Inspire Pharmaceuticals, Inc.

Other

University of North Carolina at Chapel Hill

Benjamin R Yerxa

Janet L Rideout

William Pendergast

Ward M Peterson

Sammy Ray Shaver

Edward G Brown

Karla M Jacobus

James G Douglass, Iii

Richard C Boucher

José L Boyer

David J Drutz

Christopher S Crean

Robert Plourde, Jr

Robert P Dougherty

Suhaib M Siddiqi

Dallas Croom

Arthur C Jones

Gillian M Olins

Monroe Jackson Stutts

Michael K James

Matthew S Cowlen

Jason L Vittitow

Eduardo R Lazarowski

Krzysztof Bednarski

John C Ice, Jr

Jesus Jeronimo Pintor

Maria A Peral

Cara Geary

Zhen Zhang

Edwardo R Lazarowski

Cary Geary

M Jackson Stutts

Maryse Picher

A method and preparation for the stimulation of tear secretion in a subject in need of such treatment is disclosed. The method comprises administering to the ocular surfaces of the subject a purinergic receptor agonist such as uridine 5'-triphosphate (UTP), dinucleotides, cytidine 5&#x2032;-triphosphate (CTP), adenosine 5&#x2032;-triphosphate (ATP), or their therapeutically useful analogs and derivatives, in an amount effective to stimulate tear fluid secretion and enhance drainage of the lacrimal system. Pharmaceutical formulations and methods of making the same are also disclosed. Methods of administering the same would include: topical administration via a liquid, gel, cream, or as part of a contact lens or selective release membrane; or systemic administration via nasal drops or spray, inhalation by nebulizer or other device, oral form (liquid or pill), injectable, intra-operative instillation or suppository form.

Method of increasing tear production with purinergic receptor agonists

The present invention provides a method of treating edematous retinal disorders. The method comprises administration of a pharmaceutical formulation comprising a hydrolysis-resistant P2Y receptor agonist to stimulate the removal of pathological extraneous fluid from the subretinal and retinal spaces and thereby reduce the accumulation of said fluid associated with retinal detachment and retinal edema. The P2Y receptor agonist can be administered with therapeutic and adjuvant agents commonly used to treat edematous retinal disorders. The present invention also provides a method of treating cystic fibrosis. The present invention also provides a method of treating sinusitis. The present invention further provides P-(2'-deoxycytidine 5&#x2032;-)P-(uridine 5&#x2032;-)tetraphosphate, tetra-(alkali metal) salts such as tetrasodium, tetralithium, tetrapotassium, and mixed (tetra-alkali metal) salts. The present further provides a pharmaceutical formulation comprising a P-(2&#x2032;-deoxycytidine 5&#x2032;-)P-(uridine 5&#x2032;-)tetraphosphate, tetra-(alkali metal) salt, in a pharmaceutically acceptable carrier.

P1-(2'-deoxycytidine 5&#x2032;-)P4-(uridine 5&#x2032;-)tetraphosphate, tetra-(alkali metal) salt, for treating sinusitis

The present invention are directed to P,P-di(uridine 5'-)tetraphosphate, tetra-alkali metal salts such as tetrasodium, tetralithium, tetrapotassium, and mixed tetra-alkali metal cations thereof. The tetra alkali metal salts of P,P-di(uridine 5&#x2032;-)tetraphosphate are water-soluble, nontoxic, and easy to handle during manufacture. These tetra-monovalent alkali metal salts are more resistant to hydrolysis than the mono-, di-, or tri-acid salts, therefore, they provide an improved stability and a longer shelf life for storage. The present invention also provides methods for the synthesis of P,P-di(uridine 5&#x2032;-)tetraphosphate, and its pharmaceutically acceptably acceptable salts thereof, and demonstrates the applicability to the production of large quantities. The methods substantially reduce the time required to synthesize diuridine tetraphosphate, for example, to three days or less.

Di(uridine 5'-)tetraphosphate and salts thereof

Method of treating dry eye disease with purinergic receptor agonists

The present invention relates to mononucleoside phosphate compounds that have the benefits of a dinucleotide pharmaceutical. These mononucleoside phosphates can be made from a mononucleotide that has been modified by attaching a degradation-resistant substituent on the terminal phosphate of a polyphosphate mononucleotide. By attaching this degradation-resistant substituent, the stability from degradation matches or exceeds those of certain dinucleotides. The mononucleoside phosphate compounds of the present invention are useful in preventing and treating epithelial tissue diseases or diseases or disorders associated with platelet aggregation.

Degradation-resistant mononucleoside phosphate compounds

The present invention provides a method of treating edematous retinal disorders. The method comprises administration of a pharmaceutical formulation comprising a hydrolysis-resistant P2Y receptor agonist to stimulate the removal of pathological extraneous fluid from the subretinal and retinal spaces and thereby reduce the accumulation of said fluid associated with retinal detachment and retinal edema. The P2Y receptor agonist can be administered with therapeutic and adjuvant agents commonly used to treat edematous retinal disorders. The present invention also provides a method of treating cystic fibrosis. The present invention further provides P-(2'-deoxycytidine 5&#x2032;-)P-(uridine 5&#x2032;-) tetraphosphate, tetra-(alkali metal) salts such as tetrasodium, tetralithium, tetrapotassium, and mixed (tetra-alkali metal) salts. The present further provides a pharmaceutical formulation comprising a P-(2&#x2032;-deoxycytidine 5&#x2032;-)P-(uridine 5&#x2032;-) tetraphosphate, tetra-(alkali metal) salt, in a pharmaceutically acceptable carrier.

