US 2008.0020027A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0020027 A1 Loewy et al. (43) Pub. Date: Jan. 24, 2008

(54) FILM-DELIVERING RINSE Publication Classification (75) Inventors: Zvi G. Loewy, Fair Lawn, NJ (51) Int. Cl. (US); William Zev Levine, A 6LX 9/70 (2006.01) Jerusalem (IL); Aron J. Safer, A636/00 (2006.01) Bet Shemesh (IL) A6IR 36/28 (2006.01) Correspondence Address: (52) U.S. Cl...... 424/449; 424/737; 424/773; 424/774 LAW OFFICES OF ARTHUR E. JACKSON P.O. BOX 88 HOPEWELL, NJ 08525 (57) ABSTRACT (73) Assignee: IZUN PHARMACEUTICALS Provided, among other things, is a method of treating or CORP., New York, NY (US) ameliorating an indication of mucosal or adjacent tissue comprising periodically applying to mucosa at or adjacent to (21) Appl. No.: 11/780,593 disease affected tissue a rinse comprising: an effective amount of appropriate composition of herbal bioactive com (22) Filed: Jul. 20, 2007 prising active(s) of one or more of Sambucus migra, Centella Related U.S. Application Data asiatica or Echinacea purpurea; an antimicrobially effective AV amount of a quaternary ammonium surfactant; and option (60) Provisional application No. 60/807,846, filed on Jul. ally a polymer or mixture of polymers effective to coat said 20, 2006. tissue and entrap said extract(s). US 2008/0020027 A1 Jan. 24, 2008

FILM-DELIVERING RINSE asiatica or Echinacea purpurea and (ii) polymer or mixture of polymers effective to coat said tissue and entrap said extract(s); and a film, patch or an adhesive solid formulation 0001. This application claims the priority of U.S. Pat. comprising appropriate composition of plant extract(s) com Applin. 60/807,846, filed 20 Jul. 2006. prising herbal bioactive comprising active(s) of Sambucus 0002 The present invention relates to an anti-inflamma nigra. tory oral coating that is applied as a rinse. 0003 Certain herbal extracts have been clinically shown DETAILED DESCRIPTION OF THE to be effective in treating or ameliorating certain conditions INVENTION of the mouth. Described in WO 02/094300 and PCT/US05/ 42348 corresponding to U.S. Ser. No. 11/284,078, filed 21 Nov. 2005 are a number of useful combinations of herbal 0009. 1. Plant Extracts extracts for treating or ameliorating diseases of mucosa, and 0010 Appropriate plant extract compositions for use in dosage forms for delivering the extracts to discrete regions the device include extract of Sambucus nigra (SN), and/or of the mouth. For example, Such combinations, in the plant extracts of Allium sativum (AS), Calendula officinalis delivery form described in PCT/US05/42348, have (CO), Camellia sinensis (CS), Centella asiatica (CA, also achieved, in an 80 patient trial, an average of 50% pain known as Gotu Kola), Commiphora molmol (CM), Echina reduction in the first /2 hour. In the same trial, average lesion cea purpurea (EP), Gaultheria procumbens (GP), Hyperi reductions of 40% were achieved in 4 hours. cum perforatum (HP), Krameria triandra (KT), Ligusticum 0004. The delivery devices described in the above-cited porterii-Osha (LP), Matricaria recutita, Melissa officinalis, documents can be very effective, particularly with discrete lesions. However, in Some cases of oral or other mucosal Salix alba, Thymus vulgaris, Uncaria tomentosa, Usnea disease the number of lesions can make it at best awkward barbata or Vaccinium myrtillus. The extract compositions to apply medicament delivery devices to each of the lesions. can include, for example, Sambucus migra extract in an Or, the lesions can be located in positions that may make it amount from one of the lower percentages (by weight) physically difficult or impossible to deliver a medicament recited in the next sentence to 90, 95, 96, 97,98, 99 or 100%. delivery devices to the lesions. These lower percentages are 50, 55, 60, 65, 70, 75, 80, 85, 0005 Provided herein is a rinse that provides a medica 90 or 95%. If a second or third extract is present, it may be ment-delivery coating to the soft tissue surfaces of the present, for example in amount from one of the lower mouth, or to other mucosal tissues. percentages to one of the higher percentages recited in the following sentences. Lower percentages for the second or SUMMARY OF THE INVENTION third extracts can be, for example, 0.5, 1, 2, 5, 10 or 20%. Higher percentages can be, for example, 1, 2, 5, 10, 20, 30. 