|Title of Invention||
"PREPARATION OF A DRUG FROM DRY MATURE SEEDS OF MYRISTICA FRAGRANS FOR THE TREATMENT AND CONTROL OF PSORIASIS IN HUMAN BEINGS BY EXTERNAL APPLICATION"
|Abstract||The present invention is about control and treatment of Psoriasis of plaque type, localized as well as generalized, by ethanol extract of mature dry seeds of Myristica fragrans. The main constituent of the volatile oil of M. fragrans is myristicin, which is reported to act as an analgesic, anti-inflammatory, antithrombotic and hypolepodemic agent with practically no side effects. The ethanol extract of the seeds, used in the present invention had pH of 5.5 and optical density of ----- Psoriasis, present in 1 to 3 % of most populations, is a common genetically determined non-infectious, chronic inflammatory skin disorder of unknown cause. The plaques of psoriasis are erythamatous, large and adherent with slivery scales. It may start at any age with unpredictable course. In the present invention, the ethanol extract of M. fragrans was tested against the scaly plaques of psoriasis in those cases who were resistant to local steroid applications or were on oral methotrexate therapy. In all these cases, first the itching stopped and then the plaque became soft with shedding of the scales exposing normal skin from underneath. This is a surprising effect of the present drug controlling plaques of the disease. It might prove to be a milestone for the control and treatment of psoriasis. This effect of ethanol extract of M. fragrans is being reported for the first time.|
|Full Text||3. Preamble to the description
Myristica fragrans (Nutmeg)
The principal aromatic constituent of the volatile oil of nutmeg, the dry ripe seeds of M. fragrans is myristicin or methoxysafrole.. This yields 7-16% volatile oil which contains approximately 4-8% myristicin, the nutmeg contains approximately 1.3% myristicin. In addition to it, the seed contains many other compounds also (Leung, 1980).
The chemical name of myristicin is l-allyl-5-methoxy-3, 4 methylene-dioxybenzene; CAS No. 607-91-0; empirical formula: C11H12O3; molecular weight: 192-22 (Merck Index, 1989).
Many scientists have reported different properties of the extracts of dry seeds of M. fragrans. Sell and Carlini (1976) reported anaesthetic effect of methyi-euganol and other euganol derivatives of the volatile oil fraction of M. fragrans. In Nigeria and Indonesia, the essential oil of nutmeg is used in rheumatism (Oliver-Berver, 1986, Gils and Cox, 1994), probably because the oil decreases the leve! of prostaglandins which are major mediators of the inflammatory action (Iwo, 1983). This is also a known
hemopreventor of chemically induced carcinogenesis (Singh and Rao, 1993). Its cytotoxic effect on cancer cells in vitro has been reported by Park et al (1998). Its antibacterial activity against Staphylococcus aureus has been reported by Parez and Anesini (1994). Sharma el al. (1995) and Ram el al (1996) have reported prevention of hypercholesterolemia and atherosclerosis in rabbits after supplementation with seed extract. Olajide et al. (1999) described biological effects of chloroform extract of M. fragrans in male Swiss albino mice and male wistar rats as analgesic, anti-inflammatory and antithrombotic, whereas antidiarrheal activity of crude nutmeg solution as-well as its petroleum ether extract has been reported by Grover et al. (2002). Myristicin which is the majopr component of essential oil of nutmeg is reported to posses extraordinarily potent hepatoprotective activity in mice against lipopolysaccharide (LPS) plus d-galactosamine (D-GaIN) induced hepatotoxicity (Morita et al. 2003). Though it has several other properties its toxicological effects have not been proved as yet (Hall Stror i and Thuvander, 1997).
But, till today there is no report about the effect of ethanol extract of M,fragrans against psoriasis of plaque type. Hence, this is the first report in this direction establ shing completely new invention which will prove to be the most important and effective treatment of psoriasis without any side effects. Review of literature on the present invention reveals that no attempt has been made by any other inventor on the control of psoriasis by ethanol extract of M. fragrans. The best of our knowledge no patent has been filed on this material outside or within India.
Psoriasis is a common, genetically determined noninfectious chronic skin disorder of unknown cause. It is characterized by well demarcated erythematous plaque with large, adherent silvery scales.
Between 1% and 3% of most populations has psoriasis. It may start at any age but is rare under 10 years and often seen between 1 5 and 40 years. The course of disease is unpredictable but is usually chronic with exacerbations and remissions.
