Methods for treating infection and / or inflammation of the nose, sinuses and nasopharyngeal tissues

Abstract

Compositions and methods for treating diseases and disorders of the nose, sinonasal cavity, and nasopharyngeal tissues are provided.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. Provisional Application No. 62 / 811,169, filed on February 27, 2019, the entire contents of which are incorporated herein by reference. Background Art

[0003] The nose, sinuses, and nasopharynx are important parts of the human respiratory system and can be affected by diseases or conditions that require medical intervention. Appropriate and effective treatment of these diseases and conditions is necessary to promote the patient's health and avoid complications due to the disease or condition.

[0004] The current standard of care for diseases or conditions in these areas is saline nasal sprays or rinses, as well as corticosteroids, glucocorticoids, anticholinergics and antihistamine nasal sprays, which are typically low viscosity (1-10 cP), water-based solutions or suspensions that are applied multiple times a day for a long period of time. Although steroid nasal sprays address the inflammation caused by the condition, if it is an infection, it may not address the underlying cause. These home remedies also require a high level of patient compliance to achieve efficacy. There are currently no FDA-approved antifungal agents for nasal administration. Therefore, there is a need for an effective product that is topically applied to the nasal sinuses or nasopharyngeal tissue for antifungal therapy.

[0005] With respect to the underlying cause of the condition, in some cases a fungal and / or bacterial infection, treatment involves flushing an aqueous suspension of an antimicrobial or antifungal agent in an outpatient or hospital procedure that may involve IV administration and may involve anesthesia, but is most commonly treated by the patient at home with a nasal spray, typically administered multiple times per day. Alternatively or additionally, oral antibiotics and antifungals are prescribed. These treatments are often unsuccessful, and the patient continues to suffer from chronic infection and inflammation with no viable alternatives. Therefore, there is a need for a treatment option that addresses the above-mentioned deficiencies. Summary of the invention

[0006] The present disclosure relates to methods for treating diseases and disorders of the nose, sinonasal cavity, and nasopharyngeal tissues.

[0007] In some embodiments, a method for treating a subject having a disease or condition associated with the nose, sinonasal cavity, or nasopharyngeal tissue comprises the step of topically applying a composition to the sinonasal cavity, or nasopharyngeal tissue of the subject, wherein the composition is a high viscosity cream comprising a steroid and / or an agent having antimicrobial activity. BRIEF DESCRIPTION OF THE DRAWINGS

[0008] For a more complete understanding of the present invention and its advantages, reference is now made to the following description taken in conjunction with the accompanying drawings.

[0009] Figure 1 is a bar graph representing the original symptom severity scores of 11 patients of Example 2 (F represents female, and M represents male), wherein the blue bars represent the severity scores before treatment, and the red bars represent the severity scores after treatment.

[0010] Figure 2A Endoscopic photograph of the sinuses of Patient 7 of Example 2 before treatment with the cream composition as described in Example 1 is shown.

[0011] Figure 2B Endoscopic photograph of the sinuses of Patient 7 of Example 2 prior to treatment with the cream composition described in Example 1 is shown, wherein the circled portion depicts mucus drainage.

[0012] Figure 2C Endoscopic photograph of the sinuses of Patient 7 of Example 2 prior to treatment with the cream composition described in Example 1 is shown, wherein the circled portion depicts the congestion.

[0013] Figure 2D Endoscopic photograph of the sinuses of Patient 7 of Example 2 two months after treatment with the cream composition described in Example 1.

[0014] Figure 3A Endoscopic photograph of the sinuses of Patient 11 of Example 2 before treatment with the cream composition as described in Example 1 is shown.

[0015] Figure 3B Endoscopic photograph of the sinuses of Patient 11 of Example 2 two months after treatment with the cream composition described in Example 1.

[0016] Figure 4A Shown is a histological specimen obtained from the lateral side of the middle turbinate of Patient 11 of Example 2, stained with hematoxylin and eosin just prior to initial administration.

[0017] Figure 4B Shows a histological specimen obtained from the lateral side of the middle turbinate of Patient 11 of Example 2, stained with hematoxylin and eosin 2 months after initial administration.

[0018] Figure 5A Shows the SNOT-22 scores of Patient 2 of Example 5 before and after treatment.

[0019] Figure 5B Shows the SNOT-22 scores of Patient 3 of Example 5 before and after treatment.

[0020] Figure 5C Shown are the SNOT-22 scores of Patient 6 of Example 5 before and after treatment.

[0021] Figure 5D Represents the mean SNOT-22 score for each SNOT-22 metric for Patients 1-8 in Example 5 before and after treatment (approximately 30 days).

[0022] Figure 6 Shows the total SNOT-22 scores of the patients in Example 5 before and after treatment. DETAILED DESCRIPTION

[0023] The present disclosure provides compositions and methods for treating diseases and disorders of the nose, sinonasal cavity, and nasopharyngeal tissues.

[0024] definition

[0025] As used herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0026] The term "or" as used in the claims and this disclosure is used to mean "and / or" unless explicitly stated to refer to only alternatives or the alternatives are mutually exclusive.

[0027] When used with numerical values, the use of the term "about" is intended to include + / - 10%. As an example and not limitation, if the number of amino acids is determined to be about 200, this would include 180 to 220 (plus or minus 10%).

[0028] As used herein, "antimicrobial agent" should be understood to include antimicrobial agents, such as antibacterial agents and antifungal agents.

[0029] As used herein, an "effective amount" refers to an amount sufficient to produce a desired pharmacological and / or pharmacodynamic result. For example, an effective amount for treatment is an amount that can reduce or eliminate the symptoms and / or pathology of an infection or disease. Another example is an effective amount that destroys or eradicates a biofilm that protects a pathogen to effectively eliminate the pathogen.

[0030] The terms "patient," "individual," and "subject" are used interchangeably herein and refer to a mammalian subject to be treated, with human patients being preferred. In some cases, the methods of the invention find application in experimental animals, veterinary applications, and the development of animal models of disease, including but not limited to rodents such as mice, rats, guinea pigs, and hamsters, as well as other animals including but not limited to canines, felines, equines, and primates.

[0031] "Treatment" refers to intervention for the purpose of preventing the development of a disorder or altering the pathology or symptoms of a disorder. Thus, "treatment" can refer to both therapeutic treatment and preventive or defensive measures. Those in need of treatment include those already suffering from the disorder as well as those in whom the disorder is to be prevented.

[0032] As used herein, the term "cream" refers to a semisolid formulation containing one or more medicaments dissolved or dispersed in an oil-in-water emulsion or a water-in-oil emulsion. For the avoidance of doubt, a "cream" does not include a "gel", which is a semisolid system consisting of a dispersion of small or large molecules in an aqueous liquid carrier, which is made jelly-like by the addition of a gelling agent. Thus, the term "cream" does not include a thermoreversible gel, a thermoreversible polymer, or a copolymer of polyoxyethylene and polyoxypropylene.

