A herbal preparation effective in the prevention and management of rheumatoid arthritis and associated complaints.

FIELD OF INVENTION

The present invention relates to a herbal preparation effective in the prevention and management of Rheumatoid Arthritis and associated complaints. The preparation of the present invention can also be utilized as an adjuvant therapy for those Rheumatoid Arthritis cases that entered into a condition where anxiety and depression was more prominent clinical feature than the pain and other symptoms of Rheumatojd Arthritis.

BACKGROUND OF INVENTION

Rheumatoid Arthritis is a systemic inflammatory disorder characterized by a destructive hypertrophic synovitis. It is a major cause of chronic disability and reduces life expectancy. Almost all the body organs are involved in this disease-process. The cause of Rheumatoid Arthritis is still unknown but abnormal immunological reactions are important in the pathophysiology of

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this clinical condition. There is a chronic inflammation in the synovium and may other tissues like monocytes, macrophages, T lymphocytes and B lymphocytes. They are found in large number in the hypertrophied synovium suggesting an abeerant response to a yet unidentified foreign or self antigen. The disease is strongly associated with auto-antibodies. Immunoglobulin M and rheumatoid factor is found in 80 percent of patients and classical rheumatoid factors like immunoglobulin G and A, are commonly present.

Several studies have suggested that Rheumatoid Arthritis has a complex etiology, but there is good evidence to which emphasize that it has genetic determinants in assessing the susceptibility and severity of the disease. The diseases like diabetes mellitus, autoimmune thyroiditis, anemia and primary biliary cirrhosis are seem more frequently among Rheumatoid Arthritis patients. The environmental factors also play ≠L role in the occurrence of Rheumatoid. It is observed that the disease is more common among people living in town than in rural area. In Rheumatoid Arthritis the onset of disease is usually insidious with gradual recruitment of an increasing number of joints; pain and stiffness affecting the small joints gradually increases in severity and involve the elbows, wrists, shoulders, ankles, knees and hip joint. Systemic clinical features such as malaise, weight loss, and low grade fever are common. Soft tissue swelling with tenderness restricts the

movement whereas synovial effusion and redness, and warmth of the joints occur with immobility, stiffness, etc.

For Rheumatoid Arthritis curative treatment is not-available and therefore symptomatic relief is advised. By following multi-disciplinary approach including medical, nursing, occupational therapy, physiotherapy and surgical specialization, Rheumatoid Arthritis is successfully managed by immunosuppressive drugs in combination with high dose of corticosteroids. More recently, a variety of experimental biologically active agents are being evaluated with good results. These include anti-tumour necrosis factor monoclonal antibodies, soluble tumour's necrosis factor, antibodies and inter-leukin-1 antagonists. Simple analgesic is adequate for first line agent because of the less side effects. These effective analgesic agents reduce inflammation locally in the joints. In case of elderly people and where there is renal impairment, these agents should be used cautiously. Various slow acting anti-rheumatic drugs which reduce pain and inflammation, have shown sub-optimum benefits. Methotrexate and sultasalazine are the group of drugs but due to hepatic, hemopoetic and allergic toxicity demand that their application should be monitored. Similarly, cytotoxic agents like Azathioprine are frequently used either alone or in combination with

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steroids. But severe complicated cases such as vasculitis or pleuropericarditis may require high does steroids, cyclophophamide, etc. A further generalized immunity is reduced by administration of corticosteroids or by cytotoxic drugs. Keeping such facts in view, it was thought to propose a safer remedial measure for Rheumatoid Arthritis. In Siddha and Ayurvedic system of medicine several suitable candidates are available showing maximum benefits and without any adverse reaction. In the proposed Ayurvedic formulation the hydro-alcoholic extract of Vitex negundo, Pluchea lanceolata, Indigofea, tinctoria, Enclostema littoral, Cardiospermum helicacabem and Dalbergia lancoolaria have been used in effective doses.

OBJECTS OF THE INVENTION

The main object of the present invention is to propose a herbal preparation effective in the prevention and management of Rheumatoid Arthritis and associated problems.

Another object of this invention is to propose a plant based herbal preparation effective in relief from pain, particularly morning stiffness among Rheumatoid Arthritis cases.

Still another object of the invention is to propose a herbal preparation having potential to reduce inflammation among Rheumatoid Arthritis cases.

Yet another object of this invention is to propose a herbal preparation showing potentiality in preservation of functional capacity of Rheumatoid Arthritis cases.

A further object of this invention is to propose a preparation which improves and maintains the hemoglobin content, the general blood picture including ESR among Rheumatoid Arthritis cases.

