A DELIVERY DEVICE

Abstract

The invention relates to a delivery device suitable for delivering a chemical substance, e.g. a medical device such as a catheter, a microcapsule, an implantable capsule or a P-ring, or a delivery device for use in the construction industries e.g. in the form of microcapsules comprising antifouling agent for marine paint. The delivery device comprises a closed cavity, the cavity is defined by an innermost wall surface, wherein at least a section of the inner wall surface constitutes an inner surface of a delivery membrane wherein the delivery membrane comprises an interpenetrating polymer network substrate comprising a host polymer and a guest polymer, where the guest polymer is interpenetrating the host polymer to form substantially continuous pathways within said host polymer.

Claims

1. A delivery device suitable for delivering a chemical substance comprising one or more chemical compounds, the delivery device comprises a closed cavity, the cavity is defined by an innermost wall surface, wherein at least a section of the inner wall surface constitutes an inner surface of a delivery membrane wherein the delivery membrane comprises an interpenetrating polymer network substrate comprising a host polymer and a guest polymer, where the guest polymer is interpenetrating the host polymer to form substantially continuous pathways within said host polymer.

2. The delivery device of claim 1, wherein said delivery membrane has an outer surface opposite to said inner surface of said delivery membrane, said substantially continuous pathways of said guest polymer within said host polymer extend from the inner surface to the outer surface of said delivery membrane.

3. The delivery device of claim 1 or claim 2, wherein at least a section of said delivery membrane has a thickness of from 0.1 ?m-10 cm, such as from 1 ?m to 1 cm preferably from 10 ?m to 1 mm.

4. The delivery device of any one of the preceding claims, wherein the host polymer is a cross-linked polymer such as a cross-linked elastomer, e.g. thermoplastic elastomer (TPE), polyolefin elastomer (POE), polyurethane (PU), rubber, e.g. latex rubber, silicone or any combinations thereof.

5. The delivery device of any one of the preceding claims, wherein the host polymer is physically cross-linked; the host polymer is preferably a physically cross-linked TPE.

6. The delivery device of any one of the preceding claims, wherein the host polymer is chemically cross-linked; the host polymer is preferably covalently cross-linked.

7. The delivery device of any one of the preceding claims, wherein the host polymer is an elastomer, preferably selected from thermoplastic elastomers (TPEs) polyolefin elastomers (POEs), thermoplastic polyurethane (TPU), rubber, e.g. latex rubber, silicones and/or any combinations thereof.

8. The delivery device of claim 7, wherein the host polymer comprises thermoplastic polyurethane (TPU).

9. The delivery device of claim 7, wherein the host polymer comprises silicone.

10. The delivery device of any one of the preceding claims, wherein the host polymer has a structure of a network of strand shaped filaments comprising a plurality of intrastrand pathways.

11. The delivery device of claim 10, wherein the polymer has a structure of a network of substantially flat strand shaped filaments.

12. The delivery device of claim 10 or claim 11, wherein the intrastrand pathways has a volume of at least about 30% of the total volume of the delivery membrane, such as at least about 40%, such as at least about 50%, such as at least about 60% of the total volume of the delivery membrane.

13. The delivery device of any one of the preceding claims, wherein the guest polymer comprises a gel selected from hydrogel, aerogel, xerogel or any combinations thereof.

14. The delivery device of any one of the preceding claims, wherein the guest polymer comprises a homopolymer, preferably polymerized from an acrylate monomer or a vinyl polymer, more preferably n-vinyl pyrolidone (nVP), styrene; oxygen-, phenyl, amino and nitrogen-containing acrylic and methacrylic derivatives, e.g. acrylic esters, acrylic acids, methacrylic acid and -esters, alkyl and hydroxyalkyl acrylates and methacrylates; functionalized methacrylates such as 2-hydroxyethyl methacrylate (HEMA), glycerol monomethacrylate (GMMA), heptaflurobutyl acrylate (HFBA), 2-methacryloyloxyethyl phosphorylcholine (MPC) and [2-(methacryloyloxy)ethyl]-dimethyl-(3-sulfopropyl)-ammonium hydroxide (Betain); alkyl substituted acrylates and methacrylates such as methyl methacrylate (MMA), ethyl methacrylate (EMA), butyl methacrylate (BMA), dodecyl methacrylate (DMA); PEGylated (meth)actylates such as poly(ethylene glycol) methyl ether methacrylate (PEGMEMA) and poly(ethylene glycol) methyl ether acrylate (PEGMEA); substituted 62 - and ?-lactones, lactic acid monomers; carbohydrides and fluorinated monomers; urethanes; mono- and di-functional alcohols; carboxylic acids; amines; isocyanates; epoxides; aromatics carrying alkyl group(s); sulfonated aromatics, aromatic resins; imidazole; imidazol derivatives; zwitterionic monomers; pyrazoles; quaternary ammonium monomers and any combinations thereof.

