FIELD OF THE INVENTION

The invention described in this disclosure relates to new regimens for the administration of vitamin B12 compounds to mammalian subjects (e.g., human female patients) for the promotion or maintenance of health and to compositions that are configured to facilitate the practice of such new vitamin B12 compound administration methods.

BACKGROUND OF THE INVENTION

Vitamin B12 is an essential nutrient which research has demonstrated plays a role in DNA synthesis and regulation, fatty acid synthesis, physiological energy processes, and cellular metabolism. Commonly available vitamin B12 supplements provide the vitamin B12 nutrient/active ingredient in one of two forms: cyanocobalamin or methylcobalamin. Common dosages of Vitamin B12 in leading Vitamin B12 supplements provide daily doses of between about 50 mcg (micrograms) and about 10,000 mcg. These levels reflect numerous reported clinical studies for various conditions in which the amount of continuous daily vitamin B12 supplementation associated with positive health outcomes ranged from, e.g., 20 mcg to 1,000 mcg.

Based on such clinical studies and otherwise, supplementation with vitamin B12 has been alleged to be associated with the maintenance or enhancement of a broad range of physiological conditions and processes ranging from reducing depression and cognitive impairment to treating age-related macular degeneration. Perhaps correspondingly, vitamin B12 deficiencies also have been allegedly linked with a number of negative health conditions including fatigue, shortness of breath, skin conditions, gastrointestinal problems, vision problems, nerve problems, and even cognitive functioning issues such as memory loss. Subsets of the population have been identified as being particularly susceptible to vitamin B12 deficiency, including older individuals (e.g., individuals over 50 years of age). However, other recent studies have suggested that vitamin B12 supplementation can contribute to an increased risk of cancer. Thus, the safety and risk/benefit profile of supplementation with the currently leading vitamin B12 supplement regimens may be less clear than similar leading vitamin or mineral supplements.

SUMMARY OF THE INVENTION

The invention described herein provides new methods and compositions for promoting or maintaining health or preventing or treating conditions in mammalian subjects, such as humans, such as females, for example females experiencing a recurring vaginal discharge of blood, e.g. menstruating and potentially menstruating females or females experiencing or at risk for experiencing breakthrough bleeding while on a birth control method that regulates ovulation, such as a hormonal birth control regimen.

The methods of the invention comprise administering one or more vitamin B12 compounds to such a mammalian host, typically in significantly lower amounts on a daily and/or periodic basis (e.g., over a period of about one month) than is associated with current leading vitamin B12 supplementation regimens.

The methods of the invention can in some aspects be performed for the promotion or maintenance of health or the prevention or treatment of conditions, such as the prevention or treatment of a vitamin B12 deficiency, enhancement in blood cell level, or modulation of another nutritional or medical condition that is modulated by vitamin B12. In one aspect, the inventive methods comprise administering a vitamin B12 compound-containing dosage form promoting or facilitating promotion of one or more vitamin B12-effects, such as replenishment or maintenance of healthy blood cell levels in a mammal, such as in a female (e.g., a female that experiences menstruation or breakthrough bleeding).

The inventive vitamin B-12 compound supplementation methods of the invention typically can be characterized by comprising the administration of:

(a) relatively low doses of vitamin B12 compounds (as compared to current vitamin B12 supplementation regimens), based on(i) a per-dosage (and, typically, per day) basis (e.g., by administering less than 5 mcg a day, less than 4 mcg a day, or less than about 3 mcg of a vitamin B12 compound a day, such as about 2-5 mcg/day or 2-3 mcg/day),(ii) a per treatment period basis (e.g., by delivering a maximum of 50 mcg vitamin B12 compound/month, such as a maximum of about 40 mcg/month, about 35 mcg/month, or about 30 mcg/month, for example, about 15-45 mcg/month, about 17.5-37.5 mcg/month, about 20-35 mcg/month, or about 20-30 mcg/month), or(iii) based on a regimen that is in accordance with both (i) and (ii);

(b) administration of the vitamin B12 compound(s) by way of a non-continuous, typically cyclic, administration regimen over one or more defined periods of time (e.g., administration of the vitamin B12 compound(s) during only about 7 days of a period of about a month, such as a period of 4 weeks), or

(c) a regimen that is accordance with both (a) and (b) above.

