Faecal barrier device

Abstract

A faecal barrier device is described. The faecal barrier device comprises a hydrogel scaffold; and a sacrificial filler material dispersed throughout the hydrogel scaffold. A method of manufacturing a faecal barrier device, a kit of parts comprising a faecal barrier device and use of a di- or trivalent metal cation-stabilised alginate as a faecal barrier device are also described.

Description

[0001] FAECAL BARRIER DEVICE

[0002] Background

[0003] People may spend up to 2 hours preparing for anorectal intercourse by flushing water through their rectum and then waiting for any trapped liquid to be released in a process known as anal douching. The time required for this practice is a problem as it limits sexual spontaneity. Anal douching can also cause faeces to be dislodged from higher up the gastrointestinal (Gl) tract, as well as water to become trapped and potentially being released during sex. Anal douching has also been shown to increase the spread of several sexually transmitted infections (e.g., HIV, chlamydia, gonorrhoea, syphilis, human papillomavirus, hepatitis B virus and hepatitis C virus) by roughly 3-fold. Broadly, this topic is largely stigmatised and overlooked with no adequate alternative solution presently available.

[0004] Therefore, the present inventors have sought to provide a device that enables faeces- free anorectal intercourse, without increasing the spread of sexually transmitted infections (STIs). The present inventors have found that a device in accordance with the present disclosure prevents passage of faeces beyond the sigmoid colon. The present inventors have also found that a device in accordance with the present disclosure retains its structure for at least two hours in physiological conditions, so that it may act as a faecal barrier device for a sufficient length of time, before degrading and being passed from the body.

[0005] Summary of Invention

[0006] In a first aspect, the invention provides a faecal barrier device comprising a hydrogel configured to block passage of faeces from the sigmoid colon through the rectum.

[0007] In another aspect, the invention provides a faecal barrier device comprising a hydrogel; and a sacrificial filler material dispersed throughout the hydrogel.

[0008] In a further aspect, the invention provides a device comprising a hydrogel; and a sacrificial filler material dispersed throughout the hydrogel. In a further aspect, the invention provides a device comprising a solid mass of a hydrogel; and a sacrificial filler material dispersed throughout the hydrogel. The device may be configured to block passage of faeces from the sigmoid colon through the rectum. The device may be configured to act as a suppository.

[0009] In a second aspect, the invention provides a method of manufacturing a faecal barrier device, comprising: heating an aqueous solution of a hydrogel precursor; optionally combining the heated hydrogel precursor with a filler material; and allowing the solution to cool and set, thereby forming the faecal barrier device.

[0010] In a third aspect, the invention provides a kit of parts, comprising: a faecal barrier device as described herein; and an applicator.

[0011] In a fourth aspect, the invention provides the use of a di- or trivalent metal cation- stabilised alginate as a faecal barrier device.

[0012] In another aspect, the invention provides the use of a device comprising a hydrogel as a faecal barrier device.

[0013] In another aspect, the invention provides the use of a device comprising a hydrogel; and a sacrificial filler material dispersed throughout the hydrogel as a faecal barrier device.

[0014] In a further aspect, the invention provides the use of a device comprising a hydrogel scaffold; and a sacrificial filler material dispersed throughout the hydrogel scaffold as a faecal barrier device prior to and / or during anorectal intercourse.

[0015] In another aspect, the invention provides a suppository comprising a hydrogel; and one or more active agent(s).

[0016] In another aspect, the invention provides a suppository comprising a hydrogel; a sacrificial filler material dispersed throughout the hydrogel; and one or more active agent(s).

[0017] In another aspect, the invention provides the use of a device comprising a hydrogel; and one or more active agent(s) as a suppository. In another aspect, the invention provides the use of a device comprising a hydrogel; a sacrificial filler material dispersed throughout the hydrogel; and one or more active agent(s) as a suppository.

[0018] In another aspect, the invention provides a faecal barrier device comprising a hydrogel configured to block passage of faeces from the sigmoid colon through the rectum; and one or more active agents.

[0019] In a further aspect, the invention provides a faecal barrier device comprising a hydrogel configured to block passage of faeces from the sigmoid colon through the rectum; and one or more active agents dispersed throughout the hydrogel.

[0020] In a further aspect, the invention provides a faecal barrier device comprising a hydrogel configured to block passage of faeces from the sigmoid colon through the rectum; and one or more active agents disposed on a surface of the hydrogel.

[0021] In a further aspect, the invention provides a faecal barrier device comprising a hydrogel configured to block passage of faeces from the sigmoid colon through the rectum; and one or more active agents disposed on a surface of the faecal barrier device.

[0022] Brief Description of Figures

[0023] Figure 1 shows the results of testing a device according to the present disclosure in ex vivo experiments compared with a control experiment.

[0024] Figure 2 shows the appearance of device according to the present disclosure after incubation at 37°C in phosphate buffered saline.

[0025] Figure 3 shows the appearance of a device according to the present disclosure after incubation at 37°C in phosphate buffered saline.

[0026] Figure 4 shows the change in device diameter over time.

[0027] Figure 5 shows the amount of pressure required to break the device.

[0028] Figure 6 shows the pressure required to compress the device as a function of time. Figure 7 shows sulfasalazine release from a device according to the present disclosure.

[0029] Figure 8 shows doxycycline release from a device according to the present disclosure.

[0030] Description

[0031] Before particular embodiments of the present device and other aspects are disclosed and described, it is to be understood that the present device and other aspects are not limited to the particular materials and processes disclosed herein as such and may vary to some degree. It is also to be understood that the terminology used herein is used for the purpose of describing particular embodiments only and is not intended to be limiting, as the scope of the present device and other aspects will be defined only by the appended claims and equivalents thereof.

[0032] In the present specification, and in the appended claims, the following terminology will be used.

[0033] The singular forms “a”, “an” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a filler material” includes reference to one or more of such materials.

[0034] The terms “about” and “approximately” when referring to a numerical value or range is intended to encompass the values resulting from experimental error that can occur when taking and / or making measurements.

[0035] Unless otherwise stated, references herein to “wt. / vol.%” of a component are to the weight of that component as a percentage of the total volume of the composition comprising that component on a grams / mL basis. For example, references herein to “wt. / vol.%” of, for example, a solid material such as divalent metal cations dispersed or dissolved in a liquid composition are to the weight percentage by volume of those solids in the volume of liquid, and not to the amount of that solid as a percentage of the total non-volatile solids of the composition.

[0036] Unless otherwise stated, references herein to molecular weight, or weight average molecular weight are to the molecular weight, or weight average molecular weight, of a polymer as determined using gel permeation chromatography (GPC), otherwise known as size exclusion chromatography (SEC).

[0037] As used herein, the term “faecal barrier device” refers to a device inserted through the anus and which forms a physical barrier between faeces in the sigmoid colon and the rectum. It is readily apparent that such a device will not be so large that it cannot be administered through the anus but is large enough that it forms an effective barrier preventing passage of faeces from the sigmoid colon to the rectum. Such a device may also displace residual faeces in the rectum further up the gastrointestinal tract through its insertion.

[0038] The term “hydrogel” is well understood in the art to refer to compositions formed from three-dimensional networks of natural or synthetic polymers with a fluid, primarily water, retained within the pores of the network, with high fluid (e.g. water) retention properties. It is well understood in the art that hydrogels exist in neither the solid physical state nor the liquid physical state, rather they exist in a physical state somewhere between liquid and solid but with a defined shape or 3-dimensional form. Therefore, herein the terms “a hydrogel”, “a hydrogel scaffold” and “a solid mass of a hydrogel” are interchangeable and refer to a hydrogel composition or material that retains its shape without the structural or mechanical support of a container. The three-dimensional networks of natural or synthetic polymers can be considered to form a “scaffold” in which the fluid (e.g. water) is held (which is well understood in the art), but which also provides a supporting structure for any other components included in the hydrogel.

[0039] As used herein, “hydrogel precursor” refers to compounds that, prior to manufacturing the faecal barrier device, do not exist in the form of a hydrogel, but after processing in the necessary conditions form a hydrogel as defined above.

