Title:  Compositions and methods for treating hepatitis-C

United States Patent:  6,281,191

Appl. No.:  311497

New compositions and methods for treating patients suffering from hepatitis-C, AIDS, aberrant apoptosis which include N-acetyl-D-glucosaminyl(.beta.-1-4)-N-Acetyl-muramyl-L-ananyl-D-isoglutami ne (GMDP) of at least 98% purity and provided either alone, as an active ingredient of blastolysine, or in combination with an aminosugar such as N-acetyl-glucosamine(NAG). The high purity GMDP has a decreased amount immunogenic impurities and demonstrates cell protection as opposed to solely immunostimulatory effects, while a synergistic cell protective effect is exhibited when GMDP in combined with NAG. The new compositions modulate FasL mediated apoptosis while simultaneously stimulating TNF-.alpha. production and further selectively inhibiting TNF-.alpha. receptor p55 (TNFR1), providing a treatment for patients suffering from hepatitis-C, AIDS or aberrant apoptosis.

SUMMARY OF THE INVENTION

Accordingly, one aspect of the present invention is to provide new GMDP compositions which include GMDP at a purity range of about 98-100% and which demonstrates apoptosis modulating properties and are useful for treating patients suffering from hepatitis-c and AIDS. Applicants also propose compositions which enhance GMDP antiapoptotic activity by specifically eliminating immunogenic impurities from GMDP, thus decreasing the compounds ability to stimulate macrophages mediated cytotoxicity.

Another aspect of the present invention is to provide new compositions of GMDP in combination with N-acetylglucosamine (and other glucosamines) which combination demonstrates synergistic antiapoptotic effect and are useful for treating patients suffering from hepatitis-C and/or AIDS.

Another aspect of the present invention is provide compositions useful for treating patients suffering from hepatitis-C, which compositions indude GMDP with a purity range of about 98-100% and administered either alone or in combination with glucosamines such as N-acetylglucosamine and or provide as an active ingredient of blastolysine. The therapeutic compositions are administered in a suitable pharmaceutical formulation.

Another aspect of the present invention indudes methods of modulating both TNF-.alpha. and Fas mediated apoptosis, by inhibiting the Fas antigen killing pathway, stimulating TNF-.alpha. production while concurrently inhibiting TNFR1 receptor by administering GMDP in a purity range of about 98-100% either alone or in combination with N-acetylglucosamine or as an active ingredient of blastolysine.

Still another aspect of the present invention includes methods of protecting a wide variety of mammalian cells including, human hepatocytes, insulin producing cells, and CD4+ lymphocytes from Fas ligand mediated cell lysis by administering GMDP either alone or in combination with N-acetylglucosamine and or provided as an active ingredient of blastolysine.

While another aspect of the present invention includes methods for enhancing GMDP antiapoptotic activity by specific eliminating of its immunogenic impurities, thus decreasing its ability to stimulate macrophages mediated cytotoxicity. And additionally, to increase the antiapoptotic activity even further by taking advantage of the newly discovered synergistic effect when GMDP is combined with N-acetylglucosamine which greatly increases the compositions antiapoptotic properties.

Another aspect of this invention is to provide a novel Fas Antigen treatment comprising administrating an effective dose of GMDP. Prevention of the cytotoxicity is achieved by exploiting the newly discovered phenomena--inhibition of binding Fas ligands Fas receptor by probiotic D-peptidoglycans, wherein the active component is GMDP, which effectively inhibits the Fas antigen killing pathways while concurrently upregulating Fas ligand on CD8+ lymphocytes.

Another aspect of this invention comprises vaginal and/or oral administration of the probiotic blastolysine, wherein the active component is GMDP, to prevent and reduce apoptosis of bystander cells (hepatocytes, and CD4+ lymphocytes) during active hepatitis-C, and HIV infection. This effect is crucial for stimulation of protective apoptosis which prevents healthy liver cells from complete destruction during viral infection. It is also the strong inhibition of Fas Ag killing pathways with concurrent modulation of TNF-.alpha., which physiologically contributes to prevention of the liver necrosis.

In another aspect the invention comprises the administration either orally or vaginally GMDP as a Fas inhibitor, which prevents and treats the apoptosis stimulating effect of hepatitis-C virus, HIV, and Fas Ag bearing CD8+ lymphocytes.

Another aspect of the present invention indudes the prevention and treatment of liver allograft rejection.

While another aspect of the invention includes methods of enhancing GMDP cytoprotective activity by eliminating of its immunogenic impurities and increasing its purity concentration to at least 98%. In addition, the invention relates to methods for enhancing cytoprotective composition of GMDP which comprises administration to the patient an effective amount of GMDP and aminosugars. Cytoprotective synergism is achieved by composing about 50mg/kg of body weight of N-acetyl-glucosamine, D-glucosamine, N-acetyl-galactosamine, and or mannose and non cytotoxic composition of GMDP.

Oral, vaginal, and/or rectal formulations are preferred. Above mentioned aminosugars may be present as the carriers. A daily GMDP dosage in the range of from 5mg to 80mg may be found to be acceptable, with optimal range of 10-30mg per day.

Claim 1 of 4 Claims

We claim:

1. A method for treating Hepatitis C in a patient having a detectable hepatitis C viral load, by administering blastolysin which contains GMDP as an active ingredient in a dosage range of about 0.1-1,5 mg/kg of body weight.

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