FORM - 2 THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENTS RULES, 2003
PROVISIONAL
Specification
(See section 10 and rule 13)


MEDICINAL FORMULATION
SHAH RAJESH
An Indian National of Life Force Center, 415, Krushal Commercial Complex, 4th floor, Above Shopper's Stop, G.M. Road, Chembur, Mumbai-400 089, Maharashtra, India.

THE FOLLOWING SPECIFICATION PARTICULARLY DESCRIBES THE NATURE
OF THE INVENTION.


FIELD OF THE INVENTION
The present invention relates to medicinal formulations.
Particularly, the present invention relates to a novel medicinal formulation for
the treatment of autoimmune diseases.
BACKGROUND OF THE INVENTION
Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body really attacks its own cells. This may be restricted to certain organs or involve a particular tissue in different places.
Some common autoimmune disorders include rheumatoid arthritis, psoriasis, ankylosing spondylytis, Crohn's disease, Asthma, nephritic syndrome, vitiligo, systemic lupus erythematosus (lupus) and vasculitis.
Psoriasis is a chronic, non-contagious autoimmune disease which affects the skin and joints. It commonly causes red scaly patches to appear on the skin. The scaly patches caused by psoriasis, called psoriatic plaques, are areas of inflammation and excessive skin production. Skin rapidly accumulates at these sites and takes on a silvery-white appearance. It is a chronic inflammatory skin disease characterized by hyperplasia of the epidermis (acanthosis), infiltration of leukocytes into both the dermis and the epidermis and dilatation and growth of blood vessels. Acanthosis is the result of increased proliferation and aberrant differentiation of keratinocytes.
Cytokines are signaling peptides (proteins) and they work as specialized chemical mediators. They play an important role in innate and adaptive immunity. Cytokines are released by many different types of cells and play a vital role for initiating and maintaining a wide range of diseases, which may be labeled as immunological, infectious, cancerous, endocrinal disorders, etc.
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It may be noted that each of the cytokines has multiple functions and effects on various organs, participating in the processes of various diseases. It is incorrect to say that they participate only in certain limited disease processes.
Those cytokines in particular which have defined role in triggering and maintaining certain diseases or disease process are focus for therapeutic measures. The conventional medicine offers blockers or inhibitors for certain types of cytokines to inhibit the disease producing action. For example, TNF-blockers are used for the treatment of Psoriasis and Rheumatoid arthritis. Similarly, IFN- y inhibitors are used for Crohn's disease and likewise. Such anti-mode of therapy has been found to have desired effects as well as undesired adverse effects.
l.TNF
Tumor necrosis factor (TNF) (also called as Tumor necrosis factor-alpha, denoted as TNF-a) is an important cytokine and is a key regulator of the inflammatory response, involved in regulation of immune processes, which in turn leads to a wide range of processes such as inflammation, cellular proliferation, differentiation, replication of virus, tumorogenesis, etc.
TNF is one of the proinflammaotry cytokines, others being INF-gamma, IL-6, IL-8 and IL-12. TNF induced processes lead to a range of patho-physiological situations which are found in a variety of immunologially mediated disorders such as Psoriasis, Rheumatoid Arthritis, Psoriatic arthritis, Ankylosing spondylitis, Crohn's disease, Asthma, and other chronic inflammatory events.
2. IL-8 (Interleukin 8)
IL-8 is an important pro-inflammatory cytokine, especially for psoriasis. Studies have shown the increased presence of IL-8 in the cases of psoriasis. IL-8 inhibitors have shown significant response in the treatment of psoriasis. Similarly, involvement of IL-8 has been reported in a range of chronic inflammatory diseases such as asthma, arthritis, irritable bowl syndrome (IBS)
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and other chronic inflammatory reactions. Studies have shown that there is an increased expression of epidermal IL-8 receptor in cases of psoriasis and blocking of IL-8 using IL-8 antagonists has shown improvement in lesions.
