AU2009101279A4 - Medicinal formulation containing selected cytokines - Google Patents

Medicinal formulation containing selected cytokines Download PDF

Info

Publication number
AU2009101279A4
AU2009101279A4 AU2009101279A AU2009101279A AU2009101279A4 AU 2009101279 A4 AU2009101279 A4 AU 2009101279A4 AU 2009101279 A AU2009101279 A AU 2009101279A AU 2009101279 A AU2009101279 A AU 2009101279A AU 2009101279 A4 AU2009101279 A4 AU 2009101279A4
Authority
AU
Australia
Prior art keywords
formulation
vehicle
dilution
psoriasis
tnf
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
AU2009101279A
Inventor
Shah Rajesh
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Application granted granted Critical
Publication of AU2009101279A4 publication Critical patent/AU2009101279A4/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/20Interleukins [IL]
    • A61K38/2053IL-8
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1703Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • A61K38/1709Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/191Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/20Interleukins [IL]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/21Interferons [IFN]
    • A61K38/217IFN-gamma
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0004Homeopathy; Vitalisation; Resonance; Dynamisation, e.g. esoteric applications; Oxygenation of blood
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Marine Sciences & Fisheries (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Hematology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Description

AUSTRALIA Patents Act 1990 COMPLETE SPECIFICATION INNOVATION PATENT Medicinal Formulation Containing Selected Cytokines The following statement is a full description of this invention, including the best method of performing it known to me.
TITLE MEDICINAL FORMULATION CONTAINING SELECTED CYTOKINES 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. Types of psoriasis: Plaque psoriasis: Plaque psoriasis typically appears as raised areas of inflamed skin covered with silvery white scaly skin. These areas are called plaques. Flexural psoriasis: It appears as smooth inflamed patches of skin. It occurs in the skin folds, particularly around the genitals (between the thigh and groin), the armpits, under an overweight stomach (pannus), and under the breasts. Guttate psoriasis: It is characterized by numerous small round spots appearing over large areas of the body, such as the trunk, limbs and scalp. Pustular psoriasis: It appears as raised bumps that are filled with non infectious pus (pustules). The skin under and surrounding the pustules is red and tender. Pustular psoriasis can be localised, commonly to the hands and feet (palmoplantar pustulosis), or generalised with widespread patches occurring randomly on any part of the body. Psoriatic arthritis: It involves joint and connective tissue inflammation. Psoriatic arthritis can affect any joint but is most common in the joints of the fingers and toes. This can result in a sausage-shaped swelling of the fingers and toes known as dactylitis. Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks the joints producing an inflammatory synovitis that often progresses to destruction of the articular cartilage and ankylosis of the joints. Rheumatoid arthritis can also produce diffuse inflammation in the lungs, pericardium, pleura, and sclera, and also nodular lesions, most common in subcutaneous tissue under the skin. Although 2 the cause of rheumatoid arthritis is unknown, autoimmunity plays a pivotal role in its chronicity and progression. Rheumatoid arthritis involves abnormal B cell - T cell interaction, with presentation of antigens by B cells to T cells via HLA-DR eliciting T cell help and consequent production of RF and ACPA. Inflammation is then driven either by B cell or T cell products stimulating release of TNF and other cytokines. Although TNF appears to be the dominant, other cytokines (chemical mediators) are likely to be involved in inflammation in RA. Blockade of TNF does not benefit all patients or all tissues. Blockade of IL-1, IL-15 and IL-6 also have beneficial effects and IL- 17 may be important. Ankylosing spondylitis is a chronic inflammatory arthritis. It affects joints in the spine and the sacroilium in the pelvis, causing eventual fusion of the spine. TNFa blockers (antagonists) such as etanercept, infliximab and adalimumab are effective immunosuppressants and indicated for the treatment of spondylitis. TNFa blockers have been shown to be the most promising treatment, slowing the progress of AS in the majority of clinical cases. They have also been shown to be highly effective in treating not only the arthritis of the joints but also the spinal arthritis associated with AS. A drawback is that these drugs increase the risk of infections. Vitiligo is a chronic relatively common dermatologic disorder that causes depigmentation of skin patches. It occurs when the melanocytes, the cells responsible for skin pigmentation, die or are unable to function. Vitiligo is associated with autoimmune and inflammatory diseases, commonly thyroid overexpression and underexpression. 3 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 and the like. 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 effects. 1. 