Note: Descriptions are shown in the official language in which they were submitted.
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METHOD AND COMPOSITION FOR PROPHYLAXIS AND TREATMENT OF
SYMPTOMS ASSOCIATED WITH COLD AND INFLUENZA-LIKE
ILLNESSES
FIELD
The present invention relates to a novel therapeutic use of stilbenic
phytoalexins. More specifically, the embodiments of the present invention
relate
to the prophylaxis and treatment of symptoms associated with cold and
influenza-like illnesses and the prophylaxis and treatment of congestion
associated with respiratory afflictions.
BACKGROUND
~5 It is known that many different viruses and viral strains induce symptoms
associated with respiratory viral infections. For example, the common cold and
flu are caused by members of several families of viruses including influenza,
parainfluenza viruses, rhinoviruses, respiratory syncytial viruses,
enteroviruses,
and coronaviruses. Pinpointing the specific cause of the illness is difficult
and
2o not practical since there are also a number of predisposing factors whose
contribution to the manifestation of symptoms is not fully understood. Such
factors include, but are not limited to, physical fatigue, psychological
stress, and
overall physical healthiness.
Regardless of the virus and associated factors leading to the onset of cold
25 and influenza symptoms, a number of remedies to alleviate the symptoms of
the
common cold have been suggested. The cough/cold products that are currently
marketed typically contain one or more of the following actives: nasal
decongestants such as pseudoephedrine, oxymetazoline, antihistamines such as
doxylamine, antitussives such as dextromethorphan, expectorants such as
so guaifenesin and antipyretics such as acetaminophen. In an attempt to
improve
existing cold remedies, experts in the field have suggested several
alternative
pharmacotherapies and subsequently conducted cold trials to test their
efficacy.
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2
Examples of these therapies include the use of interferon-a2 , see Douglas et
al.,
Prophylactic Efficac roof Intranasal Alpha2- Interferon Against Rhinovirus
Infection
in the Family Setting, The New England Journal of Medicine, 314, pp. 65-70,
1986; bradykinin antagonist, see Higgins et al., A Study of the Efficacy of
the
BrandYkinin Antagonist NPC567 in Rhinovirus Infections in Human Volunteers,
Antiviral Research vol. _14, pp. 339-344, 1990; glucocorticoid, see Farr et
al., A
Randomized Controlled Trial of Glucocorticoid Prophylaxis Against Experimental
Rhinovirus Infection, The Journal of Infectious Diseases vol. 162, pp. 1173-
1177,
1990; nedocromil, see Barrow et al., The Effect of Intranasal Nedocromil
Sodium
on Viral Upper Re~iratory Tract Infections in Human Volunteers, Clinical and
Experimental Allergy vol. 20, pp. 45-51, 1990; a combination of interferon-a2,
ipratropium and naproxen, see Gwaltney; Combined Antiviral and Antimediator
Treatment of Rhinovirus Colds, The Journal of Infectious Diseases vol. 166,
pp.
776-782, 1992; and zinc salts, see Potter et al., DIAS Rounds Zinc Lozenges
for
15 Treatment of Common Colds, The Annals of Pharmacotherapy vol. 27, pp. 589-
592, 1993.
A number of patents have also been issued disclosing compositions for
the treatment of the common cold and flu symptoms and their methods of use. A
sample of such patents include: U.S. Patents 5,240,694; 5,422,097, and
20 5,492,689, all to Gwaltney, disclosing treatment using combinations of
antiviral
and antiinflammatory compounds; U.S. Patents RE033,465 and 5,409,905, both
to Eby disclosing treatment using zinc salts; and U.S. Patents 4,619,934 and
4,552,899, both to Sunshine, disclosing treatment of cough and colds using
compositions comprising non-steroidal antiinflammatory drugs such as NSAIDS
25 with antihistaminically effective materials such as chlorpheniramine.
