CN103037802A - Device and method for intraocular drug delivery - Google Patents

Device and method for intraocular drug delivery Download PDF

Info

Publication number
CN103037802A
CN103037802A CN2011800266832A CN201180026683A CN103037802A CN 103037802 A CN103037802 A CN 103037802A CN 2011800266832 A CN2011800266832 A CN 2011800266832A CN 201180026683 A CN201180026683 A CN 201180026683A CN 103037802 A CN103037802 A CN 103037802A
Authority
CN
China
Prior art keywords
integrated equipment
equipment according
housing
eye
actuating mechanism
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN2011800266832A
Other languages
Chinese (zh)
Other versions
CN103037802B (en
Inventor
L·E·勒纳
I·舒巴耶夫
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
OcuJect LLC
Original Assignee
OcuJect LLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by OcuJect LLC filed Critical OcuJect LLC
Priority to CN201610621429.1A priority Critical patent/CN106137528B/en
Priority claimed from PCT/US2011/030840 external-priority patent/WO2011123722A1/en
Publication of CN103037802A publication Critical patent/CN103037802A/en
Application granted granted Critical
Publication of CN103037802B publication Critical patent/CN103037802B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00—Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/0008—Introducing ophthalmic products into the ocular cavity or retaining products therein
    • A61F9/0017—Introducing ophthalmic products into the ocular cavity or retaining products therein implantable in, or in contact with, the eye, e.g. ocular inserts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes

Landscapes

  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Anesthesiology (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Materials For Medical Uses (AREA)

Abstract

Injection devices for delivering pharmaceutical formulations into the eye are described. The devices may be integrated to include features that allow safe and atraumatic manipulation of the devices with one hand. For example, accurate placement, including proper angulation, of the device on the eye and injection of a pharmaceutical formulation into the eye can be performed using one hand. The devices may also include improved safety features. For example, the devices may include an actuation mechanism that controls the rate and depth of injection into the eye. Some devices include a dynamic resistance component capable of adjusting the amount of pressure applied to the eye surface. Related methods and systems comprising the devices are also described.