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. 4 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) 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. WN-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 Th1 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 Th1 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 5 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. IL20 is a cytokine structurally related to interleukin 10 (1110). 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(1):65-72 investigated the expression of interleukin-20 (IL-20) and its 6 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.) 6. IL-23 Interleukin 23 (1L-23) is yet another important cytokine involved in the pathophysiology of psoriasis. 11-23 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 7 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 the STAT3 protein is a crucial initiator of psoriasis. PRIOR ART: Various methods and formulations for the treatment of autoimmune diseases have been reported in several patents/ published patent applications. Following patents/applications disclose the treatment of autoimmune diseases. US Patent application No. 20080260730 discloses a method of treating autoimmune diseases such as Crohn's disease and psoriasis which comprises administering to a subject in need thereof, a therapeutically effective amount of humanized antibody HuZAF against interferon- gamma (IFN- y). US Patent application No. 20060134756 discloses a method of blocking, inhibiting, reducing, antagonizing or neutralizing the activity of IL-20 and IL-22 cytokines that are involved in inflammatory processes and human disease such as chronic inflammatory disease comprising inflammatory bowel disease, ulcerative colitis, Crohn's disease, arthritis, atopic dermatitis, or psoriasis by using anti-IL-20 and anti-IL-22RA antibodies. W02006037247 discloses the use of a type I interferon blocking agent, such as a type I IFN antagonist (e.g. anti-IFN-a antibody or antibody fragment) or type I 8 IFN receptor antagonist, for the preparation of a medicament for the prevention and treatment of psoriasis and a method of prevention and treatment of psoriasis using a type I interferon blocking agent. W02001054721 discloses a pharmaceutical composition comprising a cytokine antagonist [monoclonal anti-Type 1 -IFN or anti-IFN-a antibody] in combination with a pharmaceutically acceptable carrier in the form of solid dosage form for oral ingestion for the treatment of autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, multiple sclerosis and psoriasis. WO1998028001 discloses a pharmaceutical composition for treatment of autoimmune diseases selected from a group consisting of psoriasis, schizophrenia, Crohn's disease, systemic lupus erythematosus, rheumatoid arthritis, insulin-dependent diabetes mellitus and multiple sclerosis. The composition comprising an effective amount of one or more components selected from a group consisting of an antibody to gamma interferon, an antibody to gamma interferon receptor, gamma interferon receptor, an antibody to alpha interferon, an antibody to alpha interferon receptor, alpha interferon receptor, an antibody to tumor necrosis factor and a pharmaceutically acceptable carter. W02009033091 discloses methods for treating autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, Crohn's disease, bacterially induced colitis, asthma and inflammatory bowel disease using one or more inhibitor of STAT3. The inhibitor/ antagonist of STAT 3 disclosed is an antibody selected from a group consisting of anti IL23 receptor antibody and IL17 antibody. 9 The aforementioned prior art documents provide treatment of autoimmune diseases using blockers or inhibitors for certain types of cytokines to inhibit the disease producing action. Such anti-mode of therapy has been found to have desired effects as well as undesired effects. In accordance with the present invention it was found that the potentised cytokines are 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 auto-immune diseases and inflammations. Another object of the present invention is to provide a novel formulation which can be orally administered. Yet another object of the present invention is to provide a novel formulation which contains precisely defined antigenic material. Yet another object of the present invention is to provide a novel formulation which has a curative effect rather than symptomatic. Yet another objective of the present invention is to provide a novel formulation which has better therapeutic efficacy. 