A still further object of this invention is to propose a herbal preparation showing anti-oxidant and immuno-modulatory effects among Rheumatoid

Arthritis cases.

Yet a further object of this invention is to propose a herbal preparation effective in the prevention and management of anxiety and depression among Rheumatoid Arthritis cases.

Yet a still further object of this invention is to propose a preparation used as an adjuvant therapy along with conventional treatment among the Rheumatoid Arthritis cases.

Another object of the present invention is to propose an herbal formulation which has potential role in the regulation of the sleep pattern and to maintain the autonomic balance by regulating the sympathetic and para-sympathetic functions among Rheumatoid Arthritis cases.

STATEMENT OF INVENTION

According to this invention there is provided ά herbal preparation effective in the prevention and management of Rheumatoid Arthritis and associated complications, and particularly on the improvement of joint pain, inflammation (swelling), anti-oxidant and immuno-modulatory properties comprising at least two of the following plants selected from any of the six plants: 1. Vitex negundo, 2. Pluchea lanceolata, 3. Indigofera tinctoria, 4.Enicostemma littorale, 5. Cardiospermum helicacabum and 6. Dalbergia lanceolaria.

DETAIL DESCRIPTION OF THE INVENTION

According to this invention, there is provide a herbal preparation for the prevention and management of Rheumatoid Arthritis and associated complications, and particularly on the improvement of joint pain, inflammation (swelling), anti-oxidant and immuno-modulatory properties comprising at least two of the following plants selected from any of the six plants:

Name of the Plant

1. Vitex negundo

2. Pluchea lanceolata

3. Indigofera tinctoria

4. Enicostemma littorale

5. Cardiospermum helicacabum

6. Dalbergia lanceolaria

Preferably, the extracts of the plants may be present as follows:-

Name of the Plant Doses

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1. Vitex negundo 100-400 mg

2. Pluchea lanceolata 150-500 mg

3. Indigefera tinctoria 75-300 mg

4. Enicostemma littorale 75-300 mg

¹ 5. Cardiospermum helicacabum 100-350 mg

6. Dalbergia lanceolaria 100-350 mg

The formulation may also comprise a known additives such as minerals, vitamins, salts, filters (for capsulation/to prepare syrup/tablet) and binders, present in trace amount to the required level.

.0 Thus, any known additive or supplement is added to prepare the final preparation to the level of requirement in trace amount. Reference is made here in capsule form. However, it would be apparent that the preparation may also be in the form of syrup/tablet/capsule.

Preferably, the preparation comprises:

^L5 1. Vitex negundo 200 mg

2. Pluchea lanceolata 225 mg

3. Indigefera tinctoria 150 mg

4. Enicostemma littorale 100 mg

5. Cardiospermum helicacabum 125 mg -° 6. Dalbergia lanceolaria 125 mg

EXAMPLE 1

The hydro-alcoholic extract of Vitex negundo in the dose of 30 mg/day with the hydro-alcoholic extract of Pluchea lanceolata in the dose of 35 mg/day exhibited anti-inflammatory, analgesic and antioxidant effects among experimental rats and evident from the changes in paw volume of right and left hind paw of rats and reduction in lipid peroxidation and catalase activity. The body weight of the animals also increased along with correction of general blood pressure.

EXAMPLE 2

In pre-clinical trials when the hydroalcoholic extract of Vitex negundo (40 mg/kg/day) Pluchea lanceolata (.50 mg/kg/day^and Dalbergia lanceodaria (35 mg/kg/day) given to the rats which had developed carragenin paw edema causing by induced peritonitis and cotton pellet granuloma shows significant reduction in paw edema along with the correction of peritonitis and granuloma, indicating the potent anti-inflammatory activity of the new test formulation.

EXAMPLE 3

The above combination in the same dose exerted beneficial role on inflammatory markers like prostaglandin, cytokines, interleukins and c- reactive protein. A marked reduced in the above biological markers was observed under oral administration of the test formulation.

EXAMPLE 4

The oxidative stress determined by the assessment of lipid peroxidation, superoxide dismutase, anti-oxidant micro-nutrients, metabolic anti-oxidant i.e. albumin, ceruloplasmin, uric acid improved by the combination of hydro-alcoholic extract e.g. Enicostemma littorale (40 mg/kg/day), Cardiospermum halicacabum (50 mg/kg/day) when orally administered for a period of four weeks to the experimental animal.

EXAMPLE 5

When the animals which developed laboratory rheumatoid arthritis were treated with the hydro-alcoholic extract of Cardiospermum halicacabum (30 mg/kg/day), Enicostemma littorale (40 mg/kg/day) Indigofera tinctoria (35 mg/kg/day) showed hepatoprotective and nephroprotective effects. The liver enzymes and kidney function tests regulated under the present novel test formulations.

