U.S. patent application number 13/234862 was filed with the patent office on 2013-05-09 for therapeutic agent for intranasal administration and method of making and using same.
This patent application is currently assigned to DYNOVA LABORATORIES, INC.. The applicant listed for this patent is Lynne Millheiser. Invention is credited to Lynne Millheiser, Wayne Jeffrey Perry.
Application Number | 20130115320 13/234862 |
Document ID | / |
Family ID | 48223850 |
Filed Date | 2013-05-09 |
United States Patent
Application |
20130115320 |
Kind Code |
A1 |
Perry; Wayne Jeffrey ; et
al. |
May 9, 2013 |
THERAPEUTIC AGENT FOR INTRANASAL ADMINISTRATION AND METHOD OF
MAKING AND USING SAME
Abstract
The present invention provides a composition suitable for
intranasal administration comprising capsaicin, dihydrocapsaicin,
and nordihydrocapsaicin in the form of capsicum used as a
therapeutic agent.
Inventors: |
Perry; Wayne Jeffrey;
(Schenectady, NY) ; Millheiser; Lynne; (Chester,
NJ) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Millheiser; Lynne |
Chester |
NJ |
US |
|
|
Assignee: |
DYNOVA LABORATORIES, INC.
Morristown
NJ
|
Family ID: |
48223850 |
Appl. No.: |
13/234862 |
Filed: |
September 16, 2011 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12849088 |
Aug 3, 2010 |
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13234862 |
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11731657 |
Mar 30, 2007 |
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12849088 |
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61405390 |
Oct 21, 2010 |
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Current U.S.
Class: |
424/760 |
Current CPC
Class: |
A61K 36/81 20130101;
A61K 9/08 20130101; A61K 47/46 20130101; A61K 9/0043 20130101; A61K
47/22 20130101 |
Class at
Publication: |
424/760 |
International
Class: |
A61K 36/81 20060101
A61K036/81; A61K 9/00 20060101 A61K009/00 |
Claims
1. A composition comprising: an aqueous homeopathic dilution of
capsicum; wherein the composition is suitable for intranasal
administration to a human in need thereof; wherein fast relief is
defined as first relief from at least one rhinitis symptom
occurring within about 30 minutes of administration.
2. The composition of claim 1, wherein the homeopathic dilution of
capsicum is at a concentration of about 0.00060% to about 0.010%
w/w containing about 0.1 to about 2.0 ppm total capsaicinoids.
3. The composition of claim 1, wherein the homeopathic dilution of
capsicum is at a concentration of about 0.0020% to about 0.0080%
w/w containing about 0.3 to about 1.5 ppm total capsaicinoids.
4. The composition of claim 1, wherein the homeopathic dilution of
capsicum is at a concentration of about 0.0030% to about 0.0080%
w/w containing about 0.5 to about 1.5 ppm total capsaicinoids.
5. The composition of claim 1, comprising rosemary extract at a
concentration of about 0.02% to about 0.25% w/w.
6. The composition of claim 1, comprising rosemary extract at a
concentration of about 0.05% to about 0.08% w/w.
7. The composition of claim 1, comprising rosemary extract at a
concentration of about 0.06% to about 0.07% w/w.
8. The composition of claim 1, wherein the first relief from
symptoms occurs within about 15 minutes of administration.
9. The composition of claim 1, wherein the first relief from
symptoms occurs within about 5 minutes of administration.
10. The composition of claim 1, wherein the first relief from
symptoms occurs within about 3 minutes of administration.
11. The composition of claim 1, wherein the first relief from
symptoms occurs within about 1 minute of administration.
12. The composition of claim 1, wherein the at least one rhinitis
symptom relieved comprise nasal congestion, sinus pressure,
headache, sinus pain or a combination thereof.
13. The composition of claim 9, wherein the at least one rhinitis
symptom relieved comprise one or more of nasal congestion, sinus
pressure, headache or a combination thereof.
14. The composition of claim 1, comprising eucalyptol at a
concentration of about 0.07% to about 0.15% w/w.
15. The composition of claim 1, comprising vegetable glycerin at a
concentration of about 3.5% to about 5.0% w/w.
16. The composition of claim 1, comprising vegetable glycerin at a
concentration of about 3.9% to about 4.5% w/w.
17. The composition of claim 1, comprising ascorbic acid at a
concentration of about 0.10% to about 0.90% w/w.
18. The composition of claim 1, comprising sea salt at a
concentration of about 0.40% to about 1.2% w/w.
19. A composition comprising: an aqueous solution of capsicum at a
concentration of about 0.00060% to about 0.010% w/w containing
about 0.1 to about 2.0 ppm total capsaicinoids; wherein the
composition is suitable for intranasal administration to a human in
need thereof; wherein the first relief from at least one rhinitis
symptom occurs within about 30 minutes of administration.
20. The composition of claim 19, wherein the aqueous solution of
capsicum is at a concentration of about 0.0020% to about 0.0080%
w/w containing about 0.3 to about 1.5 ppm total capsaicinoids.
21. The composition of claim 19, wherein the aqueous solution of
capsicum is at a concentration of about 0.0030% to about 0.0080%
w/w containing about 0.5 to about 1.5 ppm total capsaicinoids.
22. The composition of claim 19, comprising rosemary extract at a
concentration of about 0.02% to about 0.25% w/w.
23. The composition of claim 19, comprising rosemary extract at a
concentration of about 0.05% to about 0.1% w/w.
24. The composition of claim 19, comprising rosemary extract at a
concentration of about 0.06% to about 0.07% w/w.
25. The composition of claim 19, wherein the first relief from at
least one symptom occurs within about 15 minutes of
administration.
26. The composition of claim 19, wherein the first relief from at
least one symptoms occur within about 5 minutes of
administration.
27. The composition of claim 19, wherein the first relief from at
least one symptom occurs within about 3 minutes of
administration.
28. The composition of claim 19, wherein the first relief from at
least one symptom occurs within about 1 minute of
administration.
29. The composition of claim 19, wherein the at least one rhinitis
symptom relieved comprises nasal congestion, sinus pressure,
headache, sinus pain or a combination thereof.
30. The composition of claim 26, wherein the at least one rhinitis
symptom relieved comprises nasal congestion, sinus pressure,
headache or a combination thereof.
31. A composition comprising: an aqueous solution of capsicum at a
concentration of about 0.00060% to about 0.010% w/w containing
about 0.1 to about 2.0 ppm total capsaicinoids; rosemary extract at
a concentration of about 0.02% to about 0.25% w/w; wherein the
composition is suitable for intranasal administration to a human in
need thereof; wherein the first relief from at lease one rhinitis
symptom occurs within about 30 minutes of administration.
32. The composition of claim 31, wherein the aqueous solution of
capsicum is at a concentration of about 0.0020% to about 0.0080%
w/w containing about 0.3 to about 1.5 ppm total capsaicinoids.
33. The composition of claim 31, wherein the aqueous solution of
capsicum is at a concentration of about 0.0030% to about 0.0080%
w/w containing about 0.5 to about 1.5 ppm total capsaicinoids.
34. The composition of claim 31, comprising rosemary extract at a
concentration of about 0.05% to about 0.1% w/w.
35. The composition of claim 31, comprising rosemary extract at a
concentration of about 0.06% to about 0.07% w/w.
36. The composition of claim 31, wherein the first relief from
symptoms occurs within about 15 minutes of administration.
37. The composition of claim 31, wherein the first relief from
symptoms occurs within about 5 minutes of administration.
38. The composition of claim 31, wherein the first relief from
symptoms occurs within about 3 minutes of administration.
39. The composition of claim 31, wherein the first relief from
symptoms occurs within about 1 minute of administration.
40. The composition of claim 31, wherein the rhinitis symptoms
relieved comprise at least one of nasal congestion, sinus pressure,
headache, sinus pain or a combination thereof.
41. The composition of claim 37, wherein the at least one rhinitis
symptom relieved comprises nasal congestion, sinus pressure,
headache or a combination thereof.
42. A composition comprising: an aqueous solution of capsicum at a
concentration of about 0.00060% to about 0.010% w/w containing
about 0.1 to about 2.0 ppm total capsaicinoids; rosemary extract at
a concentration of about 0.02% to about 0.25% w/w; wherein the
composition is suitable for intranasal administration in a human in
need thereof; wherein the first relief from at least one symptom
occurs within about 5 minutes of administration; and wherein the
symptoms comprise at least one of nasal congestion, sinus pressure,
headache or a combination thereof.
43. A composition comprising: an aqueous solution of capsicum at a
concentration of about 0.00060% to about 0.010% w/w containing
about 0.1 to about 2.0 ppm total capsaicinoids; rosemary extract at
a concentration of about 0.02% to about 0.25% w/w; eucalyptol at a
concentration of about 0.07% to about 0.15% w/w; vegetable glycerin
at a concentration of about 3.5% to about 5.0% w/w; wherein the
composition is suitable for intranasal administration in a human in
need thereof; wherein the first relief from at least one symptom
occurs within about 5 minutes of administration; and wherein
symptoms consist of at least one of nasal congestion, sinus
pressure, headache or a combination thereof.
44. The composition of claim 43, comprising ascorbic acid at a
concentration of about 0.10% to about 0.90% w/w and sea salt at a
concentration of about 0.40% to about 1.2% w/w.
45. The composition of claim 43, wherein the first relief from at
least one symptom occurs within about 3 minutes of
administration.
46. The composition of claim 43, wherein the first relief from at
least one symptom occurs within about 1 minute of
administration.
47. A composition comprising: an aqueous solution of capsicum at a
concentration of about 0.00060% to about 0.010% w/w containing
about 0.1 to about 2.0 ppm total capsaicinoids; rosemary extract at
a concentration of about 0.02% to about 0.25% w/w; wherein the
composition is suitable for intranasal administration to a human in
need thereof; wherein the composition does not require the
administration of a second agent to enable tolerance of the
composition; wherein the first relief from at least one rhinitis
symptom occurs within about 30 minutes of administration.
48. A composition comprising: an aqueous solution of capsicum at a
concentration of about 0.00060% to about 0.010% w/w containing
about 0.1 to about 2.0 ppm total capsaicinoids; rosemary extract at
a concentration of about 0.02% to about 0.25% w/w; wherein the
composition is suitable for intranasal administration to a human in
need thereof; wherein the composition is self-administered; wherein
the first relief from at least one rhinitis symptom occurs within
about 30 minutes of administration.
