U.S. patent application number 13/427034 was filed with the patent office on 2012-12-27 for use of antifungal compositions to treat upper gastrointestinal conditions.
Invention is credited to Stuart L. Weg.
Application Number | 20120329742 13/427034 |
Document ID | / |
Family ID | 38328131 |
Filed Date | 2012-12-27 |
United States Patent
Application |
20120329742 |
Kind Code |
A1 |
Weg; Stuart L. |
December 27, 2012 |
USE OF ANTIFUNGAL COMPOSITIONS TO TREAT UPPER GASTROINTESTINAL
CONDITIONS
Abstract
The present invention provides a novel method for treating oral
conditions and upper gastrointestinal conditions in a subject by
providing an inventive oral dosage form of a pharmaceutical
composition comprising an effective amount of at least one
antifungal and optionally a flavor modifier and/or salivation
component such as an herbal component. In the present invention,
the subjects have either not been diagnosed or do not have active
or recurrent fungal infections. Specifically, the present invention
is directed to chewable dosage forms.
Inventors: |
Weg; Stuart L.; (Franklin
Lakes, NJ) |
Family ID: |
38328131 |
Appl. No.: |
13/427034 |
Filed: |
March 22, 2012 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12806564 |
Aug 16, 2010 |
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13427034 |
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11668764 |
Jan 30, 2007 |
7776831 |
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12806564 |
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60764608 |
Feb 1, 2006 |
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60833433 |
Jul 26, 2006 |
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60862149 |
Oct 19, 2006 |
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Current U.S.
Class: |
514/31 |
Current CPC
Class: |
A61P 1/14 20180101; A61P
31/10 20180101; A61P 1/02 20180101; A61K 9/0056 20130101; A61K
9/0058 20130101; A61K 36/00 20130101; A61P 29/00 20180101; A61K
9/0053 20130101; A61P 1/08 20180101; A61P 1/04 20180101; A61P 1/00
20180101 |
Class at
Publication: |
514/31 |
International
Class: |
A61K 31/7048 20060101
A61K031/7048; A61P 1/02 20060101 A61P001/02; A61P 1/04 20060101
A61P001/04; A61P 1/08 20060101 A61P001/08; A61P 1/00 20060101
A61P001/00; A61P 31/10 20060101 A61P031/10 |
Claims
1. A method for treating upper gastrointestinal conditions in a
subject, which comprises administering to the subject in need
thereof a solid oral dosage form of a pharmaceutical composition
comprising an effective amount of at least one antifungal.
2. The method of claim 1, wherein the pharmaceutical composition
further comprises an effective amount of a flavor modifier.
3. The method of claim 1, wherein the pharmaceutical composition
further comprises an effective amount of at least one herbal
component.
4. The method of claim 1, wherein the subject has not been found to
have a fungal infection.
5. The method of claim 1, wherein the antifungal is selected from
the group consisting of nystatin and nystatin dehydrate.
6. The method of claim 5, wherein the antifungal is nystatin.
7. The method of claim 6, wherein the effective dosage amount of
nystatin ranges from about 5,000 units to 1,000,000 units per
day.
8. The method of claim 7, wherein the effective amount of nystatin
ranges from about 50,000 units to about 500,000 units per day.
9. The method of claim 8, wherein the effective amount of nystatin
ranges from about 80,000 units to about 200,000 units per day.
10. The method of claim 1, wherein the upper gastrointestinal
condition is selected from the group consisting of active benign
gastric ulcer, gastroesophageal reflux disease, Zollinger-Ellison
syndrome, erosive esophagitis, indigestion gastric reflux,
dyspepsia, and reflux disease.
11. The method of claim 1, wherein the flavor modifier is selected
from the group consisting of fruit flavorings, mint flavorings,
salt, and sweeteners.
12. The method of claim 11, wherein the flavor modifier is present
in amounts ranging from about 5 mg to about 100 mg.
13. The method of claim 12, wherein the flavor modifier is present
in amounts ranging from about 20 mg to about 50 mg.
14. The method of claim 1, wherein said oral dosage form is
selected from the group consisting of a pastille, lozenge, chewing
gum, chewable candy, pouch, and plugs.
15. The method of claim 1, wherein the solid oral dosage form is
administered for at least one day.
16. The method of claim 1, wherein the oral dosage form comprises a
component that induces salivation.
17. The method of claim 16, wherein the salivation enhancer is an
herbal component selected from the group consisting of ginger,
senega root, gentian, motherwort, hops, dandelion, papaya, dock or
sorrel, sunflower, calendula, nasturtium, mallow, chicory, corn
silk, clover and mixtures thereof.
18. The method of claim 1, further comprising an additive selected
from the group consisting of betaine hydrochloride, betaine beta
carotene, vitamin E, selenium, vitamin B-6, folic acid, vitamin C,
magnesium, vitamin B-1, vitamin B-2, niacinamide, vitamin B-12,
zinc, copper, biotin, pantothenic acid, dandelion root, acidophilus
dairy free, bifidus dairy free, FOS powder, chromium
polynicotinate, betaine HCl, pancreatin, papain, and pepsin.
19. A dosage form comprising an oral pharmaceutical composition
comprising: (a) an effective amount of at least one antifungal; (b)
a component that induces salivation; and (c) a carrier.
20. The dosage form of claim 19, further comprising a flavor
modifier.
21. The dosage form of claim 19, wherein the antifungal is selected
from the group consisting of nystatin and nystatin dehydrate.
22. The dosage form of claim 21, wherein the antifungal is
nystatin.
23. The dosage form of claim 22, wherein the effective dosage
amount of nystatin ranges from about 10,000 units to 1,000,000
units per day.
24. The dosage form of claim 23, wherein the effective amount of
nystatin ranges from about 50,000 units to about 500,000 units per
day.
25. The dosage form of claim 24, wherein the effective amount of
nystatin ranges from about 80,000 units to about 200,000 units per
day.
26. The dosage form of claim 19, wherein the pharmaceutical
composition provides daily effective therapy for upper
gastrointestinal symptoms.
27. The dosage form of claim 26, wherein the upper gastrointestinal
symptoms are caused by an active benign gastric ulcer,
gastroesophageal reflux disease, Zollinger-Ellison syndrome,
erosive esophagitis, indigestion gastric reflux, dyspepsia or
reflux disease.
28. The dosage form of claim 19, wherein the pharmaceutical
composition provides daily effective therapy for nausea associated
with morning sickness.
29. The dosage form of claim 20, wherein the flavor modifier is
selected from the group consisting of fruit flavorings, mint
flavorings, salt, and sweeteners.
