CN101099878A - Punctal plugs for the delivery of active agents - Google Patents

Punctal plugs for the delivery of active agents Download PDF

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Publication number
CN101099878A
CN101099878A CNA2007101379157A CN200710137915A CN101099878A CN 101099878 A CN101099878 A CN 101099878A CN A2007101379157 A CNA2007101379157 A CN A2007101379157A CN 200710137915 A CN200710137915 A CN 200710137915A CN 101099878 A CN101099878 A CN 101099878A
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CN
China
Prior art keywords
main body
activating agent
punctal plug
polymeric material
poly
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CNA2007101379157A
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Chinese (zh)
Inventor
M·J·博尔吉亚
H·朝
H·崔
W·R·拉尔多
Z·李
A·纳坦
M·J·特雷扎
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Johnson and Johnson Vision Care Inc
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Johnson and Johnson Vision Care Inc
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Publication of CN101099878A publication Critical patent/CN101099878A/en
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    • 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
    • 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
    • A61F9/007—Methods or devices for eye surgery
    • A61F9/00772—Apparatus for restoration of tear ducts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A61K9/0004—Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0048—Eye, e.g. artificial tears
    • A61K9/0051—Ocular inserts, ocular implants
    • 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
    • A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0058—Additional features; Implant or prostheses properties not otherwise provided for
    • A61F2250/0067—Means for introducing or releasing pharmaceutical products into the body
    • A61F2250/0068—Means for introducing or releasing pharmaceutical products into the body the pharmaceutical product being in a reservoir

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  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Biomedical Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Vascular Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Plastic & Reconstructive Surgery (AREA)
  • Surgery (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Materials For Medical Uses (AREA)
  • Closures For Containers (AREA)
  • Compositions Of Macromolecular Compounds (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Prostheses (AREA)

Abstract

The invention provides punctal plugs for the delivery of active agents. The plugs have a body throughout which at least one active agent is dispersed or that is coated with a polymeric material containing at least one active agent.

Description

The Punctal plug that is used for delivery of active agents
Invention field
The present invention relates to be suitable for equipment, particularly, the present invention relates to be used to carry the Punctal plug of at least a activating agent to one or more eyes, N﹠T transportation of substances.
Related application
It is 60/805,380 priority that the application requires in the U.S. Provisional Application series number that on June 21st, 2006 submitted to.
Background of invention
People's tear by lacrimal secretion and the surface of flowing through eyes to the on-swimmer's pool that is called as cus lacrimalis that is arranged in the inner junction of eyelid.From here, tear are discharged by opening little in each eyelid that is called lacrimal point and following lacrimal point respectively.From lacrimal point up and down, tear are respectively through the last lower lacrimal canaliculi of the pipe-like path that leads to lachrymal sac.Lachrymal sac is the top expansion of nasolacrimal duct, and it enters tear in the nasus system.Activating agent can be transported to N﹠T by lacrimal ductule like this, this lacrimal ductule leads to nasolacrimal duct.
Usually give disease or the discomfort of eyes administering active agents with the treatment eyes.Being used for conventional means to the eyes delivery of active agents comprises to the surface of eyes and carries out local application.Eyes are unique local applications that are suitable for, because when making up when suitable, the permeable cornea of local application activating agent also improves the treatment concentration level of ophthalmic.Being used for disease of eye or uncomfortable activating agent also can be oral or by injection, but these administration paths are disadvantageous, because in oral administration, the surfactant concentration of eyes is too low not to have required drug effect and their use to be subjected to significant system side effects and the complexity that becomes to such an extent as to can arrive, and injection has brought the risk that infects.
Most eye activating agent uses eye drop to carry at present, is effectively though use eye drop for some, its inefficiency.When the eye drop of liquid is added in the eyes, it can overflow conjunctival sac, and the capsule bag between eyes and the eyelid causes eye drop greatly to flow on the cheek and lose owing to overflowing eyelid.In addition, a big chunk eye drop that keeps on the eye surface is discharged in the lacrimal point, the concentration of diluent.
Description of drawings
Fig. 1 is the profile with Punctal plug of main body 10.Activating agent 18 is distributed in the entire body.
Fig. 2 is the profile with Punctal plug of main body 20, and this main body 20 has enlarged 22.Activating agent 28 is distributed in the entire body.
Fig. 3 is the profile that has the Punctal plug with main body 30 and eckband 34 of enlarged 32.Activating agent 38 is dispersed in the entire body 30.