49. A method for intranasal administration of an aqueous
homeopathic dilution of capsicum to a human in need thereof
comprising the steps of: administering intranasally a solution
comprising about 0.00060% to about 0.010% w/w capsicum containing
about 0.1 to about 2.0 ppm total capsaicinoids and rosemary extract
at a concentration of about 0.02% to about 0.25% w/w; effecting the
first relief from at least one symptom nasal congestion, sinus
pressure, sinus pain, headache or a combination thereof within
about 30 minutes of administration.
50. The method of claim 47 wherein the capsicum is present in
solution at a concentration of about 0.0020% to about 0.0080% w/w
containing about 0.3 to about 1.5 ppm total capsaicinoids.
51. The method of claim 47, wherein the first relief from at least
one symptom occurs within about 5 minutes of administration.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. Patent Application
No. 61/405,390, filed Oct. 21, 2010, and is a continuation-in-part
of U.S. patent application Ser. No. 12/849,088, filed Aug. 3, 2010,
which is a continuation of U.S. patent application Ser. No.
11/731,657, filed Mar. 30, 2007, now abandoned, all of which are
herein incorporated by reference in their entirety. This
application is also related to U.S. patent application Ser. No.
11/731,656, filed Mar. 30, 2007, now abandoned, which is herein
incorporated by reference in its entirety.
FIELD OF THE INVENTION
[0002] The present invention relates to a therapeutic agent capable
of intranasal administration comprising capsicum and/or
capsaicinoids as the therapeutic agent.
BACKGROUND OF THE INVENTION
[0003] Non-allergic rhinitis ("NAR") affects millions of Americans,
but the mechanism(s) remains unknown. Transient receptor potential
vanilloid-1 ("TRPV1") may be involved, as single dose studies of
intranasal capsaicin, a TRPV1 agonist, have demonstrated reduced
nasal congestion in rhinitis subjects.
[0004] Chronic rhinitis is defined as persistent inflammation of
the mucosal membranes lining the nasal cavity, characterized by
symptoms of nasal congestion, rhinorrhea, sneezing and itching with
or without post-nasal drainage. (Settipane R A, Lieberman P. Update
on nonallergic rhinitis. Ann Allergy Asthma Immunol 2001;
86:494-507; quiz-8. Wallace D V, Dykewicz M S, Bernstein D I,
Blessing-Moore J, Cox L, Khan D A, et al. The diagnosis and
management of rhinitis: an updated practice parameter. J Allergy
Clin Immunol 2008; 122:S1-84.) A diagnosis requires the exclusion
of structural abnormalities and underlying medical conditions that
can manifest with rhinitis symptoms. (Settipane R A, Lieberman P.
Update on nonallergic rhinitis. Ann Allergy Asthma Immunol 2001;
86:494-507; quiz-8. Wallace D V, Dykewicz M S, Bernstein D I,
Blessing-Moore J, Cox L, Khan D A, et al. The diagnosis and
management of rhinitis: an updated practice parameter. J Allergy
Clin Immunol 2008; 122:S1-84.) Broadly defined, rhinitis can be
divided into inflammatory and non-inflammatory rhinitis. (Wallace D
V, Dykewicz M S, Bernstein D I, Blessing-Moore J, Cox L, Khan D A,
et al. The diagnosis and management of rhinitis: an updated
practice parameter. J Allergy Clin Immunol 2008; 122:S1-84.
Bernstein J A. Characteristics of Non-Allergic Rhintiis. World
Allergy Journal 2009; 2:102-5.)
[0005] Inflammatory rhinitis includes seasonal or perennial
allergic rhinitis, entopic rhinitis and non-allergic rhinitis
eosinophilic syndrome ("NARES") whereas non-inflammatory rhinitis
includes vasomotor rhinitis ("VMR"), commonly referred to as
idiopathic rhinitis, and other non-allergic rhinitis conditions
such as rhinitis medicamentosa, gustatory rhinitis and
hormonally-induced rhinitis. (Bernstein J A. Characteristics of
Non-Allergic Rhintiis. World Allergy Journal 2009; 2:102-5. Kaliner
M. Classification of Nonallergic Rhinitis Syndromes With a Focus on
Vasomotor Rhinitis, Proposed to be known henceforth as Nonallergic
Rhinopathy. World Allergy Journal 2009; 2:98-101.) Since patients
with allergic rhinitis often exhibit significant symptoms in
response to irritant triggers, clinicians have postulated that
allergic and non-allergic rhinitis components often co-exist and
have therefore referred to this condition as "mixed rhinitis"
("MR"). (Bernstein J A, Rezvani, M. Mixed Rhinitis: A New Subclass
of Chronic Rhinitis. In: Kaliner M, ed. Current Review of Rhinitis,
2nd ed 2006; Philadelphia, Pa.:69-78.) Cross-sectional
questionnaire survey studies have estimated that up to 75% of
chronic rhinitis patients have either non-allergic or mixed
rhinitis. (Settipane R A. Demographics and epidemiology of allergic
and nonallergic rhinitis. Allergy Asthma Proc 2001; 22:185-9.)
[0006] Currently non-allergic rhinitis ("NAR") conditions are
diagnoses by exclusion, as the mechanism(s) of this disorder is
unknown and therefore, there are no specific biomarkers or tests
that establish a definitive diagnosis. (Bernstein J A.
Characteristics of Non-Allergic Rhintiis. World Allergy Journal
2009; 2:102-5. Kaliner M. Classification of Nonallergic Rhinitis
Syndromes With a Focus on Vasomotor Rhinitis, Proposed to be known
henceforth as Nonallergic Rhinopathy. World Allergy Journal 2009;
2:98-101. Brandt D, Bernstein J A. Questionnaire evaluation and
risk factor identification for nonallergic vasomotor rhinitis. Ann
Allergy Asthma Immunol 2006; 96:526-32. Garay R. Mechanisms of
vasomotor rhinitis. Allergy 2004; 59 Suppl 76:4-9; discussion-10.)
The most popular mechanism postulated for non-allergic rhinitis has
been an autonomic imbalance between the sympathetic and
parasympathetic nervous system resulting in parasympathetic
hyperactivity leading to nasal congestion and drainage. (Baraniuk J
N. Sensory, parasympathetic, and sympathetic neural influences in
the nasal mucosa. J Allergy Clin Immunol 1992; 90:1045-50. Jones A
S. Autonomic reflexes and non-allergic rhinitis. Allergy 1997;
52:14-9.) Recently, transient receptor protein ("TRP") ion channel
activation leading to trigeminal nerve depolarization has been
postulated to play an important role in NAR, as these ubiquitous
receptors can be activated by different temperatures, chemicals,
osmolality and other physical stimuli that are well recognized
triggers of symptoms in NAR patients. (Bernstein J A.
Characteristics of Non-Allergic Rhintiis. World Allergy Journal
2009; 2:102-5. Brandt D, Bernstein J A. Questionnaire evaluation
and risk factor identification for nonallergic vasomotor rhinitis.
Ann Allergy Asthma Immunol 2006; 96:526-32. Seki N, Shirasaki H,
Kikuchi M, Sakamoto T, Watanabe N, Himi T. Expression and
localization of TRPV1 in human nasal mucosa. Rhinology 2006;
44:128-34.)
[0007] Because mechanisms of NAR are poorly elucidated, there are
still only a few medications approved for the treatment of this
condition. Although clinical studies have found that the intranasal
antihistamines, azelastine and olopatidine, intranasal ipratropium
bromide and intranasal corticosteroids are relatively effective in
relieving symptoms related to NAR, it is unclear how they are
mechanistically exerting their effect. (Banov C H, Lieberman P.
Efficacy of azelastine nasal spray in the treatment of vasomotor
(perennial nonallergic) rhinitis. Ann Allergy Asthma Immunol 2001;
86:28-35. Georgitis J W, Banov C, Boggs P B, Dockhorn R, Grossman
J, Tinkelman D, et al. Ipratropium bromide nasal spray in
non-allergic rhinitis: efficacy, nasal cytological response and
patient evaluation on quality of life. Clin Exp Allergy 1994;
24:1049-55. Lieberman P L, Settipane R A. Azelastine nasal spray: a
review of pharmacology and clinical efficacy in allergic and
nonallergic rhinitis. Allergy Asthma Proc 2003; 24:95-105. Scadding
G K, Lund V J, Jacques L A, Richards D H. A placebo-controlled
study of fluticasone propionate aqueous nasal spray and
beclomethasone dipropionate in perennial rhinitis: efficacy in
allergic and non-allergic perennial rhinitis. Clin Exp Allergy
1995; 25:737-43. Ciprandi G. Treatment of nonallergic perennial
rhinitis. Allergy 2004; 59 Suppl 76:16-22; discussion-3.)
[0008] Capsaicin is a pungent substance found in capsicum spp. (red
pepper) that is known to ablate sensory nerve fibers in NAR
patients leading investigators to postulate a role for afferent
C-fibers in NAR. (Blom H M, Van Rijswijk J B, Garrelds I M, Mulder
P G, Timmermans T, Gerth van Wijk R. Intranasal capsaicin is
efficacious in non-allergic, non-infectious perennial rhinitis. A
placebo-controlled study. Clin Exp Allergy 1997; 27:796-801.) This
observation was supported by early placebo controlled studies that
treated NAR patients with topical capsaicin and found significant
improvement in symptom scores compared to placebo without changes
in levels of mast cell mediators (i.e., leukotrienes, prostaglandin
(PGD2) or tryptase) indicating that the effect of this medication
was not due to reduction in mast-cell mediated inflammation. (Blom
H M, Van Rijswijk J B, Garrelds I M, Mulder P G, Timmermans T,
Gerth van Wijk R. Intranasal capsaicin is efficacious in
non-allergic, non-infectious perennial rhinitis. A
placebo-controlled study. Clin Exp Allergy 1997; 27:796-801. Blom H
M, Severijnen L A, Van Rijswijk J B, Mulder P G, Van Wijk R G,
Fokkens W J. The long-term effects of capsaicin aqueous spray on
the nasal mucosa. Clin Exp Allergy 1998; 28:1351-8.)
[0009] Subsequently, it was discovered that capsaicin exerted its
activity through activation of the TRP vanilloid-1 ("TRPV1") ion
channel which leads to desensitization of nasal sensory neural
fibers and reduction in nasal hyperresponsiveness. (Seki N,
Shirasaki H, Kikuchi M, Sakamoto T, Watanabe N, Himi T. Expression
and localization of TRPV1 in human nasal mucosa. Rhinology 2006;
44:128-34.) Single intermittent short term dosing studies with
intranasal capsaicin in AR and NAR have confirmed that intranasal
capsaicin is effective at reducing nasal congestion and discharge.