30. The dosage form of claim 29, wherein the flavor modifier is
present in amounts ranging from about 10 mg to about 100 mg per
dosage form.
31. The dosage form of claim 30, wherein the flavor modifier is
present in amounts ranging from about 20 mg to about 50 mg per
dosage form.
32. The dosage form of claim 19, wherein the salivation component
is an herbal component selected from the group consisting of
ginger, senega root, gentian, motherwort, hops, dandelion, papaya,
dock or sorrel, sunflower, calendula, nasturtium, mallow, chicory,
corn silk, clover and mixtures thereof.
33. The dosage form of claim 19, further comprising at least one
additive selected from the group consisting of: an excipient, a
diluent, a disintegrant, a lubricant, a plasticizer, a colorant, a
dosing vehicle, and any combination thereof
34. The dosage form of claim 19, wherein the chewable dosage form
is a form selected from the group consisting of chewing gum and
chewable candy.
35. The dosage form of claim 19, further comprising an additive
selected from the group consisting of betaine hydrochloride,
betaine beta carotene, vitamin E, selenium, vitamin B-6, folic
acid, vitamin C, magnesium, vitamin B-1, vitamin B-2, niacinamide,
vitamin B-12, zinc, copper, biotin, pantothenic acid, dandelion
root, acidophilus dairy free, bifidus dairy free, FOS powder,
chromium polynicotinate, betaine HCl, pancreatin, papain, and
pepsin.
36. A method for treating nausea associated with morning sickness
in a subject in need thereof, which method comprises administering
to the subject in need thereof a solid oral dosage form of a
pharmaceutical composition comprising an effective amount of at
least one antifungal.
37. A method for treating oral conditions in a subject in need
thereof, which method comprises administering to the subject in
need thereof a solid oral dosage form of a pharmaceutical
composition comprising an effective amount of at least one
antifungal.
38. The method of claim 36, wherein the oral condition is selected
from the diseases selected from halitosis, dental plaque,
gingivitis, xerostomia, dry mouth, oral malodor and combinations
thereof.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority under 35 U.S.C. .sctn.119,
based on U.S. Provisional Application Ser. Nos. 60/764,608, filed
Feb 1, 2006; 60/833,433, filed Jul 26, 2006; and 60/862,149, filed
Oct. 19, 2006, the disclosures of which are incorporated herein by
reference in their entirety.
FIELD OF THE INVENTION
[0002] The present invention relates to methods and compositions
for treating various conditions in the upper gastrointestinal
tract. Specifically, the invention is directed to the use of
antifungal dosage forms for treating upper gastrointestinal disease
such as heartburn, reflux, gastroesophogeal reflux disease (GERD),
gastritis, dyspepsia, and nausea associated with morning sickness.
The present invention is also directed to the use of antifungal
dosage forms for the treatment of oral conditions, including
halitosis, dental plaque, gingivitis, xeorstomia, and dry
mouth.
BACKGROUND OF THE INVENTION
[0003] Upper gastrointestinal (GI) diseases affect millions of
people annually, leading to recurrent and discomforting symptoms.
Exemplary GI diseases include heartburn, reflux, gastroesophogeal
reflux disease (GERD), gastritis, and dyspepsia.
[0004] Heartburn, or pyrosis, is a sensation of pain or burning
located substernally or high in the epigastrium with radiation into
the neck and occasionally to the arms. Heartburn is associated with
the regurgitation of acid-peptic gastric juices into the esophagus.
Acid reflux can lead to heartburn in milder cases and to
gastroesophageal reflux disease in severe cases. Reflux symptoms
are often treated as an acid problem, and a typical remedy is an
antacid. GERD, also referred to as reflux or reflux esophagitis, is
a clinical condition in which the reflux of stomach acid into the
esophagus is frequent and severe enough to impact a patient's
normal functioning, to cause discomfort or pain, and/or to cause
damage to the esophagus. It has been estimated by the U.S.
Department of Health and Human Services that about seven million
people in the United States suffer from GERD.
[0005] Gastritis is pathologically an inflammatory process of the
stomach, particularly of the gastric mucosa. It has been known that
an acute gastritis is often induced by ingestion of
anti-inflammatory agents (aspirin, etc.) or alcohol (ethanol), by
emotional stress, or by the back-flow of bile into the stomach.
Gastritis may occasionally result from a mistaken ingestion of
corrosive acid or alkali.
[0006] Various approaches and medicines have been developed to
treat upper GI conditions associated with damaged or malfunctioning
mucosal tissues in the GI tract. Treatment of upper GI tract
conditions has been carried out by the use of alkaline agents and
gastric acid suppressors or by limiting consumption of foods to
bland diets. One approach to relieve symptoms of reflux or
gastritis has been to neutralize gastric acid by using antacids.
For example, aluminum and magnesium hydroxide (MAALOX.RTM. and
MYLANTA.RTM.) neutralize gastric acidity, resulting in an increase
in stomach pH and duodenal bulb pH. Antacids are fast acting and
temporary fixes of short duration. They are known to neutralize
acid in the stomach and may also act locally in the distal
esophagus. However, antacids do not always prevent heartburn when
taken before food or beverages that may provoke symptoms.
[0007] Another approach to treat upper GI conditions has been to
use H.sub.2-receptor antagonists, also known as H.sub.2-blockers,
to inhibit the action of histamine on the parietal cell, which
inhibits acid secretion. Examples of H.sub.2-receptor antagonists
include cimetidine (TAGAMET.RTM.), nizatidine (AXID.RTM.),
ranitidine hydrochloride (ZANTAC.RTM.), lansoprazole
(PREVACID.RTM.), rabeprazole (ACIPHEX.RTM.), and famotidine. U.S.
Pat. No. 5,667,794 (to Simon et al.) discloses famotidine, an
exemplary H.sub.2-receptor antagonist used for the treatment of
upper GI conditions. However, for many of these medications, there
is a delay between consumption and relief from symptoms.
Additionally, treatment can be quite costly to the average
patient.
[0008] Alternatively, upper GI conditions have been treated with
proton-pump inhibitors ("PPIs") which reduce the amount of gastric
acid produced by gastric acid-producing cells. These prescription
medications include lansoprazole (PREVACID.RTM.), esomeprazole
(NEXIUM.RTM.), omeprazole (PRILOSEC.RTM.), pantoprazole
(PROTONIX.RTM.), and omeprazole IR (ZEGERID.RTM.). However, similar
to the H.sub.2-blockers, the most popular PPIs require a
prescription and demonstrate a delay between consumption and relief
from symptoms. Various proton pump inhibitors and treatments of GI
disorders are disclosed in U.S. Pat. Nos. 6,132,770 (to Lundberg);
6,869,615 (to Chen, et al.); and 4,786,505 (to Lovgren, et
al.).
