JP2003505500A - Methods and compositions for the prevention and treatment of symptoms associated with colds and flu-like diseases - Google Patents

Abstract

  (57) [Summary] The present invention relates to the prevention and treatment of symptoms associated with colds and flu-like diseases and / or the prevention and treatment of congestion associated with respiratory disorders by administering a composition comprising a stilbene phytoalexin. Related to the method. The invention further relates to certain stilbene-based phytoalexin-containing compositions useful for such methods.

Description

Detailed Description of the Invention

FIELD The present invention relates to novel therapeutic uses of stilbene phytoalexins. In particular, embodiments of the present invention relate to the prevention and treatment of symptoms associated with colds and flu-like diseases, and the prevention and treatment of congestion (clogging) associated with respiratory disorders.

Background Many different viruses and virus strains are known to induce symptoms associated with respiratory viral infections. For example, common colds and flu include influenza, parainfluenza virus, rhinovirus, RS virus,
It is caused by members of several families of viruses, including enteroviruses and coronaviruses. It is difficult to pinpoint the exact cause of a disease because there are many predispositions whose involvement in the development of symptoms is not fully understood.
Not practical. Such factors include, but are not limited to, physical fatigue, psychological stress and general health.

Numerous therapeutic agents have been proposed to reduce the symptoms of the common cold, regardless of the virus and associated factors that cause the development of colds and influenza symptoms. Commonly marketed cough / cold products typically contain one or more of the following active substances: nasal decongestants such as pseudoephedrine, oxymetazoline, antihistamines such as doxylamine, antitussives. , Eg dextromethorphan, expectorants such as guaifenesin, as well as antipyretics such as acetaminophen. In an attempt to improve existing cold remedies, some alternative medications,
And experts in the field have proposed cold tests to be performed subsequently to test their efficacy. Examples of these therapies include interferon-α ₂
(Douglas et al., Prophylactic Efficacy of Intranasal Alpha ₂ -Interferon
Against Rhinovirus Infection in the Family Setting, The New England Jour
nal of Medicine, 314, pp.65-70, 1986), bradykinin antagonist (see
Higgins et al., A Study of the Efficacy of the Brandykinin Antagonist, N
PC567, in Rhinovirus Infections in Human Volunteers, Antiviral Research
vol. 14, pp.339-344, 1990), glucocorticoid (Farr et al., A Random
ized Controlled Trial of Glucocorticoid Prophylaxis Against Experimental
Rhinovirus Infection, The Journal of Infectious Diseases vol. 162, pp.1
173-1177, 1990), nedocromil (Barrow et al., The Effect of Intrana
sal Nedocromil Sodium on Viral Upper Respiratory Tract Infections in Hum
an Volunteers, Clinical and Experimental Allergy vol.20, pp.45-51, 1990
Gwaltney; Combined Antiviral and Antimediator Treatment of Rhinoviru (See, Interferon-α ₂ , ipratropium and naproxen)
s Colds, The Journal of Infectious Diseases vol.166, pp.776-782, 1992) and zinc salts (Potter et al., DIAS Rounds, Zinc Lozenges for Treatmen)
t of Common Colds, The Annals of Pharmacotherapy vol.27, pp.589-592, 199
3)).

A number of patents have also been issued that disclose compositions and methods for their use for the treatment of common cold and influenza conditions. Examples of such patents include: US Pat. Nos. 5,240,694, 5,422,097 and 5,492,689 which disclose treatment with a combination of antiviral and anti-inflammatory compounds.
(All Gwaltney); US Pat. No. RE033, which discloses treatment with zinc salts.
No. 465 and No. 5,409,905 (both Eby); Disclosed is treatment of cough and cold with a composition comprising a non-steroidal anti-inflammatory drug such as NSAIDS with an antihistamine active substance such as chlorpheniramine. U.S. Pat. No. 4,61
No. 9,934 and No. 4,552,899 (both Sunshine). Despite the abundance of compositions and prophylactic treatments known in the art, a consistent, effective and effective for the prevention and treatment of colds and flu-like symptoms and for the treatment of congestion associated with respiratory disorders. There remains a need to provide a secure method.

As discussed in detail below, a novel method for the prevention and treatment of colds and influenza-like symptoms by the administration of certain stilbene phytoalexins, and the treatment of congestion associated with respiratory disorders. The applicant has found a means.