Fig. 4 is the profile with Punctal plug of main body 40.Activating agent 48 is distributed in the entire body 40, and the whole main bodys except that a part of main body 41 coated film 43.
Fig. 5 is the profile with Punctal plug of main body 50, and this main body 50 has enlarged 52.Activating agent 58 is dispersed in the entire body 50, and the whole main bodys except that a part of main body 51 coated film 53.
Fig. 6 is the profile with Punctal plug of the main body 60 that has enlarged 62 and eckband 64.Activating agent 68 is dispersed in the entire body 60, and the whole main bodys except that a part of main body 61 coated film 63.
Fig. 7 is the profile with Punctal plug of main body 70, and this main body 70 has enlarged 72.The polymeric material 78 that this main body 70 is contained activating agent applies.
Fig. 8 is the profile with Punctal plug of the main body 80 that has enlarged 82 and eckband 84.The polymeric material 88 that this main body and eckband are contained activating agent applies.
Fig. 9 is the profile with Punctal plug of the main body 90 that has enlarged 92 and eckband 94.This main body contains the groove 95 that increases its surface area.The polymeric material 98 that this main body and eckband are contained activating agent applies.
Figure 10 is the 3-D view of the Punctal plug described of Fig. 6 two dimension.This Punctal plug has main body 100 and the eckband 104 that has enlarged 102.Activating agent is dispersed in the entire body 100, and the whole main bodys except that a part of main body 101 coated film 103.
The specific embodiment
The invention provides the Punctal plug that can be used for active agent delivery is given one or two nasolacrimal duct and eyes tear.In one embodiment, the invention provides Punctal plug, its comprise following, constitute and constitute by following substantially by following: have first end, second end and the main body of the side surface that between two ends, extends; Wherein in entire body, contain at least a activating agent.
In a certain Punctal plug of being described in as Fig. 1,2 and 3, activating agent is dispersed in the whole plug main body, and for example when body dissolves or when degraded, discharges activating agent, perhaps diffuses out activating agent from main body, and this depends on the material of making main body.Alternatively, as among Fig. 4,5,6 and 10 institute illustrational, activating agent be dispersed in the entire body and the whole main bodys except at least a portion Punctal plug coated the film of impermeable activating agent.Activating agent discharges by a part and a plurality of part uncoated on the main body.
Further apply Punctal plug with the polymeric material that comprises activating agent.In such embodiment and with reference to figure 9, Punctal plug has one or more on main body 90, and preferably at least two kinds of grooves 95 are to increase its surface area.When coating dissolving or degraded, activating agent is discharged from coating 98, and perhaps activating agent diffuses out from this coating, and this depends on the polymeric material of making coating.
For with active agent delivery in the tear of eyes, be inserted into Punctal plug in the lacrimal ductule and activating agent be discharged in the tear of eyes.With reference to figure 2, in order to be transported in the tear, preferably eckband 34 is connected on the main body of Punctal plug, and when Punctal plug being inserted in this lacrimal ductule, eckband 34 is resisted against dacryocanalicular outside.For with active agent delivery in nasolacrimal duct, Punctal plug is inserted, preferably be inserted in the lacrimal ductule dearly, and activating agent is released in the nasolacrimal duct.In certain embodiments of the present invention, and for example set forth among Fig. 2,3,5,6,7,8 and 9, main body contains enlarged 22,32,52,62,72,82 and 92 respectively, and they are fixed on Punctal plug in the lacrimal ductule.
As used herein, term " Punctal plug " refer to size and shape be suitable for by down or on lacrimal point be inserted into equipment in the following or superior canaliculus of eyes.
As used herein, term " activating agent " refers to energy treatment, inhibition or prevent disease or uncomfortable preparation.Representational activating agent includes but not limited to medicine and nutrient.Preferred activating agent can treat, suppress or prevent one or more, the disease or the discomfort of N﹠T.
As used herein, term " to the water miscible material of small part " thus refer to the dissolubility that in water, shows certain enough levels in case be exposed to the material that causes perceptible material dissolves in the water environment.
As used herein, term " biodegradable " material " in case refer to and be exposed to the material that is degraded to discernable degree when being present in the intravital bioactive substance of mammal usually.
As used herein, term " water-fast material " is in case refer to and be exposed to the material that can not decompose in a large number in the water.
As used herein, term " not biodegradable material " in case refer to is exposed to non-degradable material to substantial degree when being present in the intravital bioactive substance of mammal usually.
As used herein, the term film of osmotically active agent " can not " only refers to that the activating agent of the amount of unsubstantiality can pass through this film.
As used herein, term " film of the porous water " water that refers to discernable level can pass through this film.