EXAMPLE 6

The hydro-alcoholic extract of Vitex negundo (300 mg/day) and Pluchea lanceolata (350 mg/day) given to Rheumatoid arthritis subjects, reduction in pain intensity and morning stiffness were noticed. The patients, reported better feeling because of reduced pain and their movability. Both the plants have analgesic and anti-inflammatory effects as reported by several workers. Because of its analgesic and anti-inflammatory property such effects could be observed.

EXAMPLE 7

When the hydro-alcoholic extract of Vitex negundo (350 mg/day), Indigofera tinctoria (225 mg/day) was administered to Rheumatoid Arthritis patients exhibited improvement in joint pain, morning stiffness and better sleep with a good work performance in day time. The plant Enicostemma littorale ahs shown beneficial effect on central nervous system as proven by various studies.

EXAMPLE 8

The combination of hydro-alcoholic extract of Pluchea lanceolata (250

mg/day), Enicostemma littorale (175 mg/day) and Cadiospermum helicacabum (250 mg/day) when given to Rheumatoid arthritis cases, it present the patients from oxidative injury and increase in hemoglobin content of Rheumatoid arthritis patient. The Rheumatoid arthritis cases have also reported relaxation in muscle contraction of affected area. A general reduction in pain was reported.

EXAMPLE 9

When the formulation containing organic extract of Indigofera tinctoria (150 mg/day), Enicospemma littorale (200 mg/day), Cardiospermum helicacabum (250 mg/day) and Dalbergia lanceolaria (225 mg/ day) was orally administered to Rheumatoid arthritis subject, a better health status was noticed. Improvement in appetie, increase in steep hours and also increase in body weight was noticed among Rheumatoid arthritis cases. A general feeling of well being was reported by Rheumatoid arthritis cases.

EXAMPLE 10

When the Rheumatoid arthritis cases were treated combination of hydro- alcoholic extract of Vitex negundo (350 mg/ day) Pluchea lanceolata (200

mg/day) Cardiospermum helicacabum (200 ' mg/day) and Dalbergia lanceodaria (175 mg/day) showed recovery of functional capacity as there was much improvement in pain and inflammation. An improvement in depressive behaviour was also noticed in Rheumatoid arthritis cases.

EXAMPLE 11

Indigofera tinctoria (175 mg/day), Pluchea lanceolata (250 mg/day) Cardiospermum helicacabum (250 mg/day) and Vitex negundo (250 mg/day) when combined and orally given to Rheumatoid arthritis cases, a marked decrease in prostaglandin E ₂ , Interleukir^ and c-reactive protein _W ere recorded following three months of therapy. The data obtained out of this group of study indicates that the plants used for this combination has ϊ shown anti-inflammatory and analgesic effects and a is helpful in the improvement and maintenance of general health condition.

EXAMPLE 12

The most promising effect was found with the combination prepared out of hydro-alcoholic extract of Vitex negundo (200 mg/ day) Pluchea lanceolata (225 mg /day) Indigofera tinctoria (150 mg/day), Enicostemma littorale (100

mg/day), Cardiospermum helicacabum (125 mg/day) and Dalbergia lanceodaria (125 mg/kg/day) for the management of Rheumatoid arthritis. The novel proposed herbal combination is found effective in reducing pain, inflammation, morning stiffness, restoration of normal functioning and better mental status of Rheumatoid arthritis cases. A decrease in depression and anxiety score were noticed. A feeling of well being and improved work performance both physical and mental indicates the overall improvement in various functions of the body, following three months test drug treatment. Body weight and physical strength also increase.

EXAMPLE 13

The above combination of Vitex negundo (200 mg/day) Pluchea lanceolata (225 mg /day), Indigofera tinctoria (150 mg/day), Enicostemma littorale (100 mg/day), Cardiospermum helicacabum (125 mg/day) and Dalbergia lanceodaria (125 mg/day) when given to Rheumatoid arthritis subject who were receiving conventional treatment also reported better health status like improvement in mental performance, sleep pattern and significant reduction in morning

stiffness. Betterment in pain relief was also noticed in Rheumatoid arthritis cases. On comparison, the Rheumatoid arthritis cases who were kept only on conventional treatment did not show such improvement as in group where the test formulation was given along with conventional treatment.

The preparation of the present invention exhibits synergism.

It is to be noted that the present invention is susceptible to modifications, adaptations and changes by those skilled in the art. Such variant embodiments employing the concepts and features of this invention are intended to be within the scope of the present invention, which is further set forth under the following claims:-