[0040] The term “di- or trivalent metal cations” is well understood in the art to refer to ionised metal atoms with a positive charge of two (2+) or three (3+).

[0041] As used herein, “sacrificial filler material” refers to a composition that provides additional structural stability and integrity to the hydrogel forming the faecal barrier device, but degrades over time under physiological conditions to initiate breakdown of the faecal barrier device. As used herein, “acidic species” refers to a compound or compounds that release positively charged hydrogen atoms (or protons) in solution, as is well understood in the art.

[0042] The term “pKa” is well understood in the art to refer to the dissociation constant of a given molecule, describing its propensity to separate reversibly into conjugate acid and base. As is well understood, a “high” pKa value suggests a given compound is a weaker acid or a stronger base. Conversely, a “low” pKa value suggests a given compound is a stronger acid or a weaker base. It is generally accepted that “weak” acids have pKa values between 10 and 15, whilst “strong” acids have pKa values below 2 or 3.

[0043] As used herein, the term “lubricant” refers to a substance that reduces the friction between the surfaces of two or more objects interacting with one another.

[0044] Concentrations, amounts, and other numerical data may be presented herein in a range format. It is to be understood that such a range format is used merely for convenience and brevity and should be interpreted flexibly to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. For example, a weight range of about 1 wt. / vol. % to about 20 wt. / vol. % should be interpreted to include not only the explicitly recited concentration limits of about 1 wt. / vol. % to about 20 wt. / vol. %, but also to include individual concentrations such as 2 wt. / vol. %, 3 wt. / vol. %, 4 wt. / vol. %, and sub-ranges such as 5 wt. / vol. % to 10 wt. / vol. %, 10 wt. / vol. % to 20 wt. / vol. %, etc.

[0045] In the following description, for purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of the present faecal barrier device, method of manufacturing the same, kit of parts including the same and use of a divalent metal cation-stabilised alginate as a faecal barrier device. It will be apparent, however, to one skilled in the art, that the present method may be practiced without these specific details. Reference in the specification to “one example” or “an example” means that a particular feature, structure, or characteristic described in connection with the example is included in at least one example. The appearance of the phrase “in one example” in various places in the specification are not necessarily all referring to the same example. Unless otherwise stated, any feature described herein can be combined with any aspect or any other feature described herein.

[0046] Faecal barrier device

[0047] Anal douching is time-consuming, has undesirable side-effects such as trapped water in the Gl tract and increases the spread of several STIs. It is therefore an object of the present invention to provide an alternative way of preventing passage of faeces into the rectum and / or clearing the rectum of faeces in preparation for and / or during anorectal intercourse.

[0048] Faecal incontinence devices exist but are not suitable for facilitating anorectal intercourse because they either sit much lower in the rectum, sometimes as low as the anus to prevent progression of faeces beyond the anus, or contain additional features that protrude from the anus to allow mechanical removal of the device, neither of which are conducive to anorectal intercourse. Many of these devices are made from silicon as they are intended to be mechanically removed and are actively intended to not breakdown, even over an extended period of time.

[0049] It is therefore important that a device of the present invention is placed higher in the Gl tract than a faecal incontinence device and can be removed by means other than mechanical means that occupy the rectum and / or protrude from the anus. To facilitate anorectal intercourse, a device should not comprise removal means that occupy the rectum and / or anus. However, without such means, it is critical that the device of the present invention does not become stuck within the Gl tract and cannot be retrieved, as this could require medical intervention.

[0050] It is therefore another object of the invention to provide a way of preventing passage of faeces into the rectum and / or clearing the rectum of faeces that facilitates anorectal intercourse but will be removed in a suitable timeframe.

[0051] Disclosed herein is a faecal barrier device. In some examples, the faecal barrier device comprises a hydrogel configured to block passage of faeces from the sigmoid colon through the rectum. In some examples, the faecal barrier device comprises a hydrogel configured to block passage of faeces from the sigmoid colon through the rectum, and a sacrificial filler material. In some examples, the faecal barrier device comprises a solid mass of a hydrogel scaffold. In some examples, the faecal barrier device comprises a solid mass of a hydrogel scaffold; and a sacrificial filler material dispersed throughout the hydrogel scaffold. In some examples, the faecal barrier device comprises a hydrogel scaffold. In some examples, the faecal barrier device comprises a hydrogel scaffold; and a sacrificial filler material dispersed throughout the hydrogel scaffold. In some examples, the faecal barrier device comprises a hydrogel scaffold.

[0052] Also disclosed herein is a device. In some examples, the device comprises a hydrogel scaffold configured for use as a faecal barrier device, that is a hydrogel scaffold configured to block passage of faeces from the sigmoid colon through the rectum, in particular during anorectal intercourse. In some examples, the device comprises a solid mass of a hydrogel scaffold; and a sacrificial filler material dispersed throughout the hydrogel scaffold. In some examples, the device comprises a hydrogel scaffold; and a sacrificial filler material dispersed throughout the hydrogel scaffold.

[0053] In some examples, a device according to the present disclosure is intended or configured to be inserted into the anus and form a physical barrier between faeces in the sigmoid colon and the rectum. The rectum itself is usually devoid of faeces but any residual faeces in the rectum may be advantageously displaced higher up the gastrointestinal tract towards the sigmoid colon through insertion of the device. Thus, the same effect of a faeces-free rectum afforded by anal douching is achieved, but without the considerable drawbacks that accompany anal douching.

[0054] In some examples, the device retains its structural integrity so that it may act as a faecal barrier. The device may steadily disintegrate over time until it completely dissolves and / or is passed from the body. The ideal rate of dissolution will allow the barrier to remain functional for a matter of hours but completely dissolve or collapse within 8-18 hours.

[0055] To this end, the present inventors have found that hydrogels are suitable materials. Hydrogels are biocompatible, biodegradable, cheap, readily available, and easy to make. For these reasons, hydrogels are routinely used in applications where biocompatibility is required e.g., cosmetic dermal fillers. However, as yet, they have not been employed in the capacity of a faecal barrier device. To achieve a desired stability profile, the formulation of the hydrogel can be modified such that it forms a solid object with suitable mechanical properties of elastic deformability that allow it to conform to the shape of the required body part(s) while providing the necessary mechanical resistance.

[0056] Suppository

[0057] The device of the present disclosure also finds use as a suppository, either vaginal or anal. Therefore, discussion herein to the materials for the formation and use of a faecal barrier device is equally applicable to the materials for the formation and use of a device as a suppository.

[0058] The stability profile of such a composition enables its use as a suppository due to its steady degradation over time, releasing active agent(s) contained therein to the surrounding tissue, before eventual dissolution and passage from the body.

[0059] As above, the present inventors have found that hydrogels are suitable materials due to their biocompatibility, biodegradability, availability, ease of manufacture and low level of cost.

[0060] Therefore, disclosed herein is a device. In some examples, the device comprises a hydrogel scaffold configured for use as a suppository. In some examples, the device comprises a solid mass of a hydrogel scaffold; a sacrificial filler material dispersed throughout the hydrogel scaffold; and one or more active agent(s) dispersed throughout the hydrogel scaffold. In some examples, the device comprises a hydrogel scaffold; a sacrificial filler material dispersed throughout the hydrogel scaffold; and one or more active agent(s) within the hydrogel scaffold.

[0061] Hydrogel

[0062] In some examples, the hydrogel, referred to also as a hydrogel scaffold, comprises one or more synthetic and / or natural hydrogel(s). By a “synthetic hydrogel” it is meant herein that the hydrogel is composed of synthetic, or man-made, polymer chains. Polyethylene glycol is an example of a synthetic material that can form a hydrogel, as it is derived from petroleum sources. By a “natural hydrogel” it is meant herein that the hydrogel is composed of naturally occurring polymer chains. Alginate, chitosan and hyaluronic acids are known naturally occurring hydrogels. In some examples, the hydrogel scaffold comprises solely a synthetic hydrogel(s). In some examples, the hydrogel scaffold comprises solely a natural hydrogel(s). In some examples, the hydrogel scaffold comprises both a synthetic hydrogel(s) and a natural hydrogel(s).