As used herein, term " groove ", " a plurality of groove " and various deformed finger thereof are for any size of the punctal plug body of the surface area that can increase main body effectively and the indenture of shape.
The present invention comprises numerous being used for active agent delivery to the tear of eyes or the Punctal plug of nasolacrimal duct.Preferably be inserted into this Punctal plug in the lower lacrimal canaliculi, in the superior canaliculus or go up in the lower lacrimal canaliculi.If this Punctal plug is used for the tear of active agent delivery to eyes, this Punctal plug preferably has eckband at an end of main body.This eckband is the part of Punctal plug, and its end from main body extends radially outwardly into sufficient degree, makes at least a portion eckband extend beyond and be positioned at the outside of lacrimal point after Punctal plug is inserted into lacrimal ductule.This part Punctal plug that does not have eckband is inserted into down lacrimal point or goes up one of them of lacrimal point, they are openings of each eyelid superior canaliculus.With reference to figure 3, part 32 and the main body 30 that enlarges is inserted into one of them lacrimal point, and eckband 34 is resisted against the outside of lacrimal point and prevents Punctal plug landing from the lacrimal ductule, thereby keep contacting between Punctal plug and eyes tear.This eckband can be enough to Punctal plug at least partial fixing in any size and the shape at lacrimal point place.
If this Punctal plug is used for active agent delivery to nasolacrimal duct, then this Punctal plug does not preferably have eckband to make they can be inserted into one or two dacryocanalicular abundant degree of depth, thereby activating agent is discharged in the lachrymal sac.In Fig. 1,2 and 4, described to be used for the example of active agent delivery to the Punctal plug of nasolacrimal duct.
Each of the numerous Punctal plugs of the present invention has various features and advantage.For example, certain Punctal plug has the main body with first end and second end and the side surface that extends between these two ends.This side surface preferably has shape and is essentially circular outer diameter.The part of the side surface of certain Punctal plug has the external diameter bigger than the external diameter of the remainder of side surface.With reference to figure 5, the enlarged 52 of side surface is with the Punctal plug anchoring or be fixed in the lacrimal ductule.The part of this expansion can be any size or shape, and can be present on any part of side surface, as long as this enlarged is anchored at Punctal plug to small part in the lacrimal ductule.Easily, this enlarged can take to have the upside-down triangle shape on flat summit.
In some Punctal plug, at least a activating agent is arranged in, spreads all over to scatter or otherwise be included in spread all over the main body of whole Punctal plug basically, make main body itself be used as the carrier of activating agent.In certain embodiments of the present invention, preferably have in the Punctal plug of eckband at those, activating agent is discharged into from main body in the tear of eyes.Activating agent also can be discharged in the nasolacrimal duct from main body.In particular aspects of the present invention, activating agent is discharged into from main body in the tear and nasolacrimal duct of eyes.
According to the material of making main body, this activating agent can almost discharge from main body immediately, or this activating agent can be released in a continuous manner in required a period of time.For example, this main body can be by being that the polymeric material that is partially soluble in water is made at least.When in the water environment that such main body is exposed to lacrimal ductule or tear, it preferably will dissolve and release bioactive agent when it dissolves.Usually will be directly proportional with its decomposition rate by its water-soluble of making the polymeric material of main body.At least the suitable polymers that is partially soluble in water includes but not limited to gather (ethylene glycol); Poly-(ethylene oxide); Poly-(propylene glycol); Poly-(vinyl alcohol); Poly-(methacrylate hydroxyethyl ester); Poly-(vinylpyrrolidone); Polyacrylic acid; Poly-(ethyl  azoles quinoline); Poly-(DMAA); Phospholipid is such as, but not limited to the Phosphorylcholine derivant; Poly-sulfobetaines; Polysaccharide and carbohydrate, all like hyaluronic acids, dextran, hydroxyethyl-cellulose, hydroxypropyl cellulose, gelling carbohydrate gum, guar gum, Heparan sulfate, chondroitin sulfate, heparin and alginate; Protein includes but not limited to gelatin, collagen, albumin and ovalbumin; And polyamino acid.Polymeric material in this tabulation common and hydrophobic polymer, monomer or both copolymerization or blend.
