CN1917857A - Capillary moderator in an osmotic delivery system for preventing backflow into the active agent reservoir - Google Patents

Abstract

The present invention relates to apparatus and methods for preventing backflow into a beneficial agent dispensing osmotic delivery system.

Description

Anti-backflow is advanced the capillary moderator in the permeability delivery system of active agent reservoir

The cross reference of related application

[0001] rights and interests of serial the 11/052nd, No. 382 of No. the 60/543rd, 423, the U.S. Provisional Application of submitting on February 10th, 2004 and the U.S. Patent application of submitting on February 7th, 2005 are enjoyed in the application's request, and its full content is incorporated herein by reference.

Invention field

[0002] the present invention relates to the apparatus and method that anti-backflow is advanced beneficial agent dispensing osmotic delivery system.

Background of invention

[0003] can be by the long relatively sustained release of accomplished in many ways beneficial agent.A kind of fabulous method comprises uses implantable osmotic delivery system (" ODS ").Generally speaking, ODS operates from the beneficial agent that surrounding absorbs liquid and (" outlet ") discharges respective amount from another hole by a hole.Produce pressure by osmotic pumps (normally water absorbing agent), this causes that beneficial agent is from exporting reliable and constant delivery rate.

[0004] ideally, outlet should prevent that outside liquid diffusion or reflux from advancing ODS, because outside liquid may influence the utilization of beneficial agent unfriendly by for example polluting, destroy stability, dilution or others to change the beneficial agent composition.And backflow can influence the delivery rate of beneficial agent in many ways nocuously.In addition, outside liquid can cause the outlet obstruction, and this also can influence the delivery rate of beneficial agent nocuously.

[0005], and has the flow conditioner of single exit passageway and be devoted to solve the reflux problem in exit by adding slit pore (referring to United States Patent (USP) the 6th, 217, No. 906) or sliding plunger (referring to U.S.6,508,808).System with long straight exit passageway is unpractiaca for implanting application, because they have enlarged markedly the size of implant.Owing to wish that implant has as far as possible little profile, the flow conditioner with relative minor axis dimension is valuable.In the past, single exit passageway passes the shell bending and advances, and flows to produce competent the obstruction in the material by length, but will be understood that this needs creating conditions of relative complex.

[0006] has been found that now by controlling backflow to outlet adding capillary moderator of the present invention.

Summary of the invention

[0007] described beneficial agent dispensing osmotic delivery system, comprised shell, arranged beneficial agent storage storehouse in the enclosure, be arranged in the capillary moderator that the interior anti-backflow of outlet is entered beneficial agent storage storehouse with entrance and exit.In one embodiment, capillary moderator comprises the microchannel of hydrophobic coating.

[0008] described the method that anti-backflow is entered the beneficial agent storage storehouse of permeability delivery system, be included between environment and the beneficial agent storage storehouse capillary moderator is provided.

Brief description of drawings

[0009] Fig. 1 is the schematic cross sectional view of implantable osmotic delivery system.

[0010] Fig. 2 is the perspective schematic view of capillary moderator of the present invention.

[0011] Fig. 3 A is the digital picture of the SEM microphotograph of capillary moderator of the present invention.

[0012] Fig. 3 B is the digital picture of the SEM microphotograph of cognate shape of the present invention microchannel.

[0013] Fig. 4 is the sketch map of microchannel of the present invention.

[0014] Fig. 5 has shown the curve chart of the pressure of 50 μ m coated micro channels with respect to flow velocity.

The detailed description of illustrative embodiment

[0015] the present invention relates to the apparatus and method that anti-backflow is advanced beneficial agent dispensing osmotic delivery system.

[0016] permeability delivery system 10 comprises shell 12.Shell 12 can be by enough hard to resist that its content expands and not varying sized and any material shape is made.Be understandable that the liquids and gases that exist usually in 12 pairs of bodies of shell are impervious.

[0017] inlet 14 and outlet 16 are arranged in the shell 12.Inlet 14 can comprise the semipermeable membrane that allows liquid to enter shell 12.Outlet 16 comprises the microchannel of hydrophobic coating, and this discusses in more detail with reference to Fig. 2.

