citric acid

[0290] Inorganic base, e.g., KHCO3, NaHCO3, or K2CO3

[0291] Resin for stabilization, e.g., SQO 229Q resin

[0292] KHCO3, NaHCO3, or K2CO3were dissolved in glycerol overnight on a hotplate at room temperature with a magnetic stirrer with a mixing speed of 100 rpm unless otherwise specified.

[0293] When fabricating the formulation, a dual asymmetric centrifuge, SpeedMixer DAC 330-100 SE from FlackTek, was used to mix the compounds.

[0294] SQO 229Q resin was dissolved in either part A or part B for 5-15 minutes at 3500 rpm in a speedmixer unless otherwise specified.

[0295] The organic acid and the inorganic base were kept in separate phases. When, e.g., lactic acid and KHCO3were mixed during the application, they react and formed potassium lactate, water, and carbon dioxide gas (CO2). The resulting CO2causes gas domains to form in the formulation, resulting in a porous foam after curing. An excess of lactic acid in the formulation ensured that the foam was acidic, and the simultaneous presence of the lactic acid and lactate, the conjugated base, created a buffer system in the foam.

[0296] The nomenclature for concentrations refers to the rubber (silicone elastomer), and the concentration is stated as:

[0297] Phr = parts per hundred rubber. Parts per hundred rubber of a given component "x" were calculated by:

[0298] m(x)

[0299] phr = * 100

[0300]

[0301] m(silicone')

[0302] Where m(x) is the mass of a given component and m(silicone) is the mass of silicone rubber in the formulation. For example, 80 phr glycerol indicates that 80 g of glycerol is added to the formulation containing a total of 100 g of silicone rubber (part A + part B). The 80 g of glycerol can be separated into different phases of the formulation, and the 100 g of silicone rubber (part A and part B) have to be split into different phases.P471393EP00 The concentration of each component is given in the term "phr" as the content of the individual components is determined in relation to the silicone elastomer / rubber content.

[0303] Using "phr" as a concentration is practically relevant since it is known how much one needs to add relative to the silicone rubber. However, in many cases, the weight fraction is calculated. The weight fraction of a given component "x" is given by:

[0304] m(x') phrCx)

[0305] wt%(x) = - = - m(tot) phr(x) + phr i) + 100

[0306] Where m denotes the mass, m(tot) is the total mass, phr (x) is the phr of component x, and the sum over phr(i) is the summation of the phr's of all components (beside x) added to the formulation.

[0307] Methods

[0308] Ml - pH measurement

[0309] The pH was measured with an Accumet AP110 portable pH meter from Fisher Scientific, Denmark. The probe was inserted into the fluid, and the pH was recorded after the system stabilized.

[0310] M2 - Cross-section evaluation

[0311] The pore distribution throughout the foam was evaluated by visual inspection. The foam was applied in a container. After curing, the samples were cut in half vertically, and the cross-section was evaluated. The foam was acceptable when it formed a porous and homogeneous structure throughout the material.

[0312] M3 - Droplet size of emulsion

[0313] The droplet size was measured with a VHX-7000 digital microscope from Keyence. A drop of the emulsion was put on a microscope plate. The zoom was adjusted so that the droplets of the emulsified components were visible within the silicone matrix. A picture was recorded, and the droplet sizes of the glycerol domains were measured by marking the outline of the droplets with the built-in software. The droplet size was determined as an average of at least five droplets, and the standard deviation was determined using the Excel command stdev.s (Microsoft Excel Worksheet).

[0314] M4 - Pressure during foamingP471393EP00 The pressure generated during foaming was assessed by curing a foam in a sealed vial with a closed valve. Approximately 5 g formulation was injected into the vial and sealed immediately after injection. The sample was cured in the vial at 35 °C for 30 minutes in the oven. A U-shaped tube was filled with demineralized water and placed vertically, so the water level in the U-tube was leveled (The setup can be seen in Fig. 1). The water level was marked with a pen on the outside of the tube. After curing the formulation, the vial was connected to the U-column. The valve was opened, and the pressure was released in the tube, resulting in water displacement. The experiment was done in triplicates. The distance between the initial and the new water level was measured with a ruler. The generated pressure was calculated by

[0315] P = d * g * Q,

[0316] where P = generated pressure in Pa, g = earth's gravitational acceleration = 9.81 m / s2, Q = density of water in kg / m3, and d = displacement of water in m.

[0317] The pressure generated was normalized to 1 g of foam using the following calculation:

[0318] p

[0319] Generated pressure pr. g foam = -m,

[0320] foam

[0321] where P = pressure generated in Pa, and rrifoam = mass of the foam in g.

[0322] The volume of the setup parts was distributed as follows (see Fig. 1): Approximate volume of foam: 9 cm3, approximate volume of the vial for curing: 23 cm3, approximate volume of the vial and part of U-column before the water column: 75 cm3. The molar amount of released gas (n) was calculated assuming the ideal gas behavior:

[0323] p*v

[0324] n = —,

[0325] R*T

[0326] where P = generated pressure in Pa, V = volume of the displaced liquid, R = gas constant (8.314 J / (K*mol)), and T = temperature in K.

[0327] M5 - Absorption and buffer capacity

[0328] The setup for the absorption test was 3D printed using PETG filament. The setup consisted of a container with a diameter of 6 cm, a height of 7 cm, and a lid (see Fig. 2). The lid extended into the container with a cylinder of 5 cm in height and an inner diameter of 3 cm. The foam was cured inP471393EP00 the cylinder on a surface of liquid glass. The lid was placed on the liquid glass, cylinder down. The formulation was applied to the lid and cured at 35 °C for 30 minutes. After curing, the lid with the foam was removed from the liquid glass, and its weight was recorded (lid + foam). The mass of the foam was determined by subtracting the mass of the lid from the mass of the lid + foam. Approximately 8 g of foam, with a diameter of 3 cm, was used for the absorption test. A magnetic stirrer bar was placed in the container, and the container was filled with approximately 100 g thin artificial wound fluid, which was prepared before the experiment (composition: CaCk (0.368 g) and NaCI (8.298 g) dissolved in 1 L demineralized water). The container was closed with the lid containing the foam. The cylinder length ensured that the foam is under the water level in the container. The foam was in contact with the liquid throughout the experiment, even with water absorption and evaporation through the foam. The container was closed and sealed over the water but opened over the foam, which allowed evaporation through the foam. The weight of the container, magnet, artificial wound fluid, lid, and foam was recorded. The container was placed on a magnetic stirrer / hotplate. The temperature was set to 45 °C on the hotplate to simulate a temperature of around 37 °C in the fluid in the container. The temperature on the hotplate needed to be higher than the desired temperature in the fluid due to heat loss and inefficient heat transfer to the container. The stirring was 300 rpm.

[0329] The evaporation was calculated as the weight loss of the setup consisting of the container, magnet, artificial wound fluid, lid, and foam after 1, 3, and 5 days, respectively. The container was opened to record the absorption of the foam. The absorption was determined as the weight increase of the foam + lid. The lid and foam were wiped with a tissue on the surfaces to remove excessive water before weighing. To characterize the buffer capacity generated by the foam, the pH in the fluid was measured according to the description in Ml. The setup was closed again, and the new weight was recorded so that evaporation could be measured again. The experiment was done in triplicates.

[0330] M6 - Compression

[0331] The foam's compression force was measured with TA Instrument ElectroForce 3220, using either a 45 N load cell for small forces or a 250 N load cell for larger forces. Parallel plate geometry was used. Two methods were used: A compression to 50 N with force control and measuring the displacement, and compressions to 25% or 50% of the sample height controlling the displacement and measuring the required force. The frequency of both characterization methods was 0.1 Hz. The force was controlled in the case of smaller samples (less than 1 cm in height) to increase precision.P471393EP00 To determine the displacement at 50 N, approximately 2 g sample was used. The samples were cut into circular discs with a diameter of 2.5 cm and a height of 0.4 cm. The samples were placed between the two flat plates, and a pre-stress of 5 N was applied to ensure contact with the entire top surface of the foam.

[0332] When tracking the force for the 25% displacement, the samples weighed approximately 6-8 g. In the experiment with 50% displacement, the samples weighed approximately 4 g. After mounting the samples, a prestress of 1 N was applied to ensure contact over the entire top surface of the foam.

[0333] In both cases, the foams were compressed via a triangular waveform through five deformation cycles to the given force or displacement. The maximum displacement or the maximum force, respectively, was averaged over the five cycles. The compression was determined as an average over three compression tests.

[0334] M7 - Retention test

[0335] The absorption test was performed with the samples according to the description in M5, whereafter, the foams, including the absorbed liquid, were compressed with controlled displacement, as described in M6. The weight of the foams before and after compression was recorded. The samples were wiped with a paper towel before weighing to remove any surface water. The water loss was calculated as

[0336] m(loss during compression)

[0337] water loss = - — - - — - - - - * 100

[0338]

[0339] m(absorbed water)

[0340] The average retention of the foam was determined from three experiments.

[0341] M8 - Ultimate properties

[0342] A 1 cm layer of liquid glass was placed on a PET substrate on a glass plate. The formulation was applied on the liquid glass surface in lines of 8 cm length and width of 1 cm. The formulation was cured for 30 minutes at 35 °C. The final height of the cured foam was approximately 0.3 cm. The samples were soaked in demineralized water at 35 °C for 0, 1, 3, or 5 days. The samples were cut into a dogbone shape (full length 6.4 cm, length thin part 2.5 cm, width 3.1 mm, sample thickness approximately 3 mm) with a punch form. The samples were extended at a speed of 500 mm / min by an Instron 3340 materials testing system, INSTRON, US, until sample break. At least five samplesP471393EP00 were tested, and the corresponding stresses and strains were recorded. The ultimate properties are defined as the stress and the strain at break.

[0343] M9 - Rheology

[0344] The viscoelastic properties of the formulation over time, the so-called curing profiles, and the viscosity over shear rate were recorded by an oscillatory Discovery series Hybrid Rheometer (DHR-1) from TA Instruments. A 20 mm parallel plate, Peltier plate steel geometry, was used. The curing profile tracked the loss modulus (G") and the storage modulus (G'). When the storage modulus became higher than the loss modulus, the material became more solid than liquid. The cross-over point was referred to as the gel point. When both moduli reached a plateau, the curing was completed.

[0345] The curing profile was recorded at 32 °C for 1 hour at a strain of 1% and a frequency of 1 Hz. Unless otherwise specified, the formulation was applied through a mixing head onto the plate. The geometry was lowered to a gap of 0.8 mm. Full contact between the geometry and the formulation was confirmed visually, and the test was started. The viscosity of the formulation's phases was measured at 25 °C at a shear rate of 0.01 1 / s to 100 1 / s. The phases were applied separately on the plate, and the geometry was lowered to a gap of 0.8 mm. Full contact between the geometry and the formulation was confirmed visually, and the test was started.

[0346] MIO -3D printing

[0347] 3D printing was done using PETG basic filaments and a Bambu Lab XI - Carbon printer, from Bambu Lab, EU. The setup was drawn with the CAD software SolidWorks. The printing was done with a 0.4 nozzle on the engineering plate. The layer height was 0.2 mm, and wall loops were set to 3. The top shell layers were three layers before the infill and the top shell thickness was 0.6 mm. The bottom layers were set to 3, and the infill density was 25% in a grid pattern. The print was inspected for visible printing errors before use.

[0348] Mil - Antimicrobial effect

[0349] Luria Broth (LB) was used to make a bacteria stock solution. 2 g of LB powder was mixed with 200 mL of demineralized water and shaken until dissolved. This concentration was a 1:1 dilution compared to what was recommended by the manufacturer. The LB medium, glassware, and allP471393EP00 equipment used to prepare the experiment were sterilized at 121 °C for 20 min in a VX-150 autoclave from Systec, Germany. The bacteria were added to the LB solution and inoculated overnight at 37 °C at 250 rpm. 1 mL of the solution was transferred to a cuvette, and the optical density (OD) was measured at 600 nm using a UV-vis spectrophotometer (UV-1280) from Shimadzu, Japan. Sterilized LB was used as a reference on the spectrophotometer during the experiment. The OD of the bacteria solution was set to 0.05 by diluting it with sterilized LB broth, and the change of OD was measured after 1, 3, 6 or 24h, respectively. The bacteria solution was grown at a temperature of 37 °C, while shaking at 250 rpm for 1, 3, 6 or 24h, respectively. The bacterial growth in the presence of the foam was investigated, and as a reference, the bacterial growth without foam was used. The test was done with 4 mL bacteria solution in a falcon tube with and without foam. Triplicates were performed for all measurements. Further references to verify the experiment's validity included: LB broth without bacteria to ensure no contamination had occurred, and LB broth without bacteria with foam to ensure that observed growth was not resulting from a contamination within the foam. After the OD measurement, the pH of the bacterial solution was investigated with a pH strip.

[0350] Example 1 - Varying glycerol content and mixing speed

[0351] The effect of varying glycerol content and mixing speed on the glycerol domains' droplet size, the foams' density, and the foams' compression force were investigated.

[0352] Two data series were made: one with varying glycerol content and a mixing speed of 3500 rpm, and one with a constant glycerol content of 80 phr but with varying mixing speeds when preparing the emulsions.

[0353] The investigated glycerol contents were 0, 20, 40, 60, 80, and 100 phr, hereafter referred to as GO, G20, G40, G60, G80, and G100, respectively.

[0354] The investigated mixing speeds were 500, 1500, 2500, and 3500 rpm, respectively, hereafter referred to as G80_500, G80_1500, G80_2500, and G80_3500.