0006 Provided, among other things, is a method of 40 or 50%. These ranges, and any other ranges described in treating or ameliorating an indication of mucosal or adjacent this application, can include or exclude one or both end tissue comprising periodically applying to mucosa at or points. adjacent to disease affected tissue a rinse comprising: an effective amount of appropriate composition of herbal bio 0011. The term “extract’ is used herein to include all of active comprising active(s) of one or more of Sambucus the many types of preparations containing an effective nigra, Centella asiatica or Echinacea purpurea; an antimi amount of active ingredients. Thus, the extracts can be crobially effective amount of a quaternary ammonium Sur produced by cold extraction techniques using a variety of factant; and optionally a polymer or mixture of polymers different extraction solvents including, but not limited to, effective to coat said tissue and entrap said extract(s). The water, fatty solvents (such as olive oil), and alcoholic method can include, in some embodiments, applying to a portion of the mucosa a film, patch or an adhesive solid solvents (e.g. 70% ethanol). Cold extraction techniques are formulation comprising appropriate composition of herbal typically applied to softer parts of the plant Such as leaves bioactive comprising active(s) of one or more of Sambucus and flowers, or in cases wherein the desired active compo nigra, Centella asiatica or Echinacea purpurea. The method nents of the plant are heat labile. Alternatively, hot extraction can be used for treating or ameliorating mucositis secondary techniques, where such solvents are heated to a temperature to chemotherapy. above room temperature, can be used with the precise value 0007. The invention further provides a transmucosal of said temperature being dependent on factors such as the delivery rinse comprising: an effective amount of appropri properties of the chosen solvent and extraction efficacy. Hot ate composition of plant extract(s) comprising herbal bio extraction techniques are more commonly applied to the active comprising active(s) of one or more of Sambucus harder, tougher parts of the plant, such as bark, woody nigra, Centella asiatica or Echinacea purpurea; an antimi branches and larger roots. In some cases, sequential extrac crobially effective amount of a quaternary ammonium Sur tions need to be performed in more than one solvent, and at factant, and optionally a polymer or mixture of polymers different temperatures. Standard procedures for producing effective to coat mucosal tissue and entrap said extract(s). plant extracts (including hot extraction, cold extraction and 0008 Further provides is a kit for the treatment of an other techniques) are described in many publications includ indication of the mucosa or adjacent tissue comprising: ing “Medicinal plants: a field guide to the medicinal plants transmucosal delivery rinse comprising (i) an effective of the Land of Israel' (in Hebrew), author: N. Krispil, Har amount of appropriate composition of herbal bioactive com Gilo, Israel, 1986 and “Making plant medicine’, author: R. prising active(s) of one or more of Sambucus migra, Centella Cech, pub. by Horizon Herbs, 2000.

