WO2019142042A1

WO2019142042A1 - Synergistic medicinal preparation for treating skin disorders like tinea versicolor

Info

Publication number: WO2019142042A1
Application number: PCT/IB2018/060587
Authority: WO
Inventors: Jacob Varghese; Manjula BUSHAN
Original assignee: Individual
Current assignee: Individual
Priority date: 2018-01-22
Filing date: 2018-12-24
Publication date: 2019-07-25
Anticipated expiration: 2020-07-22

Abstract

The present invention relates to a synergistic formulation of medicine for treating skin disorders like tinea versicolor or pityriasis versicolor with a synergistic composition of formic acid, curcuma, Andrographolide along with water as medium. Pharmaceutical synergistic formulation to treat skin disorders like Pityriasis Versicolor comprising water, Formic Acid, extract of Curcuma longa, and Andrographlide of in the required proportions

Description

Title: SYNERGISTIC MEDICINAL PREPARATION FOR TREATING SKIN DISORDERS LIKE TINEA VERSICOLOR

The present invention relates to a synergistic formulation of medicine for treating skin disorders like tinea versicolor or pityriasis versicolor.

BACKGROUND OF THE INVENTION

Body organs aren’t all internal like the brain or the heart. There’s one we wear on the outside. Skin is our largest organ-adults carry some 8 pounds (3.6 kilograms) and 22 square feet (2 square meters) of it.

Skin disorders are common in most of the people. There are more than 40 varieties of skin diseases are identified by the medical science. Children, youngsters and adults have skin sickness. Skin disorders occurs due the infection of fungal and bacteria.

Fungal Skin Infections Fungal infections of the skin are very common and include athlete’s foot, joke itch, ringworm, and yeast infections. Ringworm Worms don’t cause ringworm. Rather, this superficial skin infection, also known as Tinea, is caused by fungi called Dermatophytes.

The fungus Malassezia is a type of yeast found on the surface of the skin. It normally doesn’t cause any health problems. In fact, many of the microbiota (or microscopic organisms), including yeasts like Malassezia, that live in large communities on your skin help protect you from infections and other pathogens that can cause harm or disease. They live alongside your body’s cells in symbiotic relationships, with skin cells and tiny organisms supporting and benefiting each other.

Sometimes, however, this yeast can grow out of control and affect the natural color or pigmentation of your skin. When this happens, you may develop patches of skin that are lighter or darker than the surrounding skin. This condition, which isn’t contagious, is known as tinea versicolor, or pityriasis versicolor. The condition occurs when a type of yeast from the Malassezia family causes an infection or suppresses your immune system.

Tinea versicolor is a common, benign, superficial cutaneous fungal infection usually characterized by hypopigmented or hyperpigmented macules and patches on the chest and the hack. In patients with a predisposition, tinea versicolor may chronically recur. The fungal infection is localized to the stratum corneum.

Tinea versicolor is caused by the dimorphic, lipophilic organisms in the genus Malassezia , formerly known as Pityrosporum. Fourteen species are recognized within this classification of yeasts, of which Malassezia globosa, Malassezia sympodialis, and Malassezia furfur are the predominant species isolated in tinea versicolor. Malassezia is extremely difficult to propagate in laboratory culture and is culturable only in media enriched with C12- to Cl 4-sized fatty acids. Malassezia is naturally found on the skin surfaces of many animals, including humans. Indeed, it can be isolated in 18% of infants and 90-100% of adults.

The organism can be found on healthy skin and on skin regions demonstrating cutaneous disease. In patients with clinical disease, the organism is found in both the yeast (spore) stage and the filamentous (hyphal) form. Factors that lead to the conversion of the saprophytic yeast to the parasitic mycelial morphologic form include a genetic predisposition; warm, humid environments; immunosuppression; malnutrition; pregnancy; and Cushing disease. Human peptide cathelicidin LL-37 plays a role in skin defense against this organism.

Even though Malassezia is a component of the normal flora, if can also be an opportunistic pathogen. The organism is considered to be a factor in other cutaneous diseases, including Pityrosporum folliculitis, confluent and reticulate papillomatosis, seborrheic dermatitis, psoriasis, and some forms of atopic dermatitis. Malassezia species have also been shown to be a pulmonary pathogen in patients with immunosuppression due to stem cell transplan ta ti on .

Tinea versicolor occurs more frequently in areas with higher temperatures and higher relative humidities. The national prevalence of this condition is 2-8% of the population. The exact incidence is difficult to assess because many individuals who are affected may not seek medical attention.

Tinea versicolor occurs worldwide, with prevalences reported to be as high as 50% in the humid, hot environment and as low as 1.1% in the colder temperatures.

Although the alteration in skin pigmentation is more apparent in darker- skinned individuals, the incidence of tinea versicolor appears to be the same in all races.

Several studies have addressed the frequency of tinea versicolor based on sex, and no dominance of either sex is apparent. Tinea versicolor is most common in persons aged 15-24 years, when the sebaceous glands are more active. The occurrence of tinea versicolor before puberty" or after age 65 years is uncommon. In more tropical countries, age frequency" varies; most cases involve people aged 10- 19 years who live in warmer, humid countries, such as Liberia and India

Tinea versicolor is a benign skin disease that causes scaly macules or papules on the skin. As the name implies ( versi means several), the condition can lead to discoloration of the skin, with colors ranging from white to red to brown. The condition is not considered contagious because the causative fungal pathogen is a normal inhabitant of the skin. Treatment leads to cessation of scaling within a few days, but discoloration may last for weeks to months. If scale cannot be provoked and new lesions are not developing, then there is no need to repeat treatment and the patient can be reassured that ongoing infection in unlikely.

Although tinea versicolor is recurrent for some patients and, therefore, a chronic disease, the condition remains treatable with the available remedies.

Patients need to realize that tinea versicolor is caused by a fungus that is normally present on the skin surface; thus, it is not considered a contagious disease. Sequelae from the disease are not permanent, and any pigmentary alterations resolve entirely 1-2 months after treatment is initiated. Treatment is needed to remedy" the condition and for prophylaxis to prevent recurrences.

Medical treatment of tinea versicolor is very" important. Patients should be informed that tinea versicolor is caused by a fungus that is normall present on the skin surface and is therefore not considered contagious. The condition does not leave any_" permanent scar or pigmentary_" changes, and any" skin color alterations resolve within 1-2 months after treatment has been initiated. Recurrence is common, and prophylactic therapy" may" help reduce the high rate of recurrence.

It is reported in Medical Journals that Tinea versicolor can be successfull treated with various agents. Effective topical agents include selenium sulfide, zinc-pyrithione, sodium sulfacetamide, ciclopirox olamine, tacrolimus, as well as azole and allylamine antifungals. Even if a small area of skin is involved, treating with topicais from the neck to the knees may make treatment more successful. Various regimens can be used. Selenium sulfide lotion is liberally applied to affected areas of the skin daily" for 2 weeks; each application is allowed to remain on the skin for at least 10 minutes prior to being washed off. In resistant cases, overnight application can be helpful. Topical azole antifungals can be applied every night for 2 weeks. Weekly application of any of the topical agents for the following few months may help prevent recurrence in patients with widespread disease, some topical antifungal therapy can be expensive. Over-the-counter shampoo formulations of selenium sulfide, zinc- pyrithione, and ketoconazole are low-cost options that are widely available and can easily be used to cover large surface areas. Topical alMamines have been demonstrated to be clinically and mycologically effective. Tacrolimus 0.03% applied topically has been shown to provide a mycologically effective treatment; however, it is not effective in speeding the reduction in appearance of hypopigmentation associated with tinea versicolor.

While oral ketoconazole is contraindicated for the treatment of tinea versicolor, the topical foam may be useful in some patients. The risk of serious liver damage, adrenal gland problems, and harmful drug interactions with use of oral ketoconazole outweighs it benefit for fungal skin infections.

Oral therapy with other systemic antifungals is effective for tinea versicolor and is often preferred by patients because of convenience and oral administration is less time consuming than topical treatment. Of course, oral therapy can be used in consort with topical regimens. Fluconazole, and itraconazole are the preferred oral agents. Various dosing regimens have been used. Fluconazole has been offered as a single 150- to 300-mg weekly dose for 2-4 weeks and is the safest oral agent. Itraconazole is usually given at 200 mg/d for 7 days. Pramiconazole and sertaconazole have also been used in the management of tinea versicolor. A review suggested the following dosing regimens: 200 mg/ d for 5 or 7 days of itraconazole, 300 mg/wk for 2 weeks of fluconazole, and 200 mg/d for 2 days of pramiconazole.

Oral therapy does not prevent the high rate of recurrence, and treatment with an oral or topical agent may need to be repeated intermittently throughout the year. Because tinea versicolor is a benign condition and oral therapy is not without risk, the decision to treat with an oral agent should be made only after a complete discussion of the risks involved. In the case of oral terbinafine, some subgroups of Mfiirfur apparently are not clinically responsive, although in vitro studies suggest fungistatic activity. Also, a regimen of 1 tablet a month of fluconazole or itraconazole has been used successfully to prophy tactically prevent recurrences.

Some methods have described successful treatment of tinea versicolor with photodynamic therapy. Photodynamic therapy (PDT) involves the use of photochemical reactions mediated through the interaction of photosensitizing agents, light, and oxygen for the treatment of malignant or benign diseases. Photodynamic therapy is a 2 -step procedure. In the first step, the photosensitizer is administered to the patient by one of several routes (eg, topical, oral, intravenous), and it is allowed to be taken up by the target cells. The second step involves the activation of the photosensitizer in the presence of oxygen with a specific wavelength of light directed toward the target tissue. Because the photosensitizer is preferentially absorbed by hyperproliferative tissue and the light source is directly targeted on the lesional tissue, photodynamic therapy achieves dual selectivity, minimizing damage to adjacent healthy structures.

Tinea versicolor has a high rate of recurrence, and prophylactic treatment with topical or oral therapy on an intermittent basis is necessary to prevent recurrences in most cases. Clotrimazole, salicylic acid ointment and other topical antifungal drugs like oral griseofulvin, ketoconazole tablets etc., are not satisfied with the efficacy and by which side effects also occur.

Recurrent episodes are very common because the yeast that causes the infection is a normal fungus that lives on skin. Medicated cleansers may be used one or two times a month to help prevent Tinea versicolor from coming back. You may need to use these cleansers if the infection keeps returning, especially if you live in a warm and humid area.

If diagnosed with Tinea versicolor, treatment will improve your long-term outlook. You may even be able to eliminate the infection. However, your skin may remain discolored for several weeks or months following treatment. Infection may also return when the weather becomes warmer and more humid. If condition returns, doctor may prescribe medication once or twice per month to prevent symptoms.

Tinea versicolor can return when the air outdoors is warm and humid, the yeast can quickly grow out of control. Some people who live in a tropical climate may need to use a medicated cleanser to prevent the yeast from overgrowing. People who live in an area that becomes warm and moist each spring may see Tinea versicolor return every year.

Even after successful treatment, your skin color may remain uneven for several weeks, or even months. Also, the infection may return in hot, humid weather. In persistent cases, you may need to take a medication once or twice a month to prevent the infection from recurring.

Pityriasis versicolor generally clears satisfactorily with treatment but often recurs when conditions are right for malassezia to proliferate. When the scaly component of Pityriasis versicolor recurs, antifungal treatment should be repeated. In those who have frequent recurrences, antifungal shampoo or oral antifungal treatment may be prescribed for one to three days each month.

Occasionally white marks persist long after the scaling and yeasts have gone and despite exposure to the sun. In such cases, further antifungal treatment is unhelpful.

Several inventions for the treatment & medication of tinea versicolor have been reported. But many of these inventions are not successful in treatment in preventive its recurrence and side effects.

Patent No. EP2387396:AGENT FOR PREVENTING AND TREATING PITYRIASIS VERSICOLOR: The present invention relates to an agent for the prophylaxis and treatment of pityriasis. The agent according to the invention comprises at least one transaminase inhibitor that effectively inhibits the development of the transamination process that is pathogenetically significant to the disease, prevents a recurrence of the disease, and is easy on the skin flora of humans. Upon entry into the environment, resistances are not induced in other fungi.

CN Patent No. 20120129800:- PITYRIASIS VERSICOLOR TREATING COMBINATION WATER AGENT:The invention relates to a pityriasis versicolor treating combination water agent, and belongs to the technical field of traditional Chinese medicine preparations, wherein the pityriasis versicolor treating combination water agent mainly comprises six bulk drugs such as glauber's salt, cortex pseudolaricis, periostracum cicadae, cortex dictamni, climbing groundsel herb and the like, and the bulk drugs are prepared into the liquid medicine for external application by using pharmaceutical equipment. The pityriasis versicolor treating combination water agent of the present invention has functions of heat clearing, dampness removing, wind-evil dispelling and itching relieving, and further has characteristics of good pityriasis versicolor treating effect, easy costing, safety and effectiveness.

CN Patent No. 101204539:- TINCTURE MEDICINE FOR TINEA VERSICOLOR:The invention relates to a Chinese traditional medicine preparation which is a tincture medicine used for treating tinea versicolor. The medicine is made from the following ingredients with a certain weight account: lOOg for hop, crude wheat germ and boneset each and 600ml of 75 per cent alcohol. The invention is characterized by novel prescription, low cost, convenient preparation and remarkable effect. CN Patent No. 104274592:- MEDICINE FOR TREATING TINEA VERSICOLOR: he invention provides a medicine for treating tinea versicolor. The medicine is characterized by being prepared from the following components in parts by weight: 40-50 parts of radix rehmanniae recen, 100- 150 parts of angelica sinensis, 25-30 parts of cassia twig, 25-30 parts of ligusticum wallichii, 25-30 parts of safflower carthamus, 25-30 parts of cortex moutan, 25-30 parts of cortex dictamni, 40-50 parts of radix polygoni multiflori, 40-50 parts of tribulus terrestris, 15-20 parts of ephedra, 10-15 parts of radix euphorbiae lantu, 40-50 parts of radix cyathulae, 40-50 parts of fructus cnidii, 25-30 parts of periostracum cicada, 60-80 parts of lonicera japonica, 40-50 parts of spina gleditsiae, 25-30 parts of saposhnicovia divaricata, 40-50 parts of radix sophorae flavescentis and 40-50 parts of rhizoma atractylodis. The medicine has the advantages of easily available raw materials, low cost, remarkable treatment effect and the like.

CN Patent No. 106581478:- MEDICINE FOR TREATING TINEA VERSICOLOR: The invention discloses a medicine for treating tinea versicolor, wherein the medicine comprises an externally applied medicine and an oral administration medicine; the externally applied medicine comprises a spartina alterniflora extract and a willow bark extract; the oral administration medicine comprises wheat germ, corn germ, herba ephedra and fiveleaf akebia fruit. In the medicine production process, small peptides, polypeptides and large peptides produced from enzymolysis of the wheat germ and the corn germ, 5% maltodextrin, starch, and oligosaccharides, polysaccharides and fine cellulose produced from enzymolysis of cellulose are fully emulsified, and coated herba ephedra and fiveleaf akebia fruit micro-powder particles have the diameter of 15 microns; the microencapsulation effect is good, absorption is easy, and the absorption rate is also greatly improved; the traditional Chinese medicine coated by the oligosaccharides, polysaccharides and fine cellulose is subjected to enzymolysis and has good curative effect on treatment of tinea versicolor together with the spartina alterniflora extract and a rhizoma atractylodis extract, has no obvious side effects occurred in the treatment process, and has short treatment cycle.

CN Patent No. 106266092:- CREAM FOR TREATING TINEA VERSICOLOR:The invention discloses cream for treating tinea versicolor and belongs to the technical field of Chinese herbal preparations. The cream is mainly prepared from six medicine raw materials, namely realgar, cortex pseudolaricis, radix sophorae flavescentis, periostracum cicada, fructus cnidii and cortex dictamni. The medicine raw materials are prepared into the cream through pharmaceutical equipment to be applied externally. The cream has the functions of clearing heat and eliminating dampness and removing toxicity and diminishing inflammation and is good in tinea versicolor treatment effect, convenient to smear, safe and effective.

US Patent No. 20020009422:- COMBINATION TANNING AND ANTIFUNGALTOPICAL SYSTEM FOR TREATING TINEA VERSICOLORrA combination tanning and antifungal topical system for treating tinea versicolor that includes a body wash, a tanning lotion and anti-fungal topical and a body spray devised to treat tinea versicolor and promote even tanning. The present invention includes the active ingredients tolnaftate and miconazole nitrate.

The closest Patent information available in using the ingredients of the present invention are follws. However the below invention doesn't specify the usage of Andrographolide as one of the main ingredeint in any of these invention.

CN Patent No. 101623480:- EXTERNAL WASHING CHINESE MEDICINAL COMPOSITION FOR TREATING TINEA COPORIS, TINEA CRURIS AND TINEA VERSICOLOR:The invention discloses an external washing Chinese medicinal composition for treating tinea corporis, tinea cruris and tinea versicolor. The composition comprises the following components in percentage by mass: 30 percent of curcuma longa, 18 percent of sophora, 18 percent of tuber stemona root, 18 percent of szechwan chinaberry fruit, and 16 percent of pseudolarix, wherein the total content of the five medicaments is 100 percent. The five medicaments are decocted with water to wash the external part of a body twice per day; and the tinea corporis, the tinea cruris and the tinea versicolor can be healed after 7 days of continuous use of the composition.

CN Patent No. 105920541:- TRADITIONAL CHINESE MEDICINAL COMPOSITION FOR TREATINGTINEA VERSILOR: The invention discloses a traditional Chinese medicinal composition for treating tinea versicolor. The traditional Chinese medicinal composition comprises the following crude traditional Chinese medicaments in parts by weight: 10 to 30 parts of lonicera japonica, 10 to 20 parts of ficus sarmentosa, 10 to 20 parts of Scutellaria baicalensis, 5 to 15 parts of salvia miltiorrhiza, 10 to 20 parts of scrophularia ningpoensis, 10 to 20 parts of mint, 10 to 20 parts of prunella vulgaris, 10 to 20 parts of Japanese knotweeds, 5 to 15 parts of coptis chinensis, 10 to 20 parts of curcuma aromatica, 10 to 20 parts of ligusticum wallichii, 5 to 15 parts of Siberian cocklour fruits, 10 to 20 parts of radix pseudostellariae, 10 to 20 parts of folium isatidis, 10 to 20 parts of roots of angled bittersweet, 5 to 15 parts of sweet wormwood herb, 10 to 20 parts of cyrtomium fortunei, 10 to 20 parts of ixora chinensis, 10 to 20 parts of rhubarb, 5 to 15 parts of impatiens balsamina, 10 to 20 parts of willow leaves, 10 to 20 parts of pratia nummularia, 5 to 15 parts of belvedere fruits and 5 to 15 parts of licorice. The traditional Chinese medicinal composition has the effects of clearing away heat and toxic materials, dispelling wind, eliminating dampness, promoting blood circulation, relieving itching and replenishing qi to invigorate the spleen, has remarkable curative effects on tinea versicolor, and can work reliably.

In any of the inventions above disclosed, the present invention with a synergistic composition of Formic Acid, Curcuma & Andrographolide along with water is not disclosed. It is for the first time the present invention discloses this novel synergistic composition.

SUMMARY OF THE INVENTION:

To solve the above mentioned problem only one way to invent a new medicines, of course there are variety of medicines available in the market for the skin diseases but all such treatments are not giving good results for all kinds skin disorders, thereby, we did a analysis on the types of skin diseases and segregated each skin diseases thereupon did a deep research on various specious of fungus and bacteria that causes the skin diseases. Therefore the invention shall be an inevitable part pathological medicine.

Primarily the invention is helpful to protect the skin, which is the largest organ of human body from a special species of fungus/ parasite. The invention only deployed for the particular kind of skin diseases no other alternatives.

It is new invention of medicine for the Tinea Versicolor skin diseases. It is a compound that consists of carboxylic acid certain percentage of curcuma longa, andrographolide and water. Its pharmaceutical technology.

The present invention relates to a herbal formulation prepared and applied topically two times daily for better results. The formulation contains the following ingredients.

• Formic acid

• Curcuma longa or turmeric

• Nilavembu or andrographolide

• Water

BREIF DESCRIPTION OF THE INVENTION:

The present invention can be described of its formulation and its composition as quantified. The components Formic Acid, Curcuma longa and Andrographolide are mixed in water in a specific quantities as described in the following paragraphs to get a synergistic formulation. The best results of the treatment of skin disease is achieved by this specific quantity of mixture.

Formic Aci as one of the ingredient; Formic acid is the simplest carboxylic acid. Formate is an intermediate in normal metabolism. It takes part in the metabolism of one-carbon compounds and its carbon may appear in methyl groups undergoing transmethylation. It is eventually oxidized to carbon diaoxide. Formate is typically produced as a byproduct in the production of acetate. It is responsible for both metabolic acidosis and disrupting mitochondrial electron transport and energy production by inhibiting cytochrome oxidase activity, the terminal electron acceptor of the electron transport chain. Cell death from cytochrome oxidase inhibition by formate is believed to result partly from depletion of ATP, reducing energy concentrations so that essential cell functions cannot be maintained. Furthermore, inhibition of cytochrome oxidase by formate may also cause cell death by increased production of cytotoxic reactive oxygen species (ROS) secondary to the blockade of the electron transport chain. In nature, formic acid is found in the stings and bites of many insects of the order Hymenoptera, including bees and ants. The principal use of formic acid is as a preservative and antibacterial agent in livestock feed. When sprayed oil fresh hay or other silage, it arrests certain decay processes and causes the feed to retain its nutritive value longer.

Curcuma as another ingredient: Curcuma longa is a member of the ginger family (Zingiberaceae) . Its rhizomes (underground stems) are the source of a bright yellow spice and dye. Turmeric is sterile (does not produce seed, but it does grow vigorously from the rhizomes). It is thought to have arisen by selection and vegetative propagation of a hybrid between wild turmeric {Curcuma aromaUcd), native to India, Sri Lanka and the eastern Himalayas, and some other closely related species.

The genus Curcuma includes many other economically important species, including C. amada (mango ginger), C. angustifolia (wild arrowroot, narrow- leaved turmeric), C. aromatica (Cochin turmeric, wild turmeric) and C. zedoana(zedoary) .

An upright, perennial herb to about 1 m tall. The rhizome (underground stem) is thick and ringed with the bases of old leaves. Turmeric only reproduces via its rhizomes.

Leaves are Large, oblong, up to 1 m long, dark green on upper surface, pale green beneath. Each leafy shoot (pseudostem) bearing 8-12 leaves. Flowers are Yellow-white, borne on a spike-like stalk 10-15 cm long. Flowers are sterile and do not produce viable seed. Seeds are Small, ovoid, brown. Not viable.

The exact origin of Curcuma longa is not known, but it is thought to originate from South or Southeast Asia, most probably from Vietnam, China or western India. It is only known as a domesticated plant and not found in the wild.

India is the world’s largest; producer, consumer and exporter of turmeric. Turmeric is also cultivated extensively in Bangladesh, China, Thailand, Cambodia, Malaysia, Indonesia and the Philippines.

Turmeric has been used in India for at least 2,500 years. It was recorded in China by 700 AD, East Africa by 800 AD and West Africa by 1200 It was introduced to Jamaica in the 18th century. Today, turmeric is widely cultivated throughout the. tropics.

Turmeric was probably cultivated at first as a dye and then became valued as a condiment as well as for cosmetic purposes. In the 13th century Marco Polo wrote of this spice, marvelling at a vegetable that exhibited qualities so similar to saffron. Familiar to the contemporary⁷ world as a prime component of curry powder, the orange-yellow rhizome's striking colour lent it a special aura in ancient India it has always been considered an auspicious material in the subcontinent, both amongst the Aryan cultures (mostly northern) and the Dravidian cultures (mostly southern), and its value may extend far in history to the beliefs of ancient indigenous peoples. Turmeric's common name in the north, haldi , derives from the Sanskrit andra , and in the south it is called manjal , a word that is frequently used in ancient Tamil literature. Turmeric has a long history of medicinal use in South Asia, cited in Sanskrit medical treatises and widely used in Ayurvedic and Unani systems. Susruta's Ayurvedic compendium, dating to 250 BC, recommends an ointment containing turmeric to relieve the effects of poisoned food.

Turmeric has been used for many conditions in traditional medicine in India, Pakistan and Bangladesh. The rhizome is the part that is most widely used. It can be prepared in various ways and is reputed to alleviate asthma and coughs. Many of its traditional uses are supported by scientific evidence.

Hot water extracts of the dried rhizome have been taken orally in Ayurvedic medicine to reduce inflammation. Turmeric is also regarded as a 'rasayana' herb, which is a branch of Ayurvedic medicine and is used to counteract ageing processes.

In Unani medicine, turmeric has been used for conditions such as liver obstruction and jaundice and has been applied externally for ulcers and inflammation. Roasted turmeric has been used as an ingredient of a preparation used to treat dysentery. Turmeric has also been used in tooth powder or paste.

A hot water extract of the. dried rhizome taken orally was reputed to slow lactation, regulate fat metabolism, help symptoms of diabetes, diarrhoea and liver diseases, and as a tonic calm the stomach. The fresh juice taken regularly on an empty stomach has been used to prevent stomach disorders. A hot water extract of the dried rhizome was reputed to have an abortion-promoting effect when taken orally or in the form of a pessary (when inserted into the vagina) .

Externally, the dried rhizome has been applied to fresh wounds and insect stings and to help the healing process in chickenpox and smallpox. Turmeric was reputed to improve complexion of the skin and has been applied externally_" to remove hair, act as a tonic and alleviate itching. Inhalation of turmeric smoke is reputed to relieve hiccups.

Turmeric rhizomes have also been mixed with other plants to produce traditional remedies for a range of conditions including tonsillitis, headaches, wounds, snake bites, stings, sprains and fractured bones.

Turmeric is not widely used in Western medicine, but has been investigated as a treatment for some conditions. Studies show that the rhizomes contain compounds that m y have therapeutic effects, which appear to support some of its uses in traditional medicine.

Turmeric has been shown to have anti- bacterial, anti-fungal, antioxidant and anti-inflammatory_" effects, to which can be added possible anti- ulcer, wound-healing, liver-protective and anti-cancer properties.

It contains yellow pigments called cureuminoids. One example of a curcuminoid is curcumin. Turmeric and curcumin are being investigated for ny beneficial effects they" might have on conditions such as cancer, dementia and irritable bowel syndrome and for potential cholesterol- lowering effects.

Some studies suggest that components of the essential oil, such as ar - fumerone, have anti-snake venom activity. The essential oil is also reported to have some insect repellent and insecticidal activity

Nilavembu or andrographolide as another ingredient: Andrographis paniculata or Nilavembu is an annual herbaceous plant in the family Acanthaceae, native to India and Sri Lanka.

It is widely cultivated in Southern and Southeastern Asia, where it has been traditionally" used to treat infections and some diseases. Mostly the leaves and roots were used for medicinal purposes. The whole plant is also used in some cases.

The main bioactive constituent of the Andrographis paniculata or Nilavembu plant is Andrographolide. In the whole plant, it is present around 81- 186 milligram per gram (mg/g). In flowers, it is detected up to 43.16 mg/g. Isoanclrographolide, Neoandrographolide and Bisandrographolide A are found in cotyledons. The high content of 14- deoxyandrographolide is found in young leaves, which varies from 10.67 to 24.54 mg / g. Other constituents such as Andrograpanin, 7-0- Methylwogonin, Skullcapfiavone Ϊ, 3,4-Dieaffeoylquinic acid, Onysilin are also present.

Andrographis paniculata or Nilavembu is an erect annual herb extremely bitter in taste in all parts of the plant body. The plant is known in north eastern India as Maha-tikta, literally "king of bitters", and known by various vernacular names (see the table below) . As an Ayurveda herb it is known as Kalmegh or Kalarnegha, meaning "dark cloud". It is also known as Nila- Vem.hu in Tamil, meaning "neem of the ground", since the plant, though being a small annual herb, has a similar strong bitter taste as that of the large Neem tree (Azadirachta. indica). In Malaysia, it is known as Hempedu Bumi, which literally means 'bile of earth' since it is one of the most bitter plants that are used in traditional medicine.

Andrographis paniculata. or Nilavembu grows erect to a height of 30-1 10 cm (12-43 in) in moist, shady places. The slender stem is dark green, squared in cross-section with longitudinal furrows and wings along the angles. The lance-shaped leaves have hairless blades measuring up to 8 cm (3.1 in) long by 2.5 cm (0.98 in). The small flowers are borne in spreading racemes. The fruit is a capsule around 2 cm (0.79 in) long and a few millimeters wide. It contains many yellow-brown seeds.

Andrographis paniculata or Nilavembu is distributed in tropical Asian countries, often in isolated patches. It can be found in a variety of habitats, such as plains, hillsides, coastlines, and disturbed and cultivated areas such as roadsides, farms, and wastelands. Native populations of A. paniculata are spread throughout south India and Sri Lanka which perhaps represent the center of origin and diversity of the species. The herb is an introduced species in northern parts of India, Java, Malaysia, Indonesia, the West indies, and elsewhere in the Americas. The species also occurs in Hong Kong, Thailand, Brunei, Singapore, and other parts of Asia where it may or may not be native. The plant is cultivated in many areas, as well.

Unlike other species of the genus, A. paniculata is of common occurrence in most places in India, including the plains and hilly areas up to 500 m (1 ,600 ft), which accounts for its wide use.

In India the major source of plant is procured from wild habitat. The plant is in Low Risk or Least Concerned in the iUCN category. Under various the Irade names, Annually on an average 2,000-5,000 tonnes (2,200-5,500 tons) of plant is traded in India.

Andrographis paniculata or Nilavembu (also called Siriyanangai) is a Siddha herb used for its antipyretic, bitter, digestive, cholagogue, hepatoprotective, and anti-inflammatory properties. It is useful in the treatment of intermittent fever, malaria, chronic fever, dengue fever, chikungunya and all diseases in which fever is the main symptom.

As reported in various publications Nilavembu alleviates fever, protects the liver, and provides strength to the body. It is also indicated in physical debility occurring after fever. It stimulates hepatic functions, improves appetite, enhances digestion, boosts metabolism, and reduces after effects of several medicines on the liver.

In addition, it is also beneficial in loss of appetite, hepatomegaly, fatty liver syndrome, incomplete evacuation, constipation, intestinal parasites, blood disorders, and skin diseases

Andrographis paniculata or Nilavembu has following medicinal properties.

1. Antipyretic

2. Anti-microbial

3. Anti-protozoan

4. Anti -infective

5. Insecticidal

6. Anti-oxidant

7. Anti-inflammatory

8. Immunostimulant

9. Anti-diabetic

10. Bitter

1 1. Blood detoxifier

12. Digestive

13. Cholagogue

14. Hepatic stimulant

15. Hepatoprotective

16. Nephropro tec l ive

Further reported Andrographis paniculata or Nilavembu also has anti proliferation activity observed in colon cancer it also modulates sexual functions by increasing blood flow to penile tissue and relaxing smooth muscles Andrographolide in it initially increase serum testosterone, but after its regular use for 6-8 weeks, testosterone starts declining to normal levels Andrographolide is the major constituent extracted from the leaves of the plant and is a bicyclic diterpenoid lactone. This bitter principle was isolated in pure form by Gorier (191 1). Systematic studies on chemistry of A. paniculata have been carried out.

Some known constituents are: 14-Deoxy- l 1-dehydroandrographolide, Plant

14-Deoxy- l 1-oxoandrographolide, Plant

5-Hydroxy -7 ,8 ,2 ' ,3 ' -Te tramethoxyflavone, Plant

5-Hydroxy-7,8,2'-Trimethoxyflavone, Tissue Culture

Andrographine, Root

Andrographolide, Plant

Neoandrographolide, Plant

Panicoline, Root

Paniculide-A, Plant

Paniculide-B, Plant

Paniculide-C, Plant

The above ingredients are synergistically mixed in a specific method in Water as medium.

The present invention can be described of its formulation and its composition asquantified. The components Formic Acid, Curcuma longa and Andrographolide are mixed in water in a specific percentage as described below to get a synergistic formulation. However the results of the treatment of skin disease is achieved by the specific quantity of mixture.

All the above ingredients are mixed together to form a paste or cream like substance for its usage on the skin affected as topical application. For best results the mixture is applied two or three times daily for better results. This medicinal formulation is used as topical application as external medicine to cure the skin disorders / diseases like tinea versicolor. This mixture / cream after preparation is administered by applying on the affected skin twice daily or as suggested by the medical professionals depending on the severity of the disease.

The method of the preparation of the above mixture can be done through laboratory preparation or industrial preparation.

Initially curcuma & Andrographolide are extracted (water based) and the extract is used in the prepration of the synergistic composition.

Take 1 kg of curcuma (turmeric) and smash it fine by using smashing machine and pour 1 litre water and mix and screen / centrifuge it for the sufficient quantity as per the requirement.

(the same method can be adopted for the andrographis extraction too).

Treatment Method: Take sufficient medicine on the surgical cotton and apply on the affected area on the skin daily two times in the morning and night and leave it .continue the same course for 10 to 15 days. During the course of treatment the affected skin gradually become more lighter and then it disappear .There is no side effects or no marks remain on the affected skin.

Claims

We Claim,

1. Pharmaceutical synergistic formulation to treat skin disorders like Pityriasis Versicolor comprising water , Formic Acid, extract of Curcuma longa, and Andrographlide of in the required proportions.

2. Pharmaceutical formulation to treat skin disorders as claimed in claim 1, wherein all the ingredients are mixed together to form a paste or cream like substance for usage.

3. Pharmaceutical formulation to treat skin disorders as claimed in claim 1, where the mixture is used for topical application on the skin preferably daily two times for effective results.