[0018] piston 18 slides and is arranged in the shell 12, separates shell, to seal and to limit two chambers, just pump chamber 20 and delivery chamber 22.Pump chamber 20 holds once the expansible penetrating agent of contact water.Penetrating agent can be for example non-volatile water soluble penetrating agent, or osmopolymer, or its mixture.In case expand, penetrating agent just applies strength and promotes piston 18 to outlet 16, thereby increases the pressure in the delivery chamber 22.

[0019] delivery chamber 22 is held the beneficial agent that will send.From the pressure that piston 18 increases beneficial agent is released outlet 16, enter environment.

[0020] according to embodiment of the present invention, system 10 can take various forms.For example, piston 18 can be prepared by multiple inert material with for example barrier film, separator, liner, flat board, spheroplast or hard metal alloys replacement of flexible membrane.In addition, system 10 can move under the situation of piston not having, and an interface is only arranged between penetrating agent/liquid additive and beneficial agent simply.

[0021] come 2-4 with the aid of pictures, outlet 16 (Fig. 1) comprise the capillary moderator 24 with a large amount of microchannels 26.Capillary moderator 24 has a large amount of microchannels 26.Microchannel 26 extends through capillary moderator 24, by arranged in arrays.Microchannel 26 prevents that liquid from flowing to beneficial agent storage storehouse from environment.

[0022] generally speaking, microchannel 26 has the diameter of 10 μ m to about 100 μ m.Preferably, microchannel 26 has the diameter of about 15 μ m to about 50 μ m.More preferably, microchannel 26 has the diameter of about 15 μ m, about 30 μ m or about 50 μ m.

[0023] microchannel 26 extends through capillary moderator 24, and therefore, the length of microchannel depends on the thickness of capillary moderator.In one embodiment, microchannel 26 has the length of about 150 μ m to about 400 μ m.Preferably, microchannel 26 has the length of about 300 μ m.

[0024] in one embodiment, the cross section of microchannel 26 is circular.Do not wish to be bound by theory, think that the circular transverse cross-sectional in the passage cross section makes the edge maximize the ratio of area, therefore, the surface energy effect of liquid also has been maximized.

[0025] in one embodiment, microchannel 26 is crenulate.

[0026] in one embodiment, interfacial tension was less than polymer or its mixture of 30dyn/cm when microchannel 26 had applied 20 ℃, and this provides low-surface-energy.Preferably, polymer can be made gas, uses by conventional plasma coated.

[0027] in one embodiment, microchannel 26 has applied hydrophobic polymer, preferred hydrophobic fluropolymer.

[0028] in one embodiment, microchannel 26 has applied one or more following materials: poly-(1,1-dihydro-perfluoro capryl methacrylate); Poly-(hexafluoropropene); Poly-(tetrafluoroethene); Poly-(vinylidene fluoride); Poly-(1); Polyisobutylene; Poly-(ethylene fluoride); Poly-(vinyl methyl ether); Polypropylene; Poly-(t-butyl styrene); Halogenated hydrocarbons comprises poly-(hexafluoroethylene) and poly-(tetrafluoroethene); Polyvinyl comprises poly-((seven fluorine isopropoxies) ethylene); The nonfluorinated acrylate copolymer comprises poly-(ethyl acrylate); The fluorinated acrylamide acid polymer, comprise poly-((1-chlorodifluoramethyl-) tetrafluoro ethyl propylene acid esters)), poly-(two (chlorodifluoramethyl-) methyl fluoride acrylate), poly-(1,1-dihydro seven fluorine butylacrylic acid esters), poly-(1,1-dihydro five fluorine isopropylacrylic acid esters), poly-(1,1-dihydro 15 fluorine octyl group acrylate), poly-(seven fluorine isopropylacrylic acid esters), poly-(5-(seven fluorine isopropoxies) amyl group acrylate), poly-(11-(seven fluorine isopropoxies) ethyl propylene acid esters), poly-(2-seven fluorine propoxyl group) ethyl propylene acid esters and poly-(nine fluorine isobutyl group acrylate); The nonfluorinated methacrylate polymer comprises poly-(isobutyl methacrylate) and poly-(metering system tert-butyl acrylate); The fluorinated methyl acrylate copolymer, comprise poly-(1,1-dihydro 15 fluorine octyl group methacrylates), poly-(17 fluorine octyl group methacrylate), poly-(seven fluorine isopropyl methyl acrylate), poly-(1-hydrogen tetrafluoro ethyl-methyl acrylate), poly-(1,1-dihydro tetrafluoro propyl methyl acid esters), poly-(1-hydrogen hexafluoro isopropyl methyl acrylate), poly-(uncle's nine fluorine butyl methyl acrylate); Polyethers comprises poly-(oxygen isobutene .)-glycol; Poly-(imines) comprises poly-((benzoylimino) ethylene), poly-((butyryl imino group) ethylene), poly-((lauroyl imino group) ethylene), poly-((oenanthyl imino group) ethylene), poly-((hexanoyl imino group) ethylene), poly-(((3-methyl) butyryl imino group) ethylene), poly-((15 fluorine stearoyl imino group) ethylene), poly-((valeryl imino group) ethylene); Or poly-(siloxanes), comprise poly-(oxygen diethyl silylene) and poly-(the oxygen dimethylated methylene is silica-based).

