WO2017009870A1 - A topical formulation for chronic skin and hair disease - Google Patents

A topical formulation for chronic skin and hair disease Download PDF

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Publication number
WO2017009870A1
WO2017009870A1 PCT/IN2016/050236 IN2016050236W WO2017009870A1 WO 2017009870 A1 WO2017009870 A1 WO 2017009870A1 IN 2016050236 W IN2016050236 W IN 2016050236W WO 2017009870 A1 WO2017009870 A1 WO 2017009870A1
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vitamin
formulation
topical formulation
range
topical
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PCT/IN2016/050236
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French (fr)
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WO2017009870A4 (en
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Pramodbhai N. AHIR
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Ahir Pramodbhai N
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/241—Lead; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/965—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of inanimate origin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
    • A61K31/592—9,10-Secoergostane derivatives, e.g. ergocalciferol, i.e. vitamin D2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
    • A61K31/593—9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/30—Zinc; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/02—Medicinal preparations containing materials or reaction products thereof with undetermined constitution from inanimate materials
    • A61K35/08—Mineral waters; Sea water
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/28—Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/12—Aerosols; Foams
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair

Definitions

  • the present invention contemplates a topical formulation of sea water extract and Vitamin D and one or more inactive excipients.
  • the present invention also relates to a topical formulation for the treatment of chronic skin and hair disease of mammals like human and animals.
  • the human body's largest organ is the integumentary system, which includes the skin, hair, nails, glands and nerve receptors. Skin weighs about 6 lbs. (2.7 kilograms) and sheds itself about once every 27 days, according to the Cleveland Clinic. In adults, skin covers a surface area of 18 square feet (1.7 square meters), according to the University of Pennsylvania Health System (Penn Medicine).
  • Skin excretes wastes, regulates temperature and prevents dehydration by controlling the level of perspiration. It also houses sensory receptors that detect pain, sensation and pressure. The skin is also the body's initial defense against bacteria, viruses and other microbes. Skin and hair provide protection from harmful ultraviolet radiation, and the skin guards against sunburn by secreting melanin, according to the American Academy of Dermatology (AAD). Human skin color is determined by the interaction of melanin, carotene and hemoglobin. Human body is a large quantity of cells in the range of 10 12 to 10 16 . New production and removal of cells is a Continues process for human health. But some time there is disturbance in cells production and removal.
  • the ultraviolet sun rays of 280 to 315 nanometers provide vitamin D3.
  • This vitamin D3 reaches to kidney and liver, after metabolism vitamin D3 converts in vitamin-D. Then it reacts with lead (pb) and converts in 1.25 dihydroxy vitamin-D which is hormonal form of vitamin-D, hence vitamin-D is not a vitamin but it is a steroid hormone. Diet is second most important reason.
  • Fast food doesn't have sufficient minerals and vitamins. Due to crop pattern (same crop in same land for several years) not using secondary elements like calcium and magnesium as well as trace elements like zinc, ferrous, copper, boron and molybdenum are not used so food grains vegetables and fruits doesn't having sufficient nutrients as the human body requires.
  • the processed drinking water contains approximate 400 to 600 total dissolve solids which are not sufficient minerals for in drinking water. Due to these reasons, normal person doesn't get sufficient minerals and vitamin D and ultimately invites chronic diseases which further increase complications and invite other health conditions.
  • US6495174 discloses a composition comprising alcoholic extracts of herbs RhizomaZinziberisRecens, Rhizomapinelliae, Floscarthami, Radix rehmanniae, Radix angelicaesinensis, Radixpaenoiaerubra, Cacumenbiotae, Semensesaminigruin,
  • US6365199 discribes a hair growth formulation comprising of lemon peel extract including bioflavonoids membrane and castor oil.
  • US6451777 discloses a composition containing a compound from the group consisting of lupanetriterpenes, derivatives of lupane, oleanane, ursanetriterpenes and salts thereof for regulating hair growth and loss of hair.
  • US6358541 disclosed improved compositions comprising saw palmetto berry extract containing phyto sterols and one or more low irritability constituents that enhance penetration of the extract into hair follicular pores, for the treatment of androgenetic alopecia.
  • US6203782 discloses methods and compositions for promoting hair growth, preventing or minimizing hair loss, enhancing or restoring hair color or remelanization and treating other hair and skin conditions.