15. The delivery device of any one of the preceding claims 1-13, wherein the guest polymer comprises a copolymer, preferably polymerised from monomers comprising silanes, e.g. tetraethylorthosilicate or tetraethoxysilane (TEOS), an acrylate monomer or a vinyl polymer, more preferably n-vinyl pyrolidone (nVP), styrene; oxygen-, phenyl, amino and nitrogen-containing acrylic and methacrylic derivatives, e.g. acrylic esters, acrylic acids, methacrylic acid and -esters, alkyl and hydroxyalkyl acrylates and methacrylates; functionalized methacrylates such as 2-hydroxyethyl methacrylate (HEMA), glycerol monomethacrylate (GMMA), heptaflurobutyl acrylate (HFBA), 2-methacryloyloxyethyl phosphorylcholine (MPC) and [2-(methacryloyloxy)ethyl]-dimethyl-(3-sulfopropyl)-ammonium hydroxide (Betain); alkyl substituted acrylates and methacrylates such as methyl methacrylate (MMA), ethyl methacrylate (EMA), butyl methacrylate (BMA), dodecyl methacrylate (DMA); PEGylated (meth)actylates such as poly(ethylene glycol) methyl ether methacrylate (PEGMEMA) and poly(ethylene glycol) methyl ether acrylate (PEGMEA); substituted ?- and ?-lactones, lactic acid monomers; carbohydrides and fluorinated monomers; urethanes; mono- and di-functional alcohols; carboxylic acids; amines; isocyanates; epoxides; aromatics carrying alkyl group(s); sulfonated aromatics: aromatic resins; imidazole; imidazol derivatives; zwitterionic monomers; pyrazoles; quaternary ammonium monomers and any combinations thereof.

16. The delivery device of claim 13, wherein the guest polymer comprises poly(2-hydroxyethyl methacryate) (PHEMA), preferably the gel is a copolymer of poly(2-hydroxyethyl methacryate) (PHEMA) and PEGMEA.

17. The delivery device of any one of the preceding claims, wherein the guest polymer has a max. water swelling at 25? C. of about 10-10000% by mass of its dry mass, such as of about 10-5000% by mass of its dry mass, such as of about 10-500% by mass of its dry mass.

18. The delivery device of any one of the preceding claims, wherein the guest polymer has a max. water swelling at 25? C. w/w of its dry mass which is higher than the max. water swelling at 25? C. w/w of the host polymer.

19. The delivery device of any one of the preceding claims, wherein the delivery membrane has a max. water swelling at 25? C. of about 5-5000% by mass of its dry mass, such as of about 10-1000% by mass of its dry mass, such as of about 10-500% by mass of its dry mass, such as of about 10-40% by mass of its dry mass.

20. The delivery device of any one of the preceding claims, wherein the guest polymer has a structure comprising a plurality of beads forming said substantially continuous pathways within said host polymer.

21. The delivery device of claim 20, wherein the plurality of beads is arranged in side-by-side formations to form said substantially continuous pathways within said host polymer.

22. The delivery device of claim 20 or claim 21, wherein the host polymer has a structure of a network of strand shaped filaments comprising a plurality of intrastrand pathways and the plurality of beads of guest polymers are arranged along said strand shaped filaments to form said substantially continuous pathways within said host polymer.

23. The delivery device of claim 22, wherein the plurality of beads of guest polymers is adhered to said strand shaped filaments to form said substantially continuous pathways within said host polymer.

24. The delivery device of any one of the preceding claims, wherein the delivery membrane comprises a continuous matrix of the host polymer and a plurality of interconnected paths of the guest polymer, wherein the interconnected paths of the guest polymer preferably extend through the whole thickness of the membrane.

25. The delivery device of any one of the preceding claims, wherein the delivery membrane comprises a continuous matrix of the host polymer and a plurality of interconnected paths of the guest polymer, the delivery membrane has an outer surface and a plurality of paths of the guest polymer coincide with said inner surface and/or said outer surface.

26. The delivery device of any one of the preceding claims, wherein the delivery membrane comprises incorporation of one or more chemical compounds in the form of water soluble particles, such as drugs, buffers, surfactants, fragrances, dyes, flavours, antioxidants, nutrients, hormones, catalysts or any combinations thereof.

27. The delivery device of any one of the preceding claims, wherein the inner surface of said delivery membrane has a surface area of at least about 0.1 cm.sup.2, such as at least about 1 cm.sup.2, such as at least about 2 cm.sup.2, such as at least about 5 cm.sup.2, such as at least about 10 cm.sup.2.

28. The delivery device of any one of the preceding claims, wherein the cavity and the inner surface of said delivery membrane is sufficiently large to load drug into said cavity via a loading lumen and/or a needle.

29. The delivery device of any one of the preceding claims, wherein the cavity is sufficiently large to load at least 50 ?l, such as at least 100 p?, such as at least 1 ml of fluid into said cavity.

30. The delivery device of any one of the preceding claims, wherein the cavity is an at least partially collapsed cavity.

31. The delivery device of any one of the preceding claims, wherein the wall comprising the innermost wall surface is inflatable.

32. The delivery device of any one of the preceding claims, wherein the cavity is or is designed to contain gas, preferably the wall comprising the innermost wall surface comprise a gas escape valve, such as a pressure relief valve.

33. The delivery device of any one of the preceding claims, wherein the delivery device is free of organic solvent other than ethanol.

34. The delivery device of any one of the preceding claims, wherein the cavity is adapted for being filled and/or refilled with one or more chemical compounds in the form of fluids and/or particles and/or particles dispersed or dissolved in a liquid, preferably the particles being selected from cells, catalysts, drugs, buffers, surfactants, fragrances, dyes, flavours or any combinations thereof, the cavity is preferably adapted for being filled with one or more chemical compounds by injecting via an inlet comprising a valve, such as an inflation lumen and/or by injection via the delivery membrane.

35. The delivery device of any one of the preceding claims, wherein the cavity comprises one or more chemical compounds in the form of fluids and/or particles, such as cells, catalysts, drugs, buffers, surfactants, fragrances, dyes, flavours or any combinations thereof.

36. The delivery device of any one of claims 26 to 35 wherein the chemical substance comprises a drug, preferably the drug is selected from anticonvulsants, analgesics, antiparkinsons, anti-inflammatories, calcium antagonists, anesthetics, antimicrobials, antimalarials, antiparasitics, antihypertensives, antihistamines, antipyretics, alpha-adrenergic agonists, alpha-blockers, biocides, bactericides, bronchial dilators, beta-adrenergic blocking drugs, contraceptives, cardiovascular drugs, calcium channel inhibitors, depressants, diagnostics, diuretics, electrolytes, enzymes, hypnotics, hormones, hypoglycemics, hyperglycemics, muscle contractants, muscle relaxants, neoplastics, glycoproteins, nucleoproteins, lipoproteins, ophthalmics, psychic energizers, sedatives, steroids sympathomimetics, parasympathomimetics, tranquilizers, urinary tract drugs, vaccines, vaginal drugs, vitamins, collagen, hyaluronic acid, nonsteroidal anti-inflammatory drugs, angiotensin converting enzymes, polynucleotides, polypeptides, polysaccharides, nicotine, adreanal hormones, painkillers, morphine, anticancer and combinations and mixtures thereof.

37. The delivery device of any one of claims 26 to 37 wherein the chemical substance comprises drug for treating symptoms of alzheimer's, such as T3D-959, donepezil, galantamine, memantine, rivastigmine or any combinations thereof.

38. The delivery device of any one of claims 26 to 37, wherein the chemical substance comprises a drug selected from components of the blood clotting cascade, such as factor VIII; birth control drugs, such as Levonorgestrel or ethinyl estradiol; anti-virus drugs (antiretroviral), such as anti-HIV drugs (dapivirine, tenofovir) or anti-hepatitis C (ribavirin).

39. The delivery device of any one of claims 26 to 38, wherein the chemical substance comprises a compound for human nutrition, such as a vitamin, a protein and/or a mineral or a component comprising one or more of the before mentioned.

40. The delivery device of any one of claims 26 to 39, wherein the chemical substance comprises a compound for microbiological nutrition, such as FeSO.sub.4.7H.sub.2O, ZnSO.sub.4, KCI, MgSO.sub.4, 7H.sub.2O, NaNO.sub.3, Glucose, NaCI, K.sub.2HPO.sub.4, NH.sub.4H.sub.2PO.sub.4, CaC1.sub.2.2H.sub.2O, FeC1.sub.3.6H.sub.2O, NaH.sub.2PO.sub.4, Na.sub.2HPO.sub.4, NaHCO.sub.3,(NH.sub.4).sub.2 SO.sub.4 or mixtures comprising any of the mentioned.

41. The delivery device of any one of claims 26 to 40, wherein the chemical substance comprises a fragrance compound, a flavour compound and/or a colour compound (e.g. pigment and dye).

42. The delivery device of any one of claims 26 to 41, wherein the chemical compound has a molar mass of up to about 300,000 g/mol., such as up to about 90,000 g/mol., such as up to about 50,000 g/mol., such as up to about 10,000 g/mol., such as up to about 5000 g/mol.

43. The delivery device of any one of claims 26 to 42, wherein the chemical compound comprises particles selected from stem cell(s), catalyst(s), nanoparticle(s) or combinations thereof.

44. The delivery device of any one of claims 26 to 43, wherein the cavity comprises particles comprising cells, such as stem cells or microorganisms, the cells are encapsulated in the cavity of the membrane and are preferably capable of producing at least one by-product which by-product is capable of migrating through the membrane, preferably via pathways of the guest polymer.

45. The delivery device of any one of claims 26 to 44, wherein the chemical substance comprises drug trapped in liposomes, preferably the liposomes are dispersed in a polar liquid, such as in an aqueous liquid.

46. The delivery device of claim 45, wherein the chemical substance comprises drug trapped in liposomes together with metal particles, preferably gold particles.

47. The delivery device of claim 45, wherein the chemical substance comprises drug trapped in liposomes together with metal particles and together with light emitting units which light emitting units can be triggered to emit light to heat the metal particles, preferably the metal particles are gold particles.

48. The delivery device of any one of the preceding claims, wherein the guest polymer is an aerogel or a xerogel of a hydrogel, preferably obtained by freeze-drying the hydrogel or by drying the hydrogel under supercritical or sub-supercritical conditions using a carrier gas such as CO.sub.2, or by evaporation of solvents (e.g. water) at ambient conditions.

49. The delivery device of any one of claims 26 to 48, wherein the chemical component is selected relative to the membrane such that it migrates/through the membrane at zero order kinetics.

50. The delivery device of any one of the preceding claims, wherein the delivery device comprises a coating on at least a part of its inner or outer surface, preferably the coating is selected from an adhesive, a biopolymer and/or a hydrophilic coating, preferably at least a part the inner surface and/or the outer surface of the delivery membrane comprises a coating.

51. The delivery device of any one of the preceding claims, wherein the delivery device comprises a coating on at least a part of its inner and/or outer surface where the coating is of a material substantially identical to the guest polymer.

52. The delivery device of any one of the preceding claims, wherein the delivery device is a balloon catheter comprising at least one balloon forming the cavity.

53. The delivery device of claim 52, wherein the delivery device is a urinary catheter, such as a Foley catheter and the delivery membrane is the balloon or a section thereof, the balloon is adapted to being inflated using an inflation liquid comprising the chemical compound.

54. The delivery device of claim 52 or claim 53, wherein the balloon is a compliant balloon, which continuously expands upon filling fluid into the balloon.

55. The delivery device of claim 52 or claim 53, wherein the balloon is a non-compliant balloon, which expands until a specific size or size range is reached upon filling fluid into the balloon.

56. The delivery device of claim 52 or claim 53, wherein the balloon is a folded balloon, which unfolds upon filling fluid into the balloon.

57. The delivery device of any one of claims 52-56, wherein the catheter comprises a diagnostic probe, said probe is preferably adapted for detection of at least one biomarker such as, but not limited to, pH value, temperature, moisture level or infection level and combinations thereof (multiplexing).

58. The delivery device of claim 57, wherein the diagnostic probe is configured for changing upon a change of the at least one biomarker, said change of the probe is preferably optically readable.

59. The delivery device of claim 57 or 57, wherein said probe is incorporated or mounted in a distal end of the catheter, such as in a distal tip of the catheter.

60. The delivery device of any one of claims 57-59, wherein the catheter comprises a read-out structure for reading the probe and transmitting the read signal to a displaying element for visually or audibly displaying, wherein the read-out structure comprises an optical or electrochemical reader.

61. The delivery device of any one of claims 57-60, wherein the catheter comprises an optical read-out structure, wherein the catheter comprises an inflation and/or a drainage tube and a distal tip, said drainage tube comprises a channel for draining urine, said channel extending to the tip and said tip comprises or carries said probe, wherein said channel is configured for functioning as a waveguide e.g. when filled with liquid, such as urine or water.

62. The delivery device of any one of claims 57-60, wherein the catheter comprises an optical read-out structure, wherein the catheter comprises a drainage tube and a distal tip, said drainage tube comprises a channel for draining urine, said channel extends to the tip and said probe is fixed on an outer surface of the tube, wherein the tube has a transparent window to said probe, wherein said channel is configured for functioning as a waveguide, e.g. when filled with liquid, such as urine or water for reading scattered light from said probe.

63. The delivery device of any one of claims 1 to 51, wherein the delivery device is a ring-shaped delivery device and the cavity is a ring-shaped or semi-ring-shaped cavity within the ring-shaped delivery device.

64. The delivery device of claim 63 wherein the delivery device is a vaginal ring preferably adapted to be positioned to surround the cervix of a female.

65. The delivery device of claim 63 or claim 64, wherein the delivery device is a contraceptive delivery device such as a vaginal ring (P-ring) containing a for preventing drug pregnancy optionally in combination with one or more other drugs, such as in the form of a drug combination for preventing HIV and/or pregnancy.

66. The delivery device of any one of claims 63-65, wherein the delivery device is a contraceptive delivery device for a mammal, such as a human or an animal e.g. a horse, a dog or a cat.

67. The delivery device of claim 63 or claim 64, wherein the delivery device contains in its cavity a drug for treating symptoms of alzheimers, such as T3D-959, donepezil, galantamine, memantine, rivastigmine or any combinations thereof.

68. The delivery device of any one of claims 1 to 51, wherein the delivery device is a capsule, such as a capsule having a volume of at least about 0.01 cm.sup.3, such as a volume of at least about 0.1 cm.sup.3.

69. The delivery device of any one of claims 1 to 51, wherein the delivery device is a capsule, such as a capsule having a volume of at least about 0.5 cm.sup.3, such as a volume of at least about 1 cm.sup.3, such as a volume of at least about 2 cm.sup.3, such as a volume of at least about 5 cm.sup.3.

70. The delivery device of claim 68 or claim 69, wherein the capsule is spherical.

71. The delivery device of claim 68 or claim 69, wherein the capsule is oblong, egg shaped, oval and/or flattened.

72. The delivery device of any one of claims 68-71, wherein the capsule has a smallest diameter of at least about 5 mm, such as at least about 1 cm, such as at least about 2 cm.

73. The delivery device of any one of claims 67-71, wherein the capsule contains in its cavity a drug for treating symptoms of alzheimers, such as T3D-959, donepezil, galantamine, memantine, rivastigmine or any combinations thereof, preferably the drug is trapped in liposomes.

74. The delivery device of any one of claims 67-71, wherein the capsule is adapted for use in waste water treatment or in fuel-cells.

75. A delivery device suitable for delivering a chemical substance comprising one or more chemical compounds, the delivery device comprises a closed cavity comprising said chemical substance, the cavity is defined by an innermost wall surface, wherein at least a section of the inner wall surface constitutes an inner surface of a delivery membrane wherein the delivery membrane comprises an interpenetrating polymer network substrate comprising a host polymer and a guest polymer, where the guest polymer is interpenetrating the host polymer to form substantially continuous pathways within said host polymer.

76. A delivery device of claim 75 wherein the delivery device is according to any one of claims 1-74 wherein said chemical substance has been filled into said closed cavity.

Description

BRIEF DESCRIPTION OF DRAWINGS AND EXAMPLE

[0162] The invention will be explained in more detail below in connection with a preferred embodiment and with reference to the drawings in which:

[0163] FIG. 1 is a chart of the mass in mg that migrates through the balloons over time in days of the IPN sample and the blind prior art sample of example 1.

[0164] FIG. 2 shows an embodiment of a delivery device of the invention in the form of a balloon catheter.

[0165] FIG. 3 is a schematic diagram of use showing an embodiment of a balloon catheter of the invention.

[0166] FIG. 4 is a schematic drawing of the human female reproductive system comprising the uterus and with an embodiment of the p-ring of the invention mounted to surround the cervix.

[0167] FIG. 5 is a schematic side view of the human female reproduction system corresponding to the drawing of FIG. 4.

[0168] FIG. 6 illustrates a capsule of an embodiment of the invention comprising a chemical substance.

[0169] FIG. 7a is a cryo-SEM image of a silicone host polymer.

[0170] FIG. 7b is a corresponding illustration of the silicone host polymer of FIG. 7a.

[0171] FIG. 8a is a cryo-SEM image of the silicone host polymer with interpenetrating guest polymer with a structure comprising a plurality of beads.

[0172] FIG. 8b is a corresponding illustration of the silicone host polymer/guest polymer IPN of FIG.8.

[0173] FIG. 9a is a SEM image of the silicone host/guest polymer IPN of FIGS. 8a and 8b which has been swollen with water.

[0174] FIG. 9b is a corresponding illustration of water swollen the silicone host polymer/guest polymer IPN of FIG. 9a.

[0175] FIG. 10 comprises the illustrations of FIGS. 7b, 8b, 9b side by side.

[0176] FIG. 11 is a SEM image of a silicone host polymer before being subjected to residual extraction.

[0177] FIG. 12 is a SEM image of the dry silicone host/guest polymer IPN of FIG. 9a.

[0178] FIG. 13 illustrates a capsule of an embodiment of the invention comprising a chemical substance comprising liposomes.

[0179] The figures are schematic and may be simplified for clarity. Throughout, the same reference numerals are used for identical or corresponding parts.

EXAMPLE 1

[0180] Diffusion of Methylene Blue in Foley Catheters

[0181] Purpose: An experiment was designed to qualitatively and quantitatively measure the diffusivity of methylene blue through the retention balloon of a urinary Foley catheter and to calculate the diffusion coefficient, D, for a catheter according to an embodiment of the invention and a prior art catheter.