Description

The equipment and the method that are used for intraocular drug delivery
The cross reference of related application
The application requires in the U.S. Provisional Application serial number 61/341 of submission on March 31st, 2010,582, in the U.S. Provisional Application serial number 61/384 of JIUYUE in 2010 submission on the 20th, 636 and the U.S. Provisional Application serial number 61/422 submitted in 13rd in December in 2010,220 priority, each described application is incorporated by reference in their entirety to this paper.
Technical field
As herein described be configured to safety and accurately the delivering drugs prescription to the eye in equipment.Especially, this equipment can integrated various features, and described feature allows the easy manipulation to equipment, and can be conducive to equipment on the eye table the location and be conducive to without wound ground injectable drug prescription within the eye.This paper has also described and has utilized the within the eye system and method for delivering drugs prescription of this equipment.
Background technology
Eyes are to comprise being permitted multipart complex organ, and described many parts make the process of seeing of having realized.Visual quality depends on situation and the cooperative ability of these parts of each body component.For example, vision can be subjected to the impact of these situations, and described situation has affected crystalline lens (for example cataract), retina (for example cytomegaloviral retinitis) or macula lutea (for example degeneration of macula).Local and the pharmaceutical formulation of whole body have been developed to treat the eye condition of these and other, but each has its defective.For example, typically, the local treatment that applies on the eye table has the short time of staying, because tear stream is gone out eyes with them.In addition, if the set goal is positioned at back room, then since the natural cover for defense that is presented by cornea and sclera and other structure be restricted to the intraocular delivery medicine.As for whole body therapeutic, usually need the medicine of high dose to reach within the eye curative level, this has increased the risk of harmful side effect.
Alternatively, the existing intravitreal injection of carrying out is filled a prescription to ophthalmic with delivering drugs partly.Increase owing to be used for the treatment of the supply of the anti-vascular endothelial growth factor medicament of acute degeneration of macula (AMD), utilize intravitreal injection to become more general.Through FDA(Food and Drug Administration) approval be used for intravitreal injection with the medicament for the treatment of AMD comprise Lucentis ( Genetech company, southern city of San Francisco, California) and Pei Jianibu sodium (
Figure BDA00002490131000022
Eyetech drugmaker, New York, New York).In addition, bevacizumab in the vitreous body ( Genentech company, southern city of San Francisco, California) be widely used in medicine and check and approve and indicate outer application with the treatment choroidal neovascularization.The interest that also has the growth of developing new drug object space face, described novel drugs are used for directly being delivered in the vitreous body so that treatment macular edema, the retinal vein occlusion and vitreous hemorrhage.
Current, commercially available intravitreal injection equipment lacks many useful in the following areas features: make the injection site expose, make equipment is stable against sclera and/or control is injected angle and the degree of depth.Many equipment of describing in patent documentation (for example WO 2008/084064 and the U.S. 2007/0005016) also are the parts of multiple component system, and described multiple component system is assembled and used normally time-consuming.The process time of the increase that these equipment are followed can transfer to increase the risk of complication.In addition, many parts itself must be operated and the risk that causes complication because of the user error can be increased.A kind of severe complication of intraocular injection is intraocular infection, is called endophthalmitis, described endophthalmitis be because the entering of causal organism (antibacterial that for example enters the ophthalmic environment from the eye table), or the wound of eye table organization (for example cornea or conjunctiva wearing and tearing).
Therefore, for the new equipment of carrying out intravitreal injection needs are arranged.The equipment that meets human engineering of simplifying injection process and reducing the complication risk is useful.Accurately and without the equipment that wound ground is injected to medicine (for example liquid, semisolid or the medicine take suspension as substrate) in the eye also be useful.
Summary of the invention
Described herein is for equipment, method and the system of delivering drugs prescription to eye.This equipment can be integrated." integrated " refers to various features and is combined in the individual equipment, and described various features for example can be conducive to safety, aseptic and accurate mode delivering drugs prescription to eye.For example, these features can be integrated in the individual equipment: thus described feature can be assisted on the eye table position of hope and correctly placed, helps positioning equipment to arrive the ophthalmic space with suitable angle, help maintenance equipment end is stablized and can not moved or slip at the eye table during whole drug injection in case equipment has been located, adjust or the control intraocular pressure, and/or help will be for example because of power or the contact of drug injection or pierce through the wound that wall of eyeball self causes and be down to minimum.More particularly, integrated equipment can be used for owing to contact with destination organization direct or wound that indirect force transmission by another tissue (for example wall of eyeball or vitreous gel) causes is down to minimum, also can be used for corneal, conjunctiva, episcleral layer, sclera and intraocular structure (include but not limited to retina, choroid, corpus ciliare and crystalline lens, and blood vessel) and be down to minimum with the wound of the nerve of these structurally associateds connection.Also can comprise such feature: described feature can be conducive to reduce the risk of intraocular infection inflammation (for example endophthalmitis) and can reduce pain.Should be understood that and pharmaceutical formulation can be delivered to any suitable target location of ophthalmic, for example anterior chamber or back room.In addition, pharmaceutical formulation can comprise any suitable activating agent and can take any suitable form.For example, pharmaceutical formulation can be solid, semisolid, liquid, etc.Pharmaceutical formulation also can be suitable for the release of any adequate types.For example, it can be suitable for at once release, controlled release, delay to discharge, discharges lastingly or mode release bioactive agent that pill discharges.
Generally speaking, equipment as herein described comprises housing, and the size and dimension of described housing is specified to be convenient to a hand operated.Typically, housing has near-end and far-end, and the housing far-end the eye contact surface.Being in its conduit of disposing front state is usually located in the housing.Conduit is in its deployable state in enclosure interior at least in part.In some cases, conduit is attached to housing slidably.The inner chamber that conduit usually has near-end, far-end and passes through its extension.Can comprise actuating mechanism within housing, described actuating mechanism may be operably coupled to conduit and is used for holding the reservoir of activating agent.Trigger can be linked to equally housing and be configured to actuating mechanism is activated.In a modification, trigger is positioned on the sidepiece of apparatus casing, the equipment at contiguous eye contact surface place terminal (distance between trigger and the equipment end between 5mm to 50mm, between the 10mm to 25mm or the scope between the 15mm to 20mm), thus can be by finger tip easy actuation trigger simultaneously the finger with the same hand the eye that equipment is positioned at hope is shown on the position.In another modification, trigger is positioned at and becomes 90 degree on the sidepiece of apparatus casing, with measurement component, thereby when the equipment end is placed on the eye table upward perpendicular to limbus of corneae, an available fingertip activation trigger that equipment is positioned at second or the 3rd finger of the same hand on the eye table.In a modification, measurement component is attached to a contact surface.In some modification, also comprise the medicine filling mechanism.
Actuating mechanism can be manual, automatic or partly automatic.In a modification, actuating mechanism is spring-loaded actuating mechanism.At this, this mechanism can comprise single spring or two springs.In another modification, actuating mechanism is pneumatically actuated mechanism.
Can be achieved and further become more meticulous by comprising that dynamic stop member to injection device makes to eye top application plus-pressure.Dynamically stop member can comprise the slidably element that is linked to housing.In some modification, slidably element comprises dynamic sleeve pipe, and described dynamic cannula configuration becomes to regulate to be applied to the amount of the pressure of eye table.In other modification, dynamically stop member is configured to the wall of eyeball tension control mechanism.
In use, equipment by like this with drug delivery to the ophthalmic space: the eye contact surface of integrated equipment is positioned at eye table upper (wherein equipment also comprises be used to the reservoir that holds activating agent and actuating mechanism), and utilize the eye contact surface to eye top application plus-pressure at place, target injection site, and subsequently by actuating mechanism being activated and activating agent being delivered to the eye from reservoir.Location, the application of force and the step of sending are finished by a hands.In some cases, before being placed on equipment on the eye to eye table application local anesthesia.Before being placed on equipment on the eye, also can show the application disinfectant to eye.
Utilize the eye contact surface to eye top application plus-pressure also can be formed between 15mm Hg to the 120mm Hg, between 20mm Hg to the 90mm Hg or the intraocular pressure of the scope between 25mm Hg to the 60mm Hg.As hereinafter further described, before the deployment of distribution member (conduit), form the pliability that intraocular pressure can reduce sclera, this then can be convenient to conduit and pierce through sclera, reduce during injection process conduit and pierce through the sense of discomfort that wall of eyeball follows and/or the backlash that prevents equipment.
Drug delivery device, its parts and/or various activating agent can be used as independent package parts and are arranged in system or the complete articles for use.System or complete articles for use can comprise one or more equipment and one or more activating agents.Equipment can be prefill or be configured for the filling of manual medicine.When comprising multiple actives, can use identical or different activating agent.Also can use the activating agent of identical or different dosage.System or complete articles for use generally include operation instruction.They also can comprise anesthetis and/or disinfectant.
Description of drawings
Figure 1A to Figure 1B illustrates the front view of exemplary eye contact surface.
Fig. 2 A to Fig. 2 C illustrates the side view of other exemplary eye contact surface, comprising measurement component.
Fig. 3 A1 to Fig. 3 A3 and Fig. 3 B1 to Fig. 3 B3 illustrate the side view of other exemplary eye contact surface.
Fig. 4 A and Fig. 4 B1 to Fig. 4 B2 illustrate axonometric chart and the front view of exemplary flanged contact surface.
Fig. 5 A1 to Fig. 5 A2 and Fig. 5 B1 to Fig. 5 B2 illustrate side view and the axonometric chart of exemplary flat and protruding eye contact surface.
Fig. 6 A1 to Fig. 6 A2 and Fig. 6 B1 to Fig. 6 B2 illustrate exemplary side view and front view soft or semisolid eye contact surface.
Fig. 7 A1 to Fig. 7 A2, Fig. 7 B1 to Fig. 7 B2, Fig. 7 C1 to Fig. 7 C2 and Fig. 7 D to Fig. 7 E illustrate other exemplary eye contact surface, comprise having the eye contact surface that height adheres to the friction interface.
Fig. 8 illustrates exemplary measurement component and how to play and make eyelid retract and measure apart from the effect of a certain distance of limbus of corneae.
Fig. 9 A to Fig. 9 C illustrates measurement component around the exemplary layout of eye contact surface.
Other exemplary measurement component is shown Figure 10 A to Figure 10 C and how they play the effect of measuring apart from a certain distance of limbus of corneae.
Figure 11 A to Figure 11 D illustrates other exemplary measurement component.
Figure 12 illustrates the exemplary apparatus that comprises the labelling end component.
Figure 13 illustrates the labelling of being done by exemplary labelling end component and can how to be used for equipment is positioned place, target injection site on the eye table.
Figure 14 A to Figure 14 C illustrates the axonometric chart of exemplary sharp-pointed conduit.
Figure 15 A1 to Figure 15 A2 illustrates the side view of exemplary ramp angles.
Figure 16 A to Figure 16 D illustrates the cutaway view of exemplary conduit geometric shape.
Figure 17 illustrates the cutaway view of other exemplary conduit geometric shape.
Figure 18 A to Figure 18 C illustrates side view and the cutaway view (A-A intercepting along the line) of exemplary conduit through flattening.
Figure 19 illustrates the exemplary mechanism of exposing for the control conduit.
Figure 20 has provided another exemplary conduit and has exposed controlling organization.
Figure 21 illustrates the exemplary apparatus with protecgulum and bonnet.
Figure 22 illustrates and can how to utilize exemplary medicine filling element to make equipment fill pharmaceutical formulation.
Figure 23 A to Figure 23 C illustrates other example of medicine filling element.
Figure 24 A to Figure 24 D illustrates exemplary medicine filling element with fenestra.
Figure 25 A to Figure 25 B illustrates the exemplary band fenestra medicine filling element with the drug source handing-over.
Figure 26 A to Figure 26 C illustrates the cut-away side view of exemplary dual spring actuating mechanism.
Figure 27 is the cut-away side view of another exemplary dual spring actuating mechanism.
Figure 28 illustrates the axonometric chart of equipment, and described equipment comprises another example of dual spring actuating mechanism, and described dual spring actuating mechanism is in it and activates front state.
Figure 29 is equipment shown in Figure 28 and the cutaway view of dual spring actuating mechanism.
Figure 30 is the cutaway view of equipment shown in Figure 28 after the dual spring actuating mechanism has activated.
Figure 31 A to Figure 31 C illustrates trigger first spring-actuated with deployment catheter with the dual spring actuating mechanism how among Figure 28.
The enlarged drawing of Figure 32 A to Figure 32 C shows the release of the stop pin among Figure 28 and how to play second of the dual spring actuating mechanism the spring-actuated effect.
Figure 33 A to Figure 33 B illustrates the equipment of Figure 28 and has exemplary filler.
Figure 34 is the axonometric chart with exemplary apparatus of pneumatically actuated mechanism.
Figure 35 A to Figure 35 B has provided the cutaway view of equipment shown in Figure 34.Figure 35 A illustrates and is in the pneumatically actuated mechanism that activates front state.Figure 35 B is illustrated in the pneumatically actuated mechanism after the deployment catheter.
Figure 36 is the cutaway view of exemplary apparatus that comprises the actuating mechanism of single spring.
Figure 37 is the cutaway view of equipment shown in Figure 36, and it is illustrated in the single spring-actuated mechanism after the deployment catheter.
Figure 38 is the cut-away side view of exemplary medicine filling piston.
Figure 39 A to Figure 39 I illustrates the various views of exemplary apparatus end.
Figure 40 illustrates the exemplary apparatus with sliding medicated cap.
Figure 41 A to Figure 41 B provides the cutaway view that another has the exemplary apparatus of dual spring actuating mechanism.
Figure 42 illustrates the amplification view of exemplary dynamic sleeve pipe.
Figure 43 A to Figure 43 D illustrates the example method of moving ahead of distribution member and drug injection.
Figure 44 A to Figure 44 D illustrates exemplary register guide parts.
Figure 45 A to Figure 45 J illustrates the various aspects of exemplary meticulous sleeve pipe mobile control unit.
Figure 46 is that the diagram of the amount of the resistance that produces according to a modification, by dynamic sleeve pipe is described.
The specific embodiment
As herein described is for the handheld device, method and the system that for example by injection pharmaceutical formulation are delivered to eye.Equipment can be with various features integrated (combination) to individual equipment, and described feature can be conducive to for example with safety, aseptic and accurate mode pharmaceutical formulation is delivered in the eye.Therefore, such feature can be integrated in the individual equipment: be down to minimum with (for example because of the power of injection or the sclera self that punctures cause) to the wound of sclera and intraocular structure thereby can assist on eye correctly to place, help to locate to arrive ophthalmic space, adjusting or control intraocular pressure and/or help with suitable angle.Equipment can be configured to disposable all or in part.
I. equipment
Generally speaking, integrated equipment as herein described comprises housing, and the size and dimension of described housing is specified to be convenient to a hand operated.Typically, housing has near-end and far-end and at the eye contact surface of housing far-end.Be in its conduit of disposing front state and can be positioned at housing.Conduit is in its deployable state in enclosure interior at least in part.In some cases, conduit is attached to housing slidably.In addition, conduit has near-end, far-end and the inner chamber by its extension usually.Can comprise actuating mechanism in housing, described actuating mechanism may be operably coupled to conduit and is used for holding the reservoir of activating agent.
Can come forming device or its part by any suitable biocompatible materials or the combination of biocompatible materials.For example, one or more biocompatible polymers for example can be used for making apparatus casing, eye contact surface, measurement component, etc.Exemplary biocompatibility and can not including but not limited to by Biodegradable material: methyl methacrylate (MMA), polymethyl methacrylate (PMMA), polyethyl methacrylate (PEM) and other acrylic acid based polymer; Polyolefin, for example polypropylene and polyethylene; Vinylacetate; Polrvinyl chloride; Polyurethane; Polyvinylpyrrolidone; 2-Pyrrolidone; Polyacrylonitrile-butadiene; Merlon; Polyamide; Fluoropolymer, for example politef is (such as Teflon TMPolymer); Polystyrene; Styrene-acrylonitrile; Cellulose acetate; Acrylonitrile-butadiene-styrene (ABS); Polymethylpentene; Polysulfones; Polyester; Polyimides; Natural rubber; Oppanol; Polymethylstyrene; Silicones; And their copolymer and mixture.
In some modification, the part of equipment or equipment (for example medicament reservoir, plunger, housing, eye contact surface or measurement component) is that the material of resin is made by comprising cyclenes.Exemplary cyclenes resin includes but not limited to: such as
Figure BDA00002490131000081
Cyclic olefin polymer (ZEON company, Tokyo, Japan) or Crystal
Figure BDA00002490131000082
Olefin polymer (assisting greatly Jinggong Co., Ltd, Tokyo, Japan) and APEL TMCyclic olefine copolymer (COC) (Mitsui Chemicals, Inc, Tokyo, Japan) commercially available prod, cyclenes-ethylene copolymer, PET series resin, polystyrene resin, polybutylene terephthalate (PBT) resin and their combination.In a modification, adopting cyclenes is that resin and cyclenes-ethylene copolymer are favourable, and described cyclenes is that resin and cyclenes-ethylene copolymer have the high grade of transparency, high-fire resistance and minimum and even do not have a chemical reaction with pharmacology product (for example protein, protein fragments, polypeptide or comprise antibody, receptor or protein-bonded chimeric molecule).
The addition homopolymer of the open loop homopolymer that cycloolefine polymer or its hydrogenation product can be the cyclenes monomers, the ring opening copolymer thing of cyclenes monomer and other monomer, cyclenes monomer, the addition copolymer of cyclenes monomer and the hydrogenation product of other monomer and this homopolymer or copolymer.Above cyclenes monomer can comprise cycloolefin monomer and polycyclic olefin monomer (comprising dicyclo and Geng Gao cycle compound).The example that is suitable for producing the cycloolefin monomer of the homopolymer of cyclenes monomer or copolymer is the cycloolefin monomer such as cyclopentenes, cyclopentadiene, cyclic ethylene, methyl cyclic ethylene and cyclo-octene; They contain 1 to 3 low alkyl group (for example methyl and/or ethyl) as substituent lower alkyl derived thing; And their acrylate derivative.
The example of polycyclic olefin monomer is dicyclopentadiene, 2,3-dihydro cyclopentadiene, dicyclo [2,2,1]-hept-2-ene" and derivant thereof, three rings [4,3,0,1 2,5]-3-decene and derivant thereof, three rings [4,4,0,1 2,5]-3-endecatylene and derivant thereof, Fourth Ring [4,4,0,1 2,5, 0 7,10]-3-dodecylene and derivant thereof, five rings [6,5,1,1 3,6, 0 2,7, 0 9,13]-4-15 carbenes and derivant thereof, five rings [7,4,0,1 2,5,0, 0 8,13, 1 9,12]-3-15 carbenes and derivant thereof and six rings [6,6,1,1 3,6, 1 10,13, 0 2,7, 0 9,14]-4-heptadecene and derivant thereof.The example of dicyclo [2,2,1]-hept-2-ene" derivant comprises 5-methyl-dicyclo [2,2,1]-hept-2-ene", 5-methoxyl group-dicyclo [2,2,1]-hept-2-ene", 5-ethylidene-dicyclo [2,2,1]-hept-2-ene", 5-phenyl-dicyclo [2,2,1]-hept-2-ene" and 6-methoxycarbonyl-dicyclo [2,2,1]-hept-2-ene".Three rings [4,3,0,1 2,5The example of]-3-decene derivant comprises 2-methyl-three ring [4,3,0,1 2,5]-3-decene and 5-methyl-three ring [4,3,0,1 2,5]-3-decene.Fourth Ring [4,4,0,1 2,5The example of]-3-endecatylene derivant comprises 10-methyl-Fourth Ring [4,4,0,1 2,5]-3-endecatylene, and three rings [4,3,0,1 2,5The example of]-3-decene derivant comprises 5-methyl-three ring [4,3,0,1 2,5]-3-decene.
Fourth Ring [4,4,0,1 2,5, 0 7,10The example of]-3-dodecylene derivant comprises 8-ethylidene-Fourth Ring [4,4,0,1 2,5, 0 7,10]-3-dodecylene, 8-methyl-Fourth Ring [4,4,0,1 2,5, 0 7,10]-3-dodecylene, 9-methyl-8-methoxyl group-carbonyl-Fourth Ring [4,4,0,1 2,5, 0 7,10]-3-dodecylene, 5,10-dimethyl-Fourth Ring [4,4,0,1 2,5, 0 7,10]-3-dodecylene.Six rings [6,6,1,1 3,6, 1 10,13, 0 2,7, 0 9,14The example of]-4-heptadecene derivant comprises 12-methyl-six ring [6,6,1,1 3,6, 1 10,13, 0 2,7, 0 9,14]-4-heptadecene and 1,6-dimethyl-six ring [6,6,1,1 3,6, 1 10,13, 0 2,7, 0 9,14]-4-heptadecene.The addition copolymer of the addition homopolymer that an example of cycloolefine polymer is at least a cyclenes monomer or at least a cyclenes monomer and at least a other olefinic monomer (for example, ethylene, propylene, 4-methylpentene-1, cyclopentenes, cyclo-octene, butadiene, isoprene, styrene or analog).Can be by for example when utilizing known catalyst, above-mentioned monomer polymerization being obtained this homopolymer or copolymer, described catalyst dissolves in the varsol and forms (Japanese Patent Application Publication (Kokai) number HEI 6-157672, Japanese Patent Application Publication (Kokai) number HEI 5-43663) by vfanadium compound or analog and organo-aluminum compound or analog.
Another example of cycloolefine polymer is the open loop homopolymer of above-mentioned monomer or the ring opening copolymer thing of above-mentioned monomer.It can be by for example obtaining with above-mentioned monomer homopolymerization or with above-mentioned monomer copolymerization when utilizing known catalyst, and described catalyst for example is (1) by platinum group metal (ruthenium for example, rhodium, palladium, osmium or platinum) halogenide or the catalyst that forms of nitrate and Reducing agent or (2) by transition metal (titanium for example, molybdenum or tungsten) chemical compound and catalyst (Japanese Patent Application Publication (Kokai) number HEI 6-157672 that forms of the organo-metallic compound (for example organo-aluminum compound or organo-tin compound) of the metal in one of I to the IV family of periodic chart, Japanese Patent Application Publication (Kokai) number HEI5-43663).
Homopolymer or copolymer can contain unsaturated bond.Can utilize known hydrogenation catalyst with homopolymer or copolymer hydrogenation.The example of hydrogenation catalyst comprises (1) Ziegler-type homogeneous catalyst, each of described Ziegler-type homogeneous catalyst is comprised of the acylate of titanium, cobalt, nickel or analog and the organo-metallic compound of lithium, aluminum or analog, (2) loaded catalyst, each of described loaded catalyst is comprised of carrier (for example carbon or aluminium oxide) and the platinum (for example palladium or ruthenium) that is carried on the carrier, and (3) each catalyst that is comprised of the complex of one of above-mentioned platinum group metal (Japanese Patent Application Publication (Kokai) number HEI 6-157672).