3. IFN-y: (Interferon gamma)
IFN-y is involved in the regulation of the immune and inflammatory responses in humans. It is produced by activated T-cells and natural killer cells. IFN-y is involved in the immunopathogenesis of various diseases which include Psoriasis, vitiligo, Crohn's disease, Ulcerative colitis, IBS, etc,
IFN-y released by Thl cells recruit leukocytes to the site of infection, resulting in increased inflammation. It also stimulates macrophages to kill bacteria that have been engulfed. IFN-y released by Thl cells is also important in regulating the Th2 response. Further, IFN-y has some anti-viral and anti-tumor effects, but these are generally weak. However, this cytokine potentiates the effects of the type I IFNs. As IFN-y is vitally implicated in the regulation of immune response, its production can lead to autoimmune disorders.
4. IL-20
Interleukin 20 (IL-20) is another important cytokine having action and involvement in multiple pathophysiological processes, one of them being Psoriasis. Some studies have indicated that overexpression of IL-20 is correlated with keratinocyte proliferation that acts through their receptor complex expressed by keratinocytes themselves. Furthermore, IL-20 can stimulate CD8-positive lymphocytes to produce Keratinocyte Growth Factor (KGF), which may contribute to sustaining the hyperproliferative status of the keratinocytes observed in Psoriasis.
A study by Frank Wang et al. published in the Journal of Investigative Dermatology (2006) 126, 1590-1599 indicated that IL-20 may be an important effector cytokine in psoriasis and its inhibition may represent a potential therapeutic target.
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IL20 is a cytokine structurally related to interleukin 10 (IL10). IL20 cytokine has been shown to transduce its signal through Signal Transducer and Activator of Transcription 3 (STAT3) in keratinocytes. A specific receptor for this cytokine is found to be expressed in skin and upregulated dramatically in psoriatic skin, suggesting a role of this protein in epidermal function and psoriasis.
Another study by Wei CC et al. published in Clin Immunol. 2005 Oct; 117(l):65-72 investigated the expression of interleukin-20 (IL-20) and its receptors on psoriatic skin by immunohistochemical analysis. Overexpression of IL-20 and its receptors was detected in the keratinocytes of the lesional skin of psoriasis and spongiotic dermatitis. The expression pattern of IL-20 spreads throughout the whole layer of epidermis, while IL-19 was expressed in up to three or four layers suprabasally. The serum level of IL-20 in psoriatic patients was significantly lower than that in healthy controls.
5. IL-17
IL17 is a proinflammatory cytokine produced by activated T cells. IL-17 regulates the activities of NF-kappaB and mitogen-activated protein kinases. Interleukin-17 can stimulate the expression of IL6 and cyclooxygenase-2 (PTGS2/COX-2), as well as enhance the production of nitric oxide (NO). High levels of IL-17 are associated with several chronic inflammatory diseases including rheumatoid arthritis, psoriasis and multiple sclerosis. IL-17 plays a significant role in the development of psoriatic lesions. The enhanced expression of both IL-23 and IL-17 within psoriatic lesions indicates that the IL-23/IL-17 cytokine axis is fully operational in the inflamed skin. (Astrid J van Beelen et al.)
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6. IL-23
Interleukin 23 (IL-23) is yet another important cytokine involved in the pathophysiology of psoriasis. IL-23 blockers have been used for the treatment of psoriasis which reconfirms its role in psoriasis.
7. STAT3 (Signal Transducer and Activator of Transcription 3)
STAT3 belong to a class of proteins called transcription factors, potent proteins that can set off a cascade of events by simultaneously activating many genes. In the case of STAT3, activation leads to the production of growth-promoting and cell survival proteins. Activated STAT3 is essential in normal skin to promote wound healing. When the healing process is complete, normal STAT3 returns to its inactive form. But when it fails to turn off, the wound healing process continues and skin cells proliferate.
A study published in Nature Medicine Journal, January 2005 describes that a protein called STAT3 is a crucial initiator of psoriasis.
In accordance with the present invention it is envisaged that the potentised cytokines should be able to produce or initiate effects contrary to the direct effects of the respective cytokines or STAT3 protein. In other words, there is a possibility that the potentised cytokines may induce antibodies in human body which may work against the respective cytokines and their activities; thereby reversing the disease process and leading to disease control as well as recovery.