[0033] In some embodiments, a method for treating a disease or condition of the nose, sinus or nasopharyngeal tissue may comprise the step of topically applying a composition to the sinus or nasopharyngeal tissue of a subject, wherein the composition is a cream having a high viscosity including a steroid and / or an agent having antimicrobial activity.

[0034] In some embodiments, the step of applying the composition is performed as a single administration, which in some cases is sufficient to provide effective treatment for a disease or condition of the nose, sinus or nasopharyngeal tissue. In certain other embodiments, the step of applying the cream composition is performed only once, for example but not limited to, every 10-21 days, every 21-30 days, every 30 to 60 days, every 60 to 90 days, every 90 to 180 days or every 180 to 365 days. It should be understood that "single administration" in most cases refers to sequential bilateral administration by intranasal administration. In some embodiments, the step of applying the cream composition is performed no more than twice, for example but not limited to, every 21, 30, 60, 90, 180 or 365 days.

[0035] In one embodiment, the step of applying the cream composition of the present disclosure includes applying the cream composition to the sinus mucosa by a first intranasal application. This initial application can be performed using a syringe connected to a tube or other similar tool. The syringe connected to the tube or other similar tool can be guided by a surgical endoscope. Then, the method can further include using an instrument to spread the cream composition in a manner sufficient to cover the diseased sinus mucosa. This one or more steps can be repeated by a second intranasal application to ensure bilateral coverage of the sinus cavity.

[0036] The amount of the cream composition applied will vary according to the size of the diseased tissue area and the degree of the patient's body size. In some embodiments, the composition can be applied in an amount of about 0.5 cubic centimeters (cc) to about 5cc per intranasal application, or in an amount of about 1cc to about 10cc per intranasal application, but more generally about 2cc to about 4cc, applied to the diseased sinus tissue, or in an amount of about 4cc to about 8cc, applied to the diseased sinus mucosal tissue. As an example but not limited to, the amount of the composition applied intranasally per time can be about 0.5cc, 0.75cc, 1cc, 1.25cc, 1.5cc, 1.75cc, 2cc, 2.25cc, 2.5cc, 2.75cc, 3cc, 3.25cc, 3.5cc, 3.75cc, 4cc, 4.5cc or 5cc. It should be understood that for complete bilateral application of the diseased sinus mucosa, these listed amounts are doubled unless otherwise stated.

[0037] In other embodiments, the composition can be administered in an amount of about 0.5 grams (g) to about 5 g per intranasal administration, or in a total amount of about 1 g to about 10 g per intranasal administration, but more typically about 2 g to about 4 g, or in a total amount of about 4 g to about 8 g.

[0038] By way of example and not limitation, the amount of the composition may be about 0.5 g, 0.75 g, 1 g, 1.25 g, 1.5 g, 1.75 g, 2 g, 2.25 g, 2.5 g, 2.75 g, 3 g, 3.25 g, 3.5 g, 3.75 g, 4 g, 4.5 g, or 5 g per intranasal administration. It should be understood that for complete bilateral administration to diseased sinus mucosa, these recited amounts are doubled unless otherwise indicated.

[0039] The compositions and methods of the present disclosure can be used to treat various conditions of the nose, sinuses and nasopharyngeal tissues. As examples but not limited to, these conditions of the nose, sinuses and nasopharyngeal tissues can include diseases, infections, symptoms and combinations thereof. By way of example but not limitation, these diseases or infections can include chronic sinusitis, acute sinusitis, mucormycosis, polymicrobial sinusitis, nasal polyps, bacterial sinusitis, allergic fungal sinusitis, chronic bacterial sinusitis, chronic allergic fungal sinusitis and sinusitis. By way of further example but not limitation, the methods of the present disclosure can be used to treat the following sinus symptoms: need to blow nose, nasal congestion, sneezing, runny nose, coughing, postnasal discharge, thick nasal discharge, ear fullness, dizziness, earache, facial pain or pressure, decreased sense of smell or taste, difficulty falling asleep, waking up at night, lack of a good night's sleep, waking up tired, fatigue, reduced productivity, reduced concentration, frustration, restlessness or irritability, sadness, embarrassment and combinations thereof. In some embodiments, the condition further comprises the need to blow the nose, nasal congestion, sneezing, runny nose, coughing, postnasal discharge, thick nasal discharge, ear fullness, dizziness, earache, facial pain or pressure, decreased sense of smell or taste, difficulty falling asleep, waking up at night, lack of a good night's sleep, waking up tired, fatigue, reduced productivity, reduced concentration, frustration, restlessness or irritability, sadness, embarrassment, or a combination thereof. Thus, these sinus symptoms may occur concurrently with illness, infection, or other condition, or may be a condition that requires self-treatment. In some embodiments, the subject previously underwent functional endoscopic sinus surgery (FESS) and thereafter developed a chronic inflammatory response. In some embodiments, the subject for whom the compositions and methods of the present invention are useful suffers from chronic allergic fungal sinusitis after FESS. In some embodiments, after FESS with or without nasal steroid sprays, oral antibiotics, and / or nasal rinses, the patient is experiencing an exacerbation of symptoms after a period of mild or no symptoms. In some embodiments, the subject underwent FESS, which resulted in abnormal nasal tissue described as hypertrophic, inflammatory, and granulation-type tissue. In further aspects of these embodiments, prior to implementation of the present method, the subject's post-FESS sinusitis was treated with nasal steroid sprays, oral antibiotics, and / or nasal rinses for a period of one year with minimal or no change in disease state. In some embodiments, the subject suffers from chronic sinus inflammation due to bacterial infection. In some embodiments, the methods of the present disclosure may be performed at the time of FESS. In some embodiments, the patient has not previously undergone FESS. In some embodiments, the methods of the present disclosure may be performed during balloon sinus dilation. In some embodiments, the compositions of the present disclosure may be administered at the time of FESS. In some embodiments, the compositions of the present disclosure may be administered during balloon sinus dilation.Even in the case where chronic inflammation is the result of bacterial infection, a cream composition comprising clotrimazole may also be useful because the active agent exhibits antibacterial activity in addition to antifungal activity against gram-positive and gram-negative microorganisms. Specifically, clotrimazole has been shown to cause a reduction in Pseudomonas aeruginosa and has antibacterial activity against streptococci, staphylococci, vaginal Haemophilus and corynebacterium. However, as discussed in further detail below, other antibiotic active agents may be substituted in the cream composition of the present disclosure. In some embodiments, the patient has no detectable microbial infection. In other embodiments, the patient has a detectable microbial infection, such as a bacterial or fungal infection. Therefore, the compositions and methods of the present disclosure may be useful in the absence or presence of a detectable microbial infection. In some embodiments, the condition may comprise a bacterial infection. In some embodiments, the condition is at least in part the result of a bacterial infection, and a biofilm has been formed on the surface of the nasal sinuses or nasopharyngeal tissue. In some embodiments, the condition may comprise a fungal infection. In some embodiments, the condition may comprise a yeast infection. In some embodiments, the condition may comprise a polymicrobial infection.

