WO2013179302A1

WO2013179302A1 - Oral anti-inflammatory formulation comprising potentised cytokine

Info

Publication number: WO2013179302A1
Application number: PCT/IN2013/000314
Authority: WO
Inventors: Rajesh Shah
Original assignee: Rajesh Shah
Priority date: 2012-05-15
Filing date: 2013-05-15
Publication date: 2013-12-05
Also published as: DE202013011988U1

Abstract

The present disclosure provides an anti-inflammatory formulation comprising a homogenized mixture of at least one potentised cytokines selected from the group consisting of IL la (interleukin 1-alpha), IL lb (interleukin 1-beta), IL 2, IL 4, IL 5, IL 6, TNF-a (Tumor Necrosis Factor-alpha), INF-γ, IL 12, IL 13, IL 17, IL 20 and IL 23.

Description

ORAL ANTI-INFLAMMATORY FORMULATION COMPRISING

POTENTISED CYTOKINE

FIELD

The present disclosure relates to a medicinal formulation for treating inflammatory diseases.

BACKGROUND

Inflammation is a key biological response and expression in most acute and chronic disease processes, induced by allergies, infection, tissue injury, metabolic factors, immunologically mediated diseases, malignancies and others. It is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process. It is a process in which the white blood cells, immunocytes and various chemicals of the body help to protect from infection (bacteria, virus, etc), foreign substances as well as internal factors.

Inflammation treatment is an important and growing area of biomedical research and health care because inflammation mediates and is the primary driver of many medical disorders and autoimmune diseases. Many researches have been carried out in the past for the treatment of inflammatory diseases by various approaches. Some of the prior art documents which disclose treatment of inflammation are described herein below:

US2006153845 discloses a method of correcting pathologic immune reactions by administering antibodies to cytokines characterized by the use of activated form of ultra-low doses of monoclonal, polyclonal, or natural antibodies to cytokines involved in the course of inflammation.

US2012100155 discloses a pharmaceutical agent for use in- .the treatment of inflammation, in a subject prone to and/or experiencing an excessive inflammatory response as a result of infection with an infectious agent and/or exposure to an allergen and/or exposure to an environmental trigger. The pharmaceutical agent comprises an agent for preventing, hindering, modulating or reducing: (a) the production, activity and/or effect of one or more cytokines; and/or (b) the functionality of one or more cells that are targets for the cytokines; and/or (c) a pathological effect caused by cells producing and/or activated by the cytokines. The pharmaceutical agent comprises an anti-cytokine antibody or a cytokine-neutralizing fraction of such an antibody.

US2012064122 discloses use of microRNA-155 to reduce tissue specific autoimmune inflammation, treat autoimmune disease and modulate expression of cytokines from dendritic cells.

US2012058205 discloses a pharmaceutical composition for treating inflammation. The composition comprises a fibrate anti-hyperlipidemic agent, a MG-CoA reductase inhibitor, an aldosterone antagonist and a pharmaceutically acceptable carrier.

WO2012026771 discloses a composition comprising Wercklea insignis extracts and fractions thereof for preventing and treating inflammatory diseases or asthma.

The known treatments mainly act by blocking 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. Accordingly, there is a need of a simple, potent and cost effective formulation which can effectively treat inflammation by modulating the cytokine signals.

OBJECTS

Some of the objects of the present disclosure, which at least one embodiment herein satisfies, are as follows:

An object of the present disclosure is to provide an oral formulation for the treatment of inflammatory diseases. Another object of the present disclosure is to provide a formulation, which is effective at low dose.

Another object of the present disclosure is to provide a simple and cost effective formulation with enhanced efficacy for the treatment of inflammatory diseases.

An additional object of the present disclosure is to provide a simple and cost effective method for the preparation of the formulation.

SUMMARY

In accordance with the present disclosure there is provided an oral anti-inflammatory formulation of potency ranging between 6c and 100000c; said formulation comprising a homogenized mixture of at least one potentised cytokine selected from the group consisting of IL la (interleukin 1-alpha), IL lb (interleukin l-beta),^"IL 2, IL 4, IL 5, EL 6, TNF-a (Tumor Necrosis Factor-alpha), INF-γ, IL 12, IL 13, IL 17, IL 20 and IL

23. ;

In one embodiment the potency ranges between 6c and 1000c.

Typically, each of the potentized cytokine is a serially diluted cytokine in at least one vehicle selected from the group consisting of normal saline, distilled water and ethyl alcohol and exhibits a potency of at least 5c, preferably between 5c and 1000c.

Typically, the proportion of the cytokine to the vehicle ranges between 1:99 and 1:1.

In one embodiment the formulation is in the form of liquid.

In another embodiment the formulation further comprises a physiologically acceptable carrier selected from the group consisting of lactose, calcium carbonate, mic ocrystalline cellulose and sucrose. Typically, the carrier is sucrose globules or lactose globules.

In one embodiment the formulation is in the form of globules soaked with antiinflammatory formulation of the present disclosure.