Phytoalexin is a protective substance produced by plants after infection that has antibacterial properties. Examples thereof include various groups of natural substances such as isoflavonoids, terpenoids, polyacetylenes and dihydrophenanthrenes. Another source of phytoalexins is Veratr from the family Liliaceae.
um grandiflorum root, Pinus sibirica of Pinaceae, Vitis vinifera of Vineaceae and Arachis hypogaea of peanut genus. Other sources include Eucalyptus eucalyptus, Polygonum genus Polygonum and Nothofagus spp. And Cudrania javanensis genus Harigwa. Phytoalexin can also occur naturally as an oligomer.

Compositions containing stilbene phytoalexins can be prepared utilizing natural sources of stilbene phytoalexins or by synthesizing stilbene phytoalexins. One type of stilbene phytoalexin that can be found in various natural sources is 3,4 ′, 5-trihydroxystilbene resveratrol.
Resveratrol is found in relative abundance in red grapes and red wine and is associated with favorable pharmacological effects, including prevention and treatment of atherosclerosis.
Studies carried out on the constituents present in red wine that elicit pharmacological effects show a protective effect of 3,4 ′, 5-trihydroxystilbene resveratrol at the cardiovascular level (eg Frankel EN, et al., 341 Lancet 454, 19
93). Recently, 3,4 ', 5-trihydroxystilbene resveratrol has been demonstrated to have activity as a cancer chemopreventive agent (Meishang Jang et al.,
275 Science 218-229, 1997). Huzhang, a dietary supplement that is the source of resveratrol, has been reported to have antioxidant properties ("Source Na
turals ”, 1997, product labeling for resveratrol).

SUMMARY The present invention is a method for the prevention and treatment of colds and flu-like symptoms and / or for the treatment of congestion associated with respiratory disorders, wherein the stilbene phytophyte has the following structure: A method comprising administering to a subject a composition having an alexin:

[Chemical 2] Where R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ are independently selected from hydrogen and hydroxy. The present invention further relates to a composition comprising the stilbene phytoalexin described above.

DETAILED DESCRIPTION While the specification concludes with claims that particularly point out and distinctly claim the invention, it is believed the present invention will be better understood from the following description. . All references cited are hereby incorporated by reference in their entireties. Citation of any reference is not an admission as to any determination as to its availability as prior art to the claimed invention. All percentages are by weight of the total composition unless otherwise stated. All ratios are weight ratios unless otherwise stated. As used herein, "comprising" means that other processes and components that do not affect the final result can be added. This term "consists of"
And "consisting essentially of".

As used herein, a "safe and effective amount" is, within the scope of sound medical judgment, sufficiently high to provide a significant positive modification of the condition to be treated, but It means a sufficiently low (reasonable benefit / risk ratio) amount of active substance to avoid serious side effects. A safe and effective amount of active agent will vary with factors such as the particular condition being treated, the age and health of the subject being treated, the severity of the condition, the duration of treatment, the nature of the combination therapy.

Symptoms associated with colds and flu-like illnesses include, but are not limited to, stuffy nose, sneezing, sinus pain, sore throat, runny nose, cough, chest pain and headache. In addition, congestion is associated with certain respiratory disorders. These respiratory disorders include viral, bacterial and fungal infections that can cause sinusitis, otitis media and pneumonia. Other respiratory disorders that cause congestion include inflammatory and immunological responses to allergens and contaminants.

Nasal congestion is generally one manifestation of congestion. Congestion is characterized by localized edema in tissues or organs that are inflamed or damaged in response to colds and respiratory disorders. Because of this, congestion is accompanied by increased fluid production in mucus producing tissues such as the nose, lungs and throat. Increased fluid production contributes to reduced airflow through the nasal passages as well as luminal sites such as the lungs. Other places where it becomes congested include the head or facial sinuses, the Eustachian tube and the throat. The sinuses and ear openings (mouths) usually remain open due to normal cell processing of mucus, foreign particles and bacterial imbalances. However, these locations and openings can become obstructed due to excessive edema, which causes pain in the sinuses, middle ear, or head. Pain is believed to be due, in part, to increased pressure in the sinuses after fluid inflow that coincides with inflammatory cell inflow resulting in more mucus or overt pus. Therefore, it is generally accepted that nasal congestion is associated with these symptoms and may occur at the same time.
A stuffy nose results in the sensation of a blocked nose and nasal passages, with the inability to direct airflow through the nostrils.