US 2008/0020027 A1 Jan. 24, 2008

-continued Plant Extract Composition: C103 C104 C1OS C106 C107 C108 C110 C111 C112 C113 C114

SN 90 90 90 90 90 90 90 90 90 90 90 EP 10 9 8 7 6 5 9 8 7 6 5 GP 1 2 3 4 5 HP 1 2 3 4 5

C11S C116 C117 C118 C119 C12O C122 C123 C124 C12S C126

SN 90 90 90 90 90 90 90 90 90 90 90 EP 10 9 8 7 6 5 9 8 7 6 5 KT 1 2 3 4 5 LP 1 2 3 4 5

0013 The above amounts provide exemplary useful (0.019 2. Polymer amounts +0.5% for amounts from 1-2%, 0.5 or 1% for 0020. The rinses of the invention contain, in certain amounts from 3-5%, 0.5, 1 or 2% for amounts from 6-10%, embodiments, polymer selected to form a film on mucosal +1, 2, 3, 4 or 5% for amounts from 70-90% (with the tissue and entrap an amount of herbal extract. Any polymer foregoing percentage ranges being of the total extract that coats the appropriate mucosal tissue can be used. Some amount by weight). illustrative examples include crosslinked polyacrylic acid 0014. In some embodiments, the solids from the extract moiety-containing polymers (which can be esterified) (e.g., (s) typically contribute amounts to the rinse from one of the CarbopolTM), carboxymethyl cellulose salts (e.g., Na-CMC), following lower endpoints or from one of the following hydroxypropylmethylcellulose (MethocelTM), hyaluronic upper endpoints. The lower endpoints are 10, 15, 20, 25 and acid, alginate gum, chitosan, pectin, locust bean gum, Xantan 30 weight percent. The upper endpoints are 15, 20, 25, 30. gum, acacia gum, the foregoing crosslinked, and the like. 35, 40 and 45 weight percent. The percent of such solids in The polymer can be water-swellable or water dispersible. the rinse can be, for example, approximately 30.0, 30.1, 30.2 Other polyanionic polymers, such as those described in U.S. and so in increments of 0.1 up to 40.0. Pat. No. 4,615,697, can be used. Or, polycationic polymers 0.015. In some embodiments the herbal bioactive can be (such as chitosan) can be used. one or more flavonoids, isoflavonoids, tocopherols, polyphe 0021 Polymers can include or consist of polyethylene/ nols, or similar agents often found in herbal extracts. polypropylene block copolymers (poloxamers). Appropri 0016 Flavonoids can include, for example, flavonols or ately selected, and in appropriate amounts, such polymers flavonolols such as, without limitation, a rutoside: rutin can provide the thermal annealing discussed below. (quercitin 3-O-rutino-side), quercitrin (quercetin 3-O- 0022 Depending on the embodiment, the film formed rhamno-side), isoquercitrin (quercetin 3-O-glucoside), with the rinse may entrap a range of percentages of the dioSmin (diosmetin 7.beta.-rutinoside), astragalin herbal extract in the rinse. Thus, the liquid portion (i.e., the (kaempferol 3-O-glucoside), kaempferol 3-O-rutinoside, non-coated portion) of the rinse can deliver medicament myricitrin (or myricetin 3-O-rhamnoside), robinin (or during the rinse and possibly for a period thereafter, while kaempferol 3-O-robinoside 7-rhamnoside), kaempferitrin the coated portion can provide longer term delivery. The (or kaempferol 3.7-O-dirhamnoside), nobiletin, tangeretin. localization of medicament at or near the affected site Or, flavonoids can include, for example, flavones such as, counterbalances any reductions in amount during the Sus without limitation, rhoifolin (or apigenin 7-O-neohesperido tained delivery portion of an administration. side), luteolin 7-O-glucoside, scutellarin (or scutellarein 0023 a. Mucoadhesive 5-O-glucoside), pectolinarin (or pectolinarigenin 7-O-ruto 0024. In certain embodiments the polymer(s), relative side), galuteolin (or luteolin 5-O-glucoside), acaciin (or amounts, and concentrations are selected to provide a film acacetin 7-O-rhamnoglucoside). Or, flavonoids can include, that is mucoadhesive. The term mucoadhesive, as used for example, flavanones such as, without limitation, liquir herein, is a material that adheres to a mucosal tissue surface itin (or liquiritin 4'-O-glucoside), maringin (or maringenin in-vivo and/or in-vitro. Such adhesion will adherently local 7-O-neohesperido-side), hesperidin (or hesperetin 7-O-rut ize the dosage form onto the mucus membrane and in certain inoside), eriodictin (or eridictiol 7-O-rhamnoside). embodiments requires the application of a force of at least 