(Blom H M, Van Rijswijk J B, Garrelds I M, Mulder P G, Timmermans
T, Gerth van Wijk R. Intranasal capsaicin is efficacious in
non-allergic, non-infectious perennial rhinitis. A
placebo-controlled study. Clin Exp Allergy 1997; 27:796-801. Blom H
M, Severijnen L A, Van Rijswijk J B, Mulder P G, Van Wijk R G,
Fokkens W J. The long-term effects of capsaicin aqueous spray on
the nasal mucosa. Clin Exp Allergy 1998; 28:1351-8. Lacroix J S,
Buvelot J M, Polla B S, Lundberg J M. Improvement of symptoms of
non-allergic chronic rhinitis by local treatment with capsaicin.
Clin Exp Allergy 1991; 21:595-600. Sanico A M, Philip G, Proud D,
Naclerio R M, Togias A. Comparison of nasal mucosal responsiveness
to neuronal stimulation in non-allergic and allergic rhinitis:
effects of capsaicin nasal challenge. Clin Exp Allergy 1998;
28:92-100. Van Rijswijk J B, Boeke E L, Keizer J M, Mulder P G,
Blom H M, Fokkens W J. Intranasal capsaicin reduces nasal
hyperreactivity in idiopathic rhinitis: a double-blind randomized
application regimen study. Allergy 2003; 58:754-61.)
[0010] However, the concentration of capsaicin used and found
effective in these studies, ranging from 30 ppm to 300 ppm, was
very irritating and required a physician to co-administer a local
anesthetic making it impractical and intolerable for patients to
self-administer the composition or use this treatment long term.
(Blom H M, Van Rijswijk J B, Garrelds I M, Mulder P G, Timmermans
T, Gerth van Wijk R. Intranasal capsaicin is efficacious in
non-allergic, non-infectious perennial rhinitis. A
placebo-controlled study. Clin Exp Allergy 1997; 27:796-801. Blom H
M, Severijnen L A, Van Rijswijk J B, Mulder P G, Van Wijk R G,
Fokkens W J. The long-term effects of capsaicin aqueous spray on
the nasal mucosa. Clin Exp Allergy 1998; 28:1351-8. Lacroix J S,
Buvelot J M, Polla B S, Lundberg J M. Improvement of symptoms of
non-allergic chronic rhinitis by local treatment with capsaicin.
Clin Exp Allergy 1991; 21:595-600. Van Rijswijk J B, Boeke E L,
Keizer J M, Mulder P G, Blom H M, Fokkens W J. Intranasal capsaicin
reduces nasal hyperreactivity in idiopathic rhinitis: a
double-blind randomized application regimen study. Allergy 2003;
58:754-61.) Applicant is not aware of any prior studies disclosing,
teaching or suggesting a composition comprising capsicum/capsaicin
present in an effective concentration, that may be
self-administered as a mono-therapy by the user. Furthermore,
Applicant is not aware of any studies demonstrating clinical
efficacy of capsicum/capsaicin at concentrations 10% or less of the
dosages used in previous rhinitis clinical trials. What is needed
in the industry is a composition comprising capsicum/capsaicin that
may be administered intranasally in an effective concentration,
allowing the user to self-administer the composition without the
need for the user to visit a physician's office for each
treatment.
[0011] According to an embodiment of the present invention, it has
been unexpectedly discovered that certain concentrations of
capsicum comprising capsaicinoids, including capsaicin, may be
self-administered by the user and provide relief from symptoms.
Previously it has not been possible to deliver an effective
concentration of capsicum intranasally without causing such
discomfort to the user requiring the use of an adjunct to
desensitize the nasal membranes in order to administer the
capsicum. What is needed in the industry is a composition
comprising capsicum/capsaicin that is effective in relieving
symptoms, but can be used without causing discomfort to the user or
requiring adjunct agents.
[0012] Applicant is not aware of any prior studies investigating
the immediate or short-term relief of symptoms provided by the
intranasal administration of capsicum as disclosed in the present
application. In addition, Applicant is not aware of any prior
studies disclosing that a low homeopathic dilution of capsicum is
clinically effective for the treatment of rhinitis.
[0013] What is needed in the industry is a nasally administered
composition that provides a rapid onset of relief for rhinitis
subjects. What is needed in the industry is an intranasally
administered composition having a rapid onset of action and
significant reduction of symptoms, that is an attractive
mono-therapy or adjunctive therapy for the management of rhinitis
symptoms, including, but not limited to, chronic rhinitis symptoms.
What is needed in the industry is an intranasally administered
composition having a quick onset of action with an average time to
first relief in less than thirty minutes, less than five minutes,
and even less than one minute.
[0014] Currently available over the counter ("OTC") medicated nasal
sprays for the relief of rhinitis symptoms necessarily contain
labels with a warning indicating that the product should not be
used for more than three days. Extended use of these known products
leads to the occurrence of rebound congestion and the potential for
addiction. These known OTC products are not suitable for use by
those with symptoms that last longer than three days, including
those suffering chronic conditions, and those suffering from
chronic rhinitis symptoms.
[0015] What is needed in the industry is an intranasally
administered composition that is well-tolerated with prolonged
treatment results and with substantially no alteration or
impairment in olfaction. What is needed in the industry is an
intranasal composition wherein users experience little to no
rebound congestion. What is needed in the industry is an intranasal
composition wherein use of the composition results in an
improvement in olfaction versus placebo after continued use.
[0016] What is needed in the industry is an intranasally
administered composition wherein during a treatment period is
significantly effective at improving nasal congestion, sinus
pressure, sinus pain and headache compared to placebo. What is
needed in the industry is a nasally administered composition that
provides safe, sustained relief over the course of a treatment
period. What is needed in the industry is a nasally administered
composition that works fast and is safe.
[0017] What is needed in the industry is an intranasally
administered composition that provides relief from at least one of
nasal congestion, sinus pressure and sinus pain with an improved
therapeutic response that continues over time with nasal
congestion, sinus pressure, sinus pain and headache significantly
improved at about 5, 10, 15 and 30 minutes and persists for nasal
congestion and sinus pain through the longest time point
measured.
SUMMARY OF THE INVENTION
[0018] An embodiment of the present invention is a composition
comprising an aqueous homeopathic dilution of capsicum, wherein the
composition is suitable for intranasal administration to a human in
need thereof, that provides fast relief, wherein the first relief
from at least one rhinitis symptom occurs within about 30 minutes
of administration. The homeopathic dilution of capsicum may be at a
concentration of about 0.00060% to about 0.010% w/w or containing
about 0.1 to about 2.0 ppm total capsaicinoids. The homeopathic
dilution of capsicum may be at a concentration of about 0.0020% to
about 0.0080% w/w or containing about 0.3 to about 1.5 ppm total
capsaicinoids. The homeopathic dilution of capsicum may be at a
concentration of about 0.0030% to about 0.0080% w/w or containing
about 0.5 to about 1.5 ppm total capsaicinoids. The composition may
comprise rosemary extract at a concentration of about 0.02% to
about 0.25% w/w, at a concentration of about 0.05% to about 0.10%
w/w, or at a concentration of about 0.06% to about 0.07% w/w. The
first relief from at least one symptom may occur within about 30
minutes of administration, within about 15 minutes of
administration, within about 5 minutes of administration, within
about 3 minutes of administration, or within about 1 minute of
administration. The rhinitis symptoms relieved may comprise at
least one of nasal congestion, sinus pressure, sinus pain,
headache, or a combination thereof. The composition may comprise
eucalyptol at a concentration of about 0.07% to about 0.15% w/w,
vegetable glycerin at a concentration of about 3.5% to about 5.0%
w/w, vegetable glycerin at a concentration of about 3.9% to about
4.5% w/w, ascorbic acid at a concentration of about 0.10% to about
0.90% w/w, sea salt at a concentration of about 0.40% to about 1.2%
w/w, potassium sorbate at a concentration of about 0.05% to about
0.3%, or a combination thereof. It is surprising and unexpected
that a homeopathic dose of capsicum, such as, but not limited to,
5% or less of therapeutic doses known in the art, is still an
effective dose. As such, it is surprising and unexpected that a
homeopathic dose of capsicum would still provide a significant
benefit as shown in an embodiment of the present invention.
[0019] An embodiment of the present invention is a composition
comprising an aqueous solution of capsicum at a concentration of
about 0.00060% to about 0.010% w/w, or containing about 0.1 to
about 2.0 ppm total capsaicinoids, including, but not limited to,
capsaicin, wherein the composition is suitable for intranasal
administration to a human in need thereof, wherein the first relief
from at least one rhinitis symptom occurs within about 30 minutes
of administration, and wherein the symptoms may comprise at least
one of nasal congestion, sinus pressure, sinus pain, headache or a
combination thereof. In an embodiment the aqueous solution of
capsicum comprises a homeopathic dilution of capsicum. In an
embodiment the aqueous solution of capsicum comprises a homeopathic
dilution of Capsicum annum. In an embodiment, the aqueous solution
of capsicum may be at a concentration of about 0.0020% to about
0.0080% w/w, or containing about 0.3 to about 1.5 ppm total
capsaicinoids. In an embodiment the aqueous solution of capsicum
may be at a concentration of about 0.0030% to about 0.0080% w/w, or
containing about 0.5 to about 1.5 ppm total capsaicinoids.
[0020] An embodiment of the present invention is a composition
comprising an aqueous solution of capsicum at a concentration of
about 0.00060% to about 0.010% w/w, resulting in about 0.1 to about
2.0 ppm total capsaicinoids. An embodiment may also comprise
rosemary extract at a concentration of about 0.02% to about 0.25%
w/w, or comprise rosemary extract at a concentration of about 0.05%
to about 0.10% w/w or about 0.06% to about 0.07% w/w, wherein the
composition is suitable for intranasal administration to a human in
need thereof, wherein the first relief from at least one rhinitis
symptom occurs within about 30 minutes of administration, and
wherein the symptoms comprise at least one of nasal congestion,
sinus pressure, sinus pain, headache or a combination thereof. In
an embodiment the aqueous solution of capsicum may or may not
comprise a homeopathic dilution of capsicum. In an embodiment the
aqueous solution of capsicum may be at a concentration of about
0.0020% to about 0.0080% w/w, or containing about 0.3 to about 1.5
ppm total capsaicinoids. In an embodiment the aqueous solution of
capsicum may be at a concentration of about 0.0030% to about
0.0080% w/w, or containing about 0.5 to about 1.5 ppm total
capsaicinoids. It is surprising and unexpected that a homeopathic
dose of capsaicin, such as, but not limited to, 5% or less of
therapeutic doses known in the art, is still an effective dose. As
such, it is surprising and unexpected that a homeopathic dose of
capsicum would still provide a significant benefit as shown in an
embodiment of the present invention.
