A method and strip for treating allergen-induced airway inflammation. The method includes applying a nasal or skin strip containing a mixture of an allergen and a pharmaceutically acceptable carrier to an individual having allergen-induced airway inflammation in a manner consistent with local nasal immunotherapy.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to local nasal immunotherapy for allergen-induced airway inflammation. More particularly, the present invention relates to an allergen strip for local nasal immunotherapy of allergic rhinitis.

2. Description of the Related Arts

Allergic Rhinitis (AR) is one of the most common allergic diseases in humans. In developed countries, more than 10% of the population suffer from AR and the disease creates burdens such as medical expenses and loss of productivity (Malone D C, et al. J Allergy Clin Immunol. (1997) 99:22-7). Allergen specific immunotherapy was introduced to treat AR by Noon in 1911 (Noon L. Lancet (1911) i:1572-3). There is good evidence that immunotherapy using inhalant allergens to treat seasonal or perennial AR and asthma is clinically effective (Bousquent J, et al. Allergy (1998) 53, suppl 54). Despite the effectiveness of subcutaneous immunotherapy, poor compliance and systemic side-effects may limit its applicability (Cohn J R, et al. J Allergy Clin Immunol. (1993) 91:734-7; Committee on the Safety of Medicine. CSM update. Desensitizing vaccines. BMJ (1986) 293:948; Greenberg M A, et al. J Allergy Clin Immunol. (1986) 77:865-70; Lockey R F, et al. J Allergy Clin Immunol (1987) 79:660-77). The reports of severe reactions questioned the safety of subcutaneous immunotherapy and raised an interest in local nasal immunotherapy (LNIT).

The clinical efficacy of LNIT has been documented in most double-blind, placebo-controlled studies carried out in AR (Georgitis J W, et al. J Allergy Clin Immunol (1983) 71:71-6; Georgitis J W, et al. J Allergy Clin Immunol (1984) 74:694-700; Andri L, et al. J Allergy Clin Immunol (1993) 91:987-96; Passalacqua G, et al. Am J Respir Crit Care Med (1995) 152:461-6; D'Amato G, et al. Clin Exp Allergy (1995) 25:141-8; Andri L, et al. Clin Exp Allergy (1995) 25:1092-9; Andri L, et al. J Allergy Clin-Immunol (1996) 97:34-41; Cirla A M, et al. Allergy (1996) 51:299-305; Bargare M, et al. J Investing Allergol Immunol (1996) 6:359-63). The allergens used for LNIT were dispensed in either powder form or an aqueous solution and tended to be inhaled into the lower airway easily. During the application of the allergens, the patient must vocalize to avoid deposition of extract in the bronchial tree. LNIT may induce asthmatic symptoms; thus, in one study, three patients in the active group withdrew from treatment because of bronchospasm after allergen application (D'Amato G, et al. Clin Exp Allergy (1995) 25:141-8). Critics of LNIT have also claimed that the treatment induces local symptoms for a prolonged period of time, however, the symptoms induced by LNIT were relatively mild.

SUMMARY OF THE INVENTION

It is therefore a primary object of the present invention to provide a safe and effective method for treating allergen-induced airway inflammation. The method comprises applying a nasal or skin strip containing a mixture of an allergen and a pharmaceutically acceptable carrier to an individual having allergen-induced airway inflammation in a manner consistent with local immunotherapy.

Another object of the present invention is to provide a nasal or skin strip for treating allergen-induced airway inflammation in an individual. The nasal or skin strip comprises a substrate, and a mixture of an allergen and a pharmaceutically acceptable carrier on the substrate.

In one embodiment, the allergen-induced airway inflammation comprises, but is not limited to, allergic rhinitis, allergic conjunctivitis, or allergic bronchial asthma. The allergen comprises, but is not limited to, dust mite extract, such as Dermatophoides pteronyssinus (Dp) extract, pollen extract, such as ragweed, mold extract, animal dander, cockroach extract, food allergen, recombinant allergen peptide, or a combination thereof. The skin or nasal strip further comprises an immunmodulatory adjucant. The immunomodulatory adjuvant includes, but is not limited to, fungal immunomodulatory protein (FIP) isolated from Flammalina velutipes, immunostimulatory sequence CpG (CpG oligodeoxynucleotides) or mycobacterium-Bacillus Calmette Guerin (BCG).