In a non-continuous administration regimen, one or more vitamin B12 compounds is administered to a subject during a certain portion of a defined period (e.g., about one week of about one month) and no vitamin B12 compound is administered to the subject during other days of the period. Such treatment and non-treatment periods can, according to certain aspects of the invention, repeat at least 2, 3, 4, 6, 9, 12, 15, 18, 20, 24, 30, 48, 60 or even more times (e.g., about 2-12 times, about 2-25 times, about 2-50 times, about 2-120 times, about 2-240 times, about 2-360 times, or even about 2-about 500 times) in a “cycle” comprising treatment days and non-treatment days. Such regimens are variously described in this disclosure as “cyclic regimens” or by similar descriptors such as “cyclic” administration, dosing, supplementation, treatment, or regimen. In some respects, the terms non-continuous, cyclic, and intermittent are used to similarly describe such methods of the invention, although a non-continuous or intermittent regimen also can more broadly indicate any regimen in which the vitamin B12 compound is not administered continuously over a longer period, even if any periods of administration of vitamin B12 compound administration and non-administration in such a regimen do not repeat in a generally regular cycle (though such an intermittent regimen can comprise several separate periods of vitamin B12 compound administration).

In one aspect of the invention, the treatment period of a cycle (i.e., the period when the vitamin B12 compound is administered to the subject) in a cyclic regimen corresponds with or is expected to correspond with the occurrence or likely occurrence of a recurring or potentially recurring physiological event in the subject. In one aspect, the expected event is a recurring vaginal discharge of blood (e.g., due to menstruation or breakthrough bleeding).

Thus, according to particular embodiments, the vitamin B12 dosage form is not administered daily but instead is administered over the course of a defined time period, which typically is a limited portion of a larger period, which can repeat 2, 3, or more times as a cycle of active treatment and inactivity (with respect to administration of the vitamin B12 compound composition). According to certain embodiments, the vitamin B12 compound is administered over the course of a treatment period comprising or consisting of, for example, 1-15 consecutive treatment days, such as for example between about 3-10 consecutive days (e.g., 2-12 days, 4-9 days, 3-9 days, or 4-8 days, such as 7 days).

In some aspects, the vitamin B12 dosage form is administered to a human female experiencing a recurring vaginal discharge of blood, or an otherwise reproductively cycling human female over a treatment period expected to correspond to the woman's monthly reproductive hormone cycle. Such a monthly reproductive hormone cycle could be a naturally occurring menstruation cycle or a cycle controlled by a hormone treatment regimen. In some aspects, the 1-15 or other selected consecutive day treatment period (e.g., a 2-12 day period, 3-10 day period, 5-9 day period, or about 7 day period) is expected to correlate with the period of the cycle when a woman's hematopoietic system is challenged and/or blood levels reduced, such as the period of time in which a vaginal discharge of blood (e.g. menstruation or a breakthrough bleed) occurs causing a depletion in otherwise normal blood cell levels.

According to some aspects, the methods of the invention comprise not administering any vitamin B12 compound dosage form to the woman on any days other than the defined treatment days of a period or a cycle. In some embodiments, days other than defined treatment days (i.e., non-treatment days of the cycle) can range from about 16-about 30 consecutive days preceding or following a vitamin B12 compound treatment period (e.g., a period of about 15-27 days, such as about 18-25 days, e.g., about 19-23 days, or more particularly about 20-22 days, such as 21 days).