[0021] A surprising and unexpected result according to an
embodiment of the present invention is that the presence of the
rosemary extract acts to increase the tolerability of the capsicum
in the composition to the user. Applicant is not aware of any
disclosure, teaching, or suggestion in the related art that the
presence of rosemary extract in a composition containing capsicum
would act to make the capsicum more tolerable to the user.
[0022] An embodiment of the present invention is a composition
comprising an aqueous solution of capsicum at a concentration of
about 0.00060% to about 0.010% w/w. An embodiment may comprise
eucalyptol at a concentration of about 0.07% to about 0.15% w/w,
wherein the composition is suitable for intranasal administration
to a human in need thereof, wherein the first relief from at least
one symptom occurs within about 30 minutes of administration, and
wherein the symptoms consist of at least one of nasal congestion,
sinus pressure, sinus pain, headache or a combination thereof. In
an embodiment the eucalyptol may be at a concentration of about
0.13% w/w. In an embodiment the aqueous solution of capsicum
comprises a homeopathic dilution of capsicum. In an embodiment the
aqueous solution of capsicum may comprise a homeopathic dilution of
Capsicum annum. In one embodiment, the aqueous solution of capsicum
may be at a concentration of about 0.0020% to about 0.0080% w/w, or
containing about 0.3 to about 1.5 ppm total capsaicinoids. In one
embodiment, the aqueous solution of capsicum may be at a
concentration of about 0.0030% to about 0.0080% w/w, or containing
about 0.5 to about 1.5 ppm total capsaicinoids. In an embodiment
the composition may also comprise rosemary extract at a
concentration of about 0.02% to about 0.25% w/w, about 0.05% to
about 0.10% w/w or comprise rosemary extract at a concentration of
about 0.06% to about 0.07% w/w. In an embodiment the composition
does not require the administration of a separate agent before,
during, and/or after administration of the composition to enable
tolerance of the composition. In an embodiment the composition is
self-administered by the human in need thereof.
[0023] In an embodiment the composition may also comprise vegetable
glycerin at a concentration of about 3.5% to about 5.0% w/w or at a
concentration of about 3.9% to about 4.5% w/w. In an embodiment the
composition may comprise ascorbic acid at a concentration of about
0.10% to about 0.90% w/w, sea salt at a concentration of about
0.40% to about 1.2% w/w, potassium sorbate at a concentration of
about 0.05% to about 0.3%, or a combination thereof. In an
embodiment the composition may provide the first relief from at
least one symptom within about 30 minutes, 15 minutes, 5 minutes, 3
minutes, or within about 1 minute of administration.
[0024] An embodiment of the present invention is a composition
comprising an aqueous solution of capsicum at a concentration of
about 0.00060% to about 0.010% w/w, or containing about 0.1 to
about 2.0 ppm total capsaicinoids and rosemary extract at a
concentration of about 0.02% to about 0.25% w/w. An embodiment may
further comprise eucalyptol at a concentration of about 0.07% to
about 0.15%, vegetable glycerin at a concentration of about 3.5% to
about 5.0% w/w or a combination thereof, wherein the composition is
suitable for intranasal administration to a human in need thereof,
wherein fast relief is first relief from at least one symptom
occurring within about 30, 15, or 5 minutes of administration,
wherein the symptoms consist of at least one of nasal congestion,
sinus pressure, sinus pain, headache or a combination thereof. The
composition may also comprise ascorbic acid at a concentration of
about 0.10% to about 0.90% w/w, sea salt at a concentration of
about 0.40% to about 1.2% w/w and potassium sorbate at a
concentration of about 0.05 to about 0.3%, or a combination
thereof. The composition may provide first relief from at least one
symptom within about 3 minutes of administration or may provide
first relief from at least one symptom within about 1 minute of
administration.
[0025] An embodiment of the present invention is an aqueous
solution suitable for intranasal administration to a human in need
thereof, comprising an aqueous solution of capsicum at a
concentration of about 0.00060% to about 0.010% w/w, or containing
about 0.1 to about 2.0 ppm total capsaicinoids, rosemary extract at
a concentration of about 0.02% to about 0.25% w/w, eucalyptol at a
concentration of about 0.07% to about 0.15%, vegetable glycerin at
a concentration of about 3.5% to about 5.0% w/w, or a combination
thereof, wherein, on introduction into the nasal cavity of a human
in need thereof, first relief from at least one symptom occurs
within about 30, 15, or 5 minutes of administration, wherein
symptoms comprise at least one of nasal congestion, sinus pressure,
sinus pain, headache or a combination thereof. In an embodiment the
aqueous solution of capsicum comprises a homeopathic dilution of
capsicum. In an embodiment the aqueous solution of capsicum may be
at a concentration of about 0.0020% to about 0.0080% w/w, or
containing about 0.3 to about 1.5 ppm total capsaicinoids.
[0026] An embodiment of the present invention is a method for
treating a human in need thereof comprising the steps of intranasal
administration of an aqueous solution of capsicum and effecting the
relief of at least one rhinitis symptom. The aqueous solution of
capsicum may comprise a homeopathic dilution of capsicum,
including, but not limited to, Capsicum annum. In an embodiment,
the composition may comprise about 0.00060% to about 0.010% w/w
capsicum, or containing about 0.1 to about 2.0 ppm total
capsaicinoids, effecting the first relief from symptoms of at least
one of nasal congestion, sinus pressure, sinus pain, headache or a
combination thereof within about 30, 15, or 5 minutes of
administration. In an embodiment the capsicum may be present in
solution at a concentration of about 0.0020% to about 0.0080% w/w,
or containing about 0.3 to about 1.5 ppm total capsaicinoids. In an
embodiment the first relief from at least one symptom may occur
within about 3 minutes or within about 1 minute of
administration.
[0027] An embodiment of the present invention is a method for
treating a human in need thereof comprising the steps of intranasal
administration of an aqueous solution of capsicum comprising about
0.00060% to about 0.010% w/w capsicum, or containing about 0.1 to
about 2.0 ppm total capsaicinoids, and rosemary extract at a
concentration of about 0.02% to about 0.25% w/w, effecting the
first relief from symptoms of at least one of nasal congestion,
sinus pressure, sinus pain, headache or a combination thereof
within about 30, 15, or 5 minutes of administration. In an
embodiment the aqueous solution of capsicum may comprise a
homeopathic dilution of capsicum, and may comprise a homeopathic
dilution of Capsicum annum. In an embodiment the capsicum may be
present in solution at a concentration of about 0.0020% to about
0.0080% w/w, or containing about 0.3 to about 1.5 ppm total
capsaicinoids. In an embodiment the first relief from at least one
symptom may occur within about 3 minutes of administration or
within about 1 minute of administration.
[0028] An embodiment of the present invention is a method for
treating a human in need thereof comprising the steps of intranasal
administration of an aqueous solution of capsicum comprising about
0.00060% to about 0.010% w/w capsicum, or containing about 0.1 to
about 2.0 ppm total capsaicinoids, and eucalyptol at a
concentration of about 0.07% to about 0.15% w/w, effecting the
first relief from symptoms of at least one of nasal congestion,
sinus pressure, sinus pain, headache or a combination thereof
within about 30, 15, or 5 minutes of administration. In an
embodiment the aqueous solution of capsicum comprises a homeopathic
dilution of capsicum. In an embodiment the capsicum may be present
in solution at a concentration of about 0.0020% to about 0.0080%
w/w, or containing about 0.3 to about 1.5 ppm total capsaicinoids.
In an embodiment the first relief from at least one rhinitis
symptom may occur within about 3 minutes of administration.
[0029] An advantage of an embodiment of the present invention is an
intranasally administered composition having a quick and/or fast
onset of action with an average time to first relief of at least
one symptom of less than about thirty minutes, about fifteen
minutes, about five minutes, about three minutes, and even less
than about one minute.
[0030] An embodiment of the present invention is an intranasally
administered composition that provides relief from at least one of
nasal congestion, sinus pressure, sinus pain and headache with an
improved therapeutic response that continues over time with at
least one of nasal congestion, sinus pressure, sinus pain and
headache significantly improved at about 5, 10, 15, 30 and/or 60
minutes. An advantage of an embodiment of the present invention is
an intranasally administered composition having a rapid onset of
action and significant reduction of symptoms that may be an
attractive mono-therapy or adjunctive therapy for the management of
rhinitis symptoms.
[0031] An embodiment of the present invention is an intranasal
composition wherein users experience little to no rebound
congestion. An advantage of an embodiment of the present invention
is an intranasal composition wherein users experience essentially
no alteration, or even an improvement, in olfaction versus placebo
after continued use. An advantage of an embodiment of the present
invention is a nasally administered composition that provides a
rapid onset of relief for rhinitis subjects, while also providing
safe, sustained relief over the course of a treatment period.
[0032] An advantage of an embodiment of the present invention is an
intranasally administered composition wherein during a treatment
period is significantly effective at improving at least one of
nasal congestion, sinus pressure, sinus pain and headache compared
to placebo.
[0033] An advantage of an embodiment of the present invention is an
intranasally administered composition that is well-tolerated and
with prolonged treatment results in substantially no reduction in
olfaction.
[0034] An advantage of an embodiment of the present invention is an
agent that may be used as a mono-therapy comprising capsaicin,
dihydrocapsaicin, and nordihydrocapsaicin and other
capsaicinoids.
[0035] In an embodiment of the present invention, the agent
comprises between about 0.000001% to about 0.01% by weight of the
total water or suspension material weight of capsicum comprising at
least, but not limited to, capsaicin, dihydrocapsaicin, and
nordihydrocapsaicin, resulting in about 0.0001 to about 1.5 ppm
total capsaicinoids.
[0036] In another embodiment of the present invention the agent
comprises between about 0.1 ppm to about 2.0 ppm total
capsaicinoids comprising at least, but not limited to, capsaicin,
dihydrocapsaicin, and nordihydrocapsaicin.
[0037] In another embodiment of the present invention, the agent
comprises capsicum, comprising capsaicin, dihydrocapsaicin, and
nordihydrocapsaicin, having a heat range of about 100,000 to about
1,000,000 Scoville Heat Units.
[0038] These and other embodiments of the present invention are
more fully described in connection with the detailed
description.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
[0039] FIG. 1 illustrates the activation of a calcium channel by
the composition of the present invention will result in an increase
in fluorescence.
[0040] FIG. 2 is schematic of the study protocol used in connection
with the present invention.
[0041] FIG. 3 is a graphic illustrating the percent improvements of
various symptoms comparing the administration of intranasally
administered capsicum composition to an administration of a
placebo.