10 Yet another object of the present invention is to provide a novel formulation which is administered in low dose. Yet another object of the present invention is to provide a novel formulation without side effects. Yet another object of the present invention 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 formulation for the treatment of autoimmune diseases, said formulation comprising a homogenized mixture of at least one serially diluted and potentised ingredient selected from a group consisting of TNF- alpha, IFN- y, IL-8, IL17, 1L-20, IL 23 and STAT 3, said dilution being effected in a vehicle selected from a group consisting of distilled water, ethyl alcohol and mixture of distilled water and ethyl alcohol. Typically, each of the serially diluted substances is Ic dilution of the original ingredient in the vehicle, each c representing a dilution of the previous stage in the vehicle where the proportion of the substance to vehicle is in the range of 1:99 to 1:1. Typically, the serial dilution is in the range of Ic to 1 million c. In accordance with another aspect of the present invention there is provided a process for making a formulation for the treatment of autoimmune diseases, said process comprising the following steps: IIl 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 I c potency; and iv. serially diluting with potentization, the primary dilution of Ic 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 1 c to 1 million c and more. Typically, the potentization is effected 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 the bottle on a hard surface. Typically, the strokes are given about 10 times. Typically, the bottle containing the preparation for stroking for potentization is a securely stoppered glass bottle. Typically, the mechanical device is used to exert a force of at least 6 dynes rhythmically at a frequency of 10 strokes in two minutes. 12 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. DETAILED DESCRIPTION OF THE INVENTION: In accordance with the present invention, there is provided a formulation for the treatment of autoimmune diseases, said formulation comprising a homogenized mixture of 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, said dilution being effected in a vehicle selected from a group consisting of distilled water, ethyl alcohol and mixture of distilled water and ethyl alcohol. About the potency: The formulation in accordance with the present invention was prepared in a range from Ic to 10 million c, where 'c' denotes centesimal potency. Homeopathic medicines prepared from the diseased body tissues or organisms are prescribed to patients in various potencies, as per the well defined parameters of potency selection. Some of the parameters may be described in brief hereunder: 1. Age: Younger patients with higher susceptibility may be prescribed medium to high potency such as 30c to 1000c. 2. Functional pathology: Patients with functional disorders are prescribed medium to high potency. 13 3. Structural pathology: Patients with structural pathology are prescribed low potency to start with. 4. Nosode: When used as a nosode, 30c potency is the ideal. It can be stepped up slowly. 5. Response: In case there is no response or the remedy stops acting, the potency can be stepped up from 30c to 50c to 100c to 500c. 6. Active pathology: In case of active pathology such as tubercular cavities or ulcers, higher potencies should be avoided. 7. Susceptibility: Higher the susceptibility, higher the potency. 8. Newer medicines in their initial evaluation period are better prescribed in 30c potency if they are prepared from organism, venoms or any toxic source. It may be noted that homeopathic preparation in potency higher than 14c are found to have no physical traces or any molecule of the original source. In other words, all preparations after 15c are free from toxic properties of the original substances. Serial Dilution And Potentization: Potentization is a mathematico-mechanical process for rendering inert or poisonous antigen containing pathological residues, to a state of physical solubility, physiological assimilability so as to enhance their therapeutic activity and harmlessness, for use as a healing remedy. 14 The primary object of potentization is to reduce all substances designed for therapeutic use to "a state of approximately perfect solution or complete ionization, which is fully accomplished only by infinite dilution." (Arrhenius.) In accordance with another aspect of the present invention, there is provided a process for making a formulation for the treatment of autoimmune diseases, 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 Ic 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 1c to 1 million c and more. In accordance with the present invention cytokines and/ or STAT3 are mixed with a vehicle selected from a group of vehicles consisting of distilled water, ethyl alcohol and mixture of ethyl alcohol and distilled water. Preferably, ethyl alcohol (90 to 100 %) is used as a vehicle. 15 The proportion of mixing of cytokines and/ or STAT3 with the vehicle can range from 1 :99 to 1:1. Preferably lOpg of cytokines and / or STAT3 is mixed with 90 ml of the vehicle. Although the dilution represented by the term 'c' means a dilution of 1 :99, for the purposes of this specification the term 'c' is deemed to mean any dilution in the range of 1 :99 to 1:1. Each resulting diluted sample is potentized typically by stroking by holding the bottle 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. Such strokes are given for about 10 times. In accordance with the preferred embodiment of this invention, the bottle containing the preparation for stroking for potentization is a securely stoppered glass bottle and a mechanical device is adopted to exert a force of at least 6 dynes rhythmically at a frequency of 10 strokes in two minutes. The cytokines and STAT 3 used in the present invention were obtained from Sigma life sciences- USA, Biovision- USA, Abnova-USA and Prospec-israel. In accordance with the present invention 1 Opg of cytokine and / or STAT3 was mixed with about 90 ml of distilled water (or ethanol) in a one dram size vial. The resultant mixture was thoroughly shaken and 10 powerful strokes are administered with a mechanical device. This mixture is labeled as Ic (1c potency) 16 In the next step 1 ml (or such small part) of 1 c is mixed with 99 parts (or such high proportion) in another vial to undergo potentization with about 10 mechanical strokes to arrive at 2c potency. Likewise, the procedure is repeated to reach to 3c, 4c,....30c..50c,..100 c, 1000c, 50000c, up to 10 million c potencies. The formulation prepared in accordance with the present invention is used in the treatment of psoriasis, rheumatoid arthritis, Crohn's disease, asthma and inflammations. 