[0355] The preparation of G80_3500 was described as an example below. The other formulations were prepared similarly by changing the glycerol content or the mixing speed.

[0356] The formulations investigated consisted of the following phases (see Table 1):

[0357] Phase IP471393EP00 Part A, glycerol, and lactic acid in the specified amounts were speed-mixed for 2 minutes at 3500 rpm, resulting in an emulsion. The lactic acid content was 0.9 phr for all formulations.

[0358] Phase II

[0359] KHCO3 was dissolved in glycerol overnight on a hotplate at room temperature with a magnetic stirrer with a mixing speed of 100 rpm.

[0360] Part B and the KHCO3-glycerol solution were speed-mixed for 2 minutes at 3500 rpm, resulting in an emulsion.

[0361] The two emulsions were then loaded into a dual-compartment syringe to store the formulation and subsequently mix it via the mixing head.

[0362] A 3D-printed PETG frame mold of height 0.4 cm was placed on a PET substrate on a glass plate. Tesa double-sided tape was placed on the PET substrate, and the mold was placed onto the tape to prevent the formulation from leaking underneath the mold. The formulation was applied in the mold, and the excess was scraped off to ensure uniform height between samples. The samples were cured at 35 °C for 30 minutes. The samples were cut into circular discs with a punch tool with a diameter of 2.5 cm. The density was measured by weighing the sample and measuring the height, and an average was made from three samples. The droplet size of the non-cured but mixed samples was measured with optical microscope according to the description in M3, as an average of at least 9 randomly chosen droplets. The compression was measured by recording the displacement at an applied force of 50 N according to the description in M6.

[0363] Table 1 Composition Example 1.

[0364] Component Phr Mass for G80 (g)

[0365] Phase 1

[0366] Part A 50 12.50

[0367] Glycerol 40 10.00

[0368] Lactic acid 0.9 0.23

[0369] Phase II

[0370]

[0371] Part B 50 12.50

[0372]

[0373] P471393EP00 Glycerol 40 10.00

[0374] KHCO3 1.0 0.25

[0375] Varying glycerol content:

[0376] The droplet size of the glycerol domains in the non-cured but mixed samples did not depend on the glycerol content (see Fig. 3). Additionally, at a glycerol content of 100 phr, the standard deviation of the droplet size was significant, indicating inhomogeneous emulsions. During the formulation preparation, it was observed that the viscosity of the emulsions increased with increasing glycerol content. This could be explained by the increasing number of glycerol droplets in the emulsions, which increased the surface and, thereby, the surface tension between the silicone matrix and the glycerol domains.

[0377] Samples prepared from G20, G40, and G60 did not result in apparent visual gas domains, meaning no visible foam was formed. This was most likely due to the formulation's low viscosity, which allowed the gas formed to escape the sample before curing. Samples made from G80 and G100 resulted in foams with visual air domains. The visual observation is supported by the measured density of the samples shown as a function of glycerol content in Fig. 4.

[0378] The displacement of the samples when compressed to 50 N was recorded and is shown in Fig. 5. The displacement of the foams increases with increasing glycerol content, confirming that increased glycerol content results in softer foams.

[0379] Varying mixing speed:

[0380] The average droplet size of the glycerol domains in the samples decreased with increasing mixing speed. Additionally, the standard deviation of the droplet size also decreased, indicating an increased homogeneity in the emulsions (see Fig. 6). The viscosity of the emulsions increased with increasing mixing speed due to the decreased size and thereby increased number of glycerol droplets. This resulted in a larger surface area and, thereby, surface tension between the silicone matrix and the glycerol domains, which increased the viscosity.

[0381] Samples prepared from G80_500 and G80_1500 did not contain apparent gas domains, meaning no foam was formed. This was most likely due to the formulation's initial low viscosity, which allowed the gas formed to escape the sample before curing. In contrast, the samples with higherP471393EP00 viscosity trapped the gas in the formulation. Samples made from G80_2500 and G80_3500 resulted in foams with visual gas domains. Visual observation was supported by the measured density of the samples shown in Fig. 7.

[0382] The displacement of samples prepared at different mixing speeds at a set force of 50 N was recorded and is shown in Fig. 8. The displacement is unaffected by the mixing speeds.

[0383] Example 2 - Dual-compartment NaHCO3formulation

[0384] This example describes the fabrication of a dual-compartment formulation containing NaHCO3as a foaming agent. Foams from this formulation were used in Example 3-8.

[0385] The formulation consists of two phases containing the components listed in Table 2.

[0386] Phase I

[0387] NaHCO3was dissolved in water by stirring on a magnetic stirrer at 300 rpm at room temperature for 10 minutes.

[0388] DBE-821 and part A were speed-mixed for 2 minutes at 3500 rpm.

[0389] Glycerol and part A with DBE-821 were mixed with a spatula until an emulsion was formed, followed by speed-mixing for 2 minutes at 2500 rpm.

[0390] The NaHCO3-water solution was mixed into the emulsion with a spatula until all water was in the emulsion, followed by speed-mixing for 1 minute at 1500 rpm to obtain a homogeneous emulsion.

[0391] Phase II

[0392] SQO 229Q. resin was dissolved in part B by speed-mixing at 3500 rpm.

[0393] Glycerol and lactic acid were added to part B with resin and mixed with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0394] The two emulsions were then loaded into a dual-compartment syringe, and foams were prepared by applying the formulation in a cavity or containers and curing at 35 °C for 30 minutes.

[0395] Table 2 Composition Example 2.

[0396] Component Phr Mass (g)

[0397]

[0398] Phase IP471393EP00 Part A 50 20.00

[0399] Glycerol 27 10.61

[0400] NaHCO31.6 0.63

[0401] Water 21 8.40

[0402] DBE-821 1.1 0.42

[0403]

[0404] Phase II

[0405] Part B 50 20.00

[0406] Glycerol 44 17.40

[0407] Lactic acid 6.3 2.52

[0408] SQ.0 0.35 0.14

[0409]

[0410]

[0411] Example 3 - Generated pressure during foaming

[0412] The pressure generated during the combined curing and foaming process was measured and calculated according to the description in M4. The generated pressure was determined using the formulation described in Example 2. The excess pressure generated in the volume of approximately 75 cm3was measured from four foams of approximately 5 g each.

[0413] The water displacement (d) was between 0.13 ±0.01 m.

[0414] The generated pressure was determined to be 0.26 ± 0.007 kPa / g foam.

[0415] The amount of gas released can be calculated under the assumption of ideal gas:

[0416] Pn

[0417] P * 7 260 — * 5.81 * 10-5m3zn = = - — i - =62C+ / -0-5) -R*T8.314 - — 77 * 297.15

[0418]

[0419] g foam mol * K

[0420] The pressure generated correlates to a release of 6.2 ± 0.5 pmol gas pr. g foam, assuming an ideal gas.

[0421] Example 4 - Conforming to cavitiesP471393EP00 The foam's ability to adapt to different wound shapes was examined by applying the formulation in cavities cut in a pork belly. The pork belly was bought in a local supermarket. The cavities were made with approximately 1-2 cm in length, 1-2 cm in depth for deep cavities, and less than 1 cm in depth for superficial cavities. The formulation used was described in Example 2.

[0422] The foams were injected in the cavities, and the pork belly with formulation was heated to approximately 35 °C for 30 minutes in a regular oven set to 50 °C hot air. The surface temperature of the pork belly was measured with an infrared thermometer. After curing, the foams were removed from the pork belly with a tweezer or by hand. The foams replicated the cavity's shape, provided a perfect fit to the cavity, and could be removed in one piece without leaving residue in the pork belly.

[0423] After that, the same experiment was performed, except the cavity was filled with demineralized water before injecting the formulation into the wet pork belly cavity. The foam cured, mimicking the 3-dimensional shape of the cavity in all cases, and was easily removed from the cavity. Pictures of the foams conforming to the cavities are shown in Fig. 9.

[0424] Example 5 - Buffer system and absorption

[0425] The buffer system and absorption of foams made from the formulation described in Example 2 were investigated according to the description in M5.

[0426] The experiments showed that the artificial wound fluid's pH decreased from 7 to 4 in the first 6 h and remained low over a 5-day period (see Fig. 10). Additionally, the foam was able to handle 0.99 g / cm2 / 24 h by absorbing 0.23 g / cm2 / 24 h in the foam and allowing evaporation of 0.76 g / cm2 / 24 h through the foam (see Fig. 11).

[0427] Example 6 - Absorption and buffer system under compression

[0428] The absorption and buffer capacity were investigated under compression. The formulation described in Example 2 was tested according to the procedure in M5, except that the foam was applied in an open cylinder with a diameter of 4 cm. After curing, the foams were pressed into a 3 cm diameter cylinder to give compression from the perimeter of the foam.

[0429] The results showed that the pH of the simulated wound was lowered from 7 to 3.76 after 24 hours and kept low over 5 days. Additionally, the foam was able to handle (absorption+ evaporation) 0.62 g / cm2 / 24 h under compression (see Fig. 12 and Fig.13). The absorption under compression was the same as the absorption with no compression described in Example 5; however, the evaporationP471393EP00 through the foam under compression decreased compared to absorption of the non-compressed foam.

[0430] Example 7 - Retention

[0431] The fluid retention of the foams after absorption was investigated according to the description in M7. The absorption test was performed with the samples according to the description in M5, and the fluid retention of the foam after compression of 25% of the sample height was tested with the formulation described in Example 2.

[0432] After compressing the foam 25% of sample height, the foam retained 97% of liquid, corresponding to a fluid loss of less than 3% of the absorbed fluid (see Fig. 14).

[0433] Example 8 - Mechanical integrity

[0434] The mechanical properties of foams before and after absorption were tested with the formulation described in Example 2. The experiment was conducted according to the description in M8. The ultimate properties of the foams after absorbing fluid for 0, 1, 2, 3, and 5 days are shown in Fig. 15 and Fig. 16. Without any water absorption, the foams could stretch 380% of the original length before the break. After absorbing water for 1, 2, 3, or 5 days, the foams could stretch approximately 150% of the original length before the break.

[0435] Example 9 - Dual-compartment system - Heat stability

[0436] The effect of heat on the curing profile and the foam porosity for two dual-compartment formulations was investigated.

[0437] The first formulation was denoted KGB, in which the KHCO3-glycerol solution was emulsified in part B, and the lactic acid was added to part A. The second formulation was denoted KGA, in which the KHCO3-glycerol solution was emulsified in part A, and the lactic acid was in part B (see Table 3). The preparation of KGB is described below as an example. KGA was prepared the same way, except part A and part B were switched as was the name of the phases:

[0438] Phase I

[0439] SQO 229Q. resin was dissolved in part A by speed-mixing at 3500 rpm.P471393EP00 Glycerol and lactic acid were added to part A with resin and mixed with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0440] Phase II

[0441] KHCO3 was dissolved in glycerol overnight on a hotplate at room temperature with a magnetic stirrer with a mixing speed of 100 rpm.

[0442] Part B was mixed with the KHCO3-glycerol solution with a spatula until an emulsion was formed, followed by 2 minutes of speed-mixing at 3500 rpm.

[0443] The two emulsions were loaded into a dual-compartment syringe, and foams were prepared by applying the formulation in a cavity or containers, followed by curing at 35 °C for 30 minutes. Table 3 Composition Example 9.

[0444] KGB KGA

[0445] Component Phr Mass (g) Component Phr Mass (g)

[0446]

[0447] Phase I

[0448] Part A 50 10.00 Part A 50 10.00 Glycerol 43 8.52 Glycerol 47 9.48 Lactic acid 6.3 1.25 KHCO3 1.8 0.36 SQ.0 0.35 0.07

[0449]

[0450] Phase II

[0451] Part B 50 10.00 Part B 50 10.00

[0452]

[0453] Glycerol 47 9.48 Glycerol 43 8.52 KHCO3 1.8 0.36 Lactic acid 6.3 1.25

[0454] SQ.0 0.35 0.07

[0455]

[0456]

[0457]

[0458]

[0459] The curing profiles and the porosity of the foams were investigated before and after heating the formulation for 3 days at 55 °C in the oven. The heating condition was chosen to resemble that of ethylene oxide (ETO) sterilization, as the formulation is planned to be sterilized with ETO sterilization. After the heat treatment, the formulation was cooled to room temperature, and the curing profile was measured according to the description in M9. The porosity of the foam wasP471393EP00 investigated by visual inspection according to the description in M2. 4 g foam was cured in a container with a diameter of 2.5 cm for 30 minutes at 35 °C in the oven for the porosity evaluation. The curing profiles, as expressed by the storage and loss modulus, showed that the rheology of the formulations before heat was the same for KGA and KGB. However, the KGB foams became softer after applying heat treatment on the formulation. In contrast, the KGA foams became harder compared to the foams from the non-heated formulations, as seen by the lower storage modulus (softer) and higher storage modulus (harder), respectively, when reaching the plateau (see Fig. 17). The cross-section of the foams revealed an increased pore size after a heat treatment on the formulation, indicating a heat-induced change (see Fig. 18).

[0460] Example 10 - Dual-compartment system - K2CO3as foaming agent

[0461] Two dual-compartment systems with K2CO3as a foaming agent were investigated to increase the heat stability of the formulation described in Example 9. The first formulation was referred to as K2CO3_KGB, in which part B contained K2CO3, and the second formulation was referred to as K2CO3_KGA, in which K2CO3was added to part A.

