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Title:  Treatment of bruxism

United States Patent:  6,632,843

Issued:  October 14, 2003

Inventors:  Friedman; Mark (5 Forest Ct., Larchmont, NY 10538)

Appl. No.:  495690

Filed:  February 1, 2000


This invention relates to the use of a composition for local percutaneous delivery of a drug such as a muscle relaxant, more particularly cyclobenzaprine in an organogel cream. The composition is applied by the patient directly to the skin over accessible muscles of mastication i.e., masseter and temporalis. The composition is rapidly absorbed through the skin to provide control of harmful habits such as bruxism and tooth clenching. The composition can also be applied to the skin overlying these muscles to control muscle hyperactivity (spasm) and/or trigger points, from other causes. The composition can be formulated to include another active agent such as a non-steroidal anti-inflammatory, for example ketoprofen. The advantage of topical administration versus systemic include use of lower doses of drug, delivery of the drug to the desired site, avoidance of the gastrointestinal tract and hepatic first-pass biotransformation and metabolism, and elimination of many of the side effects of the drug normally associated with systemic administration.


This invention relates to the use of compositions containing pharmaceutically active agents to be used for the treatment of temporomandibular disorders, including bruxism tooth grinding, tooth clenching and various car symptoms including, congestion, swallowing difficulties, tinnuitis, and pain referred from adjacent muscles. In accordance with the invention the compositions are applied topically onto the intact skin for local subcutaneous delivery of a muscle relaxant, namely cyclobenzaprine. Compositions comprising more than one active agent are within the scope of this invention and could be administered to a patient who might benefit from the differing properties of such a formulation. Thus the composition may be formulated to comprise other pharmaceutically active agents in addition to the muscle relaxant. Such agents include a non-steroidal anti-inflammatory, preferably ketoprofen, or an anxiolytic agent such as diazepam. The composition , formulated as a cream using lecithin organogel as the delivery vehicle, is applied by the patient onto the intact skin overlying accessible muscles of mastication, i.e., masseter, temporalis. Similarly application of the composition to these or other muscles may be used to control muscle spasm or hyperactivity. It may be applied to tender spots known as trigger points in the involved muscle and associated area. Once the formulations have been prepared, use of the composition is a simple matter of applying the formulation to the affected areas where transdermal delivery of the pharmaceutically active agent(s) is desired. The amount of cream applied, about one gram, is used to cover an area the size of two fingers (about one inch by two inches). The advantages of topical administration include use of lower doses of active agents, avoidance of the gastrointestinal tract and hepatic first by-pass biotrans formation and metabolism, and delivery of the drug to the a specific area (local) versus systemic distribution of the drug.

The compositions for transcutaneous delivery of pharmaceutically active agent(s) are formulated in organogel this gel comprises a biocompatible organic solvent, a polar lipid, a biocompatible surfactant, water, urca and the pharmaceutically active substance(s). The polar lipid is preferably lecithin, the biocompatible organic solvent is preferably isopropyl myristate and the surfactant preferably is docusate sodium. Preferred composition comprise preferably lecithin 10-30%, isopropyl myristate 10-30%, urea 5-20%, water 30-60% and surfactant 10-20%. After formulation of the composition with the pharmaceutically active agent, and adjustment of the pH to the desired range, the formulation thickens and forms a gel suitable for topical administration. The final pH should be in the range Of 6.0 to 7.0 . The appropriate pH is obtained by adjusting with aqucous NaOH. Depending on the chemical properties, for example the solubility characteristics of the pharmaceutically active agent the steps in compounding the composition may vary slightly. Some agents may require some heating before a consistent mixture may be achieved. The active compound is added to the mixture of the polar lipid and organic solvent. The mixture may be warmed before adding the active compound if required for solubilizing the active agent. Thorough mixing is accomplished by stirring.

Cyclobenzaprine HCI (.Flexeril, Merck) relieves muscle spasm of local origin without interfering with muscle function. There is a similarity between the effects of cyclobenzaprine and the structurally related tricyclic anti-depressants e.g. amitryptyline. Cyclobenzaprine is a 5-HT2 receptor antagonist and its muscle relaxant effect is due to inhibition of serotonergic neurons. Cyclobenzaprine significantly improves the signs and symptoms of skeletal muscle spasm. The clinical response includes improvement in local pain and tenderness and increased range of motion. Clinical improvement is often observed as early as the first 20 minutes of application. When taken orally, cyclobenzaprine is eliminated slowly with a half life as long as one to three days it is highly bound to plasma proteins, is metabolized primarily to glucuronide like conjugates and is excreted, primarily through the kidneys. First pass metabolism is avoided by topical administration

Diazepam (Valium Roche) which can be given concomitantly with Flexeril is indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety, or tension associated with stress. It is a useful adjunct for the relief of skeletal muscle spasm.

Ketoprofen (Orudis Wyeth) is another example of a drug which can be co-administered with Flexeril a non-steroidal anti-inflammatory drug with analgesic and antipyretic properties. Ketoprofen has been shown to have inhibitory effects on prostaglandin and Icukotriene synthesis, to have antibradykinin activity as well as to have lysosomal membrane stabilizing activity. When taken orally the drug is bound to plasma proteins and is excreted in the urine mainly as glucuronide like conjugates.

Formulations containing the above agents would be prepared so that cyclobenzaprine would be present in an amount of 0.5-1.0%, ketoprofen 5.0-10%, in addition to the cyclobenzaprine (0.5-1.0%), and diazepam 0.5-1.0% in addition to cyclobenzaprine (0.5-1.0%).

The composition (organogel plus the pharmaceutical active agent) is applied by the patient, usually at bed time; it can be used at other times of the day if necessary. The usual area of application is roughly that covered by two fingers, (an area of about one inch by two inches) and the amount of composition delivered would be about 1 ml (about one gram of composition).

In trials where the composition (cyclobenzaprine plus organogel) was applied in a controlled setting, sixteen out of twenty patients reported positive response within 20-25 minutes. In over 200 patients where the cream was prescribed, positive responses (within a few applications) have been reported by approximately 70% of the patients., with no side effects reported. Research has demonstrated minimal systemic effects from topical application of muscle relaxants and anti-inflammatory medications.

Claim 1 of 10 Claims

I claim:

1. A method for treating tooth grinding and tooth clenching in a patient having such condition which comprises topically applying directly to the skin overlying accessible muscles of mastication for absorption through the skin a therapeutically effective amount of a composition comprising cyclobenzaprine in a pharmaceutically acceptable carrier wherein said carrier is an organogel cream comprising lecithin, isopropyl myristate, urea, a surfactant and water.

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