In some cases, the part of equipment or equipment (for example medicament reservoir) is made by the material that comprises rubber.The example of suitable elastomeric material comprises butyl rubber (for example butyl rubber, chlorinated scoline, brombutyl and divinylbenzene copolymerization butyl rubber); Conjugated diene rubber (for example polyisoprene rubber (high to low cis-Isosorbide-5-Nitrae key), polybutadiene rubber (high to low cis-Isosorbide-5-Nitrae key) and styrene-butadiene copolymer rubber); And ethylene-propylene-propylene-diene terpolymer rubber (EPDM).Also can adopt the crosslinkable elastomeric material, and can be by above-mentioned elastomeric material and additive (for example cross-linking agent, filler and/or stiffener, coloring agent or age resister) kneading are made described crosslinkable elastomeric material to coming together.
In some cases, biocompatible materials is biodegradable polymer.The non-limiting example of suitable biodegradable polymers comprises cellulose and ester, polyacrylate (TYR derive or free acid), poly-(beta-hydroxy esters), polyamide, poly-(aminoacid), the polyglycerol fatty acid ester, poly-alkylene alkylates, polyoxyalkylene, poly-alkylene succinate, poly-anhydride, the polyanhydride ester, poly-aspartate, polylactic acid, polytetramethylene glycol, poly-(caprolactone), poly-(caprolactone)/PEG copolymer, Merlon, the Merlon that TYR is derived, polybutylcyanoacrylate, poly-two dihydros, poly-(dioxy Ketohexamethylene), poly--p-dioxy Ketohexamethylene, poly-(6-caprolactone-dimethyl trimethylene carbonate), poly-(esteramides), polyester, aliphatic polyester, poly-(ether-ether), Polyethylene Glycol/poly-(ortho esters) copolymer, poly-1,3-propanedicarboxylic acid, poly-(glycolic), poly-(Acetic acid, hydroxy-, bimol. cyclic ester), poly-(Acetic acid, hydroxy-, bimol. cyclic ester)/PEG copolymer, PLA, poly-(lactide-altogether-caprolactone), poly-(DL-lactide-co-glycolide), PLG/PEG copolymer, PLA PEG copolymer, polyphosphazene, poly phosphate, poly phosphate carbamate (polyphophoester urethanes), poly-(the propylene fumaric acid-altogether-ethylene glycol), PTMC, the polytyrosine carbonic ester, polyurethane, terpolymer (copolymer of Acetic acid, hydroxy-, bimol. cyclic ester lactide or dimethyl trimethylene carbonate), and their combination, mixture or copolymer.
Additive can be added in polymer and the polymeric blends to adjust as required its characteristic.For example, the biocompatibility plasticizer can be added into for the polymer formulators of at least a portion of equipment increasing its flexibility and/or mechanical strength, or so that the color contrast with respect to the eye table to be provided.In other cases, can add biocompatible filling material (for example granular filler, fiber and/or net) to give mechanical strength and/or rigidity to the part of equipment.
Can be by equipment as herein described be made in above-mentioned material injection moulding or compression moulding at least in part.
In some cases, comprise removably attached or integrated watch and/or amplifier element can be favourable at equipment.For example, magnifier and/or light source (for example LED lamp) removably can be attached to equipment so that equipment is terminal and injection site visual.Visual improvement can help more accurate and safely equipment is positioned target location (for example about 3.5mm to 4mm in corneoscleral junction rear), thereby avoids potentially the complication (for example retina shedding, corpus ciliare hemorrhage) of intraocular injection or to the wound of intra-ocular lens.Magnifier can be made by any suitable material, for example, it can be made by previously described any suitable nonabsorable (degradable) material, but lightweight typically, thereby make it not affect the balance of injection device.Magnifier and/or light source (for example LED) can be disposable.
Housing
The housing of equipment generally includes medicament reservoir and actuating mechanism.When the first, not during deployable state (dispose before state), conduit can be positioned within the housing.Housing can be any suitable shape, as long as it allows with a grasped and operation housing.For example, housing can be tubulose or columniform, rectangle, square, circular or oval-shaped in shape.In some modification, housing is tubulose or columniform, is similar to the cylinder of syringe.In this case, housing have about 1cm between about 15cm, about 2.5cm is extremely between about 10cm or about 4cm length between about 7.5cm extremely.For example, housing can have the length of about 1cm, about 2cm, about 3cm, about 4cm, about 5cm, about 6cm, about 7cm, about 8cm, about 9cm, about 10cm, about 11cm, about 12cm, about 13cm, about 14cm or about 15cm.But the also veining of the surface of housing, roughening or otherwise improvement in some zone (for example dash forward with protuberance, ridge, etc.) grasp and/or the operation housing with auxiliary user.
Housing can be made by any suitable material.For example (and as discussed previously), the parts of equipment can be made by any suitable biocompatible materials or the combination of biocompatible materials.The material that can be conducive to make housing includes but not limited to: cyclenes is resin, cyclenes-ethylene copolymer, PET series resin, polystyrene resin and pet resin.In a modification, adopting cyclenes is that resin and cyclenes-ethylene copolymer can be favourable, and described cyclenes is that resin and cyclenes-ethylene copolymer have the high grade of transparency, high-fire resistance and minimum and even do not have a chemical reaction with pharmacology product (for example protein, protein fragments, polypeptide or comprise antibody, receptor or protein-bonded chimeric molecule).Other material that can be conducive to make housing includes but not limited to: fluoropolymer; Thermoplastic (for example polyether-ether-ketone, polyethylene, polyethylene terephthalate, polyurethane, nylon, etc.); And silicones.In some modification, housing can be made with auxiliary affirmation catheter deployment and/or drug delivery by transparent material.Typically, material with suitable transparency is polymer, and described polymer for example is acrylic copolymer, acrylonitrile-butadiene-styrene (ABS) (ABS), Merlon, polystyrene, polrvinyl chloride (PVC), glycol-modified-polyethylene terephthalate (PETG) and styrene-acrylonitrile (SAN).Useful acrylic copolymer includes but not limited to: polymethyl methacrylate (PMMA) copolymer and styrene methyl methacrylate (SMMA) copolymer (Zylar for example
Figure BDA00002490131000121
Acrylic copolymer).
The eye contact surface
Equipment as herein described comprises without wound eye contact surface at the housing far-end usually.In some modification, the eye contact surface is attached to the housing near-end regularly.In other modification, the eye contact surface removably is attached to the housing near-end.Typically, the eye contact surface is aseptic.In some cases, the eye contact surface is disposable.During use, on the eye table that the eye contact surface of equipment is placed.
The eye contact surface can be any suitable configuration (for example size, shape, geometric shape, etc.), shows as long as its permission equipment is placed on eye without wound ground.In some modification, the eye contact surface is annular (for example Figure 1A to Figure 1B).When shape that the eye contact surface is taked to encircle, it can have about 0.3mm to about 8mm, about 1mm about 6mm or the about 2mm diameter of about 4mm extremely extremely.In other modification, the shape of eye contact surface is oval or circular.
More particularly, shown in the front view of Figure 1A to Figure 1B, the equipment end comprises the eye contact surface of annular, has formed wheel rim at the internal diameter of described eye contact surface place ring and the distance between the external diameter.In this case, the eye contact surface of the annular narrower eye contact surface (14) (wheel rim) that can be constructed with wider eye contact surface (10) (wheel rim) and less inside opening (12) (Figure 1A) or have a larger inside opening (16) (Figure 1B).Distribution member (conduit) can be the entry needle that is hidden in inside and is protected by the equipment end.Also film can be set, described film extends and crosses inside opening, and can flush or recess at the eye contact surface among the terminal inner chamber of equipment that entry needle is positioned at.
Shown in Figure 39 A to 39B, under quiescent condition, the end of distribution member can be with respect to the apparatus casing that comprises a contact surface terminal recessed, thereby when the equipment end is arranged to any surface (for example skin or wall of eyeball) when contacting, end and the surface of distribution member stand away, described distance in Figure 39 B by the arrow labelling.This distance can guarantee that the distribution member end does not directly contact with any surface before injecting program, this has prevented distribution member unexpected germ contamination of (for example skin secretion, discharge of eye or tear) from the source, and is down to minimum with bringing the vectorial risk of the intraocular infection that may cause endophthalmitis during the intraocular injection program into.
In some modification, the end of distribution member is recessed with respect to the most proximal end of apparatus casing, and stand away with the most proximal end of apparatus casing, described distance is from about 0.01mm to about 10mm, from about 0.1mm about 5mm or from about 0.5mm scope of about 2mm extremely extremely.
In another modification, the eye contact surface that directly contacts with the eye table of equipment end is annular, wherein has the gaps of about 360 degree between the inwall of apparatus casing and distribution member, and described gap is indicated by arrow in Figure 39 C.At this, the former body pollution of infected sexually transmitted disease (STD) and being placed on the eye table if the eye interface of annular becomes, then distribution member can contact and pierce through the eye table that has separated gap area with contaminated equipment end, and this risk that has prevented the unexpected germ contamination of distribution member and will bring the intraocular infection that may cause endophthalmitis into is down to minimum.On the contrary, lack this gap around distribution member (shown in Figure 39 D) meeting permission equipment end in the unexpected germ contamination of injection site.
In some modification, between the inwall of apparatus casing and distribution member, have from about 0.1mm to about 5mm, from about 0.3mm to 3mm or from about 0.5mm gap of about 2mm scope extremely.
In other modification, solid film or separator (105) are arranged, the end (107) that described solid film or separator make distribution member separates with external environment condition, and shown in Figure 39 E, wherein film or separator can be fluid-tight and/or air-locked.Film or separator can guarantee not have air to flow into or outflow equipment, have formed like this aeroseal and have kept certain constant air pressure at device interior.
In addition, film or separator can guarantee that the distribution member end does not contact with any unexpected germ contamination source (for example tear or discharge of eye) before injection process, and this has prevented the unexpected germ contamination of distribution member and has been with affiliation to cause the risk of the intraocular infection of endophthalmitis to be down to minimum during the injection process within the eye.
Film or separator that the end of the end of distribution member and apparatus casing is separated can comprise the material that is selected from a certain set, described set comprises biocompatibility and can not Biodegradable material, and described material includes but not limited to: methyl methacrylate (MMA), polymethyl methacrylate (PMMA), polyethyl methacrylate (PEM) and other acrylic acid based polymer; Polyolefin, for example polypropylene and polyethylene; Vinylacetate; Polrvinyl chloride; Polyurethane; Polyvinylpyrrolidone; 2-Pyrrolidone; The polyacrylonitrile butadiene; Merlon; Polyamide; Fluoropolymer, for example politef is (such as Teflon TMPolymer); Or PEP (FEP); Polystyrene; Styrene-acrylonitrile; Cellulose acetate; Acrylonitrile-butadiene-styrene (ABS); Polymethylpentene; Polysulfones; Polyester; Polyimides; Natural rubber; Oppanol; Polymethylstyrene; Silicones; Their derivant and copolymer and mixture.
In some modification, film or separator (30) can recess at the equipment terminus inner, thereby when contacting, described film or separator separate a segment distance with described surface with any surface (for example skin or eye table) when the equipment end is arranged to, described distance is indicated by arrow, shown in Figure 39 E.This distance can guarantee that distribution member terminal (31) did not directly contact with any surface before injection process, this has prevented distribution member unexpected germ contamination of (for example skin secretion, discharge of eye or tear) from the source, and within the eye during the injection process band affiliation cause the risk of the intraocular infection of endophthalmitis to be down to minimum.
Film or separator can be recessed at eye interface place with respect to the end of apparatus casing, and stand away at eye interface place with the end of apparatus casing, described distance is from about 0.01mm to about 10mm, from about 0.1mm about 5mm or from about 0.5mm scope of about 2mm extremely extremely.
In other modification, measurement component (32) (further describing hereinafter) can be with respect to the end (33) of apparatus casing recessed at eye contact surface place (Figure 39 F to Figure 39 H), thereby show (35) when contacting (Figure 39 I) when equipment terminal (34) and eye, measurement component (32) does not contact with eye table (35).This configuration can will be down to minimum to covering a wound risk of the delicate tissues (for example non-cuticulated epithelium of Cornea and conjunctiva) of table.Avoid direct contact between measuring cell and the eye table can be conducive to the risk that eye is shown wound (for example cornea or conjunctiva wearing and tearing) is down to minimum, this has prevented more serious complication (as the antibacterial that comprises corneal ulcer infects).In optional embodiment, the end of measuring cell (32) can be angularly away from or towards eyes (being respectively Figure 39 G and Figure 39 H).Measurement component can be with respect to a terminal recessed segment distance of apparatus casing, and described distance is from about 0.01mm to about 5mm, from about 0.1mm about 3mm or from about 0.5mm scope of about 2mm extremely extremely.
In some modification, shown in Fig. 2 A to Fig. 2 C, the equipment end also can comprise eye contact surface and the measuring device of annular, described measuring device help with respect to the tram of determining the injection site perpendicular to a certain distance of corneoscleral junction.In a modification, measurement component (20) is positioned at a side (22) of equipment end.In another modification, be positioned at more than side of equipment end more than a measurement component.Flat (Fig. 2 C) and basically outstanding above the eye contact surface at the end of this measurement component.In other modification, the end of measurement component is projection (Fig. 2 A to Fig. 2 B) above the eye contact surface, this can prevent that eyelid from slipping at the top of measurement component, prevents that thus eyelid and device terminal aseptic eye contact surface or distribution member from contacting.This then the risk of accidental pollution and intraocular infection during can reducing injection process.
In other modification, the eye contact surface comprises flange (for example Fig. 3 A1 to Fig. 3 A3, Fig. 3 B1 to Fig. 3 B3, Fig. 4 A and Fig. 4 B1 to Fig. 4 B2).Flange can be at equipment provide the contact surface of expansion between the terminal and eye table, is positioned at thus the stability of eye table increase equipment when upper when equipment, and the pressure of the per unit area of minimizing equipment-eyes interface.The pressure of the per unit area of minimizing equipment-eyes interface then can when the equipment end compresses wall of eyeball, reduce the probability of the conjunctival damage that is caused by the equipment end.It is desirable avoiding this conjunctival damage, because conjunctiva is covered by meticulous non-cuticulated epithelium, described non-cuticulated epithelium contains polyesthesia teleneuron and pain receptor.
In some modification, flange can have featheredge, and described featheredge contacts with the eye table, and allows eyelid mobile on flange top, but prevents that eyelid from contacting with the aseptic eye contact surface of equipment end.The eye contact surface can also be the flange (for example Fig. 4 A and Fig. 4 B1 to Fig. 4 B2) of annular.This annular lip can prevent that also eyelid from contacting with the aseptic eye contact surface of equipment end.
More particularly, as shown in Figure 3, flange can have featheredge (Fig. 3 A1), and described featheredge allows eyelid to slip over described flange and contacts with the axle of equipment end.In optional modification, described flange can be that thick (Fig. 3 B1) is to prevent the eyelid slides past ledge and to prevent that eyelid from contacting with equipment axis, prevents the accidental pollution of injection site thus.When the flange at the eye contact surface place of equipment end when being thick, its edge edge of its table place (for example) can be rounding to prevent the accidental injury to eye table organization (for example be coated with the conjunctiva of meticulous non-cuticulated epithelium, described non-cuticulated epithelium is rich in teleneuron and pain receptor).In the optional modification of equipment end, eye contact interface can be that flat (Fig. 3 A1 and Fig. 3 B1), protruding (Fig. 3 A2 and Fig. 3 B2) or recessed (Fig. 3 A3 and Fig. 3 B3) are to reduce the probability to the accidental injury of eye table organization (for example conjunctiva), provide simultaneously the device that is applied to power on the wall of eyeball and increases intraocular pressure so that the needle-penetration wall of eyeball, also be used for during injection process, partly fixing eyes by the friction interface that adheres to that a contact surface is provided.Fig. 4 A and Fig. 4 B to Fig. 4 B2 illustrate axonometric chart and the front view of flanged contact surface.
In also having other modification, the eye contact surface can be configured to (for example Fig. 5 and Fig. 7) flat, protruding, recessed or that tilt.In Fig. 5 A1 to Fig. 5 A2, the equipment end has flat eye contact surface.In optional embodiment, the equipment end has outstanding or protruding eye contact surface (Fig. 5 B1 to Fig. 5 B2), and this can improve the contact between showing of the inside opening of equipment end and eye when the equipment end compresses wall of eyeball and causes the recessed contracting of wall of eyeball.In also having another modification, the eye contact surface of equipment end is indentation or recessed, and this has reduced the risk to the accidental injury of eye table organization (for example conjunctiva).This configuration of the eye contact surface of equipment end can reduce the probability to the accidental injury of eye table organization (for example conjunctiva), provide simultaneously the device that is applied to pressure on the wall of eyeball and increases intraocular pressure so that the needle-penetration wall of eyeball, also be used for during injection process, rubbing interface and partly fixing eyes by providing equipment-eye table to adhere to.
More particularly, as shown in Figure 7, the eye contact surface can be flat and perpendicular to the major axis (Fig. 7 A1 to Fig. 7 A2) of described equipment, or flat and (for example tilt (Fig. 7 B1 to Fig. 7 B2) with respect to the major axis of described equipment, major axis with respect to equipment is oriented to 90 degree angle in addition, for example from about 45 degree to about 89 degree), or protruding and perpendicular to the major axis (Fig. 7 C1) of equipment, or protruding and tilt (Fig. 7 C2) with respect to the major axis of equipment, or circular (Fig. 7 D) or oval-shaped (Fig. 7 E).In a modification, the eye interface is circular or oval-shaped (for example, being similar to the end of cotton swab).The thickness of eye contact surface can be from about 0.01mm to about 10mm, from about 0.05mm to about 5mm or from about 0.1mm to about 2mm.
The eye contact surface can comprise that one or more helping is stabilized in the feature that eye is shown with it.For example, in a modification, an eye contact surface comprises a plurality of friction elements that adhere to, for example protuberance, ridge are prominent etc., described adhere to friction element increased the eye contact surface on the eye table surface attachment frictional force and do not have abrasive action.During this eye contact surface can provide or height to adhere to the friction interface upper and prevent equipment moving during the drug delivery within the eye equipment is stabilized in the eye table.In another modification, the eye contact surface comprises attaching interface, for example aspirating mechanism.Change also can help to prevent its slippage on the eye table for the manufacture of the type of the material of eye contact surface.
Material for the manufacture of the eye contact surface also can help to prevent wearing and tearing, the scraping to the eye table or stimulate.Adoptable exemplary non-lost material includes but not limited to: nylon fiber, cotton fiber, hydrogel, spongy material, polystyrene foamed material, other foam-like material, silicones, plastics, PMMA, polypropylene, polyethylene, PEP (PEF) and politef (PTEE).These materials can be smooth hard, semi-rigid or soft, and can be conducive to prevent during disposing pin through sclera conjunctiva wearing and tearing, subconjunctival hemorrhage or to other accident trauma (Fig. 6) of eye table organization.Also can adopt typically the material for the manufacture of stealthy mirror.
In some modification, the eye contact surface the edge also be rounding to prevent the accidental injury to eye table organization (for example be coated with the conjunctiva of meticulous non-cuticulated epithelium, described non-cuticulated epithelium is rich in teleneuron and pain receptor).In this case, as shown in Figure 6, the eye contact surface can have contour, and described contour is corresponding to the contour (Fig. 6 A1 to Fig. 6 A2) of equipment end.In other modification, the contour of eye contact surface can be projected into outside the contour of axle of equipment end, forms thus flange (Fig. 6 B1 to Fig. 6 B2).Flange can increase the eye contact surface of equipment end, keeps simultaneously the elongated profile of terminal axle, can easily insert between the eyelid of eyes in the crack.
The eye contact surface also can provide handing-over softness or deformable surface, and described eye table is complied with during the delivery process within the eye in described handing-over surface when being placed with against the eye table.Include but not limited to the eye table that the described handing-over surface of disclosed equipment directly contacts: the eye table of top, orbiculus ciliaris zone (described zone be defined as limbus of corneae after and around border circular areas between about 2mm to 7mm) or at about 2mm before the limbus of corneae with to reach afterwards limbus of corneae corneoscleral junction on every side between about 2mm regional.A handing-over surface of complying with eye table curvature can make it possible to form best contact interface between equipment and eyes, and can guarantee the fixing of the aseptic and eyes of intraocular drug delivery process, this then the safety that can improve injection process.Be used for the eye interface material of equipment for usually complying with the material (deformable or soft) of eye table, particularly comply with the curvature of the outer surface in the orbiculus ciliaris zone, about 2 to 5mm place after the corneoscleral junction so that the application of glass drug disposition, and comply with the corneoscleral junction zone so that the application of anterior chamber's medicine.As discussed previously, can adopt the non-keratinization conjunctiva of eye table and the eye corneal epithelium material without abrasiveness.Especially, material and its configuration are (for example, foam, braiding, knitting, interweave, fibre bundle, etc.) can comprise in can forming or high material and the configuration (for example hydrogel or cotton) that adheres to friction surface, described in or height adhere to friction surface so that eyeball can be fixed during injection process.
In some modification, the material of eye contact surface changes its characteristic when contacting with fluid, for example, reduces it and adheres to coefficient of friction (for example in the example of cotton fiber), and this can reduce the risk of conjunctiva wearing and tearing when the eye contact surface contacts with the eye table.In other modification, the material that forms the eye contact surface does not change its physics and chemistry characteristic when touching the fluid (for example tear) that covers the eye table.