[0063] In some examples, the hydrogel comprises one or more of polyacrylamide, polyethylene glycol, alginate, chitosan, carboxymethyl chitosan, agarose, gellan gum, xanthan gum, hydroxyethyl cellulose, collagen, dextran, gelatin methacrylate, polyvinyl alcohol and hyaluronic acid hydrogels. In some examples, the hydrogel comprises one or more of alginate and chitosan. In some examples the hydrogel comprises alginate. In some examples, the hydrogel comprises gelatine.

[0064] In some examples, the hydrogel is formed from a hydrogel precursor. In some examples, the hydrogel precursor is a dried solid. In some examples, the hydrogel precursor is a dry powder. In some examples, to form the hydrogel, the hydrogel precursor is reconstituted with water. In some examples, the hydrogel precursor is reconstituted with water and heated. For example, in the case of the hydrogel being an alginate hydrogel, the hydrogel precursor may be sodium alginate.

[0065] In some examples, each polymer chain of the hydrogel precursor has a weight average molecular weight of about 2000 to about 600,000 g / mol. In some examples, each polymer chain of the hydrogel precursor has a molecular weight of about 10,000 to about 500,000 g / mol, for example about 50,000 to about 250,000 g / mol, for example about 100,000 to about 150,000 g / mol.

[0066] In some examples, each polymer chain of the hydrogel precursor has a weight average molecular weight of about 2000 to about 30,000 g / mol. In some examples, each polymer chain of the hydrogel precursor has a molecular weight of about 5,000 to about 25,000 g / mol, for example about 10,000 to about 20,000 g / mol.

[0067] In some examples, each polymer chain of the hydrogel precursor has a weight average molecular weight of at least 2000 g / mol. In some examples, each polymer chain of the hydrogel precursor has a molecular weight of at least 20,000 g / mol, for example at least 30,000 g / mol, for example at least 40,000 g / mol, for example at least 50,000 g / mol. In some examples, each polymer chain of the hydrogel precursor has a weight average molecular weight of up to 50,000 g / mol. In some examples, each polymer chain of the hydrogel precursor has a molecular weight of up to 40,000 g / mol, for example up to 30,000 g / mol, for example up to 20,000 g / mol, for example about 5,000 g / mol.

[0068] In some examples, each polymer chain of the hydrogel precursor has a weight average molecular weight of from about 2000 to about 50,000 g / mol. In some examples, each polymer chain of the hydrogel precursor has a weight average molecular weight of from about 4000 to about 48,000 g / mol, for example from about 6000 to about 46,000 g / mol, for example from about 8000 to about 44,000 g / mol, for example from about 10,000 to about 42,000 g / mol, for example from about 12,000 to about 40,000 g / mol, for example from about 14,000 to about 38,000 g / mol.

[0069] In some examples, the hydrogel comprises one or more of polyethylene glycol, alginate, chitosan, agarose, gellan gum, xanthan gum and hyaluronic acid hydrogels and each polymer chain of the hydrogel precursor has a weight average molecular weight of about 3,000 to about 100,000 g / mol. In some examples, the hydrogel comprises alginate and each polymer chain of the hydrogel precursor has a weight average molecular weight of about 10,000 to about 500,000 g / mol. In some examples, the hydrogel comprises alginate and each polymer chain of the hydrogel precursor has a weight average molecular weight of about 10,000 to about 50,000 g / mol.

[0070] Alternatively, each polymer chain of the hydrogel precursor may have a viscosity average molecular weight, as determined using capillary viscometry. In some examples, each polymer chain of the hydrogel precursor has a viscosity average molecular weight of about 2000 to about 600,000 g / mol. In some examples, each polymer chain of the hydrogel precursor has a viscosity average molecular weight of about 10,000 to about 500,000 g / mol, for example about 50,000 to about 250,000 g / mol, for example about 100,000 to about 150,000 g / mol.

[0071] In some examples, each polymer chain of the hydrogel precursor has a viscosity average molecular weight of about 2000 to about 30,000 g / mol. In some examples, each polymer chain of the hydrogel precursor has a viscosity average molecular weight of about 5,000 to about 25,000 g / mol, for example about 10,000 to about 20,000 g / mol. In some examples, each polymer chain of the hydrogel precursor has a viscosity average molecular weight of at least 2000 g / mol. In some examples, each polymer chain of the hydrogel precursor has a viscosity average molecular weight of at least 20,000 g / mol, for example at least 30,000 g / mol, for example at least 40,000 g / mol, for example at least 50,000 g / mol.

[0072] In some examples, each polymer chain of the hydrogel precursor has a viscosity average molecular weight of up to 50,000 g / mol. In some examples, each polymer chain of the hydrogel precursor has a viscosity average molecular weight of up to 40,000 g / mol, for example up to 30,000 g / mol, for example up to 20,000 g / mol, for example about 5,000 g / mol.

[0073] In some examples, each polymer chain of the hydrogel precursor has a viscosity average molecular weight of from about 2000 to about 50,000 g / mol. In some examples, each polymer chain of the hydrogel precursor has a viscosity average molecular weight of from about 4000 to about 48,000 g / mol, for example from about 6000 to about 46,000 g / mol, for example from about 8000 to about 44,000 g / mol, for example from about 10,000 to about 42,000 g / mol, for example from about 12,000 to about 40,000 g / mol, for example from about 14,000 to about 38,000 g / mol.

[0074] In some examples, the hydrogel comprises one or more of polyethylene glycol, alginate, chitosan, agarose, gellan gum, xanthan gum and hyaluronic acid hydrogels and each polymer chain of the hydrogel precursor has a viscosity average molecular weight of about 3,000 to about 100,000 g / mol. In some examples, the hydrogel comprises alginate and each polymer chain of the hydrogel precursor has a viscosity average molecular weight of about 10,000 to about 500,000 g / mol. In some examples, the hydrogel comprises alginate and each polymer chain of the hydrogel precursor has a viscosity average molecular weight of about 10,000 to about 50,000 g / mol.

[0075] In some examples, the hydrogel is chemically cross-linked. By “chemically cross-linked” it is meant herein that the polymer chains of the hydrogel are cross-linked via covalent bonds. In some examples, the functional groups present in the polymer chains form covalent bonds to functional groups present in other polymer chains. In some examples, the polymer chains are modified to include thiol groups and the chemical cross-linking comprises disulfide bond formation, or the polymer chains are modified to include carbon chains bearing terminal alkene groups and the chemical cross-linking comprises formation of saturated carbon-carbon bonds.

[0076] In some examples, the hydrogel is physically cross-linked. By “physically cross-linked” it is meant herein that the polymer chains of the hydrogel are cross-linked via non- covalent interactions. In some examples, the physical cross-linking comprises hydrogen bonding, hydrophobic interactions, and ionic interactions. In some examples, the physical cross-linking comprises ionic interactions.

[0077] In some examples, the hydrogel scaffold is chemically and physically cross-linked.

[0078] In some examples, the hydrogel scaffold constitutes between about 0.01 to about 20 wt. / vol. % of the faecal barrier device. In some examples, the hydrogel scaffold constitutes between about 0.01 to about 10 wt. / vol. % of the faecal barrier device. In some examples, the hydrogel scaffold constitutes between about 0.05 to about 5 wt. / vol. % of the faecal barrier device, for example about 0.1 to about 3 wt. / vol. %, for example about 0.15 to about 2.5 wt. / vol. %, for example about 0.2 to about 2 wt. / vol. %, for example about 0.25 to about 1.5 wt. / vol. %, for example about 0.3 to about 1 wt. / vol. % of the faecal barrier device. In some examples, the hydrogel scaffold comprises an alginate hydrogel and constitutes between about 0.05 to about 5 wt. / vol. % of the faecal barrier device, for example about 0.1 to about 3 wt. / vol. %, for example about 0.15 to about 2.5 wt. / vol. %, for example about 0.2 to about 2 wt. / vol. %, for example about 0.25 to about 1.5 wt. / vol. %, for example about 0.3 to about 1 wt. / vol. % of the faecal barrier device.