Alternatively, for those Punctal plugs of main body wherein as the carrier of activating agent, the main body of this Punctal plug can be made by biodegradable polymeric material, and in a single day this material is exposed in the bioactive substance that for example exists in mammalian body usually, and chemical degradation can take place.This biodegradable material preferably is hydrolyzed under the organism condition of living.Biodegradation take place usually, more constantly release bioactive agent slower, slower so if desired than dissolving, this plug main body can be made by biodegradable material.Suitable polymeric Biodegradable material includes but not limited to the polymer and the oligomer of Acetic acid, hydroxy-, bimol. cyclic ester, lactide, 6-caprolactone and other hydroxy acid, and produces nontoxic or be present in other biodegradable polymer of intravital material as the homergy thing.Preferred poly-('alpha '-hydroxy acids) is poly-(glycolic), poly-(2-is to dioxanone); Poly-(DL-lactic acid) and poly-(L-lactic acid).Other available materials comprise poly-(aminoacid), Merlon, poly-(acid anhydride), poly-(ortho esters), poly-(phosphazine) and poly-(phosphate ester).Such as the polylactone of poly-(6-caprolactone), poly-(δ-caprolactone), poly-(δ-Wu Neizhi) and poly-(gamma-butyrolacton), also be useful for example as chitosan, alginate, collagen and gelatin.The present invention specific aspect, the polymeric material of making main body can be made of one or more dissolubilities and biodegradable mixture of polymers.
Can make from the polymeric material that wherein diffuses out by water insoluble and not biodegradable but activating agent alternatively as those punctal plug body of the carrier of activating agent.The suitable polymeric materials of this quasi-representative includes but not limited to crosslinked polymer, all like crosslinked poly-(ethylene glycol); Poly-(ethylene oxide); Poly-(propylene glycol); Poly-(vinyl alcohol); Poly-(methacrylate hydroxyethyl ester); Poly-(vinylpyrrolidone); Polyacrylic acid; Poly-(ethyl  azoles quinoline); Poly-(DMAA).These polymer can or mix with hydrophobic polymer, monomer or both copolymerization.As water insoluble and be that the other polymeric material of not biodegradable polymer includes but not limited to silicones, silicone compound; The resinous copolymeric siloxane thing, hydrophilic monomer, Polyethylene Glycol, polyvinylpyrrolidone and the glycerol of all like pHEMA (poly hydroxy ethyl acrylate); And the silicone hydrogel polymer, all like U.S. Patent numbers 5,962,548,6,020,445,6,099,852,6,367,929 and 6,822, those materials described in 016, these patents all are incorporated into this as a reference; Phospholipid includes but not limited to the Phosphorylcholine derivant; Poly-sulfobetaines; Polysaccharide and carbohydrate, all like hyaluronic acids, dextran, hydroxyethyl-cellulose, hydroxypropyl cellulose, gelling carbohydrate gum, guar gum, Heparan sulfate, chondroitin sulfate, heparin and alginate; The all like gelatins of protein, collagen, albumin and ovalbumin; Polyamino acid; Fluoropolymer polymer, all like politef (" PTFE "), polyvinylidene fluoride (" PVDF ") and special teflon; Polypropylene; Polyethylene; Nylon; And ethylene-vinyl alcohol (" EVA ").Other example water insoluble or not biodegradable or that satisfy the two suitable polymers includes but not limited to silicones, polyurethane, cyanoacrylate, polyacrylic acid, fibrin and crosslinking protein, all like albumin and collagen-gelatin.
The amount that is used in plug of the present invention activating agent beyond the Great Wall will depend on selected activating agent or multiple actives, treat fusing point and dissolubility through required dosage, required rate of release and the activating agent and the polymeric material of Punctal plug conveying.Preferably, used amount is a therapeutically effective amount, this means the effective dose that can realize required treatment, inhibition or preventive effect.Usually, use about 0.05 amount to about 20,000 microgram activating agents.Activating agent will be for about 10 to about 90% to the ratio of polymeric material, and be preferably about 20 to about 50%.
In vivo as the Punctal plug of at least a active agent carrier can utilize comprise all like solution-casts, extruding, by forming covalent bond or ionic bond chemical crosslinking, car system, pressing mold, injection molding, liquid injection molding, blowing mould and comprise that the processing of the technology such as polymerization of photopolymerization, thermal polymerization and ionization polymerization and redox polymerization makes.Join in the material that in making the main body process, constitutes main body by the living agent of will living, perhaps after they are made, activating agent is joined in the main body of Punctal plug, this activating agent can be joined in the Punctal plug, for example activator solution is immersed in the prefabricated main body.