Eye as herein described contact surface can be conducive to prevent during the injection of ophthalmic pin that conjunctiva and/or episcleral layer are hemorrhage.For example, the equipment that comprises annular eye interface can be compressed wall of eyeball, this transfers pressure is applied to the outer blood vessel of conjunctivae and selerae, reduces thus the blood flow by the there.Suppose the Oligemia by these blood vessels, then can reduce the risk of subconjunctival hemorrhage during the injection process within the eye.After the medicine application is finished within the eye, pin is recalled, but ring-shaped end can still compress wall of eyeball, apply thus lasting pressure and to the outer blood vessel of conjunctivae and selerae, also further reduce hemorrhage wind and/or extent of hemorrhage is down to minimum.
In some modification, the eye contact surface that equipment comprises plays the function of medicament reservoir.Can mix or be coated on the material of a contact surface at this medicine.Medicine can spread, adhere on the eye table from the eye contact surface subsequently.The exemplary material that is used for comprising medicine is hydrogel and its derivant.
The eye contact surface (for example also can cover distribution member (conduit) (for example entry needle), the eye contact surface can be the block that covers pin fully), this can be so that syringe can be by compressing wall of eyeball with terminal (for example far-end of block) and pressure being applied on the eyes.This then can pin with increase intraocular pressure before wall of eyeball contacts, and can be convenient to thus the pin puncture because compared to by the wall of eyeball of the puncture of the pin on the conventional syringe, wall of eyeball is more tightened.Typically, comparatively difficult with the pin puncture of conventional syringe, because the lower intraocular pressure that produces is so that wall of eyeball is comparatively yielding and easy to be mobile.In addition, the equipment that covers distribution member (conduit) is terminal, and for example entry needle also can protect described distribution member not contact contaminated because of it with the accident of eyelid.
Intraocular pressure controlling organization (wall of eyeball tension control mechanism)
Control to intraocular pressure (IOP) during delivery process (for example, intraocular injection or intravitreal injection) can be favourable.Before the deployment of distribution member (conduit), apply limited intraocular pressure and can reduce the sclera pliability, this then can reduce any discomfort sense on eye table during the injection process and/or prevent the equipment backlash.Typically, term " backlash " refers to conduit because the pliability of sclera and elasticity and the wall of eyeball that can't puncture smoothly, this so that conduit thrust and by sclera before sclera be retracted into certain one point union and oppositely promote conduit and equipment.Thereby equipment as herein described can comprise one or more IOP controlling organizations, is also referred to as in this article the wall of eyeball tension control mechanism.This is because wall of eyeball tension force ratio is relevant to and partly depends on intraocular pressure.The other factors that can affect wall tension force is scleral thickness and rigidity, and described factor can change because of patient age, sex and individual variation.
IOP mechanism can control IOP during the location in the ophthalmic of distribution member (conduit) between the placement of the target location on the eye table and fixation phase and/or during the ophthalmic of medicine or intravitreal injection or the vitreous body at the equipment end.For example, IOP mechanism can be in the ophthalmic of distribution member or vitreous body before the location or during control IOP, described distribution member is used for through sclera or through keratonyxis.In case occur by distribution member puncture eye table, typically, IOP will reduce.The minimizing of this IOP can occur after by distribution member puncture eye table immediately.
In some modification, the IOP controlling organization allow equipment (can) at the equipment end at the IOP that produces between the placement of target location on the eye table and fixation phase and/or between the ophthalmic fixation phase of distribution member between 15 to the 120mm Hg.In other modification, the IOP controlling organization allow equipment (can) producing IOP between 20 to the 90mm Hg at the equipment end between the placement of target location on the eye table and fixation phase and/or between the ophthalmic fixation phase of distribution member.In also having other modification, the IOP controlling organization allow equipment (can) producing IOP between 25 to the 60mm Hg at the equipment end between the placement of target location on the eye table and fixation phase and/or between the ophthalmic fixation phase of distribution member.
The IOP controlling organization also can allow equipment (can) within the eye any duration of injection process IOP is maintained between 10 to the 120mm Hg, or between 15 to the 90mm Hg or between 20 to the 60mm Hg.In some modification, if intraocular pressure surpasses a certain predetermined value, for example 120mm Hg or 60mm Hg or 40mm Hg, then drug injection speed is reduced by equipment or ends fully.During can being configured to drug injection within the eye, this IOP controlling organization surveys the IOP level of 90mm Hg for example or 60mm Hg or 40mm Hg.
The IOP controlling organization can comprise spring or its can comprise machinery or electric control mechanism.What generally speaking, the IOP controlling organization was configured to the frictional force of balance injection piston and fluid injecting stops pressure (propelling fluid enters the required power of pressurized eye fluid by pin).The IOP controlling organization can be linked to apparatus casing and actuating mechanism by some way, and described mode allows automatically to adjust the deployment of distribution member and the power that plunger moves ahead.That is to say that the IOP controlling organization can be configured to realize the power of predeterminated level of distribution member and predetermined intraocular pressure level.In addition, the employing of IOP controlling organization can produce than the high IOP of tranquillization IOP before the distribution element portion administration, thereby reduces the probability of sclera elasticity and equipment backlash, and is convenient to by distribution member puncture sclera.
In a modification, the IOP controlling organization is air relief valve, in case reach maximum pressure, described air relief valve makes injected current pass through from bypass.In another modification, IOP mechanism is accumulator, and described accumulator is suppressed at IOP in the specific scope.Some modification of IOP controlling organization can comprise pressure transducer.In also having another modification, the IOP controlling organization comprises slidably block, described block covered distribution member before distribution member is disposed, but can or retract for example make distribution member expose, dispose or move ahead when reaching predetermined IOP level along the surface sliding of apparatus casing.The slip of block can be manually adjustable (for example utilizing graduated disc) or automatically adjustable, stepping or increase progressively in essence.For example, as shown in figure 40, integrated injection device (500) also comprises except other element: block (502), retainer (504), trigger (506), spring (508), plunger (510), sealing member (512), medicament reservoir (514), pin (516) and syringe (518).In use, when block (502) is arranged to be applied to the eye table when upper against eye table and pressure, along with syringe (518) and pin (516) are pushed into, block a shot (502) are slidably to proximal retraction (in the direction of arrow) to retainer (504).But depression of trigger (506) (for example lever) is with retracting spring (508) subsequently, and described spring-advance plunger (510) and sealing member (512) are to pass through pin (516) injectable drug from medicament reservoir (514).In case injected medicine, block (502) slides back in pin (516) top.
Also can utilize lockable mechanism to slide to prevent block, lid or eye contact surface, or before reaching predetermined IOP, prevent the deployment of distribution member.Lockable mechanism prevents from when also being used in the IOP that does not reach predetermined blocking a shot, the slip of lid or eye contact surface.For example, when IOP reached predeterminated level (for example between 20mm Hg to the 80mm Hg), included lockable mechanism can be discharged manually or automatically on the equipment that comprises lid slidably, block etc. as herein described.This lockable mechanism can include but not limited to: height adheres to the lockable mechanism of friction surface, lock pin, interlocking ridge or any other type, and described lockable mechanism prevents that the end (for example block of equipment or lid) of equipment from sliding and thereby exposes pin.
In also having other modification, the IOP controlling organization comprises that at the block, lid or the eye contact surface that are positioned on the distribution member height adheres to friction surface or ridge.This feature can be arranged on the inner surface of block, lid or eye contact surface and be configured so that when when proximal direction slides height adheres to friction surface or ridge cooperates to provide block, lid or the contact surface resistance (increasing thus wall of eyeball tension force and IOP) to wall of eyeball with the lip-deep counter structure (for example fold, depression, protuberance, other ridge) of apparatus casing or other suitable part of appliance.In this case, the IOP controlling organization comprises dynamic stop member, as hereinafter further as described in.As mentioned before, can be configured to slide be adjustable, stepping or increase progressively in essence manually or automatically for block, lid or an eye contact surface.When adopting ridge, can adopt any suitable quantity, and they can be any suitable size, shape and geometric shape.For example, ridge can be arranged within block, lid or the eye contact surface circularly.In some cases, ridge is constructed with the surface of Different Slope.For example, distal surface can be configured to more precipitous than proximal end face.This design has been arranged, the increase that increases progressively that when near-end slides, can produce the slip that increases progressively and IOP when block, lid or eye contact surface, but also can finish block, lid or eye contact surface sliding back to above distribution member, because the slope on the prominent surface of near-end ridge reduces.
Dynamic stop member
Can be by making injection device comprise that dynamic stop member is finished and further becoming more meticulous exerting pressure to the eye table.Dynamically stop member can comprise the slidably element that is linked to housing.In some modification, slidably element comprises dynamic sleeve pipe, and described dynamic cannula configuration becomes to regulate to be applied to the amount of the pressure of eye table, as hereinafter further as described in.As discussed previously, some modification of wall of eyeball tension control mechanism plays the effect of dynamic stop member.
Dynamically stop member also can be configured to dynamic sleeve pipe.Be similar to previously described slidably block, dynamically sleeve pipe can be configured to increase the tension force of intraocular pressure and wall of eyeball before the pin injection.But dynamically sleeve pipe can be manually actuated the amount (and the amount of regulating thus wall of eyeball tension force) that is applied to the pressure on the eye table to regulate thus.Have ability that manual adjustments exerts pressure and can allow injector's (user) that the injection site is placed and injection angles has the control of improvement, and improved user and before the deployment of pin equipment stably is being positioned at the ability that eye is shown.Generally speaking, dynamically sleeve design becomes so that user can accurately be positioned at the equipment end target site of showing and the equipment end is firmly compressed wall of eyeball to increase wall tension force and intraocular pressure.Dynamic sleeve pipe is used in sleeve movement to begin before intraocular pressure to be risen to predeterminated level with the deployment of pin, as indicated above.Should be understood that term " dynamically sleeve pipe ", " sleeve pipe ", " dynamically sleeve pipe stops controlling organization " and " sleeve pipe blocking mechanism " replacedly are used in full.Dynamically sleeve pipe usually be configured so that when user when sleeve pipe applies pulling force (for example recalling), this motion can be convenient to the amount (being low to moderate 0 newton) (" N " refers to unit of force " newton ") that pin exposes and reduce pressure, and described pressure is to be applied to wall of eyeball so that sleeve pipe slides back to and exposes the required pressure of pin.Dynamically sleeve pipe also can be configured so that when user on sleeve pipe during applied thrust (for example moving ahead), this motion can offset and stop pin to expose, this can allow the equipment end to apply the pressure of increase to wall of eyeball before sleeve movement begins to expose with pin.
Dynamically some modification of sleeve pipe provides the variable force of following the U-shaped curve, as in example 1 and Figure 46 further as described in.Run into highest resistance at dynamic sleeve pipe along the initial sum destination county that housing moves at this, and between the initial sum terminal point of dynamic sleeve pipe stroke, be the resistance that reduces.In use, this is converted into and has the initial high-drag stage (when being placed at first on the wall of eyeball) drag reduction to sleeve movement succeeded by proceed in the chamber at pin during.When pin was disposed fully, typically, dynamically sleeve pipe will be at the terminal point of its travel paths, and will again run into the resistance of increase.The increase of this resistance allow sleeve pipe smoothly, stop step by step (rather than stiffly stop suddenly at destination county) will the risk of the transmission amount of damage of the power of inactive wall of eyeball being down to minimum (this turn back and the risk that will cause discomfort or injure eyes is down to minimum).Can be configured at near-end and far-end convergent at this exemplary dynamic sleeve pipe.With reference to the cutaway view among Figure 42, integrated injection device (42) comprises housing (44), whole or in part around the barrier strip (46) of housing and dynamic sleeve pipe (48), and described dynamic sleeve pipe can move ahead movably and retract on housing (44).Dynamically sleeve pipe (48) has near-end (50) and the far-end (not shown) of convergent.The end of convergent can provide the higher friction of adhering to along the initial sum destination county (being the initial sum destination county of the deployment of pin) of the travel paths of apparatus casing (44) at dynamic sleeve pipe.At the dynamic section start of sleeve movement, when its contact barrier strip (46), taperedly provide higher friction and the resistance of adhering to what near-end (50) was located.The thickness of barrier strip (46) can be change to regulate the amount of required resistance.When arriving wider interstitial segment (52), run into low motion of adhering to friction and lower drag, succeeded by at the destination county of the deployment of pin, higher adhering to rubs and higher resistance when arriving dynamic boot proximal end place tapered.Along with dynamic sleeve pipe at the far-end more convergent that becomes gradually, apparatus casing produced adhered to friction until it stops gradually fully more.Except two ends all the convergent, dynamically one of the near-end of sleeve pipe and far-end can be convergents in some modification.
Also can provide the variable frictional force of adhering to by parts (for example the circular relief band on the outer surface of equipment end or ridge are prominent).When another circular relief band or ridge approaching and on the inner surface of removable dynamic sleeve pipe were dashed forward (inner band or ridge are prominent), these parts can provide and oppositely adhere to friction.When begin at dynamic sleeve pipe mobile before outside and inner band or ridge is prominent when contacting with each other, their produce high adheres to friction and to the high-drag of dynamic sleeve movement.In case dynamically sleeve pipe begins mobile, in the relief Tape movement on the outside of apparatus casing by the relief band on the inside of moving interlocking attitude sleeve pipe, this can cause the rapid minimizing to the resistance of dynamic sleeve movement, and thereby by the pressure minimizing of equipment end on wall of eyeball.Relief interlocking band or the prominent shape of ridge have been determined the shape of drag reduction usually.For example, the minimizing of resistance can be followed the curve of sinusoidal shape.
In another modification, dynamically sleeve pipe can produce the power from its peak continuous decrease to its minimum point, described peak is (when dynamic sleeve pipe covers pin fully) before the deployment of pin, and described minimum point is to begin to move with when exposing needle point at dynamic sleeve pipe.At this, force retaining is lower until dynamic sleeve pipe stroke termination and finish the deployment of pin.The drag reduction of this pattern can be followed the curve of sinusoidal shape.
Dynamically slidably moving ahead of sleeve pipe can produce power from 0N to about 2N scope between himself and housing.In some cases, dynamically slidably moving ahead of sleeve pipe produces the power of about 1N scope extremely from about 0.1N between himself and housing.
Measurement component
Equipment as herein described can comprise measurement component, and described measurement component can help to determine at the eye table position at intraocular injection position.Integrated equipment generally includes measurement component.Measurement component is can be regularly attached or removably be attached to a contact surface.As discussed previously, thus measurement component can projection make it prevent that eyelid from contacting (for example Fig. 2 A to Fig. 2 B and Fig. 8) with the aseptic eye contact surface of equipment end above the eye table.The particular configuration of measurement component also can help to be down to the risk to the accidental pollution of aseptic medicament distribution element (conduit) (for example entry needle) minimum.This pollution may result from many reasons, and for example aseptic pin carries out accident with eyelid or other non-sterile surface and contacts.Also can be by some way that measurement component is painted to provide the eye table color contrast of (comprising conjunctiva, sclera and iris).
Generally speaking, measurement component is so that the intraocular injection position can be arranged in more accurately apart from the specific range of corneal-scleral intersection and be located before or after it, and described corneal-scleral intersection is called as " limbus of corneae ".In some modification, measurement component can be used for the intraocular injection position be arranged in after the limbus of corneae from about 1mm to about 5mm, from about 2mm about 4.5mm or from about 3mm about 4mm extremely extremely.In another modification, measurement component can be used for the intraocular injection position is arranged in after the limbus of corneae about 5mm extremely from about 2mm, or after limbus of corneae about 3.5mm place.In other modification, measurement component can be used for being arranged in the intraocular injection position within the about 3mm of limbus of corneae or the about 2mm and locating before it, or at the about 0.1mm of distance limbus of corneae between about 2mm and before it, locate.In a modification, measurement component is used for the intraocular injection position is arranged in before the limbus of corneae about 1mm to limbus of corneae between about 6mm.In another modification, about 3mm was extremely between about 4mm after measurement component was used for the intraocular injection position is arranged in limbus of corneae.
Measurement component can have any suitable configuration.For example, measurement component can be positioned at a side of a contact surface, or is positioned at more than side (for example Fig. 9, Figure 10 and Figure 11) of a contact surface.At this, when the end of measurement component was arranged in next-door neighbour's corneoscleral junction, the position of ophthalmic pin injection was arranged in apart from the limbus of corneae specified distance, for example about 3mm extremely between about 4mm limbus of corneae after.
In optional modification, measurement component comprises one or more elements (for example Fig. 9, Figure 10 and Figure 11).These elements can be from the radial stretching, extension of eye contact surface.Form measurement component by a more than element and can be conducive to guarantee perpendicular to limbus of corneae but not tangentially measured distance between limbus of corneae and the injection site, because might be this tangential situation when measuring device comprises discrete component.When the end of all elements that form measurement component alignd along corneoscleral junction, the position of ophthalmic pin injection was arranged in apart from the specific distance of limbus of corneae, for example about 3mm extremely between about 4mm limbus of corneae after.
More particularly, as shown in Figure 8, the equipment end with contact surface comprises measurement component (80), and described measurement component makes it possible to determining the injection site with respect to corneoscleral junction a distance.As discussed previously, in a modification, measurement component is positioned at a side of equipment end.In another modification, a more than measurement component is positioned at more than side of equipment end.In also having other modification, the end of measurement component can be protruding, crooked, etc., this has prevented that eyelid from slipping over measurement component and carrying out accident with the distribution member (conduit) of equipment and has contacted.In Fig. 8, distribution member (conduit) is shown fully hidden within the equipment end equally.
Fig. 9 provides other details about another modification of measurement component.Comprise annular eye contact surface (90) and measurement component (91) at this equipment end, described measurement component makes it possible to determining the injection site with respect to corneoscleral junction a distance.The periphery that contacts with the eye table of equipment end for example has the eye interface of annular, and distribution member (for example entry needle) can be hidden in the equipment terminus inner and by its protection.In Fig. 9, measurement component (91) is positioned at a side (Fig. 9 A to Fig. 9 B) of equipment end or more than side (Fig. 9 C) of equipment end.Thus, when the end of measurement component next-door neighbour corneoscleral junction was arranged, the position of ophthalmic pin injection was arranged in apart from the limbus of corneae specified distance, for example about 3mm extremely between about 4mm limbus of corneae after.The measurement component of any suitable quantity can be arranged on the equipment end, for example is attached to a contact surface.When adopting a plurality of measurement component, their available any suitable patterns are arranged in around the contact surface.For example, they can roundedly be arranged in around the contact surface or in a side of eye contact surface.They can equate or not etc. ground is not spaced apart around the contour of eye table.In other modification, measurement component can be spaced apart or spaced apart asymmetrically symmetrically around the contour of eye contact surface.These configurations can be conducive to allow syringe along the major axis slewing.
Figure 10 A provides other view of measurement component to scheming C, and described measurement component is similar to the measurement component shown in Fig. 9 A to Fig. 9 C.In Figure 10, the eye contact surface (93) of annular is shown has measurement component (93), and described measurement component makes it possible to locating to determine the injection site with respect to corneoscleral junction (94) certain distance and perpendicular to corneoscleral junction (94).Measurement component is shown the side at the equipment end, or in another modification in more than side of equipment end.Again, measurement component can comprise one or more elements.Form measurement component by a more than element and can be conducive to guarantee perpendicular to limbus of corneae but not tangentially measured distance between limbus of corneae and the injection site, because might be this tangential situation when measurement component comprises discrete component.When the end of all elements that form measurement component alignd along corneoscleral junction, the position of ophthalmic pin injection was arranged in apart from the specific distance of limbus of corneae, for example about 3mm extremely between about 4mm limbus of corneae after.