[0029] in one embodiment, come using polymer by conventional plasma coated.Coating thickness in the microchannel changes in about 2 mu m ranges at 0.50 μ m, preferred about 1 μ m.

[0030] in one embodiment, with 300 μ m thick 4 " silicon chip makes actuator 24.Use piranha clean clean wafer then.The positive photoresist rotation thick 7 μ m is coated on the wafer.Mask is used for making at needs the zone formation pattern of microchannel.Use DRIE (dark reactive ion etching) and pass the chip etching microchannel.Next, with the oxygen plasma treatment wafer removing photoresist, and clean surface.Fluoropolymer plasma treatment for example can be by 4th State, Inc., and Belmont, California, USA carries out, and is used for the coated wafers surface, comprises the microchannel.

[0031] can be used for the material of shell 12 should be enough hard, with guarantee under the pressure that shell born in implantation process or can leakage, crack under the pressure that in operation process, produces, break or twist.Shell 12 can be made with chemical inertness known in the art and biocompatible, natural or synthetic material.The material of preferred shell 12 is that material is separated in abiotic erosion, titanium for example, and it is retained in patient's body after using.Yet the material of shell 12 selectively is that material is separated in biological erosion, it after distributing beneficial agent in environment biological the erosion separate.Usually, the preferred material of shell 12 is acceptable concerning people's implant.Generally speaking, the suitable typical material that makes up shell 12 of the present invention comprises nonreactive activity polymer or biocompatible metals or alloy.Polymer comprises acrylonitrile polymer, for example acrylonitrile-butadiene-styrene terpolymer etc.; Halogenated polymer, for example politef, polytrifluorochloroethylene, tetrafluoroethene and hexafluoropropylene copolymer; Polyimides; Polysulfones; Merlon; Polyethylene; Polypropylene; Polrvinyl chloride-acrylic copolymer; Merlon-acrylonitrile-butadiene-styrene (ABS); Polystyrene etc.The metal material that is used for shell 12 comprises rustless steel, titanium, platinum, tantalum, gold and their alloy, and the rustless steel of gold-plated ferrous alloy, platinized ferrous alloy, cochrome and titanium nitride coating.

[0032] generally speaking, the material that is applicable to piston 18 is an elastomeric material, comprises above listed nonreactive activity polymer, and common lactoprene, for example polyurethane and polyamide, chlorinated rubber, SBR styrene butadiene rubbers and chloroprene rubber.

