Apparatus for administering composition for inhibiting cerebral neurovascular disorders and muscular headaches

• US 6,491,940 B1
• Filed: 01/27/2000
• Issued: 12/10/2002
• Est. Priority Date: 01/27/1999
• Status: Expired due to Term

• Current Assignee: BHL Patent Holdings LLC
• Original Assignee: Bruce H. Levin
• Inventors: Levin, Bruce H.
• Primary Examiner(s): Dees, Jose′ G.
• Assistant Examiner(s): George, Konata M
• Application Number:
  US09/492,946
• Time in Patent Office: 1,048 Days
• Field of Search: 600/120, 600/144, 600/146, 600/188, 128/207.18, 128/204.12, 128/204.11, 128/206.11, 604/514, 604/264, 424/434
• US Class Current: 424/434
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61M 11/00 Sprayers or atomisers specially adapted for therapeutic purposes in general B05B; aerosol containers B65D83/14
• CPC Class Codes: A61M 11/008 by squeezing, e.g. using a flexible bottle or a bulb
• CPC Class Codes: A61M 15/08 Inhaling devices inserted into the nose
• CPC Class Codes: A61M 2210/0618 Nose
• CPC Class Codes: A61M 2230/005 Parameter used as control input for the apparatus
• CPC Class Codes: A61M 31/00 Devices for introducing or retaining media, e.g. remedies, in cavities of the body A61M25/00 takes precedence ; introducing or retaining ophthalmic products into the ocular cavities A61F9/0008

Abstract

Methods, kits, apparatus, and compositions for inhibiting a cerebral neurovascular disorder or a muscular headache in a human patient are provided. The methods comprise intranasally administering to the patient a pharmaceutical composition comprising a local anesthetic, and preferably a long-acting local anesthetic ingredient. A composition useful for practicing the methods of the invention is described which comprises at least one local anesthetic in a pharmaceutically acceptable carrier, wherein the composition is formulated for intranasal delivery. Cerebral neurovascular disorders include migraine and cluster headache. Muscular headaches include tension headaches and muscle contraction headaches. A kit comprising the composition and an intranasal applicator and a method of systemically delivering a pharmaceutically active agent to an animal are also included in the invention. Apparatus for delivering or applying the compositions of the invention or for performing the methods of the invention are also described.

Claims

1. A dorsonasal drug delivery device comprising a body having a shape which conforms to the shape of the nasal cavity of a human, the body having a proximal end and a distal portion having a distal end, the distal portion being curved or angled with respect to a longitudinal axis of the body, the longitudinal axis of body at the distal end forming an angle of about 90 degrees to about 170 degrees with respect to the longitudinal axis at the proximal end prior to insertion of the distal end into the nasal cavity, such that when the distal portion of the body is in the apex of the nasal cavity, the distal end faces a posterior portion of the nasal cavity for dorsonasal delivery of the drug, and wherein the distal portion can be urged through a nostril of the human into the apex of the nasal cavity without injuring the human.

2. The device of claim 1, wherein the body is substantially rigid.

3. The device of claim 1, wherein the body is flexible.

4. The device of claim 1, wherein the body comprises a flexible portion.

5. The device of claim 1, wherein a lumen extends longitudinally within the body from the proximal end thereof to an outlet port at the exterior surface of the body.

6. The device of claim 5, wherein the outlet port is on the distal portion of the body.

7. The device of claim 5, wherein the lumen extends longitudinally within the body from the proximal end thereof to a plurality of outlet ports at the exterior surface of the body.

8. The device of claim 5, wherein a plurality of lumens extend longitudinally within the body from the proximal end thereof and wherein each lumen extends from the proximal end of the body to a separate outlet port.

9. The device of claim 8, wherein at least one outlet portion is at the distal end of the body.

10. The device of claim 5, wherein at least one outlet port is situated on the distal portion of the body in an orientation such that when the distal portion of the body is in the apex of the nasal cavity, the outlet port faces a posterior portion of the nasal cavity.