In Figure 11 A to Figure 11 D, also show a more than measurement component.Stretch out in the same attachment point (96) that this measurement component (95) is shown from the eye contact surface.When the end of all elements that form described measurement component alignd along corneoscleral junction, the position of ophthalmic pin injection was arranged in apart from the specific distance of limbus of corneae, for example about 3mm extremely between about 4mm limbus of corneae after.
Alternatively, measurement component can be configured to one or more flexible measuring bars.Can be used for making the flexible material of measuring bar and comprise flexible polymer, for example silicones.Shown in Figure 44 A, measure bar (800) but slave unit terminal (802), the side from eye contact surface (804) stretches out usually, thereby can be perpendicular to the distance between limbus of corneae ground measurement limbus of corneae and the injection site.Can adopt register guide parts (806) to guarantee correctly to use measurement bar (800).For example, shown in Figure 44 B, when the register guide parts are fully tightened, can determine to measure the correct location of bar (800) (thereby between measurement bar and apparatus casing (808), having formed an angle of 90 degrees).On the contrary, lax register guide parts (shown in Figure 44 C) show incorrect location.The register guide parts can be ropes.In a modification, integrated equipment comprises that at least three are measured bar.In another modification, integrated equipment comprises at least four measuring bar.When adopting a plurality of measurement bar, they can be configured in any suitable manner the end (equidistantly around the contour of eye contact surface, symmetry or asymmetrically around the contour layout of eye contact surface, etc.) around integrated equipment.For example, shown in Figure 44 D, measure bar and can be configured to cross over required an angle of 90 degrees (being that 45 degree add 45 degree) need not user with the 90 degree rotations that allow control stick hands transposition between bar farthest.
In some modification, measurement component can be configured to labelling end component (97).As shown in figure 12, show handing-over and when compressing conjunctival surface, stay visible labelling (98) (for example Figure 13) thereon with eye at the labelling end component (97) of its far-end (near eyes).The labelling end makes it possible to realize intraocular injection by the zone with respect to corneoscleral junction (99) safety of eyes, for example limbus of corneae after about 3mm extremely between about 4mm, on the zone, capsulociliary par of eyes.The diameter of labelling end can be from about 1mm to about 8mm or from about 2mm about 5mm or from about 2.3mm scope (for example Figure 12) of about 2.4mm extremely extremely.
Conduit
Intraocular drug delivery equipment as herein described can comprise any suitable conduit (or distribution member) in order to arrive the ophthalmic space and bioactive agent delivery is delivered to wherein.Conduit can have any suitable configuration, but the inner chamber that usually has near-end, far-end and pass through its extension.When the first, not disposing (before disposing) state, conduit is usually located within the housing.At deployable state the second,, namely after actuating mechanism activates, typically, conduit or its part will be stretched out from housing." near-end " means when equipment is positioned to against the eye table hands of the most close user and at the end near the end opposite of eyes.
The far-end of conduit usually is configured to sharp-pointed, that splay or otherwise can stings knockout table (for example sclera).The conduit that adopts can be any suitable specification (gauge), for example, about 25 specifications, about 26 specifications, about 27 specifications, about 28 specifications, about 29 specifications, about 30 specifications, about 31 specifications, about 32 specifications, about 33 specifications, about 34 specifications, about 35 specifications, about 36 specifications, about 37 specifications, about 38 specifications or about 39 specifications.The wall of conduit also can have any suitable thickness.For example, except conventional wall thickness (RW), the wall thickness of conduit can be designed to thin-walled (TW), spy/ultra-thin-wall (XTW/UTW) or special thin-walled (XXTW).These names are called those skilled in the relevant art and know.For example, conduit can be intubate or the pin of thin specification.In some modification, conduit can have the specification between about 25 to about 39.In other modification, conduit can have the specification between about 27 to about 35.In also having other modification, conduit can have the specification between about 30 to about 33.
That conduit can have is sharp-pointed, with the end (Figure 14 B to Figure 14 C and Figure 15 A1 to Figure 15 A2) of tip, rather than the circular distal (Figure 14 A) of picture in the pin of routine.Syringe needle with tip is formed by lateral side surfaces, described lateral side surfaces is straight at it to a terminal place that assembles, and formed ramp angles (inclined-plane and axle by pin form) assembling a place, described ramp angles can about 5 degree to (Figure 14 B) between about 45 degree, about 5 degree between about 30 degree, about 13 degree between about 20 degree or about 10 degree to the scope of (Figure 14 C) between about 23 degree.
Sharply, with the pin end of tip fibrous, the fibrous scleral tissue of needle-penetration is improved, described scleral tissue is the primary structure covering of eyes and comprises strong rubber fibril net.Therefore, this needle point can form less resistance and reduce thus the impulsive force that is passed to intraocular structure (for example retina and crystalline lens) during it pierces through wall of eyeball, then causes the less damage to intraocular structure (compared to the pin of routine) during the injection process within the eye.
In addition, this narrow ramp angles can (skin of described wall of eyeball be arranged by the Sensory nerve fibre tip fully so that pin can pierce through wall of eyeball at it, described Sensory nerve fibre tip is arranged in conjunctiva and cornea particularly thick and fast) time cause less sensation, compared to other more insensitive position, when relating to intraocular injection, the described sensation that causes can be a problem.
Narrow ramp angles also can allow the chamfer length grown and larger inclined-plane opening and thereby at the larger opening of the far-end of entry needle.When having this configuration, the power in the infusion of medicine eye chamber can reduce, and reduces thus eye inner tissue by the probability of strong injection mass stream damage, and this may occur with the short inclined-plane pin of routine the time.
In some configuration, conduit is to have one or more flat table planes and the entry needle of one or more side facets, such as Figure 16 and shown in Figure 17.This example comprises: have the needle shaft (Figure 16 A to Figure 16 C) by the prominent a plurality of tables plane of separating of sharp ridge, and the needle point with sharp side facet, described side facet is positioned at the either side on the inclined-plane of pin, about 90 degree places (Figure 17) apart from the inclined-plane.Conduit also can be bibeveled, namely has two inclined-planes, about both sides that face with each other in 180 degree and be positioned at conduit, described two inclined-planes.Conduit also can be that cated (for example scribble silicones, PTFE, etc.) is so that it pierces through wall of eyeball.
In other modification, conduit can be configured at least one direction completely or partially flattened, as along shown in the cutaway view of Figure 18 C of the line A-A of Figure 18 A intercepting.For example, conduit can be flattened on fore-and-aft direction (namely from pin its offside of inclined-plane side direction).In a modification, the outer surface of pin and inner surface are all flattened and be rendered as oval-shaped at section.In another modification, the inner surface of pin be circle and be rendered as ring at section, and the outer surface of pin is flattened can pierce through more like a cork fibrous sclera or the cornea tissue of wall of eyeball.In another modification, more than appearance plane of pin is flattened can piercing through more like a cork fibrous wall of eyeball, and the inside opening of described pin can be any shape, comprises circle or ellipse.
As discussed previously, at deployable state the second,, conduit or pin stretch out housing.The part of stretching out housing of pin can be called as the pin section of exposing.When mechanism is actuated at when activating, pin from the first, not deployable state (state before disposing) (under the described state its fully in the housing at equipment) become its outside housing second, dispose configuration, it exposes certain-length under described configuration.This length of exposing can be from about 1mm to about 25mm, from about 2mm about 15mm or from about 3.5mm scope of about 10mm extremely extremely.The pin section that these expose can enter in the vitreous chamber by sclera, choroid and corpus ciliare so that realize completely the ophthalmic puncture, is down to the risk of intraocular damage minimum simultaneously.In some modification, the about 1mm of pin Duan Zaicong that exposes is to about 5mm or from about 1mm about 4mm or from about 1mm scope of about 3mm extremely extremely.Can enter among the anterior chamber by cornea so that realize completely the ophthalmic puncture in this pin section of exposing, be down to the risk of intraocular damage minimum simultaneously.
In some modification, equipment can comprise and exposes controlling organization (9) (Figure 19 and Figure 20) for distribution member (11) (conduit).Expose controlling organization (9) usually so that the user can be set in distribution member dispose during the distribution member greatest length of exposing.In a modification, expose controlling organization and retreat stop and work by providing for pin protecting component (13).In another modification, exposing controlling organization (9) can be with the revolution ring that can dial scale.Can come exposing of metering needle by the part of millimeter or millimeter, for example 1mm, 1.5mm, 2mm, 2.5mm, 3mm, etc.Can be equipped with retraction mechanism at this equipment, described retraction mechanism control pin is retracted in the pin protecting component.This needle retraction mechanisms can be spring-actuated (Figure 20).
Equipment also can comprise detachable far-end (towards the eyes) element (for example protecgulum among Figure 21 (15)) of covering and armour tubing.In a modification, equipment also can comprise detachable near-end (away from eyes) element (for example, the bonnet among Figure 21 (19)), the proximal part of described proximal members covering and protection equipment, and for example, described equipment comprises filling docking mechanism (17).
Reservoir
Reservoir usually is contained in enclosure interior and can constructs in any suitable manner, as long as it can utilize actuating mechanism as herein described that bioactive agent delivery is delivered in the ophthalmic space.Reservoir can hold any for the ophthalmic space, for example the combination of the suitable medicine of glass intracorporeal space or prescription or medicine or prescription.Should be understood that term " medicine " and " agent " use in full convertibly at this paper.In a modification, medicament reservoir is not covered by silicone oil, its derivant or its improvement thing without silicone oil (not one of silicate-containing oil or derivatives thereof) and in inside or is lubricated, and this has guaranteed that silicone oil can not enter in the eye and causes muscae volitantes or intraocular pressure to raise.In another modification, medicament reservoir do not contain any lubricant or sealant and in inside not by any lubricated or sealing substance is lubricated, this has guaranteed that described lubricated or sealing substance can not enter in the eye and causes muscae volitantes or intraocular pressure to raise.
In some modification, reservoir is made by a kind of material, described material comprise cyclenes be resin, cyclenes-ethylene copolymer (comprise the commercially available prod such as Cyclic olefin polymer (ZEON company, Tokyo, Japan) or Crystal Olefin polymer (assisting greatly Jinggong Co., Ltd, Tokyo, Japan) and APEL TMCyclic olefine copolymer (COC) (Mitsui Chemicals, Inc, Tokyo, Japan)), cyclenes-ethylene copolymer, PET series resin, polystyrene resin, polybutylene terephthalate (PBT) resin and their combination.In a modification, adopting cyclenes is that resin and cyclenes-ethylene copolymer are favourable, and described cyclenes is that resin and cyclenes-ethylene copolymer have the high grade of transparency, high-fire resistance and minimum and even do not have a chemical reaction with pharmacology product (for example protein, protein fragments, polypeptide or comprise antibody, receptor or protein-bonded chimeric molecule).
Exemplary medicament can be selected from such as following class: antibiotic medicine (for example steroid and non-steroid); anti-infective (antibiotic for example; antifungal; antiparasitic; antiviral drugs; and disinfectant); cholinergic antagonist and agonist; epinephrine antagonist and agonist; antiglaucoma agent; neuroprotective; the medicament that is used for cataract prevention and treatment; antioxidant; hydryllin; anti-platelet agents; anticoagulant; antithrombotic agents; anti-scar agent; antiproliferative; anticarcinogen; complement inhibitor (for example; anti-C5 agent; comprise anti-C5a and anti-C5b agent); vitamin (for example, vitamin B and its derivant; vitamin A; depaxapenthenol; and tretinoin); somatomedin; be used for suppressing the medicament of somatomedin; gene therapy vector; chemotherapeutic agents; kinases inhibitor; the TYR inhibitors of kinases; PEGF(pigment epithelium somatomedin); small molecules interference RNA; its analog; derivant; coordination compound; with its improvement thing; and their combination.
Non-limiting, the concrete example of the medicine of can be separately or using as the part of composition of medicine therapy comprise Lucentis TM(Lucentis), Avastin TM(bevacizumab), Macugen TM(Pei Jianibu), steroid, for example, dexamethasone, dexamethasone sodium phosphate, triamcinolone, triamcinolone acetonide and fluocinolone acetonide, taxanes medicine, integration or anti-integrated agent, VEGF (VEGF) inhibitor (VEGF Trap), anecortave acetate (Retaane) and do not take charge of compounds of group.The non-limiting example of not taking charge of the member of compounds of group comprises sirolimus (rapamycin) and its water-soluble analogues SDZ-RAD, tacrolimus, everolimus, pimecrolimus and Zuo Tamosi and their analog, derivant, coordination compound, salt and improvement thing and their combination.
Also can comprise local anesthetic in the reservoir.For example, can adopt lignocaine, proparacaine, procaine, tetracaine, betacaine, benzocaine,
Figure BDA00002490131000311
(eutectic mixture of local anesthetic) and their combination.
Reservoir as herein described and equipment are suitable for the eye drops of very in a small amount solution, suspension, gel or semi-solid material.For example, can send about 1 μ l between about 200 μ l or about 10 μ l between about 150 μ l or about 20 μ l to the amount between about 100 μ l.For this reason, equipment has very little " dead angle " usually, and described dead angle is so that realize the very eye drops of a small amount of.
The equipment reservoir can prefill during the manufacture process or within the eye the injection before manually the filling, as hereinafter further as described in.
The medicine filler
In the time medicine or prescription will being packed into the reservoir of equipment before the injection within the eye, can adopt the filling element.The filling element can removably be attached to the far-end of housing.For example, the filling element can serve as the filling interfacing part, and described filling interfacing part is quantitatively controlled the volume of liquid, semiliquid, gel or suspension medicine in the equipment to be filled to.For example, the filling element can comprise driver plate mechanism (21) (Figure 21 and Figure 22), the volume of the medicine in the default specifically equipment to be filled to of the described driver plate permission operator of mechanism.Can be by loading from about 0.01 μ l to about 100 μ l or from about 0.1 μ l to the precision of about 10 μ l scopes.This filling element can allow take specific volume as equipment reservoir loaded with liquid, semiliquid, gel or suspension medicine, and described specific volume is equal to or less than the volume of medicine storage capsule, and this permission is filled to medicine in the equipment without air ground.This is favourable, can cause the patient to feel to see " floating thing " because inject the air of eye, and this is driving or other similarly can make the patient not accommodate when movable to divert one's attention especially.
As shown in figure 22, medicine filling mechanism (23) comprises roomy base component (25), and described base component is used for reservoir (27) by the upright filling of its (away from eyes) far away end (29).What illustrate equally is exemplary protecgulum (31) and bonnet (33), and the controlling organization dialled (21) that is used for setting filling and/or volume injected.In other modification, equipment comprises the filling mechanism such as filling interfacing part (35A), wherein (for example known bottle of the those skilled in the art) handing-over (Figure 25 A to Figure 25 B) of interfacing part (35A) and medicine storage capsule and pierce through bottle stopper and thus medicine can be packed into the equipment reservoir to touch the medicine that holds in the bottle.In Figure 25 A to Figure 25 B, docking mechanism is positioned at hanging position, thereby makes medicine bottle (37) directly be positioned the interfacing part top, thereby medicine is moved down from bottle on gravity direction.
In a modification, docking mechanism comprises pin or sharp-pointed intubate, and described pin or sharp-pointed intubate have opening or fenestra (39) at its base portion.When being in desirable loading position and loading simultaneously interfacing part and puncture to the medicine bottle, described opening or fenestra are positioned to be close to the inside face of bottle stopper, this then realized without air ground medicine being filled in the equipment and with medicine and removed fully from storage capsule.Airfree medicine filling can be favourable, because it can prevent that the patient from seeing little ophthalmic bubble or " float ".Consider and typically use little dose and expensive medicine, it also is favourable fully removing medicine.
In other modification, for example, when equipment had flat side surface (Figure 24 A to Figure 24 D) or flat front or rear surface (Figure 22), filling mechanism comprised the filling interfacing part, and described filling interfacing part is positioned at apart from these 180 degree places, flat surface.This causes the filling interfacing part to direct at upwards, can puncture to the medicament reservoir that is in hanging position, this then make realized without air ground with drug delivery to equipment, and medicine removed fully and it is packed into described equipment and can not have medicine to leave over and lose storage capsule from storage capsule.
In other modification, shown in Figure 33 A to Figure 33 B, can pass in the far-end setting of needle assembly (125) mouthful (144), the described mouth that passes into allows to be packed in the reservoir (122) from the medicine of storage capsule (146).Pass into mouthful (144) and can be arranged in any correct position on needle assembly (125) or the housing (102).For example, if necessary, thereby pass into mouth can be arranged in housing antetheca or even eye contact surface (not shown) in the front portion of medicine filling slave unit is carried out.Passing into mouthful (144) can be made by this material: described material allows sealably to be punctured by sharp-pointed conduit, for example silicones.One or more films (148) also can for example be set in eye contact surface (108) stop escape of air and/or outside germ contamination with the inner compartment that seals up housing.Can comprise also that in the wall (102) of housing one or more little holes (150) flow out from housing (102) to help controlling air.The quantity of hole (150) and diameter can be vicissitudinous speed of disposing with control (needle assembly and) pin.
In some modification, for example, when adopting pneumatically actuated mechanism, can load the filling of piston control medicine by medicine.For example, as shown in figure 38, equipment (400) can comprise medicine filling piston (402), and described medicine filling piston has near-end (404) and far-end (406).Far-end (406) is suitable for comprising threaded section (408).Thus, from container (410) by adaptor (412) with during passing into the filling of mouthful (414), rotatable and retraction medicine loads piston (402) to form negative pressure in reservoir (416) at medicine.This negative pressure is transferred to draw medicine by pin (418) and is entered reservoir (416).Receptor (420) also can be set in order to passing on the medicine that holds initial filling before the reservoir at the far-end of equipment.
Actuating mechanism
Equipment as herein described is usually included in the actuating mechanism in the housing, and described actuating mechanism is disposed from the conduit of housing and so that realized the medicine slave unit is delivered in the ophthalmic space.In other modification, conduit is disposed by the actuating mechanism that is contained in the independent socket, and described independent socket can for example utilize and be clasped or other interlocking member removably is attached to apparatus casing.Actuating mechanism can have any suitable configuration, if its can be accurately, without wound and controllably with drug delivery to the ophthalmic space.For example, actuating mechanism can be delivered to medicine or prescription in the eye via intraocular injection, and the speed of described intraocular injection is from about 1 μ l/ second to about 1ml/ second, from about 5 μ l/ second to about 200 μ l/ seconds or from the scopes of extremely about 100 μ l/ seconds of about 10 μ l/ seconds.The power that actuating mechanism can provide pin to dispose usually, described power enough comprise by force the wall of eyeball in conjunctiva, sclera and orbiculus ciliaris zone with puncture, but less than the power that causes the harmed eye inner structure owing to high speed impact.This power depends on several physical factors, includes but not limited to: the speed/rate that the pin at the specification of the pin that adopts, the contact point place between needle point and wall of eyeball is disposed, described speed/rate transfer to determine impulsive force.The exemplary scope of the power that can be produced by actuating mechanism is about 0.1N(newton) about 1.0N(newton extremely).The speed that pin is disposed also can be between about 0.05 second to about 5 seconds scope.
In some example, actuating mechanism is single spring mechanism.In other modification, actuating mechanism is dual spring mechanism.In other modification, actuating mechanism is pneumatic, the mechanism that for example adopts negative pressure (for example vacuum) or malleation to drive.In other modification, actuating mechanism is magnetic or electrically driven (operated), is for example driven by piezoelectricity or track mechanism.The actuating mechanism of these types can be configured to allow the speed of independent control drug injection and speed and the power (for example by the control of the second spring element in the dual spring modification) of power (for example by the control of the first spring element in the dual spring modification) and distribution member deployment.Exemplary dual spring mechanism is shown in Figure 26 and Figure 27.
Figure 28 also shows the exemplary integrated intraocular drug delivery equipment with the dual spring actuating mechanism.In Figure 28, equipment (100) comprises the housing (102) of have near-end (104) and far-end (106).Eye contact surface (108) is attached to far-end (106).Measurement component (110) is attached to a side of a contact surface (108).As hereinafter further as described in, the trigger (112) that operationally is bonded to housing (102) and first spring (114) of actuating mechanism and the second spring (116) cooperation are passed through opening (120) in the housing (102) to dispose pin (118), with thus from reservoir (122) delivering drugs.In Figure 29, show better the first spring (114), the second spring (116), pin (118), opening (120) and reservoir (122).Equally in Figure 29, conduit (for example pin (124)) is shown and is in its first deployable state not in housing.Pin (124) is configured to the part of assembly (125), thereby makes the motion of assembly cause the correspondence of pin (124) to be moved.Retainer (115) is arranged on the near-end (127) of assembly (125), and described retainer is connected to the far-end of the first spring (114) and the near-end of the second spring (116).Other parts of spring and equipment can be via medical grade adhesive, rub or be clasped and connect.