One method of measuring such blockage is by measuring the nasal airway resistance (NAR) of the subject. NAR is a physical measure of resistance to airflow calculated from pressure gradients through the nasal passages (eg, nostrils, turbinates) under normal breathing patterns. Congestion in nasal tissue increases NAR. Increased NAR coincides with blockade and / or perception of obstructed airways. Biological mechanisms in nasal congestion are associated with both cold- and flu-like illness-related symptoms and congestion-related congestion.

NAR is measured by auditory and passive rhinometry. Amis
, TC, Oral airway flow dynamics in healthy humans, 515 J. Physiol. Lon
d. 293-8, 1999; Baroody, FM Relationship between histamine and physiol
ogical changes during the early response to nasal antigen provocation, 8
6 J. Appl. Physiol. 659-68, 1999; Hilberg, O., Acoustic reflections duri
ng rhinometry; spatial resolution and sound loss, 84 (3) J. Appl. Physio
l. 1030-9, 1998; Hilber, O., Acoustic rhinometry: evaluation of nasal ca
vity geometry by acoustic reflection, 66 (1) J. Appl. Physiol., 295-303,
Cited 1989 as a reference incorporated herein by reference.

A. Applicants have surprisingly found that the stilbene phytoalexins of Formula 1 are useful in the prevention and treatment of symptoms associated with colds and influenza-like illnesses, as well as congestion associated with respiratory disorders. For example, administration of a safe and effective amount of a stilbene phytoalexin of the present invention to a subject already suffering from nasal congestion will result in NARs preferably about 70% to about 98%, more preferably about 80%.
To about 95%, and even more preferably about 85% to about 94%. In another example,
Administration of a safe and effective amount of a stilbene phytoalexin of the present invention to a subject prior to suffering from nasal congestion results in an increase in NAR, preferably from about 70% to about 98%, more preferably from about 80% to about 95. %, And even more preferably about 85% to about 94%.

One embodiment of the present invention comprises a cold and influenza comprising administering to a subject a composition comprising a stilbene phytoalexin having the following Formula 1 and a pharmaceutically acceptable salt or ester thereof: Regarding methods for the prevention and treatment of such symptoms:

[Chemical 3] Where R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ are independently hydrogen or hydroxyl.

Preferably “R” represents a mixture of hydrogen and hydroxyl. More preferably the stilbene phytoalexin is tetrahydroxystilbene or trihydroxystilbene, even more preferably 3,4 ′, 5-trihydroxystilbene resveratrol (hereinafter “resveratrol”), ie In this case, R ¹ , R ³ , R ⁵ are hydroxyl and R ² , R ⁴ and R ⁶ are hydrogen. Such compositions useful in the methods of the invention are discussed in further detail below.

B. Compositions One embodiment of the invention relates to compositions having a stilbene phytoalexin of formula 1. Preferably, the compositions useful in the present invention are from about 0.01% to about 99.99%, more preferably from about 0.05% to about 30%, even more preferably from about 0.1% to about 2.
Contains 5% stilbene phytoalexin of formula 1.

1. Drug A preferred embodiment of the invention relates to a composition comprising a stilbene phytoalexin of formula 1 above in combination with a drug. A non-limiting list of agents useful in the present invention is provided below, with examples:

Antihistamines such as hydroxyzine, pyrilamine, phenindamine, dexchlorpheniramine, clemastine, diphenhydramine, azelastine, acrivastine, levocacarbastine, mequitazine, astemizole, ebastine,
Loratadine, cetirizine, terfenadine, promethazine, dimenhydrinate, meclizine, triperenamine, carbinoxamine, cyproheptadine, azatadine, brompheniramine, triprrolidine, cyclizine, tondilamin, phenylamine and mixtures thereof.

Antitussives such as hydrocodone, noscapine, benzonatate, diphenhydramine, clofedianol, clobutynol, fominoben, glaucine, forcodine, dipeprol, hydromorphone, carbetapentane, caramifen, levopropoxyphene, codeine, dextromethorphan and them. Mixture of.

