Halogenated aliphatic carboxylic acids, oligomers and/or polymers thereof and their use in devitalizing external and internal neoplasms

Abstract

Halogenated aliphatic carboxylic acids, salts and / or oligomers or polymers thereof, which exhibit a devitalizing effect of neoplastic tissues, are disclosed. Methods and uses that utilize these compounds for the treatment of medical conditions associated with a neoplastic tissue are also disclosed. Further disclosed are methods and uses that utilize these compounds for reducing or abolishing blood and lymph as well local dissemination of malignant neoplastic cells during a surgical removal thereof, thereby preventing recurrences and distance metastases, and / or inducing immune response to potentially malignant, pre-malignant and / or malignant cells. Further disclosed are novel oligomeric forms of halogenated aliphatic carboxylic acids, pharmaceutical compositions containing same and uses thereof.

Description

RELATED APPLICATIONS[0001]This application is a division of U.S. patent application Ser. No. 12 / 796,804 filed on Jun. 9, 2010, which claims the benefit of priority under 35 USC 119(e) of U.S. Provisional Patent Application No. 61 / 185,226 filed Jun. 9, 2009. The contents of the above applications are all incorporated by reference as if fully set forth herein in their entirety.FIELD AND BACKGROUND OF THE INVENTION[0002]The present invention, in some embodiments thereof, relates to compounds, compositions and methods for treating disorders associated with pathological hyperplasia, metaplasia, dysplasia and neoplasia (oncoplasia) tissues, such as, for example, skin and visible mucosal tumors and lesions and internal neoplasms.[0003]Neoplasia is a general term used to describe abnormal proliferation of cells (such as malignant neoplasia). This abnormal proliferation may be a result of many disorders (such as a viral infection or cancerogenesis) and usually causes a lump or tumor. Neoplas...

AI Technical Summary

Benefits of technology

[0036]The present inventors have further uncovered that an oligomer of DPA, a tetramer in particular, is highly efficient in devitalization of all types of neoplastic cells, including malignant cells, a feature that allows performing, subsequent to, prior to or concomitant with the DPA treatment, a surgical procedure to remove the neoplastic tissue, while reducing and even abolishing dissemination of the malignant cells into blood and lymph vessels and thus avoiding distant metastases which may be fatal.

[0037]The present inventors have further uncovered that DPA, including salts and oligomers thereof, is capable of inducing systemic immunity and hence can be efficiently utilized in, for example, reducing or preventing appearance or re-appearance of malignant cells, in cases where these are likely to occur.

Problems solved by technology

It is believed that the interpretation of these signals ultimately influences the growth and differentiation of a cell, and that misinterpretation of these signals can result in neoplastic growth (neoplasia).

The efficacy of chemotherapy is often limited by severe side effects, including nausea and vomiting, bone marrow depression, renal damage and central nervous system depression.

Radiotherapy, however, is limited by possible sensitivity of the tissue surrounding the tumor and further by development of resistance thereto.

However, during the surgical manipulation, dissemination of malignant tumor cells into the blood and lymph vessels may occur, resulting in metastasis to other body locations and postoperative recurrence resulting in a poor prognosis.

Malignant melanoma, which occurs in the melanocytes, is less common than squamous or basal cell carcinoma but is much more dangerous.

The aggressiveness nature of the surgical techniques (as compared to non-surgical procedures) may lead, in some cases, to severe disfigurement due to bony involvement, loss of vision (in cases of tumors located near the eyes) and even death.

Surgical treatment is particularly problematic in treating skin tumors located near the eyes or in the nose region as well as in treating patients suffering from multiple tumors and reoccurrences.

Furthermore, surgical treatment is associated with complications such as bleaching, infections, ulcerations, pain, allergical and exematic reactions, healing problems as well as hypertrophic, kelloidal and painful scars.

Because this therapy is expensive and requires frequent visits over several weeks, it is often not an option for elderly patients with a limited support system.

Long term cosmetic results may be poor and the complications of tissue necrosis, chondritis and osteoradionecrosis may occur.

Another drawback is the risk of a radiation-induced malignant growth that may occur later, thus radiation is generally not recommended as the primary treatment in patients younger than 50 years of age.

This therapy is currently limited by its high cost and by persistent skin photosensitivity that lasts weeks.

Disadvantages are the lack of margin control, tissue necrosis, over or under treatment of the tumor, and long recovery time.

Topical drug therapy is limited by superficial basaliomas and actinic keratosis only, to lesions confined to the epidermis.

A 5% of 5-fluorouracil (5-FU) cream (Efudex®, Valeant Pharmaceuticals) used in conjugation with topical retinoids may deepen the therapeutic effect and minimize the risk of the disease persisting at the adnexal level but, the treatment is associated with many side effects.

A 5% preparation of Imiquimod cream (Aldara™, 3M Pharmaceuticals), an antiviral agent and as an interferon inducer, applied for 6 weeks has also been shown to eradicate superficial basal cell carcinoma in more than 80% of the cases but the use of imiquimod may be limited by its cost, drug contraindications and side effect.

Intralesional administration of interferon (Roferon-A®, Roche Pharmaceuticals) has been effective for treating basal cell carcinoma but this regimen requires multiple injections for several weeks, is expensive and is associated with flu-like symptoms.

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