[0040] The cream composition of the present disclosure may include steroids. Various corticosteroids, glucocorticoids or combinations thereof may be used in the compositions and methods of the present disclosure. For example, but not limited to, the corticosteroids that may be used in the compositions and methods of the present disclosure include cortisone, cortisol, hydrocortisone, methylprednisolone, prednisolone, prednisone, triamcinolone acetonide, betamethasone, ciclesonide, dexamethasone, 21-acetoxypregnenolone, alclometasone, algestrone, amcinonide, beclomethasone, budesonide, cloprednisone, clobetasol, clobetasone, clocortolone, cloprednol, corticosterone, cortisol, deflucort, desonide, dehydromethasone, dexamethasone, diflorasone, diflucortolone, difluprednate, glycyrrhetinic acid, fluzacort, fluclosonide, flumethasone, flunisol ... The present invention relates to the invention to the invention of the present invention, formocortol, halcinonide, halobetasol propionate, halometasone, halopediol acetate, hydrocortate, hydrocortisone, loteprednol etabonate, maprednione, medrysone, methylprednisone, methylprednisolone, mometasone furoate, paraflumethasone, prednicarbate, prednisolone, 25-diethylamine prednisolone acetate, prednisolone sodium phosphate, prednisolone valerate, prednilide, rimexolone, tixocortolone, triamcinolone acetonide, triamcinolone acetonide, triamcinolone caproate, etc. Esters, derivatives and salts (including hydrates and hydrochloride salts) of corticosteroids can also be used in the compositions and methods of the present invention. For example, betamethasone is commonly found as betamethasone dipropionate (which has the chemical name 9-fluoro-11β,17,21-trihydroxy-16β-methylpregna-1,4-diene-3,20-dione 17,21-dipropionate and has an empirical formula of C 28 H 37 FO7 and having a molecular weight of 504.59 g / mol), and the administered doses of betamethasone in Table 1 below are based on this specific salt.

[0041] The amount of steroid in the compositions of the present disclosure can vary according to the desired dose to be delivered based on the patient's state, patient sensitivity, biological half-life of the steroid, the patient's age, systemic factors, and other factors. In addition, the state of infection or disease and its susceptibility to steroids can also be considered. One skilled in the art can determine the appropriate dosage, including determining the "effective amount" of the composition to be administered.

[0042] Exemplary, non-limiting dosage ranges for specific steroids in the cream compositions of the methods of the present invention are shown below in Table 1. The values ​​listed in Table 1 are for the current cream compositions and assume a total single application (i.e., bilateral intranasal application to the sinus mucosa) of 5-6 g of the cream composition (i.e., 2.5-3 g per intranasal application).

[0043] Table 1: Exemplary non-limiting dosage ranges for corticosteroids (in mg / g composition)

[0044]

[0045] In some embodiments, the steroid is betamethasone or betamethasone dipropionate, and is present in the composition of the present disclosure at about 0.1 mg to about 0.5 mg / gram of cream composition or about 0.15 mg to about 0.64 mg / gram of cream composition, respectively, or more preferably at about 0.25 mg / gram of cream composition or about 0.32 mg / gram of cream composition, respectively. In another embodiment, the total dose of betamethasone dipropionate for a single administration (i.e., bilateral intranasal administration) is about 0.643 mg to about 3.25 mg, or more preferably about 0.80 mg to about 2.6 mg, or even more preferably about 0.95 mg to about 1.93 mg, and even more preferably about 1.28 mg to about 1.61 mg.

[0046] In some embodiments, the steroid is present at about 0.01% to about 1% by weight of the composition. For example, but not limited to, the steroid can be present at 0.01% to 0.5% by weight of the composition, 0.02% to 0.4% by weight of the composition, 0.03% to 0.3% by weight of the composition, 0.04% to 0.2% by weight of the composition, or 0.05% to 0.1% by weight of the composition. In some embodiments, the steroid is betamethasone dipropionate and is present at about 0.03% by weight of the composition.

[0047] Various antifungal agents can be used in the compositions and methods of the present disclosure. As an example but not limited to, such antifungal agents can include natamycin, ciclopirox, fluconazole, terbinafine, clotrimazole, ketoconazole, econazole, miconazole, nystatin, oxiconazole, terconazole, tolnaftate, efinaconazole, abafungin, terbinafine, butenafine, metronidazole, etc. and combinations thereof. In certain embodiments, the antifungal agent is clotrimazole.

[0048] Antifungal agents can be present in compositions of the present disclosure in effective amounts. In certain embodiments, the effective amount or total amount of the antifungal agent of each single application (i.e., bilateral intranasal administration) is about 20 mg to about 50 mg, and more preferably about 25 mg to about 40 mg. In certain embodiments, the amount of antifungal agent is about 2.5 mg / gram of cream composition to about 10 mg / gram of cream composition, and more preferably about 5 mg / gram of cream composition. In certain embodiments, antifungal agent is present with about 0.1 % by weight to about 5 % by weight of composition. For example, but not limited to, the antifungal agent can be present at 0.1% to 5% by weight of the composition, 0.5% to 4% by weight of the composition, 0.5% to 3% by weight of the composition, 0.5% to 2% by weight of the composition, 0.5% to 1% by weight of the composition, 1% to 5% by weight of the composition, 2% to 5% by weight of the composition, 3% to 5% by weight of the composition, 4% to 5% by weight of the composition, or about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.5%, 2.0%, 2.5%, 3.0%, 3.5%, 4.0%, 4.5%, or 5.0% by weight of the composition. In some embodiments, the antifungal agent is clotrimazole and is present at about 0.5% by weight of the composition.