Anti-inflammatory drugs, preferably non-steroidal anti-inflammatory drugs (NSAIDS), eg ketoprofen, indoprofen, indomethacin, sulindac, diflunisal, ketorolac, piroxicam, meclofenamate, benzydamine, carprofen, diclofenac, etodolac, fenbufen. , Fenoprofen, flurbiprofen, mefenamic, nabumetone, phenylbutazone, pirprofen, tolmethine, ibuprofen, naproxen, naproxen sodium, aspirin and mixtures thereof.

Analgesics such as acetaminophen. Expectorants / mucolytics such as ambroxol, bromhexine, terpine,
Guaifenesin, potassium iodide, N-acetyl cysteine and mixtures thereof. Mast cell stabilizers, preferably intranasally or orally administered mast cell stabilizers such as cromolyn, oxatamide, ketotifen, rhodoxamide, nedocromil and mixtures thereof. Leukotriene antagonists, such as zileuton et al. Methylxanthines such as caffeine, theophylline, enprophylline, pentoxifylline, aminophylline, dyphylline and mixtures thereof. Antioxidants or radical inhibitors such as ascorbic acid, tocopherols,
Pycnogenol and mixtures thereof. Steroids, preferably intranasally administered steroids such as beclomethasone, fluticasone, budesonide, mometasone, triamcinolone, dexamethasone, flunisolide, prednisone, hydrocortisone and mixtures thereof. Bronchodilators, preferably for inhalation, such as albuterol, epinephrine, ephedrine, metaproterenol, terbutaline, isoethalin, terbutaline, isoethalin, pirbuterol, bitolterol, fenoterol, limeterol, ipratroprium and mixtures thereof. Antiviral agents such as amantadine, rimantadine, enviroxime, nonoxynol, acyclovir, α-interferon, β-interferon and mixtures thereof. Biological agents such as cytokines and cell adhesion molecule inhibitors, ICAM antagonists, interleukin agonists or antagonists, hormones, polypeptides, amino acids, nucleotides, antibodies and mixtures thereof.

Acid or base addition salts, esters, metabolites, stereoisomers and enantiomers of these actives are also useful as agents in certain embodiments of the present invention, as well as safe and effective forms of these actives. Intended as an analog. It will also be appreciated that the agents are useful for more than one of the above mentioned uses, and these uses are clearly contemplated as well. This duplication is recognized in the art and it is well within the skill of the practitioner to adjust the dose etc. to suit the indication.

2. Reinforcement In a preferred embodiment, the composition further comprises a reinforcer. Fortifying agents useful in the present invention include herbs, phenols, polyphenols, anthocyanins, anthocyanosides, carotenoids, bioflavinoids, vitamins, metal ions, inorganic salts, proanthocyanidins, antioxidants and / or vegetable fibers, It is not limited to these. Examples include echinacea, tea polyphenols, epigallocatechin, β-carotene, grape seed extract, lycopene, flavone, quercetin, tocopherol, zinc, selenium, tin, ascorbic acid, calcium, N-acetylcysteine and mixtures thereof. However, the present invention is not limited to these.

3. Sources of Stilbene Phytoalexins The stilbene phytoalexins of Formula 1 can come from natural and / or synthetic sources. Orsini-F, et al., Isolation, synthesis, and antiplatelet aggre
gation activity of resveratrol 3-O-beta-D-glucopyranoside and related co
mpounds, 60 (11) J. Nat. Prod. 1082-7, 1997: Orsini-F, et al., Synthesis
of biologically active polyphenolic glycosides (combretastatin and resb
eratrol series), 301 (3-4) Carbohydr. Res. 95-109, 1997; Hain, et al.,
Expression of a stilbene synthase gene in Nicotiana tabacum results in s
synthesis of the phytoalexin resveratrol, 15 (2) Plant. Mol. Biol. 325-35
, 1990, incorporated herein by reference. In a preferred embodiment, the composition comprises a natural source material, natural source extract or natural source powder of the stilbene phytoalexin of formula 1. Examples include, but are not limited to, wine, grape, Huzhang and Polygonum cuspidatum of the genus Willis.