11. The device of claim 10, wherein the posterior portion of the nasal cavity is the sphenoethmoidal recess.

12. The device of claim 1, wherein the distal end of the body is rounded.

13. The device of claim 1, wherein the longitudinal axis of the body at the distal portion thereof forms an angle of from about 110 to about 160 degrees with the longitudinal axis of the body at the proximal end thereof.

14. The device of claim 13, wherein the longitudinal axis of the body at the distal portion thereof forms an angle of from about 120 to about 150 degrees with the longitudinal axis of the body at the proximal end thereof.

15. The device of claim 1, wherein the proximal portion of the body has an indicium for indicating the orientation of the distal portion of the body.

16. The device of claim 5, further comprising an extendable instrument situated with the lumen, wherein the extendable instrument is extendable through the outlet port.

17. The device of claim 16, wherein the extendible instrument is selected from the group consisting of a swab, a rosette, an inflatable balloon, and a needle.

18. The device of claim 17, wherein the needle is hollow, has an outlet in a distal end thereof, extends through the lumen, has a proximal end, and is connectable at its proximal end to a reservoir.

19. The device of claim 18, wherein the reservoir is selected from the group consisting of a compressible reservoir, a deformable bulb, and a syringe.

20. The device of claim 1, wherein the body has an absorbent portion on the distal portion.

21. The device of claim 5, wherein the lumen communicates at the proximal end of the body with the interior of a reservoir containing a pharmaceutical composition.

22. The device of claim 21, wherein the pharmaceutical composition comprises a long-acting local anesthetic.

23. The device of claim 21, wherein the pharmaceutical composition is delivered in a form selected from the group consisting of a liquid, a gel, a foam, a mousse, a powder, a dispersed powder, an atomized liquid, an aerosol, and a liposomal preparation.

24. A method of dorsonasally administering a composition to a human patient, the method comprising

inserting a dorsonasal drug delivery device into a nostril of the patient, wherein the device comprises a body having a shape which conforms to the shape of the nasal cavity of the patient, the body having a proximal end and a distal portion, the distal portion being curved or angled with respect to a longitudinal axis of the body, the longitudinal axis of body at the distal end forming an angle of about 90 degrees to about 170 degrees with respect to the longitudinal axis at the proximal end prior to insertion of the distal end into the nasal cavity, such that when the distal portion of the body is in the apex of the nasal cavity, the distal portion faces a posterior portion of the nasal cavity for dorsonasal delivery of the drug, and wherein the composition is present on at least a portion of the exterior surface of the body at the distal portion thereof,

urging the device through the nostril such that the distal portion of the body is in the apex of the nasal cavity, and

contacting a portion of the nasal epithelium overlying the SPG with the composition on the portion of the exterior surface.

25. A method of dorsonasally administering a composition to a human patient, the method comprising

inserting a dorsonasal drug delivery device into a nostril of the patient, wherein the device comprises a generally elongate body having a shape which conforms to the shape of the nasal cavity of the patient, the body having a proximal end and a distal portion, the distal portion being curved or angled with respect to a longitudinal axis of the body, the longitudinal axis of body at the distal end forming an angle of about 90 degrees to about 170 degrees with respect to the longitudinal axis at the proximal end prior to insertion of the distal end into the nasal cavity, such that when the distal portion of the body is in the apex of the nasal cavity, the distal portion including an outlet port faces a posterior portion of the nasal cavity for dorsonasal delivery of the drug, and a lumen extending in the body from the proximal end thereof to the outlet port,

urging the device through the nostril such that the distal portion of the body is in the apex of the nasal cavity, and

providing the composition to a portion of the nasal epithelium overlying the SPG through the outlet port by way of the lumen.