[0462] The preparation of K2CO3_KGB is described below as an example. K2CO3_KGA was prepared the same way, except that parts A and B were switched as well as the name of the phases. The composition of the two formulations can be seen in Table 4.

[0463] Phase I

[0464] SQO 229Q. resin was dissolved in part A by speed-mixing at 3500 rpm.

[0465] Glycerol and lactic acid were added to part A with resin and mixed with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0466] Phase II

[0467] K2CO3was dissolved in glycerol overnight on a hotplate at room temperature with a magnetic stirrer with a mixing speed of 100 rpm.

[0468] Part B was mixed with the K2CO3-glycerol solution with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0469] The two emulsions were then loaded into a dual-compartment syringe, and the foams were prepared by applying the formulation in a cavity or containers, followed by curing at 35 °C for 30 minutes in the oven.P471393EP00 Table 4 Composition Example 10.

[0470] K2CO3_KGB K2CO3_KGA

[0471] Component Phr Mass (g) Component Phr Mass (g) Phase 1 Phase 1

[0472] Part A 50 10.00 Part A 50 10.00 Glycerol 42 8.47 Glycerol 48 9.53

[0473] Lactic acid 6.2 1.25 K2CO3 1.2 0.25

[0474] SQO 0.35 0.07

[0475] Phase II Phase II

[0476] Part B 50 10.00 Part B 50 10.00 Glycerol 48 9.53 Glycerol 42 8.47 K2CO3 1.2 0.25 Lactic acid 6.2 1.25

[0477] SQO 0.35 0.07

[0478]

[0479] The curing profiles of K2CO3_KGA and K2CO3_KGB were investigated according to the description in M9. Both K2CO3_KGA and K2CO3_KGB had higher initial viscosity and longer curing time, than the formulation with KHCO3described in Example 9 (see Fig. 19). The formulation KGA_K2CO3 did not cure after curing for 30 minutes at 35 °C in the oven. The foams from KGB_K2CO3 were softer, compared to the foams containing KHCO3 described in Example 9. The increased softness of KGB_K2CO3 compared to KGB was determined from the decreased value of the storage modulus.

[0480] Example 11 - Three-phase system - Part B separated from acid and base

[0481] The formulation in this example was prepared as a three-phase system, to increase the heat stability of the formulation.

[0482] The investigated formulation consisted of the following phases (see Table 5):

[0483] Phase I

[0484] SQO 229Q resin was dissolved in part A by speed-mixing at 3500 rpm.P471393EP00 Lactic acid was mixed into part A with resin with a spatula, followed by 2 minutes speedmixing at 3500 rpm.

[0485] Phase II

[0486] Glycerol and part B were mixed with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500rpm.

[0487] Phase III

[0488] K2CO3 was dissolved in glycerol overnight on a hotplate at room temperature with a magnetic stirrer with a mixing speed of 100 rpm.

[0489] Table 5 Composition Example 11.

[0490] Component Phr Mass (g)

[0491] Phase 1

[0492] Part A 50 10.00

[0493] Lactic acid 6.2 1.25

[0494] SQ.0 0.35 0.07

[0495] Phase II

[0496] Part B 50 10.00

[0497] Glycerol 42 8.47

[0498] Phase III

[0499] Glycerol 48 9.53

[0500] K2CO3 1.2 0.25

[0501]

[0502] The viscosity of the phases was evaluated visually by observing the flow, when the containers were tilted. Phase I and phase III had much lower viscosity compared to phase II; therefore, the formulation was not loaded into a syringe. The phases were mixed in quantities to ensure a ratio of 1:1 between part A and part B and the desired glycerol content. For example, for 5 g foam, 1.43 g of phase I, 2.33 g of phase II, and 1.24 g of phase III were needed. The phases were speed-mixed for 30 seconds at 3500 rpm, and cured for 30 minutes at 35 °C, resulting in a fully cured sample.P471393EP00 However, the samples did not appear porous, indicating that no foam was formed. This can be explained due to the foaming process started in the speedmixer, and due to the rotational forces, the gas escaped the formulation before curing.

[0503] The curing profile was measured according to the description in M9. The phases of the formulation were speed-mixed for 30 seconds at 3500 rpm and transferred to the rheometer using a spatula. The curing profile was investigated before and after heating the formulation for 3 days at 55 °C in closed containers in the oven. The formulation was cooled down to room temperature before measuring the curing profile again. The results showed that the storage and loss modulus curves changed shape after the formulation was exposed to heat. They became less sharp indicating a slower curing process (see Fig. 20).

[0504] Example 12 - Three-phase system - K2CO3-glycerol solution as a separate phase and lactic acid with glycerol in phase I

[0505] A three-phase system was prepared, where K2CO3and part B were in separate phases to avoid any reactions between the base and the silicone hydride. Glycerol and lactic acid were emulsified in part A, resulting in a formulation with only one phase as an emulsion (phase I).

[0506] The investigated formulation consisted of the following phases (see Table 6):

[0507] Phase I

[0508] SQO 229Q. resin was dissolved in part A by speed-mixing at 3500 rpm.

[0509] Lactic acid and glycerol were mixed into part A and resin with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0510] Phase II

[0511] Part B was used as a separate phase.

[0512] Phase III

[0513] K2CO3 was dissolved in glycerol overnight on a hotplate at room temperature with a magnetic stirrer with a mixing speed of 100 rpm.P471393EP00 Table 6 Composition Example 12.

[0514] Component Phr Mass (g)

[0515] Phase 1

[0516] Part A 50 10.00

[0517] Lactic acid 6.2 1.25

[0518] Glycerol 42 8.47

[0519] SQ.0 0.35 0.07

[0520] Phase II

[0521] Part B 50 10.00

[0522] Phase III

[0523] Glycerol 48 9.53

[0524] K2CO3 1.2 0.25

[0525]

[0526] The viscosity of the phases was evaluated visually by observing the flow when the containers were tilted. Phase II and phase III were not emulsions and had much lower viscosity than phase I; therefore, the formulation was not loaded into a syringe. Phase I, II, and III were mixed in a ratio of 2:1:1 (2.5 g: 1.25 g: 1.25 g) to ensure a mixing ratio of part A: part B 1:1, as recommended by the manufacturer. The formulation was speed-mixed in a container for 30 seconds at 3500 rpm and cured in the oven for 30 minutes at 35 °C, resulting in a cured sample. However, the samples did not appear porous, indicating that no foam was formed. The foaming process started in the speedmixer, and due to the rotational forces, the gas escaped the formulation before curing. The curing profile was measured according to the description in M9. The phases of the formulation were transferred into a container, speed-mixed for 30 seconds at 3500 rpm, and transferred to the rheometer with a spatula. The curing profile was investigated before and after heating the formulation for 3 days at 55 °C in closed containers in the oven. The formulation was cooled down to room temperature before measuring the curing profile again. The curing profile showed similar curing profiles before and after heat indicating a heat stable formulation (see Fig. 21).

[0527] Example 13 - Three-phase system - Formulation with KHCO3as foaming agentP471393EP00 This example describes a three-phase system, with emulsions in all phases of the formulation. The heat stability of the formulation was investigated.

[0528] The investigated formulation consisted of the following phases (see Table 7):

[0529] Phase I

[0530] - SQO 229Q resin was dissolved in part A by speed-mixing at 3500 rpm.

[0531] Lactic acid and glycerol were mixed into part A with resin with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0532] Phase II

[0533] Part B and glycerol were mixed with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0534] Phase III

[0535] KHCO3 was dissolved in glycerol overnight on a hotplate at room temperature with a magnetic stirrer with a mixing speed of 100 rpm.

[0536] Part A was mixed with the KHCO3-glycerol solution with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0537] The three phases were then loaded into a four-compartment syringe with phase II in two compartments, ensuring a mixing ratio of 1:2:1 (phase I: phase II: phase III).

[0538] Table 7 Composition Example 13.

[0539] Component Phr Mass (g)

[0540]

[0541] Phase I

[0542] Part A 25 10.00

[0543] Lactic acid 5.7 2.29

[0544] Glycerol 18 7.25

[0545] SQO 0.33 0.13

[0546]

[0547] Phase II

[0548]

[0549] Part B 50 20.00

[0550] Glycerol 48 19.34

[0551]

[0552] P471393EP00 Phase III

[0553]

[0554] Part A 25 10.00

[0555] Glycerol 23 9.21

[0556] KHCO31.2 0.46

[0557] The formulation was stored at 55 °C for 3 days to mimic the condition of ETO sterilization, then it was further heated for an additional 3 weeks at 45 °C. After each heat treatment, 2 g foams were prepared in containers with a diameter of 2.5 cm, and cured for 30 minutes at 35 °C, resulting in fully cured foams. The foams were immersed in 15 g demineralized water, soaked for 4 days, and the pH of the demineralized water was measured according to the description in Ml.

[0558] The pH decreased to 3.40 using the formulation after the first heat treatment (3 days 55 °C), while the pH decreased to 4.29 using the formulation with the additional heat treatment (3 days 55 °C followed by 3 weeks at 45 °C). The higher pH after the longer heat treatment indicated that part of the lactic acid disappeared from the formulation, when it was heated either by evaporation or reaction.

[0559] Example 14 - Three-phase system - Formulation with high glycerol content

[0560] A three-phase system was investigated with an increased glycerol content compared to Example 13, and the heat stability of the formulation was examined.

[0561] The formulation investigated consisted of the following phases (see Table 8):

[0562] Phase I

[0563] SQO 229Q. resin was dissolved in part A by speed-mixing at 3500 rpm.

[0564] Lactic acid and glycerol were mixed into part A with resin with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0565] Phase II

[0566] Part B and glycerol were mixed with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0567] Phase IIIP471393EP00 KHCO3was dissolved in glycerol overnight on a hotplate at room temperature with a magnetic stirrer with a mixing speed of 100 rpm.

[0568] Part A was mixed with the KHCO3-glycerol solution with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0569] The three emulsions were then loaded into a four-compartment syringe with phase II in two compartments, ensuring a mixing ratio of 1:2:1 (phase I: phase II: phase III).

[0570] The formulation was applied in a container and cured for 30 minutes at 35 °C in the oven resulting in solid foams.

[0571] Table 8 Composition Example 14.

[0572] Component Phr Mass (g)

[0573] Phase 1

[0574] Part A 25 5.00

[0575] Lactic acid 5.8 1.16

[0576] Glycerol 20 4.08

[0577] SQ.0 0.36 0.07

[0578] Phase II

[0579] Part B 50 10.00

[0580] Glycerol 53 10.63

[0581] Phase III

[0582] Part A 25 5.00

[0583] Glycerol 25 5.06

[0584] KHCO31.3 0.25

[0585]

[0586] The viscosity of the phases was evaluated by visual inspection. The phases exhibited more resistance to flow when the container was tilted, in contrast to the formulation described in Example 13. This indicates that higher viscosity was achieved with the higher glycerol content as also observed in Example 1.P471393EP00 Then the heat stability of the formulation was examined. First, formulation was stored at 55 °C for 3 days to mimic the condition of ETO sterilization, then it was further heated for an additional 3 weeks at 45 °C. After each heat treatment, 2 g foams were prepared in containers with a diameter of 2.5 cm, and cured for 30 minutes at 35 °C. After curing, the foams were immersed in 15 g demineralized water, soaked for 4 days, and the pH of the demineralized water was measured according to the description in Ml.

[0587] The pH of the demineralized water decreased to 3.43 using the formulation after the first heat treatment (3 days at 55 °C), and the pH of the demineralized water decreased to 5.24, after heating the formulation further (3 days at 55 °C followed by 3 weeks at 45°C). The higher pH after the longer heat treatment showed that part of the lactic acid disappeared from the formulation, when heated, either by evaporation or reaction.

[0588] Example 15 - Three-phase system - Formulation with silicone oil

[0589] This example describes a formulation with silicone oil in phase I to increase the viscosity of that phase.

[0590] The investigated formulation consisted of the following phases (see Table 9):

[0591] Phase I

[0592] SQO 229Q. resin was dissolved in part A by speed-mixing at 3500 rpm.

[0593] Silicone oil was added to part A with resin, and speed-mixed for 2 minutes at 3500 rpm. Lactic acid was added to the phase, and mixed with a spatula, followed by 2 minutes speedmixing at 3500 rpm.

[0594] Phase II

[0595] Part B and glycerol were mixed with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0596] Phase III

[0597] KHCO3was dissolved in glycerol overnight on a hotplate at room temperature with a magnetic stirrer with a mixing speed of 100 rpm.

[0598] Part A was mixed with the KHCO3-glycerol solution with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.P471393EP00 Table 9 Composition Example 15.

[0599] Component Phr Mass (g)

[0600] Phase 1

[0601] Part A 30 6.00

[0602] Lactic acid 5.7 1.14

[0603] Silicone oil (T45) 7.9 1.58

[0604] SQ.0 0.32 0.06

[0605] Phase II

[0606] Part B 50 10.00

[0607] Glycerol 38 7.56

[0608] Phase III

[0609] Part A 20 4.00

[0610] Glycerol 23 4.55

[0611]

[0612] The viscosity of the phases was evaluated visually by observing the flow, when the containers were tilted. The viscosity of phase I was still insufficient compared to the other phases; therefore, the formulation was not loaded into a syringe. Phase I, II, and III were speed-mixed for 30 seconds at 3500 rpm with a ratio of 1:2:1 (e.g., 0.5 g: 1 g:0.5 g), respectively.