In Figure 30, the second spring (116) may be operably coupled to plunger (132) by the frictional fit in the compartment (134) of plunger (132).State before actuating, as shown in figure 29, plunger (132) and the second spring (116) remain on the appropriate location by pin (118).Pin (118) is located movably and plunger (132) combination at plunger groove (138), and via the frictional fit with plunger groove (138) and housing (102) plunger (132) is locked in the appropriate location.
By actuating trigger first spring (114) of actuating mechanism activated pin (124) disposed to the ophthalmic space, that is to say, it with pin (124) from its first not deployable state (Figure 29) move to its second deployable state (Figure 30).With reference to Figure 30 and Figure 31 A to Figure 31 C, by the actuating of the first spring (114) is occured by for example one or two finger depression of trigger (112), described finger is press push button (126) also.Shown in Figure 31 A and Figure 31 B, button (126) is configured with button groove (128), and described button groove allows button (126) to align with passage (130) in the housing (102).In case align with passage (130), button (126) can slide along passage (130) and advance.Can manually be controlled by user, automatically be controlled or both control in combination along the mobile speed of passage (130) by spring tension.This motion of button (126) allows the first spring (114) expansion to prop up retainer (115), thereby can dispose needle assembly (125) and pin (124).Passage in the housing can have any suitable configuration.For example, shown in Figure 31 C, passage (130) can be helical cuts in the housing to allow rotation or the gyrate of pin when moving ahead, this can be convenient to the needle-penetration wall of eyeball.
Typically, the actuating of the first spring (114) actuating that can cause the second spring (116) is gone forward side by side in the ophthalmic space drug delivery is gone out equipment.For example, as shown in figure 30, the tension force that the first spring (114) props up retainer (115) (described retainer also is connected to the near-end of the second spring (116)) plays the effect of expansion the second spring (116), thereby assembly (125) is moved ahead in housing (102).Shown in Figure 32 A to Figure 32 C, when arriving opening (120) with the pin (118) of plunger (132) combination movably, they are deployed away by opening (120).Pin (118) slave unit is discharged, is allowed the second spring (116) to prop up plunger (132) free wxpansion subsequently, releases equipment with the medicine that will be positioned at thus reservoir (122).Opening (120) can be covered by film or sealing (140), and described film or sealing can pierce through to provide the visual cues of delivering drugs by pin (118).
Also can adopt the dual spring actuating mechanism shown in Figure 41 A to Figure 41 B.With reference to figure 41A, integrated equipment (600) comprises actuating mechanism, and described actuating mechanism comprises the first spring (602) and the second spring (604).In use, when depression of trigger (606) (for example lever), the first spring (602) is released with impeller-hub on the direction of arrow (608), and this transfers the end with pin (610) release equipment (600).The continuing to move ahead of axle (608) promoted injection cannula (612) and top seal (614), thereby can send medicine in the reservoir (616) by pin (610).With reference to figure 41B, in case injectable drug, short teat (618) movably in conjunction with shell nozzle (620) to discharge thus the second spring (604), this is mobile with retraction pin (610) (not shown) backward with axle (608) subsequently.
In some modification, adopted single spring-actuated mechanism, such as Figure 36 and shown in Figure 37.When adopting single spring, except having removed the second spring from, actuating mechanism is configured to be very similar to dual spring mechanism mentioned above.Therefore, before it activates under the state, as shown in figure 36, and can be by by for example one or two be pointed depression of trigger (304) and activates single spring (302) with the equipment (300) of single spring (302), described finger is press push button (306) also.Button 306 is configured with button groove (308), and described button groove allows the interior passage (not shown) of button (306) and housing (310) to align.In case align with passage, button (306) can slide along passage and move ahead.This motion of button (306) allows spring (302) to prop up plunger (312) expansion, thereby can dispose needle assembly (314) and pin (316).When movably in conjunction with the opening (320) in pin (318) the arrival housing (310) of plunger (312), they are deployed away by opening (320).Pin (318) slave unit discharges, allows subsequently spring (302) to prop up further expansion of plunger (312), releases equipment with the medicine that will be positioned at thus reservoir (322).Although not shown at this, opening (320) can be covered by film or sealing, and described film or sealing can pierce through to provide the visual cues of delivering drugs by pin (318).
Also can adopt pneumatically actuated mechanism.In a modification, shown in Figure 34 and Figure 35 A and Figure 35 B, pneumatically actuated mechanism is to comprise plunger, pin and shell nozzle to the described same way as of single spring and dual spring mechanism.But, utilized piston to slide and advanced the interior needle assembly of housing, rather than utilized spring to dispose needle assembly and plunger.For example, in Figure 34, comprise piston (202) and trigger (204) with the equipment of pneumatically actuated mechanism (200).Piston (202) is used for the housing (206) of air compressing to equipment (202).If necessary, can come control piston to squeeze into compressed-air actuated amount in the equipment by graduated disc or other mechanism's (not shown).The near-end of housing also can be configured to for example have flange, fold or other plugging structure, and described plugging structure allows piston (202) to enter housing but can not be from housing rectilinear motion out.When depression of trigger (208), a pair of lock pin (210) also is depressed to allow thus to promote forward needle assembly (212) by the compressed air that piston (202) forms.This moving ahead of needle assembly (212) is deployed to slave unit out (Figure 35 B) with pin (214).As discussed previously, also be provided with pin (216), described pin is similar to the pin that above plunger (218) is locked in the appropriate location.Because travelling forward of needle assembly (212) and opening (220) from housing (206) when being discharged from equipment, compressed air further moves forward plunger (218) with the medicine slave unit that promotes thus to be arranged in reservoir (222) out when them.Also can comprise rotating dog (224), described rotating dog allows needle assembly (212) to rotate with respect to housing (206) when being discharged by the needle assembly (212) that slides.
As mentioned before, trigger can be linked to housing and be configured to actuating mechanism is activated.In a modification, trigger be positioned at apparatus casing a side, near the equipment at eye interface place terminal (for example the distance between trigger and the equipment end can be between 5mm to 50mm, between the 10mm to 25mm or the scope between the 15mm to 20mm), thereby make trigger can be by fingertip activation simultaneously equipment by the eye table position of the finger locating on the same hand in hope.In another modification, trigger is positioned at a side that becomes 90 degree with measurement component of apparatus casing, thereby when the eye contact surface is placed on the eye table perpendicular to limbus of corneae ground, can come actuating trigger by the finger tip of second or the 3rd finger that equipment is positioned at the same hand that eye shows.
Some modification of equipment can comprise control stick in order to initiate plunger motion.In these cases, control stick can be used the mechanical system actuating plunger, for example by spring-actuated, is similar to mentioned above.In other modification, the actuating of plunger can occur by the combination of machinery and manual feature.For example, can assist the initiation plunger motion by the manual force that is applied on the control stick, the while has also adopted for generation of the spring-actuated mechanism of mechanical force so that plunger moves forward with injectable drug in equipment barrel.Be connected at control stick in the situation of plunger, the beginning of plunger motion and drug injection are by manual components control, and the speed of fluid injecting is controlled by mechanical force.Because manual force and the combination of mechanical force in the same way can apply the manual force that reduces to plunger at this, be convenient to thus be positioned at stablizing of an equipment at the upper place, accurate injection site of table.
Control stick can be arranged between terminal 10mm to 50mm equipment and the handing-over of eye table and locate, or locates between the terminal 20mm to 40mm of equipment.Being arranged in such a way control stick can make it possible to a hands without wound and operating equipment accurately.
Shown in Figure 43 A to 43D, the dynamic sleeve pipe (704) that exemplary integrated equipment (700) comprises housing (702), can slide thereon, eye contact surface (706), plunger (708) and be used for manual actuation plunger (708) with the control stick (710) by pin (712) injectable drug.Figure 43 B shows the enlarged drawing of the eye contact surface (706) shown in Figure 43 A, dynamic sleeve pipe (704), plunger (708) and pin (712).In use, after being placed on eye contact surface (706) on the eyes, institute's applied pressure can make dynamic sleeve pipe (704) slide back to (on the direction of arrow) to expose pin and to allow the needle-penetration wall of eyeball automatically.Can manually advance slidably subsequently control stick (710) (on the direction of arrow shown in Figure 43 C) to advance plunger (708).When finishing by pin (712) injectable drug, can manually advance slidably dynamic sleeve pipe (704) to cover pin, shown in Figure 43 D.
Can manually make dynamic sleeve pipe move ahead slidably or retract by meticulous moving control mechanism (being also referred to as moving control mechanism).In these cases, dynamically sleeve pipe can comprise that height adheres to friction surface, and described surface is positioned on the outer surface of sleeve pipe, and the motion of the auxiliary sleeve pipe of available finger tip.In a modification, height adheres to friction surface can be impressed or comprise the labelling with saw tooth pattern.In other modification, shown in Figure 45 A, platform or mat (for example finger tip pad) (900) can be attached to the outer surface of sleeve pipe (902) to help manually propelling or retraction sleeve pipe.Platform or mat can comprise that also height adheres to friction surface (904), and the axonometric chart on described surface, side view and top view are shown in Figure 45 B, Figure 45 C and Figure 45 D.Typically, platform or mat (900) comprise base portion (912) in order to be attached to sleeve pipe (902).Base portion (912) can be any suitable configuration.For example, the base portion of platform or mat can be configured to cylindrical (Figure 45 H) or have narrow the part (part that diameter is less), for example dumbbell or apple core shaped (Figure 45 I).
Some modification of equipment described herein comprises the grasping member with retraction slit or passage, described retraction slit or passage and dynamic stop member combined effect with drug injection in.With reference to figure 45A, grasping member (906) can be to locate to link (usually affixed) to the parts of apparatus casing (908) at the near-end (912) of sleeve pipe (902).Grasping member (906) can be configured to comprise retraction slit (910) at Qi Bizhong.In use, when sleeve pipe (902) is retracted, as among Figure 45 J by shown in the direction of arrow, the base portion of mat or platform (912) moves into slit (910).Retraction slit (910) can be configured to the consistent passage of width (Figure 45 F) or have the passage of keyhole type configuration, for example has at the near-end of slit or far-end and narrows part (Figure 45 G) or amplifier section (Figure 45 E).The retraction slit can for example provide sensory feedback when arriving the terminal point of retraction.The configuration of the base portion of platform or mat may be selected to and makes it that frictional fit with slit is provided.For example, when slit had the part of narrowing, base portion can have the part of narrowing equally.
When adopting grasping member, equipment also can comprise lockable mechanism.In a modification, when arriving the terminal point that sleeve pipe bounces back and pin exposes/disposes, wide of the sleeve pipe slit with wide of the grasping member slit and housing in opening and the register in the plunger axis, this allow platform base portion insert plunger axis with it with respect to platform locking, described platform has become the actuator lever that is used for the hand injection medicine.The narrow section of base portion enters the narrow section of sleeve pipe slit, and this makes platform with respect to the sleeve pipe release, allows it to shift to the equipment end.In another modification, when the platform base portion arrived the terminal point of retraction slit, it can be pressed into the opening in the plunger axis and become lock pin with connecting platform and plunger.When it was depressed, its narrow section entered the keyhole slit in the sleeve pipe, and became can move and shift to cannula end (with platform base portion and sleeve pipe release) in slit.
Wish to control the amount of pressure that is applied to by the equipment end on the eye table when disposing pin during its ophthalmic puncture when user, moving control mechanism is favourable.Moving control mechanism has been arranged, and user can utilize finger tip to reduce or increase the counteracting force that exposes of adjusting sleeve pipe motion and pin.
For example, when if user is applied to pulling force described height and adheres on the friction surface (height that is about to sleeve pipe adheres to friction surface and is pulled away from the equipment end), this motion can be convenient to pin and expose and reduce and be applied to wall of eyeball so that sleeve pipe slides back to and expose the amount (being low to moderate 0 newton) of the required pressure of pin.In another modification, if user applied thrust (height that is about to sleeve pipe adheres to friction surface and pushes the equipment end to), this motion can hinder and stop pin to expose, and this can allow the equipment end before the beginning that sleeve movement and pin expose the pressure that increases to be applied to wall of eyeball.
In use, available second or the 3rd finger sliding platform or mat.Again, this allows the injector manually to adjust the resistance of sleeve pipe and moving along the equipment end.For example, also promote thus sleeve pipe by promote forward mat with finger tip, injector's (when the equipment end is positioned on the eye table) when the beginning of process provides some resistance (and pin need to keep being covered fully).The injector will unclamp his/her finger tip with the deployment that realizes pin and it is through sclerotic puncture from casing cushion subsequently.Some modification of equipment can comprise at the destination county in sleeve pipe path that also step or annular ridge are prominent, thereby is pulled back through after this step at sleeve pipe, and it will trigger spring-actuated plunger motion automatically.The finger tip pad is used in and retracts the described step of sleeve pipe process when pin is disposed end to activate plunger motion and drug injection.
When adopting platform or mat, can make at sleeve pipe to begin to move the amount minimizing that is applied to epibulbar pressure with equipment before exposing pin, and allow thus according to the patient customized amount of exerting pressure of difference.
On the other hand, thus expose 1mm or still less when dynamically sleeve pipe can provide step-type pin to expose to make pin run into maximum resistance at eye table place when the needle-penetration wall of eyeball.Remainder at this pin is positioned at inside pipe casing, and its section of not exposing a little or growing is farthest screened in narrow withdrawing from aperture or the duct at least.This sleeve design can be down to the risk of pin bending minimum compared to having the long conventional syringe that exposes pin.This design can make it possible to utilize the risk that can not increase its bending when the puncture wall of eyeball than the pin of small dimension.Less gauge can make its more comfortable and wound still less during the puncture of its ophthalmic.
II. method
This paper has also described the method for utilizing integrated intraocular drug delivery equipment.Generally speaking, method may further comprise the steps: the eye contact surface of equipment is positioned on the table, utilizes the eye contact surface at place, target injection site pressure to be put on eye and show, and by actuating mechanism is activated the reservoir of activating agent slave unit is delivered in the eye.Typically, location, the application of force and the step of sending are to be finished by a hands.
Utilize the eye contact surface that pressure is put on the eye table and also can be used for producing intraocular pressure, described pressure is between 15mm Hg to the 120mm Hg, between 20mm Hg to the 90mm Hg or the scope between 25mm Hg to the 60mm Hg.As discussed previously, before the deployment of distribution member (conduit), produce intraocular pressure and can reduce the sclera pliability, this then can be convenient to conduit and pierce through sclera, reduce any uncomfortable sensation on eye table during the injection process, and/or prevent the backlash of equipment.Can utilize air relief valve, pressure transducer, accumulator, pressure transducer or parts to produce manually or automatically or keep intraocular pressure control, described parts are for example prominent for the slidably block with lockable mechanism as discussed previously and/or ridge.
The pain that each layer (for example being rich in the conjunctiva of pain nerve ending) that utilizes equipment can reduce the needle-penetration wall of eyeball according to described method followed.Can by before pin injection and/or during apply mechanical pressure in the injection site of conjunctiva and wall of eyeball and be provided within the eye the anaesthetic effect at place, injection site during the injection process.Apply the consolidation (and increasing its elasticity) that mechanical pressure also can temporarily increase intraocular pressure and increase wall of eyeball to wall of eyeball, be convenient to thus the needle-penetration sclera.In addition, the ocular fluids that applies the displaceable inside ofeye of mechanical pressure to wall of eyeball is to form potential space for by the equipment injectable drug.
Equipment can be used for treating any suitable eye situation.Exemplary eye situation includes but not limited to: the retina of any type or macular edema and the disease relevant with retina or macular edema, for example, age-related macular degeneration, diabetic macular edema, cystoid macular edema and postoperative macular edema; Retinal vascular occlusive disease, for example CRVO(central retinal vein occlusion), the BRVO(branch retinal vein occlusion), the CRAO(central retinal artery occlusion), BRAO(branch retinal artery occlusion) and the ROP(retinopathy of prematurity), neovascular glaucoma; Uveitis, center serous chorioretinopathy become; And diabetic retinopathy.
When adopting dexamethasone sodium phosphate solution to treat the eye situation, can by each single injection device be administered to the dexamethasone sodium phosphate in the eye dosage can about 0.05mg between about 5.0mg, about 0.1mg is extremely between about 2.0mg or about 0.4mg scope between about 1.2mg extremely.
In some modification, before being placed on equipment on the eye, local anesthetic is applied on the eye table.Can adopt any suitable local anesthetic.Exemplary local anesthetic includes but not limited to: lignocaine, proparacaine, procaine, tetracaine, betacaine, benzocaine, bupivacaine,
Figure BDA00002490131000411
Figure BDA00002490131000412
(eutectic mixture of local anesthetic) and their combination.In a modification, local anesthetic comprises lignocaine.When adopting lignocaine, can in such concentration range, provide: from about 1% to about 10%, from about 1.5% to about 7% or from about 2% to about 5%.In another modification, local anesthetic mixes with another medicament of the anaesthetic effect of phyenlephrinium or reinforcement and/or prolong drug prescription.Can provide local anesthetic by any suitable form.For example, it can be used as solution, gel, ointment etc. provides.
Also can before being placed on equipment on the eyes, disinfectant be applied on the eye table.The example of suitable disinfectant includes but not limited to: iodine tincture, povidone iodine
Figure BDA00002490131000413
Chlorhexidine, Saponin, antibiotic, salt and its derivant and their combination.Disinfectant can or can not make up application with local anesthetic.When disinfectant comprises povidone iodine
Figure BDA00002490131000414
The time, the concentration of povidone iodine can be from about 1% to about scope of 10%, from about 2.5% to about 7.5% or from about 4% to about 6%.
During delivery process, equipment as herein described can be configured so that entry needle enters eyes with the right angle perpendicular to wall of eyeball (sclera).In other cases, equipment can be configured so that entry needle is parallel to the iris plane earth enters eyes by cornea anterior chamber.
III. system and kit utility
This paper has also described system and the kit utility that comprises intraocular drug delivery equipment.Kit utility can comprise one or more integrated drug delivery devices.This equipment can be pre-installed and be filled with activating agent.When comprising the equipment of a plurality of prefills, they can pack respectively and accommodate identical activating agent or different activating agents, and accommodate the activating agent of same dose or various dose.
System and kit utility also can comprise the manually equipment of filling for the treatment of of one or more respectively packings.If equipment is before manually filling to be used, then a or many parts of active groups of packing respectively can be bonded in the kit utility.Be similar to device systems or the kit utility of prefill, the respectively activating agent of packing in system herein and the kit utility can be identical or different, and can be identical or different by the dosage that the activating agent that each is packed respectively provides.
Certainly, system and kit utility can comprise prefill equipment, the equipment that is used for manually filling and any combination of activating agent.Should also be understood that the operation instruction that also can comprise equipment.In some modification, one or more respectively measurement components of packing can be arranged in system and the kit utility for removably being attached to equipment.Also can comprise local anesthetic and/or disinfectant.
IV. example
Following example is used for more completely describing the method for using intraocular injection equipment mentioned above.Should be understood that this example is used for limiting the scope of the invention never in any form, but propose for purposes of illustration.
Example 1: by the resistance of dynamic sleeve pipe generation
The intraocular injection equipment that will comprise the pin of 30 specifications is fixed to Imada tension test bed and mobile against Imada 10N ergometer ground with 10mm/ minute speed, and described pin is by dynamic sleeve pipe (two-way convergent design, namely each end of sleeve pipe is convergent) covering.When analog casing motion in practice makes sleeve pipe be pushed back to expose pin, measured resistance.This has produced the power of " U " shape and the curve of sleeve pipe displacement, as shown in figure 46.At the resistance of the initial sum destination county of sleeve pipe mobile route greater than the resistance in the middle of the path.In Figure 46, the diagram scope of the resistance that produces can zero newton between about 2 newton or in about 0.1 newton between about 1.0 newton.
In one case, the pin that equals 30 or 31 specifications at the resistance of the section start in the sleeve pipe path required power of human sclera (for example between 0.2 newton to 0.5 newton) that punctures.When adopting the sleeve pipe of higher drag, at the resistance of the section start in sleeve pipe path greater than the pin of 30 or 31 specifications required power of human sclera (for example greater than 1 newton) that punctures.But power is enough low so that the patient is comfortable and avoid potential injury (for example surpassing 60mm Hg to avoid increasing intraocular pressure) to eyes.Centre in the sleeve movement path, resistance approach zero newton.