[0182] Materials and Methods: Two catheters were obtained from Bactiguard. One of the catheters was treated by removing the balloon and replacing it with an IPN of silicone as host polymer and hydrogel as guest polymer where the hydrogel content was 24% (called the IPN catheter). The other catheter was untreated (called the prior art catheter). The IPN catheter and the prior art catheter were inflated with aqueous glycol solution to check for any leaking. After rinsing and cleaning them, they were each filled with 10 ml 10 mg/mL aqueous methylene blue solution and each catheter was partly (including the tip (16), hole for drainage (26), balloon (18) and ? of the shaft (12) on FIG. 2) submerged into 1 L distilled water with stirring at 200 rpm at ambient temperature. The volumes were kept constant during the experiment. The concentration of methylene blue in the 1 L surrounding water was periodically measured by applying a Thermo Scientific Evolution 220 UV-vis spectrophotometer at 664 nm.

[0183] Results: The experiment showed that methylene blue migrates through the balloon material on the IPN catheter turning the surrounding liquid blue. Over the period of the experiment (24 days) it was not possible to detect methylene blue in the surrounding liquid of the prior art catheter. This strongly indicates that methylene blue cannot diffuse through the prior art balloon, but the IPN treatment (current invention) enables diffusion.

[0184] FIG. 1 is a chart of the mass in mg that diffuses through the balloons over time in days of the IPN catheter and the blind prior art catheter (blind sample).

[0185] The blind sample showed no diffusion into the solvent whereas the IPN catheter had a lag-phase of 3 days before methylene blue could be detected in the solvent.

[0186] The diffusion coefficients, D, of methylene blue in IPN catheter and blind sample can be estimated by the equation (1).

[00001]$\begin{array}{cc}D=\frac{Q.Math.X}{?.Math..Math.c.Math.A.Math.t}& \left(1\right)\end{array}$

[0187] Where Q is the total amount of methylene blue (permeant) that has passed through an area, A, during time, t. X is the thickness of the balloon and ?c is the difference in concentration between the outer surface and the inner surface of the balloon.

[0188] Qcan be obtained by determining the linear regression for the IPN after the lag-phase has ended i.e. from day 3 to day 14 on FIG. 1. The linear regression is given by equation (2)

m=0.061.Math.t?0.1236 (2)

[0189] Q is the slope of the linear regression, i.e. 0.061 mg per day.

[0190] It is not possible to measure the thickness of the balloon, X when the balloon is inflated. However, X can be estimated by assuming that the volume of the balloon material does not change when the balloon is inflated. In the inflated condition the shape of the balloon can be approximated by a spherical shell and in the un-inflated (relaxed) condition the shape of the balloon can be approximated with a hollow cylinder. The volume of the balloon material can be calculated from the relaxed condition and can then be used to calculate the thickness of the balloon in the inflated condition.

[0191] The volume of a hollow cylinder, V.sub.hc, is given by equation (3).

V.sub.hc=h.Math.?.Math.(r.sub.1.sup.2?r.sub.2.sup.2) (3)

[0192] Where h (2.50 cm) is the height of the cylinder and r.sub.1(0.365 cm) and r.sub.2(0.315 cm) is the outer and inner radii respectively. This yields a total volume of the balloon material of V.sub.hc=0.2670 cm.sup.3.

V.sub.hc=2.50 cm.Math.?.Math.((0.365 cm).sup.2?(0.315 cm).sup.2)=0.2670 cm.sup.3 (4)

[0193] As the cavity between the shaft and the balloon is filled with the inflation liquid, the balloon material will assume the shape of a spherical shell. However, the volume of the balloon material will still be V.sub.ss=V.sub.hc=0.2670 cm.sup.3. The volume of a spherical shell, V.sub.ss, is given by equation (5).

[00002]$\begin{array}{cc}{V}_{\mathrm{ss}}=\frac{4}{3}.Math.?.Math.\left(r_1^3-r_2^3\right)& \left(5\right)\end{array}$

[0194] The thickness of the balloon material in the inflated state, X is given by equation (6).

X=r.sub.1?r.sub.2 (6)

[0195] r.sub.1 can be measured to 1.25 cm. The inner radius, r.sub.2, can be calculated by isolating r.sub.2 in equation (5). This is given by equation (7).

[00003]$\begin{array}{cc}{r}_2=\sqrt[3]{r_1^3-\frac{3.Math.V_{\mathrm{ss}}}{4.Math.?}}-\sqrt[3]{{\left(1.25.Math..Math.\mathrm{cm}\right)}^3-\frac{3.Math.0.2670.Math..Math.\mathrm{cm}}{4.Math.?}}=1.2362.Math..Math.\mathrm{cm}& \left(7\right)\end{array}$

[0196] Xcan now be calculated from equation 6. This is given by equation (8).

X=1.25 cm?1.2362 cm=0.0138 cm (8)

[0197] Now, we have values for the parameters in the numerator in equation (1) and we need to find values for the denominator.

