Intranasal administration

Abstract

Intranasal administration of proteins, such as insulin and insulin analogues, in particular immunogenic proteins to the upper posterior region of a nasal cavity of a subject, and in particular the olfactory bulb region.

1 - 5 . (canceled) 
     
     
         6 . A method of delivering a protein formulation to the upper posterior region of a nasal cavity of a subject for uptake into the central nervous system (CNS) of the subject, the method comprising:
 positioning a delivery device including a mouthpiece and a nosepiece relative to the subject, including fitting the nosepiece to one nostril of the subject;   the subject exhaling through the mouthpiece of the delivery device to cause closure of the oropharyngeal velum of the subject and create a flow of exhalation breath through the nosepiece; and   delivering the formulation through a nozzle of the nosepiece of the delivery device into the nasal cavity of the subject;   wherein the flow of exhalation breath through the nosepiece entrains the protein formulation delivered from the nozzle;   wherein the protein formulation comprises a solubilized protein formulation including a solubilizing agent to maintain the protein in solution following delivery and a proteolytic agent.   
     
     
         7 . The method of  claim 6 , further comprising:
 replacing the nosepiece following each delivery.   
     
     
         8 . The method of  claim 6 , wherein the protein formulation further includes an immunomodulator configured to prevent an immune response by the subject to the protein. 
     
     
         9 . The method of  claim 6 , wherein the protein formulation further includes an uptake agent configured to allow the protein to be taken up from the olfactory region in the upper posterior region. 
     
     
         10 . The method of  claim 6 , wherein the protein comprises insulin or an insulin analogue. 
     
     
         11 . The method of  claim 6 , wherein the protein comprises an oxytocic hormone, carbetocin, demoxytocin, oxytocin or a pharmaceutically-acceptable derivative or analogue thereof. 
     
     
         12 . The method of  claim 6 , wherein the protein comprises an oxytocin antagonist, atosiban or a pharmaceutically-acceptable derivative or analogue thereof. 
     
     
         13 . The method of  claim 6 , wherein the protein comprises:
 (i) an antidiurectic hormone, argipressin, lypressin, desmopressin, felypressin, ornipressin, terlipressin, vasopressin or a pharmaceutically-acceptable derivative or analogue thereof;   (ii) a corticotrophic hormone, corticotrophin, tetracosactide or a pharmaceutically-acceptable derivative or analogue thereof;   (iii) a corticotrophic releasing hormone, corticorelin or a pharmaceutically-acceptable derivative or analogue thereof;   (iv) an omatotrophic hormone, mecasermin, somtrem, somatropin or a pharmaceutically-acceptable derivative or analogue thereof;   (v) a somatotrophic hormone receptor antagonist, pegvisomant or a pharmaceutically-acceptable derivative or analogue thereof;   (vi) an omatotrophic releasing hormone, sermorelin, somatorelin or a pharmaceutically-acceptable derivative or analogue thereof;   (vii) a somatotrophic release inhibitor, lanreotide, octreotide, somatostatin, vapreotide or a pharmaceutically-acceptable derivative or analogue thereof;   (viii) a gonadotrophic hormone, choriogonadotrophin alfa, chorionic gonadotrophin, a follicle stimulating hormone, follitropin alfa, follitropin beta, a luteinising hormone, lutropin alfa, menotrophin, urofollitropin or a pharmaceutically-acceptable derivative or analogue thereof;   (ix) a gonadotrophic releasing hormone, buserelin, deslorelin, gonadorelin, goserelin, histrelin, leuprorelin, naferlin, triptorelin or a pharmaceutically-acceptable derivative or analogue thereof;   (x) an onadotrophic releasing hormone antagonist, abarelix, cetorelix, ganirelix or a pharmaceutically-acceptable derivative or analogue thereof;   (xi) a thyrotrophic hormone, thyrotrophin, thyrotrophin alfa or a pharmaceutically-acceptable derivative or analogue thereof;   (xii) a thyrotrophic releasing hormone, posatirelin, protirelin, taltirelin or a pharmaceutically-acceptable derivative or analogue thereof;   (xiii) a lactotrophic hormone, prolactin or a pharmaceutically-acceptable derivative or analogue thereof;   (xiv) a metabolic peptide, an insulin-like growth factor, a glucagon, a growth hormone, PYY3-36 or a pharmaceutically-acceptable derivative or analogue thereof;   (xv) a calcitonin, elcatonin, salcatonin or a pharmaceutically-acceptable derivative or analogue thereof;   (xvi) a melanocyte stimulating hormone;   (xvii) a nerve growth factor;   (xviii) an epidermal growth factor;   (xix) an epoetin or a pharmaceutically-acceptable derivative or analogue thereof;   (xx) an interleukin;   (xxi) a protein involved in one or both of blood coagulation and fibrinolysis; or   (xxii) an antibiotic.   
     
     
         14 . The method of  claim 9 , wherein the protein formulation is configured to allow the protein to be taken up from the olfactory region within about 10 minutes following delivery. 
     
     
         15 . The method of  claim 9 , wherein the protein formulation is configured to allow the protein to be taken up from the olfactory region within about 5 minutes following delivery. 
     
     
         16 . The method of  claim 6 , wherein delivering the protein formulation provides for uptake of the protein to the CNS without triggering an immune response. 
     
     
         17 . The method of  claim 6 , wherein the protein formulation further comprises one or more of trypsin, chymotrypsin, N terminal peptidases or C terminal peptidases. 
     
     
         18 . The method of  claim 9 , wherein the protein formulation further includes a cyclodextrin configured to allow the protein to be taken up from the olfactory region in the upper posterior region. 
     
     
         19 . The method of  claim 6 , wherein the protein formulation is delivered when a flow rate developed through a delivery channel of the delivery device reaches a predetermined value. 
     
     
         20 . The method of  claim 6 , wherein the protein formulation is delivered as an aerosol spray. 
     
     
         21 . The method of  claim 20 , wherein the protein formulation is delivered as a powder aerosol spray. 
     
     
         22 . The method of  claim 20 , wherein the protein formulation is delivered as a liquid aerosol spray.