[0079] It will be appreciated that increases in, for example, molecular weight, and concentration of hydrogel precursor used in preparing the hydrogel scaffold will increase the strength or structural integrity of the hydrogel scaffold. The greater the strength or structural integrity of the hydrogel, the longer it will likely survive without degradation under physiological conditions.

[0080] Sacrificial filler material

[0081] A sacrificial filler material can be included to provide structural stability and integrity to the hydrogel scaffold of the faecal barrier device of the present invention. The sacrificial filler material can be selected or configured to ultimately degrade over time to leave the remaining hydrogel scaffold, which is less structurally sound, allowing the device of the present invention to collapse under the pressure, temperature, pH and / or ionic composition of the descending colon, as well as dissolving to completely be passed from the Gl tract.

[0082] It is important that the sacrificial filler material breaks down over time by some mechanism. The mechanism is not particularly limited. In some examples, the sacrificial filler material degrades due to a change in ionic concentration, temperature, pH etc.

[0083] In some examples, the sacrificial filler material is a polymer-based filler material. In some examples, the sacrificial filler material comprises one or more natural and / or synthetic polymer-based filler materials. In some examples, the polymer-based filler material is plant-based and / or animal-based. In some examples, the polymer-based filler material is plant-based. In some examples, the polymer-based filler material is animal-based. In some examples, the polymer-based filler material comprises both plant- and animalbased polymer-based compounds. In some examples, the sacrificial filler material comprises agar, carrageenan, and gelatine. In some examples, the sacrificial filler material is selected from agar, carrageenan and gelatine. In some examples, the sacrificial filler material is gelatine. In some examples, the gelatine is derived from bovine, porcine, or fish sources.

[0084] In some examples, the sacrificial filler material may be a material used as a suppository base such as is used in existing anal suppositories. The sacrificial filler material may be an oleagineous sacrificial filler material, such as cocoa butter or a hard fat such as a (hydrogenated) vegetable oil or an animal fat that melts at body temperature. Examples of such sacrificial filler materials include the Witepsol® series of products used in suppositories due to their melting points being at or just below physiological temperatures.

[0085] In some examples, the sacrificial filler material has a melting point of between about 25°C and about 45°C. In some examples the sacrificial filler material has a melting point of between about 27.5°C and about 42.5°C, more preferably about 30°C and about 40°C, more preferably about 32.5°C and 37.5°C, more preferably about 35°C. In some examples, the sacrificial filler material has a melting point of at least 25°C, at least 27.5°C, at least 30°C, at least 32.5°C, at least 35°C, at least 37.5°C, at least 40°C, at least 42.5°C and at least about 45°C.

[0086] In some examples, the sacrificial filler material has a melting point of no more than 45°C, no more than 42.5°C, no more than 40°C, no more than 37.5°C, no more than 35°C, no more than 32.5°C, no more than 30°C, no more than 27.5°C and no more than 25°C.

[0087] In some examples, the sacrificial filler material has a melting point of 32.5°C, 35°C, 37.5°C or 40°C.

[0088] Gelatine has a melting temperature between 31.7-34.2°C. It is therefore expected that it will lose mechanical strength within the body.

[0089] The melting temperature of the sacrificial material can be measured using any known technique, such as, for example differential scanning calorimetry or differential thermal analysis.

[0090] In some examples, the sacrificial filler material has a weight average molecular weight of from about 90,000 to about 250,000 g / mol. In some examples, the sacrificial filler material has a weight average molecular weight of from about 100,000 to about 240,000 g / mol, for example from about 120,000 to about 220,000 g / mol, for example from about 140,000 to about 200,000 g / mol, for example from about 160,000 to about 180,000 g / mol.

[0091] In some examples, the sacrificial filler material has a weight average molecular weight of at least about 90,000 g / mol. In some examples, the sacrificial filler material has a weight average molecular weight of at least about 100,000 g / mol, for example at least about 120,000 g / mol, for example at least about 140,000 g / mol, for example at least about 160,000 g / mol, for example at least about 180,000 g / mol, for example at least about 200,000 g / mol, for example at least about 220,000 g / mol, for example at least about 240,000 g / mol.

[0092] In some examples, the sacrificial filler material has a weight average molecular weight of no more than about 250,000 g / mol. In some examples, the sacrificial filler material has a weight average molecular weight of no more than about 240,000 g / mol, for example no more than about 220,000 g / mol, for example no more than about 200,000 g / mol, for example no more than about 180,000 g / mol, for example no more than about 160,000 g / mol, for example no more than about 140,000 g / mol, for example no more than about 120,000 g / mol, for example no more than about 100,000 g / mol.

[0093] In some examples, the sacrificial filler material is gelatine and has a weight average molecular weight of from about 160,000 to about 180,000 g / mol.

[0094] In some examples, the sacrificial filler material constitutes between about 0.1 to about 10 wt. / vol.% of the faecal barrier device. In some examples, the sacrificial filler material constitutes between about 0.25 to about 7.5 wt. / vol.% of the faecal barrier device, for example about 0.5 to about 5 wt. / vol.%, for example about 0.75 to about 4 wt. / vol.%, for example about 1 to about 3 wt. / vol.%, for example about 2 to about 3 wt. / vol.% of the faecal barrier device.

[0095] In some examples, the sacrificial filler material constitutes from about 0.1 to about 45 wt. / vol. % of the faecal barrier device. In some examples, the sacrificial filler material constitutes from about 0.25 to about 44 wt. / vol. % of the faecal barrier device, for example from about 0.5 to about 42 wt. / vol. %, for example from about 0.75 to about 40 wt. / vol. %, for example from about 1 to about 38 wt. / vol. %, for example from about 1.25 to about 36 wt. / vol. %, for example from about 1.5 to about 34 wt. / vol. %, for example from about 1.75 to about 32 wt. / vol. %, for example from about 2 to about 30 wt. / vol. %, for example from about 2.25 to about 28 wt. / vol. %, for example from about 2.5 to about 26 wt. / vol. %, for example from about 2.75 to about 24 wt. / vol. %, for example from about 3 to about 22 wt. / vol. %, for example from about 3.25 to about 20 wt. / vol. %, for example from about 3.5 to about 18 wt. / vol. %, for example from about 3.75 to about 16 wt. / vol. %, for example from about 4 to about 14 wt. / vol. %, for example from about 4.25 to about 12 wt. / vol. %, for example from about 4.5 to about 10 wt. / vol. % of the faecal barrier device. In some examples, the sacrificial filler material constitutes about 30 wt. / vol. % of the faecal barrier device. In some examples, the sacrificial filler material constitutes about 25 wt. / vol. % of the faecal barrier device.

[0096] Di- or trivalent metal cations

[0097] In some examples, the hydrogel is physically cross-linked. In some examples, the hydrogel is physically cross-linked through ionic interactions. In some examples, the hydrogel is physically cross-linked by metal cations. In some examples, the hydrogel is cross-linked by di- or trivalent metal cations. In some examples, the di- or trivalent metal ions are selected from alkaline earth metals and transition metals. In some examples, the di- or trivalent metal ions are selected from Mg2+, Ca2+, Sr2+, Ba2+, Cu2+, Zn2+, Mn2+, Fe2+, Cr3+and Fe3+and combinations thereof. In some examples, the di- or trivalent metal cations are selected from Ca2+, Zn2+and Sr2+. In some examples, the di- or trivalent metal cations are Ca2+ions.

[0098] In some examples, the hydrogel scaffold comprises alginate physically cross-linked by metal cations. In some examples, the hydrogel scaffold comprises alginate cross-linked by di- or trivalent metal cations. In some examples, the hydrogel scaffold comprises alginate cross-linked by alkaline earth metals and transition metals. In some examples, the hydrogel scaffold comprises alginate cross-linked by di- or trivalent metal ions selected from one or more of Mg2+, Ca2+, Sr2+, Ba2+, Cu2+, Zn2+, Mn2+, Fe2+, Cr3+and Fe3+. In some examples, the hydrogel scaffold comprises alginate cross-linked by di- or trivalent metal cations are selected from one or more of Ca2+, Zn2+and Sr2+. In some examples, the hydrogel scaffold comprises alginate cross-linked by Ca2+ions.