[0009] To solve some of the difficulties associated with current
treatments, combination treatments of antacids with
H.sub.2-receptor antagonists or PPIs have been proposed. However,
recent studies have shown that H.sub.2-receptor antagonists or and
PPIs may cause and increase incidence of hip fractures. (See Yang
et al., JAMA. 2006 Dec. 27; 296(24):2947-53). U.S. Pat. No.
5,229,137 (to Wolfe) describes compositions and methods which
require the simultaneous administration of an H.sub.2-receptor
antagonist with an antacid to provide immediate, lasting relief
from pain, discomfort and symptoms associated with episodic
heartburn. WO 92/00102 describes co-administration of
H.sub.2-receptor antagonists with antacids for treating gastric
disorders such as hyperacidity. WO 93/12779 describes compositions
of H.sub.2 antagonists with antacids for treating gastric disorders
such as hyperacidity. U.S. Pat. No. 5,817,340 describes
compositions of famotidine with antacids for treating
gastrointestinal distress.
[0010] U.S. Pat. No. 4,861,592 describes oral compositions
containing cimetidine and aluminum hydroxide-magnesium carbonate
co-dried gel for treating duodenal, gastric, recurrent and stomal
ulceration, and reflux esophagitis. U.S. Pat. No. 4,824,664
describes effervescent compositions containing cimetidine and
sodium bicarbonate for treating duodenal and gastric ulcers. U.S.
Pat. Nos. 5,169,640 and 5,188,839 describe compositions containing
cimetidine, aluminum hydroxide gel, and magnesium hydroxide, for
treating duodenal, gastric, recurrent and stomal ulceration, and
reflux esophagitis.
[0011] While the methods in art have some effectiveness in
relieving the pain and discomfort associated with upper GI
symptoms, there exists a need for developing innovative
compositions and methods for preventing and treating upper-GI
symptoms (related to acid reflux) that can be taken quickly,
inexpensively, and with fast resolution of symptoms. The present
invention addresses these needs with the novel use of antifungal
agents.
SUMMARY OF THE INVENTION
[0012] The present invention provides a method for treating upper
gastrointestinal conditions in a subject, which method includes
administering to the subject in need thereof a solid oral dosage
form of a pharmaceutical composition containing an effective amount
of an antifungal and, wherein the subject has not been diagnosed
with a gastric or esophogeal fungal infection. In certain
embodiments of the invention, the pharmaceutical composition
further comprises a flavor modifier and/or one or more herbal
component and/or a vitamin component. In particular embodiments,
the oral dosage form comprises a component that induces salivation,
including for example an herbal component.
[0013] In one embodiment, at least one antifungal is selected from
the group consisting of nystatin, nystatin dehydrate, nystop,
mycostatin, bio-statin, mykinac, nilstat, nystex, o-v statin,
amphotericin, amphotericin B, amphotec, fungizone, undecyne,
undecylenic acid, zinc undecylenate, gentian, amphocin, gentian
root, gentian violet, and combinations thereof. In a preferred
embodiment, the antifungal is nystatin.
[0014] In certain embodiments, the effective amount of nystatin
ranges from about from about 10,000 units to about 1,000,000 units
in powder form. More particularly, the amount ranges from about
50,000 units to about 500,000 units, even more particularly from
about 80,000 to about 200,000 units. The oral dosage form is
administered at least once a day.
[0015] In a specific embodiment, the oral dosage form is a solid
oral controlled release form; in particular, it can be selected
from a group consisting of a tablet, capsule, particle, powder,
sachet, a wafer, a chewable tablet, a buccal tablet, a sublingual
tablet, a quick-dissolve tablet, an effervescent tablet, a granule,
a pellet, a bead, a pill, a troche, a sprinkle, a film, a dry
syrup, a reconstitutable solid, a suspension, pastille, lozenge,
gum, lollipop, chewing gum or chewable candies, pouch or plugs
(similar to chew/dip strands), caplet, or a strip. In a specific
embodiment, the oral dosage form is a pastille, lozenge, chewing
gum, chewable candy, pouch or plug.
[0016] According to the invention, the upper gastrointestinal
condition is selected from the group consisting of active benign
gastric ulcer, gastroesophageal reflux disease (GERD),
Zollinger-Ellison syndrome, erosive esophagitis, indigestion
gastric reflux, dyspepsia, reflux disease, or nausea associated
with morning sickness.
[0017] The present invention also provides for the treatment of
oral conditions including halitosis, dental plaque, gingivitis,
xerostomia, dry mouth, oral malodor and combinations thereof.
[0018] In one specific embodiment, the compositions are used in the
evening or at night before sleep to aid in controlling or
preventing snoring, night coughing, aspirations (and therefore
aspirational pneumonia).
[0019] The invention also provides for the oral dosage form
containing a pharmaceutical composition, which includes an
effective amount of an antifungal; preferably a flavor modifier;
and a carrier. In certain embodiments, the solid oral dosage form
further contains at least one additive selected from the group
consisting of: an excipient, a diluent, a disintegrant, a
lubricant, a plasticizer, a colorant, a dosing vehicle, and any
combination thereof.
[0020] The compositions of the present invention may also contain
one or more additives selected from the group consisting of betaine
hydrochloride, betaine beta carotene, vitamin E, selenium, vitamin
B-6, folic acid, vitamin C, magnesium, vitamin B-1, vitamin B-2,
niacinamide, vitamin B-12, zinc, copper, biotin, pantothenic acid,
dandelion root, acidophilus dairy free, bifidus dairy free, FOS
powder, chromium polynicotinate, betaine HCl, pancreatin, papain,
and pepsin.
DETAILED DESCRIPTION
[0021] It has now been discovered that antifungal compounds, such
as nystatin, can be effectively used to achieve the desired
symptomatic relief of upper gastrointestinal conditions. The
invention is based in part on the unexpected discovery that
sustained release of nystatin is capable of resolving
gastroesophageal reflux disease (GERD) in otherwise healthy
adults.
[0022] The subject invention advantageously provides a dosage form
for oral administration containing an antifungal medicament to
treat symptoms of upper gastrointestinal conditions. The treatable
symptoms include but are not limited to heartburn, indigestion,
acid reflux, reflux esophagitis, gastroesophogeal reflux disease,
gastritis, dyspepsia and other acid-related upper GI conditions. In
a further embodiment, treatable symptoms include nausea associated
with pregnancy, e.g., morning sickness. It has been discovered that
the oral dosage form is beneficial in the treatment of upper GI
conditions in individuals not diagnosed with or does not have a
gastric fungal infection. The antifungal oral dosage form provides
sustained relief of discomforting symptoms and lasting therapeutic
effect.