OBJECTS OF THE INVENTION
One of the objects of the present invention is to provide a novel formulation for the treatment of psoriasis, auto-immune diseases and inflammations.
Another object is to provide a novel formulation which can be orally
administered.
Yet another object is to provide a novel formulation which contains precisely defined antigenic material.
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Yet another object is to provide a novel formulation which has a curative effect rather than symptomatic.
Yet another objective is to provide a novel formulation which has better therapeutic efficacy.
Yet another object is to provide a novel formulation which is administered in low dose.
Yet another object is to provide a novel formulation without side effects.
Yet another object is to provide a novel formulation which is easy to manufacture.
SUMMARY OF THE INVENTION
In accordance with the present invention, there is provided a medicinal formulation for the treatment of autoimmune diseases, said formulation comprising at least one serially diluted and potentised ingredient selected from a group consisting of TNF- alpha, IFN- y, IL-8, IL17, IL-20, IL 23 and STAT
3.
Typically, the vehicle used for serial dilution is selected from a group consisting of distilled water, ethyl alcohol and mixture thereof.
Typically, the potentization is effected by stroking.
Typically, the stroking is achieved by holding a bottle containing the diluted ingredient in a closed fist and striking the fist on a hard surface repeatedly at a regular frequency or by exercising similar powerful stroke using a mechanical device which can strike a bottle on a hard surface.
Typically the serial dilution is in the range of lc to 1 million c.
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Typically, the formulation prepared in accordance with the present invention is used in the treatment of psoriasis, rheumatoid arthritis, Crohn's disease, asthma and inflammations.
In accordance with another aspect of the present invention, there is provided a process for making a medicinal formulation, said process comprising the following steps:
i. obtaining predetermined quantity of at least one ingredient selected from a group consisting of TNF- alpha, IFN- y, IL-8, IL 17, IL-20, IL 23 and STAT 3;
ii. mixing the ingredients obtained in step (i) in a ratio of about 1:1 to about 1:10;
iii. diluting the mixture obtained in step (ii) with appropriate amount of vehicle to obtain a primary dilution of 1 c potency; and
iv. serially diluting with potentization, the primary dilution of lc potency in step (iii) with the vehicle in a ratio of original dilution to vehicle in the range of 1:1 to 1:99 to obtain diluted and potentized formulation of lc to 1 million c and more.
ANECDOTAL STUDIES:
1. A 40 year old female patient was presented with psoriasis. Initially she was prescribed Natrum Mur 200 (a conventional homeopathic medicine) which did not show any remission. She was then prescribed a formulation prepared in accordance with the present invention (TNF-a-lOc) which brought in significant improvement in her psoriatic lesions by about 40% in six weeks. Subsequently, she was treated with increased potency of the present formulation (TNF-a-15c and 30c). Excellent results were seen and there was 60 % reduction in the lesion.
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2. A 54 year old male patient was presented with acute cellulitis with severe inflammation, redness, swelling and pain with impending boil. The patient was prescribed TNF-a-30c, four times a day. After one day of treatment, the pain was relieved and swelling was subsided in two days of treatment.
3. A 45 year old male patient was approached with psoriasis on palms and soles. He was prescribed TNF-a-30c, three times a day for a month. The treatment was continued for four months. During 4 month of continuation with TNF-a-30c, the patient improved and showed significant recovery.
4. A 10 year old boy suffering from psoriasis was presented with mild to moderate lesions on various places of the body. He was prescribed TNF-a-50c potency. He responded quickly and significantly.
5. A 43 year female was presented with severe lesions of oral Lichen Planus. She was prescribed TNF-a-30c for 10 days. After 10 days of treatment, she improved by over 90%.
While considerable emphasis has been placed herein on the specific ingredients of the preferred formulation, it will be appreciated that many additional ingredients can be added and that many changes can be made in the preferred formulation without departing from the principles of the invention. These and other changes in the preferred formulation of the invention will be apparent to those skilled in the art from the disclosure herein, whereby it is to-be distinctly
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understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the invention and not as a limitation.