0017. Isoflavonoids can include, for example: formonon about 50 dynes/cm to separate the mucoadhesive material etin 7-O-glucoside (or ononin), afromosin 7-O-glucoside (or from the mucus membrane. wistin), genistein (or genistein 7-O-glucoside), daidzin, gly 0025 Appropriately selected, the polymer composition citin, genistein 6-O-malonylglucoside, daidzein 6-O-malo is, in certain embodiments, less adhesive on teeth. nylglucoside, genistein 6-O-acetyl-glucoside, iridin (or iri 0026 Crosslinked polyacrylic acid-moiety-containing genin 7-O-glucoside), irisolone, tectoridin (or tectorigenin polymers and/or polysaccharide gums (e.g. chitosan) can be 7-O-glucoside) or shekanin. used to achieve Such mucoadhesion. 0018. If any one of these specific bioactive agents is (0027 b. Thermal Annealing Polymer included in the rinse it can be used in an amount corre 0028. In certain embodiments, the polymer comprise sponding to the amount found in one of the above-described polymers that reversible gel at temperatures approaching eXtractS. 35°C., but are water dispersible attemperatures of about 25° US 2008/0020027 A1 Jan. 24, 2008

C. or less. Thus, film-forming at the mucosal Surface can be 0038. In some embodiments, the plasticizers can contrib increased, as a more liquid rinse can be applied, and gel ute amounts to the rinse from one of the following lower forming is accentuated at or near the warmer Surfaces of endpoints or from one of the following upper endpoints. The tissue. lower endpoints are 10, 15, 20, 25 and 30 weight percent. 0029 Such thermal annealing is provided by, for The upper endpoints are 15, 20, 25, 30, 35, 40 and 45 weight example, polyethylene/polypropylene block copolymers, percent. The percent of plasticizers in the rinse can be, for Such as polyethylene-polypropylene-polyethylene triblock example, approximately 30.0, 30.1, 30.2 and so in incre copolymers. Examples can include the Poloxamer (i.e., ments of 0.1 up to 40.0. PluronicTM) polymers available from BASF, such as Polox 0039. 6. Alcohol-Free Rinses amer 407, 338, 237, 188, and the like, provided in the 0040. In certain embodiments, the rinse lacks propyl or polymer component (as all or a part thereof). ethyl alcohols in amounts that are antimicrobially effective. 0030 3. Rinse 0041 7. Illustrative Indications; Treatment Parameters 0031. In certain embodiments, the rinse comprises an 0042 Indications treated with the methods and devices of effective amount of an appropriate composition of herbal the invention include any indication of mucosal tissue, or bioactive comprising active(s) of one or more of Sambucus tissue sufficiently adjacent to mucosal tissue, treatable with nigra, Centella asiatica or Echinacea purpurea, and an the plant extracts and/or described antimicrobial agents. For antimicrobially effective amount of a quaternary ammonium example, oral indications and microbial indications (such as compound that is Surface active. microbial lesions) can be treated with the methods and 0032 4. Antimicrobial Agents devices. 0043 Oral indications appropriate for treatment with the 0033. In certain embodiments the rinse includes antimi invention include, without limitation, periodontal disease, crobial agents in amounts effective to reduce the growth of gingivitis, aphthous ulceration (e.g., canker Sores, recurrent one or more gingivitis-associated microbes. Antimicrobial aphthous stomatitis, recurrent ulcerative stomatitis), agents can be surface active quaternary ammonium com mechanical trauma, thermal trauma, the oral lesions, dry pounds, chlorohexidine, Zinc salt(s) (e.g., chloride), fluoride mouth (xerostomia), mucositis or eruptions of lichen planus, salt(s) (e.g., Na/Sn fluoride), triclosan, benzydamine, chlo bullous pemphigoid, pemphigus Vulgaris, dermatitis herpe robutanol, chlorothymol, thymol, methyl salicylate, men tiformis or angular chelitis, recurrent herpes, other microbial thol, alkyl sulfate salt(s) (e.g., sodium lauryl Sulfate), per (including viral) eruptions of the oral mucosa, lesions (in oxides (e.g., hydrogen peroxide), and the like cluding the foregoing and Such as mucositis) secondary to 0034. In certain embodiments the rinse includes an anti chemotherapy or radiation treatment, lesions resulting from microbially effective amount of a quaternary