[0099] In some examples, the di- or trivalent metal cations exist in a compound prior to crosslinking the hydrogel precursor, wherein any suitable counterion to the di- or trivalent metal cations is permitted. In some examples, the counterion is selected from chloride, phosphate, carbonate and sulphate. In some examples, the counterion is selected from carbonate and chloride. In some examples, the counterion is carbonate.

[0100] In some examples, the compound in which the di- or trivalent metal cations exist prior to cross-linking the alginate is insoluble or only sparingly soluble in aqueous solution. In some examples, the compound in which the di- or trivalent metal cations exist prior to cross-linking the alginate is selected from CaCh, SrCh, ZnCh, CaCCh, SrCCh and ZnCCh and combinations thereof.

[0101] In some examples, when present, the di- or trivalent metal cations constitute between about 0.01 to about 3 wt. / vol. % of the faecal barrier device. In some examples, the di- or trivalent metal cations constitute between about 0.025 to about 2 wt. / vol. % of the faecal barrier device, for example about 0.05 to about 1.5 wt. / vol. %, for example about 0.075 to about 1 wt. / vol. %, for example about 0.09 to about 0.5 wt. / vol. %, for example about 0.1 to about 0.2 wt. / vol. % of the faecal barrier device. In some examples, when present, the di- or trivalent metal cations are present in the faecal barrier device or in the final solution which forms the device in a concentration of at least 1 mM, for example at least 2 mM, for example at least 5 mM, for example at least 7.5 mM, for example at least 10 mM, for example at least 12.5 mM, for example at least 15 mM, for example about 20 mM. In some examples, when present, the di- or trivalent metal cations are present in the faecal barrier device or in the final solution which forms the device in a concentration of up to 20 mM, for example up to 15 mM, for example up to 12.5 mM, for example up to 10 mM, for example up to 7.5 mM, for example up to 5 mM, for example up to 2 mM, for example about 1 mM.

[0102] It will be appreciated that increasing the concentration of the metal cations will increase the strength or structural integrity of the hydrogel scaffold as the degree of cross-linking will increase. The greater the strength or structural integrity of the hydrogel, the longer it will likely survive without degradation under physiological conditions.

[0103] Acidic species

[0104] As part of formation of the hydrogel, an acidic species can be added to slow down the reaction of the hydrogel precursor into a hydrogel scaffold, allowing for the hydrogel scaffold to form objects of sufficient size to act as a faecal barrier device.

[0105] In some examples, the acidic species has a pKa between about 15 and about 3. The acidic species has a pKa of between about 12 and about 4, for example between about 5 and 11 , for example between about 6 and 10, for example between about 7 and 9.

[0106] In some examples, the acidic species has a pKa of at least about 3, at least about 4, at least about 5, at least about 6, at least about 7, at least about 8, at least about 9, at least about 10, at least about 11 , at least about 12, at least about 13, at least about 14, at least about 15.

[0107] In some examples, the acidic species has a pKa of no more than about 15, no more than about 14, no more than about 13, no more than about 12, no more than about 11 , no more than about 10, no more than about 9, no more than about 8, no more than about 7, no more than about 6, no more than about 5, no more than about 4, no more than about 3. A pKa of this nature means that the acidic species is a moderate / weak acid i.e., protons are released into solution at a reasonable rate, but not too quickly. In some examples, the acidic species is a “latent” acidic species i.e., it does not exist in acidic form, but must first be “deprotected” to reveal the acidic moiety. In some examples the acidic species is an ester, such as a carboxylic ester, or a carboxylic anhydride. In some examples, the acidic species is selected from glucono-8-lactone (GDL), citric acid (or monosodium citrate), or abscisic acid.

[0108] In some examples, the conjugate base of the acidic species remains in the composition of the hydrogel scaffold after formation of the device, acting as a marker of the method of manufacture. In some examples, the conjugate base is gluconate.

[0109] In some examples, the conjugate base of the acidic species constitutes between about 0.05 to about 5 wt. / vol.% of the faecal barrier device. In some examples, the conjugate base of the acidic species constitutes between about 0.01 to about 4 wt% of the faecal barrier device, for example about 0.02 to about 2 wt%, for example about 0.025 to about 1 wt%, for example about 0.03 to about 0.5 wt%, for example about 0.04 to about 0.1 wt% of the faecal barrier device.

[0110] Lubricant

[0111] In some examples, the faecal barrier device according to the present invention, further comprises a lubricant. This is beneficial within the final product, as released lubricant will further facilitate anorectal intercourse.

[0112] Bio-compatible lubricants are well-known within the art and the particular lubricant used is not particularly limited. However, in some examples, the lubricant is selected from glycerine, propylene glycol and dimethicone.

[0113] In some examples, the lubricant constitutes between about 1 to about 10 wt. / vol.% of the faecal barrier device. In some examples, the lubricant constitutes between about 2 to about 9 wt. / vol.% of the faecal barrier device, for example about 3 to about 8 wt. / vol.%, for example about 4 to about 7 wt. / vol.%, for example about 5 to about 6 wt. / vol.% of the faecal barrier device. Composition of device

[0114] In some examples, the hydrogel scaffold constitutes about 0.01 to about 10 wt. / vol.% of the faecal barrier device; when present the sacrificial filler material constitutes about 0.1 to about 10 wt. / vol.% of the faecal barrier device; and, when present, the divalent metal cations constitute about 0.01 to about 3 wt. / vol.% of the faecal barrier device. In some examples, the hydrogel scaffold constitutes about 0.05 to about 5 wt. / vol.% of the faecal barrier device; the sacrificial filler material when present constitutes about 0.7 to about 4 wt. / vol.% of the faecal barrier device; and, when present, the divalent metal cations constitute about 0.05 to about 1.5 wt. / vol.% of the faecal barrier device. In some examples, the hydrogel scaffold constitutes about 0.3 to about 1 wt. / vol.% of the faecal barrier device; the sacrificial filler material when present constitutes about 2 to about 3 wt. / vol.% of the faecal barrier device; and, when present, the divalent metal cations constitute about 0.1 to about 0.2 wt. / vol.% of the faecal barrier device. In some examples, the hydrogel scaffold constitutes from about 0.01 to about 10 wt. / vol. % of the faecal barrier device; when present the sacrificial filler material constitutes from about 0.1 to about 45 wt. / vol. % of the faecal barrier device; and, when present, the divalent metal cations constitute from about 0.01 to about 3 wt. / vol. % of the faecal barrier device.

[0115] In some examples, the faecal barrier device comprises: the hydrogel scaffold in an amount between about 0.05 to about 5 wt. / vol. %; a sacrificial filler material between about 0.75 to about 4 wt. / vol. %; di- or trivalent metal cations between about 0.025 to about 2 wt. / vol. %; and an acidic species between about 0.02 to about 2 wt%.

[0116] In some examples, the hydrogel scaffold comprises an alginate hydrogel and constitutes between about 0.05 to about 5 wt. / vol. % of the faecal barrier device, for example about 0.1 to about 3 wt. / vol. %, for example about 0.3 to about 1 wt. / vol. % of the faecal barrier device, gelatine as a sacrificial filler material in an amount between about 0.1 to about 10 wt. / vol. % of the faecal barrier device; calcium carbonate as a source of di- or trivalent metal cations in an amount between about 0.025 to about 2 wt. / vol. %; and glucono-8- lactone as an acidic species in an amount between about 0.02 to about 2 wt%.

[0117] In some examples, the hydrogel scaffold comprises an alginate hydrogel and constitutes between about 0.05 to about 5 wt. / vol. % of the faecal barrier device, for example about 0.1 to about 3 wt. / vol. %, for example about 0.3 to about 1 wt. / vol. % of the faecal barrier device, gelatine as a sacrificial filler material in an amount between about 0.1 to about 30 wt. / vol.% of the faecal barrier device; calcium carbonate as a source of di- or trivalent metal cations in an amount between about 0.025 to about 2 wt. / vol. %; and glucono-8- lactone as an acidic species in an amount between about 0.02 to about 2 wt. / vol. %.

