INTRANASAL ADMINISTRATION
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.