ALPHA LIPOIC ACID, EPIGALLOCATECHIN 3-GALLATE, AND CURCUMIN AS A MEDICAMENT FOR THE TREATMENT OF ARTHRITIS AND SARS-COV-2

Abstract

Solubilized Alpha Lipoic Acid, solubilized Epigallocatechin 3-gallate, and solubilized Curcumin in combination as therapeutic agent(s) for the prophylaxis and/or treatment of arthritis including, without limitation, fibrotic disease, inflammatory disease, neurodegenerative disease, autoimmune disease, or heart and vascular disease as a consequence of arthritic pathophysiology, and viral infections including SARS-CoV-2 infections. There is also described the use of the solubilized therapeutic agent(s) for oral administration, and for inhalative administration.

Claims

1. A therapeutic composition, comprising: solubilized Alpha Lipoic Acid, solubilized Epigallocatechin 3-gallate, and solubilized Curcumin in combination, as a therapeutic medicament for use in the treatment of arthritis.

2. A therapeutic composition, comprising: solubilized Alpha Lipoic Acid, solubilized Epigallocatechin 3-gallate, and solubilized Curcumin in combination, as a therapeutic medicament for use in the treatment of SARS-CoV-2 infection.

3. A pharmaceutical product, comprising a combination of solubilized Alpha Lipoic Acid, solubilized Epigallocatechin 3-gallate, and solubilized Curcumin in a therapeutically effective amount, and a pharmaceutically acceptable carrier, N-(2-Hydroxyethyl)hexadecanamide as excipient, and/or diluents for use in the treatment of arthritis or for use in the treatment of SARS-CoV-2 infection.

4. The pharmaceutical product according to claim 3, which comprises solubilized Alpha Lipoic Acid, solubilized Epigallocatechin 3-gallate, and solubilized Curcumin in combination, a pharmaceutically acceptable carrier, N-(2-Hydroxyethyl)hexadecanamide as excipient, and/or diluents for use in the treatment of at least one disease or disorder selected from the group consisting of an autoimmune disease, a fibrotic disease, an inflammatory disease, and a neurodegenerative disease, with arthritic involvement.

5. The composition according to claim 1, which comprises solubilized Alpha Lipoic Acid, solubilized Epigallocatechin 3-gallate, and solubilized Curcumin in combination, for use in the treatment of at least one disease or disorder selected from the group consisting of an autoimmune disease, a fibrotic disease, an inflammatory disease, and a neurodegenerative disease, with arthritic involvement.

6. The pharmaceutical product according to claim 3, which comprises solubilized Alpha Lipoic Acid, solubilized Epigallocatechin 3-gallate, and solubilized Curcumin in combination, a pharmaceutically acceptable carrier, N-(2-Hydroxyethyl)hexadecanamide as excipient, and/or diluents for use in the treatment of rheumatoid arthritis, arthrosis, osteoarthritis, gout, or systemic lupus erythematodus.

7. The composition according to claim 1, which comprises solubilized Alpha Lipoic Acid, solubilized Epigallocatechin 3-gallate, in combination, for use in the treatment of rheumatoid arthritis, arthrosis, osteoarthritis, gout, or systemic lupus erythematodus.

8. The composition according to claim 1, which comprises solubilized Alpha Lipoic Acid, solubilized Epigallocatechin 3-gallate, and solubilized Curcumin in combination for use in the treatment of at least one symptom of arthritis selected from the group consisting of pain, walking-induced pain, and physical exercise-induced pain.

9. The composition according to claim 1, which comprises solubilized Alpha Lipoic Acid, solubilized Epigallocatechin 3-gallate, and solubilized Curcumin in combination for use in the treatment of arthritis to achieve alleviation of pain, pain-free walking, or pain-free physical exercise.