[0023] The terms used in this specification generally have their
ordinary meanings in the art, within the context of this invention
and in the specific context where each term is used. Certain terms
are defined below to provide additional guidance in describing the
compositions and methods of the invention and how to make and use
them.
Definitions
[0024] The term "treat" is used herein to mean to relieve or
alleviate at least one symptom of a disease in a subject. Within
the meaning of the present invention, the term "treat" also denotes
to arrest, delay the onset (i.e., the period prior to clinical
manifestation of a disease) and/or reduce the risk of developing or
worsening a disease.
[0025] The term "prevent" or prevention is used in terms of
prophylactic administration of a pharmaceutical composition prior
to the onset of disease or to prevent recurrence of a disease.
Administration of the oral dosage form to prevent the disease need
not absolutely preclude the development of symptoms. Prevent can
also mean to reduce the severity of the disease or its
symptoms.
[0026] The phrase "pharmaceutically acceptable" as used in
connection with compositions of the invention, refers to molecular
entities and other ingredients of such compositions that are
physiologically tolerable and do not typically produce untoward
reactions when administered to a mammal (e.g., human). Preferably,
as used herein, the term "pharmaceutically acceptable" means
approved by a regulatory agency of the Federal or a state
government or listed in the U.S. Pharmacopoeia or other generally
recognized pharmacopoeia for use in mammals, and more particularly
in humans.
[0027] The term "therapeutically effective" as applied to dose or
amount refers to that quantity of a compound or pharmaceutical
composition that is sufficient to result in a desired activity upon
administration to a mammal in need thereof. As used herein with
respect to the pharmaceutical compositions comprising an
antifungal, the term "therapeutically effective amount/dose" refers
to the amount/dose of a compound or pharmaceutical composition that
is sufficient to produce an effective response upon administration
to a mammal.
[0028] The term "about" or "approximately" means within an
acceptable error range for the particular value as determined by
one of ordinary skill in the art, which will depend in part on how
the value is measured or determined, i.e., the limitations of the
measurement system. For example, "about" can mean within 3 or more
than 3 standard deviations, per the practice in the art.
Alternatively, "about" can mean a range of up to 20%, preferably up
to 10%, more preferably up to 5%, and more preferably still up to
1% of a given value. Alternatively, particularly with respect to
biological systems or processes, the term can mean within an order
of magnitude, preferably within 5-fold, and more preferably within
2-fold, of a value.
[0029] The term "amount" as used herein refers to quantity or to
concentration as appropriate to the context. In the present
invention, the effective amount of an antifungal compound refers to
an amount sufficient to treat symptoms associated with upper
gastrointestinal diseases. The effective amount of a flavor
modifier refers to an amount sufficient to counter the bad tastes
of antifungal compounds. The effective amount of a drug that
constitutes a therapeutically effective amount varies according to
factors such as the potency of the particular drug, the route of
administration of the formulation, and the mechanical system used
to administer the formulation. A therapeutically effective amount
of a particular drug can be selected by those of ordinary skill in
the art with due consideration of such factors.
[0030] "Nausea associated with pregnancy" refers to morning
sickness, evening sickness, and hyperemesis gravidarum, without
limitation.
Pharmaceutical Formulation
[0031] The pharmaceutical formulations of the present invention are
directed to use of oral dosage forms comprising at least one
antifungal active ingredient to treat upper GI conditions; in some
cases, without testing for a fungal infection. In specific
embodiments, the oral dosage form includes at least one flavor
modifier, and additives as necessary including, for example, bases,
stabilizers, and/or fillers.
[0032] As used herein, the term "active ingredient" or "active
agent" refers to one or more compounds that have some antifungal
property. Accordingly, more than one type of antifungal compound
may be added to the formulation of the invention. The formulation
of the invention may comprise any pharmaceutically acceptable
antifungal that may be orally administered to a subject.
Formulations including active ingredients in amounts appropriate
for the desired pharmacological properties at the dosage
administration can be prepared. An "active ingredient" of the
present invention can be any non-active compound, including but not
limited to antifungals, H.sub.2-blockers, and proton pump
inhibitors.
Antifungals
[0033] The pharmaceutical compositions of the present invention
include at least one active ingredient that is a pharmaceutically
acceptable antifungal agent. Exemplary antifungal agents include,
but are not limited to, at least on of the following: nystatin,
amphotericin B, natamycin, miconazole, ketoconazole, clotrimazole,
econazole, mebendazole, bifonazole, butoconazole, fenticonazole,
isoconazole, oxiconazole, sertaconazole, sulconazole,
thiabendazole, tiaconazole, fluconazole, itraconazole,
ravuconazole, posaconazole, voriconazole, terbinafine, amorolfine,
naftifine, butenafine, caspofungin, micafungin, flucytosine,
undycene, undecylenic acid, zinc undecylenate, gentian,
griseofulvin, gentian root, gentian violet, and combinations
thereof. Examples of imidazole antifungals are disclosed in U.S.
Pat. No. 6,656,928 (to McAdden), which is incorporated herein by
reference.
[0034] In a specific embodiment of the invention, the antifungal is
nystatin. Nystatin is disclosed, for example, in U.S. Pat. No.
4,006,222 (to Metzger), which is incorporated herein by reference
in its entirety. In another embodiment, the antifungal is
amphoteracin B, as disclosed for example in U.S. Pat. No. 4,902,789
(to Michel, et al.), also incorporated herein by reference in its
entirety.
[0035] The antifungal is present in each dosage form in amounts
ranging from about 5,000 units to about 1,000,000 units in powder
form. Preferably, the amount ranges from about 50,000 units to
about 500,000 units, more preferably from about 80,000 to about
200,000 units. In certain embodiments, the dosage form may include
a combination therapy with one or more active ingredients,
including but not limited to antacids or H-blockers. For example,
an embodiment may contain an antifungal and a histamine
H.sub.2-receptor antagonist. Examples of H.sub.2-receptor
antagonists include cimetidine (TAGAMET.RTM.), nizatidine
(AXID.RTM.), ranitidine hydrochloride (ZANTAC.RTM.), rabeprazole
(ACIPHEX.RTM.), and famotidine. U.S. Pat. No. 5,667,794 (to Simon
et al.), incorporated herein by reference, discloses famotidine, an
exemplary H.sub.2-receptor antagonist used for the treatment of
upper GI conditions.