Despite the
abundance of compositions and preventative treatments known in the art, there
remains a need to provide a consistent, effective, and safe method for the
prophylaxis and treatment of cold and influenza-like symptoms as well as
treatment of congestion associated with respiratory afflictions.
so As discussed in detail below, Applicants have discovered new means for
the prophylaxis and treatment of cold and influenza-like symptoms as well as
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treatment of congestion associated with respiratory afflictions via
administration
of certain stilbenic phytoalexins.
Phytoalexins are defense substances with antimicrobial properties which
are produced by plants after infections. They include various groups of
natural
s substances (e.g., isoflavonoids, terpenoids, polyacetylenes and
dihydrophenanthrenes). Different sources of phytoalexin include the roots of
Veratrum grandiflorum, the bark of Pinus sibirica, Vitis vinifera, and Arachis
hypogaea. Other sources include Eucalyptus, Polygonum and Nothofagus
species and Cudrania javanensis. Phytoalexins can also exist naturally as an
oligomer.
Compositions comprising stilbenic phytoalexins can be prepared either
utilizing natural occurring sources of stilbenic phytoalexins or synthesizing
stilbenic phytoalexins. One type of stilbenic phytoalexin that can be found in
a
variety of naturally occurring sources is 3,4',5-trihydroxystilbene
resveratrol.
15 Reservatrols are found in relatively large amounts in red grapes and red
wine
and implicated for favorable pharmacological effects that include the
prevention
and therapy of atherosclerosis. Research conducted on the components present
in red wine that exert pharmacological effects indicates 3,4',5-
trihydroxystilbene
resveratrol's protective effects at the cardiovascular level. See, for
example,
2o Frankel E. N., et al., 341 Lancet 454, 1993. Recently, it has been
demonstrated
that 3,4',5-trihydroxystilbene resveratrol has activity as a cancer
chemopreventive
(Meishang Jang et al., 275 Science 218-229, 1997). The dietary supplement
Huzhang, a source of resveratrol, is reported to have antioxidant properties
(product label for Resveratrol from "Source Naturals," 1997).
25 SUMMARY
The present invention is directed to methods for the prophylaxis and
treatment of cold and influenza-like symptoms and/or treatment of congestion
associated with respiratory afflictions comprising administering to a subject
a
composition having a stilbenic phytoalexin having the structure:
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R1
R2 CH C R5
R3 R4
wherein R', R2, R3, R4, R5, and R6 are independently selected from hydrogen
and
hyd roxy.
The present invention is further directed to compositions including the
above stilbenic phytoalexin.
DETAILED DESCRIPTION
While the specification concludes with claims which particularly point out
and distinctly claim the invention, it is believed the present invention will
be better
understood from the following description.
All cited references are incorporated herein by reference in their entireties.
Citation of any reference is not an admission regarding any determination as
to
its availability as prior art to the claimed invention.
All percentages are by weight of total composition unless specifically
stated otherwise.
15 All ratios are weight ratios unless specifically stated otherwise.
Herein, "comprising" means that other steps and other ingredients which
do not affect the end result can be added. This term encompasses the terms
"consisting of and "consisting essentially of'.
Herein, "safe and effective amount" means an amount of active high
2o enough to provide a significant positive modification of the condition to
be
treated, but low enough to avoid serious side effects (at a reasonable
benefit/risk
ratio), within the scope of sound medical judgment. A safe and effective
amount
of active will vary with the particular condition being treated, the age and
physical
condition of the subject being treated, the severity of the condition the
duration of
25 the treatment, the nature of concurrent therapy and like factors.
Non-limiting symptoms associated with cold and influenza-like illnesses
include nasal congestion, sneezing, sinus pain, sore throat, runny nose,
cough,
chest pain and headaches. In addition, congestion is associated with certain
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respiratory afflictions. These respiratory afflictions include viral,
bacterial, and
fungal infections which may lead to sinusitis, otitis media, and pneumonia.
Other
respiratory afflictions that result in congestion include inflammatory and
immunological responses to allergens and pollutants.
s Nasal congestion is one manifestation of congestion generally.