In accordance with another aspect of the present disclosure there is provided a process for preparing the anti-inflammatory formulation; said process comprising the following steps:

1. obtaining pre-determined quantity, of at least one cytokine selected from the group consisting of IL la (inter leukin 1 -alpha), IL lb (inter leukin 1-beta), IL 2, IL 4, IL 5, IL 6, TNF-a (Tumor Necrosis Factor-alpha), INF-γ, IL 12, IL 13, IL 17, IL 20 and IL 23;

ii. mixing with potentization at least one cytokine and at least one vehicle selected from the group consisting of normal saline, distilled water and ethyl alcohol to obtain a primary dilution, wherein the ratio of cytokine to vehicle ranges from 1:99 to 1:1; and

iii. serially diluting with potentization the primary dilution with a vehicle selected from the group consisting of normal, saline, distilled water and ethyl alcohol in a ratio of 1:99 to 1:1 to obtain a formulation of a potency ranging between 6c and 100000c.

In another embodiment of the present disclosure the process for preparing the formulation comprising the following steps:

- obtaining pre-determined quantity of at least two cytokines selected from the group consisting of IL la (interleukin 1 -alpha), IL lb (interleukin 1-beta), IL

2, IL 4, IL 5, IL 6, TNF-a (Tumor Necrosis Factor-alpha), INF-γ, IL 12, EL 13, IL 17, IL 20 and IL 23;

- i diluting with potentization each of the cytokines separately with at least one vehicle selected from the group consisting of normal saline, distilled water and ethyl alcohol in a ratio of 1:99 to 1:1 to obtain a primary dilution of each of the cytokines; - mixing the primary dilutions of at least two cytokines in a ratio of 1 : 1 to 1: 10 to obtain a mixture; and

- serially diluting with potentization the mixture with a vehicle selected from the group consisting of normal saline, distilled water and ethyl alcohol in a ratio of 1:99 to 1: 1 to obtain a formulation of a potency ranging between 6c and 100000c.

- obtaining pre-determined quantity of at least two cytokines selected from the group consisting of IL la (interleukin 1 -alpha), IL lb (interleukin 1-beta), EL 2, IL 4, IL 5, IL 6, TNF-a (Tumor Necrosis Factor-alpha), INF-γ, IL 12, IL 13, IL 17, IL 20 and IL 23;

- mixing with potentization at least two cytokines together in a ratio of 1: 1 to 1 :10 along with at least one vehicle selected from the group consisting of normal saline, distilled water and ethyl alcohol to obtain a primary dilution, wherein the ratio of cytokines to vehicle ranges from 1 : 99 to 1: 1; and

- serially diluting with potentization the primary dilution with a vehicle selected from the group consisting of normal saline, distilled water and ethyl alcohol in a ratio of 1 :99 to 1: 1 to obtain a formulation of a potency ranging between 6c and 100000c.

In accordance with still another embodiment of the present disclosure the process for preparing the formulation comprising the following steps:

- obtaining predetermined quantity of at least two cytokines selected from the group consisting of IL la (interleukin 1 -alpha), EL lb (interleukin 1-beta), EL 2, IL 4, IL 5, IL 6, TNF-a (Tumor Necrosis Factor-alpha), ENfF-γ, IL 12, IL 13, IL 17, IL 20 and IL 23;

- diluting with potentization each of the cytokines separately with at least one vehicle selected from the group consisting of normal saline, distilled water and ethyl alcohol in a ratio of 1:99 to 1:1 to obtain a primary dilution of each of the cytokines;

- serially diluting with potentization the primary dilution of each of the cytokines with a vehicle selected from the group consisting of normal saline, distilled water and ethyl alcohol in a ratio of 1:99 to 1:1 to obtain serially diluted cytokines;

- mixing with potentization at least two serially diluted cytokines in a ratio of 1 :

1 to 1 : 10 to obtain a mixture; and

- serially diluting with potentization the mixture with a vehicle selected from the group consisting of normal saline, distilled water and ethyl alcohol in a ratio of 1:99 to 1:1 to obtain a formulation of a potency ranging between 6c and 100000c.

In one embodiment the process further comprises a step of soaking carrier globules with the formulation. The carrier globules are sucrose globules or lactose globules.

Typically, the potentization is effected by holding a securely stoppered glass bottle containing the diluted cytokine in a closed fist and striking on a hard surface repeatedly at a frequency of 10 strokes in two minutes.

Alternatively, the potentization is effected by a mechanical device which strikes a bottle on a hard surface and exerts a force of at least 6 dynes rhythmically at a frequency of.10 strokes in two minutes.

In accordance with another aspect of the present disclosure there is provided a method of treating inflammation/inflammatory disease or disorder; said method comprising administering a therapeutically effective amount of an oral anti-inflammatory formulation of potency ranging between 6c and 100000c to a subject in need thereof; said formulation comprising a homogenized mixture of at least one potentised cytokine selected from the group consisting of IL la (interleukin 1 -alpha), IL lb (interleukin 1-beta), IL 2, IL 4, IL 5, IL 6, TNF-a (Tumor Necrosis Factor-alpha), INF-γ, IL 12, IL 13, IL 17, IL 20 and IL 23.

DETAILED DESCRIPTION

Homeopathic medicine is micro-dosed natural substance derived from botanical, animal or mineral sources. Homeopathic remedies are prepared by serial dilution with shaking by forceful striking on hard surface; the process is termed as succussiori. Each dilution followed by succussion is assumed to increase the effectiveness. This process is called potentization. Dilution often continues until none of the original substance remains. This process transforms the original substance into a therapeutically active medicine.