[0036] Alternatively, embodiments may contain an antifungal and a
proton pump inhibitor. Examples of PPIs include but are not limited
to lansoprazole (PREVACID.RTM.), esomeprazole (NEXIUM.RTM.),
omeprazole (PRILOSEC.RTM.), pantoprazole (PROTONIX.RTM.), and
omeprazole IR (ZEGERID.RTM.). Various proton pump inhibitors are
disclosed in U.S. Pat. Nos. 6,132,770 (to Lundberg); 6,869,615 (to
Chen, et al.); and 4,786,505 (to Lovgren, et al.), all of which are
incorporated herein by reference in their entirety.
Flavor Modifiers
[0037] In certain embodiments, the pharmaceutical composition of
the present invention also preferably includes at least one flavor
modifier. The flavor modifiers, or taste masking components, are
components to mask or lessen the unpleasant tastes commonly known
to be associated with antifungal compounds. Inclusion of taste
masking components is particularly desirable when administration is
prolonged in the oral cavity, such as compositions in the form of
lozenges. Non-limiting examples of taste masking components include
fruit flavorings, mint flavorings, salt, or sweeteners.
[0038] Examples of sweeteners include, but are not limited to,
stevia (stevioside), Nutrasweet, and Splenda, as well as any
non-nutritive sweeteners, also called sugar substitutes or
artificial sweeteners, including but not limited to saccharin,
cyclamate, aspartame, sucralose, and acesulfame potassium.
Additionally, sugar alcohols or other nutritive sweeteners derived
from fruits or produced commercially from dextrose may be used. The
most common include: sorbitol, mannitol, xylitol, maltitol,
sorbitol, and mannitol. In some embodiments, the flavor modifiers
do not contain sugar and the dosage form is sugar-free. In a
specific embodiment, the sweetener is stevia.
[0039] U.S. Pat. Nos. 5,972,374 (to Theisen), 5,523,105 (to
Ishikawa, et al.), and 5,425,962 (to Johnson, et al.) disclose mint
oils and flavorants and their uses in various products such as gum
and medications. Other exemplary flavor modifiers and/or flavorants
include, but are not limited to fruit flavorings such as grape,
cherry, lemon, or other citrus flavors; other acceptable nonfood
flavorings such as tutti frutti flavor; and herbal flavorings.
Flavor modifiers may be artificial or juice extracts.
[0040] The flavor modifiers may be present in varying amounts,
depending on the particular antifungal used. In certain
embodiments, the flavor modifiers are present in amounts ranging
from about 5 mg to about 100 mg per dosage form, preferably from
about 20 mg to about 50 mg per dosage form.
Herbal Components
[0041] The pharmaceutical composition of the present invention may
also includes at least one component that induces salivation. In
particular, the pharmaceutical composition includes an herbal
component that induces salivation. Inducing salivation in a subject
improves the efficacy of the composition and ultimately enhances
treatment of the gastrointestinal conditions.
[0042] Any components which will promote salivation may be used in
the present invention. In particular, bitter herbs are used to
promote salivation. Herbal component(s) of the present invention
can be selected from a group consisting of, but not limited to,
ginger, senega root, gentian, motherwort, hops, dandelion, papaya,
dock or sorrel, sunflower, calendula, nasturtium, mallow, chicory,
corn silk, clover and mixtures thereof. In other embodiments,
nonherbal salivation enhancing components are also
contemplated.
[0043] The salivation inducing components may be present in varying
amounts, depending on the particular antifungal used and depending
on what particular dosage form is used.
Vitamins or Food Additives
[0044] The therapeutic composition of the present invention may
also contain vitamins or food additives that deliver or increase
hydrochloric acid, gastric juices, and enzymes. Such additives
include but are not limited to an effective amount of betaine
hydrochloride, betaine beta carotene, vitamin E, selenium, vitamin
B-6, folic acid, vitamin C, magnesium, vitamin B-1, vitamin B-2,
niacinamide, vitamin B-12, zinc, copper, biotin, pantothenic acid,
dandelion root, acidophilus dairy free, bifidus dairy free, FOS
powder, chromium polynicotinate, betaine HCl, pancreatin, papain,
and pepsin.
[0045] Dandelion Root supports the digestive tract. It primarily
works with the liver and gallbladder by stimulating digestive
enzymes produced by each organ. It also stimulates digestion and
can help with those who suffer from constipation and acid reflux.
This herb is also high in many vitamins and minerals. Vitamins
found in food are better absorbed and retained by the body. These
types of additive ingredients not only giving the digestive system
support, but also by giving a natural source of vitamins and
minerals. Other additives such as kelp, sea vegetation, alfalfa,
trace minerals, and molybdenum, which also have high concentrations
of minerals, could be substituted. As for digestive support, other
items such as juniper, aloe vera, burdock, ginger root, and
artichoke also have potent effects on supporting the digestive
tract and could be substituted.
[0046] Probiotic (acidophilus dairy free/bifidus dairy free)
bacteria favorably alter the intestinal micro-flora balance,
inhibit the growth of harmful bacteria, promote good digestion,
boost immune function, and increase resistance to infection.
Individuals with flourishing intestinal colonies of beneficial
bacteria are better equipped to fight the growth of disease-causing
bacteria. Probiotics are important in finishing the digestive
process and therefore can increase the absorption of nutrients.
[0047] Fructo-oligosaccharides (FOS) are naturally occurring
carbohydrates that cannot be digested or absorbed by humans but
support the growth of bifidobacteria, one of the beneficial
bacterial strains. Friendly bacteria support digestion, elimination
and the absorption of nutrients in the body.
[0048] Betaine (hcl/gastric acid) may also be added to the
compositions of the present invention. One of the most important
parts of digestion occurs in the stomach, where gastric (stomach)
acid helps break down proteins for further digestion in the small
intestine. This increased digestion aids in the absorption of
nutrients that support the nervous system.
[0049] Papain/Pancreatin/Pepsin are digestive enzymes (also called
pancreatic enzymes) include three classes of enzymes: proteolytic
enzymes needed to digest protein, lipases needed to digest fat, and
amylases needed to digest carbohydrates. Pancreatic enzymes should
be used with to support the digestive process. Allergies are
triggered by partially undigested protein, while protoolytic
enzymes reduce allergy symptoms. Proteolytic enzymes such as
trypsin, chymotrypsin, and bromelain are partially absorbed by the
body. Proteolytic enzymes may improve immune system ftinction, a
common problem with people with allergies and nervous system
weakness. Papain, pancreatin and, pepsin are contemplated in the
compositions of the present invention, however other items such as
papaya, and pineapple also have high concentrations of these
digestive enzymes could be substituted.
