Compositions for delivery of therapeutics into the eyes and methods for making and using same

Abstract

The present invention provides for compositions for administering a therapeutically effective amount of a therapeutic component. The compositions may include an ophthalmically acceptable carrier component; a therapeutically effective amount of a therapeutic component; and a retention component which may be effective to reduce wettability, induce viscosity, increase muco-adhesion increase meniscus height on a cornea of an eye and/or increase physical apposition to a cornea of an eye of a composition.

1 - 40 . (canceled) 
     
     
         41 . A composition for administering a therapeutic component to a human or animal, the composition comprising:
 an ophthalmically acceptable carrier component;   a therapeutic component; and   a retention component in an amount effective to provide the composition with a viscosity greater than the viscosity of saline containing 0.5% (w/v) carboxymethylcellulose having an average molecular weight of 90,000.   
     
     
         42 . The composition of claim  1  wherein the composition has one or more of the following characteristics selected from the group consisting of:
 a. a surface tension greater than or equal to human tear fluid; 
 b. an advancing contact angle greater than or equal to human tear fluid; 
 c. the retention component at a concentration present in the composition is effective to increase human tear fluid surface tension; 
 d. is substantially ineffective to reduce the surface tension of tear fluid in an eye after the composition is administered to the eye; 
 e. is substantially ineffective to wet a dermal eyelid of a human eye after the composition is administered to the human eye; 
 f. has a reduced viscosity relative to a substantially identical composition which has sufficient viscosity to be substantially excluded from an eye by a mechanical action of an eye lid of the eye after the substantially identical composition is administered to the eye; 
 g. is shear thinning; 
 h. has increased muco-adhesion relative to saline containing 0.5% (w/v) carboxymethylcellulose having an average molecular weight of 90,000; 
 i. the retention component is selected from polyanionic components and mixtures thereof, 
 j. the polyanionic component of the retention composition is selected from the group consisting of anionic cellulosic derivatives and mixtures thereof, 
 k. the polyanionic component of the retention composition is selected from carboxymethyl celluloses and mixtures thereof, 
 l. the retention component includes a first polyanionic component portion having a first molecular weight; and a second polyanionic component portion having a second molecular weight; the first and second polyanionic component portions being present in an amount effective to facilitate the administration of the therapeutic component into an eye when the composition is administered to the eye, the first and second molecular weights being different; 
 m. the retention component includes a first polyanionic component portion having a first molecular weight; and a second polyanionic component portion having a second molecular weight; the first and second polyanionic component portions being present in an amount effective to facilitate the administration of the therapeutic component into an eye when the composition is administered to the eye, the first and second molecular weights being different, wherein the first molecular weight is greater than the second molecular weight and the composition provides for an increased penetration of the therapeutic component through a cornea of an eye relative to a substantially identical composition having an equal total amount of the polyanionic component and substantially no first polyanionic component portion; 
 n. the retention component includes a first polyanionic component portion having a first molecular weight; and a second polyanionic component portion having a second molecular weight; the first and second polyanionic component portions being present in an amount effective to facilitate the administration of the therapeutic component into an eye when the composition is administered to the eye, the first and second molecular weights being different, wherein the first molecular weight is greater than the second molecular weight and the composition provides for an increased physical apposition on a cornea of an eye when the composition is administered to the cornea relative to a substantially identical composition having an equal total amount of the polyanionic component and substantially no first polyanionic component portion; 
 o. the retention component includes a first polyanionic component portion having a first molecular weight; and a second polyanionic component portion having a second molecular weight; the first and second polyanionic component portions being present in an amount effective to facilitate the administration of the therapeutic component into an eye when the composition is administered to the eye, the first and second molecular weights being different, wherein the first molecular weight is greater than the second molecular weight and the composition provides for an increased retention to a cornea of an eye when the composition is administered to the cornea relative to a substantially identical composition having an equal total amount of the polyanionic component and substantially no first polyanionic component portion; and 
 p. the retention component includes a first polyanionic component portion having a first molecular weight; and a second polyanionic component portion having a second molecular weight; the first and second polyanionic component portions being present in an amount effective to facilitate the administration of the therapeutic component into an eye when the composition is administered to the eye, the first and second molecular weights being different, wherein the polyanionic component is selected from the group consisting of anionic cellulosic derivatives, anionic homopolymers and copolymers comprising units of one or more of acrylic acid, methacrylic acid, metal acrylates and metal methacrylates, and mixtures thereof. 
 
     
     
         43 . The composition of  claim 41  wherein the therapeutic component comprises a material selected from the group consisting of NNDA antagonists, antibacterials, antihistarnines, decongestants, antiinflammatories, antiparasitics, miotics, sympathomimetics, anticholinergics, adrenergics, aritivirals, local anesthetics, antifungals, amoebicidals, trichomonocidals, analgesics, mydriatics, antiglaucoma drugs, carbonic anhydrase inhibitors, ophthalmic diagnostic agents, ophthalmic agents used as adjuvants in surgery, chelating agents, antineoplastics, antihypertensives, muscle relaxants, diagnostics, adrenergic anesthetics, beta blockers, alpha-2-agonists, cycloplegics, postaglandins, derivatives thereof and mixtures thereof. 
     
     
         44 . The composition of  claim 41  wherein the therapeutic component is effective to reduce the intraocular pressure of an eye when the composition is administered to the eye. 
     
     
         45 . The composition of  claim 41  wherein the therapeutic component comprises a quinoxaline component. 
     