Potentization is a mathematico-mechanical process for rendering inert or poisonous substances, chemicals, antigens, substances containing pathological residues, to a state of physical solubility, physiological assimilability so as to enhance their therapeutic activity and harmlessness, for use as a therapeutic agent.

The primary object of potentization is to reduce all substances designed for therapeutic use to "a state of approximately perfect solution or complete ionization, whichls fully accomplished only by infinite dilution." (Arrhenius.) ^{1 1}

The Homeopathic Law of Similars states that any substance which has a capacity to cause certain symptoms also has a potential of removing the same, if administered in small (potentized) dose.

Cytokines are proteins which are key mediators of both local and systemic immune- inflammatory responses that are secreted by various types of immune cells and serve as signaling chemicals which play vital role in governing the direction, amplitude, and duration of the inflammatory response.

There are two main categories of cytokines: pro-inflammatory and anti-inflammatory. Pro-inflammatory cytokines are produced predominantly by activated immune cells such as microglia and are involved in the amplification of inflammatory reactions.

Anti-inflammatory cytokines are involved in the reduction of inflammatory reactions.

In accordance with the present disclosure, there is provided an oral formulation for the treatment of inflammation. The formulation mainly contains at least one cytokine in potentized form. Particularly, the anti-inflammatory formulation in accordance with the present disclosure contains a homogenized mixture of at least two potentised cytokines. The potency of the formulation in accordance with the present disclosure ranges between 6c and 100000c. In one embodiment the potency ranges between 6c and 1000c.

In accordance with the present disclosure the cytokines include but are not limited to IL la (interleukin 1-alpha), IL lb (interleukin 1-beta), EL 2, EL 4, EL 5, IL 6, Tumor Necrosis Factor-alpha (TNF-a), INF-gamma, IL 12, IL 13, IL 17, II 20 and IL 23.

In accordance with the present disclosure the potentized cytokine is a serially diluted cytokine in at least one vehicle selected from the group consisting of normal saline, distilled water and ethyl alcohol. The proportion of the cytokine to the vehicle ranges between' 1 :99 and 1: 1. The potency of the cytokine Used in the formulation of the present disclosure ranges between lc 'to 100000c, where 'c' denotes centesimal potency. In one embodiment the potency is at least 5c. In accordance with exemplary embodiment of the present disclosure the potency ranges between 5c and 1000c.

In one embodiment the formulation is in the form of liquid.

The anti- inflammatory formulation further contains a physiologically acceptable carrier selected from the group consisting of lactose, calcium carbonate, microcrystalline cellulose and sucrose. Typically, the carrier is sucrose globules or lactose globules. In one embodiment the formulation is in the form of globules soaked with antiinflammatory formulation of the present disclosure.

The following list states the role of the cytokines used in the anti inflammatory^{^} formulation of the present disclosure in various diseases; which also implies their application for the same diseases, when used in a homeopathic form.

10. IL-12 Allergies IL-12 is linked with

autoimmunity, inflammation.

IL-13 Airway hyper reactivity and Allergic inflammation

mucus overproduction in asthma.

Asthma, Bronchitis, Bronchactatis

Allergies, allergic inflammation

12. IL-17 Rheumatoid arthritis, Psoriasis Inflammation and autoMultiple sclerosis immunity. IL-17, a

proinflammatory cytokine that enhances T cell priming and stimulates the production of proinflammatory

molecules such as IL-1, IL-6, TNF-alpha, NOS-2, and chemokines resulting in inflammation.

13. IL-20 Psoriasis Epidermal inflammation and psoriasis

14. IL 23 Inflammation coexisting with Important part of the

infections. (Cellulitis, etc.) inflammatory response

against infection.

"IL" refers to "Interleukin".

In accordance with another aspect of the present disclosure there is provided a method of treating inflammation/inflammatory disease or disorder; said method comprising administering a therapeutically effective amount of an oral anti-inflammatory formulation of potency ranging between 6c and 100000c to a subject in need thereof; said formulation comprising a homogenized mixture of at least one potentised cytokine selected from the group consisting of IL la (interleukin 1 -alpha), EL lb (interleukin 1-beta), IL 2, IL 4, IL 5, EL 6, TNF-a (Tumor Necrosis Factor-alpha), INF-γ, IL 12, IL 13, EL 17, IL 20 and IL 23.

The inflammatory diseases which can be treated using the formulation .of the present disclosure include but are not limited to acute or chronic inflammation found in inflammatory skin diseases such as eczema, psoriasis, urticaria, skin infections; inflammatory arthritis such as rheumatoid arthritis, psoriatic arthritis, Ankylosing spondylitis, osteoarthritis; inflammatory bronchial diseases such as asthma, Chronic Obstructive Pulmonary disease (COPD), bronchitis, bronchiolitis; and other miscellaneous inflammatory disorders such as gastritis, otitis, myositis, neuritis and colitis.

The formulation of the present disclosure when used as an anti-inflammatory agent also reduces related symptoms and conditions such as pain, swelling, cough, itching, bronchospasm, fever and the like. Inflammation is the key pathophysiological process in all of the above disease conditions; which can be addressed by using potentized cytokines as supportive or principal treatment modality.