[0050] Any suitable medicament for oral cleansing, breath
freshening or the like can be added to the film formulation. The
medicaments can include, for example, a pH control agent, such as
urea and buffers, inorganic components for tartar or caries
control, such as phosphates and fluorides, a breath freshening
agent, such as zinc gluconate, an anti-plaque/anti-gingivitis
agent, such as chlorohexidene, CPC, and triclosan, a saliva
stimulating agent including, for example, food acids such as
citric, lactic, maleic, succinic, ascorbic, adipic, fumaric and
tartaric acids, a pharmaceutical agent, a nutraceutical agent, a
vitamin, a mineral, other like medicaments or combinations
thereof.
Additional Additives
[0051] The therapeutic composition of the present invention may
also contain additional additives, including polymer or therapeutic
agent stabilizers, such as but not limited to sucrose, salts, and
pH adjusting agents; and preservatives including antioxidants such
as butylated hydroxytoluene, and antibacterials. Alternative
additives are disclosed in detail below.
[0052] Thus, the pharmaceutical composition may include one or more
additives, depending on the pharmaceutically acceptable carrier, a
base, a preservative, a dye, a binder, a suspending agent, a
dispersing agent, a stabilizer, a colorant, a disintegrant, an
excipient, a diluent, a lubricant, a plasticizer, an oil or any
combination of any of the foregoing. Suitable pharmaceutically
acceptable additives include, but are not limited to, ethanol;
water; glycerol; aloe vera gel; allantoin; glycerin; vitamin A and
E oils, citric acid; mineral oil; PPG2 myristyl propionate;
vegetable oils and solketal. Examples of additional additives
include, but are not limited to, sorbitol; talc; stearic acid; and
dicalcium phosphate.
[0053] Suitable binders, fillers and/or bases include, but are not
limited to, starch; gelatin; natural sugars, such as glucose,
sucrose and lactose; corn sweeteners; natural and synthetic gums,
such as acacia, tragacanth, vegetable gum, and sodium alginate;
carboxymethylcellulose; polyethylene glycol; waxes; and the
like.
[0054] Suitable disintegrators include, but are not limited to,
starch such as corn starch, methyl cellulose, agar, bentonite,
xanthan gum and the like.
[0055] Suitable lubricants include, but are not limited to, sodium
oleate, sodium stearate, magnesium stearate, sodium acetate, and
the like.
[0056] The composition may also include suitable preservatives,
e.g., sodium benzoate, and other additives the may render the
composition more suitable for application, e.g., sodium chloride,
which affects the osmolarity of the preparation.
[0057] Suitable dispersing and suspending agents include, but are
not limited to, synthetic and natural gums, such as bentoite,
vegetable gum, tragacanth, acacia, alginate, dextran, sodium
carboxymethylcellulose, methylcellulose, polyvinyl-pyrrolidone and
gelatin.
[0058] A suitable pharmaceutical diluent is, but is not limited to,
water.
[0059] Under ordinary conditions of storage and use, the
preparations of the present invention can also contain a
preservative to prevent the growth of microorganisms. The
therapeutic composition can be stable under the conditions of
manufacture and storage and preferably preserved against the
contaminating action of microorganisms such as bacteria and fungi.
A carrier liquid can be a solvent of dispersion medium containing,
for example, water, ethanol, polyol (e.g., glycerol, propylene
glycol, and liquid polyethylene glycol, and the like), and suitable
mixtures thereof. The prevention of the action of microorganisms
can be brought about by various antibacterial and antifungal
agents, for example, parabens, chlorobutanol, phenol, sorbic acid,
thimerosal, benzoic acid, alcohol, benzalkonium chloride and the
like. In many cases, it will be preferable to include isotonic
agents, e.g., sugars, phosphate buffers, sodium benzoate, sodium
chloride, or mixtures thereof.
Modes of Administration
[0060] The therapeutic composition can be administered in a variety
of oral dosage forms adapted to the chosen route of administration.
Administration in this situation can include, for example, use of a
tablet, capsule, particle, powder, sachet, pastille (e.g., as
disclosed in U.S. Pat. No. 4,725,440), lozenge, chewing gum,
chewable candies (i.e. gummy type or taffy) pouch or plugs (similar
to chew/dip strands), lollipop, caplet, coated or encapsulated
chewable capsules, or other solid oral dosage form of the
formulation. In particular, the solid oral dosage form is a chewing
gum or chewable candy, which while being sustained in the mouth,
the nystatin is slowly dissolved and mixed with saliva. The saliva
is then swallowed thereby coating mucosal surfaces in the
esophagus, esophagogastric (EG) junction, and stomach, particularly
the antrum of the stomach.
[0061] In a specific embodiment, the solid oral dosage form may be
in the form of an edible wax. The dosage form is made according to
known methods in the art, including for example, heating an edible
wax at a temperature above its melting point; heating an edible oil
at a temperature above the melting point of the edible wax; mixing
the melted wax with the oil along with the pharmaceutical
formulation, and homogenizing the mixture.
[0062] In yet another embodiment, the antifungal agent can be
formulated for sublingual and/or oral pharyngeal administration.
For example, nystatin can be incorporated in a chewable "candy"
matrix, such as that described in U.S. Pat. No. 4,671,953 (to
Stanley, et al.), or in a gum base.
[0063] The oral dosage forms of the present invention provide the
advantage of a sustained-release system, whereby effective amounts
of antifungal are released over time. Various types of
sustained-release materials have been established and are well
known by those skilled in the art.
Methods of Treatment
[0064] The therapeutic composition of the present invention may be
administered to a host subject (patient) to achieve any desired
effect in the clinical outcome of the targeted upper
gastrointestinal condition. Preferably the subject is a mammal, and
more preferably a human. The human may be from an adult or
pediatric population.
[0065] Specifically, in the present invention, the subject is one
who has either not been diagnosed with a fungal infection or who
has not been diagnosed with recurrent fungal infections. The
present invention is directed to subjects needing relief and
treatment of upper gastrointestinal diseases, independent of any
fungal infection (i.e., candida).
[0066] The terms "upper gastrointestinal condition" refers to
symptoms affecting the proximal part of the gastrointestinal tract,
which consists of the mouth, pharynx, esophagus, and stomach
(including the antrum, pylorus and pyloric sphincter proximal to
the pylorus valve).