The film of available impermeable activating agent applies all surface except that the part of punctal plug body, and wherein said main body is used as the carrier of activating agent, makes this activating agent only be released from uncoated main part.Uncoated part can if there are words in eckband, comprise eckband at any part place of main body, and this depends on the position of wishing that activating agent discharges.In certain embodiments of the present invention, when being inserted into Punctal plug in the lacrimal ductule, the uncoated part of main body is faced eyes, and activating agent is discharged in the tear of eyes.In the present invention was aspect other, when being inserted into Punctal plug in the lacrimal ductule, the uncoated part of main body was in the face of nasolacrimal duct, and activating agent is discharged in the nasolacrimal duct.In additional embodiments of the present invention, when being inserted into Punctal plug in the lacrimal ductule, the uncoated part of main body is faced eyes and nasolacrimal duct, and activating agent is discharged in the tear and nasolacrimal duct of eyes.
This coating is preferably made by the material of impermeable activating agent, and these materials include but not limited to ethylene-vinyl alcohol, vinyl-vinyl-acetic ester, cellulose derivative, such as cellulose acetate, polydimethylsiloxanederivative derivative and polyurethane.In some Punctal plug, this film is impermeable water, and activating agent diffuses out by uncoated main part passively.This film can be made by the material that epimere is listed.
In other Punctal plugs, this film is water permeable but impermeable activating agent.After in being inserted into lacrimal ductule, water is diffused in the main body to produce osmotic gradient by this film, for example as U.S. Patent number 6,923, and 800 and 5,817, described in 335, it all is incorporated into this as a reference.Then utilize osmotic gradient to force activating agent by uncoated main part.Water permeable but the film of impermeable activating agent can be by comprising for example HYTREL  polybutylene terephthalate (PBT) flexible body, cellulose ether, cellulose esters, enhancing mobile polyvinyl acetate base ester copolymer and ethylene-vinyl alcohol.
With reference to figure 7 and 8, in certain embodiments, activating agent is not contained in the main body, but main body 70 and 80 is applied with polymeric material 78 and 88 respectively, and this polymeric material contains at least a activating agent and the impermeable activating agent of this main body.The thickness of coating can increase, and the size of main body can reduce pro rata, to increase the amount of the activating agent that Punctal plug can hold.This coating can be any thickness that is enough to hold required active dose like this.Some such Punctal plug also can have groove to increase its surface area on main body.This groove can be any size or shape.
This coating can be made by the polymeric material that is partially soluble in water at least.When in the water environment that this coating is exposed to lacrimal ductule or tear, it preferably dissolves and discharge activating agent when it dissolves.The dissolubility of the polymeric material of this manufacturing coating in water will be directly proportional with its rate of dissolution.At least the suitable polymeric material that is partially soluble in water includes but not limited to for example poly-(ethylene glycol); Poly-(ethylene oxide); Poly-(propylene glycol); Poly-(vinyl alcohol); Poly-(methacrylate hydroxyethyl ester); Poly-(vinylpyrrolidone); Polyacrylic acid; Poly-(ethyl  azoles quinoline); Poly-(DMAA); Phospholipid includes but not limited to the Phosphorylcholine derivant; Poly-sulfobetaines; Polysaccharide and carbohydrate include but not limited to hyaluronic acid, dextran, hydroxyethyl-cellulose, hydroxypropyl cellulose, gelling carbohydrate gum, guar gum, Heparan sulfate, chondroitin sulfate, heparin and alginate; Protein includes but not limited to gelatin, collagen, albumin and ovalbumin; And polyamino acid.Polymeric material in this tabulation is usually with hydrophobic polymer, monomer or both copolymerization or mix.
Alternatively, this coating can be made by biodegradable material, and in a single day this material is exposed to can chemical degradation when for example being present in the intravital bioactive substance of mammal usually.This Biodegradable material preferably is hydrolyzed under the organism condition of living.Biodegradation take place slower, slower so if desired than dissolving usually, release bioactive agent more constantly, this coating can be made by biodegradable material.Suitable polymerization Biodegradable material includes but not limited to the polymer and the oligomer of Acetic acid, hydroxy-, bimol. cyclic ester, lactide, 6-caprolactone and other hydroxy acid, and produces nontoxic or be present in the other biological degradable polymer of intravital material as the homergy thing.Preferred poly-('alpha '-hydroxy acids) is poly-(glycolic), poly-(2-is to dioxanone); Poly-(DL-lactic acid) and poly-(L-lactic acid).Other available materials comprise poly-(aminoacid), Merlon, poly-(acid anhydride), poly-(ortho esters), poly-(phosphazine) and poly-(phosphate ester).Such as the polylactone of poly-(6-caprolactone), poly-(δ-caprolactone), poly-(δ-Wu Neizhi) and poly-(gamma-butyrolacton), also be useful for example as chitosan, alginate, collagen and gelatin.The present invention specific aspect, the polymeric material of making coating can be made of one or more dissolubilities and biodegradability mixture of polymers.
