Compositions for Improved Neuroprotective Effects and Methods of Making Same

Abstract

A micro-nutrient composition for a human subject suffering from a glaucomatous disease, wherein the micro-nutrient composition comprises a formulation for reversing mitochondrial dysfunction in glaucomatous disease. Formulations for improving outcomes based on resolving conditions at the cellular response level in certain individuals suffering from particular diseases. More particularly, the invention relates to compositions affecting the eye, such as glaucoma.

Claims

1. A micro-nutrient formulation for a human subject suffering from a disease, the formulation comprising: a) curcumin; b) Gingko biloba extract; c) citicoline; d) coenzyme Q10; e) N-acetyl-cysteine; f) alpha-lipoic acid; g) grape see extract; and h) green tea extract.

2. The formulation of claim 1 wherein the formulation is further comprised of biotin, L-taurine powder, niacinamide powder, nicotinamide adenine dinucleotide, dragon berry, bitter blocker 10002185, and citric acid powder.

3. The formulation of claim 2 wherein the formulation is further comprised of fisetin, quercetin, luteolin and sucralose.

4. The formulation of claim 2 wherein the formulation is further comprised of astaxanthin and flavonoid complex.

5. The formulation of claim 3 wherein the formulation is further optionally comprised of one or more of monk fruit, silica dioxide, soluble corn fiber and L-leucine.

6. The formulation of claim 4 wherein the formulation is further optionally comprised of one or more of monk fruit, silica dioxide, soluble corn fiber and L-leucine. The formulation of claim 3 wherein the formulation in a soluble powder form.

8. The formulation of claim 4 wherein the formulation in a soluble powder form.

9. The formulation of claim 3 wherein the disease is a neurodegenerative disease.

10. The formulation of claim 9 wherein the disease is glaucoma.

11. The formulation of claim 4 wherein the disease is a neurodegenerative disease.

12. The formulation of claim 11 wherein the disease is glaucoma.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0013] Mitochondrial dysfunction and death are increasingly implicated in retinal ganglion cell death in glaucoma and neuronal death in other neurodegenerative disorders. Mitochondria become dysfunctional and die prior to neuronal cell death.

[0014] Formulations with IOP-independent neuroprotective effects could be additive in slowing progression rates by reversing mitochondrial dysfunction. Furthermore, stabilizing mitochondria could shift the treatment paradigm to an earlier stage of disease (prior to retinal ganglion cell death) which would greatly improve therapeutic outcomes.

[0015] The following examples are intended to illustrate the invention by way of example only, and are not intended to limit the scope of the invention.

EXAMPLE 1

Randomized, Double-Blind, Placebo Control Trial on the Efficacy of a Novel Neuroprotective Combination in Glaucoma

[0016] A proprietary formulation was developed, which combined a cocktail of mitochondrial protectants with specific antioxidants to arrive at the final micro-nutrient composition for use in the treatment of glaucoma patients. The proprietary formulation comprised curcumin, Ginkgo biloba extract, citicoline, coenzyme Q10, N-acetyl-cysteine, alpha-lipoic acid, grape seed extract and green tea extract. A representative list of ingredients that make up the final micro-nutrient compositions as tested can be found below at Table 1.

TABLE-US-00001 TABLE 1 Micro-nutrient ingredient listing Weight range Component (mgs) Curcumin/curcuminoids 400-600 N-acetyl cysteine powder 300-500 Ginkgo biloba powder 60-180 R-lipoic acid (sodium salt) 80% 50-150 Citicoline 50-150 Grape seed extract powder (95%) 50-150 Green tea extract (98%) 50-150 Biotin (water soluble) 1% 10-30 L-taurine powder 400-600 Niacinamide powder (USP) 200-300 Fisetin 25-75 Quercetin (95%) 50-150 Luteolin 50-150 Nicotinamide adenine dinucleotide 5-15 Coenzyme Q10 50-150 Dragon berry 300-500 Bitter blocker 10002185 200-400 Citric acid powder (USP) 400-800 Sucralose 100-200

[0017] To test the efficacy of this formulation, a trial was conducted on 14 patients (28 total eyes). The patients were randomized into two groups: Group I was given placebo and Group II was given the proprietary formulation.

[0018] Patients were tested with visual fields (VF), optical coherence tomography (OCT) and retinal metabolic analysis (RMA) at baseline, 1 month and 3 months post-randomization. RMA measures adjusted mitochondrial flavoprotein fluorescence (aFPF) and its average curve width (ACW), which are markers of mitochondrial oxidative stress. Hierarchical mixed effects linear models were tested for changes in VF, OCT and RMA indices over time.