Congestion is characterized by localized edema at tissues or organs that are
inflamed or injured in response to colds and respiratory ailments. To this
end,
congestion is accompanied by increased fluid production at mucus producing
tissues such as the nose, lungs, and throat. The increased fluid production is
responsible for reducing airflow through a lumenal site such as nasal passages
or
even the lungs. Other locations that become congested include the head or
facial sinuses, ear canals, and the throat. Sinus and otic openings (ostia)
are
usually kept open by normal cellular processing of mucus, foreign particles
and
bacterial imbalances. However, these locations and openings can become
clogged due to excessive edema which results in sinus, middle ear or head
pain.
The pain is believed to result from the increased pressure in the sinuses
following
a fluid influx that is coincident with an inflammatory cell influx which
results, in
part, to make more mucus or frank pus. Therefore, it is generally accepted
that
nasal congestion is associated and may be coincident with these conditions.
2o Nasal congestion results in the sensation of one's nose and nasal passages
being blocked with the inability to conduct airflow through the nares.
One method of measuring such blockage is by measuring a subject's
nasal airway resistance (NAR). NAR is a physical measure of resistance to air
flow, calculated from pressure gradients, through the nasal passage (e.g.
naves,
25 turbinates) under normal breathing patterns. Congestion in nasal tissues
increases NAR. Increases in NAR coincide with the sensation of blocked and/or
clogged airways. The biological mechanisms in nasal congestion are relevant to
both symptoms associated with cold and influenza-like illnesses and congestion
associated with respiratory afflictions.
3o NAR is measured by acoustic and passive rhinometry. Amis, T.C., Oral
airwa~r, flow dynamics in healthy humans, 515 J. Physiol. Lond. 293-8, 1999;
Baroody, F.M. Relationship between histamine and physiological chances during
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the early response to nasal antigen provocation, 86 J. Appl. Physiol. 659-68,
1999; Hilberg, O., Acoustic reflections during rhinometry~ spatial resolution
and
sound loss, 84(3) J. Appl. Physiol. 1030-9, 1998; Hilber, O., Acoustic
rhinometry:
evaluation of nasal cavity aeometr~y acoustic reflection, 66(1 ) J. Appl.
Physiol.,
295-303, 1989 are cited as references incorporated herein.
A. Method
Applicants have surprisingly discovered stilbenic phytoalexins of Formula
1 are useful in the prophylaxis and treatment of symptoms associated with cold
and influenza like illnesses as well as congestion associated with respiratory
afflictions. For example, administering a safe and effective amount of a
stilbenic
phytoalexin of the present invention to a subject already suffering from nasal
congestion decreases NAR by; preferably about 70% to about 98%; more
preferably about 80% to about 95%; even more preferably about 85% to about
94%. In another example, administering a safe and effective amount of a
~ 5 stilbenic phytoalexin of the present invention to a subject prior to
suffering from
nasal congestion minimizes increases in NAR by; preferably about 70% to about
98%; more preferably about 80% to about 95%; even more preferably about
85% to about 94%.
An embodiment of the present invention relates to a method for the
2o prophylaxis and treatment of cold and influenza-like symptoms including
administering to a subject a composition including a stilbenic phytoalexin
having
the following chemical Formula 1:
R1
CH CH R5
R3
25 Formula 1
where R', R2, R3, R4, R5, and R6 are independently hydrogen or hydroxyl; and
medicinally acceptable salts or esters thereof.
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Preferably "R" represents mixtures of hydrogen and hydroxyl More
preferably the stilbenic phytoalexin is a tetrahydroxystilbene or
trihydroxystilbene;
more preferably still, 3,4',5 - trihydroxystilbene resveratrol (hereinafter
"resveratrol"), i.e., where R', R3, R5, and are hydroxyl and R2, R4, and R6
are
s hydrogen.
Such compositions useful in the methods of the present invention are
discussed in more detail, below.