[0118] In some examples, a device according to the present disclosure has a width, length or depth between about 10 mm to about 42 mm. In some examples, the device has a width, length or depth each between about 15 mm to about 40 mm, for example about 20 mm to about 39 mm, for example about 26 mm to about 38mm.

[0119] In some examples, a device according to the present disclosure has a width, length or depth of at least about 10 mm, at least about 15 mm, at least about 20 mm, at least about 22 mm, at least about 24 mm, at least about 26 mm, at least about 28 mm, at least about 30 mm, at least about 32 mm, at least about 34 mm, at least about 36 mm, at least about 38 mm, at least about 40 mm.

[0120] In some examples, a device according to the present disclosure has a width, length or depth of no more than 10 mm, no more than 15 mm, no more than 20 mm, no more than 22 mm, no more than 24 mm, no more than 26 mm, no more than 28 mm, no more than 30 mm, no more than 32 mm, no more than 34 mm, no more than 36 mm, no more than 38 mm, no more than 40 mm.

[0121] In some examples, a device according to the present disclosure has a width, length or depth of about 10 mm, about 15 mm, about 20 mm, about 22 mm, about 24 mm, about 26 mm, about 28 mm, about 30 mm, about 32 mm, about 34 mm, about 36 mm, about 38 mm, about 40 mm.

[0122] In some examples, a device according to the present disclosure has a defined shape or form or 3-dimensional appearance due to the formation of the hydrogel scaffold. In some examples the device is in the shape of a sphere, a cylinder or an egg.

[0123] In some examples, a device according to the present disclosure is in the shape of a sphere with a diameter of between about 10 and about 40 mm. In some examples, the diameter is between about 15 and about 40 mm, between about 24 and about 39 mm, between about 26 and about 38 mm. In some examples, a device according to the present disclosure is in the shape of a sphere with a diameter of at least about 10 mm, at least about 15 mm, at least about 20 mm, at least about 22 mm, at least about 24 mm, at least about 26 mm, at least about 28 mm, at least about 30 mm, at least about 32 mm, at least about 34 mm, at least about 36 mm, at least about 38 mm, at least about 40 mm.

[0124] In some examples, a device according to the present disclosure is in the shape of a sphere with a diameter of no more than 10 mm, no more than 15 mm, no more than 20 mm, no more than 22 mm, no more than 24 mm, no more than 26 mm, no more than 28 mm, no more than 30 mm, no more than 32 mm, no more than 34 mm, no more than 36 mm, no more than 38 mm, no more than 40 mm.

[0125] In some examples, a device according to the present disclosure is in the shape of a sphere with a diameter of about 10 mm, about 15 mm, about 20 mm, about 22 mm, about 24 mm, about 26 mm, about 28 mm, about 30 mm, about 32 mm, about 34 mm, about 36 mm, about 38 mm, about 40 mm.

[0126] Anal suppositories are often referred to as being “bullet-shaped” or “torpedo-shaped” (l.e. generally cylindrical or elongate with one or both ends being tapered) and it is foreseen that a device according to the present disclosure may also be bullet-shaped or torpedo-shaped, with a largest diameter (l.e. at the widest point) being of a diameter as discussed above in connection with spherical devices.

[0127] In some examples, a device according to the present disclosure is a suppository comprising a hydrogel as described herein; and one or more active agent(s). In some examples, a device according to the present disclosure is a suppository comprising a hydrogel; a sacrificial filler material dispersed throughout the hydrogel; and one or more active agent(s). In some examples, the one or more active agent(s) is / are dispersed throughout the device. In some examples, the one or more active agent(s) is / are disposed on a surface of the device.

[0128] In some examples, a device according to the present disclosure may further comprise one or more active agents. In some examples, the one or more active agents includes a pharmaceutical therapeutic agent for treating or preventing a viral or bacterial infection such as treating or preventing an STI such as HIV or chlamydia. In some examples, the one or more active agent(s) is / are dispersed throughout the device. In some examples, the one or more active agent(s) is / are disposed on a surface of the device.

[0129] Method of manufacturing

[0130] Disclosed herein is a method of manufacturing a faecal barrier device. In some examples, the method of manufacturing a faecal barrier device comprises heating an aqueous solution of a hydrogel precursor; optionally combining the heated hydrogel precursor with a sacrificial filler material; and allowing the solution to cool and set, thereby forming the faecal barrier device.

[0131] In some examples, prior to cooling, the solution comprises the hydrogel precursor in amounts as described previously. In some examples, prior to cooling, the solution comprises the hydrogel precursor and the sacrificial filler material, in amounts as described previously. Thus, in some examples, prior to cooling, the solution comprises the hydrogel precursor in an amount of about 0.01 to about 10 wt. / vol.%, and a balance of water. In some examples, prior to cooling, the solution comprises the hydrogel precursor in an amount of about 0.01 to about 10 wt. / vol.%, and a balance of water. In some examples, prior to cooling, the solution comprises the hydrogel precursor in an amount of about 0.01 to about 20 wt. / vol.%, or about 0.01 to about 10 wt. / vol.%; the sacrificial filler material in an amount of about 0.1 to about 10 wt. / vol.%; and a balance of water. In some examples, prior to cooling, the solution comprises the hydrogel precursor in an amount of about 0.01 to about 20 wt. / vol.%, or about 0.01 to about 10 wt. / vol.%; the sacrificial filler material in an amount of about 0.1 to about 45 wt. / vol. %, or about 0.1 to about 10 wt. / vol. %; and a balance of water. In some examples, the solution comprises the hydrogel precursor in an amount of about 0.1 to about 3 wt. / vol. %; the sacrificial filler material in an amount of about 0.5 to about 5 wt. / vol. %; and a balance of water. In some examples, the solution comprises the hydrogel precursor in an amount of about 0.2 to about 2 wt. / vol. %; the sacrificial filler material in an amount of about 0.75 to about 4 wt. / vol. %; and a balance of water. In some examples, the solution comprises the hydrogel precursor in an amount of about 0.3 to about 1 wt. / vol. %; the sacrificial filler material in an amount of about 1 to about 3 wt. / vol. %; and a balance of water.

[0132] Casting large objects out of a hydrogel can be a technical challenge due to the rate at which hydrogels set. However, unexpectedly, the present inventors have found that they were able to slow the setting time of hydrogels. Without being bound by any theory, to slow the setting of the hydrogel to obtain devices with defined shapes the present inventors have used metal salts which are insoluble or only partially soluble in water, e.g., calcium carbonate, and a slow-release (or “latent”) acid species e.g., glucono-8-lactone. When setting of the hydrogel is desired, the latent acid species is added which first hydrolyses before releasing H+ions. This gradual acidification slowly liberates metal cations from the insoluble salt which crosslink the hydrogel precursor, allowing a working time for the solution to be poured into moulds.

[0133] Therefore, in some examples, the method of manufacturing a faecal barrier device further comprises, prior to allowing the solution to cool, combining di- or trivalent metal cations with the solution of heated hydrogel precursor (and optional sacrificial filler material) to form a second solution; allowing the second solution to cool; combining the second solution with an acidic species to form a third solution; and allowing the third solution to cool and set, thereby forming the faecal barrier device. The di- or trivalent metal cations and acidic species may alternatively be combined with the solution of hydrogel precursor simultaneously, either by simultaneous addition of two separate solutions or by addition of a single solution including the di- or trivalent metal cation and the acidic species.