ammonium trauma (including chemical or other burns), lesions second compound that is surface active. Such antimicrobial Surfac ary to systemic disease, lesions resulting from autoimmune tants can include, for example, 1-alkylpyridinium salts, disease, lesions with idiopathic causes, or the like. The where alkyl is C8-C36 (or C8-C20, or C10-C20), and herbal component of the rinse typically includes components wherein the carbon ring members can be substituted with up selected to reduce inflammation. In certain embodiments, to two C1-C7 alkyl groups. For example, the rinse can the herbal component is effective to reduce matrix metallo include cetylpyridinium chloride. protease(s) expressed at or near the mucosal membrane, 0035. In some embodiments, the quaternary ammonium and/or to reduce cytokine(s) expressed at or near the compound(s) typically contribute amounts to the rinse from mucosal membrane. one of the following lower endpoints or from one of the 0044. In the case of mucositis secondary to chemotherapy following upper endpoints. The lower endpoints are 0.01, or radiation treatment, the rinse can be administered after the 0.02, 0.03, 0.04 and 0.05 weight percent. The upper end primary chemotherapy treatment, but before symptoms of points are 5, 4, 3, 2, 1, 0.9, 0.8, 0.7, 0.6,0.5, 0.25, 0.15, 0.14, mucositis are apparent. 0.13, 0.12, 0.11, 0.10, 0.09 and 0.08 weight percent. 0045. In many embodiments, the treated tissue is in the 0.036 5. Penetrants mouth. In other embodiments, the treatment tissue is at or 0037 Plasticizers, penetration enhancers, flavoring adjacent to other mucosal tissue. Such as nasal, anal, vaginal, agents, preservatives, coloring agents, Surfactants and the and the like. like can be included in the rinse. Plasticizers will generally 0046 8. Solid Dosage Forms for Use with the Rinse modify the feel, softness, flexibility of the film. Penetration 0047. In certain embodiments, the rinse is administered enhancers may, in some cases, act as plasticizers. Examples in conjunction with another administration form, such as an of plasticizers include, without limitation, glycerol, propy film, patch or mucoadhesive solid dosage form. This solid lene glycol, Sorbitol, fatty acid esters (such as glyceryl dosage form can be applied before, concurrently, or after oleate), and the like. Examples of penetration enhancers administration of the rinse. The solid forms can help deliver include, without limitation, fatty acid esters, fatty alcohol medicament to more severely affected, or more mechani ethers, PEG-C10-C30alkyl, N-lauroyl sacrcosine, sorbitan cally accessible tissue, while the rinse delivers medicament monolaurate, Stearyl methacrylate, N-Dodecylazacyclohep elsewhere. The medicament in the solid form can be the tan-2-one, N-dodecyl-2-pyrrolidinone, N-dodecyl-2-piperi same or different from that of the rinse. However, herbal dinone, 2-(1-nonyl)-1,3-dioxolane, N-(2-methoxymethyl) extracts and extract mixtures as described above are usefully dodecylamine, N-dodecylethanolamine, N-dodecyl-N-(2- employed. Similarly, quaternary amine Surfactants are use methoxymethyl)acetamide, 1-N-dodecyl-2-pyrrolidone-5- fully employed. For example, the dosage described in WO carboxylic acid, 2-pentyl-2-oxo-pyrrolidineacetic acid, 02/094300 and PCT/US05/42348 can be employed. Or, the 2-dodecyl-2-oxo-1-pyrrolidineacetic acid, 2-dodecyl-2-oxo film described in the an application, filed Jun. 20, 2007, 1-pyrrolidineacetic acid, 1-azacylioheptan-2-one-dodecy titled “Anti-Inflammatory Dissolvable Film, Ser. No. lacetic acid, and the like. 11/765,587, can be employed. US 2008/0020027 A1 Jan. 24, 2008

0048 9. Antiinflamatory Agents 0053. The following examples further illustrate the 0049. In certain embodiments, the rinse further compris present invention, but of course, should not be construed as ing anti-inflammatory agent(s). Such as steroidal or nonste in any way limiting its scope. roidal anti-inflammatory agents. Steroidal anti-inflammatory agents, include but are not limited to, corticosteroids such as Definitions hydrocortisone, hydroxyltriamcinolone, alpha-methyl dex 0054 The following terms shall have, for the purposes of amethasone, dexamethasone-phosphate, beclomethasone this application, the respective meanings set forth