10. The composition according to claim 1 in a pharmaceutical product for use in oral treatment.

11. The composition according to claim 1 in a pharmaceutical product for use in an inhalation treatment.

12. The composition according to claim 2 in a pharmaceutical product for use in oral treatment.

13. The composition according to claim 2 in a pharmaceutical product for use in an inhalation treatment.

Description

BRIEF DESCRIPTION OF THE DRAWING

[0148] FIG. 1 is a flowchart illustrating a virus inhibition assay pertaining to the following Example 5.

[0149] FIG. 2 shows blotter results of two different experiments with solubilized products of Examples 2 and 3.

EXAMPLE 5

[0150] SARS-CoV-2 Inhibition Assay

[0151] The virus strain SARS-CoV-2 was isolated from a male patient and amplified in Vero cells.

[0152] B4. Viral titers were determined by an endpoint titration assay.

[0153] FIG. 1 shows a flowchart of a Virus Inhibition Assay. As shown in FIG. 1, for Western Blot analysis, Vero B4 cells were infected with SARS-CoV-2 (multiplicity of infection=0.02) for 1 h, washed and further treated with solubilized drug sample interventions. 72 hours post infection, virus-containing cell culture supernatants were harvested and released virions were purified through 20% (w/v) sucrose cushion.

[0154] Vero B4 cells were maintained in DMEM containing 10% FCS, 2 mM L-glutamine, 100 U/mL penicillin, and 100 μg/mL streptomycin. Confluent monolayers of Vero B4 cells were infected in FCS free DMEM with SARS-CoV-2.

[0155] 72 hours post infection, cells were lysed in radio immunoprecipitation assay buffer (150 mM NaCl, 50 mM Tris-HCl pH 8.0, 1% NP-40, 0.5% Na-deoxycholate, 0.1% SDS, 10 mM EDTA, 5 mM NEM, and 1 mM PMSF and further used for Western Blot analysis.

[0156] SDS-PAGE and Western Blotting

[0157] Protein samples were separated by SDS-PAGE, transferred onto nitrocellulose membranes, blocked with 3% BSA and incubated with the appropriate primary antibody. Viral proteins were detected by antibodies derived from convalescent SARS-CoV-2 patient sera. The anti-human secondary antibody coupled to horseradish peroxidase was obtained from Dianova, Hamburg, Germany.

[0158] As shown in FIG. 2, in two different experiments (Exp. 1 and Exp. 2), the solubilized products of the Example 2 (solubilized Alpha Lipoic Acid), and of the Example 3 (solubilized Curcumin) strongly inhibited SARS-CoV-2 nucleoprotein production at physiological conditions of the solubilized products, and stopped the viral spread.

EXAMPLE 6

[0159] We performed a clinical observational study, including 26 patients with primary arthritis of the knee or coxarthrosis administering to each patient solubilized Alpha Lipoic Acid, Curcumin and EGCG once a day over a period of 8 weeks. The oldest subject was 90 years old, the youngest 29. The average age was 65 years. Before the start of the study, the pain intensity on the visual analog scale and the pain-free walking distance were recorded. The statistical classification was carried out for the pain intensity using the Wilcoxon test in Spss. The change in walking distance was assessed in Spss using t-test analysis.

[0160] After completing the study, a reduction in pain perception was documented in our patients cohort.

[0161] For the test parameter pain intensity, a strong decrease of Wilcoxon z-value by −3.836 was observed, the resulting effect size being 0.7523.

[0162] In the present cohort, the effect size is 0.7523>0.5, which is a strong effect in terms of the difference in pain intensity before and after the end of the observation period.

[0163] Note: Effect limits between 0.1-0.3 are considered weak; 0.3-0.5 are considered average; greater than 0.5 are considered strong effects, rated according to Cohen.

[0164] The mean, pain-free walking distance before the start of therapy was 1268.27 m, after the study period increased significantly to 2036.54 m.

[0165] The results of this study show a dramatic and statistically significant improvement of the primary arthritis of the knee or coxarthrosis after oral treatment with the solubilized combination of the invention.