[0033] penetrating agent can be tablet, and it is to be used to promote the mobile imbibition agent of beneficial agent.Penetrating agent can be penetrating agent (osmagent), osmopolymer or the two mixture.The kind that belongs to the penetrating agent category, non-volatile the kind promptly water-soluble and osmotic gradient that the infiltration of generation promotion water flows into is very many.Example is well known in the art, comprise magnesium sulfate, magnesium chloride, potassium sulfate, sodium chloride, sodium sulfate, lithium sulfate, sodium phosphate, dipotassium hydrogen phosphate, d-mannitol, sorbitol, inositol, carbamide, Magnesium succinate, tartaric acid, Raffinose and various monosaccharide, oligosaccharide and polysaccharide, for example sucrose, glucose, lactose, fructose and glucosan, and the different types of mixture of any of these.The kind that belongs to the osmopolymer category is to change widely once the contact expansible hydrophilic polymer of water and these.Osmopolymer can be plant source or zoogenous, or synthetic, and the example of osmopolymer is well known in the art.Example comprises: molecular weight 30,000-5,000,000 poly-(hydroxyl-allyl methyl acrylate), molecular weight 10,000-360,000 poly-(vinyl arsenic pyrrolidone), anion and cationic water gel, polyelectrolyte complex compound, optional and Biformyl, formaldehyde or glutaraldehyde cross-linking have a 200-30, poly-(vinyl alcohol) with low acetate ester residue of 000 degree of polymerization, methylcellulose, the mixture of crosslinked agar and sodium carboxymethyl cellulose, the mixture of hydroxypropyl methylcellulose and sodium carboxymethyl cellulose, N-vinyl lactam polymer, polyoxyethylene-polyoxypropylene gel, polyoxy butylene-polyethylene block copolymer gel, carob, carbopol gel, polyester gel, polyurea gel, polyethers gel, polyamide gels, peptide-based gel, the polyamino acid gel, poly-cellulose gel, molecular weight 250,000-4,000,000 carbopol acid carboxyl polymer, the Cyanamer polyacrylamide, crosslinked indenes-maleic anhydride polymer, molecular weight 80,000-200,000 Good-Rite polyacrylic acid, molecular weight 100,000-5,000,000 Polyox polyethylene oxide polymer, starch graft copolymer and Aqua-Keeps acrylate polymer polysaccharide.