[0613] The samples did not appear porous, indicating that no foam was formed. The foaming process started in the speedmixer, and due to the rotational forces, the gas escaped the formulation before curing. Furthermore, the samples were sticky after curing them at 35 °C for 30 minutes in the oven, and therefore this formulation was not investigated further.

[0614] Example 16 - Three-phase system - Changing emulsion component in phase I with DBE-821 to stabilize emulsion

[0615] In this example, formulations with different emulsified components in phase I were investigated. PPG2000, PPG1000, or PEG400 were used next to the lactic acid to increase the stability of the formulation.P471393EP00 DBE-821 was added to all formulations to increase the stability of the emulsion. The example below was described with PPG2000; however, the same applies for all emulsified components unless otherwise specified.

[0616] The investigated formulations consisted of the following phases (see Table 10):

[0617] Phase I

[0618] DBE-821 was speed-mixed with part A at 3500 rpm for 2 minutes.

[0619] Lactic acid and PPG2000 were mixed into part A with DBE-821 with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 1000 rpm.

[0620] Phase II

[0621] SQO 229Q. resin was dissolved in part B.

[0622] Glycerol was mixed into part B with resin with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 2500 rpm.

[0623] Phase III

[0624] KHCO3 was dissolved in glycerol overnight on a hotplate at room temperature with a magnetic stirrer with a mixing speed of 100 rpm.

[0625] Part A was mixed with the KHCO3-glycerol solution with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0626] The three emulsions were then loaded into a four-compartment syringe with phase II in two compartments, ensuring a mixing ratio of 1:2:1 (phase I: phase II: phase III). Approximately 4 g formulation was applied in containers with a diameter of 2.5 cm, followed by curing at 35 °C for 30 minutes.

[0627] Table 10 Composition Example 16.

[0628] Component Phr Mass (g)

[0629] Phase 1

[0630] Part A 25 10.00

[0631] Lactic acid 5.7 2.29

[0632] PPG2000 18 7.20

[0633] DBE-821 0.46 0.18

[0634]

[0635] P471393EP00 Phase II

[0636] Part B 50 20.00

[0637] Glycerol 48 19.16

[0638] SQO 0.46 0.18

[0639]

[0640] Phase III

[0641]

[0642] Part A 25 10.00

[0643] Glycerol 23 9.21

[0644] KHCO31.2 0.46

[0645] The appearance of the foam was evaluated visually both in one piece and after cutting the foams in half vertically. The stickiness of the foams was examined by touch.

[0646] The foams cured completely after 30 minutes at 35 °C and showed similar porosity. However, all formulations resulted in soft and sticky foams. The softest and most sticky foam was with PPG2000, followed by PPG1000, then PEG400. No further investigation was carried out using DBE-821 in combination with these emulsion components due to the undesired features of the foams.

[0647] Example 17 - Three-phase system - Changing emulsion component in phase I with SQO 229Q resin to stabilize emulsion

[0648] Emulsion components with different molecular weight were investigated to ensure a stable formulation with desired properties (less sticky and soft compared to foams from formulation described in Example 16). PEG200, PEG400, PEG600, or PPG2000 were used in phase I next to the lactic acid, and SQO 229Qwas added to increase the stability of the emulsion.

[0649] The example below was described with PEG400, however, the same applies for all emulsion components unless otherwise specified.

[0650] The formulations investigated consisted of the following phases (see Table 11):

[0651] Phase I

[0652] SQO 229Q resin was dissolved in part A by speed-mixing at 3500 rpm.P471393EP00 Lactic acid and PEG400 were added to the phase and mixed with a spatula until an emulsion was formed followed by 2 minutes speed-mixing at 3500 rpm.

[0653] Phase II

[0654] Part B and glycerol were mixed with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0655] Phase III

[0656] KHCO3 was dissolved in glycerol overnight on a hotplate at room temperature with a magnetic stirrer with a mixing speed of 100 rpm.

[0657] Part A was mixed with the KHCO3-glycerol solution with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0658] The three emulsions were then loaded into a four-compartment syringe with phase II in two compartments ensuring a mixing ratio of 1:2:1 (phase I: phase II: phase III). Approximately 4 g of foam was applied in a cup with a diameter of 2.5 cm and cured at 35 °C for 30 minutes.

[0659] Table 11 Composition Example 17.

[0660] Component Phr Mass (g)

[0661] Phase 1

[0662] Part A 25 10.00

[0663] Lactic acid 5.7 2.29

[0664] PEG400 18 7.25

[0665] SQ.0 0.33 0.13

[0666] Phase II

[0667] Part B 50 20.00

[0668] Glycerol 48 19.34

[0669] Phase III

[0670] Part A 25 10.00

[0671] Glycerol 23 9.21

[0672] KHCO3 1.2 0.46

[0673]

[0674] P471393EP00 The porosity of the foam was investigated by visual inspection according to the description in M2. The stickiness of the foam was examined by touch.

[0675] The foams cured completely after 30 minutes at 35 °C and showed similar porosity in all cases. However, all formulations resulted in soft and sticky foams. The softest and most sticky foam was the one with PPG2000, followed by PEG600, PEG400, and PEG200. No further investigation was carried out with these formulations.

[0676] Example 18 - Three-phase system - Changing emulsion component in phase I with SQO 229Q resin to stabilize emulsion 2

[0677] Formulations with different emulsion components in phase I were examined in a lower concentration compared to the formulations in Example 17. 10 phr of PPG1000, PPG2000, PEG200, or water were applied in phase I.

[0678] The example below shows a formulation with PPG2000; however, the same applies for all investigated emulsion components unless otherwise specified.

[0679] The investigated formulations consisted of the following phases (see Table 12):

[0680] Phase I

[0681] SQO 229Q resin was dissolved in part A by speed-mixing at 3500 rpm.

[0682] Lactic acid and PPG2000 were speed-mixed for 2 minutes at 3500 rpm separately.

[0683] The lactic acid-PPG2000 mixture was added to part A with resin and mixed with a spatula until an emulsion was formed followed by 2 minutes speed-mixing at 1000 rpm.

[0684] Phase II

[0685] Part B and glycerol were mixed with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0686] Phase III

[0687] KHCO3was dissolved in glycerol overnight on a hotplate at room temperature with a magnetic stirrer with a mixing speed of 100 rpm.

[0688] Part A was mixed with the KHCO3-glycerol solution with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.P471393EP00 The three emulsions were then loaded into a four-compartment syringe with phase II in two compartments, ensuring a mixing ratio of 1:2:1 (phase I: phase II: phase III). Approximately 4 g of foam was applied in a container with a diameter of 2.5 cm and cured for 30 minutes at 35 °C in the oven.

[0689] Table 12 Composition Example 18.

[0690] Component Phr Mass (g)

[0691] Phase 1

[0692] Part A 25 10.00

[0693] Lactic acid 5.4 2.15

[0694] PPG2000 10 4.14

[0695] SQ.0 0.22 0.09

[0696] Phase II

[0697] Part B 50 20.00

[0698] Glycerol 32 12.75

[0699] Phase III

[0700] Part A 25 10.00

[0701] Glycerol 15 6.07

[0702] KHCO3 0.76 0.30

[0703]

[0704] The porosity of the foam was investigated by visual inspection according to the description in M2. The stickiness of the foam was examined by touch.

[0705] During preparation of the formulation, it was observed that the formulations were less viscous compared to the ones in Example 16. The formulation flowed easier than formulations described in Example 16, when tilting the containers.

[0706] The PPG2000 resulted in the most sticky and softest foams, followed by PPG1000, then PEG200. The hardest and least sticky foam was made with water. Water as an emulsion component was investigated further due to the improved foam properties.P471393EP00 Example 19 - Formulation with PEG200 and water in phase I

[0707] A mixture of PEG200 and water, as the emulsified components in phase I, was investigated in this formulation. The effect of using a PEG-water mixture on the droplet size, pH, and curing profile was investigated. The mass ratios between PEG200: water was 1:0, 1:1, 1:2, or 0:1, referring to formulation with only PEG200 in phase I, one with half PEG200 and half water, one with 1 / 3 PEG200 and 2 / 3 water, and a formulation with only water in phase I.

[0708] The example below describes a formulation with PEG200; however, the same applies for all formulations with the different mass ratios between PEG and water, unless otherwise specified. The investigated formulations consisted of the following phases (see Table 13):

[0709] Phase I

[0710] SQO 229Q. resin was dissolved in part A by speed-mixing at 3500 rpm.

[0711] Lactic acid and PEG200 were speed-mixed for 2 minutes at 3500 rpm.

[0712] The lactic acid-PEG200 mixture was added to part A with resin and mixed with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0713] Phase II

[0714] Part B and glycerol were mixed with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0715] Phase III

[0716] KHCO3 was dissolved in glycerol overnight on a hotplate at room temperature with a magnetic stirrer with a mixing speed of 100 rpm.

[0717] Part A was mixed with the KHCO3-glycerol solution with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0718] The three emulsions were then loaded into a four-compartment syringe with phase II in two compartments, ensuring a mixing ratio of 1:2:1 (phase I: phase II: phase III). The formulation was applied in a container and cured for 30 minutes at 35 °C, resulting in cured foams.

[0719] Table 13 Composition Example 19.

[0720] Component Phr Mass (g)

[0721]

[0722] Phase IP471393EP00 Part A 25 10.00

[0723] Lactic acid 5.4 2.15

[0724] PEG200 10.4 4.14

[0725] SQ.0 0.22 0.09

[0726]

[0727] Phase II

[0728] Part B 50 20.00

[0729] Glycerol 32 12.75

[0730]

[0731] Phase III

[0732]

[0733] Part A 25 10.00

[0734] Glycerol 15 6.07

[0735] KHCO30.76 0.30

[0736] The droplet size of phase I was investigated according to the description in M3. The pH measurement was performed by immersing 2 g foam in 15 g of demineralized water for 1 day, whereafter the pH of the water was measured. The formulation was then heated at 45 °C for 1 week, a new 2 g foam was made and submerged in 15 g demineralized water. The pH was measured after 1 day of soaking. The curing profile of the formulations was investigated according to the description in M9. For further evaluation, approximately 4 g of foam was cured in a container with a diameter of 2.5 cm. The porosity of the foam was investigated by visual inspection according to the description in M2, and the softness and the stickiness of the foam was examined by touch. All foams cured completely after 30 minutes at 35 °C. The foam from the formulation with only water in phase I was harder, than the rest. The droplet sizes of the phase I are listed in Table 14. The droplet size increased with increased water content. The pH measurement showed the same pH for the foams before and after heating the formulation (see Table 15). The curing profile was investigated before and after heating the formulation (for 45 °C for 1 week), and the results showed, that the formulation cured after 30 minutes in all cases (see Fig. 22-25). The curing profile of the formulation with only water showed an increased initial viscosity after heating the formulation, indicated by a higher starting point of the loss and storage modulus.P471393EP00 Table 14 Droplet sizes in phase I for the formulation described in Example 19

[0737] PEG200 PEG200_Waterl:l PEG200_Waterl:2 Water Droplet size of 2.78 3.69 4.09 8.17 phase 1 [pm]

[0738]

[0739] Table 15 pH of foams from the formulations described in Example 19

[0740] PH PEG200 PEG200_Waterl:l PEG200_Waterl:2 Water Before heat 3.05 2.95 2.73 2.88

[0741] 1 week 45 °C 2.93 2.72 2.80 2.85

[0742]

[0743] Example 20 - Formulation with varying KHCO3content

[0744] The density and pore size of the foams were investigated with varying foaming agent (KHCO3) content. The lactic acid concentration was also increased with the increased KHCO3 concentration to ensure that the same amount of lactic acid was left in the foams after the foaming process (reaction between lactic acid and KHCO3). Formulation with PEG200, water, or a mixture of PEG200 and water (mass ratio 1:1) in phase I was investigated.

[0745] The example below describes the formulation with PEG200; however, the same applies for the rest of the formulations, unless otherwise specified. The formulations were named as COMPONENT_BZ, where COMPONENT is either PEG200, Water, or Mix and Z is the KHCO3 content in phr. The formulations investigated were: PEG200_B0.8, PEG200_B1.2, PEG200_B1.4, Water_B0.8, Water_B1.2, Water_B1.4, Mix_B0.8, Mix_B1.2, and Mix_B1.4.

[0746] The formulations investigated consisted of the following phases described with PEG200, as an example (see Table 16):

[0747] Phase I

[0748] SQO 229Q resin was dissolved in part A by speed-mixing at 3500 rpm.

[0749] Lactic acid and PEG200 were speed-mixed for 2 minutes at 3500 rpm.P471393EP00 The lactic acid-PEG200 mixture was added to part A with resin and mixed with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0750] Phase II

[0751] Part B and glycerol were mixed with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0752] Phase III

[0753] KHCO3 was dissolved in glycerol overnight on a hotplate at room temperature with a magnetic stirrer with a mixing speed of 100 rpm.

[0754] Part A was mixed with the KHCO3-glycerol solution with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0755] The three emulsions were then loaded into a four-compartment syringe with phase II in two compartments, ensuring a mixing ratio of 1:2:1 (phase I: phase II: phase III). Approximately 4 g of formulation was cured for 30 minutes at 35 °C in a container with a diameter of 2.5 cm.

[0756] Table 16 Compositions Example 20.