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-10c) 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. 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 the swelling 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 then continued for four months. During 4 month of continuation with TNF-a 30c, the patient improved and showed significant recovery. 17 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%. 6. A 38 year male was presented with severe psoriasis. He was prescribed TNF a-30c followed by 50 c. After 10 weeks of treatment, the patient improved remarkably. 7. A 34 year female was presented with psoriasis. Initially she was prescribed TNF-a which showed partial improvement. Later she was given STAT30. After treatment all the skin lesions disappeared. 8. A 43 year male was presented with plaque psoriasis. He was prescribed TNF a of 30c potency. Further, the potency was increased to 50c which did not show remission. Later he was prescribed IFN-g and IL-8 combination in 30c potency which was subsequently increased to 50c. After treatment, he showed significant improvement. 9. A 50 year male was presented with psoriasis. Initially he was prescribed TNF-a of 30c potency which did not show remission. Later he was prescribed IFN-g and IL-8 combination in 40c potency which was subsequently increased to 50c. After treatment he showed significant improvement. 18 10. An eighteen years old girl presented with severe plaque psoriasis was prescribed TNF-a 30c which showed partial improvement. She was then prescribed 1L-8 in 20c potency which resulted in further improvement. Later, she was prescribed IFN-g alone followed by combination of TNF and IFN-g. The improvement in her skin lesions accelerated significantly. 11. A 24 year male was presented with extremely severe psoriasis. He was prescribed TNF-a alone in potency starting from 10 to 50c which showed slight improvement. Later he was treated with a combination of IFN-g and IL-8 in 30c potency which resulted in almost 100 % improvement. 12. A 31 year male presented with severer form of psoriasis on his lower limbs. He was given TNF-a to which he showed slight improvement. Then he was treated with a combination of TNF-a and IL-8 for which he showed further improvement but did not show any remission. Later he was prescribed 1L-20 which resulted in significant improvement. 13. A 22 year old girl presented with a severe eczema on her legs for twelve years with history of lesions of Lichen planus around the eczematous lesions. The conventional homeopathic medicine did not show any remission. Initially she was prescribed TNF and then a combination of IL-8 and IFN-g followed by IL-20 in 30c potency. After three months treatment she showed significant improvement (over 80%). Later she was given IL-17 which resulted in 90% recovery. 14. A 40 year female was presented with severe plaque psoriasis associated with Psoriatic arthritis. She was given TFN-a which showed partial relief. Then a 19 combination of TNF with IL-8 was prescribed for which she showed slight improvement. Later she was treated with a combination of TNF, IL-8 and IFN g, further she was given a combination of TNF, IL-8, IFN-g and 1L-20 followed by a combination of TNF, IL-8, IFN-g, IL-20 and IL-17. The combination resulted in significant improvement. 15. A 34 year male patient was presented initially with psoriasis. He was prescribed IL-8 which showed almost 100 % recovery. Later, he developed Psoriatic arthritis with swelling of small and large joints. He was then prescribed IL-17 which showed significant improvement. 16. A 34 year female was presented with rheumatoid arthritis with SLE. She was prescribed IL-17 in 13c potency which showed slight relief. She was then prescribed IL-17 in 30c potency which showed slight recovery. Later she was prescribed IL-20 in 30c potency. She showed significant improvement, however, complete remission was not achieved. 17. A 6 year old child presented with vitiligo on legs and hands did not respond to the conventional homeopathic medicine. The child was then prescribed IFN g-30c potency to achieve some definitive regimentation in two spots of vitiligo, which was significant. 18. A 5 year old male child was suffered with Nephrotic Syndrome and was dependent on cortisone. Furthermore, his urine proteins were not coming under control. He was prescribed IFN-g 30c. The protein amount was reduced from ++++ (4*) to ++ (2*) for the first time in three months. However, this improvement was not sustained. 