[0198] ?c is the concentration difference between the outer surface and the inner surface of the balloon material. As the initial concentration of methylene blue is 10 mg/ml and the cavity between the shaft and the balloon material is filled with 10 ml, there is 100 mg methylene blue in the cavity. As can be seen on FIG. 1 about 1 mg methylene blue is migrated though the balloon material over a period of 20 days. This is only 1%. It is therefore safe to assume that the concentration at the inner surface is 10 mg/ml throughout the experiment. As there is constant mixing on the outside of the catheter the concentration can be assumed to be homogenously distributed. Again, 1 mg methylene blue in 1 L=1000 ml water is 0.001 mg/ml=0 mg/ml. Therefore ?c is about 10 mg/ml throughout the experiment.

[0199] A is the surface area of the balloon material in the inflated condition. The area of a sphere with radius r=1.25 cm is given by equation (9).

A=4.Math.?.Math.r.sup.2=4.Math.?.Math.(1.25 cm).sup.2=19.63 cm.sup.2 (9)

[0200] now, we can estimate the diffusion coefficient of methylene blue though the balloon material by inserting in equation (1). This is given by equation (10).

[00004]$\begin{array}{cc}D=\frac{Q.Math.X}{?.Math..Math.c.Math.A.Math.t}=\frac{0.061.Math..Math.\mathrm{mg}.Math.0.0138.Math..Math.\mathrm{cm}}{10.Math..Math.\mathrm{mg}/{\mathrm{cm}}^3.Math.19.63.Math..Math.{\mathrm{cm}}^2.Math.86400.Math..Math.s}=4.95.Math.{10}^{-11}.Math.{\mathrm{cm}}^2/s& \left(10\right)\end{array}$

[0201] As it was not possible to detect any methylene blue in the surrounding liquid of the prior art catheter throughout the experiment the diffusion coefficient is D=0 cm.sup.2/s.

[0202] Conclusions: Methylene blue diffused from the cavity through the balloon material on the IPN catheter into the solvent, while no diffusion with the prior art catheter was observed. The diffusion coefficient for the delivery membrane of the IPN catheter was calculated to be 4.95.Math.10.sup.?11 cm.sup.2/s.

[0203] The balloon catheter shown in FIG. 2 is of the Foley type and comprises a catheter body 12 with a proximal end 14 and a distal end 16. The catheter also includes a balloon 18, an inflation lumen 20, a drainage lumen 22, and an adapter 24.

[0204] The balloon 18 is deflated for insertion into a patient. The balloon 18 is disposed near the distal end 16. The inflation lumen 20 extends within the catheter body 12 from the proximal end 14 to the balloon 18, in fluid communication with the balloon 18, for inflating and deflating the balloon 18.

[0205] The catheter drainage lumen 22 extends from the proximal end 14 to the distal end 16. The distal end 16 includes an opening 26 in fluid communication with the drainage lumen 22 to facilitate drainage of urine from the bladder of a patient.

[0206] In the shown embodiment the balloon 18 is the delivery membrane, which can be inflated e.g. with a fluid comprising chemical substances for being delivered through the delivery membrane as discussed above.

[0207] FIG. 3 is a schematic diagram of use another embodiment of a balloon catheter of the invention.

[0208] The balloon catheter shown in FIG. 3 comprises a catheter body 12 with a proximal end and a distal end with a probe 4. The catheter also includes a balloon 8 expanded with a fluid comprising chemical substances to be delivered through the balloon wall which constitutes the delivery membrane. The catheter further comprises an inflation lumen 2, a drainage lumen 1. A cut-out section of the body illustrates that the inflation lumen 2 and the drainage lumen 1 extend along the body.

[0209] As illustrated in FIG. 3 the balloon catheter is used by a patient.

[0210] The probe 4 is advantageously as described above, e.g. a probe with an optical biomarker.

[0211] The inflation lumen is configured for functioning as a waveguide e.g. when filled with liquid. For reading out a laser 3 is arranged to transmit a beam via the inflation lumen. The probe 4 is positioned such that at least a part of a light beam fed to the channel (inflation lumen) 2 reaches the probe 4, such that reflected or scattered light can be detected by an optical reader 9. And a readout spectrum can be obtained as illustrated with the spectrum 9a. Thereby the channel forms a light beam path for the detection.

[0212] The human female reproductive system shown in FIG. 4 comprises the uterus 31, the fallopian tubes 32, the ovaries 33 and the cervix 34. The lower part of the cervix 34a leads into the vagina 35 and the P-ring 36a is mounted in the vagina to surround the lower part of the cervix 34a. Reference 36b illustrated the p-ring prior to mounting.

[0213] FIG. 5 is a schematic side view of the human female reproduction system corresponding to the drawing of FIG.4. It is illustrated that the P-ring is very flexible and is easily bendable by hand.

[0214] The capsule shown in FIG. 6 comprises a capsule wall 40 constituting the delivery membrane and forming a cavity comprising the chemical substances 41a in a fluid 41. In the shown embodiment a section of the capsule is cut out for illustrative purposes. In an alternative embodiment the whole cavity encapsulated by the capsule wall 40 is filled with a chemical substance in dry form.