This coating is made by polymeric material water insoluble and not biodegradable but that activating agent can diffuse out from it alternatively.The polymeric material that this type is suitable typically includes but not limited to crosslinked poly-(ethylene glycol); Poly-(ethylene oxide); Poly-(propylene glycol); Poly-(vinyl alcohol); Poly-(methacrylate hydroxyethyl ester); Poly-(vinylpyrrolidone); Polyacrylic acid; Poly-(ethyl  azoles quinoline); Poly-(DMAA).These polymer can with hydrophobic polymer, monomer or both copolymerization or blend.As water insoluble and be that the other polymer of not biodegradable polymer includes but not limited to silicones, silicone compound; The resinous copolymeric siloxane thing, for example, the hydrophilic monomer of pHEMA (hemacol), Polyethylene Glycol, polyvinylpyrrolidone and glycerol and silicone hydrogel polymer, include but not limited to U.S. Patent number 5,962,548,6,020,445,6,099,852,6,367,929 and 6,822, those materials described in 016, these patents all are incorporated into this as a reference; Phospholipid includes but not limited to the Phosphorylcholine derivant; Poly-sulfobetaines; Polysaccharide and carbohydrate, all like hyaluronic acids, dextran, hydroxyethyl-cellulose, hydroxypropyl cellulose, gelling carbohydrate gum, guar gum, Heparan sulfate, chondroitin sulfate, heparin and alginate; Protein includes but not limited to gelatin, collagen, albumin and ovalbumin; Polyamino acid; Fluoropolymer polymer, all like PTFE, PVDF and special teflon; Polypropylene; Polyethylene; Nylon; And EVA.Additional example water-fast, not biodegradable or that satisfy the two suitable polymers includes but not limited to silicones, polyurethane, cyanoacrylate, polyacrylic acid, fibrin and crosslinking protein, all like albumin and collagen-gelatin.
Be used to less the Punctal plug that polymeric material that a kind of activating agent makes applies for main body wherein, this main body is at first utilized and is comprised for example solution-cast, extruding, makes by the suitable treatments of chemical crosslinking, car system, pressing mold, injection molding, liquid injection molding, blowing mould that forms covalent bond or ionic bond and the polymerization that comprises photopolymerization, thermal polymerization and ionization polymerization and redox polymerization etc.Then this main body utilization is comprised that the polymeric material that the usefulness of following various processing contains activating agent applies, these processing include but not limited to that dip-coating, spin coating, vapor deposition apply, adsorb, mix adhesion, plasma coated, the powder coated of laminate, prefabricated coating and comprise the spraying of electronics spraying.This coating can be aggregated on the surface of Punctal plug, absorb through the mechanism interlocking, through the solvent carrier evaporation and precipitate, precipitation or solidify when cooling, the chemical bonding through using cross-linking agent is perhaps through binding agent and combination.Alternatively, this coating can be one or two the form of non-bonding lining around the main body of this plug and eckband.
The amount that is used in plug of the present invention activating agent beyond the Great Wall will depend on selected a kind of activating agent or multiple actives, treat the fusing point through required dosage, required rate of release and the activating agent and the material of Punctal plug conveying.Preferably, used amount is a therapeutically effective amount, this means the effective dose that can realize required treatment, inhibition or preventive effect.Usually, use about 0.05 amount to about 8,000 microgram activating agents.
Punctal plug described herein can be used for for one or more treatments, inhibition or prevents numerous diseases and uncomfortable carry various activating agents.Each Punctal plug can be used for carrying at least a activating agent and can be used for carrying dissimilar activating agents.For example, Punctal plug can be used for carrying be used for the treatment of, hydrochloric acid nitrogen  Si spit of fland, emedastine two fumarates, epinastine hydrochloride, ketotifen fumarate, hydrochloric acid levocabastine, Olopatadine hydrochloride, pheniramine and the antazoline phosphate of inhibition and Polyglucan.This Punctal plug can be used for carrying mast cell stabilizers, and all like sodium cromoglicate, U-42585E, Buddhist nun examine meter sodium and permirolast potassium more.
This Punctal plug can be used for carrying iridodilator and cycloplegic, all like phenylephrine alkali, atropine sulfate, melyltropeine, scopolamine HBr, cyclopentolate hydrochloric acid, tropicamide and phenylephrine hydrochloride.This Punctal plug can be used for carrying the ophthalmology dyestuff, all like but be not limited to that tiger red (rose begal), sissamine are green, indocyanine green, calcein and fluorescein.