20 19. A 37 year male was presented with psoriasis. He was prescribed IL-23 in 20c and 30c potencies. After treatment he showed significant improvement. 20. A 48 year male was presented with psoriasis. He was prescribed IL-23. After treatment, he showed significant improvement. 21. A 42 year male was presented with psoriasis on the back, hands and legs. He was prescribed IL-23. He improved significantly. 22. A 36 year female was presented with large patches of psoriasis on her chest, hands and back. She was prescribed with TNF-a. Then she was prescribed a combination of TNF-a and IFN-g. Later she was given a combination of TNF-a, IFN-g and IL-20, followed by a combination of TNF-a, IFN-g, IL-20, 1L-23 and IL-17. After treatment she showed significant improvement and all her lesions disappeared. 23. A 43 year male was presented with a history of an old and resistant patch of psoriasis on his ankle for 15 years. He attempted for the conventional treatment which did not show remission. Later, he was prescribed a combination of TNF, IL-8 and IFN-g, followed by a combination of IL-20, IL-23 and IL-17 which showed significant improvement and his patch disappeared. 25. A 40 year female was presented with extensive psoriasis and psoriatic arthritis. She was prescribed a combination of TNF, IL-8 and IFN-g. Later she was given IL-20 followed a combination of IL-23 and IL-17. She had shown significant wonderful improvement and complete remission. 21 26. A 32 year male was presented with acute inflamed piles with severe pain. He was prescribed TNF-a which showed significant relief from pain and inflammation. 27. A 49 year male was presented with ankylosing spondylitis. He was prescribed IL-17 in 20c potency. Afterwards, the potency was increased subsequently to 30c and 50c potency for which he showed remarkable improvement in pain and stiffness. 28. A 26 year female was presented with multiples sclerosis. She was prescribed IL-17 in 30c potency. Afterwards, the potency was increased subsequently to 40c, 100c and 150c for which she showed remarkable improvement. 29. 35 year male was presented with psoriatic arthritis. He was prescribed IL- 17 for which he showed improvement. 30. A 1 year and three months old child was presented with extensive plaque psoriasis all over the body. The child was treated with conventional allopathic as well homeopathic medicine which did not show remission. He was then prescribed a combination of TNF, IL-8 and IFN-g. Later a combination of IL 20, IL-23 and IL-17 was given for which the child showed improvement. Further, the child was prescribed STAT3 in 25c potency for which the child showed significant improvement. 31. A 60 year male was presented with psoriasis and psoriatic arthritis with pain and swelling. He was prescribed STAT3 in 25c potency. Afterwards, the potency was increased to 30c. He showed significant improvement. 22 32. A 45 year male was presented with psoriasis. He was prescribed a combination of TNF, IL-8 and IFN-g followed by a combination of IL-20, IL-23 and IL- 17 for which he showed improvement. However, he was left with a few resistant spots for which he was later prescribed STAT3 25c for a period of six weeks which resulted into complete recovery. 33. A 54 year male was presented with a history of psoriasis for five years. He was prescribed a combination of TNF and IL-8. Later he was given a combination of TNF, IL-8, [FN-g, IL-20, 1L-23 and IL-17 for a period of 4 months for which he showed improvement. However, some of the resistant spots did not show remission. He was then prescribed a combination of TNF, IL-8, IFN-g, IL-20, IL-23, IL-17 and STAT3 in 30c potency. He showed significant improvement. 34. A 29 year male was presented with Guttate Psoriasis. He was prescribed a combination of TNF and IL-8. Then he was given a combination of IFN-g, IL 20, IL-23 and IL-17 for which he showed partial improvement. After a gap of 4 weeks, he was given STAT3 30c for a period of 8 weeks. Excellent results were seen and there was a significant reduction in the lesion. 35. A 30 year male was presented with a history of moderate psoriasis on legs for a year. He attempted conventional treatment which did not show any remission. He was then prescribed STAT3 in 30c potency for a period of 8 weeks which resulted in almost 100% recovery. 36. A 14 year old girl was presented with psoriasis. She was prescribed STAT3 in 25c potency for period of 6 weeks which resulted in 90% improvement. 23 37. A 31 year male was presented with psoriasis. He was prescribed STAT3 in 25c potency for which a significant improvement was achieved. 38. A 38 year female was presented with psoriasis and psoriatic arthritis. She was given a combination of IL-8 and IFN-g followed by a combination of IL-8, IFN-g, IL-20, 1L-23 and IL- 17 for a period of 1 year. She showed improvement, however there was a severer relapse which did not respond to the same combination administered for about 10 weeks. She was then prescribed STAT30 in 25c potency for a period of three weeks for which she showed remarkable improvement. On continuing the same treatment for eight more weeks, significant improvement was achieved. 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 understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the invention and not as a limitation. 24