below. dipropionates, clobetasol Valerate, desonide, desoxymetha Sone, desoxycorticosterone acetate, dexamethasone, dichlo Effective Amount risone, diflorasone diacetate, diflucortolone Valerate, flua 0055 To treat the indications of the invention, an effec drenolone, fluclorolone acetonide, fludrocortisone, tive amount of a pharmaceutical compound will be recog flumethasone pivalate, fluosinolone acetonide, fluocinonide, nized by clinicians but includes an amount effective to treat, flucortine butylesters, fluocortolone, fluprednidene (flupred reduce, alleviate, ameliorate, eliminate or prevent one or nylidene) acetate, flurandrenolone, halcinonide, hydrocorti more symptoms of the disease sought to be treated or the Sone acetate, hydrocortisone butyrate, methylprednisolone, condition sought to be avoided or treated, or to otherwise triamcinolone acetonide, cortisone, cortodoxone, fluc produce a clinically recognizable favorable change in the etonide, fludrocortisone, difluorosone diacetate, fluradre pathology of the disease or condition. Thus, an effective nolone, fludrocortisone, difluorosone diacetate, fluradre amount can be, for example, an amount that reduces the nolone acetonide, medrysone, amcinafel, amcinafide, severity or duration of oral lesions, ulcerations, bleeding, betamethasone and the balance of its esters, chloropred irritation, Swelling, erythema, or the like. nisone, chlorprednisone acetate, clocortelone, clescinolone, dichlorisone, diflurprednate, flucloronide, flunisolide, fluo Microbial Infections romethalone, fluperolone, fluprednisolone, hydrocortisone 0056 Microbial infections include, without limitation, Valerate, hydrocortisone cyclopentylpropionate, hydrocor bacterial, mycobacterial, fungal and viral infections. tamate, meprednisone, paramethasone, prednisolone, pred nisone, beclomethasone dipropionate, triamcinolone, and Treatment mixtures thereof. 0057. “Treatment’ means the management and care of a 0050. Other anti-inflammatory agents useful in the com patient for the purpose of combating a disease, disorder or positions include the nonsteroidal anti-inflammatory agents. condition. The term is intended to include the delaying of the The variety of compounds encompassed by this group are progression of the disease, disorder or condition, the alle well-known to those skilled in the art. For detailed disclo viation, amelioration or relief of symptoms and complica Sure of the chemical structure, synthesis, side effects, etc. of tions, and/or the cure or elimination of the disease, disorder non-steroidal anti-inflammatory agents, reference can be had or condition. The animal to be treated can be a mammal, in to standard texts, including Anti-inflammatory and Anti particular a human being. Rheumatic Drugs, K. D. Rainsford, Vol. I-III, CRC Press, 0.058 Publications and references, including but not lim Boca Raton, (1985), and Anti-inflammatory Agents, Chem ited to patents and patent applications, cited in this specifi cation are herein incorporated by reference in their entirety istry and Pharmacology 1. R. A. Scherrer, et al., Academic in the entire portion cited as if each individual publication or Press, New York (1974). reference were specifically and individually indicated to be 0051 Specific non-steroidal anti-inflammatory agents incorporated by reference herein as being fully set forth. Any useful in the composition invention include, but are not patent application to which this application claims priority is limited to: 1) the oxicams, such as piroXicam, isoxicam, also incorporated by reference herein in the manner tenoxicam, Sudoxicam, and CP-14.304; 2) the salicylates, described above for publications and references. Such as aspirin, disalcid, benorylate, trilisate, Safapryn, Sol 0059 While this invention has been described with an prin, diflunisal, and fendosal; 3) the acetic acid derivatives, emphasis upon preferred embodiments, it will be obvious to Such as diclofenac, fenclofenac, indomethacin, Sulindac, those of ordinary skill in the art that variations in the tolimetin, isoxepac, furofenac, tiopinac, Zidometacin, ace preferred devices and methods may be used and that it is matacin, fentiazac, Zomepirac, clindanac, oxepinac, felbi intended that the invention may be practiced otherwise than nac, and ketorolac; 