B. Compositions
An embodiment of the present invention relates to compositions having a
stilbenic phytoalexin of Formula 1.
Preferably the compositions useful in the present invention include from
about 0.01 % to about 99.99% of the stilbenic phytoalexin of Formula 1; more
preferably from about 0.05% to about 30%; and more preferably still from about
0.1 % to about 25%.
~ 5 1. Pharmaceutical Agents
A preferred embodiment of the present invention relates to compositions
including a stilbenic phytoalexin of Formula 1, above, in combination with a
pharmaceutical agent. A non-limiting list of pharmaceutical agents useful in
the
present invention, with examples, include:
2o Antihistamines, including, Hydroxyzine, Pyrilamine, Phenindamine,
Dexchlorpheniramine, Clemastine Diphenhydramine, Azelastine, Acrivastine,
Levocarbastine, Mequitazine, Astemizole, Ebastine, Loratadine, Cetirizine,
Terfenadine, Promethazine, Dimenhydrinate, Meclizine, Tripelennamine,
Carbinoxamine, Cyproheptadine, Azatadine, Brompheniramine, Triprolidine,
2s Cyclizine, Thonzylamine, Pheniramine, and mixtures thereof.
Antitussives, including, Hydrocodone, Noscapine, Benzonatate,
Diphenhydramine, Chlophedianol, Clobutinol, Fominoben, Glaucine, Pholcodine,
Zipeprol, Hydromorphone, Carbetapentane, Caramiphen, Levopropoxyphene,
Codeine, Dextromethorphan, and mixtures thereof.
so Antiinflammatories preferably Non-Steroidal Anti-inflammatories
NSAIDS including, Ketoprofen, Indoprofen, Indomethacin, Sulindac, Diflunisal,
Ketorolac, Piroxicam, Meclofenamate, Benzydamine, Carprofen, Diclofenac,
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Etodolac, Fenbufen, Fenoprofen, Flurbiprofen, Mefenamic, Nabumetone,
Phenylbutazone, Pirprofen, Tolmetin, Ibuprofen, Naproxen, Sodium naproxen,
Aspirin, and mixtures thereof.
Anal ec~sics, including, Acetaminophen.
Expectorants/Mucolytics, including, Ambroxol, Bromhexine, Terpin,
Guaifenesin, Potassium iodide, N-Acetylcysteine, and mixtures thereof.
Mast Cell Stabilizers preferable intranasally or orally administered mast
cell stabilizers, including, Cromolyn, Oxatamide, Ketotifen, Lodoxamide,
Nedocromil, and mixtures thereof.
Leukotriene Antagonists, including, Zileuton and others.
Methylxanthines, including, Caffeine, Theophylline, Enprofylline,
Pentoxifylline, Aminophylline, Dyphylline, and mixtures thereof.
Antioxidants or radical inhibitors, includingi Ascorbic acid, Tocopherol,
Pycnogenol, and mixtures thereof.
Steroids, preferably intranasally administered steroids, including,
Beclomethasone, Fluticasone, Budesonide, Mometasone, Triamcinolone,
Dexamethasone, Flunisolide, Prednisone, Hydrocortisone and mixtures thereof.
Bronchodilators preferably for inhalation, including, Albuterol,
Epinephrine, Ephedrine, Metaproterenol, Terbutaline, Isoetharine, Terbutaline,
2o Isoetharine, Pirbuterol, Bitolterol, Fenoterol, Rimeterol, Ipratroprium,
and
mixtures thereof.
Antivirals, including, Amantadine, Rimantadine, Enviroxime, Nonoxinols,
Acyclovir, Alpha-Interferon, Beta-Interferon, and mixtures thereof.
Biologics, including, cytokine and celladhesion molecule inhibitors, ICAM
antagonists, interleukin agonists or antagonists, hormones, polypeptides,
amino
acids, nucleotides, antibodies, and mixtures thereof.