[0049] In some embodiments, the composition of the present disclosure may further include an antibiotic. For example, but not limited to, such antibacterial agents may include flucloxacillin, triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether), alcohols (including ethanol and isopropanol), peroxides (including benzoyl peroxide), iodine, benzethonium chloride, chloroxylenol, and aminoglycoside antibiotics such as ciprofloxacin and its salts or derivatives.By way of example and not limitation, other antibiotics may include amikacin, gentamicin, kanamycin, neomycin, netilmicin, streptomycin, tobramycin, paromomycin, geldanamycin, herbimycin, loracarbef, ertapenem, doripenem, imipenem, meropenem, cefaclor, cefoperazone, cefoxitin, cefprozil, cefuroxime, cefuroxime, cefoperazone, cefditoren, cefpodoxime, ceftazidime, ceftibuten, cefazolin, ceftriaxone, cefepime, ceftoroxine, vancomycin, azithromycin, clarithromycin, dirithromycin, erythromycin, roxithromycin, tadalafil, telithromycin, spectinomycin, aztreonam, amoxicillin, ampicillin , azocillin, carbenicillin, cloxacillin, dicloxacillin, flucloxacillin, mezlocillin, methicillin, nafcillin, oxacillin, piperacillin, ticarcillin, bacitracin, colistin, polymyxin B, siroxacin, clavulanic acid, enoxacin, gatifloxacin, levofloxacin, lomefloxacin, moxifloxacin, norfloxacin, ofloxacin, trovafloxacin, grifloxacin, sparfloxacin, AL-15469A, AL-38905, OP-145, mafenide, prontocil, sulfacetamide, sulfamethoxazole, sulfamethoxazole, sulfonamide, sulfasalazine, sulfisoxazole, trimethoprim, trimethoprim-sulfamethoxazole, demeclocycline, doxycycline, minocycline Cyclin, oxytetracycline, tetracycline, linezolid, asabromin, chloramphenicol, clindamycin, lincomycin, ethambutol, fosfomycin, fusidic acid, furazolidone, isoniazid, linezolid, metronidazole, mupirocin, nitrofurantoin, plate mycin, pyrazinamide, quinupristin, dalfopristin, rifampicin, thiampicin, metronidazole, amoxicillin / clavulanic acid, maximin H5, dermatophyte, moth blood, male antimicrobial peptide, silkworm antimicrobial peptide, horny toxin, bee toxin, claw toad toad toad antimicrobial peptide, skin antimicrobial peptide, bombyx mori antimicrobial peptide, frog antimicrobial peptide-1, glycosides of sharp locust vine and toad antimicrobial peptide II, CAP18, LL37, bee antimicrobial peptide, induced bee antimicrobial peptide, pig antimicrobial Peptide, indesidin, frog antimicrobial peptide, porcine antimicrobial peptide, speed peptide, defensin, drosophilin, alamycin, pesignan or MSI-78, MSI-843, MSI-594, horseshoe crab antimicrobial peptide, colicin, purulent, clebicin, subtilisin, epidermoidin, hebiclein, blevicin, halophilin, agrobacterium, avermitin, leucrosin, clovatin, devocin, volgamycin, entresin, ervincin, glycosylcerin, lactic acid bacteria, lactococcin, lioucocin, leucocin, pediocin, plant lactobacillus, sake lactobacillus, thiofollicles, vibrioin, varrenan, nisin, etc. and their salts or derivatives.

[0050] The therapeutically active agents (steroids and / or antimicrobials) contemplated within the scope of the present invention are understood to include hydrophobic compounds, hydrophilic compounds, and amphiphilic compounds. They may be in the form of free acids, free bases, or pharmaceutically acceptable salts and include derivatives, esters, or prodrugs. It should be understood that the cream compositions of the present disclosure may include only steroids, only antimicrobials (antifungals, antibacterials, or combinations thereof), or a combination of steroids and antimicrobials. The type of therapeutically active ingredient in the cream composition may be determined based on the condition being treated, and in some cases only steroids may be required, while in other cases only antimicrobials are required, and in other cases both steroids and antimicrobials are required. Therefore, in some embodiments, the cream composition does not include an antimicrobial. In other embodiments, the cream composition does not include a steroid. In this case, by way of example but not limitation, the cream composition may include only a steroid as a therapeutically active agent, i.e., the cream composition does not include an antimicrobial. In other cases, by way of example and not limitation, the cream composition may include only an antimicrobial agent as the therapeutic agent, ie, the cream composition does not include a steroid.

[0051] In some embodiments, the total amount of the cream composition applied to the affected area of ​​the subject (i.e., bilateral intranasal administration) is from about 4 grams to about 10 grams, and more preferably from about 5 grams to about 8 grams. It should therefore be understood that the amount of cream composition applied per intranasal administration is from about 2 grams to about 5 grams, and more preferably from about 2.5 grams to about 4 grams.

[0052] The compositions described herein are sufficiently viscous so that they remain in contact with the tissues of the nose, sinonasal cavities, and nasopharynx for a sufficient period of time to provide effective treatment of these tissues.

[0053] It will be understood by those of ordinary skill in the art that the viscosity value of a cream depends largely on the method of measuring viscosity. Thus, the viscosity values ​​of the cream compositions of the present disclosure are those produced by a Brookfield HBT with Spindle 21 at room temperature, and include the following viscosity values ​​under the corresponding described conditions: (1) about 220,000 centipoise (cP) to about 260,000 cP at a shear rate of 0.5 RPM (30% torque at a factor of 8000); (2) about 140,000 cP to about 170,000 cP at a shear rate of 1.0 RPM (39% torque at a factor of 4000); (3) about 75,000 cP to about 90,000 cP at a shear rate of 2.0 RPM (41% torque at a factor of 2000); (4) about 55,000 cP to about 60,000 cP at a shear rate of 2.5 RPM (42% torque at a factor of 1600); The viscosity profiles of the cream compositions are as follows: (1) about 15,000 cP to about 20,000 cP at a shear rate of 50.0 RPM (50% torque at a factor of 800); (2) about 30,000 cP to about 55,000 cP at a shear rate of 5.0 RPM (50% torque at a factor of 800); (3) about 19,000 cP to about 32,000 cP at a shear rate of 10.0 RPM (60% torque at a factor of 400); (4) about 10,000 cP to about 19,000 cP at a shear rate of 20.0 RPM (73% torque at a factor of 200); and (5) about 5,000 cP to about 10,000 cP at a shear rate of 50.0 RPM (97% torque at a factor of 80) (collectively referred to herein as the "cream composition viscosity profiles"). For the avoidance of doubt, as used herein and in the amended claims, the term "cream composition viscosity profile" refers to the above viscosity values ​​under the stated conditions using a Brookfield HBT with Spindle 21 at room temperature.

[0054] Various topical analgesics may also be used in the compositions described herein. These include, but are not limited to, nonsteroidal anti-inflammatory drugs, lidocaine, capsaicin, amitriptyline, glyceryl trinitrate, opioids, menthol, pimecrolimus, phenytoin, and the like.

[0055] Various other materials can be used in the compositions described herein. These materials include, but are not limited to, astringents (such as aluminum acetate) and topical anti-infectives (such as neomycin, clenchronor or chloramphenicol). By way of further example and without limitation, the composition may further include any of cetostearyl alcohol, hexadecyl esters wax, sorbitan monostearate, benzyl alcohol, propylene glycol, 2-octyldodecanol, polysorbate 60, sodium hydroxide, carbomer 940NF, water, and combinations thereof.

[0056] The pharmaceutical compositions described herein will preferably have a pH of less than about 7, as the use of compositions having a higher pH may promote or be insufficient to prevent the growth of bacteria and / or fungi in the target tissue. In some cases, the specific pH or pH range specified for the pharmaceutical composition may depend on the specific corticosteroid or combination of corticosteroids selected for the composition, as the pH may have an effect on the solubility and / or shelf life of these materials.

[0057] The pharmaceutical compositions and methods of use thereof will now be described with reference to the following non-limiting examples.