[0027] 4. Forms and Administration The compositions useful in the present invention may be in the form of solids, semi-solids, liquids, semi-liquids, powders, granules, liposomes, tablets, capsules, gels, lozenges, dentifrices and mouthwashes. The compositions useful in the present invention can be incorporated into microspheres, microcapsules, nanoparticles, liposomes, etc. for controlled release. The composition further comprises an anti-precipitation agent,
It is convenient to include solubilizers, stabilizers, pH adjusters and / or dispersants. In a preferred embodiment, the composition is in the form of herbs. Herbal forms useful in the present invention include tea, decoction, beverages, candies or other confectionery, foods, enteral liquid nutrition products, mouthwashes, lozenges, dentifrices and dietary or dietary supplements. , But not limited to these. Routes of administration of the compositions of the present invention include any suitable route that results in blood levels that provide prophylactic and therapeutic benefits. Suitable routes of administration include, but are not necessarily limited to, oral, topical, parenteral, cutaneous, nasal, rectal, vaginal, ocular, inhalation or combinations thereof. Preferably the route of administration is oral or nasal.

[0028]

【Example】

The following examples further describe and demonstrate the preferred embodiments within the scope of the present invention. The examples are given by way of illustration only and are not limiting of the invention, as numerous modifications are possible without departing from the spirit and scope of the invention.
All ingredients are based on the weight of 100 g of the composition.

Examples 1 and 2 Examples of toothpaste and dentifrice gel compositions of the present invention are made in a conventional manner by mixing the following ingredients: Example 1 Example 2 Ingredients (wt%) ( Wt%) Sorbitol 41.44 35.00 Saccharin sodium 0.46 0.20 FD & C blue (1% solution) --- 0.05 Precipitated silica 20.00 25.00 Sodium fluoride 0.24 0.24 Perfume 1. 00 1.50 Sodium alkyl sulfate 4.00 1.20 Trisodium phosphate 1.45 ――― 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 Sufficient amount Sufficient amount

Examples 3 and 4 Examples of mouthwash compositions of the present invention are prepared in a conventional manner by mixing the following ingredients: Example 3 Example 4 Ingredients (wt%) (wt%) Cetylpyridinium chloride 0.045 0.045 Domiphene bromide 0.005 0.005 Alcohol (standard modification No. 40) 16.25 8.50 Glycerin 10.00 7.50 Poloxamer 407 0.20 0.20 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% solution) 0.04 0.12 FD & C Blue (1% solution) ) 0.003 ――― FD & C Yellow (1% solution) ――― 0.001 Saccharin 0.06 0.08 Mint oil 0.14 ――― Peaminto oil --- 0.12 resveratrol 0.30 0.20 purified water sufficient amount sufficient amount

[0031]   Example 5   Examples of dental solutions of the present invention are made by mixing the following ingredients: Ingredient (% by weight) Resveratrol 1.00 Perfume 0.10 Polysorbate 80 0.25 Saccharin sodium 0.05 Methylparaben 0.20 Propylparaben 0.10 Sufficient water

Example 6 An example of an oral gel composition of the present invention is made by mixing the following ingredients: Ingredient (wt%) Hydroxyethyl Cellulose 2.50 Sodium Fluoride 0.09 Sodium Saccharin 0.05 FD & C Green No. 3 (1% solution) 0.01 Resveratrol 1.00 Purified water Sufficient amount

Example 7 An example of an intranasal spray solution is prepared by mixing the following ingredients: Ingredients Gram resveratrol 1.0 Nonionic detergent ¹ 0.70 Disodium hydrogen phosphate 0.11 Potassium dihydrogen phosphate 0.38 Benzalkonium chloride 0.04 Chlorhexidine gluconate 0.26 EDTA disodium 0.01 Perfume ² Camphor and eucalyptol ³ Purified water sufficient amount up to 100 g 1. Available as Tyloxapol from Nycomed, Inc. 2. A flavoring agent used at some level to provide a pleasant taste. 3. Added at some level to provide a pleasant in-use scent. Add all ingredients to cold water and stir until dissolved while maintaining cold water temperature. The solution is adjusted to pH 5.5-6.5. Add sufficient water and filter through a cellulose acetate membrane filter. Fill a manually operated nasal sprayer with the composition.
Spray about 5-500 μl of solution into each nostril. Repeat 3 times a day.