The acid or base addition salts, esters, metabolites, stereoisomers and
enantiomers of these actives are also contemplated as pharmaceutical agents
useful in certain embodiments of the present invention, as well as the
analogues
of these actives that are safe and effective. It is also recognized that a
pharmaceutical agent may be useful for more than one of the above uses, and
these uses are clearly contemplated as well. This overlap is recognized in the
art
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and adjusting dosages and the like to fit the indication is well within the
purview
of the skilled medical practitioner.
2. Enhancing Agents
In a preferred embodiment, the composition further includes an enhancing
agent. Enhancing agents useful in the present invention include, but not
limited
to, herbs, phenols, polyphenols, anthocyamins, anthocyanosides, carotenoids,
bioflavinoids, vitamins, metal ions, mineral salts, proanthocyanidins,
antioxidants,
and/or vegetal fibers. Non-limiting examples include echinacea, tea
polyphenols,
epigallocatechin, beta carotene, grape seed extracts, lycopenes, flavones,
quercetin, tocopherol, zinc, selenium, stannous, ascorbic acid, calcium, N-
acetyl
cysteine, and mixtures thereof.
3. Sources of Stilbenic Phytoalexins
The stilbenic phytoalexin of Formula 1 may originate from natural and/or
synthetic sources. Orsini-F, et al., Isolation s~rnthesis and antiplatelet
~ 5 aggregation activity of resveratrol 3-O-beta-D-glucopyranoside and related
comeounds, 60(11 ) J. Nat. Prod. 1082-7, 1997: Orsini-F et. al., S~rnthesis of
biologically active polyphenolic c~lycosides (combretastatin and resveratrol
series), 301 (3-4) Carbohydr. Res. 95-109, 1997: Hain, et. al., Expression of
a
stilbene synthase gene in Nicotiana tabacum results in synthesis of the
20 ~hytoalexin resveratrol, 15(2) Plant. Mol. Biol. 325-35, 1990 are cited as
references incorporated herein.
In a preferred embodiment, the composition includes natural source
products, natural source extracts, or natural source powders of the stilbenic
phytoalexins of Formula 1. Non-limiting examples include wine, grapes,
Huzhang,
25 and Polygonum cuspidatum.
4. Form and Administration
The compositions useful in the present invention may be a solid, semi-
solid, liquid, semi-liquid; in the form of powders, granules, liposomes,
tablets,
capsules, gels, lozenges, dentifrice, and mouthwash.
3o The compositions useful in the present invention may be incorporated into
microspheres, microcapsules, nanoparticles, liposomes and the like for
controlled
release. Furthermore, the compositions may, in addition, conveniently comprise
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suspending, solubilizing, stabilizing, pH-adjusting agents and/or dispersing
agents.
In a preferred embodiment, the composition is in the form of a herbal
medicament. Herbal medicament forms useful in the present invention include,
5 but are not limited to, teas, decoctions, beverages, candies or other
confection,
foods, enteral liquid nutritional products, mouthwashes, lozenges,
dentifrices,
and dietary or nutritional supplements.
The administrative route of the compositions of the present invention
includes any suitable route which leads to a concentration in the blood that
provides a prophylactic and treatment benefit. Suitable administration routes
include, but are not necessarily limited to: oral, oral topical, parenteral,
cutaneous, nasal, rectal, vaginal, ocular, inhalant, or combinations thereof.
Preferably the administrative route is oral or nasal.
EXAMPLES
~ 5 The following examples further describe and demonstrate the preferred
embodiments within the scope of the present invention. The examples are given
solely for the purpose of illustration, and are not to be construed as
limitations of
the present invention since many variations thereof are possible without
departing from its spirit and scope. All ingredients are by weight of 100
grams of
2o the composition:
Examples 1 and 2
Examples of toothpaste and tooth gel compositions of the subject invention are
made by conventional processes by mixing the following:
Example 1 Example 2
25 Ingredients Wt. % Wt.
Sorbitol 41.44 35.00
Saccharin Sodium 0.46 0.20
FD&C Blue (1 % sol'n) ------- 0.05
Precipitated Silica 20.00 25.00
3o Sodium Fluoride 0.24 0.24
Flavor 1.00 1.50
Sodium Alkyl Sulfate 4.00 1.20
Trisodium Phosphate 1.45 ------
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Monosodium Phosphate 0.59 ------
Carbopol 940 0.30 0.25
Xanthan Gum 0.48 0.65
Titanium Dioxide 0.53 ------
Resveratrol 2.00 1.00
Purified Water q.s. q.s.