[0058] Examples

[0059] Example 1

[0060] A pharmaceutical composition in the form of a cream is prepared. The composition contains betamethasone dipropionate as the first active ingredient, which is a synthetic glucocorticoid that is an analog of prednisolone (betamethasone dipropionate is the 17,21-dipropionate of betamethasone). Betamethasone dipropionate has C 28 H 37 FO7 has an empirical formula and a molecular weight of 504.59 g / mol and has the following structural formula:

[0061]

[0062] The cream composition further includes a second active ingredient, clotrimazole, an antimicrobial agent. The cream composition further includes various inactive ingredients, as shown in Table 2 below, which shows each active and inactive ingredient expressed in weight % based on the total weight of the cream composition.

[0063] Table 2: List of active and inactive substances by weight

[0064] weight% Betamethasone dipropionate 0.0322 Clotrimazole 0.5000 Cetearyl Alcohol 6.0000 Cetyl Esters Wax 1.5000 Sorbitan monostearate 2.5000 Benzyl alcohol 0.5000 Propylene glycol 15.0000 2-Octyldodecanol 6.7500 Polysorbate 60 3.7500 Sodium hydroxide QS* Carbomer 940NF 0.5000 water 62.9679

[0065] * "Sufficient amount" means that the material is varied slightly as needed to adjust the pH.

[0066] The viscosity profile of the above cream compositions was measured at room temperature using a Brookfield HBT with Spindle 21, which resulted in the values ​​in Table 3 below under the corresponding conditions.

[0067] Table 3: Viscosity test results

[0068] Viscosity test

[0069] Brookfield HBT with Spindle 21

[0070] RPM %Torque factor cP 0.5 30 8000 240,000 1.0 39 4000 156,000 2.0 41 2000 82,000 2.5 42 1600 67,200 5 50 800 40,000 10 60 400 24,000 20 73 200 14,600 50 97 80 7,760 100 Unreadable 40 ---

[0071] *All torque values ​​after five full revolutions

[0072] The density of the above cream composition was measured to be 0.9 g / cc.

[0073] The cream composition of this Example 1 was used in the following Examples 2-5.

[0074] Example 2

[0075] This example demonstrates the efficacy of the cream composition described in Example 1 in 11 subjects (6 females and 5 males, ranging in age from 17 to 72 years) who met the following criteria:

[0076] 1-year or more previous endoscopic sinus surgery, with at least maxillary antrostomy and ethmoid sinusectomy

[0077] 2- Chronic severe nasal congestion and discharge not resolved by medical therapy (including nasal irrigation).

[0078] 3- Visual or CT signs of inflammation and chronic disease.

[0079] Patients were treated by Dr. Patrick Slater at the Austin Ear Clinic in Austin, TX. Before treatment, symptom severity was assessed by physician observation (inflammation) (visual inspection for congestion, fullness, and inflammation), and patients rated the severity of congestion, fullness, and drainage on a scale of 1 to 10, with 10 being the most severe. The mean severity score for the 11 patients was 8.62.

[0080] The patient was not sedated during the treatment application, but lidocaine was applied topically by spray, followed by pantocaine. The cream composition of Example 1 was then applied topically to the sinus mucosa by bilateral intranasal application using a sinus suction tube connected to a syringe, and then spread over the inflamed area with the tip of the tip. For a total application amount of 3-9 g of the cream composition, the application amount of the cream composition per intranasal application was 1.5 g to 4.5 g. After approximately 4 weeks of treatment, the patient returned to the clinic for a follow-up visit to assess the severity of symptoms according to the above scale.

[0081] Results: All 11 patients noted an increase in congestion during the first 1-3 days after treatment, but this resolved quickly and all patients noted a marked improvement in congestion and drainage approximately 4 weeks after initial application. Most patients reported that their permeability (no congestion) and drainage were at levels not seen in years. The mean symptom severity improved to 2.53. Visual inspection after 2-6 months noted that the mucosa often returned to a normal appearance. Figure 1Each patient's individual severity score before and after treatment is shown in , where a severity score of 1 refers to normal sinus health. Figures 2A-2D Patient 7 (from Figure 1 )Before treatment( Figures 2A-2C ) and 2 months after treatment ( Figure 2D ) of the sinus mucosa. Figure 2D As shown, patient 7 showed complete resolution of inflammation (red mucosa shown in Figures 2A-2C in), mucus drainage (mucus in Figure 2B circled in the middle) and decreased congestion (congestion in Figure 2C (circled in the middle). Figure 3A-3B Patient 11 (from Figure 1 )Before treatment( Figure 3A ) and 2 months after treatment ( Figure 3B ) of the sinus mucosa. Before treatment, Figure 3A The left nasal cavity is shown with the middle turbinate indicated in the circle. The middle turbinate shows marked congestion, edema, and granulation changes with mild hemorrhage. The area lateral to the middle turbinate shows polypoid changes and mild mucopurulence from the ostiomeatal complex. After treatment, Figure 3B All lesions observed prior to treatment were shown to be reduced, most notably a reduction in systemic inflammatory response highlighted by a reduction in congestion, edema and granulation changes.

[0082] Figures 4A-4B Provided just before initial administration ( Figure 4A ) and 2 months after treatment ( Figure 4B ) from the side of the middle turbinate of patient 11 (from Figure 1 ) Histological samples were obtained using a pair of cup forceps, stored in formalin, and stained with hematoxylin and eosin, and photographed by a pathologist using standard techniques using high magnification. The tissue before treatment showed a clear presence of eosinophils (shown in red), while the tissue after treatment showed a significant reduction in the presence of eosinophils. Without being bound by theory, it is believed that the reduction in eosinophils can reduce sinus inflammation by reducing edema, thick mucus production, and polyp formation (which can be caused by inflammatory mediators released by eosinophils).

[0083] This example demonstrates essentially complete resolution of symptoms and inflammation, which has rarely been achieved with previous standard medical therapy.

[0084] Example 3 - Case Study

[0085] Patient History: A 59 year old male patient presented with a history of bilateral sinus congestion, foul odor, and shortness of breath over the past 3-4 months. The patient complained of a yellow-green purulent discharge with sinus pressure over the past few months. He had a history of recurrent sinus infections over the past 2 to 3 years. The patient underwent a FESS procedure approximately 19 years ago, after which his sinus symptoms resolved. The symptoms began to recur approximately 3 years ago, and he has been on maximal allergy management since then. The patient graded his sinus congestion as an 8 on the severity scale described in Example 2 above. He also reported a severe sinus infection and bronchitis that occurred approximately 2 months prior to visiting the clinic in Example 2, and was taking amoxicillin under the care of his primary physician. He reported a significant increase in left sinus congestion, shortness of breath, and purulent drainage since the infection.

[0086] Diagnosis: Endoscopy revealed mucin, mucosal inflammation, and crusting. CT scan showed bilateral FESS of the maxillary, ethmoid, and frontal sinuses with mild thickening of the mucosa throughout the body. Cultures of samples from the crusting grew fungi of the Fusarium species.