[0042] FIG. 4 are graphics illustrating symptom scores relative to
time for various symptoms comparing the administration of
intranasally administered capsicum composition to an administration
of a placebo.
DETAILED DESCRIPTION OF THE INVENTION
[0043] Capsicum is derived from several Capsicum pepper varieties.
The Capsicum variety utilized in embodiments of the present
invention is derived from cayenne pepper plants, which may comprise
at least one of Capsicum baccatum, Capsicum annum, and Capsicum
frutescens, or a combination thereof. The capsicum comprises
capsaicin, dihydrocapsaicin, and nordihydrocapsaicin and possibly
other capsaicinoids as active ingredients. The capsicum utilized in
an embodiment of the present invention may comprise an all natural,
water soluble and/or soluble liquid suspension material. The
aqueous solution of capsicum may comprise a homeopathic dilution of
capsicum. The aqueous solution of capsicum may comprise a
homeopathic dilution of Capsicum annum. The use of capsicum
comprising capsaicin, dihydrocapsaicin, nordihydrocapsaicin, and
possibly other capsaicinoids as opposed to synthetic capsaicin may
allow for repeated use and effective delivery without causing an
uncomfortable and/or intolerable burning sensation in the nasal
mucosa of the user. However, it is within the scope of the present
invention that a combination of at least one synthetic capsaicinoid
could also be used.
[0044] Embodiments of the present invention relate to an agent
comprising capsicum comprising capsaicin, dihydrocapsaicin,
nordihydrocapsaicin, and other capsaicinoids to relieve at least
one rhinitis symptom in a human in need thereof. The aqueous
solution of capsicum may comprise a homeopathic dilution of
capsicum.
[0045] In an embodiment of the present invention, the composition
may comprise between about 0.000001% to about 0.008% by weight of
the total water or suspension material weight of capsicum
comprising capsaicin, dihydrocapsaicin, and nordihydrocapsaicin
among others, resulting in about 0.0001 to about 1.5 ppm total
capsaicinoids.
[0046] In an embodiment of the present invention the composition
comprises between about 0.1 to about 2.0 ppm total capsaicinoids
present in capsicum, including, but not limited to, capsaicin,
dihydrocapsaicin, and nordihydrocapsaicin.
[0047] In an embodiment of the present invention the composition
may comprise capsicum including capsaicin, dihydrocapsaicin, and
nordihydrocapsaicin and possibly other capsaicinoids having a heat
range of between about 100,000 to about 1,000,000 Scoville Heat
Units. The capsicum including, but not limited to, capsaicin,
dihydrocapsaicin, and nordihydrocapsaicin is present in a
non-caustic and safe amount.
[0048] In an embodiment the aqueous solution of capsicum comprises
a homeopathic dilution of capsicum. In an embodiment the aqueous
solution of capsicum comprises a homeopathic dilution of Capsicum
annum.
[0049] An embodiment of the present invention comprises rosemary
extract at a concentration of about 0.02% to about 0.50% w/w in
addition to the capsicum. The composition may comprise rosemary
extract at a concentration of about 0.05% to about 0.10% w/w, or at
a concentration of about 0.06% to about 0.07% w/w.
[0050] A surprising and unexpected result according to an
embodiment of the present invention is that the presence of the
rosemary extract acts to increase the tolerability of the capsicum
in the composition to the user.
[0051] Applicant is not aware of any disclosure, teaching, or
suggestion in the art that the addition of rosemary extract in a
composition containing capsicum would act to make the capsicum more
tolerable to the user.
[0052] An embodiment of the present invention may comprise
eucalyptol at a concentration of about 0.07% to about 0.15% w/w in
addition to the capsicum.
[0053] An embodiment of the present invention may comprise at least
one of vegetable glycerin at a concentration of about 3.5% to about
5.0% w/w, vegetable glycerin at a concentration of about 3.9% to
about 4.5% w/w, ascorbic acid at a concentration of about 0.10% to
about 0.90% w/w, sea salt at a concentration of about 0.40% to
about 1.2% w/w, potassium sorbate at a concentration of about 0.05%
to about 0.30% or a combination thereof, in addition to the
capsicum.
[0054] In an embodiment of the present invention the composition
may be an intranasal spray. In a further embodiment of the present
invention, the composition may be an intranasal spray wherein the
capsicum is released in a metered dose. In yet another embodiment
of the present invention the composition may be an intranasal spray
wherein the capsicum is released in a time released dose. In yet
another embodiment of the present invention the composition may be
disposed in, about and/or around a swab for intranasal
delivery.
[0055] An embodiment of the invention relates to a method of
treating a human in need thereof, by delivering the composition
described herein and wherein capsicum including, but not limited
to, capsaicin, dihydrocapsaicin, and nordihydrocapsaicin is the
effective agent. The method comprises the intranasal administration
of capsicum comprising, but not limited to, capsaicin,
dihydrocapsaicin, and nordihydrocapsaicin effecting the relief of
at least one rhinitis symptom. It will be apparent to one skilled
in the art that the following are examples of formulations and many
more formulations are possible and fall within embodiments of the
present invention as disclosed and claimed herein.
Example 1
[0056] It is hypothesized that capsicum, comprising capsaicinoids,
including capsaicin, and possibly other ingredients in Applicant's
composition, used for relief of rhinitis and allergic symptoms act
via activation of TRP-family receptors. Applicant has developed an
in vitro fluorometric assay to measure receptor activity in the
presence of various concentrations of capsaicin/capsaicinoids. The
activation of the receptors in the in vitro assay correlates with
Applicant's demonstrated symptom relief as evidenced in the
examples below. Specifically, the goal of the in vitro assay is to
quantitatively measure TRPV activation to determine the dose
response of airway component cells to Applicant's compositions
comprising capsaicin/capsaicinoids. To this end, Applicant
developed a new assay for transient receptor protein vanilloid
("TRPV") activation in cells. The assay is fluorometric in nature,
relying upon a calcium-binding fluor, Fura-4. (available from
Invitrogen Life Sciences and other vendors). Fura-4 fluoresces at a
specific wavelength when it binds to calcium. Cells are loaded with
Fura-4, and under digital confocal observation exposed to
capsaicin/capsaicinoid containing compositions. The signal
intensity over single cells is captured for 0.5-5 minutes and the
result expressed as normalized (to baseline) signal intensity over
time.
[0057] As shown in FIG. 1, the activation of a calcium channel by
the composition will result in an increase in fluorescence. In the
case of TRPV channels, since the channels are activated transiently
(hence the name, Transient Receptor Potential V channels, TRPV,)
the signals rapidly diminish in 1-2 minutes. The effects of the
capsaicin/capsaicinoid-containing compositions to TRPV1 knockout
cells (gene targeted ablation of the TRPV1, capsaicin receptor) is
shown. Applicant performed the assay using compositions comprising
varying levels of capsaicin/capsaicinoids, shown in FIG. 1, and
achieved a dose-response, demonstrating that the in vitro assay
distinguishes responses of about 1 ppm (n=14), 0.5 ppm (n=12), 0.25
ppm (n=8) and 0.10 ppm (n=4) concentration of total capsaicinoids,
including capsaicin. The concentration at 1 ppm is about 0.0064%
w/w capsicum, 0.5 ppm concentration is about 0.0032% w/w capsicum,
0.25 ppm concentration is about 0.0016% w/w capsicum, and the 0.10
ppm concentration is about 0.0008% capsicum. Responses are
statistically different at the peak of activation (P<0.05). Mean
(curves) and standard deviation (vertical lines) of fluorescent
intensities of cells treated with the indicated compositions are
shown. Formulations were perfused at time=0, and intensity plotted
vs. time (seconds). Each signal was normalized to the baseline
reading of that cell or part of a cell before infusion (to account
for differential loading of Fura-4 and baseline differences in
intracellular calcium levels). Applicant is not aware of any known
in vitro studies that show the receptor response resulting from the
administration of homeopathic doses of capsicum/capsaicinoid
containing compositions.
[0058] In addition to the dose-response, the assay demonstrates
that there is no calcium uptake in the blank sample (no aromatics,
no capsaicinoids, n=1, Preliminary Data). Cells with gene targeted
ablation of the TRPV1 channel ("TRPV1 KO") also show no increase in
signal (n=1, Preliminary Data), supporting that the signal
activated by the capsaicin/capsaicinoid containing formulations is
indeed TRPV1-dependent. Applicant concludes from the data that the
capsaicin response is primarily due to TRPV1, but expects that
other TRPs will respond to the aromatics and the affect may be
different in different cell types.
[0059] The results of this study indicate that a range of
capsaicinoids from about 0.1 ppm to about 1 ppm total capsaicinoids
significantly activates the TRPV channels over the controls.
Applicant may easily extrapolate this data to reasonably infer and
support a concentration range of capsaicin/capsaicinoids that will
be effective at relieving rhinitis symptoms in humans in need
thereof. Various formulations and concentrations of
capsaicin/capsaicinoids have been used by Applicant to successfully
treat these symptoms as shown in Examples 2-5 below. The following
examples of formulations of compositions wherein the total
capsaicinoids provide quick, effective relief from symptoms.
Example 2
[0060] A clinical study was performed to assess the efficacy and
safety of a newly formulated intranasally administered capsicum
composition ("ICX") used continuously over a two week treatment
period in chronic rhinitis subjects who have a significant
component of NAR. The ICX formulation comprises from about 0.00060%
to about 0.010% w/w, or comprising about 0.1 to about 2.0 ppm total
capsaicinoids, about 0.0020% to about 0.0080% w/w, resulting in
about 0.3 to about 1.5 ppm total capsaicinoids, or preferably about
0.0030% to about 0.0080% w/w, resulting in about 0.5 to about 1.5
ppm total capsaicinoids. The ICX formulation further comprises
rosemary extract at a concentration of about 0.02% to about 0.25%
w/w, eucalyptol at a concentration of about 0.07 to about 0.15%,
vegetable glycerin at a concentration of about 3.5% to about 5.0%
w/w, ascorbic acid at a concentration of about 0.10% to about 0.90%
w/w and sea salt at a concentration of about 0.40% to about 1.2%
w/w. One embodiment may also comprise potassium sorbate at a
concentration of about 0.05% to about 0.30%. One embodiment of the
ICX formulation comprises about 0.0064% w/w capsicum, about 0.11%
w/w eucalyptol, about 0.067% w/w rosemary extract, about 0.4 to
about 0.7% w/w each ascorbic acid and sea salt, about 4.4% w/w
vegetable glycerin, in purified water.