[0067] The compositions of the invention may be used for the
treatment or prevention of gastrointestinal conditions. Such
conditions include, but are not limited to: gastritis; peptic
ulcer; reflux esophagitis; dyspepsia; gastric ulcers;
gastroesophageal reflux disease (GERD); severe erosive esophagitis;
and pathological hypersecretory conditions such as Zollinger
Ellison Syndrome. The methods and composition of the present
invention may also be useful in the treatment of H. pylori
infection and conditions associated with H. pylori infection (e.g.,
ulcers, gastric carcinoma, non-ulcer dyspepsia, gastritis, and
esophageal lesions associated with gastro-esophageal reflux
disease). Other examples of the gastrointestinal disorder include,
but are not limited to, gastrointestinal diseases, such as acute
gastritis, chronic superficial gastritis, atrophic gastritis,
antral gastritis, senile gastritis, bile-regurgitational gastritis,
esophagitis, gastric neurosis, as well as various consequent
conditions including gastric hyperacidity, hypochlorhydria,
gastrointestinal discomfort after meals, gastritis caused by taking
acidic drugs such as salicylates (e.g., aspirin), gastric
discomfort after drinking, and gastric discomfort due to fasting.
Symptoms often associated with these conditions include
indigestion, heartburn, burping, coughing, wheezing, chest pain,
stomach pain, feeling bloated, emesis, and hematemesis. U.S. Pat.
Nos. 5,601,848 and 5,256,684 (to Marshall), and 5,977,159 (to
Fandriks, et al.) disclose treatment of a variety of these upper GI
disorders, and are incorporated herein by reference in their
entirety. The present invention also provides the benefit of
reducing or eliminating the use of H.sub.2-receptor antagonists or
PPIs, thereby reducing the incidence of hip fractures.
[0068] In another embodiment of the present invention, the
pharmaceutical compositions are used to treat morning sickness in
pregnant women. In particular embodiments, the classic nausea and
vomiting in early pregnancy is treated. Cases can range in degree
from mild to severe, and symptoms usually begin soon after the
first missed period. Morning sickness, i.e., nausea and vomiting
experienced during the first and second trimesters of pregnancy, is
experienced by approximately half of all pregnant women, however it
is particularly common in cases of multiple pregnancy and
hydatidiform mole. (Kousen, M., "Treatment of nausea and vomiting
in pregnancy", Am Fam Physician, 48:1279 (1993)). These symptoms
appear to be related to hormonal issues in early pregnancy. These
women may or may not have heartburn or signs of GERD and are
previously not symptomatic people who have a self limiting disease.
In another embodiment, the pregnant women may have preexisting
disease (although may not be symptomatic) such as GERD or dyspepsia
who develop those GI symptoms during the pregnancy that appear
related to the preexisting condition with exacerbation due to
anatomical changes or other pregnancy issues. This development may
occur at any time during pregnancy. Hyperemesis gravidarum, i.e.,
persistent nausea and vomiting during pregnancy, can lead to a
reduction in fluid and electrolyte levels, as well as a jeopardized
nutritional status if the condition is not treated. The condition
is characterized by prolonged and severe nausea and vomiting,
dehydration, ketosis, and body weight loss. Other complications may
include hyponatraemia, hypokalaemia, a low serum level, metabolic
hypochloraemic alkalosis, ketonuria, liver function test
abnormalities, abnormal thyroid function tests, and suppressed
thyroid-stimulating hormone levels. Nelson-Piercy, C., "Treatment
of nausea and vomiting in pregnancy. When should it be treated and
what can be safely taken?", Drug Saf, 19(2):155-64 (1998).
[0069] In another embodiment of the present invention, the
pharmaceutical compositions of the present invention may be used to
treat oral conditions. The oral conditions include but are not
limited to halitosis, dental plaque, gingivitis, xerostomia, dry
mouth, oral malodor or combinations thereof. Halitosis is produced
by the production and liberation of volatile compounds, mainly
volatile derivatives of sulphur, such as hydrogen sulphide and
methylmercaptane. According to the localization of the origin of
the unpleasant odour, it can be classified as oral (localised in
lips, tongue, teeth, dental prosthetic elements, periodontal
tissues, oropharynx) or non-oral [caused by diseases of the
respiratory tract, systemic diseases (hepatic dysfunction,
cirrhosis, diabetic ketoacidosis, carcinomas and certain metabolic
diseases in which an enzymatic anomaly occurs), diseases of the
gastrointestinal tract and certain foods, drinks, tobacco and
medicaments].
[0070] Treatment of these conditions is accomplished by
administering to a patient an effective amount of the
pharmaceutical composition according to the present invention. The
effective amount may be administered once or multiple times daily,
as necessary. Alternatively, the dosage form may be taken once
every other day, or once or twice weekly.
[0071] Treatment duration can be short-term, e.g., several hours
(for example 8-14 hours), or long-term, e.g., a number of days or
indefinitely until the attending physician deems further
administration no longer is necessary.
EXAMPLES
[0072] The present invention will be better understood by reference
to the following proposed clinical study example, which is provided
as exemplary of the invention, and not by way of limitation.
Example 1
Use of Nystatin Chewing Gum to Treat Indigestion
[0073] The present Example demonstrates the use of Nystatin chewing
gum to treat indigestion. Once patients present with symptoms of
indigestion, Nystatin chewing gum is prescribed to the patient. The
Nystatin chewing gum is prepared with 100,000 units of nystatin
(powder) and 30 mg stevia in a polyethene glycol base with tuffi
fruitti flavoring and citric acid as a stabilizer.
[0074] The patient is instructed to chew one piece of gum at the
onset of indigestion symptoms. The chewing gum is sustained in the
patient's mouth for at least 30 minutes, and repeated every 4 to 6
hours, or as needed. The chewing gum is taken for 10 consecutive
days, and continued longer if necessary.
[0075] The symptoms of indigestion are reviewed at baseline, and at
1, 3, 5, 7 and 10 days following initiation of treatment.
Example 2
Use of Nystatin Lozenges to Treat Upper Gastrointestinal
Conditions
[0076] The present Example provides a clinical trial protocol
focusing on GERD, dyspepsia and heartburn, with dosages as low as
100,000 units of nystatin in sugar-free lozenges every other
day.
[0077] Therefore, patients with these gastrointestinal conditions
are a selected and treated with lozenges over a fixed time.
Symptoms and other medication usage are measured before and after
this therapy and then followed up to determine if there is
improvement in treated patients symptoms and/or reduction in there
medication use.