[0087] Treatment and Results: The cream composition of Example 1 was applied bilaterally to the ethmoid sinuses and the maxillary antrostomy area as described in Example 2. The patient was instructed not to use nasal sprays for 2 to 3 days and was asked to follow up after 2 weeks.

[0088] At follow-up, the patient reported an improvement of nearly 50% in his symptoms. Nasal odor, congestion, and purulent discharge were significantly reduced, and the severity of his symptoms was rated as a 4 according to the scale described in Example 2. The cream composition of Example 1 was reapplied to the ethmoid sinuses and maxillary antrostomy area and recalled after 2 weeks.

[0089] At visit 2 after the second application, the patient reported an 80-90% reduction in the thick greenish-yellow purulent drainage and the presence of some clear and frothy drainage. There is no congestion at present. Nasal microscopic examination was clear without any crusting or thick purulent mucin. The patient was recalled 3 months later.

[0090] Example 4 - Case Study

[0091] Patient History: A 53-year-old female patient presented with bilateral sinus congestion, ear and sinus pressure, dyspnea, anosmia, and constant thick nasal discharge from her nose. Over the past year, the severity of her symptoms increased. She complained of severe facial pressure, fever, pain in the upper teeth, purulent discharge, and bad breath. The patient was treated with antibiotics in the past, but did not experience any improvement in symptoms. She had a history of multiple FESS surgeries (antrostomy, ethmoidectomy, sphenoidectomy) over the past 9 years for her chronic sinus problems. The patient was given a Medrol dosage pack and a nebulizer, but she still felt insufficient air.

[0092] Intranasal examination and diagnostic imaging: Intranasal examination revealed mucosal inflammation, pus, and congested tissue with crusting. The patient graded her sinus congestion as a 9 based on the severity scale described in Example 2. CT sinuses was recommended and showed chronic pan-sinus disease with open ethmoidectomy and obstructed bilateral maxillary antrostomies.

[0093] Treatment: After informed consent, the patient was placed in the supine position. The nasal cavity was sprayed with tetracaine spray without epinephrine. The cream composition of Example 1 was applied to the maxillary sinus mucosa, ostiomeatal complex, and nasal mucosa using a sinus aspiration tube connected to a syringe. At 24-hour follow-up, the patient reported nasal fullness, pressure, and congestion. The patient was recalled for follow-up after 10 days.

[0094] At the 10-day follow-up, the patient's symptoms had returned to 3 on the severity scale after the first application, with a decrease in active purulent drainage. The cream was reapplied and the patient was recalled 4 weeks later.

[0095] At 4-week follow-up, the patient showed improvement in sinus congestion and drainage symptoms. Inflammation of the mucosa had subsided. She had mild facial pressure and upper tooth pain. The cream was reapplied in the maxillary sinus area. After the third application 4 weeks later, the patient reported relief of her symptoms.

[0096] Example 5

[0097] This example further demonstrates the efficacy of the cream composition described in Example 1 in 8 subjects who met the following inclusion criteria:

[0098] 1. Men aged between 18 and 80 years old or non-pregnant or non-lactating women

[0099] 2. Able to understand and provide signed informed consent.

[0100] 3. FESS within the past 20 years but not less than 6 months before

[0101] 4. Clinical diagnosis of exacerbation of sinusitis (suspected or confirmed to be of bacterial, fungal, yeast, or polymicrobial (bacterial, fungal, and / or yeast) cause) with signs and symptoms such as congestion, discharge, nasal and / or sinus inflammation, and current episode >1 month duration. If bilateral sinus disease is present, both sinuses will be treated.

[0102] 5. Congestion score of at least 3 (5 is poor) on a five-point scale (the lowest score without discharge).

[0103] 6. Willing to undergo biopsy at baseline and discharge visit.

[0104] 7. Willing to undergo CT imaging at baseline and discharge visit.

[0105] 8. Willing to undergo microbiological sampling of affected sinuses at baseline and discharge visits.

[0106] 9. Willing to self-report sinus signs and symptoms daily (Appendix 2)

[0107] 10. Females of childbearing potential must have a negative urine pregnancy test at screening and agree to use one of the following acceptable birth control methods:

[0108] a. Surgical sterility (hysterectomy or bilateral oophorectomy)

[0109] b. Surgical sterility (bilateral tubal ligation, surgery performed at least 6 weeks before the start of the study)

[0110] c. Intrauterine device (IUD) placed for at least 3 months

[0111] d. Abstinence (no sexual intercourse)

[0112] e. Use of a spermicide-containing barrier method (condom or diaphragm) for at least 14 days prior to screening and throughout the study

[0113] f. Stable hormonal contraceptive use for at least 3 months prior to and during the study

[0114] 11. Agree to avoid immersing the sinuses in water during the study

[0115] 12. Patients taking analgesics or other non-steroidal maintenance medications (e.g., for arthritis) will be permitted during this study, provided that the dose has been stable for at least 8 weeks prior to inclusion and must remain stable during the study.

[0116] 13. Usually active, or considered by the investigator to be in generally good health based on medical history and physical examination.

[0117] 14. Patients and / or caregivers who are able to adhere to the visit schedule and protocol requirements and complete the entire study.

[0118] Patients who met any of the following criteria were excluded.

[0119] 1. Women who are pregnant, breastfeeding, or wish to become pregnant during the study

[0120] 2. Signs and symptoms of a current sinusitis episode of less than 1 month in the affected sinus designated as the "study sinus"

[0121] 3. Diabetes mellitus, immunodeficiency, allergy or intolerance to corticosteroids, history of oral steroid-dependent conditions, clinical evidence of acute bacterial sinusitis, or clinical evidence of invasive fungal sinusitis.

[0122] 4. History or diagnosis of glaucoma or ocular hypertension, presence of grade +3 or higher cataract, or presence of posterior subcapsular cataract.

[0123] 5. Clinical diagnosis of sinonasal disease other than exacerbation of sinusitis (e.g., congenital sinonasal anomalies, obstructive bone exostosis or tumors, upper respiratory tract infection including varicella and herpes simplex infection, cellulitis)

[0124] 6. Glaucoma or cataract of grade 2 or above.

[0125] 7. Known or suspected hypersensitivity or allergy to clotrimazole, betamethasone dipropionate, or any other component of the study drug

[0126] 8. Local sinus abnormalities, such as abscesses or obvious polyps within the affected sinuses

[0127] 9. Patients who are unwilling to stop using nasal medications, rinses or sprays within 3 days after study drug administration

[0128] 10. Previous sinus surgery in the affected sinus within 3 months of study enrollment

[0129] 11. Use of any systemic antimicrobial drugs within 2 weeks before registration

[0130] 12. Patients with any type of device (such as PROPEL) in the nose or sinuses

[0131] 13. Surgery performed within the nose or sinuses after application of study medication during the duration of the study, unless prescribed by the PI after the patient has withdrawn from the study

[0132] 14. Previous registration in this study.

[0133] 15. Oral steroids.