[0757] PEG2OO_E 10.8 PEG200J 11.2 PEG200_Bl.5 Component Phr Mass (g) Phr Mass (g) Phr Mass (g)

[0758]

[0759] Phase I

[0760] Part A 25 10.00 25 10.00 25 10.00 Lactic acid 5.4 2.15 5.8 2.31 6.0 2.42 PEG200 10 4.14 10 4.17 10 4.17 SQ.0 0.22 0.09 0.22 0.09 0.22 0.09

[0761]

[0762] Phase II

[0763] Part B 50 20.00 50 20.00 50 20.00 Glycerol 32 12.75 33 13.12 33 13.36

[0764]

[0765] Phase III

[0766]

[0767] Part A 25 10.00 25 10.00 25 10.00 Glycerol 15 6.07 15 6.08 15 6.07

[0768]

[0769]

[0770] P471393EP00 KHCO3 0.76 0.30 1.2 0.49 1.5 0.61

[0771] The density was calculated by dividing the weight of the cured sample with the volume. The volume was determined from the height of the foam (h) and the diameter of the container (2.5 cm).

[0772] / 2.5\2

[0773] Volume = h * n * —

[0774]

[0775] \ 2 )

[0776] The cross-section of the foams was evaluated according to the description in M2.

[0777] The foam with PEG200 and the highest KHCO3content (PEG200_B1.5) showed the lowest density among all foams (see Table 17). A higher density was measured in the case of the formulations with the highest KHCO3 content with water (Water_B1.5) and with the mixture (Mix_B1.5). In the cases of the formulations with water and the mixture, a lower viscosity of the formulations was observed while preparing the phases, and a solid layer in the bottom of the cured samples was visible (see Fig. 26). This indicated that the viscosity was insufficient to keep the formed gas trapped in the sample.

[0778] Table 17 Density of foams from Example 20.

[0779] Density (g / cm3) _B0.8 _B1.2 _B1.5

[0780] PEG200 0.70 0.76 0.62

[0781] Water 0.75 0.76 0.93

[0782] Mix 0.71 0.77 0.67

[0783]

[0784]

[0785] Example 21 - Formulation with varying acid concentration

[0786] The effect of the increasing lactic acid concentration on the pH of the buffer system was investigated.

[0787] The investigated formulations consisted of the following phases (see Table 18):

[0788] Phase I

[0789] SQO 229Q. resin was dissolved in part A by speed-mixing at 3500 rpm.

[0790] Lactic acid and water were speed-mixed for 2 minutes at 3500 rpm.P471393EP00 The lactic acid-water mixture was added to part A with resin and mixed with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0791] Phase II

[0792] Part B and glycerol were mixed with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0793] Phase III

[0794] KHCO3 was dissolved in glycerol overnight on a hotplate at room temperature with a magnetic stirrer with a mixing speed of 100 rpm.

[0795] Part A was mixed with the KHCO3-glycerol solution with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0796] The three emulsions were then loaded into a four-compartment syringe with phase II in two compartments, ensuring a mixing ratio of 1:2:1 (phase I: phase II: phase III). 2 g of foams were applied in a container with a diameter of 2.5 cm and cured at 35 °C for 30 minutes in the oven. Table 18 Compositions Example 21.

[0797] LA3.6 LA5.2 LA6.7 LA8.2 Component Phr Mass (g) Phr Mass (g) Phr Mass (g) Phr Mass (g)

[0798]

[0799] Phase I

[0800] Part A 25 10.00 25 10.00 25 10.00 25 10.00 Lactic acid 3.6 1.42 5.2 2.07 6.7 2.69 8.2 3.26 Water 12 4.79 10 4.14 8.8 3.53 7.4 2.95 SQ.0 0.40 0.16 0.40 0.16 0.40 0.16 0.40 0.16

[0801]

[0802] Phase II

[0803] Part B 50 20.00 50 20.00 50 20.00 50 20.00 Glycerol 32 12.75 32 12.75 32 12.75 32 12.75

[0804]

[0805] Phase III

[0806]

[0807] Part A 25 10.00 25 10.00 25 10.00 25 10.00 Glycerol 15 6.07 15 6.07 15 6.07 15 6.07

[0808]

[0809]

[0810]

[0811]

[0812] P471393EP00 KHCO30.76 0.30 0.76 0.30 0.76 0.30 0.76 0.30

[0813] For the pH measurement, the foams were placed in 15 g of demineralized water for 24 h, and the pH of the water was measured according to Ml. The results showed that the pH decreased with increased lactic acid content (see Table 19).

[0814] Table 19 pH of formulations described in Example 21.

[0815] Formulation PH

[0816] LA3.6 3.29

[0817] LA5.2 2.89

[0818] LA6.7 2.40

[0819] LA8.2 2.63

[0820]

[0821] Formulation LA3.6 was further tested for conformity to cavities in pork belly according to the description in Example 4, except that the cavities were rinsed with 1% acetic acid solution in demineralized water or with 5% acetic acid solution in demineralized water before applying the foams in the cavity.

[0822] The formulation conformed to the cavities in the pork belly and could be removed in one piece after curing for 30 minutes in a regular oven. The surface temperature of the pork belly was measured with an infrared thermometer and controlled to 35 °C.

[0823] Example 22 - Formulation with pH indicator

[0824] A formulation option with pH indicator in either phase I, II, or III was investigated to ensure proper mixing of the phases, confirm the acidity of the foams, and change color after depletion of lactic acid. Bromothymol blue was yellow in acidic environment, blue in alkaline environment, and green in a neutral solution. The color change of the dye was investigated during application of the formulations, and the properties of the foam were evaluated after curing.

[0825] The formulation below was described with the indicator in phase III as an example; however, the same applies to formulations with the indicator in different phases unless otherwise specified.P471393EP00 The investigated formulations consisted of the following phases (see Table 20):

[0826] Phase I

[0827] SQO 229Q. resin was dissolved in part A by speed-mixing at 3500 rpm.

[0828] Lactic acid and water were speed-mixed for 2 minutes at 3500 rpm.

[0829] The lactic acid-water mixture was added to part A with resin and mixed with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0830] Phase II

[0831] Part B and glycerol were mixed with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0832] Phase III

[0833] KHCO3 was dissolved in glycerol overnight on a hotplate at room temperature with a magnetic stirrer with a mixing speed of 100 rpm.

[0834] Bromothymol blue was dissolved in the KHCO3-glycerol solution by magnetic stirring at room temperature until a uniform solution was obtained.

[0835] The solution was mixed into part A with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0836] When the indicator was added to phase I in the formulation, the indicator was dissolved in the water and mixed with lactic acid prior forming the emulsion. When the indicator was applied in phase II, the indicator was dissolved in glycerol, similarly as described above.

[0837] The three emulsions were then loaded into a four-compartment syringe with phase II in two compartments ensuring a mixing ratio of 1:2:1 (phase I: phase II: phase III). The formulations were applied in a container with a diameter of 2.5 cm and cured for 30 minutes at 35 °C.

[0838] Table 20 Composition Example 22.

[0839] Component Phr Mass (g)

[0840]

[0841] Phase 1

[0842]

[0843] Part A 25 5.00

[0844] Lactic acid 5.4 1.07

[0845]

[0846] P471393EP00 Water 10 2.02

[0847] SQ.0 0.48 0.10

[0848]

[0849] Phase II

[0850] Part B 50 10.00

[0851] Glycerol 32 6.38

[0852] Phase III

[0853]

[0854] Part A 25 5.00

[0855] Glycerol 15 3.04

[0856] KHCO30.76 0.15

[0857] Bromothymol blue 0.089 0.02

[0858] The color change during applying the formulation was evaluated by visual inspection. The initial color of the phases before mixing and the color change after mixing were recorded.

[0859] When the indicator was present in phase III, the initial color of phase III was blue, indicating an alkaline pH, while phase I and II were white. During application, the color of the phases changed to a uniform yellow color indicating an acidic formulation. The uniform yellow color appeared halfway through the mixing head, showing a proper mixing after half the length of the mixing head.

[0860] When the indicator was added to phase I, the initial color of phase I was yellow, indicating an acidic pH, while phase II and III were white. In this case, the color change was more subtle, as the mixed formulation also resulted in a yellow color.

[0861] When the indicator was added in phase II, the initial color of phase II was green, indicating a neutral pH, while phase I and III were white. During application, the color of the phases changed to a uniform yellow color indicating an acidic formulation. The uniform yellow color appeared halfway through the mixing head, showing a proper mixing after half the length of the mixing head.

[0862] Example 23 - Formulations with different acids and combinations - Lactic acid and citric acid Formulations with increased acid content and a combination of acids were prepared to provide stronger acidic environment in the foam. Formulation with high lactic acid content (LA), citric acidP471393EP00 (CA), and lactic acid-citric acid combination (LA_CA) were prepared. The effect of the acid content on the foam's buffer capacity was investigated.

[0863] The investigated formulations consisted of the following phases (see Table 21):

[0864] Phase I

[0865] Acid solutions for the three formulations:

[0866] LA: Lactic acid and water were speed-mixed for 2 minutes at 3500 rpm. LA_CA: Citric acid was dissolved in water at room temperature and lactic acid was mixed to the citric acid-water-solution.

[0867] CA: In the case of increased citric acid concentrations, citric acid was dissolved in glycerol overnight on a hotplate at room temperature with a magnetic stirrer with a mixing speed of 100 rpm.

[0868] SQO 229Q. resin was dissolved in part A by speed-mixing at 3500 rpm. The formulation with only citric acid (CA) was prepared without resin, as the citric acid was dissolved in glycerol instead of water.

[0869] The acid solution was added to part A with resin and mixed with a spatula until an emulsion was formed followed by 5 minutes speed-mixing at 2500 rpm.

[0870] Phase II

[0871] Part B, PEG200, and glycerol were mixed with a spatula until an emulsion was formed, followed by 5 minutes speed-mixing at 3500 rpm Phase III

[0872] KHCO3was dissolved in glycerol overnight on a hotplate at room temperature with a magnetic stirrer with a mixing speed of 100 rpm.

[0873] Part A was mixed with the KHCO3-glycerol solution with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0874] The emulsions were then loaded into a four-compartment syringe with phase II in two compartments, ensuring a mixing ratio of 1:2:1 (phase I: phase II: phase III). Approximately 2 g formulation was applied in containers with a diameter of 2.5 cm, followed by curing at 35 °C for 30 minutes.P471393EP00 Table 21 Composition Example 23.

[0875] LA LA_CA CA

[0876] Component Phr Mass (g) Phr Mass (g) Phr Mass (g)

[0877]

[0878] Phase I

[0879] Part A 25 10.00 25 10.00 25 10.00 Lactic acid 21 8.25 10 3.99

[0880] Water 2.6 1.03 8.7 3.49

[0881] Glycerol 21 8.56

[0882] Citric acid 4.5 1.80 13 5.00

[0883] SQ.0 0.7 0.29 0.7 0.29

[0884]

[0885] Phase II

[0886] Part B 50 20.00 50 20.00 50 20.00 Glycerol 45 18.13 45 18.13 55 22.13 PEG200 2.5 1.00 2.5 1.00 2.5 1.00

[0887]

[0888] Phase III

[0889] Part A 25 10.00 25 10.00 25 10.00

[0890]

[0891] Glycerol 23 9.11 23 9.11 23 9.11 KHCO31.1 0.46 1.1 0.46 1.1 0.46

[0892]

[0893]

[0894]

[0895]

[0896]

[0897] The softness and the stickiness of the foam was evaluated by touch, and buffer capacity was measured by soaking a 2 g foam in 15 g artificial wound fluid (composition: CaCI2(0.368 g) and NaCI (8.298 g) dissolved in 1 L demineralized water), soaked for 24 hours, then the pH of the water was measured according to the description in Ml.

[0898] The foams cured completely after 30 minutes at 35 °C. The LA foam was soft and sticky, while the LA_CAfoam resulted in a stronger and less sticky foam. In the case of the formulation CA, the cured sample did not appear porous, indicating that no foam was formed.P471393EP00 The pH of the artificial wound fluid was lowered to 2.69, 2.83, and 2.82 for foams from formulation LA, LA_CA, and CA, respectively. Foams from formulation LA resulted in the lowest pH.

[0899] Example 24 - Formulations with additional crosslinker

[0900] Formulation with high lactic acid content, acetic acid, and a combination of lactic acid and acetic acid were prepared. Additional crosslinker (HMS-301) was added to the formulations, as the formulation with high lactic acid content (see Example 23) were soft and sticky. The cross-section, softness and stickiness of the foams were investigated.

[0901] The investigated formulations consisted of the following phases (see Table 22):

[0902] Phase I

[0903] SQO 229Q. resin was dissolved in part A by speed-mixing at 3500 rpm.

[0904] The acid / acid mixture (lactic acid, acetic acid, and the lactic acid-acetic acid mixture) and water were speed-mixed for 2 minutes at 3500 rpm.

[0905] The acid-water mixture was added to part A with resin and mixed with a spatula until an emulsion was formed followed by 5 minutes speed-mixing at 2500 rpm.

[0906] Phase II

[0907] Part B, PEG200, HMS-301 and glycerol were mixed with a spatula until an emulsion was formed, followed by 5 minutes speed-mixing at 3500 rpm.

[0908] Phase III

[0909] KHCO3 was dissolved in glycerol overnight on a hotplate at room temperature with a magnetic stirrer with a mixing speed of 100 rpm.

[0910] Part A was mixed with the KHCO3-glycerol solution with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0911] The emulsions were then loaded into a four-compartment syringe with phase II in two compartments, ensuring a mixing ratio of 1:2:1 (phase I: phase II: phase III). Approximately 2 g formulation was applied in containers with a diameter of 2.5 cm, followed by curing at 35 °C for 30 minutes.P471393EP00 Table 22 Composition Example 24.