Claims (94)

1. integrated equipment that is used for intraocular drug delivery, described integrated equipment comprises:
Housing, the size and dimension of described housing are specified to be convenient to a hand operated, and housing has near-end and far-end;
Eye contact surface at the housing far-end;
Measurement component;
The conduit in housing at least in part, the inner chamber that described conduit has near-end, far-end and extends through described conduit;
Actuating mechanism, described actuating mechanism are contained in the housing and the reservoir that may be operably coupled to described conduit and be used for holding activating agent;
Trigger, described trigger are linked to described housing and are configured to trigger described actuating mechanism; And
Be linked to the dynamic stop member of described housing.
2. integrated equipment according to claim 1, wherein said dynamic stop member comprises the slidably element that is linked to described housing.
3. integrated equipment according to claim 2, wherein slidably element comprises dynamic sleeve pipe, described dynamic sleeve pipe has near-end, far-end and inner surface.
4. integrated equipment according to claim 3, wherein dynamically near-end and the far-end of sleeve pipe are convergents.
5. integrated equipment according to claim 4, wherein the dynamic sleeve pipe of convergent and housing are created in 0N to the power between about 2N.
6. integrated equipment according to claim 4, wherein the dynamic sleeve pipe of convergent and housing are created in about 0.1N to the power between about 1N.
7. integrated equipment according to claim 3, wherein dynamically the inner surface of sleeve pipe comprises one or more high friction surfaces that adhere to.
8. integrated equipment according to claim 7, its middle shell comprises one or more high friction surfaces that adhere to.
9. integrated equipment according to claim 8, wherein dynamically the one or more high friction surface that adheres to of sleeve pipe and housing is created in 0N to the power between about 2N.
10. integrated equipment according to claim 8, wherein dynamically the one or more high friction surface that adheres to of sleeve pipe and housing is created in the extremely power between about 1.0N of about 0.1N.
11. integrated equipment according to claim 3, wherein dynamically sleeve pipe also comprises meticulous sleeve pipe mobile control unit.
12. integrated equipment according to claim 1, wherein the eye contact surface comprises ring, flange or their combination.
13. integrated equipment according to claim 12, wherein the eye contact surface comprises ring.
14. integrated equipment according to claim 13, its medium ring have at about 0.3mm to the diameter between about 8mm.
15. integrated equipment according to claim 1, wherein the eye contact surface is flat, protruding or recessed.
16. integrated equipment according to claim 1, wherein the eye contact surface comprises one or more attached components.
17. integrated equipment according to claim 1, wherein the eye contact surface comprises attaching member.
18. integrated equipment according to claim 17, wherein attaching member comprises aspirating mechanism.
19. integrated equipment according to claim 1, wherein the eye contact surface comprises the material that is selected from a set, and described set comprises nylon fiber, cotton fiber, hydrogel, spongy material, polystyrene foam, other foamed materials, silicones, plastics, polypropylene, polyethylene, politef and their combination.
20. integrated equipment according to claim 1, wherein actuating mechanism comprises manual actuation mechanism.
21. integrated equipment according to claim 20, wherein manual actuation mechanism comprises control stick so that slidably the moving ahead of plunger.
22. integrated equipment according to claim 1, wherein actuating mechanism comprises self actuating mechanism.
23. integrated equipment according to claim 22, wherein self actuating mechanism comprises spring-loaded actuating mechanism.
24. integrated equipment according to claim 23, wherein spring-loaded actuating mechanism is configured to bioactive agent delivery to be delivered to the ophthalmic space from about 1 μ l/ second to the speed of about 1ml/ scope second.
25. integrated equipment according to claim 24, wherein spring-loaded actuating mechanism is to deliver to bioactive agent delivery the ophthalmic space from about 10 μ l/ seconds to the speed of about 100 μ l/ scopes second.
26. integrated equipment according to claim 23, wherein spring-loaded actuating mechanism produces about 0.1N to the power of about 1.0N.
27. integrated equipment according to claim 23, wherein spring-loaded actuating mechanism comprises the first spring and the second spring.
28. integrated equipment according to claim 27, wherein the second spring is configured to the delivery rate disposing plunger and control activating agent.
29. integrated equipment according to claim 27, wherein the first spring be configured to conduit from first not deployable state move to the second deployable state and control speed and the power of the deployment of conduit.
30. integrated equipment according to claim 1, wherein actuating mechanism is automatically actuating mechanism of part.
31. integrated equipment according to claim 30, wherein part automatically actuating mechanism comprise control stick so that slidably the moving ahead of plunger.
32. integrated equipment according to claim 30, wherein the automatic actuating mechanism of part comprises spring-loaded actuating mechanism.
33. integrated equipment according to claim 32, wherein spring-loaded actuating mechanism is configured to bioactive agent delivery to be delivered to the ophthalmic space from about 1 μ l/ second to the speed of about 1ml/ scope second.
34. integrated equipment according to claim 32, wherein spring-loaded actuating mechanism is to deliver to bioactive agent delivery the ophthalmic space from about 10 μ l/ seconds to the speed of about 100 μ l/ scopes second.
35. integrated equipment according to claim 32, wherein spring-loaded actuating mechanism produces about 0.1N to the power of about 1.0N.
36. integrated equipment according to claim 32, wherein spring-loaded actuating mechanism comprises the first spring and the second spring.
37. integrated equipment according to claim 36, wherein the second spring is configured to the delivery rate disposing plunger and control activating agent.
38. integrated equipment according to claim 36, wherein the first spring be configured to conduit from first not deployable state move to the second deployable state and control speed and the power of the deployment of conduit.
39. integrated equipment according to claim 1, wherein actuating mechanism is pneumatically actuated mechanism.
40. integrated equipment according to claim 1, wherein activating agent is selected from the set that comprises following material: the steroid antibiotic medicine; the non-steroid antibiotic medicine; anti-infective; antiallergic agent; cholinergic antagonist and agonist; epinephrine antagonist and agonist; antiglaucoma agent; neuroprotective; the medicament that is used for cataract prevention and treatment; antiproliferative; anticarcinogen; complement inhibitor; vitamin; somatomedin; be used for suppressing the medicament of somatomedin; gene therapy vector; chemotherapeutic agents; kinases inhibitor; small molecules interference RNA; their analog; derivant; with the improvement thing; and their combination.
41. integrated equipment according to claim 1, wherein activating agent is selected from the set that comprises following material: Lucentis, bevacizumab, Pei Jianibu, dexamethasone, dexamethasone sodium phosphate, triamcinolone, triamcinolone acetonide, fluocinolone acetonide, taxanes medicine, VEGF Trap, anecortave acetate and do not take charge of compounds of group.
42. integrated equipment according to claim 36, wherein do not take charge of compounds of group and be selected from the set that comprises following material: sirolimus, SDZ-RAD, tacrolimus, everolimus, pimecrolimus, Zuo Tamosi, CCI-779, AP23841 and ABT-578, their analog, derivant, coordination compound, salt and improvement thing and their combination.
43. integrated equipment according to claim 1, wherein reservoir is that resin is made by cyclenes.
44. described integrated equipment according to claim 40, wherein the reservoir derivant of silicate-containing oil or silicone oil not.
45. integrated equipment according to claim 1, wherein measurement component is attached to a contact surface.
46. integrated equipment according to claim 1, wherein measurement component comprises one or more elements that radially extend.
47. described integrated equipment according to claim 46, wherein one or more elements that radially extend comprise the far-end of projection.
48. described integrated equipment according to claim 46, wherein one or more elements that radially extend are flexible.
49. described integrated equipment according to claim 48, wherein measurement component comprises the register guide parts.
50. integrated equipment according to claim 1, wherein the reservoir prepackage is filled with activating agent.
51. integrated equipment according to claim 3, wherein dynamically one of the near-end of sleeve pipe and far-end are convergents.
52. a method that is used for intraocular drug delivery, described method comprises:
Utilize measurement component that a contact surface of integrated equipment is positioned at the eye table upward to determine the injection part bit position, integrated equipment also comprises housing, distribution member, dynamic stop member, is used for holding reservoir and the actuating mechanism of activating agent;
Utilize dynamic stop member that pressure is applied to the place, target injection site that eye is shown; And
By triggering actuating mechanism activating agent is delivered to the eye from reservoir,
Wherein location, the application of force and the step of sending are finished by a hands.
53. 2 described methods according to claim 5, wherein the injection site at about 1mm before the limbus of corneae to limbus of corneae between about 6mm.
54. 2 described methods according to claim 5, wherein the injection site after limbus of corneae about 3mm between about 4mm.
55. 2 described methods according to claim 5, wherein activating agent is prefilled within the reservoir.
56. 2 described methods wherein utilize the medicine filling mechanism that activating agent is filled in the reservoir according to claim 5.
57. 2 described methods according to claim 5, wherein activating agent is selected from the set that comprises following material: the steroid antibiotic medicine; the non-steroid antibiotic medicine; anti-infective; antiallergic agent; cholinergic antagonist and agonist; epinephrine antagonist and agonist; antiglaucoma agent; neuroprotective; the medicament that is used for cataract prevention and treatment; antiproliferative; anticarcinogen; complement inhibitor; vitamin; somatomedin; be used for suppressing the medicament of somatomedin; gene therapy vector; chemotherapeutic agents; kinases inhibitor; small molecules interference RNA; their analog; derivant; coordination compound; with the improvement thing; and their combination.
58. 2 described methods according to claim 5, wherein activating agent is selected from the set that comprises following material: Lucentis, bevacizumab, Pei Jianibu, dexamethasone, dexamethasone sodium phosphate, triamcinolone, triamcinolone acetonide, fluocinolone acetonide, taxanes medicine, VEGF Trap, anecortave acetate and do not take charge of compounds of group.
59. 8 described methods according to claim 5, wherein do not take charge of compounds of group and be selected from the set that comprises following material: sirolimus, SDZ-RAD, tacrolimus, everolimus, pimecrolimus, Zuo Tamosi, CCI-779, AP23841 and ABT-578, their analog, derivant, coordination compound, salt and improvement thing and their combination.
60. 2 described methods according to claim 5, wherein activating agent is used for the treatment of the eye situation, and described eye situation is selected from the set that comprises following situation: macular edema, cystoid macular edema, diabetic macular edema, postoperative macular edema, retinal edema, age-related macular degeneration, BRVO, CRVO, uveitis and center serous chorioretinopathy become.
61. 2 described methods according to claim 5, wherein actuating mechanism is to deliver to bioactive agent delivery the ophthalmic space from about 1 μ l/ second to the speed of about 1ml/ scope second.
62. 2 described methods according to claim 5, wherein actuating mechanism is to deliver to bioactive agent delivery the ophthalmic space from about 5 μ l/ seconds to the speed of about 200 μ l/ scopes second.
63. 2 described methods according to claim 5, wherein actuating mechanism is to deliver to bioactive agent delivery the ophthalmic space from about 10 μ l/ seconds to the speed of about 100 μ l/ scopes second.
64. 2 described methods according to claim 5, wherein actuating mechanism produces the extremely power of about 1.0N of about 0.1N.
65. 2 described methods according to claim 5, wherein dynamically stop member comprises slidably element, and described slidably element is linked to the housing of integrated equipment.
66. 5 described methods according to claim 6, wherein slidably element comprises dynamic sleeve pipe, and described dynamic sleeve pipe has the near-end of convergent and the far-end of convergent.
67. 5 described methods according to claim 6, a step that wherein pressure is applied to the eye table make slidably element retract to expose distribution member.
68. 7 described methods comprise that also manual actuation plunger is with the step of active agent delivery according to claim 6.
69. 2 described methods wherein are applied to pressure a step of table and comprise slidably moving ahead of dynamic stop member according to claim 5.
70. 9 described methods according to claim 6, wherein dynamically slidably moving ahead of sleeve pipe produces power from 0N to about 2N between himself and housing.
71. 9 described methods according to claim 6, wherein dynamically slidably moving ahead of sleeve pipe produces the power of about 1N extremely from about 0.1N between himself and housing.
72. 9 described methods according to claim 6, it is manually adjustable wherein slidably moving ahead.
73. 9 described methods according to claim 6, it is automatically adjustable wherein slidably moving ahead.
74. 2 described methods according to claim 5, wherein dynamically stop member comprises the wall of eyeball tension control mechanism.
75. an integrated equipment that is used for intraocular drug delivery, described integrated equipment comprises:
Housing, the size and dimension of described housing are specified to be convenient to a hand operated, and housing has near-end and far-end;
Eye contact surface at the housing far-end;
Measurement component;
The conduit in housing at least in part, the inner chamber that described conduit has near-end, far-end and extends through described conduit;
Actuating mechanism, described actuating mechanism are contained in the housing and the reservoir that may be operably coupled to described conduit and be used for holding activating agent;
Trigger, described trigger are linked to described housing and are configured to trigger described actuating mechanism; And
Be linked to the wall of eyeball tension control mechanism of described housing.
76. 5 described integrated equipments according to claim 7, wherein said wall of eyeball tension control mechanism comprises the slidably block with lockable mechanism.
77. 6 described integrated equipments according to claim 7, wherein lockable mechanism is manually operated mechanism.
78. 6 described integrated equipments according to claim 7, wherein lockable mechanism is the mechanism of automatic operation.
79. 6 described integrated equipments according to claim 7, wherein lockable mechanism comprises lock pin.
80. 6 described integrated equipments according to claim 7, wherein slidably block comprises one or more high friction surfaces that adhere to.
81. the ridge that 0 described integrated equipment according to claim 8, wherein one or more height adhere on the inner surface that friction surface is included in block slidably is prominent.
82. 5 described integrated equipments according to claim 7, wherein the wall of eyeball tension control mechanism comprises pressure transducer.
83. 5 described integrated equipments according to claim 7, wherein the wall of eyeball tension control mechanism comprises accumulator.
84. a method that is used for intraocular drug delivery, described method comprises:
Utilize measurement component that the eye contact surface of integrated equipment is positioned the eye table upward to determine the injection part bit position, integrated equipment also comprises housing, distribution member, wall of eyeball tension force control assembly, is used for holding reservoir and the actuating mechanism of activating agent;
Utilize wall of eyeball tension force control assembly that pressure is applied to the place, target injection site that eye is shown; And
By triggering actuating mechanism activating agent is delivered to the eye from reservoir,
Wherein location, the application of force and the step of sending are finished by a hands.
85. 4 described methods wherein are applied to pressure a step of table and comprise slidably moving ahead of wall of eyeball tension force control assembly according to claim 8.
86. 5 described methods according to claim 8, wherein slidably moving ahead of wall of eyeball tension control mechanism produces power from 0N to about 2N scope between himself and housing.
87. 5 described methods according to claim 8, wherein slidably moving ahead of wall of eyeball tension force control assembly produces the power of about 1N scope extremely from about 0.1N between himself and housing.
88. an injection device that is used for intraocular drug delivery, described injection device comprises:
Housing, the size and dimension of described housing are specified to be convenient to a hand operated, and housing has near-end and far-end;
Eye contact surface at the housing far-end;
The conduit in housing at least in part, the inner chamber that described conduit has near-end, far-end and extends through described conduit;
Actuating mechanism, described actuating mechanism are contained in the housing and the reservoir that may be operably coupled to described conduit and be used for holding activating agent;
Trigger, described trigger are linked to described housing and are configured to the described actuating mechanism of triggering; And
Dynamic stop member.
89. 8 described injection devices according to claim 8, wherein dynamically stop member comprises dynamic sleeve pipe, and described dynamic sleeve pipe has near-end, far-end and inner surface.
90. 9 described injection devices according to claim 8, wherein dynamically near-end and the far-end of sleeve pipe are convergents.
91. 9 described injection devices according to claim 8, wherein dynamically one of the near-end of sleeve pipe and far-end are convergents.
92. 9 described injection devices according to claim 8, wherein dynamically the inner surface of sleeve pipe comprises that ridge is prominent.
93. 8 described injection devices according to claim 8, wherein dynamically sleeve pipe also comprises meticulous sleeve pipe mobile control unit.
94. 8 described injection devices according to claim 8, wherein said injection device also comprises measurement component.
CN201180026683.2A 2010-03-31 2011-03-31 Equipment and method for intraocular drug delivery Active CN103037802B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201610621429.1A CN106137528B (en) 2010-03-31 2011-03-31 Apparatus and method for intraocular drug delivery