The psoriatic plaques vary enormously between size and shape. They often start out discoid but end up polycyclic as several lesions coalesce. The main abnormality in this disease is increased epidermal proliferation due to excessive division of cells in the
basal layers, in addition to division of cells above this layer also. This increase has been calculated to be 27 times the number of mitosis in uninvolved skin where the mitosis is limited to the basal layer. The increased epidermis cell proliferation is also related to the increased replications and metabolism of dermal fibroblasts. Both dermal and epidermal abnormalities appear to be necessary for sustenance of psoriasis. Therefore, the transit time of keratinocytes through the epidermis is shortened and the epidermal turnover time falls from 28 to 5 or 6 days.
These skin lesions of psoriasis are variably pruritic. Traumatized areas often develop lesions of psoriasis in prone cases. In addition, other external factors may exacerbate psoriasis including infections, stress and medication (Lithium, beta blockers and antimalarials). Psoriasis is of the following types:-Plaque type
This is the most common variety of psoriasis. Patients with this have stable, slowly growing plaques which remain basically unchanged for long periods of tirnj. The most common areas affected are the elbows, knees, gluteal cleft and the scalp. Involvement tends to be symmetric. Inverse psoriasis
It affects the intertriginous regions including the axilla, groin, submammary regions and navel. It also tends to affect the scalp and soles. The individual lesions are sharply demarcated but may be moist due to their location. It rarely remits spontaneously. Eruptive psoriasis
This is most common in children and young adults. It develops acutely in individuals without psoriasis or in those with chronic plaque psoriasis. Patients | resent with many small erythematous droplet shaped scaly papules, frequently after upper respiratory tract infection with ß-hemolytic streptococci
The skin becomes universally red and scaly. Shivering compensates for the considerable heat loss. This unpleasant variant may be initiated by the irritant effect of tar or dithranol or the withdrawal of systemic or potent topical corticosteroids.
Patients with psoariasis may also develop pustural lesions. The generalized form is a rare but serious type of psoriasis. The outset is sudden with myriads of small sterile pustules erupting on an erythematous base. The patient is ill with swinging pyrexia. malaise, diarrhea and arthralgias.
The localized form which most often involves the palms and soles is more common. The eruption consists of numerous small sterile pustules lying on an erythematous base, which leave brown macules or scaling in their wake. About 10 percent of people with psoriasis can also develop psoriatic arthritis.
Treatment of psoriasis depends on the types, location and extent of disease. But, in general, all patients should be instructed to avoid excessive drying or irritation of their skin and to maintain adequate cutaneous hydration. Plaque type of psoriasis may be treated with topical application of crude Coal tar, Dithranol, Calcipotrial, Retinoids or glucocorticoids.
Widespread plaque type of psoriasis is also treated with light therapy, i.e. either sunlight or ultraviolet light fUV-A). Ultraviolet B (UV-B) spectrum is given alone or combined with coal tar or anthralin (Ingram regimen). The combination of the ultraviolet A (UV-A) spectrum with either oral or topical psoralens (PUVA) is also given for effective treatment. But this treatment, if given for a long period, increases the risk of skin aging, freckling, squamous cell cancer and melanoma of the skin.
If all these treatments fail, Methotrexate, an oral anticancer drug is given. It produces dramatic clearing of psoriatic patches, but at the same time, it produces many side effects also, including upset stomach, nausea, dizziness and liver disease which requires careful monitoring.
Cyclosporine, an immunosuppressant drug, may also be given in cases with widespread psoriatic plaques, but again it potentially affects the kidneys and blood pressure.
Thus, there is no permanent cure for psoriasis, though the above-mentioned drugs and treatments can relieve and control it, often for long periods of time. It may be persistent though it has got the tendency of recurrence with variable periods of remission.
Psoriasis does not affect the overall general health. If it is widespread, it can certainly cause a great deal of skin discomfort and emotional embarrassment and can affect job and leisure time activities.
The fluctuating nature of remission, persistence, severity and type of psoriasis is well known. None of the conventional treatments is capable of increasing the interval periods of remission of the disease and its severity; rather it becomes ineffective in giving relief with prolonged use. Its cure is not possible, as its etiology is still poorly understood..
The present drug starts acting by reducing the pruritis in psoriatic plaques. This stops further injury to the affected skin as scratching is known to increase the disease.
After a few applications, the psoriatic plaques start becoming softer and gradually the scales are shed off from the affected area exposing normal skin. Ti may be possible that it interrupts and stops abnormally high rate of proliferation of epidermal cells of the skin. Once this treatment is started, no other conventional treatment is required including glucocorticoids which is well known for its deleterious side effects and also its effectiveness after prolonged use and greater severity of remission.Since the present drug is derived from an edible spice, which is commonly used in Indian kitchen, it may also be formulated for oral administration for the control of this disease. Till date its toxic effects have not been reported until and unless given in very high doses.
The preparation of a drug by ethanol extraction of mature dry seeds of Myrislica fragrans which can effectively be used for the treatment and control psoriasis is a completely new invention. Preparation of such a drug was not known earlier to this invention as is obvious from the review of literature. The present drug is highly effective against psoriasis of plaque type, more effective than other conventional drugs including glucocorticoids therapy.
. Description - Complete specification
The dry mature seeds of"Myhsticafragrans were powdered in a pastle and mortar. One kilogram of this powder was immersed in 1.5 1 of ethanol in a conical flask and kept at room temperature (25 ±2° C) for a period of 10 days. The flask was shaken manually several times daily for 10 days. After this period the material was filtered through cotton and the filtrate was collected in glass beakers.
The filtrate was left in the beaker for one week at the above temperat are for evaporation of ethanol. The pH of the filtrate was 5.5 and the optical density was 7 50 nm.
The patients were divided into two groups. One group had localized plaques of psoriasis on hand, foot, scalp etc, and was resistant to local application of glucocorticoids as well as other convectional treatments.
The other group was suffering from psoriasis with widespread plaques on the body including scalp, anterior abdominal wall and extensor surfaces of limbs. This group had started psoriasis during early adolescence and at the time of consultation (25-40 yrs.) oral methotrexate therapy combined with local applications of glucocorticoids was being administered. In both the groups, the ethanol extract (drug) was applied gently on the plaques after initial testing for allergy.
After applications of the drug within 2-3 days the patients starting feeling reduction in itching. Within 2 to 3 weeks of the application the itching had completely stopped and there was 50-90% reduction in itching, scaling and thickness of the plaques. After 4-6 weeks, the plaques disappeared leaving smooth hypopigmented spots on the affected area, which took its own time in normalization.
The plaques on sole took a little more time in healing as compared to the plaques on dorsum of foot, which took more time in healing as compared to those on the dorsum of hand. The plaques on the palm took least time in improvement and completely disappeared without leaving any hypopigmented mark.
In all these cases systemic as well topical glucocorticoids were gradually stopped and only the present drug was continued. With the use of the new drug, the period of interval for the remission was observed to be prolonged and the frequency and intensity of remission became quite low.
This is in contrast to those cases who are on systemic and topical steroid therapy only because in such cases the period of interval of remission of the disease becomes gradually shortened with increasing intensity of the remission and progressive ineffectiveness of the treatment. Ultimately the disease becomes persistent. The intensity of the disease varies from person to person.
In the other group, which was on systemic methotrexate therapy, the s eroid herapy was gradually withdrawn after starting local application of the drug c n the plaques on different parts of the body including the extensor surfaces and scalp. Gradually, the dose of methotrexate was also reduced. It resulted into surprising improvement in the disease with complete clearing of the psoriatic patches. The trial to stop methotrexate completely resulted into a very mild remission of the disease, so it was continued in minimum possible doses.
Thus, the drug indirectly protects the affected patients from undesirable side effects of steroids as well as methotrexate therepy and completely heals the plaques of psoriasis without any side effects proving itself a milestone in the world of medicine.
We claim a novel and original preparation of a drug by ethanol extraction of mature dry seeds of"Myristica fragrans which can very effectively treat and control Psoriasis of plaque type in human beings without any side effects.
|Indian Patent Application Number||834/DEL/2004|
|PG Journal Number||17/2008|
|Date of Filing||06-May-2004|
|Name of Patentee||SINGH UDAI PRATAP|
|Applicant Address||A-2, NEW MEDICAL ENCLAVE, B.H.U., VARANASI-221005, INDIA.|
|PCT International Classification Number||A61K 35/00|
|PCT International Application Number||N/A|
|PCT International Filing date|