[0034] in one embodiment of the invention, the beneficial agent that comprises in the chamber 22 is a flowable composition, and for example liquid, suspension or slurry are introduced in the shell 12 after penetrating agent and piston 18 have inserted.Select a ground, this flowable composition can be injected by the slit in the port with syringe needle, and slit allows bubble-free perfusion in the port.The present invention is used for the administration of general beneficial agent, and it comprises any physiology or pharmacological active substance.Beneficial agent can be any known agent, for example medicament, medicine, vitamin or nutrient etc.Beneficial agent also can be and is delivered to for example reagent in pond, passage and storage storehouse etc. of any kind aqueous environment.The included types of agents that meets this description is Biocide, biocide, nutrient, vitamin, food supplement, sterilant, fertility inhibitor and fertility promoters.Can comprise the medicine that acts on peripheral nerve, adrenoreceptor, cholinoceptor, skeletal muscle, cardiovascular system, smooth muscle, blood circulation, synapse (synoptic) position, neural effector binding site, endocrine and hormone system, immune system, reproductive system, skeletal system, autocoid system, digestion and Excretory system, histamine system and central nervous system by the medicament that the present invention sends.Suitable reagent can be selected from for example synthetic analogues of albumen, enzyme, hormone, polynucleotide, nucleoprotein, polysaccharide, glycoprotein, lipoprotein, polypeptide, steroid, analgesic, local anaesthetics, antibiotic, antiinflammatory corticosteroid, medicament for the eyes and these kinds.The example of the medicine that can send by system of the present invention includes but not limited to ethionic acid prochlorperazine (prochlorperzine edisylate), ferrous sulfate, aminocaproic acid, mecamylamine hydrochloride, procaine amide hydrochloride, amfetamine sulfate, methamphetamine hydrochloride, benzamphetamine hydrochloride, isoproterenol sulfate, phenmetrazine hydrochloride, bethanechol chloride, methacholine chloride, Pilocarpine Hydrochloride, atropine sulfate, scotropin, isopropamide iodide, tridihexethyl chloride, phenformin hydrochloride, methylphenidate hydrochloride, Oxtriphylline, cefalexin hydrochloride, diphenidol, bornamine, prochlorperazine maleate, phenoxybenzamine, thiethylperzine maleate, anisindione (anisindone), diphenadione, erythrityl tetranitrate, digoxin, isoflurophate, acetazolamide, methazolamide, bendroflumethiazide, chloropromaide, tolazamide, chlormadinone acetate, phenaglycodol, allopurinol, Aluminum Aspirin, methotrexate, acetylsulfafurazole, erythromycin, hydrocortisone, acetic acid hydrocortisone (hydrocorticosterone acetate), cortisone acetate, dexamethasone and derivant thereof be betamethasone for example, triamcinolone, methyltestosterone, the 17-S-estradiol, ethinylestradiol, ethinylestradiol 3-methyl ether, prednisolone, 17-OH progesterone acetate, 19-is nor--Progesterone, norgestrel, norethindrone (norethindrone), norethindrone (norethisterone), norethiederone, Progesterone, norgesterone, Norethynodrel, aspirin, indomethacin, naproxen, fenoprofen, sulindac, indoprofen, nitroglycerin, sorbide nitrate, Propranolol, timolol, atenolol, alprenolol, cimetidine, clonidine, imipramine, levodopa, chlorpromazine, methyldopa, dihydroxyphenylalanine, theophylline, calcium gluconate, ketoprofen, ibuprofen, cefalexin, erythromycin, haloperidol, zomepirac, ferrous lactate, vincamine, diazepam, phenoxybenzamine, diltiazem, milrinone, capropril, Cefamandole Nafate (mandol), quanbenz, hydrochlorothiazide, ranitidine, flurbiprofen, fenufen, fluprofen, tolmetin, alclofenac, mefenamic acid, flufenamic acid, difuinal, nimodipine, nitrendipine, nisoldipine, nicardipine, felodipine, lidoflazine, tiapamil, gallopamil, amlodipine, mioflazine, lisinopril, enalapril, enalaprilat, captopril, ramipril, famotidine, nizatidine, sucralfate, etintidine, tetratolol, minoxidil, chlordiazepoxide, diazepam, amitriptyline and imipramine.Further example is albumen and peptide, include but not limited to insulin, colchicine, glucagon, thyrotropin, parathyroid hormone and pituitary hormone, calcitonin, feritin, prolactin antagonist, thyroliberin, thyrotropin, follicle stimulating hormone, chorionic-gonadotropin hormone, gonadotropin releasing hormone, bovine growth hormone, pig growth hormone, oxytocin, vassopressin, GRF, prolactin antagonist, somatostatin, lypressin, Pancreozymin, metakentrin, LHRH, LHRH agonist and antagonist, leuprorelin acetate, interferon, interleukin, growth hormone, human growth hormone for example, bovine growth hormone and pig growth hormone, the fertility inhibitor is prostaglandin for example, fertility promoters, somatomedin, thrombin, human pancreas's releasing factor, analog and derivant with these chemical compounds, with the acceptable salt of the pharmacy of these chemical compounds, or their analog or derivant.Beneficial agent can be present among the present invention with number of chemical form and physical form, for example solid, liquid and slurry.At molecular level, various forms can comprise acceptable acid-addition salts of uncharged molecules, molecular complex and pharmacy and base addition salts, for example hydrochlorate, hydrobromate, sulfate, laruate, oleate and Salicylate.For acid compound, can use slaine, amine salt or organic cation salt.Also can use derivant for example ester, ether and amide.Activating agent can use separately or mix with other activating agent.

[0035] for the administration of beneficial agent, system of the present invention can be subcutaneous or intraperitoneal implant, or implant at aqueous body fluids any other position of can be used for activating in the biological environment of osmotic engine therein.System of the present invention also is used for physiology or the outer environment of aqueous environment.For example, this system can be used for sending the intravenous system (being attached to for example IV pump or bag or IV bottle) of beneficial agent.They also can be used for for example blood oxygenator, kidney dialysis and electrophoresis.In addition, system of the present invention can be used for biological technical field, for example nutrient or growth regulating chemical compound is delivered to the cell culture thing.