[0019] As shown below at Table 2, the clinical characteristics of the treatment versus placebo groups are identified. None of the variables differed significantly between groups (P>5%).

TABLE-US-00002 TABLE 2 Demographic and clinical characteristics of the study sample Study Criteria Placebo Formulation Categorical n % n % Gender (F) 4 57 5 71 Migraine 1 14 1 14 Sleep apnea 4 57 3 42 Raynaud's 1 14 2 28 Adverse events 1 14 1 14 Continuous Median IQR Median IQR IOP (mmHg) 17.75 6.00 13.50 7.00 CDR .70 .40 .70 .30 OCTmacH (microns) 75.50 22.00 69.75 25.25 OCTdisc (microns) 68.00 11.00 76.50 28.00 MD (dB) 3.07 4.29 1.41 3.25 PSD (dB) 4.42 5.67 3.44 3.23 VFI (%) 93.50 15.00 96.50 8.00 Fovea (dB) 34.00 3.50 33.50 2.50 HbA1C 5.70 .30 5.50 .40 LogMAR1 .02 .12 .02 .04 Ocular meds 1.00 2.00 3.00 3.00

[0020] During follow-up, there were no significant changes in VF (MD, PSD) or OCT (macular RGC) indices over time in either group (all P>5%). A significant decrease was shown in optic nerve aFPF and ACW from baseline to 1 month in the treatment group (=39, P=0.003 and =25, P=0.01, respectively) but not in patients treated with placebo (P=0.47 and 0.23) (Tables 3 and 4).

TABLE-US-00003 TABLE 3 Results of mixed effects linear models testing the relationship between RMA parameters and change between baseline and follow-up visit in treatment group Parameter 95% Confidence Interval P-value Optic disc aFPF 39.78 66.30 13.26 .003 Optic disc ACW 25.07 44.20 5.93 .010

TABLE-US-00004 TABLE 4 Results of mixed effects linear models testing the relationship between RMA parameters and change between baseline and follow-up visit in placebo group Parameter 95% Confidence Interval P-value Optic disc aFPF 15.54 57.75 26.66 .470 Optic disc ACW 11.90 31.57 7.75 .235

[0021] The results surprisingly showed that this proprietary formulation provided neuroprotective benefits to the tested class of patients. The above data evidence a reversal of mitochondrial dysfunction and should serve as a viable therapy for glaucoma patients.

[0022] An alternative embodiment to the above described, representative list of ingredients that make up the final micro-nutrient compositions of the present invention may also be in the following form described at Table 5:

TABLE-US-00005 TABLE 5 Alternative embodiment of micro-nutrient ingredient listing Weight range Component (mgs) Curcumin/curcuminoids 400-600 N-acetyl cysteine powder 300-500 Ginkgo biloba powder 60-180 R-lipoic acid (sodium salt) 80% 50-150 Citicoline 50-150 Grape seed extract powder (95%) 50-150 Green tea extract (98%) 50-150 Biotin (water soluble) 1% 15-15 L-taurine powder 400-600 Niacinamide powder (USP) 200-300 Nicotinamide adenine dinucleotide 5-15 Coenzyme Q10 50-150 Dragon berry 300-500 Bitter blocker 10002185 200-400 Citric acid powder (USP) 400-800 Astaxanthin 1-10 Flavonoid Complex 200-300

[0023] In addition to the components mentioned supra, the alternative embodiment of the micro-nutrient composition may also, optionally, include one or more of the following: monk fruit, silica dioxide, soluble corn fiber and L-leucine. Preferably, the alternative embodiment of the micro-nutrient composition is formulated in a soluble powder form.

[0024] It will be appreciated that details of the foregoing embodiments, given for purposes of illustration, are not to be construed as limiting the scope of this invention. Although several embodiments of this invention have been described in detail above, those skilled in the art will readily appreciate that many modifications are possible in the exemplary embodiments without materially departing from the novel teachings and advantages of this invention. Accordingly, all such modifications are intended to be included within the scope of this invention, which is defined in the following claims and all equivalents thereto. Further, it is recognized that many embodiments may be conceived that do not achieve all of the advantages of some embodiments, particularly of the preferred embodiments, yet the absence of a particular advantage shall not be construed to necessarily mean that such an embodiment is outside the scope of the present invention.