[0215] The capsule of FIG. 13 comprises a capsule wall 80 constituting the delivery membrane and forming a cavity comprising the chemical substances. The chemical substance comprises drug 81 trapped in liposomes 82 together with gold nanoparticles 83, and one or more light emitting units 84, such as quantum dot(s) or micro light-emitting diode(s).

[0216] One of the Liposomes is illustrated in enlarged view and here it can be seen that the liposome 82 comprises a lipid bilayer 85 with polar ends 86 turning inwards and outwards.

[0217] The drug 81, 81a is preferably Rivastigmine.

[0218] The light emitting unit 84 may advantageously be triggered from external impact e.g. as described above. When the light emitting unit 84 emits light it will be absorbed by the gold particles 83, and the temperature of the gold particles 83 will increasing. When the liposomes reaches a certain temperature they rupture as shown with the ruptured liposome 81a and the drug will be released from the liposome. The released drug may now freely migrate across the delivery membrane 80 membrane to the target spot for the drug, e.g. if implanted in the brain to the exposed brain tissue. Rivastigmine can thereby be released to the brain tissue with a desired release profile. When the amount of liposomes are reduced or there is no more left the substance within the capsule 88 may be withdrawn using a needle and it may be replaced with fresh substance.

[0219] The silicone host polymer shown in FIG. 7a is a PDMS silicone polymer cooled in liquid nitrogen (T??196? C.) and removed from the nitrogen immediately prior to acquiring the cryo-sem image. The morphology/structure of PDMS have been frozen by placing the sample in liquid nitrogen, which has a temperature below the glass transition temperature of silicone (Tg=?125? C.). It can be seen that the host polymer has a structure of a network of strand shaped filaments 51a and comprises a plurality of intrastrand pathways 52a. The strand shaped filaments are substantially flat.

[0220] In FIG. 7b the same host polymer is illustrated with the network of strand shaped filaments 51b and the intrastrand pathways 52b.

[0221] FIG. 8a show the same silicone host polymer with interpenetrating guest polymer also in liquid nitrogen (T??196? C.) with a structure comprising a plurality of beads 63a forming a substantially continuous pathways within the host polymer. The guest polymer has been loaded into the host polymer using CO.sub.2 in dense gas state as solvent. It can be seen that the plurality of beads 63a of guest polymers are arranged along the strand shaped filaments 61a to form the substantially continuous pathways within the host polymer. It can be seen that the intrastrand pathways 62a are only partly filled. It is believed that this has the effect of making the final IPM delivery membrane very pliable and soft.

[0222] It can be seen that the guest polymer has affinity to the host polymer.

[0223] FIG. 8b illustrates the silicone host polymer with interpenetrating guest polymer of FIG. 8a and it can be seen more clearly that the beads 63b of guest polymers are arranged along the strand shaped filaments 61b to form the substantially continuous pathways within the host polymer and that the intrastrand pathways 62b are only partly filled.

[0224] In FIG. 9a the silicone host/guest polymer IPN of FIGS. 8a and 8b which has been swollen with water at room temperature. The strand shaped filaments 71a are almost fully covered with the beads 73a which have swollen and thereby increased in size. In the SEM image the intrastrand pathways 72a can only slightly be seen. In the corresponding illustration in FIG. 9b it can be seen that the guest polymer beads 73b has been swollen. For illustrative purpose the swollen guest polymer beads are illustrated in less swollen state than in the real life cry-SEM image of FIG. 9a.

[0225] However, it can be seen that the swollen guest polymer beads takes up more of the intrastrand pathways 72b between the strand shaped filaments 71b.

[0226] In FIG. 10 the illustrations of FIGS. 7b, 8b, and 9b are shown side by side and it can be seen how the host alone differs from the silicone host/guest polymer IPN and further the changes when the silicone host/guest polymer IPN is swollen with water.

[0227] FIG. 11 shows a SEM picture the PDMS silicone polymer at room temperature. There is no visible network of strand shaped filaments and intrastrand pathways, because the temperature is much higher than the glass transition temperature of silicone (Tg=?125? C.).

[0228] In FIG. 12 a SEM image of the dry silicone host/guest polymer IPN at room temperature of FIG. 9a is shown and it can be seen that the surface as a structure comprising a plurality of bead like structures. The guest polymer (hydrogel) has a Tg of 100? C. and is solid at room temperature. Therefore the hydrogel takes the shape as solid beads. The host polymer (silicone) has a Tg of ?125? C. and therefore behaves as a liquid at room temperature and embeds the solid hydrogel beads.

[0229] Although embodiments have been described and shown in detail, the invention is not restricted to these, but may also be embodied in other ways within the scope of the subject matter defined in the following claims. In particular, it is to be understood that other embodiments may be utilized and structural and functional modifications may be made without departing from the scope of the present invention.