Claims (5)

1. A formulation for the treatment of autoimmune diseases, said formulation comprising a homogenized mixture of 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, said dilution being in the range of Ic to 1 million c effected in a vehicle selected from a group consisting of distilled water, ethyl alcohol and mixture of distilled water and ethyl alcohol said generally diluted.
2. A formulation as claimed in claim 1, wherein each of the serially diluted ingredients is lc ingredients being a lc dilution of the original ingredient in the vehicle, each c representing a dilution of the previous stage in the vehicle where the proportion of the substance to vehicle is in the range of 1:99 to 1:1, wherein the serial dilution is in the range of 1 c to 1 million c.
3. A process for making a formulation according to claims I to 2, said process comprising the following steps: i. obtaining a 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 25 iv. serially diluting with potentization, the primary dilution of Ic 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 1 c to 1 million c and more.
4. A process for making a formulation as claimed in claim 3, wherein potentization is effected by holding a bottle preferably a securely stoppered glass bottle containing the diluted ingredient in a closed fist and striking the fist on a hard surface repeatedly at a regular frequency preferably about 10 times or by exercising similar powerful stroke using a mechanical device which can strike a bottle on a hard surface.
5. A process for making a formulation as claimed in claim 3, wherein a mechanical device is used to exert a force of at least 6 dynes rhythmically at a frequency of 10 strokes in two minutes. Jogias Patent and Trade Mark Attorneys 11 December 2009 26
AU2009101279A 2009-05-19 2009-12-11 Medicinal formulation containing selected cytokines Ceased AU2009101279A4 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN1261/MUM/2009 2009-05-19
IN1261MU2009 2009-05-19