Embodiment

[0036] in test, the actuator of the present invention with 50 μ m and 30 μ m microchannels has successfully stoped the external pressure of 0.4psi and 0.8psi.What Fig. 5 showed is the curve chart of the pressure of 50 μ m coated micro channels with respect to flow velocity.

[0037] the open of every piece of patent, patent application and the publication of quoting as proof herein or describing all is incorporated herein by reference in full.

[0038] each is carefully stated all combinations and the subgroup that scope all comprises this scope and closes and the concrete numerical value that wherein comprises.

[0039] except described herein those, various distortion of the present invention all are conspicuous to those skilled in the art from above-mentioned description.These distortion also expection drop within the scope of institute's accessory claim.

Claims (20)

1. be used for beneficial agent dispensing osmotic delivery system, comprise:

Shell with entrance and exit;

Arrange beneficial agent storage storehouse in the enclosure;

Be arranged in the outlet in case non-return flows to the capillary moderator in beneficial agent storage storehouse.

2. the system of claim 1 further comprises the osmotic pumps that is suitable for causing the beneficial agent sustained release.

3. the system of claim 1, wherein, described capillary moderator has a large amount of microchannels of arranging between environment and beneficial agent storage storehouse.

4. the system of claim 3, wherein, described microchannel prevents that fluid from flowing into beneficial agent storage storehouse from environment.

5. the system of claim 3, wherein, described microchannel has the diameter of about 10 μ m to about 100 μ m.

6. the system of claim 3, wherein, described microchannel has the diameter of about 15 μ m to about 50 μ m.

7. the system of claim 3, wherein, described microchannel has the diameter that is selected from about 15 μ m, about 30 μ m and about 50 μ m.

8. the system of claim 3, wherein, described microchannel has the length of about 150 μ m to about 400 μ m.

9. the system of claim 3, wherein, described microchannel has the length of about 300 μ m.

10. the system of claim 3, wherein, described microchannel is crenulate.

11. the system of claim 3, wherein, described microchannel has applied hydrophobic polymer.

12. the system of claim 3, wherein, described microchannel has applied hydrophobic fluoropolymer polymer.

13. the system of claim 11, wherein, described polymer is selected from least a in the following polymer: poly-(1,1-dihydro-perfluoro capryl methacrylate); Poly-(hexafluoropropene); Poly-(tetrafluoroethene); Poly-(vinylidene fluoride); Poly-(1); Polyisobutylene; Poly-(ethylene fluoride); Poly-(vinyl methyl ether); Polypropylene; Poly-(t-butyl styrene); Halogenated hydrocarbons comprises poly-(hexafluoroethylene) and poly-(tetrafluoroethene); Polyvinyl comprises poly-((seven fluorine isopropoxies) ethylene); The nonfluorinated acrylate copolymer comprises poly-(ethyl acrylate); The fluorinated acrylamide acid polymer, comprise poly-((1-chlorodifluoramethyl-) tetrafluoro ethyl propylene acid esters)), poly-(two (chlorodifluoramethyl-) methyl fluoride acrylate), poly-(1,1-dihydro seven fluorine butylacrylic acid esters), poly-(1,1-dihydro five fluorine isopropylacrylic acid esters), poly-(1,1-dihydro 15 fluorine octyl group acrylate), poly-(seven fluorine isopropylacrylic acid esters), poly-(5-(seven fluorine isopropoxies) amyl group acrylate), poly-(11-(seven fluorine isopropoxies) ethyl propylene acid esters), poly-(2-seven fluorine propoxyl group) ethyl propylene acid esters and poly-(nine fluorine isobutyl group acrylate); The nonfluorinated methacrylate polymer comprises poly-(isobutyl methacrylate) and poly-(metering system tert-butyl acrylate); The fluorinated methyl acrylate copolymer, comprise poly-(1,1-dihydro 15 fluorine octyl group methacrylates), poly-(17 fluorine octyl group methacrylate), poly-(seven fluorine isopropyl methyl acrylate), poly-(1-hydrogen tetrafluoro ethyl-methyl acrylate), poly-(1,1-dihydro tetrafluoro propyl methyl acid esters), poly-(1-hydrogen hexafluoro isopropyl methyl acrylate), poly-(uncle's nine fluorine butyl methyl acrylate); Polyethers comprises poly-(oxygen isobutene .)-glycol; Poly-(imines) comprises poly-((benzoylimino) ethylene), poly-((butyryl imino group) ethylene), poly-((lauroyl imino group) ethylene), poly-((oenanthyl imino group) ethylene), poly-((hexanoyl imino group) ethylene), poly-(((3-methyl) butyryl imino group) ethylene), poly-((15 fluorine stearoyl imino group) ethylene), poly-((valeryl imino group) ethylene); Or poly-(siloxanes), comprise poly-(oxygen diethyl silylene) and poly-(the oxygen dimethylated methylene is silica-based).