[0061] Forty-two informed, consented patients with a significant
component of NAR were randomized to receive either ICX (n=20) or a
filtered water control (n=22) administered 1-2 puffs in each
nostril twice daily over 2 weeks. The primary endpoint was change
in total nasal symptom scores ("TNSS") from baseline to end of
study. Secondary endpoints included changes in individual symptom
scores (nasal congestion, sinus pain, sinus pressure, headache,
sneezing, rhinorrhea, and post-nasal drainage) over two weeks and
average time to first relief. Mean TNSS and individual symptom
scores were also recorded after single dosing with ICX vs. placebo
at 5, 10, 15, 30 and 60 minute intervals. Rhinitis quality-of-life
domains at end of study, and use of rescue medication and safety
endpoints were also analyzed. All data was analyzed by the
Statistical Analysis System ("SAS").
[0062] Statistically significant differences in changes from
baseline to end of study between the ICX and placebo groups were
observed for TNSS and each individual symptom (p<0.01). The
average time to first relief for ICX subjects was 52.6 seconds
which was significantly less than placebo (p<0.01). For ICX
subjects, nasal congestion, sinus pain, sinus pressure and headache
were significantly improved at 5, 10, 15, 30, which persisted up
until 60 minutes for nasal congestion and sinus pain (p<0.05).
No significant difference between groups in adverse events or
rescue medication was observed. ICX subjects experienced no rebound
congestion and demonstrated an improvement in olfaction versus
placebo at the end of study visit.
[0063] This is the first controlled clinical trial to demonstrate
that the ICX composition comprising capsicum provides a rapid onset
of relief for rhinitis subjects, while also providing safe,
sustained relief over the course of the two week treatment
period.
[0064] This was a randomized, placebo controlled, double-blind
parallel study including patients previously diagnosed with
non-allergic rhinitis ("NAR") or "mixed rhinitis" defined as
allergic rhinitis ("AR") with significant NAR triggers. (Bernstein
J A. Characteristics of Non-Allergic Rhintiis. World Allergy
Journal 2009; 2:102-5. Bernstein J A, Rezvani, M. Mixed Rhinitis: A
New Subclass of Chronic Rhinitis. In: Kaliner M, ed. Current Review
of Rhinitis, 2nd ed 2006; Philadelphia, Pa.:69-78
[0065] Forty-two patients between the ages of 18-60 were enrolled
in this study. All subjects signed an informed consent approved by
a central IRB prior to enrollment. Subjects were required to have a
diagnosis of NAR with or without an allergic component (i.e. mixed
rhinitis) for at least six months prior to enrollment. Mixed
rhinitis was defined as being skin prick test positive, defined as
a wheal 3 mm in diameter than saline control with surrounding
erythema, to one or more aeroallergens in addition to having
significant symptoms induced by chemical irritants, strong odors,
weather or temperature changes. (Bernstein J A, Rezvani, M. Mixed
Rhinitis: A New Subclass of Chronic Rhinitis. In: Kaliner M, ed.
Current Review of Rhinitis, 2nd ed 2006; Philadelphia, Pa.:69-78.)
The magnitude of each subject's non-allergic rhinitis component was
confirmed using a gender specific irritant index score previously
demonstrated to correlate with a diagnosis of NAR or MR. (Bernstein
J A. Characteristics of Non-Allergic Rhintiis. World Allergy
Journal 2009; 2:102-5.) Twenty subjects received ICX and 22
received placebo control (filtered water). Thirty-three of the 42
participants had a diagnosis of MR, and 9 had an NAR diagnosis.
These diagnoses were evenly distributed between the ICX and placebo
groups. All subjects enrolled into this study and randomized to ICX
or placebo control and who received at least one dose of study drug
were included in this intent-to-treat analysis.
[0066] All subjects were required to have previously experienced
symptomatic relief while using their currently prescribed rhinitis
medications and were required to exhibit moderate to severe
rhinitis symptoms while off these medications at the time of
randomization. Symptom severity was defined as a morning or evening
nasal congestion and/or post nasal drainage score of at least 5 out
of 10 on three separate symptom assessments during the 7 day
pre-randomization medication wash-out period. This included being
symptomatic at least 24 hours prior to and including the day of
randomization. Subjects were required to comply with all study
related visits and procedures and had to be in generally good
health without any uncontrolled chronic health problems.
[0067] Subjects were excluded if they had an acute sinus infection
in the past 30 days, had a history of nasal polyps or other nasal
structural problems, were treated with oral corticosteroids in the
past 7 days, were active smokers or had passive smoke exposure at
least six months prior to enrollment. Finally, pregnant women were
not permitted to participate and women of child bearing age were
required to use acceptable birth control throughout the study.
[0068] There were a total of three study visits and one interim
phone call, as shown in FIG. 2.
[0069] During visit one, subjects who signed an informed consent
and met all inclusion/exclusion criteria (except for symptom
scores), were removed from all rhinitis medications for 7 days to
determine if they would fulfill the symptom entry criteria. They
were permitted to use diphenhydramine 25 mg up to 200 mg/day as
rescue medication throughout the study. During visit two, subjects
who fulfilled all inclusion/exclusion criteria including the
symptom score criteria, were randomized to receive either ICX or
filtered water placebo, 1-2 puffs each nostril, twice daily. During
visit 2, subjects were given their first dose of study drug or
placebo in the office. Using the stopwatch method, subjects clicked
the stopwatch when they felt the first onset of symptom relief.
(Black P, Max M B, Desjardins P, Norwood T, Ardia A, Pallotta T. A
randomized, double-blind, placebo-controlled comparison of the
analgesic efficacy, onset of action, and tolerability of ibuprofen
arginate and ibuprofen in postoperative dental pain. Clin Ther
2002; 24:1072-89.) They were then immediately instructed to
complete a symptom score card. Subjects also completed symptom
score cards at 5, 10, 15, 30 and 60 minute intervals during this
visit.
[0070] An interim phone call to the subject's home was made 7 days
later to confirm compliance with completing home symptom diaries
and to assess for adverse events and rescue medication
requirements. The study ended at visit three, two weeks after
randomization (visit 2).
[0071] During each visit, all subjects had a directed medical
history, nasal examination, and a review of concomitant and/or
rescue medications. During visits 1 and 3, all subjects underwent
acoustic rhinometry and automated olfactometry to assess nasal
congestion and smell, respectively. (Bernstein J A, Bernstein I L.
A novel case of mealworm-induced occupational rhinitis in a school
teacher. Allergy Asthma Proc 2002; 23:41-4. Rezvani M, Brandt D,
Bernstein J A, Hastings L, Willwerth J. Investigation of olfactory
threshold responses in chronic rhinitis subtypes. Ann Allergy
Asthma Immunol 2007; 99:571-2.) Pregnancy tests were performed on
all women of child bearing age at visits 1 (screening) and 2
(randomization). Rescue medication and adverse events were assessed
at visit 2, during the interim phone call, and at visit 3.
[0072] Symptom scores and rescue medication requirements,
consisting of diphenhydramine 25-50 mg up to four times a day
(maximum dose 200 mg/day), were recorded on subject's home diaries
over the three week study period.
[0073] The primary endpoint was the change in the 12 hour
reflective total TNSS recorded by the patient each evening in a
daily diary, from baseline to the end of the study (2 weeks). TNSS
was a composite score that included nasal congestion, post-nasal
drainage, sneezing, rhinorrhea, sinus pain, sinus pressure and
headache. These symptoms were chosen based on the "Allergies in
America survey" which cited these as the worst symptoms and/or
co-morbid conditions experienced by chronic rhinitis patients.
(Blaiss M S, Meltzer E O, Derebery M J, Boyle J M. Patient and
healthcare-provider perspectives on the burden of allergic
rhinitis. Allergy Asthma Proc 2007; 28 Suppl 1:S4-10.) Each symptom
was rated on a 10 point Likert scale and therefore, the highest
possible TNSS was 70, where a higher score reflects more intense
symptoms.
[0074] Secondary endpoints included changes in 12 hour reflective
symptom scores of nasal congestion, post-nasal drainage, sneezing,
rhinorrhea, sinus pain, sinus pressure and headache recorded at
home daily by patients on diary cards over a 2-week period and the
time to first relief of symptoms recorded in the physician office
at visit 2, after single dosing with ICX or placebo.
[0075] Other endpoints included changes in symptom scores (TNSS,
nasal congestion, post-nasal drainage, sneezing, rhinorrhea, sinus
pain, sinus pressure and headache) at the time to first relief and
assessment of rescue medication requirements during the entire 2
week study period.
[0076] Adverse events, olfaction as measured using an automated
olfactometer (Osmic Enterprises, LLC) (Rezvani M, Brandt D,
Bernstein J A, Hastings L, Willwerth J. Investigation of olfactory
threshold responses in chronic rhinitis subtypes. Ann Allergy
Asthma Immunol 2007; 99:571-2), and nasal congestion using an
acoustic rhinometer (Ecco Vision, Hood Instruments, Pembroke,
Mass.) to assess for increased nasal resistance (i.e., a rebound
effect) (Bernstein J A, Bernstein I L. A novel case of
mealworm-induced occupational rhinitis in a school teacher. Allergy
Asthma Proc 2002; 23:41-4) were recorded and assessed prior to
randomization while off all rhinitis medications and at the end of
study.
[0077] The sample sizes for the ICX drug and placebo control groups
were chosen based on feasibility and other intranasal capsaicin
studies that reported clinically meaningful results. (Blom H M, Van
Rijswijk J B, Garrelds I M, Mulder P G, Timmermans T, Gerth van
Wijk R. Intranasal capsaicin is efficacious in non-allergic,
non-infectious perennial rhinitis. A placebo-controlled study. Clin
Exp Allergy 1997; 27:796-801.) For sample sizes of 20 per group,
the power was 80% to detect a difference of 2 units in TNSS mean
scores from baseline to 14 days between the drug and placebo groups
assuming a 2-tailed alpha=0.05. The effect size (ratio of mean
difference to TNSS standard deviation) was equal to 0.8.
[0078] For all analyses a p-value<0.05 was used to judge
statistical significance unless stated otherwise. The analyses were
performed using SAS for Windows, version 9.2, SAS Institute, Cary
N.C.
[0079] Subject demographics: The demographic characteristics of the
subject population are summarized in Table 1.
TABLE-US-00001 TABLE 1 Demographic Characteristics of Study
Participants Capsaicin (N = 20) Placebo (N = 22) All (N = 42) AGE,
mean (min, 46.9 (36, 59) 45.2 (29, 58) 46.0 (29, 59) max) RACE, N
(%) Caucasian 17 (85%) 17 (77%) 34 (81%) African American 2 (10%) 5
(23%) 7 (17%) Other 1 (5%) 0 (0%) 1 (2%) GENDER, N (%) Male 4 (20%)
3 (14%) 7 (17%) Female 16 (80%) 19 (86%) 35 (83%) Note: No
significant differences were seen between the ICX72 and placebo
groups (p > .05).