26. A method of dorsonasally administering a composition to a human patient, the method comprising

inserting a dorsonasal drug delivery device into a nostril of the patient, wherein the device comprises a generally elongate body having a shape which conforms to the shape of the nasal cavity of the patient, the body having a proximal end, a distal portion which has a distal end, the distal portion being curved or angled with respect to a longitudinal axis of the body, the longitudinal axis of body at the distal end forming an angle of about 90 degrees to about 170 degrees with respect to the longitudinal axis at the proximal end prior to insertion of the distal end into the nasal cavity, such that when the distal portion of the body is in the apex of the nasal cavity, the distal end faces a posterior portion of the nasal cavity for dorsonasal delivery of the drug, and a lumen extending in the body from the proximal end thereof to an outlet port on the distal portion thereof,

urging the device through the nostril such that the distal portion of the body is in the apex of the nasal cavity,

urging an elongate instrument through the lumen and into the apex of the nasal cavity, wherein the elongate instrument is selected from the group consisting of an extendable instrument comprising the composition, a swab impregnated with the composition, a rosette impregnated with the composition, a needle coated with the composition, an inflatable instrument comprising the composition, a balloon coated with the composition, a balloon impregnated with the composition, a hollow instrument having a lumen for providing the composition, and a hollow needle having a lumen for providing the composition, whereby the composition is provided to a portion of the nasal epithelium overlying the SPG.

27. An anatomically adapted dorsonasal delivery nozzle for dorsonasally administering a composition to a human patient, the nozzle comprising a body having

a delivery lumen extending therethrough from a proximal end of the body to an outlet port at a distal portion of the body, and

an exterior portion having

(i) a flattened portion situated peripherally between the proximal end and the distal portion for seating the nozzle against the nasal septum of the patient,

(ii) an anterior portion situated peripherally between the proximal end and the distal portion for seating the nozzle against a portion of the external nasal cartilage of the patient, and

(iii) an indented portion situated peripherally between the proximal end and the distal portion for seating the nozzle against a nasal concha of the patient,

wherein when the nozzle is seated, the outlet port is situated within the nasal cavity of the patient such that an axis extending through the discharge port is offset from the apex of the nasal cavity by no more than about 30 degrees.

28. The nozzle of claim 27, wherein when the nozzle is seated, the outlet port is situated within the nasal cavity of the patient such that the axis extending through the discharge port is offset from the apex of the nasal cavity by no more than about 15 degrees.

29. The nozzle of claim 27, wherein the body further includes a distal seating portion for seating the nozzle against the superior surface of the nasal cavity, wherein when the nozzle is seated, the outlet port is situated within the nasal cavity of the patient such that the axis extending through the discharge port is offset from the apex of the nasal cavity by no more than about 30 degrees.

30. The nozzle of claim 27, wherein the body is deformable.

31. The nozzle of claim 30, wherein the body is deformable at a certain condition, but is less deformable at a different condition, whereby the nozzle may be adapted to the nasal cavity of the patient at the certain condition and thereafter used at the different condition.

32. The nozzle of claim 31, wherein the body is adapted to the nasal cavity of the patient at a temperature at which the body is deformable, and wherein the body is thereafter used at a temperature at which the body is less deformable.

33. A method of dorsonasally administering a composition to a human patient, the method comprising

a) seating within the nasal cavity of the patient an anatomically adapted dorsonasal delivery nozzle, the nozzle comprising a body having

a delivery lumen extending therethrough from a proximal end of the body to an outlet port at a distal portion of the body, and

an exterior portion having

(i) a flattened portion situated peripherally between the proximal end and the distal portion for seating the nozzle against the nasal septum of the patient,

(ii) an anterior portion situated peripherally between the proximal end and the distal portion for seating the nozzle against a portion of the external nasal cartilage of the patient, and

(iii) an indented portion situated peripherally between the proximal end and the distal portion for seating the nozzle against a nasal concha of the patient,

wherein when the nozzle is seated, the outlet port is situated within the nasal cavity of the patient such that the axis extending through the discharge port is offset from the apex of the nasal cavity by no more than about 30 degrees, and thereafter

b) providing the composition to the delivery lumen, whereby the composition is dorsonasally administered to the patient.

