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Title:  Formulations and methods for treating chronic migraine

United States Patent:  6,517,832

Issued:  February 11, 2003

Inventors:  Marrongelle; Jeffrey L. (1629 Long Run Rd., Orwigsburg, PA 17972); Staverosky; Thomas J. (1537 Mineral Springs Rd., Reading, PA 19602)

Appl. No.:  935945

Filed:  August 24, 2001


A prophylactic treatment for the human malady clinically described as migraine headache comprising daily administration in unit dosage form of a first formulation which comprises a major amount of bioactive peptides and a minor amount of probiotics. Concurrently, daily administration in dosage form of a second formulation of a major amount of active components like malic acid, sylibum marianum, acetyl-L-cysteine, copper chelate, zinc gluconate, aspartate and bromelain. A minor amount of plant derivatives excipients comprise the balance of the second formulation. Preferably, these plant derivatives include beet root, powder, watercress, celery, dandelion, capsicum and artichoke extract.


Accordingly, the inventive methods provides for concurrent administration of two discrete formulations of known beneficial substances, the first formulation is a blend of select ingredients and is thought to improve digestion in most patients.

Formulation I is a unique blend of two ingredients in a gelatin capsule, which blend primarily serves to focus on returning the digestive system to normal function. The first composition of Formulation I is a fish protein concentrate of bioactive peptide. The second composition of the group are probiotics, which are known to be beneficial bacteria, that normally inhabit a mammalian digestive (intestinal) tract, such as the acidophilus microorganism found in yogurt. It is an important agent, shown to be effective in absorbing toxins from both the small intestine and the bowel. This two part formulation is assembled in the weight ratios set out in Working Example I, as in Foundation Formula of The Forever Well entity, Reading, Pa.

The second formulation (II) is a combination of as many as 21 substances, all known to be both benign and beneficial, included selected vitamins, trace minerals, herbs, micronutrients, and macronutrients (Renew Formula.RTM., of the Foreverwell entity). They are assembled in the weight ratios set out in Working Example II. They are well adapted to using standard gelatin capsules as the unit dosage form.

Of the vitamins, included are vitamin B complex species, like B1, B6, and inositol (cis-1,2,3,5-trans, 4, 6, cyclohexanehexol). The trace minerals include magnesium as the aspartate, copper as a chelate, manganese as glycerolphosphate, and zinc as the gluconate. Herbs include silybum marianum (milk thistle), beet root powder, watercress, celery, dandelion, parsley, and capsicum. Micro-nutrients are malic acid, proanthocyanidins, N-Acetyl-L-Cysteine, and SOD (superoxide dismutase). The macro-nutrients include pyridoxal-5 phosphate, and Agaricus Blazei.

Pharmaceutically acceptable formulations for oral administration may take the form of, for example, tablets or capsules prepared by conventional means, with acceptable excipients, such as binding agents, for example, maize starch, or hydroxymethyl cellulose; fillers, for example, lactose, sucrose, mennitol, and maize starch; lubricants, for example, stearic acid, polyethylene glycol, magnesium stearate, metallic or silica, disintegrants, for example, potato starch, or wetting agents, e.g., sodium lauryl sulfate. The tablets may be coated by methods well known in the arts.

Liquid preparations for oral administration may take the form of, for example, aqueous or oily solutions, syrups, elixirs, emulsions or suspensions, or they may be presented as a dry product for reconstitution with water or other suitable vehicle before use. Such liquid preparations may be prepared by conventional means, with pharmaceutically acceptable additives, such as suspending agents, for example, sorbitol syrup, glucose-sugar syrup, or gelatin; emulsifying agents such as lecithin, acacia, or sorbitan mon-oleate; non-aqueous vehicles like oily esters, or ethyl alcohol; and preservatives like methyl or propel p-hydroxy benzoates, or sorbic acid. Such liquid preparations may also contain conventional buffers, flavoring, coloring, and sweetening agents, as appropriate. The prophylactic effects for relief of migraine are effected by taking three capsules (500 mg each) of Formulation I, along with two capsules of Formulation II (400 mg each) before each of the two largest meals of the day, on a daily basis, longer term for an adult in the weight range of 125-200 lb. To limit initial digestive disturbances, take a reduced regimen for the first week. For the initial regime, the reduced dosage of the two capsules is 1400 mg daily.