This Punctal plug can be used for carrying corticosteroid, all like dexamethasone sodium phosphates, dexamethasone, fluorometholone, fluorometholone acetate, loteprednol etabonate, Inflamase, medroxyprogesterone, rimexolone and fluorometholone ketal.This Punctal plug can be used for carrying the on-steroidal antiinflammatory, and is all like but be not limited to flurbiprofen sodium, suprofen, diclofenac sodium, ketorolac tromethamine, cyclosporin A, rapamycin methotrexate, azathioprine and bromocriptine.
This Punctal plug can be used for carrying anti-infectious preparation, and is all like but be not limited to tobramycin, Moxifloxacin; ofloxacin, Gatifloxacin, ciprofloxacin; gentamicin, sulfisoxazolone diethanolamine, sulfacetamide sodium; vancomycin, polymyxin B, amikacin; norfloxacin succinil, levofloxacin, sulfisoxazole diolamine; the sulfacetamide sodium tetracycline, doxycycline, dicloxacillin sodium; cephalexine, amoxicillin/clavulanate, ceftriaxone; Cefspan; erythromycin, ofloxacin, azithromycin; gentamicin, sulfadiazine and ethamine pyridine pyridine.
This Punctal plug can be used for conveying and is suitable for the glaucomatous preparation of one or more treatments, inhibition and prevention, includes but not limited to epinephrine, comprises picture: dipivalyl epinephrine, and alpha-2 adrenergic receptor comprises picture apraclonidine and brimonidine; Beta-blocker comprises the picture betaxolol, carteolol, levobunolol, metipranolol and timolol; Directly miotic comprises as ear and pilocarpine in many; Acetylcholinesteraseinhibitors inhibitors comprises picture physostigmine and echothiophate; Carbonic anhydrase inhibitors comprises the picture acetazolamide, brinzolamide, dorzolamide and methazolamide; Prostaglandin and prostamides comprise the picture latanoprost, bimatoprost, uravoprost and Unoprostone cidofovir.
This Punctal plug can be used for carrying anti-virus formulation, includes but not limited to Fomivirsen sodium, foscarnet sodium, Ganciclovir Sodium, valganciclovir hydrochloride, trifluorothymidine, acyclovir, and famciclovir.This Punctal plug can be used for carrying local anesthetic, include but not limited to tetracaine hydrochloride, proxymetacaine hydrochloride, proxymetacaine hydrochloride and fluorescein sodium, oxybuprocaine and fluorescein sodium (benoxinate and fluorescein sodium), oxybuprocaine and fluorexon disodium (benoxnate and fluorexon disodium).This Punctal plug can be used for carrying antifungal preparation, for example comprises fluconazol, flucytosine, amphotericin B, itraconazole and ketocaonazole.
This Punctal plug can be used for carrying analgesic, includes but not limited to acetaminophen and codeine, acetaminophen and hydrocodone, acetaminophen, ketorolac tromethamine, ibuprofen aluminum, and tramadol.This Punctal plug can be used for delivery of vascular and shrinks medicine, includes but not limited to ephedrine hydrochloride, naphcon, hydrochloride phenylephrine, tetrahydrozoline hydrochloride and oxymetazoline.This Punctal plug can be used for carrying vitamin at last, and antioxidant, and dietetic product include but not limited to Vitamin A, D and E, phylloxanthin, taurine, glutathion, zeaxanthin, fatty acid etc.
The activating agent that this Punctal plug is carried can be mixed with and contain excipient, include but not limited to synthetic and natural polymer, for example comprise polyvinyl alcohol, Polyethylene Glycol, polyacrylic acid, hydroxy methocel, glycerol, hypromellose, polyvinylpyrrolidone, card ripple Bo Er, propylene glycol, hydroxypropyl guar, glucam-20, hydroxypropyl cellulose, Sorbitol, glucose, polysorbate, mannitol, glucosan, the polysaccharide of modification and glue, phosphoric acid matter and propyl group pyridine.

Claims (16)

1, a kind of Punctal plug, comprise have first end, the main body and at least a activating agent that is included in the entire body of second end and the side surface that between two ends, extends.
2, Punctal plug as claimed in claim 1, wherein said main body is made of polymeric material, and this polymeric material is to be partially soluble in water at least, dissolving in time, and when it dissolves, discharge described activating agent.