In accordance with another aspect of the present disclosure there is also provided a process for preparing the anti-infiammatory formulation.

In one exemplary embodiment the process involves the following steps:

In the first step, pre-determined quantity of at least one cytokine selected from the group consisting of IL la (interleukin 1 -alpha), IL lb (interleukin 1-beta), IL 2, IL 4,

EL 5, IL 6, TNF-a (Tumor Necrosis Factor-alpha), INF-γ, IL 12, EL 13, IL 17, EL 20 and IL 23 is obtained.

In the next step, the obtained at least one cytokine and at least one vehicle selected from the group consisting of normal saline, distilled water and ethyl alcohol are mixed with potentization in a ratio of 1 : 99 to 1 : 1 to obtain a primary dilution.

The primary dilution is then serially diluted with potentization with a vehicle selected from the group consisting of normal saline, distilled water and ethyl alcohol in a ratio Of 1 :99 to 1: 1 to obtain a formulation of a potency ranging between 6c and 100000c.

In another exemplary embodiment the process involves the following steps:

In the first step, pre-determined quantity of at least two cytokines selected from the group consisting of IL la (interleukin 1 -alpha), IL lb (interleukin 1-beta), IL 2, EL 4, IL 5, IL 6, TNF-a (Tumor Necrosis Factor-alpha), INF-γ, IL 12, IL 13, IL 17, EL 20 and IL 23 is obtained. vehicle alcohol

In the next step, the primary dilutions of at least two cytokines in a ratio of 1 : 1 to 1 : 10 are mixed to obtain a mixture. The mixture is then serially diluted with potentization . with a vehicle selected from the group consisting of normal saline, distilled water and ethyl alcohol in a ratio of 1:99 to 1:1 to obtain a formulation of a potency ranging between 6c and 100000c.

In accordance with still another exemplary embodiment of the present disclosure the process involves the following steps:

In the first step, pre-determined quantity of at least two cytokines selected from the group consisting of IL la (interleukin 1 -alpha), EL lb (interleukin 1-beta), IL 2, IL 4, IL 5, IL 6, TNF-a (Tumor Necrosis Factor-alpha), INF-γ, DL 12, IL 13, JL 17, EL 20 and EL 23 is obtained.

In the next step, at least two cytokines are then mixed together with potentization in a ratio of 1: 1 to 1:10 along with at least one vehicle selected from the group consisting of normal saline, distilled water and ethyl alcohol to obtain a primary dilution. The ratio of cytokines to vehicle is maintained in a range from 1 :99 to 1 : 1. '

The primary dilution is further serially diluted with potentization with a vehicle selected from the group consisting of normal saline, distilled water and ethyl alcohol in a ratio of 1 :99 to 1:1 to obtain a formulation of a potency ranging between 6c and 100000c.

In the first step, predetermined quantity of at least two cytokines selected from the group consisting of EL la (interleukin 1-alpha), IL lb (interleukin 1-beta), EL 2, DL 4, DL 5, IL 6, TNF-a (Tumor Necrosis Factor-alpha), INF-γ, EL 12, EL 13, EL 17, EL 20 and EL 23 is obtained.

In the next step, each of the cytokines is diluted with potentization separately with at least one vehicle selected from the group consisting of normal saline, distilled water and ethyl alcohol in a ratio of 1:99 to 1:1 to obtain a primary dilution of each of the cytokines.

The primary dilution of each of the cytokines is serially diluted with potentization with a vehicle selected from the group consisting of normal saline, distilled water and ethyl alcohol in a ratio of 1:99 to 1:1 to obtain serially diluted cytokines. Then, at least two serially diluted cytokines are mixed with potentization in a ratio of 1 : 1 to 1 : 10 to obtain a mixture. Finally, the mixture is serially diluted with potentization with a vehicle selected from th& group consisting of normal saline, distilled water and ethyl alcohol in a ratio of 1:99 to 1:1 to obtain a formulation of a potency ranging between 6c and 100000c.

The process of the present disclosure further comprises a step of soaking the carrier globules with the formulation of the present disclosure. The potentization is effected by holding a securely stoppered glass bottle containing the diluted cytokine in a closed fist and striking on a hard surface repeatedly at a frequency of 10 strokes in two minutes.

Alternatively, the potentization is effected by a mechanical device which strikes a bottle on a hard surface and exerts a force of at least 6 dynes rhythmically at a frequency of 10 strokes in two minutes.

In accordance with the present disclosure it is found that the potentised cytokines are able to produce or initiate effects contrary to the direct effects of the respective cytokines. 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.

The present disclosure is further illustrated herein below with the help of the following examples. The examples used herein are intended merely to facilitate an understanding of ways in which the embodiments herein may be practiced and to further enable those of skill in the art to practice the embodiments herein. Accordingly, the examples should not be construed as limiting the scope of the embodiments herein.

Example 1:

l(^g of cytokine (IL-1) was mixed with about 90 ml of distilled water in a one dram size vial. The resultant mixture was thoroughly shaken and 10 powerful strokes were given using, a mechanical device. This mixture was labeled as lc (lc potency).

In the next step, lml of lc mixture was mixed with 99 parts of vehicle (normal saline) in another vial to undergo potentization with about 10 mechanical strokes to arrive at 2c potency. Likewise, the procedure was repeatejd to reach to 3c, 4c,....30c..50c,..100 ^■ c, 1000c, 50000c, up to 10 million c potencies.