A proposed dose of the compounds of the invention for oral administration to a human (about 160 lb.) body weight, for the treatment of migraine, is 2300-4600 mg of capsule daily of the ingredients, which dose could be administered up to eight times per day, but more usually one to four times a day, in divided dosages, as noted. It should be understood that unless otherwise indicated, the dosages are referred to in terms of the weight of the active components of the two formulations.

            COMPOSITION               AMOUNT PER CAPSULE
            Bioactive peptides               375 mg
            Probiotics                     62.5 mg

Bioactive peptides which as are available in a particular predigested fish protein concentrate are sold under the trade name Seacure and made available by Proper Nutrition, Inc., Reading, Pa.

Probiotics such as are made available in various strains and custom blends by Nebraska Cultures and other providers. These beneficial intestinal bacteria assist in the digestion and absorption of food. the selected blend used in Foreverwell Foundation formula includes the DDS-1 strain of acidophilus, Lactobacilus bulgaricus, Bifido bacterium, and Enterococcus fascium.

The DDS-1 strain of the acidophilus is described in product sheets and is available from Nebraska Cultures, Walnut Creek, Calif. L. bulgaricus is also available from Nebraska Cultures, as is bifidobacterium bifidum and enterococcus faecium. The last species is also sourced in U.S. Pat. No. 5,589,168, granted Dec. 31, 1996 to Allen et al, titled "PROBIOTIC.".

        COMPOSITION                      AMOUNT PER CAPSULE
        Malic Acid                              70 mg
        Silybum marianum                        15 mg
        N-Acetyl-L-cysteine1               40 mg
        Copper chelate                           1 mg
        Zinc gluconate                           5 mg
        Magnesium aspartate                     10 mg
        Proanthocyanidins2                 10 mg
        Manganese glycerolphosphate              1 mg
        B1 thiamine mononitrate                  5 mg
        B2 -Riboflavin                           5 mg
        Inositol (hexahydroxycyclohexane)             5 mg
        Beet root powder                        10 mg
        Watercress                               5 mg
        Celery                                   5 mg
        Dandelion                                5 mg
        Capsicum                                 5 mg
        Artichoke Extract                      100 mg
        SOD (superoxide dismutase)3            250 mcg
        Pyridoxal 5 Phosphate (B6)              25 mg
        Agaricus Blazei                         75 mg
        Bromelain                              100 mg
        TOTAL                                  498 mg
    1 Acetyl derivative of L-cysteine, an amino acid. Osilated as the HCl
     salt preparation per Monograph 2787, Merck Index, Eleventh Ed. (1989).
    2 An analog of cyandin chloride, a substituted benzyopyrylium
     preparation and properties Monograph 2694, Merck Index, 11th Edition
    3 Superoxide dismutase extracts of ox erythroctes are disclosed in the
     scientific literature. French patent application Ser. No. 73.13670, filed
     April 16, 1973, describes superoxide dismutase extracts from marine
     bacteria strains, as well as a process for their preparation, which
     process does not form any part of the present invention.

The other ingredients are readily available from various suppliers of natural supplement components. Proanthocyanidins are an antioxidant component of grape seed. Capsicum is cayenne pepper, and Agaricus Blazei is a mushroom. Bromelain is a digestive enzyme derived naturally from pineapple, and which is commercially available from makers of nutritional supplements.

The several components of the Renew Formula (Working Example II) recite the optimal number of elements blended for a unit dosage, such as per capsule. Still, the essential components are malic acid, silybum marianum, the L-cysteine derivative, magnesium aspartate, copper chelate, and zinc gluconate (Cu/Zn ratio of 1:5). The other minor concentration elements are useful adjuncts for optimal effectiveness, but they are not essential to an effective unit dosage. For the Foundation Formula (R), unit dosages, both the bioactive pepides and probiotics are needed for their efficacy.

Claim 1 of 8 Claims

What is claimed is:

1. A first pharmaceutical composition, in unit dosage form which comprises a major percent by weight of bioactive peptides consisting essentially of fish protein concentrate and a minor percent by weight of probiotics selected from the group consisting of DDS-1 strain of Lactobacillus acidophilus, Lactobacillus bulgaricus, Bifidobacterium bifidum and Enterococcus faecium.

If you want to learn more about this patent, please go directly to the U.S. Patent and Trademark Office Web site to access the full patent.



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