3, Punctal plug as claimed in claim 1, wherein said main body is made of polymeric material, and this polymeric material is biodegradable, degraded in time, and when it is degraded, discharge described activating agent.
4, Punctal plug as claimed in claim 1, wherein said main body is made of polymeric material, and this polymeric material is water insoluble and is not biodegradable, and described activating agent diffuses out from material passively.
5, a kind of Punctal plug, comprise main body, the side surface that this main body has first end, second end and extends between two ends, and at least a activating agent is comprised in the entire body, and all surfaces except at least a portion main body is applied by the film of impermeable activating agent.
6, Punctal plug as claimed in claim 5, wherein said side surface have shape and are essentially circular outer diameter.
7, as the Punctal plug of claim 5 or 6, wherein said main body is made of polymeric material, and this material is to be partially soluble in water at least, dissolving in time, and when it dissolves, discharge described activating agent by uncoated main part.
8, as the Punctal plug of claim 5 or 6, wherein said main body is made of polymeric material, and this material is biodegradable, degraded in time, and when it is degraded, discharge described activating agent by uncoated main part.
9, as the Punctal plug of claim 5 or 6, wherein said main body is made of polymeric material, and this material is water-fast and is not biodegradable.
10, Punctal plug as claimed in claim 9, wherein said activating agent diffuses out passively by uncoated main part.
11, Punctal plug as claimed in claim 9, wherein said film is a water permeable, water is diffused in the main body producing osmotic gradient by this film, and forces activating agent by uncoated main part by this osmotic gradient.
12, a kind of Punctal plug, comprise main body, the side surface that this main body has first end, second end and extends between two ends, and the part of this side surface has the size bigger than the size of the remainder of this side surface, and the polymeric material of the involved at least a activating agent of wherein said main body applies, and impermeable this activating agent of this main body.
13, as the Punctal plug of claim 12, wherein said side surface has shape and is essentially circular outer diameter.
14, as the Punctal plug of claim 12 and 13, wherein said coating is made of polymeric material, and this material is to be partially soluble in water at least, dissolving in time, and when it dissolves, discharge this activating agent.
15, as the Punctal plug of claim 12 and 13, wherein said main body is made of polymeric material, and this material is biodegradable, degraded in time, and when it is degraded, discharge this activating agent.
16, as the Punctal plug of claim 12 and 13, wherein said main body is made of polymeric material, and this material is water-fast and is not biodegradable, and activating agent diffuses out from material passively.
CNA2007101379157A 2006-06-21 2007-06-21 Punctal plugs for the delivery of active agents Pending CN101099878A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
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CN102378619A (en) * 2009-03-31 2012-03-14 庄臣及庄臣视力保护公司 Methods and apparatus for dispensing medicaments into a punctal plug
EP4103194A4 (en) * 2020-02-12 2024-03-06 Glia, Llc Progesterone combinations

Families Citing this family (7)

* Cited by examiner, † Cited by third party
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TWI542338B (en) * 2008-05-07 2016-07-21 壯生和壯生視覺關懷公司 Ophthalmic devices for the controlled release of active agents
WO2010071844A1 (en) * 2008-12-19 2010-06-24 Qlt Plug Delivery, Inc Substance delivering punctum implants and methods
JP5885244B2 (en) * 2009-01-23 2016-03-15 マティ セラピューティクス，インク． Sustained release delivery of one or more drugs
EP3223793B1 (en) * 2014-11-25 2023-06-28 Eximore Ltd. Compositions and methods for delivering a bio-active agent or bio-active agents
JP2018525078A (en) * 2015-07-22 2018-09-06 インセプト・リミテッド・ライアビリティ・カンパニーＩｎｃｅｐｔ，Ｌｌｃ Coated punctum plug
US11458041B2 (en) 2015-10-08 2022-10-04 Ocular Therapeutix, Inc. Punctal plug and bioadhesives
WO2020198246A1 (en) * 2019-03-26 2020-10-01 The General Hospital Corporation Anti-microbial methods and materials

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102378619A (en) * 2009-03-31 2012-03-14 庄臣及庄臣视力保护公司 Methods and apparatus for dispensing medicaments into a punctal plug
EP4103194A4 (en) * 2020-02-12 2024-03-06 Glia, Llc Progesterone combinations

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AR061552A1 (en) 2008-09-03
JP2008049129A (en) 2008-03-06
CA2592364A1 (en) 2007-12-21
BRPI0705487A (en) 2008-09-16
AU2007202875A1 (en) 2008-01-17
SG138565A1 (en) 2008-01-28

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