     
         46 . The composition of  claim 45  wherein the quinoxaline component is selected from the group consisting of compounds having the formula: 
       
         
           
           
               
               
           
         
       
       and ophthalmically acceptable acid addition salts thereof and mixtures thereof, wherein R 1  and R 2  each is independently selected from the group consisting of H, alkyl radicals containing 1 to 4 carbon atoms and alkoxy radicals containing 1 to 4 carbon atoms, the 2-imidazolin-2-ylamino group may be in any of the 5-, 6-, 7-, or 8-positions of the quinoxaline nucleus, and the R 3 , R 4  and R 5  each is located in one of the remaining 5-, 6-, 7-, or 8-positions of the quinoxaline nucleus and is independently selected from the group consisting of Cl, Br, H and alkyl radicals containing 1 to 3 carbon atoms. 
     
     
         47 . The composition of  claim 46  wherein the 2-imidazolin-2-ylamino group is in the 6-position of the quinoxaline nucleus, R 3  is in the 5-position of the quinoxaline nucleus and is selected from the group consisting of Cl, Br, and alkyl radicals containing 1 to 3 atoms, and R 4  and R 5  are both H. 
     
     
         48 . The composition of  claim 47  wherein R 3  is Br. 
     
     
         49 . The composition of  claim 41  wherein the therapeutic component comprises a material selected from the group consisting of hypotensive lipid components, pyranoquinolinone derivatives, compounds having retinoidlike activities, ketorolac/pyrrole-1 carboxylic acids, ofloxacins/benzoxazine derivatives, memantines and mixtures thereof. 
     
     
         50 . The composition of  claim 41  wherein the therapeutic component comprises bimatoprost. 
     
     
         51 . The method of administering a therapeutic component comprising:
 administering a composition of  claim 41  to a cornea of an eye.   
     
     
         52 . A composition for administering a therapeutic component to a human or animal, the composition comprising:
 an ophthalmically acceptable carrier component;   a therapeutic component; and   a polyanionic component including a first polyanionic component portion having a first molecular weight, and a second polyanionic component portion having a second molecular weight, the first and second polyanionic component portions being present in an amount effective to facilitate the administration of the therapeutic component through a cornea of an eye when the composition is administered to the eye, the first and second molecular weights being different.   
     
     
         53 . The composition of  claim 52  has a characteristic selected from the group consisting of:
 a. the first molecular weight is greater than the second molecular weight and the composition, when administered to an eye, provides for an increased penetration of the therapeutic component through a cornea of the eye relative to a substantially identical composition having an equal total amount of the polyanionic component and substantially no first polyanionic component portion; 
 b. the first molecular weight is greater than the second molecular weight and the composition provides for an increased retention to a cornea of an eye when the composition is administered to the cornea relative to a substantially identical composition having an equal total amount of the polyanionic component and substantially no first polyanionic component portion; 
 c. the first molecular weight is greater than the second molecular weight and an increased amount of the therapeutic component passes through a cornea of an eye when the composition is administered to the cornea relative to a substantially identical composition having an equal total amount of the polyanionic component and substantially no first polyanionic component portion; 
 d. the polyanionic component is selected from the group consisting of anionic cellulosic derivatives, anionic homopolymers and copolymers comprising units of one or more of acrylic acid, methacrylic acid, metal acrylates and metal methacrylates, and mixtures thereof; 
 e. the therapeutic component is selected from the group consisting of NT4DA antagonists, antibacterials, antihistamines, decongestants, antiinflammatories, antiparasitics, miotics, sympathomimetics, anticholinergics, adrenergics, antivirals, local anesthetics, antifungals, amoebicidals, trichomonocidals, analgesics, mydriatics, antiglaucoma drugs, carbonic anhydrase inhibitors, ophthalmic diagnostic agents, ophthalmic agents used as adjuvants in surgery, chelating agents, antineoplastics, antihypertensives, muscle relaxants, diagnostics, adrenergic anesthetics, beta blockers, alpha-2-agonists, cycloplegics, postaglandins, derivatives thereof and mixtures thereof; and 
 f. the therapeutic component is effective to reduce the intraocular pressure of an eye when the composition is administered to the eye. 
 
     
     
         54 . The composition of claim  27  wherein the therapeutic component comprises a quinoxaline component. 
     
     
         55 . The composition of  claim 54  wherein the quinoxaline component is selected from the group consisting of compounds having the formula: 
       
         
           
           
               
               
           
         
       
       and ophthalmically acceptable acid addition salts thereof and mixtures thereof, wherein R 1  and R 2  each is independently selected from the group consisting of H, alkyl radicals containing 1 to 4 carbon atoms and alkoxy radicals containing 1 to 4 carbon atoms, the 2-imidazolin-2-ylamino group may be in any of the 5-, 6-, 7-, or 8-positions of the quinoxaline nucleus, and the R 3 , R 4  and R 5  each is located in one of the remaining 5-, 6-, 7-, or 8-positions of the quinoxaline nucleus and is independently selected from the group consisting of Cl, Br, H and alkyl radicals containing 1 to 3 carbon atoms. 
     
     
         56 . The composition of  claim 55  wherein the 2-imidazolin-2-ylamino group is in the 6-position of the quinoxaline nucleus, R 3  is in the 5-position of the quinoxaline nucleus and is selected from the group consisting of Cl, Br, and alkyl radicals containing 1 to 3 atoms, and R 4  and R 5  are both H. 
     
     
         57 . The composition of  claim 56  wherein R 3  is Br. 
     
     
         58 . The composition of  claim 57  wherein the therapeutic component comprises a material selected from the group consisting of hypoterisive lipid components, pyranoquinolinone derivatives, compounds having retinoid-like activities, ketorolac/pyrrole-1 carboxylic acids, ofloxacins/benzoxazine derivatives, memantines and mixtures thereof. 
     
     
         59 . The composition of  claim 57  wherein the therapeutic component comprises bimatoprost. 
     
     
         60 . A method of administering a therapeutic component comprising:
 administering a composition of  claim 52  to cornea of an eye.