Examples 3 and 4
Examples of mouthwash compositions subject invention are
of the made by
conventional processes by
mixing the following:
Example 3 Example 4
Ingredients Wt. % Wt.
Cetylpyridinium Chloride 0.045 0.045
Domiphen Bromide 0.005 0.005
Alcohol (Standard
Denatured No. 40) 16.25 8.50
Glycerin 10.00 7.50
Poloxamer 407 0.20 0.20
2o Sodium Hydroxide 0.003 0.003
Sodium Benzoate 0.05 0.54
Benzoic Acid 0.005 0.003
Tween 80 0.03 0.12
FD&C Green (1 % sol'n) 0.04 0.12
FD&C Blue (1 % sol'n) 0.003 ------
FD&C Yellow (1 % sol'n) ------- 0.001
Saccharin 0.06 0.08
Peppermint Oil 0.14 -------
Spearmint Oil ------- 0.12
so Resveratrol 0.30 0.20
Purified water q.s. q.s.
Example 5
An example of a dental solution of the subject invention is made by mixing the
following:
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Ingredients (Wt. %~
Resveratrol 1.00
Flavor 0.10
Polysorbate 80 0.25
Saccharin Sodium 0.05
Methylparaben 0.20
Propylparaben 0.10
Water q~s~
Example 6
An example of an oral gel composition of the subject invention is made by
mixing the following:
Ingredients Wt.
Hydroxyethyl Cellulose 2.50
Sodium Fluoride 0.09
Saccharin Sodium 0.05
FD&C Green No. 3 (1 % sol'n) 0.01
Resveratrol 1.00
2o Purified Water q.s.
Example 7
An example of an intranasal spray solution is made by mixing the
following:
2s Ingredient Grams
Resveratrol 1.0
Nonionic detergent ~ 0.70
Dibasic sodium phosphate 0.11
Monobasic potassium phosphate
0.38
3o Benzalkonium chloride 0.04
Chlorhexidine gluconate 0.26
Disodium EDTA 0.01
Flavoring 2
Camphor and eucalyptol 3
35 Purified water QS to 100
grams
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1 Available as Tyloxapol from Nycomed, Inc.
2 Flavoring used at a level in order to provide a pleasing taste.
3 Added at a level in order to provide a pleasant in-use scent.
Add all ingredients to chilled water and stir until dissolved , while
s maintaining the chilled water temperature. Adjust this solution to pH of 5.5
to 6.5.
QS with water and filter through a cellulose acetate membrane filter. Fill
manually operated nasal sprayers with the composition. Spray from about 5 to
500 microliters of solution into each nostril. Repeat three times daily.
Example 8
An example of an intranasal drop solution is made by mixing the following:
Ingredients Grams
Methylcellulose gum 0.115
Sodium chloride 0.350
Monobasic potassium phosphate 0.540
Dibasic potassium phosphate 0.310
Poloxamer block co-polymer' 0.145
Propylene glycol 1.170
Resveratrol 0.568
2o Benzalkonium chloride 0.025
Flavoring 2
Camphor and eucalyptol 3
Purified water QS to 100 grams
1 Available as Pluronic 127 from BASF Corporation.
2s 2 Flavoring used at a level in order to provide a pleasing taste.