[0134] 16. Systemic glucocorticoids other than inhaled asthma medications

[0135] 17. Systemic or topical immunosuppressive drugs or immunomodulators (e.g., azathioprine, infliximab, calcineurin inhibitors).

[0136] 18. Current enrollment in an investigational drug or device study or participation in such a study within 30 days of entry into this study.

[0137] 19. Any significant medical or psychiatric / psychiatric condition that, in the opinion of the PI, would interfere with the ability to provide informed consent or comply with study instructions, or that could confound the interpretation of study results or place the patient at undue risk (this should include: recent (within the past 12 months) history of or potential for alcohol or substance abuse.

[0138] When a diagnosis of worsening sinusitis after FESS lasting more than 1 month was made, patients were screened, examined, and completed the Nasal Sinus Outcomes Test (SNOT-22). The SNOT-22 provides an assessment of sinus health and is based on a 0-5 scoring system (0 = no problems, 1 = very mild problems, 2 = mild or mild problems, 3 = moderate problems, 4 = severe problems, and 5 = the worst possible problems). The 22 measures are:

[0139] 1. Need to blow your nose;

[0140] 2. Nasal congestion;

[0141] 3. Sneezing;

[0142] 4. Runny nose;

[0143] 5. Cough;

[0144] 6. Postnasal discharge;

[0145] 7. Thick nasal discharge;

[0146] 8. Ear fullness;

[0147] 9. Dizziness;

[0148] 10. Earache;

[0149] 11. Facial pain / pressure;

[0150] 12. Decreased sense of smell / taste;

[0151] 13. Difficulty falling asleep;

[0152] 14. Waking up at night;

[0153] 15. Lack of a good night's sleep;

[0154] 16. Waking up tired;

[0155] 17. Fatigue;

[0156] 18. Reduced productivity;

[0157] 19. Reduced concentration;

[0158] 20. Frustrated / restless / irritable;

[0159] 21. Sadness; and

[0160] 22. Awkward.

[0161] In addition to the biopsy samples, microbiological samples from the sinuses were collected prior to treatment and at the discharge visit to assess eosinophil counts in a subset of patients. The patients then underwent mechanical cleansing of the sinuses by standard techniques, if necessary. The composition of Example 1 was then applied to the sinuses to be treated using a 4-inch flexible tip applicator connected to a syringe containing the composition of Example 1. 0.5 cc to 5 cc was applied per sinus.

[0162] After 30+ / -7 days of initial treatment, patients were evaluated at the discharge visit, where a CT scan was performed to evaluate the treated sinuses in addition to microbiological samples from the treated sinuses and biopsies of the maxillary ethmoid junction or lateral middle turbinate from a subset of patients. Patients also completed a SNOT-22 assessment at the discharge visit. The discharge visits for patients 4 and 5 were after 63 and 45 days of treatment, respectively.

[0163] The patient received the following amounts of the composition:

[0164] Patient number Amount of drug administered, g 1 4.69 2 7.14 3 5.36 4 9.26 5 8.65 6 9.79 7 8.1 8 8.22

[0165] exist Figures 5A-5C SNOT-22 results for patients 2, 3, and 6 are provided separately in . Patient 2 was evaluated after 29 days of treatment, patient 3 was evaluated after 35 days of treatment, and patient 6 was evaluated after 27 days of treatment. At baseline, patient 2 tested positive for 2+ Pseudomonas aeruginosa (mucoid strains) and 2+ Pseudomonas aeruginosa (non-mucoid strains), as well as 1+ dematiaceous fungi. At baseline, patient 3 tested positive for 1+ Staphylococcus aureus. At baseline, patient 6 had no detectable bacterial or fungal infections. One patient (patient 1) was found to be ineligible for study criteria after the start of the study; this patient stated that his sinus symptoms were well controlled with nasal sprays. Figure 5D Mean results for each SNOT-22 metric before treatment and after approximately 30 days of treatment are shown in FIG.

[0166] As shown in these figures, the composition was effective in improving the patient's sinus health as evidenced by a decrease in the overall mean SNOT-22 score and by significant decreases in the majority of the 22 sinus health measures. Figure 6 A summary of total SNOT-22 scores before and after treatment is provided for patients 1-8, and the efficacy of treatment is also demonstrated by a significant decrease in total SNOT-22 scores for eligible patients (patients 2-8).

[0167] Example 6 - Case Study

[0168] A 39-year-old woman reports 10 sinus infections in the past year. She had had very similar episodes 4 years previously and has been receiving multiple rounds of oral antibiotics, including trimethoprim-sulfamethoxazole and erythromycin. She has been taking nasal steroids and nasal antihistamine sprays. She has not undergone sinus surgery.

[0169] She had been scheduled for standard endoscopic sinus surgery two years ago but cancelled the surgery due to moving to Texas. Her symptoms over the years also included intense sinus pressure in the frontal and maxillary sinus regions. A previous CT scan showed pan-sinus disease with significant 4+ mm mucosal changes, with mucopurulent drainage from her bilateral sinus bones noted on physical examination.

[0170] She underwent balloon sinuplasty of 6 sinuses bilaterally approximately 2 years ago. The nasal symptoms and recurrent sinus infections resolved completely, along with her nasal congestion and drainage. This “normalcy” continued for approximately a year without any signs of infection. In the following months, she suffered from chronic sinus infections with facial pressure, pain, drainage, and mucopurulent discharge. These symptoms persisted for several months without relief, including antibiotic therapy. CT showed bilateral maxillary and frontal sinus disease, however, it was reduced compared to the previous CT scan performed before the balloon sinuplasty.

[0171] Recently, she had the betamethasone / clotrimazole cream of Example 1 applied to her bilateral ostiomeatal complexes (OMC) in the office under local anesthesia, placing approximately 2cc of the ointment in each OMC area. She did not use antibiotics after the OMC application, and at a follow-up visit approximately 5 days after the application, she had complete resolution of all symptoms, including fullness, pressure, pain, congestion, drainage, and essentially all of the sinus discomforts listed above. Prior to treatment, the patient reported her symptoms of congestion and drainage as 7-8 out of 10, and after treatment both symptoms were 1 out of 10.

[0172] She has resumed her baseline medical therapy with nasal sprays and antihistamines for nasal symptoms. At last evaluation, she was stable with complete resolution of nasal drainage, facial pain, nasal congestion, and runny nose.

[0173] All references, including publications, patent applications, and patents, cited herein are hereby incorporated by reference to the same extent as if each reference were individually and specifically indicated to be incorporated by reference and were set forth in its entirety herein.

[0174] Unless otherwise stated, the terms "comprising", "having", "including" and "containing" should be interpreted as open terms (i.e., meaning "including but not limited to"). Unless otherwise stated herein, the recitation of numerical ranges herein is intended only as a shorthand method of individually referring to each individual numerical value falling within the range, and each individual numerical value is incorporated into the specification as if it were individually stated herein. All methods described herein can be performed in any suitable order, unless otherwise stated herein or the context is otherwise clearly contradictory. The use of any and all examples or exemplary language (e.g., "such as") provided herein is intended only to better illustrate the present invention, and does not limit the scope of the present invention unless otherwise required. No language in the specification should be interpreted as indicating that any unclaimed element is essential to the practice of the present invention.