[0912] LA_HMS LA AA HMS AA_HMS Component Phr Mass (g) Phr Mass (g) Phr Mass (g)

[0913]

[0914] Phase I

[0915] Part A 25 10.00 25 10.00 25 10.00

[0916] Lactic acid 21 8.25 10 3.99

[0917] Water 2.6 1.03 12 4.89 20 8.08

[0918] Acetic acid 1.0 0.40 3.0 1.19

[0919] SQ.0 0.7 0.29 0.7 0.29 0.7 0.29

[0920]

[0921] Phase II

[0922] Part B 50 20.00 50 20.00 50 20.00 Glycerol 43 17.13 43 17.13 43 17.12 PEG200 2.5 1.00 2.5 1.00 2.5 1.00

[0923] HMS-301 2.5 1.00 2.5 1.00 2.5 1.00

[0924]

[0925] Phase III

[0926]

[0927] Part A 25 10.00 25 10.00 25 10.00 Glycerol 23 9.11 23 9.11 23 9.11

[0928] KHCO3 1.1 0.46 1.1 0.46 1.1 0.46

[0929] The cross-section of the foams was evaluated according to the description in M2, and the softness and stickiness of the foam was evaluated by touch.

[0930] The foams did not cure completely after 30 min, so they were kept in the oven for an additional 30 minutes. After 1 of hour curing, the LA_AA_HMS foam was still too soft, and deformed during removal. The LA_HMS and the AA_HMS foam cured fully and resulted in porous, strong and less sticky foams (see Fig. 27).

[0931] Example 25 - Formulation with lactic acid and citric acid combination with varying citric acid concentrationP471393EP00 Formulations with lactic acid-citric acid combination were prepared with varying citric acid concentrations. The effect of the acid content on the foam's buffer capacity was investigated. The investigated formulations consisted of the following phases (see Table 23):

[0932] Phase I

[0933] SQO 229Q. resin was dissolved in part A by speed-mixing at 3500 rpm.

[0934] Citric acid was dissolved in water at room temperature, and lactic acid was mixed into the solution.

[0935] The solution was added to part A with resin and mixed with a spatula until an emulsion was formed, followed by 5 min speed-mixing at 2500 rpm.

[0936] Phase II

[0937] Part B, PEG200, and glycerol were mixed with a spatula until an emulsion was formed, followed by 5 minutes speed-mixing at 3500 rpm.

[0938] Phase III

[0939] KHCO3 was dissolved in glycerol overnight on a hotplate at room temperature with a magnetic stirrer with a mixing speed of 100 rpm.

[0940] Part A was mixed with the KHCO3-glycerol solution with a spatula until an emulsion was formed, followed by 2 minutes speed-mixing at 3500 rpm.

[0941] The emulsions were then loaded into a four-compartment syringe with phase II in two compartments, ensuring a mixing ratio of 1:2:1 (phase I: phase II: phase III). The formulation was applied to liquid glass and cured for 30 minutes at 35 °C. After curing, the foams were cut out with a punch tool of 0.8 cm diameter, resulting in foams of 0.15 ± 0.01 g.

[0942] Table 23 Composition Example 25.

[0943] LA_CA4.5 LA_CA6

[0944] Component Phr Mass (g) Phr Mass (g)

[0945]

[0946] Phase I

[0947]

[0948] Part A 25 10.00 25 10.00

[0949] Lactic acid 5.7 2.28 5.7 2.28

[0950] Water 13 5.19 11 4.59P471393EP00 Citric acid 4.5 1.80 6.0 2.40

[0951] SQ.0 0.7 0.29 0.7 0.29

[0952]

[0953] Phase II

[0954] Part B 50 20.00 50 20.00

[0955] Glycerol 45 18.13 45 18.13

[0956] PEG200 2.5 1.00 2.5 1.00

[0957]

[0958] Phase III

[0959]

[0960] Part A 25 10.00 25 10.00

[0961] Glycerol 23 9.11 23 9.11

[0962] KHCO31.1 0.46 1.1 0.46

[0963] The buffer capacity of the foams was investigated by soaking the foams in 4 g LB broth (the LB broth solution was made according to the suggestion of the manufacturer 2 g powder to 100 ml water), soaked for 24 hours, then the pH was measured according to the description in Ml. Three parallel measurements were conducted.

[0964] The pH measurement results showed that the LA_CA4.5 and the LA_CA6 decreased the pH of the LB broth from 7.1 to 6.1 ± 0.1 and 6.1 ± 0.4, respectively.

[0965] Example 26- Formulation with lactic acid and citric acid combination - Antimicrobial effect of the foam

[0966] In this example, formulation LA_CA6, described in Example 25, was further investigated. Its antimicrobial properties against Escherichia coli (E. coli) were measured by measuring optical density (OD) in a liquid sample. E. coli is a gram-negative bacterium commonly present in chronic wounds.

[0967] The phases were loaded into a four-compartment syringe with phase II in two compartments, ensuring a mixing ratio of 1:2:1 (phase I: phase II: phase III). The formulation was applied on liquid glass followed by curing for 30 min at 35 °C. After curing the foams were cut out with a punch tool of 2 cm diameter resulting in a foam of 1.2 ± 0.1 g.P471393EP00 The antimicrobial effect of the foam was investigated according to the description in Mil. The results are shown in Fig. 28. The OD of the bacterial solution without the foam increased to 2.2. (The increase in OD value does not correlate to a linear increase in the bacterial concentration when OD > 1, due to the spectrophotometer's limitation in high turbidity.) The bacterial solution with the foam reached a maximum OD of 0.4 after 6 h. After 6 h, the OD did not increase further, indicating that the bacterial growth had stopped in the LB broth solutions containing foams. The pH of the bacterial solution increased from 7 to 8 over 24 h; however, in the presence of the foam, the pH decreased from 7 to 3.5 over 24 h.

[0968] Example 27 - Formulation with lactic acid and high citric acid concentration - Antimicrobial effect of the foam

[0969] A formulation with lactic acid and a higher citric acid concentration was prepared (compared to the formulation LA_CA6 in Example 25) to increase the foam's antimicrobial properties. The foam's antimicrobial properties against Escherichia coli (E. coli) were investigated by optical density (OD) measurement in a liquid sample.

[0970] The investigated formulation consisted of the following phases (see Table 24):

[0971] Phase I

[0972] SQO 229Q resin was dissolved in part A by speed-mixing at 3500 rpm.

[0973] Citric acid was dissolved in water at room temperature, and lactic acid was mixed into the solution.

[0974] The solution was added to part A with resin and mixed with a spatula until an emulsion was formed, followed by 5 min speed-mixing at 2500 rpm.

[0975] Phase II

[0976] Citric acid was dissolved in glycerol overnight on a hotplate at room temperature with a magnetic stirrer with a mixing speed of 100 rpm.

[0977] Part B, PEG200, and glycerol were mixed with a spatula until an emulsion was formed, followed by 5 min speed-mixing at 3500 rpm.

[0978] Phase III

[0979] KHCO3was dissolved in glycerol overnight on a hotplate at room temperature with a magnetic stirrer with a mixing speed of 100 rpm.P471393EP00 Part A was mixed with the KHCO3-glycerol mixture with a spatula until an emulsion was formed, followed by 5 min speed-mixing at 3500 rpm.

[0980] The three emulsions were then loaded into a four-compartment syringe with phase II in two compartments, ensuring a mixing ratio of 1:2:1 (phase I: phase II: phase III). All parts of the applicator were rinsed with ethanol to prevent bacteria from entering the formulation during application.

[0981] Table 24 Composition Example 27.

[0982] Component Phr Mass (g)

[0983] Phase 1

[0984] Part A 25 10.00

[0985] Lactic acid 5.7 2.28

[0986] Water 11 4.59

[0987] Citric acid 6.0 2.40

[0988] SQ.0 0.72 0.29

[0989] Phase II

[0990] Part B 50 20.00

[0991] Glycerol 35 14.13

[0992] Citric acid 10 4.00

[0993] PEG200 2.5 1.00

[0994] Phase III

[0995] Part A 25 10.00

[0996] Glycerol 23 9.11

[0997] KHCO3 1.1 0.46

[0998]

[0999] The formulation was applied to liquid glass and cured for 30 min at 35 °C. After curing, the foams were cut out with a punch tool of 2 cm diameter, resulting in a foam of 0.79 ± 0.07 g.P471393EP00 The antimicrobial effect of the foam was investigated according to the description in Mil, except that only one experiment was run instead of three parallels, and the pH of the LB broth was not measured. The OD of the bacterial solution without the foam increased from OD 0.05 to 2.0. (The increase in OD value does not correlate to a linear increase in the bacterial concentration when OD > 1, due to the spectrophotometer's limitation in high turbidity.) The bacterial solution with the foam reached a maximum OD of 0.28 after 6 h, indicating that the bacterial growth had stopped in the broths containing foams (see Fig. 29).

[1000] Example 28 - Preparation of mixtures with different phases

[1001] Phase la: Lactic acid and citric acid were fully dissolved in deionised water at room temperature. Add acid water mixture to the silicone part A. Hand mix until a viscous emulsion was formed, then speedmix at 2500rpm for 5 minutes.

[1002] Phase lb: Bicarbonate or carbonate (KHCO3, NaHCO3, K2CO3, Na2CO3) was fully dissolved in glycerol at room temperature. Add alkaline glycerol mixture to the silicone partA. Hand mix until a viscous emulsion was formed, then speedmix at 3500rpm for 5 minutes.

[1003] Phase II: Add glycerol to the silicone partB. Hand mix until a viscous emulsion was formed, then speedmix at 3500rpm for 5 minutes.

[1004] The detailed composition of the samples with different bicarbonate or carbonate is shown below. The molar amount of CO2from the alkaline raw materials is the same in all four samples.

[1005] KHCO3

[1006] Table 25 - Example 28.

[1007] Phase la Mass (g) Weight percentage (wt.%)

[1008] Silbione S4410QC partA 20.00 51.87

[1009] Lactic acid 4.57 11.85

[1010] Citric acid 9.19 23.83

[1011] Water 4.80 12.45

[1012] Total 38.56 100

[1013]

[1014] P471393EP00

[1015] Table 26 - Example 28.

[1016] Phase lb Mass (g) Weight percentage (wt.%) Silbione S4410QC partA 20.00 51.11

[1017] Glycerol 18.06 46.15

[1018] KHCO3 0.91 2.33

[1019] Catalyst 0.16 0.41

[1020] Total 39.13 100

[1021]

[1022] Table 27 - Example 28.

[1023] Phase II Mass (g) Weight percentage (wt.%) Silbione S4410QC partB 40.00 51.91

[1024] Glycerol 37.06 48.09

[1025] Total 77.06 100

[1026]

[1027] Table 28 - Example 28.

[1028] Final mixture (la+lb+ll) Mass (g) Weight percentage (wt.%) Silbione S4410QC partA 40.00 25.85

[1029] Silbione S4410QC partB 40.00 25.85

[1030] Glycerol 55.12 35.62

[1031] Lactic acid 4.57 2.95

[1032] Citric acid 9.19 5.94

[1033]

[1034] P471393EP00

[1035] Water 4.80 3.10

[1036] KHCO3 0.91 0.59

[1037] Catalyst 0.16 0.10

[1038] Total 154.75 100

[1039]

[1040] NaHCO3

[1041] Table 29 - Example 28.

[1042] Phase la Mass (g) Weight percentage (wt.%) Silbione S4410QC partA 20.00 51.87

[1043] Lactic acid 4.57 11.85

[1044] Citric acid 9.19 23.83

[1045] Water 4.80 12.45

[1046] Total 38.56 100

[1047]

[1048] Table 30 - Example 28.

[1049] Phase lb Mass (g) Weight percentage (wt.%) Silbione S4410QC partA 20.00 51.31

[1050] Glycerol 18.06 46.33

[1051] NaHCO30.76 1.95

[1052] Catalyst 0.16 0.41

[1053] Total 38.98 100

[1054]

[1055] P471393EP00

[1056] Table 31 - Example 28.

[1057] Phase II Mass (g) Weight percentage (wt.%) Silbione S4410QC partB 40.00 51.91

[1058] Glycerol 37.06 48.09

[1059] Total 77.06 100

[1060]

[1061] Table 32 - Example 28.

[1062] Final mixture (la+lb+ll) Mass (g) Weight percentage (wt.%) Silbione S4410QC partA 40.00 25.87

[1063] Silbione S4410QC partB 40.00 25.87

[1064] Glycerol 55.12 35.65

[1065] Lactic acid 4.57 2.96

[1066] Citric acid 9.19 5.94

[1067] Water 4.80 3.10

[1068] NaHCO30.76 0.49

[1069] Catalyst 0.16 0.10

[1070] Total 154.60 100

[1071]

[1072] K2CO3

[1073] Table 33 - Example 28.

[1074] Phase la Mass (g) Weight percentage (wt.%) Silbione S4410QC partA 20.00 51.87

[1075]

[1076] P471393EP00

[1077] Lactic acid 4.57 11.85

[1078] Citric acid 9.19 23.83

[1079] Water 4.80 12.45

[1080] Total 38.56 100

[1081]

[1082] Table 34 - Example 28.