Example 2:

20μg of cytokines (IL-1 and TNF-a, in 1:1 proportion) was mixed with about 90 ml of ethanol in a one dram size vial. The resultant mixture was thoroughly shaken and 10 powerful strokes were given using a mechanical device. This mixture was labeled as lc (lc potency). -

The process of example 1 was repeated to obtain a formulation having 30c potency. Example 3:

In the first step, 10μ§ of cytokine (IL-2) was obtained and serially diluted with potentization as per the process of example 1 to obtain 5c potency sample. In the second step, l0μg of cytokine (INF-γ) was obtained and serially diluted with potentization as per the process of example 1 to obtain 5c potency sample. Both the samples were mixed together with potentization to obtain a mixture. 1 ml of the mixture was mixed then with 99 parts of distilled water in another vial to undergo potentization with about 10 mechanical strokes to arrive at 6c potency. The 6c potency sample was then further serially diluted with potentization to obtain a formulation having 30c potency.

Anecdotal Studies:

Provided herein below are some case studies involving the use of the formulation of the present disclosure:

1. A 26 years old lady was presented with extensive psoriasis. She was receiving various medicines for over five years. She experienced a flare up with new spots psoriasis appearing almost all over body including genitals.

She was then prescribed a formulation (IL 2, 10c) prepared in accordance with the present disclosure which brought in about 40% relief in most of her psoriasis spots within 6 weeks. All inflamed lesions, scaling, itching and painfulness reduced significantly. Subsequently, she was treated with higher potency formulation (IL 2, 30c). Excellent results were seen and there was more than 60% relief in most of her psoriasis spots.

2. A 30 years old lady was presented with severe palmo-planter psoriasis with psoriatic arthritis. She was prescribed a formulation (IL2, 30c) prepared in accordance with the present disclosure thrice a day. There was about 30% relief in her inflamed psoriatic lesions as well as psoriatic arthritis in nine weeks.

3. A 14 years old school girl was under treatment for very severe and extensive eczema since long. She responded partly to various medicines given. She was presented with very severe, acutely inflamed eczematous lesions on most parts of her body, with cellulitis, oozing, pain, itching, infection and feverish feeling. Her eczema was immunologically mediated allergic expression. She had lesions on legs, scalp, hands, neck, chest, etc.

She was prescribed a formulation IL 2, 10c followed by a formulation IL 2, 30c prepared in accordance with the present disclosure for eight weeks. Almost 80% i

recovery was observed in this case without any other homeopathic or other mode of medication.

4. A 40 years old lady was suffering from chronic psoriasis on many parts of body for ten years. She was presented with severe flare up of psoriasis and was then prescribed the formulation of the present disclosure IL 2, 10c; IL 2, 20c and IL 2, 30c over a period of about six weeks. 40% of her inflamed psoriatic lesions and scaling improved within one month.

5. A 31 years old lady was presented with extensive psoriasis. She was prescribed IL 10c earlier. Still she had acute, inflamed, scaly, itching lesions all over her body. She was , then prescribed IL2, 20c followed by IL2 30c, for 12 weeks. About 40% improvement in most of the areas was observed.

6. A 25 years old person was suffering from chronic eczema especially on face and was under treatment, He responded well to certain medicine. After his visit to Kashmir, he was presented with severe flare up of eczema. He was then prescribed IL 2 in 12 c and 30c potency, three times a day for about two months. His acute flare up was resolved significantly.

7. A 26 years old lady was presented with severe and chronic atopic dermatitis with severe urticarial. She was administering antihistamines for over two years: She was prescribed IL 4, in 30c and 50c potency for 3 months. Excellent improvement was i

observed. Her inflamed lips (cheilitis) due to atopic inflammation and urticaria came under control. 8. A 30 years old male was presented with urticaria and patches of dermatitis on many parts of the body. He was prescribed IL 4, in 20c, 30c and 40c potency over three months. He responded significantly. The severity, intensity and duration of dermatitis and urticaria reduced and he could stop his other anti-histamine medications.

9. A 77 years old gentleman was under care for chronic urticaria. He stopped responding to regular homeopathic medicines at a stage. He was then prescribed IL 4, 10c and 30c three times a day for about six weeks. Excellent improvements in his urticarial rashes were observed.

10. A 43 years old lady presented with chronic asthma, bronchitis and high blood pressure was prescribed IL 4, 30c and then 50c potencies for about three months. A significant control in respect of her asthma and bronchitis was observed.

11. A 38 years old male was presented with acute flare up of urticaria. He was prescribed IL 4, 30c and 40c potency during acute flare up. His acute flare up resolved completely.

12. A 40 years old male was presented with chronic bronchitis and chronic obstructive pulmonary diseases. He was addicted to smoking for over 15 years. He experienced cough, chest pain, breathlessness, eosinophilia and weakness. He was prescribed IL 5, 30c potency. An improvement was found in about six weeks.

13. A male patient was presented with acute flare up of inflamed eczema lesions on neck. He was prescribed IL 5, 30c potency. In three weeks time, his inflammation resolved completely.