In a second embodiment, the allergen is in a dosage of 0.01˜10 μg, preferably 0.01˜1 μg. The FIP is in a dosage of 0.01˜10 μg, preferably 0.5 μg.

In another embodiment, the substrates of the nasal or skin strip include nitrocellulose (NC), polyvinylidene fluoride (PVDF), nylon, filter papers, fabric, cloth, polyethylene, polypropylene, composite fibers, flexible medical grade materials, or a combination thereof. The pharmaceutically acceptable carrier includes, but is not limited to, detergent, lipid solvent, glycerol, PBS, normal saline, water, petrolatum, or vaseline. The detergent includes lecithin or alpha hydroxyl acid, and the lipid solvent includes alcohol or mint.

Further scope of the applicability of the present invention will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.

DETAILED DESCRIPTION OF THE INVENTION

Previous study shows that nasal provocation tests with allergen disc paper can cause immediate nasal allergic reaction with trivial lower airway spasm or lower airway hyperresponsivity (Tsai Jaw-Ji, et al. Int Arch Allergy Immunol (1995) 106: 286-290). LNIT with a steady dosage of allergen has also been reported to have clinical efficacy and tolerability for AR (Bertoni M, et al. Ann Allergy Asthma Immunol (1999) 82:47-51). These reports indicate allergen disc paper with predefined dosage can be carried out for LNIT.

In order to avoid the potential risk of a systemic reaction, which may be caused by incorrect administration of allergen extract, allergen nasal or skin strips are used for LNIT. The present invention features a nasal or skin strip for treating or diagnosing allergen-induced airway inflammation in an individual. The nasal or skin strip comprises a substrate, and a mixture of an allergen and a pharmaceutically acceptable carrier on the substrate.

The present invention also features a method for diagnosing or treating allergen-induced airway inflammation. The method comprises applying a nasal or skin strip containing a mixture of an allergen and a pharmaceutically acceptable carrier to an individual having allergen-induced airway inflammation. For the purposes of diagnosis or treatment, the responsiveness of the individual, for example, release of symptoms, can be measured or monitored.

The "allergen-induced airway inflammation" used herein comprises, but is not limited to, allergic rhinitis, allergic conjunctivitis, or allergic bronchial asthma.

The "allergen" used herein comprises dust mite extract, pollen extract, mold extract, animal dander, cockroach extract, food allergen, recombinant allergen peptide or a combination thereof. The skin or nasal strip further comprises an immunomodulatory adjuvant. The "immunomodulatory adjuvant" used herein comprises fungal immunomodulatory protein (FIP) isolated from Flammalina velutipes, immunostimulatory sequence CpG (CpG oligodeoxynucleotides) or mycobacterium-Bacillus Calmette Guerin (BCG).

In one embodiment, the allergen extract is in a dosage of 0.01˜10 μg, preferably 0.01˜1 μg; the FIP is in a dosage of 0.01˜10 μg, preferably 0.5 μg.

The preparation of the nasal or skin strip is described in the subsequent Materials and Methods section. In general, the allergen extract is in a concentration of 1˜1000 μg/ml, preferably 1˜ μg/ml; the FIP is in a concentration of 1˜1000 μg/ml, preferably 250 μg/ml.

The "substrate" of the nasal or skin strip used herein includes nitrocellulose (NC), polyvinylidene fluoride (PVDF), nylon, filter papers, fabric, cloth, polyethylene, polypropylene, composite fibers, flexible medical grade materials, or a combination of above mentioned materials.

The "pharmaceutically acceptable carrier" used herein includes, but is not limited to, detergent, lipid solvent, glycerol, PBS, normal saline, water, petrolatum, or vaseline. The detergent includes lecithin or alpha hydroxyl acid, and the lipid solvent includes alcohol or mint. The glycerol is used in a concentration of 50% or more.
 

Claim 1 of 10 Claims

1. A method for treating allergen-induced airway inflammation, comprising the step of:

applying a nasal strip comprising a mixture of an allergen and a pharmaceutically acceptable carrier to the nostril of an individual having allergen-induced airway inflammation for local nasal immunotherapy.

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