34. In a manually pressure-actuated drug delivery device comprising an intranostril applicator for insertion into a nostril of a patient, a drug container, and a manually pressure-actuated actuator fixed to at least one of the applicator and the container and actuatably fluidly connecting the applicator and the container, whereby the drug from the container is provided to the applicator upon application of pressure by the patient to the actuator,

the improvement comprising the actuator being positioned with respect to the intranostril applicator in such a way that actuating pressure must be applied to the actuator in a direction which is not co-linear with the axis of the nostril into which the applicator is inserted.

35. In a manually pressure-actuated drug delivery device comprising a body having an intranostril applicator for insertion into a nostril of a patient, a drug container, and a manually pressure-actuated actuator fixed to at least one of the applicator and the container and actuatably fluidly connecting the applicator and the container, whereby drug from the container is provided to the applicator upon application of pressure by the patient to the actuator,

the improvement comprising the actuator being positioned with respect to the intranostril applicator in such a way that actuating pressure must be applied to the actuator in a direction which is not parallel to the axis of the nostril into which the applicator is inserted.

36. The device of claim 35, wherein the actuator is positioned such that actuating pressure must be applied to the actuator in a direction which is offset by at least about 15 degrees from the axis of the nostril into which the applicator is inserted.

37. The device of claim 36, wherein the actuator is positioned such that actuating pressure must be applied to the actuator in a direction which is offset by at least about 30 degrees from the axis of the nostril into which the applicator is inserted.

38. The device of claim 37, wherein the actuator is positioned such that actuating pressure must be applied to the actuator in a direction which is offset by at least about 45 degrees from the axis of the nostril into which the applicator is inserted.

39. The device of claim 38, wherein the actuator is positioned such that actuating pressure must be applied to the actuator in a direction which is offset by at least about 60 degrees from the axis of the nostril into which the applicator is inserted.

40. The device of claim 39, wherein the actuator is positioned such that actuating pressure must be applied to the actuator in a direction which is offset by about 90 degrees from the axis of the nostril into which the applicator is inserted.

41. A systemic drug delivery device comprising a body having a shape which conforms to the shape of the nasal cavity of a human, the body having a proximal end and a distal portion which can be urged through a nostril of the human into the apex of the nasal cavity without injuring the human, the distal portion having a distal end and being curved or angled with respect to a longitudinal axis of the body, the longitudinal axis of body at the distal end forming an angle of about 90 degrees to about 170 degrees with respect to the longitudinal axis at the proximal end prior to insertion of the distal end into the nasal cavity, such that when the distal portion of the body is in the apex of the nasal cavity, the distal portion faces a posterior portion of the nasal cavity for dorsonasal delivery of the drug, wherein the body has an applicator portion in the form of at least one of

(a) a portion on which the drug is present,

(b) a portion to which the drug may be supplied, and

(c) a lumen through which the drug may be delivered,

the applicator portion being adapted for location in close anatomic proximity to a highly vascularized portion of the nasal epithelium when the distal portion of the body is in the apex of the nasal cavity.

42. An anatomically adapted intranasal delivery nozzle for systemically administering a composition to a human patient, the nozzle comprising a body having

a delivery lumen extending therethrough from a proximal end of the body to an outlet port, and

an exterior portion having

(i) a flattened portion situated peripherally between the proximal end and the distal portion for seating the nozzle against the nasal septum of the patient,

(ii) an anterior portion situated peripherally between the proximal end and the distal portion for seating the nozzle against a portion of the external nasal cartilage of the patient, and

(iii) an indented portion situated peripherally between the proximal end and the distal portion for seating the nozzle against a nasal concha of the patient,

wherein when the nozzle is seated, the outlet port is situated within the nasal cavity of the patient such that the axis extending from the discharge port extends through a highly vascularized portion of the nasal epithelium.