[1083] Phase lb Mass (g) Weight percentage (wt.%) Silbione S4410QC partA 20.00 50.66

[1084] Glycerol 18.06 45.74

[1085] K2CO31.26 3.19

[1086] Catalyst 0.16 0.41

[1087] Total 39.48 100

[1088]

[1089] Phase II Mass (g) Weight percentage (wt.%) Silbione S4410QC partB 40.00 51.91

[1090] Glycerol 37.06 48.09

[1091] Total 77.06 100

[1092]

[1093] Table 35 - Example 28.

[1094] Final mixture (la+lb+ll) Mass (g) Weight percentage (wt.%) Silbione S4410QC partA 40.00 25.79

[1095]

[1096] P471393EP00

[1097] Silbione S4410QC partB 40.00 25.79

[1098] Glycerol 55.12 35.54

[1099] Lactic acid 4.57 2.95

[1100] Citric acid 9.19 5.93

[1101] Water 4.80 3.09

[1102] K2CO31.26 0.81

[1103] Catalyst 0.16 0.10

[1104] Total 155.10 100

[1105]

[1106] Na2CO3

[1107] Table 36 - Example 28.

[1108] Phase la Mass (g) Weight percentage (wt.%) Silbione S4410QC partA 20.00 51.87

[1109] Lactic acid 4.57 11.85

[1110] Citric acid 9.19 23.83

[1111] Water 4.80 12.45

[1112] Total 38.56 100

[1113]

[1114] Phase lb Mass (g) Weight percentage (wt.%) Silbione S4410QC partA 20.00 51.05

[1115] Glycerol 18.06 46.09

[1116]

[1117] P471393EP00

[1118] Na2CO30.96 2.45

[1119] Catalyst 0.16 0.41

[1120] Total 39.18 100

[1121]

[1122] Table 37 - Example 28.

[1123] Phase II Mass (g) Weight percentage (wt.%) Silbione S4410QC partB 40.00 51.91

[1124] Glycerol 37.06 48.09

[1125] Total 77.06 100

[1126]

[1127] Table 38 - Example 28.

[1128] Final mixture (la+lb+ll) Mass (g) Weight percentage (wt.%) Silbione S4410QC partA 40.00 25.84

[1129] Silbione S4410QC partB 40.00 25.84

[1130] Glycerol 55.12 35.61

[1131] Lactic acid 4.57 2.95

[1132] Citric acid 9.19 5.94

[1133] Water 4.80 3.10

[1134] Na2CO30.96 0.62

[1135] Catalyst 0.16 0.10

[1136] Total 154.80 100

[1137]

[1138] P471393EP00 Results of the foam samples

[1139] A home-made 3D printing device was used to inject the three-phase mixture into a 10 mL polypropylene (PP) syringe. The initial height of the mixture was approximately 20 mm. Immediately after injection, the syringe was placed in a 35°C oven and cured for 30 minutes. After complete curing, the height increase of the sample inside the syringe was measured. For each formulation, triplicate samples were prepared to calculate the average and standard deviation. Table 39 - Example 28.

[1140] Foam Height increase (%) Density (g / cm3)

[1141] KHCO350 ±4 0.81 ± 0.02

[1142] NaHCO340 ± 5 0.84 ± 0.01

[1143] K2CO322 ± 4 1.06 ± 0.07

[1144] Na2CO318 ± 2 1.07 ± 0.06

[1145]

[1146] The reason for not testing other bicarbonates or carbonate

[1147] LiHCO3: unstable, low toxicity; Li2CO3: more toxic than LiHCO3

[1148] NH4HCO3, (NH4)2CO3: low toxicity, and release NH3

[1149] CaCO3, MgCO3: very low solubility in water, and hardly dissolves

[1150] Ca(HCO3)2, Mg(HCO3)2: they are unstable and decompose into solid carbonate. They only exist in water, but the typical concentration in water is mg / L.

[1151] An attempt was made to prepare a comparable glycerol-based component by continuously introducing CO2gas into aqueous suspensions of CaCO3, MgCO3, Ca(OH)2, and Mg(OH)2. However, even after a few days at room temperature, the solid precursors did not dissolve, making it impractical to synthesize a formulation comparable to those described above.

[1152] Example 29 - Influence of Formulation and Mixing Conditions on Droplet Size and Stability in Elastomer-Based EmulsionsP471393EP00 Aim

[1153] The influence of glycerol content and mixing conditions on the droplet size and stability of emulsions prepared using two elastomer systems is investigated. The two elastomer systems are: Silbione 4410 QC RTV and Sylgard 184. Emulsions will be formulated with varying glycerol concentrations (20, 40, 80, 120, and 150 phr), and their properties will be evaluated under different mixing speeds using two types of mixers: a Speedmixer (3500 rpm and 2000 rpm) and a homogenizer (13500 rpm and 24000 rpm). The goal is to demonstrate that emulsion characteristics are dependent mainly on the composition.

[1154] Objectives

[1155] This experiment covers:

[1156] - Effect formulation composition on emulsion stability

[1157] - Effect of mixing parameters on emulsion stability

[1158] The objectives and questions outlined in this document serve as a guiding framework for the research process. They play a crucial role in directing data collection and analysis.

[1159] Materials

[1160] Table 40 - Example 29.

[1161] LOT / Batch / CAS number Name Description

[1162] LOT: 222341014 A Silbione RTV 4410 QC A Elkem, France

[1163] LOT: H04702R028 Sylgard 184 base Dow, US

[1164] NA Parafilm

[1165] NA Speedmixing cups: clear cup Synergy Devices Limited, UK and white lid (size: max 20

[1166] mL, max 60)

[1167]

[1168] Equipment: A list of all equipment used.

[1169] Table 41 - Example 29.

[1170] ID Name Description

[1171] DAC 330-100 SE SpeedMixer FlackTek, Germany

[1172] Ultra-Turrax T25 Homogenizer Janke and Kunkel, Germany

[1173]

[1174] P471393EP00 VHX-7000 Digital Microscope Keyence, US

[1175]

[1176] Methods

[1177] Preparation of the samples

[1178] Sample prepared with speedmixer:

[1179] Silbione S4410 QC part A (S4410) / Sylgard 184 base (S184) was mixed with the glycerol solution with a spatula until an emulsion was formed, followed by 2 minutes speedmixing at 2000 rpm / 3500 rpm.

[1180] Table 42 - Example 29.

[1181] Component Silicone Mass (g) Glycerol Mass (g)

[1182] S4410-20phr 5 1

[1183] S4410-40phr 5 2

[1184] S4410-80phr 5 4

[1185] S4410-120phr 5 6

[1186] S4410-150phr 5 7,5

[1187] S184-20phr 5 1

[1188] S184-40phr 5 2

[1189] S184-80phr 5 4

[1190] S184-120phr 5 6

[1191] S184-150phr 5 7,5

[1192]

[1193] Samples prepared with Homogenizer:

[1194] Silbione S4410 QC part A (S4410) / Sylgard 184 base (S184) was mixed with the glycerol solution with a spatula until an emulsion was formed, followed by 2 minutes homogenizing at 13500 rpm / 24000 rpm. To be able to mix the samples with homogenizer, twice the amount of silicone which has been used for speedmixer, should be used.P471393EP00 Table 43 - Example 29.

[1195] Component Silicone Mass (g) Glycerol Mass (g)

[1196] S4410-20phr 10 2

[1197] S4410-40phr 10 4

[1198] S4410-80phr 10 8

[1199] S4410-120phr 10 12

[1200] S4410-150phr 10 15

[1201] S184-20phr 10 2

[1202] S184-40phr 10 4

[1203] S184-80phr 10 8

[1204] S184-120phr 10 12

[1205] S184-150phr 10 15

[1206]

[1207] Measurement

[1208] The droplet size was measured with a VHX-7000 digital microscope from Keyence. A drop of the separate emulsions was put on a microscope plate. The zoom was adjusted so that the droplets of the emulsified components were visible within the silicone matrix (1000x magnification). A picture was recorded, and the size of the droplets was measured by marking the outline of the droplet with the built-in software. The droplet size was determined as an average of ten droplets, and the standard deviation was determined using the Excel command stdev.s (Microsoft Excel Worksheet). The measurements have been done over 14 days.

[1209] Results

[1210] Emulsion droplet size and stability were influenced by both glycerol content and mixing conditions. For Silbione 4410 QC, emulsions prepared with the Speedmixer at 2000 rpm exhibited larger initial droplet sizes (e.g., 9 ± 2 pm at 20 phr) and a tendency to increase over time, particularly at higher glycerol loadings (e.g., 12 ± 2 pm at 80 phr on Day 3). At 3500 rpm, droplet sizes were generally smaller (e.g., 5 ± 2 pm at 20 phr) and more stable, though samples with 120 phr glycerol showed noticeable growth (8 ± 2 pm by Day 1). In contrast, homogenization at 13500 rpm and 24000 rpm produced significantly finer emulsions (mostly 1-3 pm) with minimal change over 14 days, except for slight coalescence at 120 phr glycerol. For Sylgard 184, droplet sizes were consistently smallerP471393EP00 than those of Silbione under comparable conditions, with Speedmixer samples remaining around 3 pm and homogenized samples near 1-2 pm throughout the test period. Emulsions with 150 phr glycerol could not be prepared successfully under any condition. Red-marked cells in the tables indicate samples that became unstable or exhibited phase separation during storage, which was most common at high glycerol contents (>120 phr) and lower shear conditions. Figure 30 shows this phase separation. Orange-marked cells in the table indicates the points which the emulsions start to get unstable. Overall, the results confirm that droplet size and stability depend on both composition and mixing speed, with no single optimal rpm across all formulations. Figure 31-34 illustrates this trend.

[1211] Speedmixer:

[1212] Table 44 - Example 29.

[1213] S4410-2000 Day 0 (pm) Day 1 (pm) Day 3 (pm) Day 7 (pm) Day 14 (pm) rpm

[1214] 20 phr 9 ± 2 10 ± 5 10 ± 5 10 ± 2 11 ± 1 40 phr 9 ± 2 10 ± 4 10 ± 3 10 ± 3 9 ± 1 80 phr 9 ± 2 8 ± 3 12 ± 2

[1215] 120 phr 8 ± 1 11 ± 3

[1216] 150 phr

[1217]

[1218] Table 45 - Example 29.

[1219] S4410-3500 Day 0 (pm) Day 1 (pm) Day 3 (pm) Day 7 (pm) Day 14 (pm) rpm

[1220] 20 phr 5 ± 2 5 ± 2 6 ± 1 7 ± 2 7 ± 1 40 phr 5 ± 1 6 ± 1 6 ± 1 7 ± 1 7 ± 1 80 phr 5 ± 1 6 ± 1 5 ± 1 9 ± 2

[1221]

[1222] P471393EP00 120 phr 4 ± 1 8 ± 2

[1223] 150 phr

[1224]

[1225] Table 46 - Example 29.

[1226] S184-2000 rpm Day 0 (pm) Day 1 (pm) Day 3 (pm) Day 7 (pm) Day 14 (pm) 20 phr 3 ± 1 4 ± 1 5 ± 2 7 ± 1 6 ± 1 40 phr 2 ± 0,2 3 ± 1 5 ± 1 6 ± 1 6 ± 1 80 phr 3 ± 0,4 4 ± 1 5 ± 1 5 ± 2 7 ± 1 120 phr

[1227] 150 phr

[1228]

[1229] Table 47 - Example 29.

[1230] S184-3500 rpm Day 0 (pm) Day 1 (pm) Day 3 (pm) Day 7(pm) Day 14 (pm) 20 phr 3 ± 0,5 3 ± 0,5 3 ± 0,4 3 ± 0,6 3 ± 0,6 40 phr 3 ± 0,2 3 ± 0,4 3 ± 0,7 3 ± 0,4 3 ± 0,5 80 phr 3 ± 0,4 3 ± 0,6 3 ± 0,4 3 ± 1 3 ± 0,6 120 phr 3 ± 1

[1231] 150 phr

[1232]

[1233] Homogenizer:P471393EP00 Table 48 - Example 29.

[1234] S4410-13500 Day 0 (pm) Day 1 (pm) Day 3 (pm) Day 7 (pm) Day 14 (pm) rpm

[1235] 20 phr 2 ± 0,4 2 ± 0,5 2 ± 0,6 4 ± 2 4 ± 0,6 40 phr 2 ± 0,7 2 ± 0,5 2 ± 0,3 3 ± 2 4 ± 0,3 80 phr 2 ± 0,5 3 ± 0,8 5 ± 2

[1236] 120 phr 5 ± 2

[1237] 150 phr

[1238]

[1239] Table 49 - Example 29.

[1240] S4410-24000 Day 0 (pm) Day 1 (pm) Day 3 (pm) Day 7 (pm) Day 14 (pm) rpm

[1241] 20 phr 2 ± 0,8 2 ± 0,7 3 ± 0,7 5 ± 2 4 ± 0,6 40 phr 2 ± 0,5 2 ± 0,4 4 ± 1 5 ± 2 4 ± 0,7 80 phr 3 ± 0,7 2 ± 0,6 4 ± 3

[1242] 120 phr 5 ± 1

[1243] 150 phr

[1244]

[1245] Table 50 - Example 29.

[1246] S184-13500 Day 0 (pm) Day 1 (pm) Day 3 (pm) Day 7 (pm) Day 14 (pm) rpm

[1247] 20 phr 2 ± 0,6 2 ± 0,5 3 ± 0,7 4 ± 2 4 ± 1 40 phr 1 ± 0,6 1 ± 0,6 2 ± 0,6 4 ± 2 4 ± 1

[1248]

[1249] P471393EP00 80 phr 1 ± 0,4 1 ± 0,3 3 ± 1 4 ± 2 4 ± 0,6 120 phr 3 ± 3

[1250] 150 phr

[1251]

[1252] Table 51 - Example 29.