[0134] In some examples, prior to cooling, the third solution comprises, in addition to the hydrogel precursor and sacrificial filler material in the amounts described above, the di- or trivalent metal cations in an amount of about 0.01 to about 3 wt. / vol.%; and the acidic species in an amount of about 0.05 to about 5 wt. / vol.%. In some examples, the third solution comprises the di- or trivalent metal cations in an amount of about 0.05 to about 1 .5 wt. / vol.%; and the acidic species in an amount of about 0.02 to about 2 wt. / vol.%. In some examples, the third solution comprises the di- or trivalent metal cations in an amount of about 0.075 to about 1 wt. / vol.%; and the acidic species in an amount of about 0.025 to about 1 wt%. In some examples, the third solution comprises the di- or trivalent metal cations in an amount of about 0.09 to about 0.5 wt. / vol.%; and the acidic species in an amount of about 0.03 to about 0.05 wt. / vol.%. In some examples, the third solution comprises the di- or trivalent metal cations in an amount of about 0.1 to about 0.2 wt. / vol.%; and the acidic species in an amount of about 0.04 to about 0.1 wt. / vol.%.

[0135] The solution, or the third solution, may be cooled to less than 20 °C, for example less than 15 °C, for example less than 10 °C, for example less than 5 °C, for example between 0 to 5 °C. Components used in the method of manufacturing the faecal barrier device are as described herein.

[0136] Kit of parts

[0137] Disclosed herein is a kit of parts. In some examples, the kit of parts comprises a faecal barrier device according to the present disclosure; and an applicator. In some examples, the kit of parts comprises a faecal barrier device according to the present disclosure; and packaging comprising deionised water or a sterile buffer solution in which the faecal barrier device is contained or stored. In some examples, the kit of parts comprises a faecal barrier device according to the present disclosure; packaging comprising a sterile buffer solution in which the faecal barrier device is contained or stored; and an applicator. The packaging may be hermetically sealed, for example by comprising a non-breathable film.

[0138] In some examples, the sterile buffer solution comprises water. In some examples, the sterile buffer solution has a pH of about 6 to about 9, about 7 to about 8, about 7.5. In some examples, the sterile buffer solution comprises phosphate ions, sodium ions, chloride ions, potassium ions. In some examples, the sterile buffer solution is selected from Phosphate Buffered Saline (PBS), HEPES and Tris buffer. In some examples, the sterile buffer solution has been heat-treated, or sterilised using gamma irradiation or ethylene oxide gas. In some examples, the sterile buffer solution has been filtered. In some examples, the sterile buffer solution has been heat-treated and filtered.

[0139] Uses

[0140] In some examples, a di- or trivalent metal cation-stabilised alginate may be used as a faecal barrier device. In some examples, the di- or trivalent metal cation-stabilised alginate is inserted into the rectum prior to anorectal intercourse and remains there during anorectal intercourse.

[0141] In some examples, the di- or trivalent metal cation-stabilised alginate may be a faecal barrier device as has been described herein.

[0142] In some examples, a faecal barrier device according to the present disclosure may be used as a faecal incontinence device. In some examples, a faecal barrier device according to the present disclosure may be used to deliver active agents. In some examples, the active agents include antimicrobials, antiretrovirals (PrEP), biologies and bacteriophages. In some examples, the active agents are dispersed throughout the faecal barrier device. In some examples, the active agents are disposed on a surface of the faecal barrier device.

[0143] It is well understood in the art that hydrogels can be loaded with active compounds. In some examples, devices of the present disclosure may be used to deliver active compounds to the correct part of the body in a behaviourally congruent manner. In some examples, devices of the present disclosure offer protection against many different sexually transmitted infections (e.g., chlamydia, gonorrhoea, syphilis, and HIV). From a public health perspective this has the potential to drastically reduce STI spread during anorectal intercourse.

[0144] In some examples, a device comprising a hydrogel as described herein; and one or more active agent(s) may be used as a suppository. In some examples, a device as described herein comprising a hydrogel; a sacrificial filler material dispersed throughout the hydrogel; and one or more active agent(s) may be used as a suppository. In some examples, a device according to the present disclosure may be used as a suppository. In some examples, a di- or trivalent metal cation-stabilised alginate comprising one or more active agent(s) may be used as a suppository.

[0145] Examples

[0146] Embodiments of the present invention will now be described, purely by way of example.

[0147] Devices, compositions and method of manufacture

[0148] Example faecal barrier devices were made as follows:

[0149] Example 1

[0150] Sodium alginate 4 g (Special Ingredients - SKU 5060341111082) was added to 1000 mL distilled water (to give 0.4 w / v%) and heated to 70°C. Bovine gelatine 26.3 g (2.6% w / v, Dr. Oetker - 7656436) was added to the alginate and after complete dissolution the solution was left to cool to 40°C. Calcium carbonate 1.22 g (Intralabs - 180105 / 001) was resuspended in 20ml of distilled water and then the solution added to the alginate- gelatine mix to a final concentration of 12.2 mM. Glucono-5-lactone 4.34 g (Ebay - 325032929955) was resuspended in 20ml of distilled water and then the solution added to the alginate-gelatine mix to a final concentration of 24.4 mM. The mixture was then poured into moulds and left overnight at 4°C to set.

[0151] Example 2

[0152] In another example, 16g sodium alginate (viscosity average molecular weight 12-40 kDa) was added to 200ml of distilled water and blended with a handheld mixer to produce a mixture of 8% w / v. 50g of porcine gelatine (weight average molecular weight 160-180 kDa) was added to 142.5ml of dH2O at room temperature and left to stand for 10 minutes. The gelatine mixture is then heated to 70°C until fully dissolved and then 17.5ml of the sodium alginate solution (8% w / v) was added. The resulting solution was mixed thoroughly. 0.4g of Calcium Carbonate was resuspended in 20ml of distilled water then added to the alginate-gelatine mix to a final concentration of 20.0 mM. The resulting solution was mixed thoroughly. 0.36g of glucono-b-lactone was resuspended in 20ml of dH2O then added to the alginate-gelatine mix to a final concentration of 10.1 mM. The resulting solution was mixed thoroughly. Some devices had the active agents Doxycycline hyclate (97.4mM) and Sulfasalazine (62.7mM) added to the mixture directly after the addition of glucono-b-lactone. The resulting solutions were mixed thoroughly and then poured into moulds and left overnight at 4°C to set. The final formulation comprises gelatine 25 wt. / vol. %, alginate 0.7 wt. / vol. %, glucono-b-lactone 10.1 mM (0.18 wt. / vol. %) and CaCCh 20 mM (0.2 wt. / vol. %).

[0153] Example 3

[0154] In another example, 10g sodium alginate (viscosity average molecular weight 12-40 kDa) was added to 500ml of distilled water and blended with a handheld mixer to produce a mixture of 2% w / v. 150g of porcine gelatine (weight average molecular weight 160-180 kDa) was added to 142.5ml of dH2O at room temperature and left to stand for 10 minutes. The gelatine mixture is then heated to 70°C until fully dissolved and then 17.5ml of the sodium alginate solution (2% w / v) was added. The resulting solution was mixed thoroughly. 1g of Calcium Carbonate was resuspended in 20ml of distilled water then added to the alginate-gelatine mix to a final concentration of 20.0 mM. The resulting solution was mixed thoroughly. 3.8g of glucono-b-lactone was resuspended in 20ml of dH2O then added to the alginate-gelatine mix to a final concentration of 10.1 mM. The resulting solution was mixed thoroughly. Some devices had the active agents Doxycycline hyclate (97.4mM) and Sulfasalazine (62.7mM) added to the mixture directly after the addition of glucono-6-lactone. The resulting solutions were mixed thoroughly and then poured into moulds and left overnight at 4°C to set. The final formulation comprises gelatine 30 wt. / vol. %, alginate 0.7 wt. / vol. %, glucono-6-lactone 11.23 mM (0.2 wt. / vol. %) and CaCCh 19.98 mM (0.2 wt. / vol. %).

[0155] Faecal barrier device

[0156] As a proof of concept, anorectal intercourse was modelled using pigs’ rectums (ex vivo) and a prosthetic penis to demonstrate that hydrogel-based faecal barrier devices can function to prevent faeces transfer (Figure 1). The experiment was designed so any faeces residing in the rectum should be moved by the device, resulting in the prosthetic penis contacting the area of the rectum where the faeces had originally resided. In addition to preventing passage of faeces beyond the sigmoid colon, this suggests that as a result of its insertion, the device can displace faeces further up the Gl tract.