14. A male patient of 64 years old was suffering from interstitial lung disease. Particularly, he was suffering from inflamed lung tissues leading to cough and difficulty in breathing on least exertion. He was prescribed IL 5, three times a day for a month. A noticeable improvement was found in six weeks. 15. A 23 years old girl with chronic pan-ulcerative colitis was under treatment for a long time. During one of her acute flare ups, she had over 20 loose motions with passing of blood and mucus. She was then prescribed IL 8, in 30c potency, three times a day for a month. Significant improvement was observed.

16. A 36 years old female was presented with acute flare up of very severe ulcerative colitis with severe gingivitis and post withdrawal of corticosteroids. She was prescribed EL 8 in 30c potency three times a day. The significant improvement was observed.

17. A 36 years old man presented with ulcerative colitis was prescribed IL 8 in 10c, 20c and 30c. A significant improvement was observed.

18. A 30 years old male was approached for. the treatment of Ulcerative Colitis. He was prescribed IFN-g, in 10c, 20c and 30c potency over six months. It produced remarkable improvement in his ulcerated colon and the symptoms thereof.

19. A 49 years old male was presented with vitiligo that appears after itching and inflammation. He was prescribed IFN-g, in 20c, 40c potencies. A marginal regimentation on some places was found.

20. A 40 years old male was suffering from oral Lichen Planus. He was prescribed EFN-g, in 40c potency for over three months. A significant reduction in inflammatory lesions was found.

21. A 35 years old male was under treatment for Ulcerative colitis. He was then prescribed TNF-a, in 40c potency, three times a day for a month. A notable improvement was observed.

22. A 50 years old male was under treatment for chronic oral lichen planus, an autoimmune disorder leading to inflammation and erosion of oral mucosa. He was prescribed TNF-α, in 30c potency when he had an acute flare up. He responded in excellent way and his acute inflammatory state resolved completely.

23. A 12 years old female child was suffering with vitiligo. She was prescribed TNF- a, in 10c, 20c and 40c, for about three months. Re-pigmentaiton on some of the postinflammatory vitiligo spots was observed.

24. A 24 years old female patient was suffering from eczema and had stopped responding to any medication at one stage. She was prescribed TNF-a, 10c and then 40c. Her inflamed eczematous lesions responded quickly, in about ten days' time.

25. A 21 years old man was suffering from sero-negative arthritis with pain and stiffness in joints and muscles. He was prescribed TNF-a, 10c. He responded excellently with respect to all the signs and symptoms related to inflammation.

27. A 14 years old girl was presented with resistant, relapsed eczema on her face, with inflamed lesions around eyes. She was prescribed IL 12, 30c. She showed improved in about two weeks.

28. A 35 years old female was presented with asthma, bronchitis, cough and breathlessness. She was prescribed IL 13, 30c, three times a day. A significant improvement was observed within six weeks.

29. A 32 years old lady was suffering from Multiple Sclerosis with symptoms such vertigo, painfulness, weakness of limbs, etc. She was prescribed IL 17, 30c potency. She administered this medicine for over six months. Significant changes in her symptoms were observed.

30. A 41 years old lady suffering from psoriasis was prescribed IL 17, 50c potency in a flare up. She improved significantly in two weeks. 31. A 36 years old man was under treatment for chronic psoriasis with acute flare-up of inflamed lesions. He stopped responding to regular medicine. He was prescribed EL 20, 20c potency, thrice a day for two weeks. Significant reduction of acute crisis was observed. Also most of his lesions were improved in about eight weeks.

32. A 45 years old male was under the treatment for chronic guttate psoriasis. At one stage, he stopped improving and was presented with acute flare up with increased scaling. He was prescribed EL 20, 20c, thrice a day for two weeks. His scaling and inflammation were reduced. The medicine was continued for over three months, in 30c and 50c potency. Improved results were observed.

33. A 30 years old male, during an acute flare up of psoriasis was prescribed EL20 in 20c potency and then 30c. He showed considerable improvement in acute stage.

34: A 57 years old man was presented with Chronic Mastoiditis, inflammation- of mastoid associated with Chronic Suppurative Otitis Media. He reported that he is suffering with severe pain in his left ear with discharge and low-grade fever since over a month and he already took antibiotics for several days, which didn't provide him significant relief. His x-ray showed sclerotic changes in left mastoid with changes suggestive of chronic Mastoiditis and preliminary destruction of the left bone with cavity formation suggestive of cholesteatoma. "^,— -·*

He was prescribed a homeopathic medicine, Silica 30, three times a day for seven days. However, he didn't find any relief. Then he was prescribed EL-1 (alpha and beta), 30c potency, three times a day for seven days. Significant reduction in mastoid inflammation and pain in ear was reported after seven days. Further, his feverish feeling was reduced drastically. The medicine worked efficiently as an antiinflammatory, analgesic and anti-pyretic medicine in a chronic case.

35: A 51 years old male was presented with chronic psoriasis. He was under homeopathic treatment for a year which gave him partial relief with some relapses. He was then prescribed IL-2, 30c potency, thrice a day for a month. About 30% improvement was found with some relapses. He was further prescribed IL-1 (alpha and beta), 30c potency, along with IL-2, 30c potency, thrice a day for a month. After this treatment he reported significant reduction in the inflamed lesions of psoriasis on many parts of the body. Further, his itching was reduced drastically. In this case, .a combination of IL-1 with IL-2 proved to be effective.