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US34158210P 2010-03-31 2010-03-31
US61/341,582 2010-03-31
US38463610P 2010-09-20 2010-09-20
US61/384,636 2010-09-20
PCT/US2011/030840 WO2011123722A1 (en) 2010-03-31 2011-03-31 Device and method for intraocular drug delivery

Related Child Applications (1)

Application Number Title Priority Date Filing Date
CN201610621429.1A Division CN106137528B (en) 2010-03-31 2011-03-31 Apparatus and method for intraocular drug delivery

Publications (2)

Publication Number Publication Date
CN103037802A true CN103037802A (en) 2013-04-10
CN103037802B CN103037802B (en) 2016-08-24

Family

ID=47017193

Family Applications (2)

Application Number Title Priority Date Filing Date
CN201180026683.2A Active CN103037802B (en) 2010-03-31 2011-03-31 Equipment and method for intraocular drug delivery
CN201610621429.1A Active CN106137528B (en) 2010-03-31 2011-03-31 Apparatus and method for intraocular drug delivery

Family Applications After (1)

Application Number Title Priority Date Filing Date
CN201610621429.1A Active CN106137528B (en) 2010-03-31 2011-03-31 Apparatus and method for intraocular drug delivery

Country Status (4)

Country Link
EP (1) EP2552349A4 (en)
JP (2) JP5931847B2 (en)
CN (2) CN103037802B (en)
AU (1) AU2011235002B2 (en)

Cited By (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105246529A (en) * 2013-05-03 2016-01-13 科尼尔赛德生物医学公司 Apparatus and methods for ocular injection
CN105979914A (en) * 2013-12-18 2016-09-28 诺华股份有限公司 Systems and methods for subretinal delivery of therapeutic agents
CN105979985A (en) * 2013-10-07 2016-09-28 奥库杰克特有限责任公司 Intraocular delivery devices and methods therefor
CN106029137A (en) * 2014-01-21 2016-10-12 肠外技术有限责任公司 Force actuated injection device
CN106232170A (en) * 2014-02-17 2016-12-14 杰夫·贝克 The system and method detected and prevent wet type from injecting
CN106456757A (en) * 2014-05-12 2017-02-22 福尔密孔股份公司 Pre-filled plastic syringe containing VEGF antagonist
CN106975128A (en) * 2014-02-26 2017-07-25 普乐药业有限公司 Device for delivery of particles
CN107809962A (en) * 2015-05-19 2018-03-16 伊西康有限责任公司 With the administration device with gripping features portion end cap
TWI622414B (en) * 2015-08-28 2018-05-01 拜耳保健公司 System and method for syringe fluid fill verification and image recognition of power injector system features
CN108697413A (en) * 2015-09-25 2018-10-23 埃德温·瑞安 Dynamic support for ophthalmological instruments
CN109121390A (en) * 2014-06-06 2019-01-01 轨道生物医学有限公司 Therapeutic agent delivery device with convergence lumen
US10188550B2 (en) 2013-06-03 2019-01-29 Clearside Biomedical, Inc. Apparatus and methods for drug delivery using multiple reservoirs
CN109843229A (en) * 2016-09-30 2019-06-04 领视药公司 By the pinpoint accuracy drug delivery of dual domain device for eyes
CN111712229A (en) * 2017-09-15 2020-09-25 奥叙拉尔有限公司 Ophthalmic delivery device
US10952894B2 (en) 2010-10-15 2021-03-23 Clearside Biomedical, Inc. Device for ocular access
US10973681B2 (en) 2016-08-12 2021-04-13 Clearside Biomedical, Inc. Devices and methods for adjusting the insertion depth of a needle for medicament delivery
CN112972682A (en) * 2014-10-19 2021-06-18 阿祖拉眼科有限公司 Compositions and methods for treating meibomian gland dysfunction
CN114191120A (en) * 2021-12-20 2022-03-18 山东大学 Orthodontic tooth surface acid etching device
WO2022236778A1 (en) * 2021-05-13 2022-11-17 Beijing Sightnovo Medical Technology Co., Ltd Medical penetration device and system
US11596545B2 (en) 2016-05-02 2023-03-07 Clearside Biomedical, Inc. Systems and methods for ocular drug delivery
US11752101B2 (en) 2006-02-22 2023-09-12 Clearside Biomedical, Inc. Ocular injector and methods for accessing suprachoroidal space of the eye
US12011457B2 (en) 2016-04-14 2024-06-18 Azura Ophthalmics Ltd Selenium disulfide compositions for use in treating meibomian gland dysfunction

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PL2391419T3 (en) 2009-01-29 2019-12-31 Forsight Vision4, Inc. Posterior segment drug delivery
US9504603B2 (en) 2012-04-02 2016-11-29 Ocuject, Llc Intraocular delivery devices and methods therefor
SG11201607021VA (en) * 2014-02-26 2016-09-29 Allergan Inc Intraocular implant delivery apparatus and methods of use thereof
EP3377009B1 (en) * 2015-11-20 2020-10-28 ForSight Vision4, Inc. Porous structures for extended release drug delivery devices
CN111278401B (en) * 2017-05-30 2023-08-15 艾克思摩尔有限公司 Compositions and methods for delivering antibiotic macrolides to treat dry eye syndrome
CN109431678B (en) * 2018-12-17 2021-05-28 中国医学科学院北京协和医院 Transscleral drug delivery system
CN110471318B (en) * 2019-06-26 2022-05-10 康美药业股份有限公司 Intelligent control system of pharmacy heating furnace
FI129077B (en) * 2020-06-29 2021-06-30 Optomed Oyj Contact arrangement for eye examining instrument, eye examining instrument and method of contacting between eye and eye examining instrument
WO2024099420A1 (en) * 2022-11-11 2024-05-16 Beijing Sightnovo Medical Technology Co., Ltd Drug-containing devices, suprachoroidal space implants, and adapters for injection
WO2024099421A1 (en) * 2022-11-11 2024-05-16 Beijing Sightnovo Medical Technology Co., Ltd Precise and controlled injection for intercostal nerve block

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20010008961A1 (en) * 1998-08-03 2001-07-19 Hecker Karl I. Injection apparatus and method of using same
US20030060763A1 (en) * 2000-01-06 2003-03-27 Penfold Philip Leslie Guide means for intraocular injection
US20070005016A1 (en) * 2005-06-20 2007-01-04 Williams David F Ocular injection device and method
US20100030150A1 (en) * 2007-01-09 2010-02-04 Fovea Pharmaceuticals Apparatus for intra-ocular injection
US7678078B1 (en) * 2008-10-21 2010-03-16 KMG Pharma LLC Intravitreal injection device, system and method

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1230219C (en) * 2001-04-13 2005-12-07 贝克顿迪肯森公司 Prefillable intradermal injector
US7481818B2 (en) * 2003-10-20 2009-01-27 Lifescan Lancing device with a floating probe for control of penetration depth
US20080097390A1 (en) * 2006-09-27 2008-04-24 Alcon Manufacturing, Ltd. Spring actuated delivery system
ES2336611T3 (en) * 2007-03-14 2010-04-14 Wavelight Ag APPARATUS FOR THE COUPLING OF AN ELEMENT TO THE EYE.
US20090005788A1 (en) * 2007-06-26 2009-01-01 Rathert Brian D Intraocular Lens Injector
US20100305514A1 (en) * 2008-01-10 2010-12-02 Bausch & Lomb Incorporated Intravitreal injection system having coaxial cannulae and use thereof

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20010008961A1 (en) * 1998-08-03 2001-07-19 Hecker Karl I. Injection apparatus and method of using same
US20030060763A1 (en) * 2000-01-06 2003-03-27 Penfold Philip Leslie Guide means for intraocular injection
US20070005016A1 (en) * 2005-06-20 2007-01-04 Williams David F Ocular injection device and method
US20100030150A1 (en) * 2007-01-09 2010-02-04 Fovea Pharmaceuticals Apparatus for intra-ocular injection
US7678078B1 (en) * 2008-10-21 2010-03-16 KMG Pharma LLC Intravitreal injection device, system and method

Cited By (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11752101B2 (en) 2006-02-22 2023-09-12 Clearside Biomedical, Inc. Ocular injector and methods for accessing suprachoroidal space of the eye
US11944703B2 (en) 2006-02-22 2024-04-02 Clearside Biomedical, Inc. Ocular injector and methods for accessing suprachoroidal space of the eye
US10952894B2 (en) 2010-10-15 2021-03-23 Clearside Biomedical, Inc. Device for ocular access
US10722396B2 (en) 2013-05-03 2020-07-28 Clearside Biomedical., Inc. Apparatus and methods for ocular injection
US10517756B2 (en) 2013-05-03 2019-12-31 Clearside Biomedical, Inc Apparatus and methods for ocular injection
CN105246529B (en) * 2013-05-03 2019-06-14 科尼尔赛德生物医学公司 Device and method for ocular injection
US11559428B2 (en) 2013-05-03 2023-01-24 Clearside Biomedical, Inc. Apparatus and methods for ocular injection
US10555833B2 (en) 2013-05-03 2020-02-11 Clearside Biomedical, Inc. Apparatus and methods for ocular injection
CN105246529A (en) * 2013-05-03 2016-01-13 科尼尔赛德生物医学公司 Apparatus and methods for ocular injection
US10188550B2 (en) 2013-06-03 2019-01-29 Clearside Biomedical, Inc. Apparatus and methods for drug delivery using multiple reservoirs
CN105979985A (en) * 2013-10-07 2016-09-28 奥库杰克特有限责任公司 Intraocular delivery devices and methods therefor
CN105979985B (en) * 2013-10-07 2021-11-02 奥库杰克特有限责任公司 Intraocular delivery device and method thereof
CN105979914B (en) * 2013-12-18 2018-03-27 诺华股份有限公司 System and method for being delivered under the retina of therapeutic agent
US10010447B2 (en) 2013-12-18 2018-07-03 Novartis Ag Systems and methods for subretinal delivery of therapeutic agents
CN105979914A (en) * 2013-12-18 2016-09-28 诺华股份有限公司 Systems and methods for subretinal delivery of therapeutic agents
CN106029137A (en) * 2014-01-21 2016-10-12 肠外技术有限责任公司 Force actuated injection device
CN106232170A (en) * 2014-02-17 2016-12-14 杰夫·贝克 The system and method detected and prevent wet type from injecting
CN106975128A (en) * 2014-02-26 2017-07-25 普乐药业有限公司 Device for delivery of particles
CN106975128B (en) * 2014-02-26 2021-02-26 普乐药业有限公司 Device for delivering particles
CN106456757A (en) * 2014-05-12 2017-02-22 福尔密孔股份公司 Pre-filled plastic syringe containing VEGF antagonist
CN109121390A (en) * 2014-06-06 2019-01-01 轨道生物医学有限公司 Therapeutic agent delivery device with convergence lumen
CN109121390B (en) * 2014-06-06 2020-12-11 陀螺仪治疗学有限公司 Therapeutic agent delivery device with converging lumen
US11633410B2 (en) 2014-10-19 2023-04-25 Azura Ophthalmics Ltd Compositions and methods for the treatment of meibomian gland dysfunction
CN112972682A (en) * 2014-10-19 2021-06-18 阿祖拉眼科有限公司 Compositions and methods for treating meibomian gland dysfunction
CN107809962B (en) * 2015-05-19 2021-02-02 伊西康有限责任公司 Applicator instrument with end cap with gripping feature
CN107809962A (en) * 2015-05-19 2018-03-16 伊西康有限责任公司 With the administration device with gripping features portion end cap
TWI622414B (en) * 2015-08-28 2018-05-01 拜耳保健公司 System and method for syringe fluid fill verification and image recognition of power injector system features
US11278449B2 (en) 2015-09-25 2022-03-22 Edwin Ryan Dynamic support for ophthalmic device
CN108697413A (en) * 2015-09-25 2018-10-23 埃德温·瑞安 Dynamic support for ophthalmological instruments
US11998484B2 (en) 2015-09-25 2024-06-04 Edwin Ryan Dynamic support for ophthalmic device
US12011457B2 (en) 2016-04-14 2024-06-18 Azura Ophthalmics Ltd Selenium disulfide compositions for use in treating meibomian gland dysfunction
US11596545B2 (en) 2016-05-02 2023-03-07 Clearside Biomedical, Inc. Systems and methods for ocular drug delivery
US10973681B2 (en) 2016-08-12 2021-04-13 Clearside Biomedical, Inc. Devices and methods for adjusting the insertion depth of a needle for medicament delivery
CN109843229A (en) * 2016-09-30 2019-06-04 领视药公司 By the pinpoint accuracy drug delivery of dual domain device for eyes
CN111712229A (en) * 2017-09-15 2020-09-25 奥叙拉尔有限公司 Ophthalmic delivery device
WO2022236778A1 (en) * 2021-05-13 2022-11-17 Beijing Sightnovo Medical Technology Co., Ltd Medical penetration device and system
CN114191120A (en) * 2021-12-20 2022-03-18 山东大学 Orthodontic tooth surface acid etching device

Also Published As

Publication number Publication date
CN103037802B (en) 2016-08-24
JP2013523283A (en) 2013-06-17
JP5931847B2 (en) 2016-06-08
EP2552349A4 (en) 2017-12-06
CN106137528B (en) 2020-12-01
JP2016135355A (en) 2016-07-28
AU2011235002B2 (en) 2016-08-11
JP6302504B2 (en) 2018-03-28
CN106137528A (en) 2016-11-23
AU2011235002A1 (en) 2012-10-18
EP2552349A1 (en) 2013-02-06

Similar Documents

Publication Publication Date Title
CN103037802B (en) Equipment and method for intraocular drug delivery
US11865039B2 (en) Intraocular delivery devices and methods therefor
JP6941649B2 (en) Needle assembly
US10905587B2 (en) Device and method for intraocular drug delivery
US10251779B2 (en) Device and method for intraocular drug delivery
US9421129B2 (en) Intraocular delivery devices and methods therefor
CA2795096A1 (en) Device and method for intraocular drug delivery
US20220015945A1 (en) Device and method for intraocular drug delivery
US20240139025A1 (en) Luer taper with low dead space element

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant