Title:  Method for treating acute mountain sickness

United States Patent:  6,511,964

Issued:  January 28, 2003

Inventors:  Butler; Terri L. (Kirkland, WA); St. Cyr; John (Coon Rapids, MN); Johnson; Clarence A. (Wyoming, MN)

Assignee:  Bioenergy, Inc. (Ham Lake, MN)

Appl. No.:  821238

Filed:  March 29, 2001

Persons encountering high altitudes without being acclimatized can prevent or alleviate the symptoms of acute mountain sickness by administration of ribose one to four times a days, beginning immediately on encountering high altitudes and continuing for at least five days.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides a method of alleviating the symptoms of acute mountain sickness (AMS) of a human, by the oral, intravenous or peritoneal administration of and effective amount of ribose to said human. AMS commonly occurs in persons going abruptly from near sea level to a higher elevation. Depending on individual susceptibility, AMS can occur at relatively low altitudes. Persons who are exposed to, for example, carbon monoxide from smoking, or persons with preexisting conditions such as asthma are among those groups that are particularly susceptible to AMS. Altitudes above about 1,000 meters are at significantly lower oxygen tension and atmospheric pressure than at sea level and such more susceptible persons may begin experiencing AMS at this altitude. At altitudes between 1,500 and 3,000 meters, up to 25% of unacclimatized travelers experience AMS. At higher altitudes, both the incidence and severity of AMS increase.

AMS is characterized by a constellation of symptoms. Headache is the main symptom. Nausea, vomiting, dyspnea, insomnia, lethargy, loss of energy, impaired cognition and balance. The onset of symptoms typically occurs within hours to three days after arrival at the high altitude. These symptoms may resolve after several days, but can lead to fatal conditions of cerebral edema and pulmonary edema. Even those experiencing no or minimal symptoms at rest will be more affected if they attempt to exercise.

Travelers who are able to acclimatize gradually, preferably at several stages of increasing altitude, are less affected by AMS. If slow acclimatization is not possible, several medications have been used for the prevention or amelioration of AMS. Acetazolamide is a carbonic anhydrase inhibitor, which creates a metabolic acidosis due to a renal loss of bicarbonate and an inhibition of red blood cell enzymes with a retention of carbon dioxide. If acetazoamide is taken daily, starting three days before reaching altitude, sleep is improved, exercise performance is improved and higher altitudes can be tolerated. Dexamethasone is a catabolic steroid that is effective in reducing vasogenic cerebral edema. It has been found to reduce the symptoms of AMS due to exposure to very high altitudes. Nifedipine, a calcium-channel blocker, may prevent pulmonary problems. The usefulness of these two agents at intermediate altitudes is unclear.

Many persons travel to high altitudes expressly for the purpose of sports, such as skiing and golf. Others are exposed to airplane cabin pressures that are equivalent to altitudes of 2,000 to 4,000 meters for flights as long as eight to twelve hours. All of these subjects would benefit from an easily obtainable, non-prescription agents that would enable them to exercise more comfortably without incurring the headache, lethargy or more severe symptoms of AMS. It has been found as a preliminary result that various persons exercising at high altitudes felt more energetic and did not have AMS when ingesting ribose.

It must be cautioned that persons cannot rely on the compositions and methods of this invention to prevent or give total relief to AMS. If symptoms are severe, it is imperative to evacuate the person to lower altitudes and professional medical care.

For the purpose of describing this invention, the following terms have the following meanings:

1. "Ribose" means a monosaccharide, including but not limited to, ribose, and any 5-carbon precursor of ribose, D-ribose, ribulose, xylitol and xylulose.

2. "Hypoxia" means any state in which the tissue oxygen saturation is reduced to a less than optimal level. Hypoxia includes anoxia, ischemia and poisoning with toxic agents such as carbon monoxide and cyanide which interfere with oxygen utilization. Hypoxia may be chronic as in congestive heart failure, coronary artery disease, peripheral vascular disease or pulmonary dysfunction, or transient as in anesthesia, surgical procedures or exposure to high altitudes.

3. "Hypoxic threshold" is that basal level where oxygen saturation of tissues is less than optimal. A raised hypoxic threshold increases tolerance to situations which would otherwise result in hypoxia.

4. "Ischemia" is that state of hypoxia caused by reduced circulation of blood to tissue.

5. "Acute mountain sickness" (AMS) is the condition brought on exposure by low oxygen tension combined with low atmospheric pressure. AMS occurs when mammals are brought suddenly to high altitudes, without acclimatization. AMS can also occur on long airplane flights which simulate high altitude.

In co-pending patent application Ser. No. 09/290,789 (the "'789 Application"), now U.S. Pat. No. 6,159,942, the teaching of which is hereby incorporated by reference, it is disclosed that administration of D-ribose increases the energy level of mammals by stimulating the synthesis of ATP. Examples therein show that ATP levels in the skeletal muscle of healthy mammals under normal conditions of oxygen availability increase upon ribose administration and that the increase is correlated with an increase in performance and activity levels. It is also shown that administration of D-Ribose provides some benefit even to patients with coronary artery disease.

The invention described in the parent to this application, U.S. patent application, Ser. No. 09/406,266, filed Sep. 24, 1999, now U.S. Pat. No. 6,218,366 the teaching of which is hereby incorporated, was based on the discovery that administration of ribose can also increase the tolerance of tissue to low oxygen availability, that is, to hypoxia. In patients with ischemic heart disease, regions of the heart may be poorly perfused, dysfunctional, but still viable. Myocardial ischemia limits blood flow and therefore the available supply of oxygen. This limited availability of oxygen affects oxidative metabolism, which ultimately negatively affects the production of ATP, essential for maintenance of contractility and cellular integrity. Varied states of ischemia exist. However, either transient or chronic ischemia may result in partial reduction of myocardial ATP with subsequent impairment of contractile function, which can lead to heart failure but not cell death.

Therapeutic intervention is variable and must be tailored to each patient. Non-surgical therapies may offer a primary mode of treatment. The first line of action includes angiotensin-converting inhibitors, digoxin and diuretics. So-called inotropic agents such as dobutamine, arbutamine, dopamine, amrinone and milronine, which increase stroke volume and cardiac output, have been universally used for treatment of cardiac dysfunction, which can be manifested by edema, dyspnea, pulmonary congestion and organ hypoperfusion. Many previous studies have investigated the use of ribose in healthy animals such as dogs, rats and swine that have been subjected to ischemic insult. While such studies may suggest therapies for humans with cardiovascular disease, Energy and oxygen availability can each independently influence tissue integrity and function. Although ribose has been shown to enhance energy levels under conditions of normal oxygen availability, the present invention surprisingly shows that when ribose is present, tissue can endure low oxygen availability while still maintaining normal function, without being subjected to the deleterious effects due to low oxygen. Even if energy is available in sufficient quantities, but oxygen is low, adverse effects may still occur in the hypoxic tissue. These effects include pH changes, imbalance in intermediate metabolites and the like. In other words, ribose ameliorates the effects of hypoxia, that is, it raises the hypoxic threshold.

Many patients suffering from "silent" cardiovascular disease, that is, such patients are unaware of their condition of chronic hypoxia. The treadmill test has been extensively used to raise the oxygen demand of the heart and uncover the low hypoxic threshold. However, treadmill testing may not be the test of choice in all situations. Dobutamine has been found particularly useful for simulating exercise in patients with coronary artery disease. The infusion of dobutamine produces a stressful myocardial condition similar to that produced by exercise, while the patient is in a controlled hospital setting, with intravenous infusion, in which intervention is readily available. It is theorized that dobutamine increases myocardial stroke volume and cardiac output while reducing ventricular volume and mitral regurgitation due to its vasodilating effects. Because of these multiple effects, dobutamine has been investigated extensively as an agent to increase sensitivity in identifying segmental wall motion activity by echocardiography.

One of the causative factors of AMS is hypoxia and some of the symptoms of AMS are common to those of hypoxia at sea level. It may be expected therefore that the administration of ribose would alleviate lethargy. However, hypoxia does not normally cause headache, cerebral edema, nausea and pulmonary edema. The present invention is directed to amelioration or prevention of the symptoms of AMS, wherein the stress of low oxygen tension is compounded by low atmospheric pressure, which deleteriously affects breathing, leading to pulmonary edema with accompanying cough and edema.

Claim 1 of 4 Claims

We claim:

1. A method to prevent or alleviate the symptoms of acute mountain sickness in a mammal experiencing the symptoms of acute moutain sickness, the method comprising administering an amount of ribose to the mammal effective to prevent or alleviate said symptoms.
 

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