14. the system of claim 12, wherein, the coating layer thickness in the described microchannel is changing in about 2 mu m ranges about 0.50 μ m.

15. the system of claim 12, wherein, the coating layer thickness in the described microchannel is about 1 μ m.

16. anti-backflow is advanced the method in the beneficial agent storage storehouse of permeability delivery system, comprising:

Between environment and beneficial agent storage storehouse, provide capillary moderator.

17. the method for claim 16, wherein, described capillary moderator has a large amount of microchannels that extend through it.

18. the method for claim 17, wherein, described microchannel is crenulate.

19. the method for claim 17 further comprises and uses the hydrophobic polymer coated micro channels.

20. the method for claim 19, wherein, described polymer is selected from least a in the following polymer: poly-(1,1-dihydro-perfluoro capryl methacrylate); Poly-(hexafluoropropene); Poly-(tetrafluoroethene); Poly-(vinylidene fluoride); Poly-(1); Polyisobutylene; Poly-(ethylene fluoride); Poly-(vinyl methyl ether); Polypropylene; Poly-(t-butyl styrene); Halogenated hydrocarbons comprises poly-(hexafluoroethylene) and poly-(tetrafluoroethene); Polyvinyl comprises poly-((seven fluorine isopropoxies) ethylene); The nonfluorinated acrylate copolymer comprises poly-(ethyl acrylate); The fluorinated acrylamide acid polymer, comprise poly-((1-chlorodifluoramethyl-) tetrafluoro ethyl propylene acid esters)), poly-(two (chlorodifluoramethyl-) methyl fluoride acrylate), poly-(1,1-dihydro seven fluorine butylacrylic acid esters), poly-(1,1-dihydro five fluorine isopropylacrylic acid esters), poly-(1,1-dihydro 15 fluorine octyl group acrylate), poly-(seven fluorine isopropylacrylic acid esters), poly-(5-(seven fluorine isopropoxies) amyl group acrylate), poly-(11-(seven fluorine isopropoxies) ethyl propylene acid esters), poly-(2-seven fluorine propoxyl group) ethyl propylene acid esters and poly-(nine fluorine isobutyl group acrylate); The nonfluorinated methacrylate polymer comprises poly-(isobutyl methacrylate) and poly-(metering system tert-butyl acrylate); The fluorinated methyl acrylate copolymer, comprise poly-(1,1-dihydro 15 fluorine octyl group methacrylates), poly-(17 fluorine octyl group methacrylate), poly-(seven fluorine isopropyl methyl acrylate), poly-(1-hydrogen tetrafluoro ethyl-methyl acrylate), poly-(1,1-dihydro tetrafluoro propyl methyl acid esters), poly-(1-hydrogen hexafluoro isopropyl methyl acrylate), poly-(uncle's nine fluorine butyl methyl acrylate); Polyethers comprises poly-(oxygen isobutene .)-glycol; Poly-(imines) comprises poly-((benzoylimino) ethylene), poly-((butyryl imino group) ethylene), poly-((lauroyl imino group) ethylene), poly-((oenanthyl imino group) ethylene), poly-((hexanoyl imino group) ethylene), poly-(((3-methyl) butyryl imino group) ethylene), poly-((15 fluorine stearoyl imino group) ethylene), poly-((valeryl imino group) ethylene); With poly-(siloxanes), comprise poly-(oxygen diethyl silylene) and poly-(the oxygen dimethylated methylene is silica-based).

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