3 Added at a level in order to provide a pleasant in-use scent.
Add all ingredients except methylcellulose to chilled water and stir until
dissolved, while maintaining the chill water temperature. Adjust this solution
to
pH of 6.5 - 7.0 and filter through a cellulose acetate membrane filter. Add
the
3o methylcellulose to the chilled solution, QS with water, and stir under
refrigeration
to hydrate. Fill dropper vials with the solution and cap. Apply one drop of
the
solution to each nostril with the head tilted upward. Hold head briefly in
this
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position to permit spreading of the solution over the nasal turbinates. Repeat
3
times daily.
Example 9
s An example of an intranasal powder is made by mixing the following:
Inclredients Grams
Resveratrol 5.0
Dextrose powder 1.0
Ethanol 1.0
Flavoring '
camphor and eucalyptol 2
Lactose powder QS to 100 grams.
1 flavoring is used in an appropriate amount to provide a pleasing taste.
2 added at an appropriate level to provide a pleasant in use scent.
~5 Mix resveratrol with the dextrates in a V-mixer. Micronize this mixture in
a
fluid energy mill at 100 pounds per square inch dry air pressure. Mix the
micronized material by geometric addition with the lactose in a V-mixer.
Dissolve
camphor, eucalyptol, and flavors in ethanol, spray coating the powder with the
liquid in a V-mixer. Evaporate the ethanol after mixing by pan drying. Fill
dry
2o powder nasal inhalation metering pumps with the powder. Such pumps include
Prohaler DPI from Valois Corporation. Apply ten milligrams of the powder to
each nostril while inhaling. Repeat three times daily.
Example 10
An example of an inhalant is made by mixing the following:
2s Ingredients Grams
Resveratrol 0.60
Sorbitan trioleate 0.40
Propellant 114' 49.50
Propellant2 49.51
30 1 Freeon 114 E.I. Dupont
2 Freeon 12 E.I. Dupont
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Micronize the resveratrol in a fluid energy mill at 100 pounds per square
inch pressure. Dissolve the sorbitan trioleate in the mixed propellants.
Disperse
the resveratrol in the sorbitan trioleate / propellant liquid. Fill the
suspension in to
the canister of a pressurized metered dose inhaler using standard filling
s techniques. Administer 100 to 200 microliters from the metered dose inhaler
into
the mouth, while inhaling.
Example 11
An example of sublingual tablet made by mixing the following:
Ingredients Grams
Resveratrol 10
Lactose $6
Sucrose $7
Acacia 10
~ 5 Talc
Magnesium stearate 1
Water q~s~
Put resveratrol and excipient through a 60-mesh screen and blend.
Moisten with water to make a stiff mass; pass through an 8-mesh screen and dry
2o at 40C. Reduce the particle size by passing the dried granulation through a
10
mesh screen; blend in lubricants and compress. Mold tablet into a flat,
elliptical
or capsule-shaped tablet. Place tablet under tongue or between gum and cheek.
Example 12
2s An example of sublin gual tablet made by mixing
the following:
Ingredients Grams
Resveratrol 4.4
Lactose 32.25
Polyethylene glycol 0.35
3o Alcohol-water (60:40) q.s.
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Screen and blend powders; moisten the blend with alcohol-water (60:40)
to which the polyethylene glycol has been added, and mold the tablets into a
flat,
elliptical or capsule-shaped tablet. Place tablet under tongue or between gum
and cheek.
Example 13
An example of a liquid composition administered to the sublingual
mucosae or in the buccal cavity.
Ingredients Grams
Resveratrol 5
Ethanol $0
Mineral oil 12
Hydroxypropyl cellulose 2
Menthol 1
Water q.s.
Lastly, methods and compositions of the present invention are further
believed to improve the general maintenance and wellness of respiratory
health.
Indeed the prophylactic effect of the stilbenic phytoalexins of Formula 1 on
2o symptoms, are believed to be attributable, in part, to increased general
respiratory health
While the invention has been described in terms of its preferred
embodiments, those skilled in the art will recognize that the invention can be
practiced with considerable modification within the spirit and scope of the
appended claims.