Example 8 An example of an intranasal drip solution is prepared by mixing the following ingredients: Ingredients Gram methylcellulose gum 0.115 Sodium chloride 0.350 Potassium dihydrogen phosphate 0.540 Dihydrogen phosphate Potassium 0.310 Poloxamer block copolymer ¹ 0.145 Propylene glycol 1.170 Resveratrol 0.568 Benzalkonium chloride 0.025 Perfume ² Camphor and eucalyptol ³ Purified water sufficient amount up to 100 g 1. Available as Pluronic 127 from BASF Corporation. 2. A flavoring agent used at some level to provide a pleasant taste. 3. Added at some level to provide a pleasant in-use scent. All components except methyl cellulose are added to cold water and stirred while maintaining the cold water temperature until dissolved. The solution is adjusted to pH 6.5-7.0 and filtered through a cellulose acetate membrane filter. Methylcellulose is added to the cold solution, sufficient water is added and stirred under cooling to hydrate. Fill the dropping vial with the solution and cap. Apply 1 drop of solution to each nostril while tilting the head upwards. Hold the head in this position for a short time to spread the solution over the turbinate. Repeat 3 times a day.

Example 9 An intranasal powder example is made by mixing the following ingredients: Ingredients Gram resveratrol 5.0 Dextrose powder 1.0 Ethanol 1.0 Flavor ¹ Camphor and Eucalyptol ² 100 g Lactose powder up to 1. A suitable amount of flavoring agent is used to provide a pleasant taste. 2. Added at appropriate levels to provide a pleasant in-use scent. Mix resveratrol with dextrate in a V-mixer. Micronize this mixture in a fluid energy mill at 100 pounds per square inch dry air pressure. V
The finely divided material is mixed with lactose in a mixer by geometric addition. camphor,
Eucalyptol and flavor are dissolved in ethanol and the powder is spray coated with the liquid in a V mixer. After mixing, the ethanol is evaporated by drying the dish. Dry powder Fill a nasal inhalation metering pump with powder. An example of such a pump is the Prohaler DPI from Valois Corporation. Apply 10 mg of powder to each nostril while inhaling. Repeat 3 times a day.

Example 10 An inhalation example is prepared by mixing the following ingredients: Ingredients Gram resveratrol 0.60 sorbitan trioleate 0.40 Propellant 114 ¹ 49.50 Propellant ² 49. 51 1 Freeon 114 EIDupont 2 Freeon 12 EIDupont Resveratrol is micronized in a fluid energy mill at 100 pounds per square inch pressure. Dissolve sorbitan trioleate in the mixed propellant. Disperse resveratrol in sorbitan trioleate / propellant liquid. Fill the suspension into a canister of a metered dose inhaler using standard filling techniques. 1 from a metered dose inhaler
Administer 00-200 μl into the mouth with inhalation.

Example 11 An example of a sublingual tablet is prepared by mixing the following ingredients: Ingredients Gram resveratrol 10 Lactose 86 Sucrose 87 Acacia 10 Talc 6 Magnesium stearate 1 Water Sufficient 60 mesh screen. Add resveratrol and excipients through and mix. Moisten with water to make a hard mass, pass through an 8 mesh screen and dry at 40 ° C. Pass the dry granulation through a 10 mesh screen to reduce particle size,
Mix in lubricant and compress. Mold tablets into flat oval or capsule shaped tablets. Place the tablet under the tongue or between the gum and cheek.

Example 12 An example of a sublingual tablet is prepared by mixing the following ingredients: Example 12 Ingredients Gram resveratrol 4.4 Lactose 32.25 Polyethylene glycol 0.35 Alcohol-water (60 : 40) Sufficient Screen powder and mix. The formulation to which polyethylene glycol has been added is moistened with alcohol-water (60:40) and tablets are formed into oblate or capsule shaped tablets. Place the tablet under the tongue or between the gum and cheek.

