Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2000-06-19
2002-11-26
Jarvis, William R. A. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C514S863000
Reexamination Certificate
active
06486152
ABSTRACT:
BACKGROUND OF THE INVENTION
The invention relates to topical formulations of carbamazepine and their use in treating skin conditions such as psoriasis.
Carbamazepine and derivatives are well-known as systemic bioactive agents useful as anticonvulsants. They are used in treating central nervous system such as epilepsy. A review of patents referring to carbamazepine reveals that there has been ongoing research into oral formulations of carbamazepine, intravenous formulations, sustained release delivery systems including a transdermal patch, and uses for treating other central nervous system disorders, motion sickness, parkinsonian syndromes, drug dependency such as alcoholism, and cocaine use. These formulations are all directed to systemic applications, and the therapeutic targets are all essentially neurological diseases and conditions.
Systemic use of drugs has disadvantages, such as the need for high dosages, side effects at regions of the body unrelated to the affected tissue, toxicity to the liver or other organs, and slow or overly long-lasting results. Carbamazepine may cause neuropathy, adverse hematologic effects such as anemia, and a hypersensitivity syndrome including dermatitis. The side effects can be severe requiring discontinuation of therapy in some patients. Nonetheless, carbamazepine has been believed to be a drug that is only effective in systemic applications. Its mechanisms of action and metabolism are poorly understood. It would be desirable to find new ways of delivering carbamazepine with reduced side effects.
Psoriasis is a disease of poorly understood etiology. There has been a limited arsenal of therapeutic methods useful in treating the disease, including physical treatment (sun, local heating, mud treatment), and steroids. The beneficial effects of these approaches are limited. None is effective in all cases, and the failure rate is high. Any effective new method of treatment would be of enormous value in relieving the pain of people with psoriasis.
SUMMARY OF THE INVENTION
According to the invention, topical formulations of carbamazepine comprise a pharmaceutically acceptable vehicle in which a suitable concentration of carbamazepine is dissolved or suspended, the drug and vehicle interacting such that a topically effective amount of the carbamazepine may be transferred to epidermal tissue to which the formulation is applied. The invention also encompasses a method of treating psoriasis comprising applying an effective amount of a topical formulation of carbamazepine to the affected area until the condition is improved. This provides a new treatment modality using a new active agent.
A therapeutic formulation comprises a topically acceptable semisolid vehicle and carbamazepine, the vehicle consisting of components that are compatible with the carbamazepine, and the carbamazepine being in a concentration sufficient to permit a therapeutically effective amount of the carbamazepine to be absorbed from the formulation into the skin of a patient. The vehicle may be a cream, ointment, or gel. A method of treating a skin condition of a patient such as psoriasis comprises applying carbamazepine topically to the patient's skin until the condition improves. A method of administering carbamazepine to a patient comprises applying a formulation comprising carbamazepine locally to an affected area, preferably topically to the patient's skin.
Further objectives and advantages will become apparent from a consideration of the description and drawings.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
In describing preferred embodiments of the present invention illustrated in the drawings, specific terminology is employed for the sake of clarity. However, the invention is not intended to be limited to the specific terminology so selected, and it is to be understood that each specific element includes all technical equivalents which operate in a similar manner to accomplish a similar purpose.
It was observed that an HIV positive patient suffering from psoriatic erythroderma exhibited improvement when he accidentally ingested 200-400 mg/day of Tegretol® carbamazepine for two weeks. The condition flared up again after he stopped taking the medication. The condition improved once again when he intentionally began taking the medication for a second time. His mood was affected, too. Smith and Skelton, New England Journal of Medicine, Dec. 26, 1996, page 1999.
According to the invention, similar effectiveness may be achieved in a topical formulation whose use minimizes the psychological and other side effects of carbamazepine administered systemically. Such a formulation is a semisolid or non solid suitable for spreading on the affected tissue of a patient. The formulation may be a cream, ointment, gel, lotion, or liquid, and may be occlusive and moisturizing. An oil-in-water emulsion providing an elegant cream base is most preferred. A liquid is desirable for treating the scalp.
The components of the formulation are selected to be compatible, stable, topically acceptable, and able to support carbamazepine in a chemically stable state, and to deliver it into the skin of a patient upon application. The carbamazepine may be present as a suspension or a solution. A solution is preferred in order to facilitate prompt drug delivery. Carbamazepine is practically insoluble in water but is soluble in alcohols, acetone, and propylene glycol. Accordingly, propylene glycol containing vehicles are preferred.
The carbamazepine may be made into pharmaceutical compositions with appropriate pharmaceutically acceptable carriers or diluents and may be formulated into semi-solid or liquid forms. Methods known in the art can be utilized to control release or absorption of the composition over time. A pharmaceutically-acceptable form should be employed which does not in effectuate the compositions of the present invention.
The compositions may be used alone or in appropriate association, as well as in combination with, other pharmaceutically-active compounds. The formulation may further comprise antiinflammatory components such as steroids or non-steroid compounds, and may comprise local anesthetics. The method and composition of the invention may be used in combination or in rotation with other treatment regimes, to avoid the desensitization effect occurring with psoriasis and other skin diseases.
“Non-solid” is meant to exclude solid dosage forms such as tablets, and includes gels, creams, ointments, lotions, liquids, and suspensions.
The term “treatment” is intended to encompass administration of compounds according to the invention prophylactically to prevent or suppress an undesired condition, and therapeutic administration to eliminate or reduce the extent or symptoms of the condition. Treatment according to the invention may be for a human or an animal having a disease in need of such treatment.
The “effective amount” of the composition is such as to produce the desired effect in a host which can be monitored using several end-points known to those skilled in the art. For example, one desired effect might comprise reduction of psoriatic inflammation. Such effects could be monitored in terms of a therapeutic effect, e.g., alleviation of some symptom associated with the disease being treated, or particularized assays. These methods described are by no means all-inclusive, and further methods to suit the specific application will be apparent to the ordinary skilled artisan.
Furthermore, the amounts of each active agent included in the compositions employed in the examples described herein provide general guidance of the range of each component to be utilized by the practitioner upon optimizing the method of the present invention for practice either in vitro or in vivo. Moreover, such ranges by no means preclude use of a higher or lower amount of a component, as might be warranted in a particular application. For example, the actual dose and schedule may vary depending on whether the compositions are administered in combination with other pharmaceutical compositions, or depending
Coles Marc
Keren Gad
Gollin Michael A.
Jarvis William R. A.
Kim Vickie
Taro Pharmaceutical Industries Ltd.
Venable
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