This invention pertains to cardiac medication and specifically to the treatment of angina with a mixture of nitroglycerin (NTG) and menthol containing substances (MCS).
Nitroglycerin spray is widely used in patients with coronary artery disease and angina.
Nitroglycerin (NTG) is the most common medication taken for quickly alleviating the pain experienced by someone having an angina attack. The principal pharmacological action of NTG is relaxation of the vascular smooth muscle, producing a vasodilatory effect on both peripheral arteries and veins with more prominent effects on the latter.
NTG, taken sublingually, is very effective; anginal pain usually subsides within minutes. NTG also improves exercise tolerance in patients with exertional angina when used prophylactically. The beneficial effect of NTG is dose related.
NTG is commonly supplied in tablet or liquid form for sublingual delivery. Typically, in liquid form, a pump spray applicator is used and is set to deliver 400 mcg NTG per single spray dosage. It is known in the prior art to add peppermint oil as an inactive ingredient to NTG in the liquid form for sublingual delivery. A commonly used product is manufactured and sold under the US Registered trademark xe2x80x9cNITROLINGUALxe2x80x9d(copyright) Pumpspray by First Horizon Pharmaceutical Corporation, Roswell, Ga.
The most common side effects associated with NTG medication are headache and syncope. These undesirable side effects are dose related but the effects can vary from patient to patient. For some patients, the side effects can be so intense that they will refuse to take the NTG medication.
It has been discovered that the use of menthol containing substances (MCS), when used in conjunction with NTG can potentiate the effect of NTG when it is administered to a patient sublingually. Accordingly, MCS permits the usage of a lower minimal effective NTG dosage. In other words, a mixture of MCS with a less than the 400 mcg standard dosage of NTG will provide the same effect as a standard 400 mcg dosage of NTG.
As used in this specification, MCS is used to collectively refer to substances from which Menthol is derived. Substances which are considered to be MCS include peppermint oils, (Ex Mentha Piperita and Ex Mentha Arvensis), peppermint flavor, spearmint oil, or synthetically produced Menthol.
One advantage of combining a reduced amount of NTG with MCS is that the amount of NTG contained in each spray dosage is less while still providing the same level of anginal pain relief but without the patient having to experience the typical dosage related side effects, specifically, headache and fainting he/she would otherwise suffer. A second advantage for using a NTG/MCS combination is the reduced dosage cost since less NTG is required.
By way of example, an approximate 1% Menthol solution can be prepared and mixed in a 50/50 volumetric proportion with NTG solution. The resulting anti-anginal medication can be used for sublingual delivery by aerosol or pump spray. For example, only 200 mcg NTG is used rather than the typical 400 mcg NTG dosage. The NTG anti-anginal effect obtained is as effective as if double the dosage of NTG was used, i.e. 400 mcg NTG; but the dose related side effects are reduced dramatically.
A solution containing 50% vol. standard NTG NITROLINGUAL(copyright) Pumpspray (400 mcg/spray) and 50% vol. 1% Menthol was tested. The solution was indicative of the benefit available to a patient. However, the combination tested should not be interpreted as the only proportional combination covered by this invention. Although the testing was based on a 50/50 combination, reducing the dosage from 100% NTG NITROLINGUAL(copyright) Pumpspray (400 mcg/spray) to a dosage of 90% NTG NITROLINGUAL(copyright) Pumpspray (400 mcg/spray)/10% Menthol solution should also alleviate, to some degree, the side effects experienced by patients.
Further, menthol oils have a long lasting strong aromatic character. When this strong odor is coupled with the proven therapeutic effect of NTG, over time, the minimal effective NTG dosage may be reduced as a result of a learned conditioned reflex that the body associates with NTG. It is possible that over time, a patient may have the dosage of NTG reduced while the proportion of MCS is increased as the patient""s body learns to associate MCS with the anti-anginal effect of NTG.
USPTO Backgrounds
USPTO Backgrounds