There were no significant differences between subjects in the ICX
and placebo groups with respect to age, race and gender.
[0080] Mean Changes in TNSS and Individual Symptom Scores from
Baseline to End of Study for ICX and Placebo Groups: Mean baseline
symptom scores of the ICX and placebo groups were not significantly
different as shown in Table 2.
TABLE-US-00002 TABLE 2 Mean Change from Baseline to End of Study
(Standard Error) of TNSS and Individual Symptom Scores for ICX72
and Placebo Groups ICX72 (N = 20) Placebo (N = 22) Change: Change:
Baseline- % Rel Baseline- % Rel Symptom Baseline End Change
Baseline End Change TNSS* 23.7 (2.2) 12.4 (1.1) 52% 26.0 (2.2) 7.7
(1.2) 30% Nasal Congestion 5.1 (0.5) 2.7 (0.3) 53% 5.3 (0.4) 1.4
(0.3) 27% Sinus Pressure 5.4 (0.5) 3.3 (0.3) 62% 3.7 (0.4) 1.5
(0.3) 29% Sinus Pain 4.5 (0.5) 2.8 (0.3) 64% 4.8 (0.5) 1.6 (0.3)
33% Headache 4.9 (0.5) 3.2 (0.4) 65% 4.8 (0.5) 1.8 (0.3) 37%
Sneezing 1.6 (0.4) 0.9 (0.2) 53% 2.4 (0.4) 0.8 (0.2) 19% Rhinorrhea
2.6 (0.5) 0.5 (0.3) 19% 2.6 (0.4) 0.6 (0.3) 24% PND 4.7 (0.5) 2.2
(0.4) 47% 5.6 (0.5) 1.7 (0.3) 30% Note: For each variable, baseline
differences between groups were not statistically different (p >
0.05). Percent relative change of each symptom was larger for
ICX72, compared with placebo, except rhinorrhea. Mean changes from
baseline to end of study were significantly different between ICX72
and placebo for TNSS, nasal congestion, sinus pressure, sinus pain
and headache (p < 0.006 for each variable determined by
Bonferroni adjustment, overall p-value = 0.05).
[0081] The mean differences between the ICX and placebo groups with
respect to changes in TNSS, nasal congestion, sinus pressure, sinus
pain and headache from baseline to end of study were statistically
greater for ICX compared to placebo (p<0.01). FIG. 3 illustrates
the magnitude of this effect for TNSS and the individual symptoms
that significantly improved. No significant differences between
groups in changes from baseline to end of study were observed for
sneezing, post-nasal drip and rhinorrhea (p>0.05).
[0082] Times to first relief: The average time to first relief for
ICX was equal to 52.6 seconds (0.8 min), which was significantly
lower than the average time of first relief for placebo subjects
(p<0.01). Eighty percent of subjects receiving ICX experienced
first relief in less than one minute compared to 45% of subjects
receiving placebo (p<0.05). Symptoms that significantly improved
at time to first relief were nasal congestion, sinus pressure and
headache (p<0.05) as shown in Table 3.
TABLE-US-00003 TABLE 3 Mean Change from Baseline to First Relief
(Standard Error) of TNSS and Individual Symptom Scores for ICX72
and Placebo Groups ICX72 (N = 20) Placebo (N = 22).sup.a Change:
Change: Baseline- Baseline- First % Rel First % Rel Symptom
Baseline Relief Change Baseline Relief Change TNSS 23.7 (2.2) 3.4
(1.5) 14% 26.0 (2.2) 2.3 (7.7) 9% Nasal Congestion 5.1 (0.5) 1.3
(0.4) 25% 5.3 (0.4) 0 (2.2) 0% Sinus Pressure 5.4 (0.5) 1.7 (0.5)
32% 3.7 (0.4) -0.1 (1.9) -1% Sinus Pain 4.5 (0.5) 1.2 (0.6) 27% 4.8
(0.5) -0.2 (2.7) -5% Headache 4.9 (0.5) 2.2 (0.6) 44% 4.8 (0.5)
-0.1 (2.0) -2% Sneezing 1.6 (0.4) 1.2 (0.3) 75.0% 2.4 (0.4) 0.5
(1.8) 19% Rhinorrhea 2.6 (0.5) -2.3 (0.6) -89% 2.6 (0.4) -1.9 (4.3)
-74% PND 4.7 (0.5) 0.4 (0.7) 7% 5.6 (0.5) -0.6 (5.4) -10% .sup.aN =
22 placebo patients at baseline = 22. Four patients had missing
data at first relief for each symptom. When a symptom at first
relief was missing, less relief was assumed than was determined
from all reported symptom changes at first relief, after adjusting
for baseline. The minimum values at first relief of missing data
were symptom-specific. Mean symptom changes in the placebo group
were obtained from Tobit analysis, which accounts for the upward
bias of changes calculated from observed data only. The probability
of unreported symptoms reflecting less relief than the minimum
relief of all other patients was combined with the probabilities of
the observed symptom values at first relief, to estimate mean
changes at first relief of each symptom for the placebo group.
Note: For each variable, baseline differences between groups were
not statistically different (p > 0.05). Mean changes from
baseline to first relief were significantly different between ICX72
and placebo for sinus pressure and headache only (p < 0.006 for
each variable determined by Bonferroni adjustment, overall p-value
= 0.05).
[0083] Improvement in TNSS and Symptoms Scores for Intranasal
Capsaicin Compared to Placebo At Fixed Time Periods: This analysis
required subjects to complete symptom score questionnaires at fixed
time periods beginning at 5 minutes up to 60 minutes after the
first dose. Differences were statistically significant for nasal
congestion, sinus pressure, sinus pain and headache at 5, 10, 15
and 30 minutes which persisted for nasal congestion, sinus pressure
and sinus pain up to 60 minutes (p<0.05).
[0084] Rescue medications: Fewer subjects in the ICX group (n=6;
30% of subjects) compared to the placebo group (n=10; 45% of
subjects), reported rescue medication usage during the first week
after randomization.
[0085] Similarly, fewer subjects in the ICX group (n=4; 20% of
subjects) versus the placebo group (n=10; 45%) reported use of
rescue medications during the second week after randomization.
[0086] Safety Analyses:
[0087] Olfactometry: The olfactory threshold means of ICX and
placebo subjects at baseline and end of study are summarized in
Table 4.
TABLE-US-00004 TABLE 4 Mean Change from Baseline to End of Study
(Standard Error) of Olfactory Thresholds for ICX72 and Placebo
Groups. ICX72 (N = 14) Placebo (N = 17) Change: Baseline- Change:
Baseline- Baseline End Baseline End Olfactory 6.7 -1.0 6.1 +0.1
Threshold (0.4) (0.6) (0.6) (0.5) N = number of patients A negative
change (higher value at end of study) indicates improved olfaction.
Baseline (defined as data collected during visit 2 pre-drug)
differences between groups were not significantly different (p >
.05). Mean changes from baseline to end of study were not
significantly different between ICX72 and placebo groups (p >
.05). End of study means were significantly different between ICX72
(7.7) and placebo (6.0) (p < .05).
There were no significant differences between baseline or the
change from baseline to end of study olfactory threshold means for
ICX and placebo subjects (p>0.05). However, ICX subjects, had
significantly higher olfactory threshold means compared to placebo
at visit 3 (p<0.05) indicating that their sense of smell was
actually improved during the end of study visit compared to
placebo.
[0088] Acoustic Rhinometry: There was no significant difference in
nasal mean cross sectional areas or volumes at baseline (when
subjects were removed from rhinitis medications) compared to end of
study between ICX and placebo subjects (data not shown). This
indicates that increased nasal resistance, which is what would be
seen with rebound nasal congestion, was not a side effect when ICX
was used continuously over 2 weeks.
[0089] Adverse Events: There was no significant difference between
ICX and placebo in reported adverse events. Reported adverse events
included increased nasal congestion, headaches, post-nasal
drainage, rhinorrhea, transient stinging/burning, blood tinged
mucus and fatigue. Ten percent of subjects on ICX and 27% on
placebo, respectively (p=0.24) reported adverse events during the
first week after randomization whereas, 45% of subjects on ICX and
32% on placebo (p=0.53) reported adverse events during the second
week after randomization.
[0090] The results of this study clearly demonstrate that
continuous treatment with ICX over a two week period was
significantly effective at improving TNSS, nasal congestion, sinus
pressure, sinus pain and headache compared to placebo. Furthermore,
ICX has a quick onset of action as the average time to first relief
was less than one minute (52.6 seconds). This rapid improvement was
most pronounced for nasal congestion, sinus pressure and sinus
pain.
[0091] Interestingly, this improved therapeutic response continued
over time as nasal congestion, sinus pressure, sinus pain and
headache were significantly improved for ICX versus placebo at 5,
10, 15 and 30 minutes and persisted for nasal congestion and sinus
pain up until 60 minutes. Thus, the rapid onset of action resulting
in significant reduction of symptoms makes ICX an attractive
mono-therapy or adjunctive therapy for the management of chronic
rhinitis symptoms.
[0092] Prolonged treatment with ICX resulted in no alteration in
olfaction and in fact appeared to improve olfaction in patients
receiving ICX versus placebo at end of study. Furthermore, subjects
receiving ICX continuously over two weeks showed no rebound
congestion as reflected by improved symptom scores and no change in
nasal cross sectional area measured by acoustic rhinometry. Other
than a transient stinging sensation, ICX was well tolerated.
[0093] Several important points regarding this study should be
emphasized. First, this is the first study to demonstrate that
continuous daily treatment with a composition comprising a lower
concentration of intranasal capsicum (ICX) over a two week period
is safe and effective at improving chronic rhinitis symptoms.
Second, in that all subjects in this trial were required to have a
significant component of NAR as part of their enrollment criteria,
the beneficial effect of ICX supports an important mechanistic role
for TRP ion channels, specifically TRPV1 in NAR.
[0094] The robust effect of ICX on improving rhinitis symptoms and
headaches suggest overlapping neurogenic mechanistic pathways for
MR, NAR and headaches, perhaps in part involving TRP ion channels,
that require further investigation. (Rapoport A M, Bigal M E,
Tepper S J, Sheftell F D. Intranasal medications for the treatment
of migraine and cluster headache. CNS Drugs 2004; 18:671-85.)