[object Object]

The present invention provides a method of stimulating cervical and vaginal secretions in a mammal by treatment with P2Yand/or P2Ypurinergic receptor agonists. Treatment of vaginal dryness associated with menopause, chemotherapy, and various disease states as well as the treatment of vulvar pain is discussed. Suitable agonists such as UTP, CTP, ATP, dinucleotides and analogs thereof are disclosed.

Method of promoting cervical and vaginal secretions

The present invention provides a method of preventing or treating an inflammatory disease, including but not limited to, sinusitis, rhinitis, conjunctivitis, asthma, dermatitis, inflammatory bowel disease, inflammatory collagen vascular diseases, glomerulonephritis, inflammatory skin diseases, and sarcoidosis. The method comprises administrating to a subject a pharmaceutical formulation comprising a nucleotide receptor agonist, such as nucleoside diphosphate, nucleoside triphosphate, or dinucleoside polyphosphate, according to general formula Ia, Ib, IIa, IIb, or III. Preferred indications of the present invention are perennial allergic rhinitis, seasonal allergic rhinitis, infectious allergic rhinitis, and allergic conjunctivitis.

Method for treating or preventing inflammatory diseases

A method and preparation for reducing dry eye symptoms and promoting tear secretion in a subject in need of such treatment is disclosed. The method comprises administering to the eyes of the subject a non-drying antihistamine compound, such as epinastine hydrochloride, in an amount effective to reduce dry eye symptoms and stimulate tear fluid secretion. Pharmaceutical formulations and methods of making the same are also disclosed. Methods of administering the compound include topical administration via a liquid, gel, cream, or as part of a contact lens or a continuous or selective release device; or systemic administration via nasal drops or spray, inhalation by nebulizer or other device, oral form (liquid or pill), injectable, intra-operative instillation or suppository form.

Method of treating dry eye disease with non-drying antihistamines

A method and preparation for enhancing drainage of lacrimal system in a subject in need of such treatment is disclosed. The method comprises administering to the ocular surfaces of the subject a purinergic receptor agonist such as uridine 5'-triphosphate (UTP), dinucleotides, cytidine 5&#x2032;-triphosphate (CTP), adenosine 5&#x2032;-triphosphate (ATP), or their therapeutically useful analogs and derivatives, in an amount effective to stimulate tear fluid secretion and enhance drainage of the lacrimal system. Pharmaceutical formulations and methods of making the same are also disclosed. Methods of administering the same would include: topical administration via a liquid, gel, cream, or as part of a contact lens or selective release membrane; or systemic administration via nasal drops or spray, inhalation by nebulizer or other device, oral form (liquid or pill), injectable, intra-operative instillation or suppository form.

Method of enhancing drainage of lacrimal system with purinergic receptor agonists

The present invention provides a method of treating edematous retinal disorders. The method comprises administration of a pharmaceutical formulation comprising a hydrolysis-resistant P2Y receptor agonist to stimulate the removal of pathological extraneous fluid from the subretinal and retinal spaces and thereby reduce the accumulation of said fluid associated with retinal detachment and retinal edema. The P2Y receptor agonist can be administered with therapeutic and adjuvant agents commonly used to treat edematous retinal disorders. The pharmaceutical formulation useful in this invention comprises a P2Y receptor agonist with enhanced resistance to extracellular hydrolysis, such as dinucleoside polyphosphate compounds, or hydrolysis-resistant mononucleoside triphosphate salts. The present invention also provides P-(2'-deoxycytidine 5&#x2032;-)P-(uridine 5&#x2032;-)tetraphosphate, tetra-(alkali metal) salts such as tetrasodium, tetralithium, tetrapotassium, and mixed (tetra-alkali metal) salts. The present further provides a pharmaceutical formulation comprising a P-(2&#x2032;-deoxycytidine 5&#x2032;-)P-(uridine 5&#x2032;-)tetraphosphate, tetra-(alkali metal) salt, in a pharmaceutically acceptable carrier.

Pharmaceutical formulation comprising dinucleoside polyphosphates and salts thereof

This invention is directed to a method of preventing or treating diseases or conditions associated with platelet aggregation. The method is also directed to a method of treating thrombosis. The method comprises administering to a subject a pharmaceutical composition comprising a therapeutic effective amount of P2Yreceptor antagonist compound, wherein said amount is effective to bind the P2Yreceptors on platelets and inhibit ADP-induced platelet aggregation. The P2Yreceptor antagonist compounds useful for this invention include mononucleoside 5'-monophosphates, mononucleoside polyphosphates, and dinucleoside polyphosphates of general Formula I, or salts thereof. The present invention also provides novel compounds of mononucleoside 5&#x2032;-monophosphates, mononucleoside polyphosphates, and dinucleoside polyphosphates. The present invention further provides pharmaceutical formulations comprising mononucleoside 5&#x2032;-monophosphates, mononucleoside polyphosphates, or dinucleoside polyphosphates.

Composition and method for inhibiting platelet aggregation

The present invention are directed to P, P-di(uridine 5'-)tetraphosphate, tetra-alkali metal salts such as tetrasodium, tetralithium, tetrapotassium, and mixed tetra-alkali metal cations thereof. The tetra alkali metal salts of P, P-di(uridine 5&#x2032;-)tetraphosphate are water-soluble, nontoxic, and easy to handle during manufacture. These tetra-monovalent alkali metal salts are more resistant to hydrolysis than the mono-, di-, or tri-acid salts, therefore, they provide an improved stability and a longer shelf life for storage. The present invention also provides methods for the synthesis of P, P-di(uridine 5&#x2032;-)tetraphosphate, and its pharmaceutically acceptably acceptable salts thereof, and demonstrates the applicability to the production of large quantities. The methods substantially reduce the time required to synthesize diuridine tetraphosphate, for example, to three days or less.

Growing community of inventors

Raleigh, NC, United States of America

Benjamin R Yerxa