Together the treatment period (treatment days) and non-treatment period (or days) of a combined defined period of a cycle make up what can be considered the total period of the cycle (which may be called a cycle period or simply a cycle). Thus, e.g., a treatment period of about 7 days and a non-treatment period of about 21 days make up a total cycle period of about 28 days.

In certain embodiments, the invention provides a method for providing a vitamin B12 compound dosage form to a subject over the course of a restricted time period such as over the course of between about 1-about 15 consecutive days (e.g., about 4-9 days, such as about 7 days) wherein the total amount of vitamin B12 compound administered to the woman in any treatment period (and thus any total cycle period) does not exceed about 35 mcg, does not exceed about 30 mcg, or more particularly does not exceed 25 mcg. In one example of such an aspect, the invention provides methods that comprise administering a vitamin B12 compound, such as a natural or bioidentical methylcobalamin composition, or a composition comprising a derivative or analog thereof, for a period of only about 3-10 days, such as about 5-9 days, such as about 7 days, in each cycle of about 25-30 days, e.g., about 28 days).

In some aspects, the method of administration comprises repeating the cycle of vitamin B12 treatment period followed by a non-vitamin B12 treatment period at least two times (e.g., at least three times, at least six times, at least 12 times, at least 18 times, at least 24 times, or longer than 24 times such as even about 2-35 times, about 2-50 times, about 2-100 times, about 2-250 times, about 2-350 times, about 2-450 times, about 2-600 times, or even about 2-650 times).

According to certain embodiments, the invention provides a method of facilitating the promotion of or promoting the maintenance or restoration of blood cell levels in females experiencing a recurring vaginal discharge of blood or in females of an age that is within one or two years (before or after) a typical menstruation age. In one aspect, the female subject is at least about 12 years of age. Typically, the female subject is at least about 13-about 15 years of age and typically is at most about 50, about 55, or even about 50-60 years of age (e.g., about 14-54, about 12-60, about 12-52, about 13-55, or about 13-58 years of age).

According to certain embodiments, the invention provides a method of promoting the maintenance or restoration of blood cell levels during a recurring period associated with a physiological process, such as recurring vaginal discharge bleeding, which may be, e.g., to an otherwise normal blood cell levels in a female experiencing a recurring vaginal discharge of blood (or to an amount closer to such levels than would otherwise be the case without the treatment—such as at least about 10% more, at least about 20% more, at least about 25% more, at least about 33% more, at least about 50% more, at least about 75% more, or at least about 90% more of blood cell levels, in at least a significant number of subjects receiving such a treatment, than the level observed in such subjects not receiving the treatment).

In some aspects of the invention, the vitamin B12 compound is delivered in a pharmaceutically acceptable dosage form. In some aspects of the invention, the dosage form is administered orally. In particular aspects of the invention, the dosage form is a pharmaceutically acceptable tablet configured for oral administration.

In some aspects of the invention, the vitamin B12 compound comprises, is predominately composed of, consists essentially of, or consists of (within the limits of ordinary detection) a methylcobalamin compound, which may be a form of methylcobalamin or, e.g., a derivative or analog of methylcobalamin. In some aspects of the invention, the vitamin B12 compound is a form of either naturally sourced/occurring methylcobalamin (i.e., methylcobalamin obtained from naturally occurring sources) or bioidentical methylcobalamin, which form may be, for example, a methylcobalamin salt.

The invention also provides compositions comprising one or more vitamin B12 compound dosage forms which facilitate practicing the vitamin B12 compound administration regimens of the invention. In one aspect, the vitamin B12 compound composition is a package comprising a number of unit doses of vitamin B12 dosage forms for facilitating an intended administration regimen. In one embodiment, the dosage forms are individually packaged in the composition. In a more particular aspect, the individually packaged dosage forms are packaged with one or more additional dosage form products that are administered on non-treatment days of a cyclic regimen of the invention. In a still further particular aspect, the additional dosage forms comprise the dosage forms that make up a triphasic hormonal birth control regimen which is taken on non-treatment days of a cyclic regimen.