[0157] Pigs’ faeces was inserted from the intestinal side of a pig’s rectum. A device of the present invention (38mm diameter) was inserted through the anus into the rectum. A prosthetic penis was then inserted and removed to a depth of 5.4 inches five times in succession. The prosthetic penis was then photographed, and the rectum cut open to visualise any faeces spread (n=1 , five technical replicates shown). As can be seen in Figure 1 , a device of the present invention prevented transfer of faeces to the prosthetic penis, unlike in the control experiment performed in the absence of the device.

[0158] Device stability

[0159] To model the stability of a device of the present invention, example devices were subjected to the conditions of the human body, particularly those of the Gl tract.

[0160] Devices made to the specification above were incubated in phosphate-buffered saline (PBS) at 37°C, which has a pH of 7.4. At several intervals, the devices were removed from the PBS and the diameter measured. The results are set out in Figures 2, 3 and 4. At the same intervals following incubation in PBS at 37°C, devices made to the specification above were tested for the compressive force required to break the ball. The results are set out in Figure 5. Figure 5 includes a plot of the internal resting pressure across the anal canal, as measured by Seong et al (J Neurogastroenterol Motil, Vol 17 No 3 July 2011 pp300-304), as a reference point to indicate the usability and long term instability of the devices described.

[0161] As can be seen from the results of these tests, devices according to the present disclosure retain their integrity for extended periods of time at body temperature, up to 6 hours, demonstrating their suitability as a faecal barrier device. However, the same devices also lose integrity under pressure at body temperature, to the point that they will break down within a satisfactory timeframe and not remain in the Gl tract possibly requiring medical intervention.

[0162] At the same intervals following incubation in PBS at 37°C, devices made to the specification above were tested for the compressive force required to compress the ball. The results are set out in Figure 6. Figure 6 includes a plot of the internal resting pressure across the anal canal, as measured by RJ Felt-Bersma et al (Hepatogastroenterology, Vol 38 No 5 October 1991 pp444-449), as a reference point to indicate the usability and long term instability of the devices described.

[0163] Active agent release

[0164] Devices made to the specification above in Example 2 were incubated in phosphate- buffered saline (PBS) at 37°C, which has a pH of 7.4. At the time points indicated in Figs. 7C and 7D, samples of PBS were taken.

[0165] For experiments measuring the concentration of sulfasalazine, a LT-4500 plate reader (Labtech) was used to measure absorbance at 405nm in flat bottom 96 well plates (ADVANGENE - CC Plate-PS-96A-F-C-S). For experiments measuring the concentration of doxycycline hyclate a CLARIO Star Plus plate reader (BMG LabTech) was used to measure absorbance at 350nm in UV-Star 96 well plates (Greiner bio-one - 675801).

[0166] In both cases, a standard of the active agents at a known concentration was used to produce a calibration curve (Figs. 7A, 7B and 8A). This allowed the active agents’ concentration and, subsequently, percentage of drug released from the device to be calculated. The results are set out in Figures 7D and 8B.

[0167] As can be seen from the results of these tests, devices according to the present disclosure steadily release active agents, demonstrating their suitability for therapeutic applications.

Claims

Claims1 . A faecal barrier device, comprising: a hydrogel configured to block passage of faeces from the sigmoid colon through the rectum.

2. The faecal barrier device according to claim 1 , further comprising a sacrificial filler material dispersed throughout the hydrogel.

3. The faecal barrier device according to claim 1 or claim 2, wherein the device has a width, length or depth between about 10 mm to about 42 mm.

4. The faecal barrier device according to any one of claims 1 to 3, wherein the faecal barrier device is in the shape of a sphere, cylinder or egg.

5. The faecal barrier device according to claim 2, wherein the sacrificial filler material has a melting point of between about 30°C and about 40°C.

6. The faecal barrier device according to claim 5, wherein the sacrificial filler material is selected from one or more of agar, carrageenan and gelatine.

7. The faecal barrier device according to any one of claims 1 to 6, wherein the hydrogel comprises one or more synthetic and / or natural hydrogels.

8. The faecal barrier device according to any one of claims 1 to 7, wherein: the hydrogel comprises one or more of polyacrylamide, polyethylene glycol, alginate, chitosan, carboxymethyl chitosan, agarose, gellan gum, xanthan gum, hydroxyethyl cellulose, collagen, dextran, gelatin methacrylate, polyvinyl alcohol and hyaluronic acid hydrogels.

9. The faecal barrier device according to any one of claims 1 to 8, wherein the hydrogel comprises alginate cross-linked by di- or trivalent metal cations.

10. The faecal barrier device according to claim 9, wherein the di- or trivalent metal cations are selected from Mg2+, Ca2+, Sr2+, Ba2+, Cu2+, Zn2+, Mn2+, Fe2+, Cr3+and Fe3+.

11. The faecal barrier device according to any one of claims 1 to 10, wherein the hydrogel constitutes about 0.01 to about 10 wt. / vol.% of the faecal barrier device, the sacrificial filler material, when present, constitutes about 0.1 to about 10 wt. / vol.% of the faecal barrier device and, when present, the divalent metal cations constitute about 0.01 to about 3 wt. / vol.% of the faecal barrier device.

12. The faecal barrier device according to any one of claims 1 to 11 , further comprising a conjugate base of an acidic species, wherein the acidic species has a pKa between about 10 to about 3.

13. The faecal barrier device according to claim 12, wherein the conjugate base is gluconate.

14. The faecal barrier device according to any one of claims 1 to 13, further comprising a lubricant, for example wherein the lubricant is glycerine.

15. The faecal barrier device according to any one of claims 1 to 14, further comprising an active agent.

16. A method of manufacturing a faecal barrier device, comprising: heating an aqueous solution of a hydrogel precursor; optionally combining the heated hydrogel precursor with a sacrificial filler material; and allowing the solution to cool and set, thereby forming the faecal barrier device.

17. The method of manufacturing a faecal barrier device according to claim 16, further comprising: prior to allowing the solution to cool, combining di- or trivalent metal cations with the solution to form a second solution; allowing the second solution to cool; combining the second solution with an acidic species to form a third solution; and allowing the third solution to cool and set, thereby forming the faecal barrier device.

18. The method of manufacturing a faecal barrier device according to claim 17, wherein, prior to cooling, the third solution comprises: the di- or trivalent metal cations in an amount of about 0.01 to about 3 wt. / vol.%;the acidic species in an amount of about 0.05 to about 5 wt. / vol.%.

19. The method of manufacturing a faecal barrier device according to claim 17 or 18, wherein: the di- ortrivalent metal cations are selected from Mg2+, Ca2+, Sr2+, Ba2+, Cu2+, Zn2+, Mn2+, Fe2+, Cr3* and Fe3+; and / or the acidic species has a pKa between about 10 to about 3.

20. The method of manufacturing a faecal barrier device according to any one of claims 17 to 19, wherein the acidic species is glucono-8-lactone.21 . The method of manufacturing a faecal barrier device according to any one of claims 16 to 20, wherein, prior to cooling, the solution or the third solution comprises: the hydrogel precursor in an amount of about 0.1 to about 10 wt. / vol.%; the sacrificial filler material in an amount of about 0.1 to about 10 wt. / vol.%; and a balance of water.

22. The method of manufacturing a faecal barrier device according to any one of claims 16 to 21 , wherein: the hydrogel precursor comprises one or more of polyacrylamide, polyethylene glycol, alginate, chitosan, carboxymethyl chitosan, agarose, gellan gum, xanthan gum, hydroxyethyl cellulose, collagen, dextran, gelatin methacrylate, polyvinyl alcohol and hyaluronic acid hydrogel precursors; and, when present the sacrificial filler material comprises one or more of agar, carrageenan and gelatine.

23. A kit of parts, comprising: a faecal barrier device according to any one of claims 1 to 15; and an applicator.

24. Use of a di- or trivalent metal cation-stabilised alginate as a faecal barrier device.

25. The use of claim 24, wherein the faecal barrier device is inserted into the rectum prior to anorectal intercourse.

26. The use of claim 24 or 25, wherein the faecal barrier device is as described in any one of claims 1 to 15.

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