4) the fenamates, such as mefenamic, as specifically described herein. Accordingly, this invention meclofenamic, flufenamic, niflumic, and tolfenamic acids; includes all modifications encompassed within the spirit and 5) the propionic acid derivatives, such as ibuprofen, scope of the invention as defined by the claims that follow. naproxen, benoxaprofen, flurbiprofen, ketoprofen, fenopro What is claimed: fen, fenbufen, indopropfen, pirprofen, carprofen, oxaprozin, 1. A method of treating or ameliorating an indication of pranoprofen, miroprofen, tioxaprofen, Suprofen, alminopro mucosal or adjacent tissue comprising periodically applying fen, and tiaprofenic; 6) the pyrazoles, such as phenylbuta to mucosa at or adjacent to disease affected tissue a rinse Zone, oxyphenbutaZone, feprazone, azapropaZone, and tri comprising methaZone; and mixtures of the foregoing. an effective amount of an appropriate composition of 0.052 Mixtures of these steroid and/or non-steroidal anti herbal bioactive comprising active(s) of one or more of inflammatory agents can be employed, as well as the phar Sambucus migra, Centella asiatica or Echinacea pur mologically acceptable salts and esters of these agents. For purea, ane example, etofenamate, a flufenamic acid derivative, is par an antimicrobially effective amount of a quaternary ticularly useful for topical application. ammonium Surfactant, and US 2008/0020027 A1 Jan. 24, 2008

2. The method of claim 1, wherein the rinse further 11. The rinse of claim 10, further comprising: comprises: a polymer or mixture of polymers effective to coat a polymer or mixture of polymers effective to coat said mucosal tissue and entrap said extract(s). tissue and entrap said extract(s). 12. The rinse of claim 10, wherein the quaternary surfac 3. The method of claim 1, further comprising applying to tant comprises a 1-alkylpyridinium salt, where alkyl is C8-C36. a portion of the mucosa a film, patch or an adhesive solid 13. The rinse of claim 10, wherein the 1-alkylpyridinium formulation comprising appropriate composition of herbal salt is a cetylpyridinium salt. bioactive comprising active(s) of one or more of Sambucus 14. The rinse of claim 11, wherein the rinse further forms nigra, Centella asiatica or Echinacea purpurea. a mucoadhesive coating on mucosal Surfaces. 4. The method of claim 1, wherein the quaternary ammo 15. The rinse of claim 11, wherein the rinse reversibly nium surfactant comprises a 1-alkylpyridinium salt, where forms a gel at about 35° C., and a more liquid-like state at alkyl is C8-C36. 250 C. 5. The method of claim 4, wherein the 1-alkylpyridinium 16. The rinse of claim 10, wherein herbal bioactive salt is a cetylpyridinium salt. comprising active(s) of Sambucus nigra comprises 51 to 6. The method of claim 2, wherein the rinse forms a 100% by weight of plant active solids in the rinse. mucoadhesive coating on mucosal Surfaces. 17. The rinse of claim 15, wherein a second plant extract 7. The method of claim 2, wherein the rinse reversibly comprises from 1 to 50% by weight of plant active solids in forms a gel at about 35° C., and a more liquid-like state at the rinse. about 25° C. 18. A kit for the treatment of an indication of the mucosa 8. The method of claim 1, comprising treating or amelio or adjacent tissue comprising: rating mucositis secondary to chemotherapy. transmucosal delivery rinse comprising (i) an effective 9. The method of claim 1, wherein the active(s) of one or amount of appropriate composition of herbal bioactive more of Sambucus migra, Centella asiatica or Echinacea comprising active(s) of one or more of Sambucus purpurea comprise an antiinflammatory amount. nigra, Centella asiatica or Echinacea purpurea and (ii) 10. A transmucosal delivery rinse comprising: polymer or mixture of polymers effective to coat said an effective amount of appropriate composition of plant tissue and entrap said extract(s); and extract(s) comprising herbal bioactive comprising a film, patch or an adhesive Solid formulation comprising active(s) of one or more of Sambucus migra, Centella appropriate composition of plant extract(s) comprising asiatica or Echinacea purpurea; and herbal bioactive comprising active(s) of Sambucus an antimicrobially effective amount of a quaternary nigra. ammonium Surfactant, and