36. 41 years old man was presented with severe Ankylosing Spondylitis with back, shoulder and neck pain, stiffness and immobility. He was suffering with aforesaid problem since over two years. He was prescribed IL 17, 30c potency, thrice a day for 2 weeks. After the treatment he got partial relief. However, considering the severity of inflammation, affecting multiple joints, he was then prescribed a combination of various cytokines. He was prescribed IL-1, IL-2, TNF-a, IL 12 and INF-g, 30c potency, thrice a day for a month. He reported significant reduction in pain and his overall health was also improved, including better mobility, reduced stiffness and better sleep.

37. A 40 years old female was with Rheumatoid Arthritis (moderate) with vitiligo multiple patches). She was suffering with aforesaid problem since last 4-5 years.

Considering autoimmune nature of her pathology, which is influenced by cytokines such as IL-2, IFN-g, IL 6, TNF-a, IL 12; she was prescribed a combination of these cytokines in 30c potency, thrice a day for a month. Her pain in joints reduced considerably. The medicine was continued for six more months. Various potencies were used in the course of treatment, such as 30c, 50c, 100c, 400c and 500c. A significant reduction in pain was found. Also partial reduction in her vitiligo spots was also reported.

38. A 40 years old man was presented with Ankylosing Spondylitis. He was suffering from the same since last 8 years. Further, he reported that he is also suffering with Anxiety Neurosis since last six months. He was earlier diagnosed as a case of fibromyalgia but his clinical picture was in favor of Ankylosing Spondylitis, in spite of HLA-B27 being negative. He was prescribed TNF-a, IL-17, TL 2 and IL 13 in 30c potency for a month. It was found that there is reduction in pain. The medicine of the present disclosure was continued for six months in various potencies such as 50c, 100c,: and 300c. A significant reduction in pain was found during and after the treatment.

39: Two years old female child was presented with Atopic Dermatitis and Asthmatic bronchitis. Her skin was affected with eczematous lesions on face, popliteal fossa, legs, abdomen, etc., with itching, occasional bleeding spots and roughness. She already had been given plenty of immunosuppressive medicines like cortisone for asthma as well as for eczema. Both the diseases are immunologically mediated conditions, where cytokines play vital role. She was prescribed a combination of those cytokines which are known to play role in the pathophysiology of such diseases, such as IL 1, IL-2, IL 5, TNF-a, INF-g, IL-12, IL-13; all in 30c potency to start with, thrice a day for a month. She reported slow and steady improvement in her atopic lesions. There was also reduction in frequency of attacks of wheezing in the course of eight months.

40. A 50 years old man was presented with chronic psoriasis. He was suffering with the same since last 20 years. He was prescribed IL 2 and EL 12 in 30c potency for a resistant patch on his limbs. He responded very well and his- psoriatic eruptions reduced which did not respond to earlier medicines.

41. A 7 years old girl was presented with psoriasis with frequent colds. She was prescribed IL 2, 30c potency for three months. She showed remarkable improvement in both the conditions.

42. A 44 years old woman was represented with recurring Psoriatic arthritis with fever. She already took methotrexate on two occasions in the past which didn't help her. She was prescribed IL 2, IL, 1, TNF-a, and INF-g, in 30c potency thrice a day for two weeks. Her fever was demolished in three days and eruptions subsided slowly. Throughout this specification the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.

The use of the expression "at least" or "at least one" suggests the use of one or more elements or ingredients or quantities, as the use may be in the embodiment of the disclosure to achieve one or more of the desired objects or results.

Any discussion of documents, acts, materials, devices, articles or the like that has been included in this specification is solely for the purpose of providing a context for the disclosure. It is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the disclosure as it existed anywhere before the priority date of this application.

The numerical values mentioned for the various physical parameters, dimensions or quantities are only approximations and it is envisaged that the values higher/lower than the numerical values assigned to the parameters, dimensions or quantities fall within the scope of the disclosure, unless there is a statement in the specification specific to the contrary. ^

While considerable emphasis has been placed herein on the particular features of this disclosure, it will be appreciated that various modifications can be made, and that many changes can be made in the preferred embodiment without departing from the principles of the disclosure. These and other modifications in the nature of the disclosure or the preferred embodiments 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 disclosure and not as a limitation.

Claims

Claims:

1. An oral anti-inflammatory formulation of potency ranging between 6c and 100000c; said formulation comprising a homogenized mixture of at least one potentised cytokine selected from the group consisting of IL la (interleukin 1- alpha), TL lb (interleukin 1-beta), IL 2, IL 4, IL 5, IL 6, TNF-a (Tumor Necrosis Factor-alpha), INF-γ, IL 12, IL 13, IL 17, IL 20 and IL 23.

2. The formulation as claimed in claim 1, wherein the potency ranges between 6c and 1000c.

3. The formulation as claimed in claim 1, wherein each of the potentized cytokine is a serially diluted cytokine in at least one vehicle selected from the group consisting of normal saline, distilled water and ethyl alcohol and exhibits a potency of at least 5c, preferably between 5e and 1000c.

4. The formulation as claimed in claim 3, wherein the proportion of the cytokine to the vehicle ranges between 1 :99 and 1:1.