[0095] There are several potential limitations of this study that
warrant discussion. First, similar to what has been encountered for
other intranasal medications (Banov C H, Lieberman P. Efficacy of
azelastine nasal spray in the treatment of vasomotor (perennial
nonallergic) rhinitis. Ann Allergy Asthma Immunol 2001; 86:28-35.),
it was not possible to formulate a placebo that caused mild
transient stinging similar to the ICX formulation used in this
trial. However, in order to ensure that the study remained blinded
to the subject, both the clinical research coordinator and
investigator used common written instructions to direct the patient
through different procedures thereby limiting any unnecessary
conversations during the study visits that could bias the subject
or coordinator. Second, it is worth noting that subjects receiving
placebo in some instances experienced modest improvement in TNSS
and specific symptom scores compared to baseline. The therapeutic
effect of placebo in clinical trials has been well established.
(Spector S L. The placebo effect is nothing to sneeze at. J Allergy
Clin Immunol 1992; 90:1042-3.) However, the finding that ICX had a
faster onset of action and greater overall improvement in nasal
congestion and TNSS compared to a placebo control at various time
points throughout the study is a testimonial to its robust
therapeutic benefits.
[0096] In summary, this is the first controlled clinical trial to
demonstrate that ICX provides a rapid onset of relief for rhinitis
subjects with a non-allergic component, while also providing safe,
sustained relief over the course of the two week treatment
period.
Example 3
[0097] One example of the present invention relates to a headache
relief composition. The headache relief composition provides relief
of symptoms such as migraines, general headaches, tension, chronic
and occasional headaches, and dizziness, and visual distortions
associated with headaches. The headache relief composition
comprises capsicum comprising capsaicin, dihydrocapsaicin, and
nordihydrocapsaicin, feverfew extract, eucalyptol, peppermint oil,
rosemary extract, vegetable glycerin, ascorbic acid, citric acid,
and sea salt. An embodiment may comprise potassium sorbate at a
concentration of about 0.05% to about 0.30% w/w.
[0098] The feverfew extract relieves and prevents headache
symptoms. The eucalyptol is used to ameliorate the sensory
experience and soothe the nasal mucosa. The peppermint oil relieves
and helps prevent headache symptoms. The rosemary extract is an
anti-microbial agent and a natural preservative which protects and
stabilizes the headache relief composition. In a surprising and
unexpected result, the rosemary extract was also found to make the
sensory experience due to the presence of capsicum in the
composition more tolerable to the user, without negatively
affecting the efficacy of the composition. The vegetable glycerin
is a moisturizer, assists the capsaicinoids contained in the
capsicum to maintain its potency and effectiveness for longer
periods of time, shortens the length of time of the burning
sensation associated with the capsaicinoids in the capsicum without
reducing its effectiveness, and stabilizes the formula. The
ascorbic acid adjusts the pH supports the immune system, and acts
as a natural preservative. The citric acid further adjusts the pH
level and stabilizes the formula. Any other suitable pH modulator
may be used to adjust and/or maintain the pH of the composition.
The sea salt acts as a nasal cavity cleanser which helps flush out
bacteria, and dried or clogged mucous which can affect the
performance of nerve receptors in the trigeminal region.
[0099] In another embodiment of the present invention, the headache
relief composition may be homeopathic wherein the eucalyptol is
used to ameliorate the sensory experience and soothe the nasal
mucosa, and the feverfew extract is for headache relief.
Furthermore, the headache relief composition may include both
eucalyptol and feverfew extract as a tincture.
[0100] In still another embodiment of the present invention, the
headache relief composition may include between about 0.0044% to
0.0047% by weight of the total water weight of capsicum comprising,
but not limited to, capsaicin, dihydrocapsaicin, and
nordihydrocapsaicin, or about 0.7 to about 1.5 ppm total
capsaicinoids.
[0101] One example of the headache relief composition in accordance
with an embodiment of the present invention in 5 gallons of
purified water includes:
[0102] 0.0044% to 0.0047% by weight of the total water weight of
capsicum;
[0103] 0.10% by weight of the total water weight of feverfew
extract;
[0104] 0.0027% by weight of the total water weight of peppermint
oil;
[0105] 0.13% by weight of the total water weight of eucalyptol;
[0106] 0.08% by weight of the total water weight of rosemary
extract;
[0107] 3.65% by weight of the total water weight of vegetable
glycerin;
[0108] 0.53% by weight of the total water weight of sea salt;
[0109] 0.83% by weight of the total water weight of ascorbic
acid;
[0110] 0.26% by weight of the total water weight of citric
acid.
[0111] In another embodiment, the headache relief composition may
be administered as a preventative and symptomatic tool. In one
embodiment the composition may further comprise from about 0.05% to
about 0.30% w/w or about 0.12% by weight of the total water weight
of potassium sorbate.
Example 4
[0112] Another example of the present invention relates to an
allergy relief composition. The allergy relief composition provides
relief of symptoms caused by allergies such as nasal congestion,
sinus pressure, and headaches. The allergy relief composition
includes capsicum comprising capsaicin, dihydrocapsaicin, and
nordihydrocapsaicin, nettle extract, eucalyptol, rosemary extract,
vegetable glycerin, ascorbic acid, citric acid, and sea salt.
[0113] The nettle extract helps relieve and desensitize allergy
symptoms and related allergy triggers. The eucalyptol is used to
ameliorate the sensory experience and soothe the nasal mucosa. The
rosemary extract is an anti-microbial agent and a natural
preservative which protects and stabilizes the allergy relief
composition. In a surprising and unexpected result, the rosemary
extract was also found to make the sensory experience due to the
presence of capsicum in the composition more tolerable to the user,
without negatively affecting the efficacy of the composition. The
vegetable glycerin is a moisturizer, assists the capsaicinoids
contained in the capsicum to maintain their potency and
effectiveness for longer periods of time, shortens the length of
time of the burning sensation associated with the capsaicinoids in
the capsicum without reducing its effectiveness, and stabilizes the
formula. The ascorbic acid adjusts the pH level, supports the
immune system, and acts as a natural preservative. The citric acid
adjusts the pH level and stabilizes the formula. Any other suitable
pH modulator may be used to adjust and/or maintain the pH of the
composition. The sea salt acts as a nasal cavity cleanser which
helps flush out bacteria, and dried or clogged mucous therefrom.
The potassium sorbate may be used as a preservative.
[0114] In another embodiment of the present invention, the allergy
relief composition may be homeopathic wherein the eucalyptol is
used to ameliorate the sensory experience and soothe the nasal
mucosa. Furthermore, the homeopathic allergy relief composition may
include eucalyptol as a tincture and nettle extract as a
tincture.
[0115] In still another embodiment of the present invention, the
allergy relief composition may include between about 0.0029% to
0.0032% by weight of the total water weight of capsicum comprising
capsaicin, dihydrocapsaicin, and nordihydrocapsaicin, providing
about 0.4 to about 0.5 ppm total capsaicinoids.
[0116] Another embodiment of the allergy relief composition in 5
gallons of purified water includes:
[0117] 0.0029% to 0.0032% by weight of the total water weight of
capsicum;
[0118] 0.10% by weight of the total water weight of nettle
extract;
[0119] 0.13% by weight of the total water weight of eucalyptol;
[0120] 0.08% by weight of the total water weight of rosemary
extract;
[0121] 3.65% by weight of the total water weight of vegetable
glycerin;
[0122] 0.53% by weight of the total water weight of sea salt;
[0123] 0.83% by weight of the total water weight of ascorbic acid;
and
[0124] 0.26% by weight of the total water weight of citric
acid.
[0125] In another embodiment, the allergy relief composition may be
administered as a preventative and symptomatic tool. In an
embodiment, the composition may further comprise potassium sorbate
at a concentration of about 0.05% to about 0.30% w/w.
Example 5
[0126] Another example of the present invention relates to a cold
relief composition. The cold relief composition prevents and
provides relief of symptoms caused by colds, flu, and poor immune
system performance. The cold relief composition comprises capsicum
including, but not limited to, capsaicin, dihydrocapsaicin, and
nordihydrocapsaicin, echinacea extract, eucalyptol, golden seal
extract, spearmint oil, vegetable glycerin, ascorbic acid, citric
acid and sea salt.
[0127] The echinacea extract and the golden seal extract support
the immune system. The eucalyptol is used to ameliorate the sensory
experience and soothe the nasal mucosa. The spearmint oil provides
a sweet taste. The vegetable glycerin is a moisturizer, assists the
capsaicinoids contained in the capsicum to maintain its potency and
effectiveness for longer periods of time, shortens the length of
time of the burning sensation associated with the capsaicinoids in
the capsicum without reducing its effectiveness, and stabilizes the
formula. The ascorbic acid adjusts the pH level, supports the
immune system, and acts as a natural preservative. The citric acid
adjusts the pH level and stabilizes the formula. Any other suitable
pH modulator may be used to adjust and/or maintain the pH of the
composition. The sea salt acts as a natural preservative.
[0128] In another embodiment of the present invention, the cold
relief composition may be homeopathic wherein the eucalyptol is
used to ameliorate the sensory experience and soothe the nasal
mucosa, and the echinacea extract and golden seal extract provide
immune system support. Furthermore, the homeopathic cold relief
composition may include eucalyptol as a tincture, echinacea extract
as a tincture, and golden seal extract as a tincture.
[0129] In still another embodiment of the present invention, the
cold relief composition may comprise between about 0.0024% to
0.0027% by weight of the total water weight of capsicum comprising
capsaicin, dihydrocapsaicin, and nordihydrocapsaicin, providing
about 0.3 to about 0.7 ppm total capsaicinoids.
[0130] One example of the cold relief composition in accordance
with an embodiment of the present invention in 5 gallons of
purified water includes:
[0131] 0.0024% to 0.0027% by weight of the total water weight of
capsicum;
[0132] 0.20% by weight of the total water weight of echinacea
extract;
[0133] 0.13% by weight of the total water weight of eucalyptol;
[0134] 0.15% by weight of the total water weight of golden seal
extract;
[0135] 0.013% by weight of the total water weight of spearmint
oil;
[0136] 0.53% by weight of the total water weight of sea salt;
[0137] 3.65% by weight of the total water weight of vegetable
glycerin;
[0138] 0.83% by weight of the total water weight of ascorbic acid;
and
[0139] 0.26% by weight of the total water weight of citric
acid.
[0140] In another embodiment, the cold relief composition may be
administered before coming into contact with potential germs such
as crowded environments, malls, schools, and airplanes.
[0141] While in the foregoing specification this invention has been
described in relation to certain preferred embodiments thereof, and
many details have been set forth for the purpose of illustration,
it will be apparent to those skilled in the art that the invention
is susceptible to additional embodiments and that certain details
described herein can be varied considerably without departing from
the basic principles of the invention.
* * * * *