Publications (1)

Publication Number Publication Date
AU2009101279A4 true AU2009101279A4 (en) 2010-01-14

Family

ID=41508625

Family Applications (1)

Application Number Title Priority Date Filing Date
AU2009101279A Ceased AU2009101279A4 (en) 2009-05-19 2009-12-11 Medicinal formulation containing selected cytokines

Country Status (2)

Country Link
AU (1) AU2009101279A4 (en)
WO (1) WO2010134086A1 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE202013011988U1 (en) * 2012-05-15 2015-04-01 Rajesh Shah Anti-inflammatory formula

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030191061A1 (en) * 1994-03-31 2003-10-09 Brewitt Barbara A. Treatment methods using homeopathic preparations of growth factors
US20020049422A1 (en) * 1994-03-31 2002-04-25 Brewitt Barbara A. Homeopathic preparations
FR2729082A1 (en) * 1994-08-05 1996-07-12 World Trust Investment Sa Homeopathic compsn. for restoring immune system function
UA76640C2 (en) * 2002-08-02 2006-08-15 Олєг Ільіч Епштєйн Method for correcting pathological immune responses and homeopathic medicinal agent

Also Published As

Publication number Publication date
WO2010134086A1 (en) 2010-11-25

Similar Documents

Publication Publication Date Title
Christophers et al. Psoriasis
AU2011287292B2 (en) Combination pharmaceutical composition and methods of treating and preventing the infectious diseases
Cunha et al. Role of cytokines in mediating mechanical hypernociception in a model of delayed-type hypersensitivity in mice
CN111265500B (en) Pharmaceutical composition for preventing and treating COVID-19 and preparation method thereof
CN112135623B (en) Compositions and methods relating to the treatment of disease
EP2442832A1 (en) Compositions and methods for treatment of multiple sclerosis
Kadagothy et al. Perspective insights of small molecules, phytoconstituents and biologics in the management of psoriasis: A focus on targeting major inflammatory cytokine pathways
MXPA04007311A (en) Treatment of ms with goat serum.
TW200800247A (en) Method of treatment using interferon-τ
AU2009101279A4 (en) Medicinal formulation containing selected cytokines
RU2192882C1 (en) Medicinal agent and method of treatment of pathological syndrome caused by hemopoiesis impairment
CN1192929A (en) Oral medicinal preparation
AU2009100451A4 (en) Medicinal formulation containing a combination of HIV Type I and HIV Type II
CN116019813A (en) Application of Vesatolimod in preparation of medicines for preventing and/or treating central nervous system diseases
JPH09504792A (en) Treatment for rheumatoid arthritis
CN101961454A (en) Application of resina draconis to preparing compound enema for treating ulcerative colitis
WO2022173328A1 (en) Tolerogenic peptide compound
CN107998116B (en) Application of acetamide in anti-psoriasis medicine
RU2172182C1 (en) Method and drug for prevention and treatment of immune system diseases
US10441540B2 (en) Liposomal lupeol acetate and the use thereof in preparing drugs for rheumatoid arthritis
WO2003037372A1 (en) Method for restoring disordered physiological processes and a medicament for carrying out said method
CN107349204A (en) Tetraodotoxin is preparing application, pharmaceutical composition and externally applied drug in treating herpes zoster disorder agent composition
KR20080074583A (en) A drug, food and cosmetics containing hyaluronic acid for curing and preventing allergy disease
CN106539816A (en) Application of the ring dinucleotides in preventing and treating multiple sclerosis
CN106539815A (en) Application of the ring dinucleotide in preventing and treating multiple sclerosis

Legal Events

Date Code Title Description
TH Corrigenda

Free format text: IN VOL 23, NO 50, PAGE(S) 11667 UNDER THE HEADING INNOVATION PATENTS FILED - NAME INDEX UNDER THE NAME SHAH RAJESH, APPLICATION NO. 2009101279, UNDER INID (54), CORRECT THE TITLE TO MEDICINAL FORMULATION CONTAINING SELECTED CYTOKINES

FGI Letters patent sealed or granted (innovation patent)
MK22 Patent ceased section 143a(d), or expired - non payment of renewal fee or expiry