Example 13 Example of a liquid composition administered to the sublingual mucosa or into the oral cavity. Ingredients Gram resveratrol 5 Ethanol 80 Mineral oil 12 Hydroxypropylcellulose 2 Menthol 1 Water Sufficiently Lastly, the methods and compositions of the present invention are further believed to improve overall maintenance and health of respiratory health. In fact, the protective effects of stilbene phytoalexins of formula 1 on symptoms appear to be due, in part, to an increase in overall respiratory health. Although the invention has been described with respect to 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.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61K 9/16 A61K 9/16 9/20 9/20 9/48 9/48 35/78 35/78 X 45/00 45/00 47/02 47/02 47/46 47/46 A61P 11/00 A61P 11/00 11/02 11/02 31/16 31/16 (81) Designated country EP (AT, BE, CH , CY, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE), OA (BF, BJ, CF, CG, CI, CM, GA, GN , GW, ML, MR, NE, SN, TD, TG), AP (GH, GM, KE, LS, MW, MZ, SD, SL, SZ, TZ, UG, ZW), EA (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), AE, AG, AL, AM AT, AU, AZ, BA, BB, BG, BR, BY, BZ, CA, CH, CN, CR, CU, CZ, DE, DK, DM, DZ, EE, ES, FI, GB, GD, GE , GH, GM, HR, HU, ID, IL, IN, IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MA, MD, MG, MK, MN, MW, MX, MZ, NO, NZ, PL, PT, RO, RU, SD, SE, SG, SI, SK, SL, TJ, TM, TR, TT, TZ, UA, UG, UZ , VN, YU, ZA, ZW (72) Inventor Gantenberg, Nicholas Seymour United States Ohio, Liberty, Tunship, Maple, Creek, Drive 7097 (72) Inventor Singer, Robert Ernest Junia United States Oha Ohio, Fairfield, Kingsmont, Court 3F Term (reference) 4C076 AA09 AA19 AA29 AA31 AA36 AA53 BB01 BB22 CC03 CC11 CC15 DD22 EE58 FF36 FF39 FF51 4C084 AA19 MA02 MA16 MA21 MA52 MA57 MA41 MA43 NA NA14 ZA082 ZA361 ZA601 ZA612 ZA622 ZB112 ZB332 ZC022 ZC132 ZC751 4C088 BA32 MA01 MA16 MA21 MA24 MA27 MA34 MA35 MA37 MA41 MA43 NA01 NA05 NA14 ZA36 ZA59 ZA60 ZB33 MA61 MA41 MA61 MA41 MA41 MA41 MA41 MA41 MA41 MA41 MA41 MA01 MA02 MA01 MA01 MA02 MA02 MA01 MA01 MA02 MA01 MA02 MA41 MA01 MA02 MA41 MA01 MA02 MA41 MA01 MA01 MA01 MA01 MA02 MA41 MA01 MA02 MA41 MA41 MA41 MA41 NA05 NA14 ZA08 ZA36 ZA60 ZA61 ZA62 ZB11 ZB33 ZC02 ZC13 ZC75

Claims (8)

[Claims] 1. A method for producing a composition for use as a prophylactic and therapeutic agent for blood stasis associated with colds and influenza-like symptoms and respiratory disorders, wherein the composition has the following structural formula: A stilbene phytoalexin and a pharmaceutically acceptable salt or ester thereof, wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ are independently selected from hydrogen and hydroxy. Including the method. 2. The method according to claim 1, wherein the stilbene phytoalexin is trihydroxystilbene or tetrahydroxystilbene, preferably 3,4 ′, 5-trihydroxystilbene resveratrol. 3. The method according to claim 1, wherein the composition contains 0.01% to 99.99% stilbene phytoalexin. 4. The method according to claim 1, wherein the composition further comprises a natural source product, natural source extract or natural source powder of stilbene phytoalexin. 5. The method according to claim 1, wherein the composition is a herbal medicine. 6. The composition is a solid, semi-solid, liquid or semi-liquid, powder,
A method according to claims 1 to 5 in the form of granules, liposomes, tablets, capsules, gels, lozenges, dentifrices and mouthwashes. 7. The composition comprises herbs, phenols, polyphenols, anthociamines, anthocyanosides, carotenoids, bioflavinoids, vitamins,
7. The method of claims 1-6, further comprising a toughening agent selected from the group consisting of inorganic salts, metal ions, antioxidants, vegetable fibers and mixtures thereof. 8. The composition comprises an antihistamine, an antitussive, an antiinflammatory, an analgesic, a mast cell stabilizer, a leukotriene antagonist, methylxanthine, an antioxidant, a steroid, a bronchodilator, an antiviral agent, and an organism. 8. The method of claims 1-7, comprising a drug selected from the group consisting of drugs and mixtures thereof.