Patient Selection
[0078] Patient who have complaints of GERD, Heartburn or Dyspepsia
and are under the care of a physician are acceptable for this trial
with the following exceptions: [0079] 1) Under 14 years of age;
[0080] 2) Pregnant or lactating; [0081] 3) New prescription
medication of any type in the week before starting the trial;
[0082] 4) New non-prescription or nutraseutical remedy for the
above complaints within a week of this trial; and [0083] 5)
Medically or surgically unstable (for example: new onset angina,
treatment for H pylori, uncontrolled hypertension or arrhythmia,
Gaul bladder attack, etc.).
Treatment Protocol
[0084] One Lozenge (100,000 nystatin units/dose) is dissolved in
the mouth three times a day. Lozenges are not taken within 30
minutes of eating and are not followed by any liquids for at least
20 minutes.
[0085] Patients are provided with a ten day supply of lozenges.
They continue the trial medication until the supply is used or they
cannot tolerate them.
[0086] Concurrent medications used for the above complaint such as
prilosec, turns, etc. are permitted. Patients are encouraged to
wean off these medications on their own as the trial
progresses.
Documentation and Records
[0087] Pretrial: Brief medical history and vital signs including
dosages of all medications and remedies listed. The patient's
doctor must approve the patient for the study and "order" the
medication.
[0088] Beginning point evaluation: "Please tell me how bad your
daily complaint is." "On a scale of zero to ten, where zero is no
symptoms at all and ten is your worst day ever." "How are you doing
now with whatever remedy you may use?"
[0089] Post trial (immediately after finishing the course of
lozenges): The patients are interviewed to determine what level the
complaint is now at by repeating the zero to ten scale description
used in the pretrial evaluation. Next, the interviewer must
determine if any remedies used pretrial have been increased,
decreased, changed, or stopped.
[0090] There should also be noted any other side effects, either
positive or negative. The ordering doctor should be aware of all
outcome information.
[0091] The patients should be seen again in at least a month to
monitor if any improvement has been sustained.
[0092] Drop outs: Any patient who does not complete the trial
should be questioned for adverse reactions, which should be
reported to the doctor. The reason for dropping out should be
noted. Data from a patient who starts a new medication or becomes
medically or surgically unstable during the trial cannot be
included in the results.
SUMMARY AND DISCUSSION
[0093] Study Patients fall into three categories: [0094] 1)
Symptomatic taking nothing [0095] 2) Symptomatic on a remedy [0096]
a. Prescription [0097] b. non-prescription/nutraseutic [0098] 3)
Not Symptomatic on a and/or b
[0099] End Points: [0100] 1) Improvement in the reported number
scale of the patient; and/or [0101] 2) reduction or elimination of
pretrial remedies.
Example 3
Use of Nystatin Lozenges to Treat Nausea Associated with Morning
Sickness in Pregnant Women
[0102] The present Example provides a clinical trial protocol
focusing on the treatment of nausea associated with morning
sickness in pregnant women, with dosages as low as 5,000 units of
nystatin in sugar-free lozenges every day.
Patient Selection
[0103] Patients for this study experience nausea due to sickness
during pregnancy. Patients can be at any stage of pregnancy.
[0104] Patients may also experience GERD or dyspepsia.
Treatment Protocol
[0105] One lozenge (5,000 nystatin units/dose) is dissolved in the
mouth three times a day. Lozenges are not taken within 30 minutes
of eating and are not followed by any liquids for at least 20
minutes.
[0106] Patients are provided with a 14-day supply of lozenges. They
continue the trial medication until the supply is used or they
cannot tolerate them.
[0107] Concurrent medications used for nausea are permitted.
Patients are encouraged to wean off these medications on their own
as the trial progresses.
Documentation and Records
[0108] Pretrial: Brief medical history and vital signs including
dosages of all medications and remedies listed. The patient's
doctor must approve the patient for the study and "order" the
medication.
[0109] Beginning point evaluation: "Please tell me how bad your
daily complaint is." "On a scale of zero to ten, where zero is no
symptoms at all and ten is your worst day ever." "How are you doing
now with whatever remedy you may use?"
[0110] Post trial (immediately after finishing the course of
lozenges): The patients are interviewed to determine what level the
complaint is now at by repeating the zero to ten scale description
used in the pretrial evaluation. Next, the interviewer must
determine if any remedies used pretrial have been increased,
decreased, changed, or stopped.
[0111] There should also be noted any other side effects, either
positive or negative. The ordering doctor should be aware of all
outcome information.
[0112] The patients should be seen again in at least a month to
monitor if any improvement has been sustained.
[0113] Drop outs: Any patient who does not complete the trial
should be questioned for adverse reactions, which should be
reported to the doctor. The reason for dropping out should be
noted. Data from a patient who starts a new medication or becomes
medically or surgically unstable during the trial cannot be
included in the results.
SUMMARY AND DISCUSSION
[0114] Study Patients we capture fall into three categories: [0115]
1) Symptomatic taking nothing [0116] 2) Symptomatic on a remedy
[0117] a. Prescription [0118] b. non-prescription/nutraseutic
[0119] 3) Not Symptomatic on a and/or b
[0120] End Points: [0121] 1) Improvement in the reported number
scale of the patient; and/or [0122] 2) reduction or elimination of
pretrial remedies.
Example 4
Use of Nystatin Chewing Gum to Halitosis
[0123] The present Example demonstrates the use of Nystatin chewing
gum to treat halitosis. Once patients present with symptoms of
chronic or persistent halitosis (e.g., accompanying chronic
sinusitis), Nystatin chewing gum is prescribed to the patient. The
Nystatin chewing gum is prepared with 100,000 units of nystatin
(powder) and 30 mg stevia in a polyethene glycol base with tuffi
fruitti flavoring and citric acid as a stabilizer.
[0124] The patient is instructed to chew one piece of gum at the
onset of indigestion symptoms. The chewing gum is sustained in the
patient's mouth for at least 30 minutes, and repeated every 4 to 6
hours, or as needed. The chewing gum is taken for 10 consecutive
days, and continued longer if necessary.
[0125] The symptoms of indigestion are reviewed at baseline, and at
1, 3, 5, 7 and 10 days following initiation of treatment.
[0126] The present invention is not to be limited in scope by the
specific embodiments described herein. Indeed, various
modifications of the invention in addition to those described
herein will become apparent to those skilled in the art from the
foregoing description and the accompanying figures. Such
modifications are intended to fall within the scope of the appended
claims.
[0127] It is further to be understood that all values are
approximate, and are provided for description.
[0128] Patents, patent applications, publications, product
descriptions, and protocols are cited throughout this application,
the disclosures of which are incorporated herein by reference in
their entireties for all purposes.
* * * * *