[1253] S184-24000 Day 0 (pm) Day 1 (pm) Day 3 (pm) Day 7 (pm) Day 14 (pm) rpm

[1254] 20 phr 1 ± 0,7 2 ± 0,6 3 ± 1 6 ± 3 5 ± 2 40 phr 1 ± 0,3 1 ± 0,6 3 ± 0,8 5 ± 2 4 ± 2 80 phr 1 ± 0,1 1 ± 0,4 2 ± 0,9 3 ± 0,7 4 ± 1 120 phr

[1255] 150 phr

[1256]

[1257] Conclusion:

[1258] This study demonstrated that emulsion droplet size and stability for Silbione 4410 QC and Sylgard 184 are strongly dependent on both glycerol content and mixing conditions. Higher shear rates (homogenizer at 13500-24000 rpm) consistently produced smaller and more stable droplets compared to lower shear mixing (Speedmixer at 2000-3500 rpm); however, this won't affect the stability of the samples and the stability is mainly governed by the formulation. Increasing glycerol content after 80 phr generally led to reduced stability, with phase separation observed at high loadings (>120 phr), particularly under low shear conditions. No single mixing speed ensured optimal stability across all formulations, confirming that emulsion behavior is governed by the interplay between composition and processing parameters rather than a fixed rpm setting.

[1259] Example 30 - Three-compartment formulation with 90 or 100 phr glycerolP471393EP00 In this example, a three-compartment formulation is made.

[1260] Preparation of Phase la:

[1261] • The amount of silanol trimethylsilyl modified Q resin (SQO) was dissolved in Silbione S4410QC Part A by handmixing with a spatula for a few minutes and then speedmixing for 5 minutes at 3500 rpms. Then lactic acid and glycerol were added separately in the solution, handmixed in between and speedmixed for 2 minutes at 3500 rpms.

[1262] Preparation of Phase lb:

[1263] • Potassium bicarbonate was dissolved in glycerol overnight, then added in Silbione S4410QC Part A, handmixed and finally speedmixed for 2 minutes at 3500rpms.

[1264] Preparation of Phase II:

[1265] • Glycerol was added to Silbione S4410QC Part B, handmixed and then speedmixed for 2 minutes at 3500 rpms.

[1266] The detailed compositions of the formulations are listed below.

[1267] Table 52 - Composition of formulation with 90 phr glycerol - Example 30.

[1268] Component Mass (g) Weight percentage (wt.%)

[1269] Phase la

[1270] Silbione S4410QC Part A 20.0 12.7

[1271] Glycerol 14.5 9.22

[1272] Lactic acid 4.6 2.91

[1273] SQO 0.26 0.17

[1274] Phase lb

[1275] Silbione S4410QC Part A 20.0 12.7

[1276]

[1277] P471393EP00 Glycerol 18.4 11.7 Potassium bicarbonate 0.92 0.59

[1278] Phase II

[1279] Silbione S4410QC Part B 40.0 25.4 Glycerol 38.7 24.6

[1280] Table 53 - Composition of formulation with 1 10 phr glycerol - Example = 30

[1281] Component Mass (g) Weight percentage (wt.%)

[1282] Phase la

[1283] Silbione S4410QC Part A 20.0 12.1 Glycerol 16.3 9.88 Lactic acid 4.66 2.82

[1284] SQ.0 0.29 0.17

[1285] Phase lb

[1286] Silbione S4410QC Part A 20.0 12.1 Glycerol 20.24 12.3 Potassium bicarbonate 1.01 0.61

[1287] Phase II

[1288] Silbione S4410QC Part B 40.0 24.2 Glycerol 42.5 25.8

[1289]

[1290] Testing pH of produced foamsP471393EP00 Each phase was loaded into separate syringes up to 10 mL and a heat treatment was performed by placing the syringes in an oven with 20% fan, at 55°C for 72 hours. After this initial heat treatment, the syringes were left in the oven with 20% fan, at 45°C for 3 weeks.

[1291] After the initial heat treatment and after each week that the syringes stayed in the oven at 45°C, the syringes were taken out of the oven to make foams. In order to achieve this, a home-made 3D printing dispensing device was used to connect the syringes and apply each formulation in small plastic cups of maximum 5 mL capacity. Approximately 2 g of formulation were applied in the cups, and they were then placed in the oven with 20% fan, at 35°C for 30 minutes to cure the foams. After the foams were cured they were placed in bigger plastic cups of maximum 20 mL capacity and 15 g of demineralized water were added in the cups with the foam. The foams were left immersed in water for 4 days and then the pH of the water was measured using a pH probe. The results are presented on the table below.

[1292] Table 54 - Results of pH measurements for three-compartment formulations with 90 and 100 phr glycerol - Example 30

[1293] 3 days at 55°C 1 weekat45°C 2 weeks 45°C 3 weeks 45°C Formulation with

[1294] 90 phr glycerol 3.4 3.78 4.2 4.29 Formulation with

[1295] 100 phr glycerol 3.43 3.79 4.95 5.24

[1296]

[1297] The formulations presented instability over extended heat treatment, hence the increase in the pH over time.

[1298] Two-compartment formulation with 90 phr glycerol

[1299] This formulation consisted of two different phases.

[1300] Preparation of Phase I:

[1301] The amount of silanol trimethylsilyl modified Q. resin (SQO) was dissolved in Silbione S4410QC Part B by handmixing with a spatula for a few minutes and then speedmixing forP471393EP00 10 minutes at 3500 rpms. Then lactic acid and glycerol were added separately in the solution, handmixed in between and speedmixed for 2 minutes at 3500 rpms.

[1302] Preparation of Phase II:

[1303] • Potassium bicarbonate was dissolved in glycerol overnight, then added in Silbione S4410QC Part A, handmixed and finally speedmixed for 2 minutes at 3500rpms.

[1304] The detailed compositions of the formulations are listed below.

[1305] Table 54 - Composition of a two-compartment formulation with 90 phr glycerol - Example 30

[1306] Component Mass (g) Weight percentage (wt.%) Phase I Silbione S4410QC Part B 40.0 25.2 Glycerol 34.1 8.52 Lactic acid 5.0 1.25 SQ.0 0.28 0.07

[1307]

[1308] Phase II

[1309]

[1310] Silbione S4410QC Part A 40.0 25.2

[1311] Glycerol 37.9 23.9

[1312] Potassium bicarbonate 1.46 0.92

[1313] Testing stability of formulation at room temperature

[1314] Each phase was loaded into separate syringes up to 10 mL and a heat treatment was performed by placing the syringes in an oven with 20% fan, at 55°C for 72 hours. After this initial heat treatment, the syringes were left at room temperature.P471393EP00 Rheological measurements were conducted before and after the initial heat treatment and after 1 month storage at room temperature. Foams were created for each of the above time points using a home-made 3D printing dispensing device to apply each formulation in small plastic cups of maximum 5 mL capacity. Approximately 2 g of formulation were applied in the cups, and they were then placed in the oven with 20% fan, at 35°C for 30 minutes, to cure the foams.

[1315] After the foams were cured they were removed from the cups, cut in half and pictures of their cross sections were taken. The results are presented below.

[1316] Table 55 - Results of rheological measurements at different time points for two compartment formulation with 90 phr glycerol - Example 30

[1317] Shear rate: 11 / s, 25°C 32°C

[1318] Time Phase 1 (Pas) Phase II (Pas) Initial viscosity (Pas) Gel point (s) Curing (min)

[1319] Before heat

[1320] m 209 83 39 34 treatment

[1321] After heat

[1322] 370 178 102 6 29 treatment

[1323] month at RT 373 103 16 26

[1324]

[1325] Figure 35 shows the results before heat treatment (A), after heat treatment ( B) and after 1 week at RT(C).

[1326] The formulation showed both increased viscosity of Phase I and increased pore size of foams after heat treatment.

Claims

P471393EP00 Claims1. A multiphase silicone composition comprisinga. a first phase comprising silicone, wherein said silicone comprises a vinyl- functionalized silicone polymer, and optionally a catalyst,b. a second phase comprising silicone, wherein said silicone comprises a cross linker, c. optionally a third phase,wherein at least one of said phases in the composition comprises an acid, and wherein at least one of said phases in the composition comprises a base, wherein said base is a carbonate or a bicarbonate, and wherein said acid and said base is present in difference phases in the composition, and wherein at least one of said phases in the composition comprises glycerol, and wherein at least one of said phases of said composition is an emulsion.

2. A multiphase silicone composition comprisinga. a first phase comprising silicone, wherein said silicone comprises a vinyl- functionalized silicone polymer, and optionally a catalyst,b. a second phase comprising silicone, wherein said silicone comprises a cross linker, c. optionally a third phase,wherein at least one of said phases in the composition comprises an acid, and wherein at least one of said phases in the composition comprises a base, wherein said base is a carbonate or a bicarbonate, and wherein said acid and said base is present in difference phases in the composition, and wherein at least one of said phases in the composition comprises glycerol, and wherein at least one of said phases of said composition is an emulsion,wherein said base is potassium bicarbonate (KHCO3), sodium bicarbonate (NaHCO3), potassium carbonate (K2CO3) or sodium carbonate (Na2CO3), andwherein said glycerol is in an amount of above 60 phr.

3. The composition according to any of the previous claims, wherein said catalyst is a Pt catalyst.P471393EP00 4. The composition according to any of the previous claims, wherein said phases in the composition when mixed together creates a foam.

5. The composition according to any of the previous claims, wherein said acid and said base forms a buffer system upon mixing.

6. The composition according to any of the previous claims, wherein said acid is an organic acid.

7. The composition according to any of the previous claims, wherein said acid is a citric acid, or a lactic acid.

8. The composition according to any of the previous claims, wherein at least one of said phases in the composition comprises at least two different acids, preferably lactic acid and citric acid.

9. The composition according to any of the previous claims, wherein said base is a water- or glycerol-soluble carbonate.

10. The composition according to any of the previous claims, wherein said base is potassium bicarbonate (KHCO3), sodium bicarbonate (NaHCO3), potassium carbonate (K2CO3) or sodium carbonate (Na2CO3).

11. The composition according to any of the previous claims, wherein said base is a bicarbonate, such as potassium bicarbonate (KHCO3) or sodium bicarbonate (NaHCO3).

12. The composition according to any of the previous claims, wherein said base is a potassium bicarbonate (KHCO3).

13. The composition according to any of the previous claims, wherein said composition comprises a resin, preferably silanol-trimethylsilyl modified Q. resin.P471393EP00 14. The composition according to any of the previous claims, wherein said resin is in an amount of 0.1 - 10 parts per hundred rubber or preferably 0.1 - 5 parts per hundred rubber (phr).

15. The composition according to any of the previous claims, wherein said composition comprises a pH indicator.

16. The composition according to any of the previous claims, wherein said pH indicator is selected among a red cabbage extract, Anthocyanin, Bromothymol blue, Bromophenol blue and Bromocresol purple.

17. The composition according to any of the previous claims, wherein said glycerol is in an amount of about 80 phr or about 100 phr.

18. The composition according to any of the previous claims, wherein said glycerol is in an amount of above 60 phr.

19. The composition according to any of the previous claims, wherein said glycerol is in an amount of 60 - 140 phr, 65 - 135 phr, 70-130 phr, 75 - 125 phr, 80 - 120 phr, 85 - 115 phr, 90 - 110 phr, 95 - 105, or about 100 phr.

20. The composition according to any of the previous claims, wherein said mixing is performed at a level of about 500 - 5000 rpm, about 700 - 4000 rpm, or preferably about 800 - 3800 rpm.

21. The composition according to any of the previous claims, wherein said mixing speed is performed at a level of 500 rpm, 1500 rpm, 2500 rpm or 3500 rpm.

22. The composition according to any of the previous claims, wherein said mixing speed is performed by a dual asymmetric centrifuge, such as a dual asymmetric centrifuge SpeedMixer DAC 330-100 SE.

23. A method of producing the composition according to any of the previous claims, wherein said method comprises the steps of:P471393EP00 a. Providing a first silicone material comprising a vinyl-functionalized silicone polymer, and optionally comprising a catalyst,b. Providing a second silicone material comprising a cross linker, c. Providing glycerol, an acid, and a base,d. Mixing said first silicone material, and optionally said glycerol and optionally said acid / or base, to provide a first phase, e. Mixing said second silicone material, and optionally said glycerol and optionally said acid and / or base, to provide a second phase, and f. Loading said first phase and said second phase into separate compartments in a compartment syringe,wherein at least one of said phases comprises glycerol, andwherein at least one of said phases is an emulsion.

24. The method according to claim 23, wherein said method comprises a step of mixing a third phase, wherein said third phase comprises a silicone material, a base, an acid and / or glycerol.

25. The method according to any of claims 23-24, wherein said compartment syringe is a dual compartment syringe, three-compartment syringe, or a four-compartment syringe.

26. The method according to any of claims 23-25, wherein said mixing is performed at a level of about 500 - 5000 rpm, about 700 - 4000 rpm, or preferably about 800 - 3800 rpm.

27. The method according to any of claims 23-26, wherein said mixing speed is performed at a level of 500 rpm, 1500 rpm, 2500 rpm or 3500 rpm.

28. The method according to any of claims 23-27, wherein said mixing speed is performed by a dual asymmetric centrifuge, such as a dual asymmetric centrifuge SpeedMixer DAC 330-

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