[0175] Preferred embodiments of the present invention are described herein, including the best mode known to the inventor for implementing the present invention. For those of ordinary skill in the art, upon reading the foregoing description, variations of these preferred embodiments will become apparent. The inventor expects the technician to appropriately adopt such variations, and the inventor wishes that the present invention be implemented in a manner different from that specifically described herein. Therefore, the present invention includes all modifications and equivalents of the subject matter described in the appended claims as permitted by applicable law. In addition, any combination of the above-mentioned elements in all possible variations thereof is included in the present invention, unless otherwise noted herein or the context is otherwise clearly contradictory.

Claims

1. Use of a composition for the preparation of a medicament for treating a subject suffering from a condition associated with sinonasal or nasopharyngeal tissue, wherein the composition is for topical administration to the sinonasal or nasopharyngeal tissue of the subject, wherein the composition is a cream having a viscosity, as measured by a Brookfield HBT with Spindle 21 at room temperature, of (1) 220,000 centipoise (cP) to 260,000 cP at a shear rate of 0.5 RPM, 30% torque at a factor of 8,000; (2) 140,000 cP to 170,000 cP at a shear rate of 1.0 RPM, 39% torque at a factor of 4,000; (3) 75,000 cP to 90,000 cP at a shear rate of 2.0 RPM, 41% torque at a factor of 2,000; (4) 200,000 cP to 250,000 cP at a shear rate of 2.5 RPM, 40% torque at a factor of 2,000; (5) at a shear rate of 5.0 RPM, 55,000 cP to 74,999 cP at a torque of 42% at a factor of 1,600; (5) at a shear rate of 5.0 RPM, 32,000 cP to 55,000 cP at a torque of 50% at a factor of 800; (6) at a shear rate of 10.0 RPM, 19,000 cP to 32,000 cP at a torque of 60% at a factor of 400; (7) at a shear rate of 20.0 RPM, 10,000 cP to 19,000 cP at a torque of 73% at a factor of 200; or (8) at a shear rate of 50.0 RPM, 5,000 cP to 10,000 cP at a torque of 97% at a factor of 80, and wherein the cream further comprises a steroid.

2. The method of claim 1, wherein the steroid is selected from the group consisting of cortisone, cortisol, hydrocortisone, methylprednisolone, prednisolone, prednisone, triamcinolone acetonide, betamethasone, ciclesonide, dexamethasone, esters and salts thereof, and combinations thereof.

3. The use according to claim 1, wherein the steroid is betamethasone or an ester or salt thereof.

4. The use according to claim 1, wherein the steroid is betamethasone dipropionate.

5. Use according to any one of claims 1 to 4, wherein the steroid is present in the composition in an amount of 0.1 to 100 mg per gram of the composition.

6. The use according to claim 4, wherein the steroid is present in an amount of 0.322 mg per gram of the composition.

7. The use according to claim 6, wherein the total amount of the composition administered to the subject is 4 to 8 grams.

8. The use according to any one of claims 1 to 4, wherein the condition associated with the nasal sinuses or nasopharyngeal tissue is selected from mucormycosis, chronic sinusitis, acute sinusitis, bacterial sinusitis, chronic bacterial sinusitis, polymicrobial sinusitis, nasal polyps, allergic fungal sinusitis, chronic allergic fungal sinusitis and sinusitis.

9. The use according to any one of claims 1 to 4, wherein the subject has undergone sinus surgery prior to administration of the composition.

10. The use according to any one of claims 1 to 4, wherein the disorder associated with the nasal sinuses or nasopharyngeal tissue is chronic allergic fungal sinusitis, and wherein the subject has undergone functional endoscopic sinus surgery prior to administration of the composition.

11. The use according to any one of claims 1 to 4, wherein the step of administering is performed no more than once on the subject.

12. The use according to any one of claims 1 to 4, wherein the step of administering is performed no more than once within a period of 10 days.

13. The use according to any one of claims 1 to 4, wherein the step of administering is performed no more than once within a 21 day period.

14. The use according to any one of claims 1 to 4, wherein the step of administering is performed no more than once within a 30 day period.

15. The use according to any one of claims 1 to 4, wherein the step of administering is performed no more than once within a 60 day period.

16. The use according to any one of claims 1 to 4, wherein the step of administering is performed no more than once within a 90 day period.

17. The use according to any one of claims 1 to 4, wherein the step of administering is performed no more than once within a 180 day period.

18. The use according to any one of claims 1 to 4, wherein the step of administering is performed no more than once within a 365 day period.

19. The use according to any one of claims 1 to 4, wherein the composition further comprises cetearyl alcohol, cetyl esters wax, sorbitan monostearate, benzyl alcohol, propylene glycol, 2-octyldodecanol, polysorbate 60, sodium hydroxide, carbomer 940 NF and water.

20. The use according to claim 1, wherein the condition is the result of Gram-negative bacteria.

21. The use according to claim 1, wherein the condition is the result of Gram-positive bacteria.

22. The use according to claim 1, wherein the condition is the result of a fungus.

23. The use according to claim 1, wherein the condition is a result of yeast.

24. The use according to claim 1, wherein the condition is polymicrobial, comprising a combination of bacteria and / or fungi.

25. The use of claim 1, wherein the condition is the result of inflammation without an identified microbial infection.

26. The use according to claim 1, wherein the condition is an exacerbation of sinusitis following sinus surgery.

27. The use according to any one of claims 1 to 4 and 20 to 26, wherein the subject suffers from one or more sinus conditions selected from the group consisting of needing to blow the nose, nasal congestion, sneezing, runny nose, coughing, postnasal discharge, thick nasal discharge, ear fullness, dizziness, ear pain, facial pain or pressure, decreased sense of smell or taste, difficulty falling asleep, waking up at night, lack of a good night's sleep, waking up tired, fatigue, decreased productivity, decreased concentration, frustration, restlessness or irritability, sadness, embarrassment, and combinations thereof.

28. The use according to any one of claims 1 to 4 and 20 to 26, wherein the condition associated with the nasal sinuses or nasopharyngeal tissue comprises the need to blow the nose, nasal congestion, sneezing, runny nose, coughing, postnasal discharge, thick nasal discharge, ear fullness, dizziness, ear pain, facial pain or pressure, decreased sense of smell or taste, difficulty falling asleep, waking up during the night, lack of a good night's sleep, waking up tired, fatigue, reduced productivity, reduced concentration, frustration, restlessness or irritability, sadness, embarrassment or a combination thereof.

29. The use according to any one of claims 1 to 4 and 20 to 26, wherein the composition does not comprise an agent having antimicrobial activity.

30. The use according to claim 24, wherein the fungus is yeast.

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