5. The formulation as claimed in claim 1, further comprises a physiologically - acceptable carrier selected from the group consisting of lactose, calcium carbonate, microcrystalline cellulose and sucrose.

6. The formulation as claimed in claim 5, wherein the carrier is sucrose globules or lactose globules.

7. A process for preparing the formulation as claimed in claim 1, said process comprising the following steps:

i. obtaining pre-determined quantity of at least one cytokine selected from the group consisting of IL la (interleukin 1 -alpha), IL lb (interleukin 1-beta), IL 2, IL 4, IL 5, IL 6, TNF-a (Tumor Necrosis Factor-alpha), INF-γ, IL 12, EL 13, EL 17, IL 20 and IL 23; ii. mixing with potentization at least one cytokine and at least one vehicle selected from the group consisting of normal saline, distilled water and ethyl alcohol in a ratio of 1 :99 to 1:1 to obtain a primary dilution; and

iii. serially diluting with potentization the primary dilution with a vehicle selected from the group consisting of normal saline, distilled water and ethyl alcohol in a ratio of 1:99 to 1:1 to obtain a formulation of a potency ranging between 6c and 100000c.

8. . A process for preparing the formulation as claimed in claim 1; said process comprising the following steps:

i. obtaining pre-determined quantity of at least two cytokines selected from the group consisting of IL la (interleukin 1 -alpha), EL lb (interleukin 1-beta), EL 2, EL 4, EL 5, IL 6, TNF-a (Tumor Necrosis Factor-alpha), INF-γ, EL 12, EL 13, EL 17, EL 20 and EL 23; ii. diluting with potentization each of the cytokines separately with at least one vehicle selected from the group consisting of normal saline, distilled water and ethyl alcohol in a ratio of 1:99 to 1:1 to obtain a primary dilution of each of the cytokines; '

iii. mixing the primary dilutions of at least two cytokines in a ratio of 1: 1 to 1 : 10 to obtain a mixture; and

iv. serially diluting with potentization the mixture with a vehicle selected from the group consisting of normal saline, distilled water and ethyl alcohol in a ratio of 1:99 to 1:1 to obtain a formulation of a potency ranging between 6c and 100000c.

9. A process for preparing the formulation as claimed in claim 1, said process comprising the following steps:

i. obtaining pre-determined quantity of at least two cytokines selected from the group consisting of EL la (interleukin 1 -alpha), EL lb (interleukin 1-beta),

EL 2, EL 4, IL 5, IL 6, TNF-a (Tumor Necrosis Factor-alpha), INF-γ, IL 12, IL 13, IL 17, EL 20 and EL 23;

ii. mixing with potentization at least two cytokines together in a ratio of 1 : 1 to 1:10 along with at least one vehicle selected from the group consisting of normal saline, distilled water and ethyl alcohol to obtain a primary dilution, wherein the ratio of cytokines to vehicle ranges from 1:99 to 1:1; and iii. serially diluting with potentization the primary dilution with a vehicle selected from the group consisting of normal saline, distilled water and ethyl alcohol in a ratio of 1:99 to 1:1 to obtain a formulation of a potency ranging between 6c and 100000c. A process for preparing the formulation as claimed in claim 1, said process comprising the following steps:

i. obtaining predetermined quantity of at least two cytokines selected from the group consisting of IL la (interleukin 1 -alpha), IL lb (interleukin 1- beta), IL 2, IL 4, IL 5, IL 6, TNF-a (Tumor Necrosis Factor-alpha), INF- γ, IL 12, IL 13, EL 17, IL 20 and IL 23; ii. diluting with potentization each of the cytokines separately with at least one vehicle selected from the group consisting of normal saline, distilled water and ethyl alcohol in a ratio of 1 :99 to 1:1 to obtain a primary dilution of each of the cytokines;

iii. serially diluting with potentization the primary dilution of each of the cytokines with a vehicle selected from the group consisting of normal saline, distilled water and ethyl alcohol in a ratio of 1:99 to 1:1 to obtain serially diluted cytokines; .

iv. mixing with potentization at least two serially diluted cytokines in a ratio of 1 : 1 to 1 : 10 to obtain a mixture; and

11. The process as claimed in claims 7, 8, 9 and 10 further comprises a step of soaking the carrier globules with the formulation.

12. The process as claimed in claims 7, 8, 9 and 10, wherein the potentization is effected by holding a securely stoppered glass bottle containing the diluted cytokine in a closed fist and striking on a hard surface repeatedly at a frequency of 10 strokes in two minutes.

13. The process as claimed in claims 7, 8, 9 and 10, wherein the potentization is effected by a mechanical device which strikes a bottle on a hard surface and exert a force of at least 6 dynes rhythmically at a frequency of 10 strokes in two minutes.

14. A method of treating inflammation/inflammatory disease or disorder; said method comprising administering a therapeutically effective amount of an oral anti-inflammatory formulation of potency ranging between 6c and 100000c to a subject in need thereof; said formulation comprising a homogenized mixture of at least one potentised cytokine selected from the group consisting of IL la- (interleukin 1 -alpha), IL lb (interleukin 1-beta), TL 2, TL 4, TL 5, IL 6, TNF-a (Tumor Necrosis Factor-alpha), INF-γ, IL 12, IL 13, IL 17, IL 20 and IL 23.