  • the compositions include as an essential component a treatment agent in an amount effective for treating the condition, preferably selected from the class of herbs consisting of Foeniculumvulgares (fennel seed), Pimpinellaanisum (anise), Carumcarvi (caraway seeds) and mixtures thereof with each other and/or other herbs.
  • US5000949 discloses a hair grooming composition, which promotes scalp and hair health and growth, comprising petroleum jelly, an oil extract of cactus, glycerin and oil of clover or other odorant and method of producing the composition.
  • an eczema treatment method comprises application of a therapeutically effective composition in the form of an aqueous topical cream to an affected area of an exterior skin region of a patient, the aqueous topical cream comprising water, a water-soluble organic liquid, a surface active agent, and vitamin D3 compound.
  • US5834016 relates to a liposome based topical formulation, particularly a formulation providing good penetration of biological active substances into the skin, and being particularly suitable for the treatment of psoriasis.
  • the invention relates to a liposome based formulation for the topical treatment of psoriasis containing Vitamin D, or a derivative thereof, particularly calcitriol, as an active ingredient.
  • US20110076328 describes a composition for the treatment or prevention of a disorder resulting in hair loss comprises a cardiac glycoside as active principal.
  • US20120199152 discloses a composition for topical treatment of hair loss/alopecia including three natural, active ingredients, caffeine, saw palmetto berry extract, and epigallocatechin-3-gallate (EGCG). The invention also provides methods for using this composition to treat hair loss.
  • EGCG epigallocatechin-3-gallate
  • US20130078301 describes method for stimulating hair growth includes providing a topical composition including a purified oil extract from Melaleucaalternifolia, also known as tea tree. The method may further include applying the topical composition to the skin surrounding the follicles of the human hair at least once a day.
  • a method for preventing the loss of human hair includes providing a topical composition including a purified oil extract from Melaleucaalternifolia, also known as tea tree. The method may further include applying the topical composition to the skin surrounding the follicles of the human hair at least once a day.
  • WO2014027363 describes an invention relates to an intra-dermally, sub-dermally or topically administrable growth factor concentrate derived from approximately 500 x 106 to 1500 [chi] 106 human platelets per ml for treating hair loss.
  • the concentrate comprises approximately 800 to 1200 pg/ml of Epidermal growth factor (EGF), 20 to 80 pg/ml of Vascular Endothelial growth factor (VEGF), 15 to 30 pg/ml of Basic fibroblast growth factor (b-FGF), 30000 to 40000 pg/ml of Transforming growth factor- [beta] (TGF- [beta]) and 100000 to 200000 pg/ml of Platelet Derived growth factor- AB (PDGF- AB).
  • EGF Epidermal growth factor
  • VEGF Vascular Endothelial growth factor
  • b-FGF Basic fibroblast growth factor
  • TGF- [beta] Transforming growth factor- [beta]
  • alopecia In present days common treatments for alopecia include hair transplantation, oral, and topical application of drugs and in some case natural solutions. Hair transplantation methods are usually painful, costly, and frequently result in an undesirable, unnatural appearance.
  • the predominant oral as well as topical preparations are chemical products such as Rogaine ® and Regaine ® , Propecia ® and Proscar ® ' Andolactone ® , Androcur ® , Eulexin ® .
  • oral contraceptives containing estrogens and/or estradiol
  • tretinoin tretinoin
  • azelaic acid are drugs that have been the subject of scientific studies for their potential to enhance hair growth.
  • Psoriasis is very well known and can be defined as an inflammatory skin disease of unknown cause which is usually chronic, frequently recurrent and acute in nature. This skin disease produces lesions that occur predominantly at certain sites, such as elbows, knees and scalp, although other areas of the body may be also inflamed. Psoriasis consists of dull, red, well-defined patches that are usually covered by distinctive silvery scales which, when removed, disclose tiny capillary bleeding points. These lesions spread by peripheral extension and may involve huge areas of the body. The patches are not constant in size, shape and location. Recent studies have shown that psoriasis can have a substantial impact on quality of life, even in patients with low severity psoriasis.
  • Psoriasis affects an estimated 2-3 percent of the world's population.125 million people worldwide have psoriasis, according to the World Psoriasis Day consortium. According to the US National Institutes of Health (NIH), between 5.8 and 7.5 million Americans have psoriasis, a prevalence of over 2%. A prevalence of 1.5% has been identified in the UK (Gelfand et al, 2005).
  • Eczema is the term used to describe a number of skin conditions including contact dermatitis, atopic dermatitis and seborrhoeic dermatitis. These conditions are characterized by pruritus (itchiness), erythema (redness), excoriation (scratches, scabs), induration (swelling) and papulation (bumpiness) of the skin.
  • causes can range from allergic reactions to external substances, as in contact dermatitis, to internal causes as in atopic dermatitis or a yeast infection as in seborrhoeic dermatitis. Symptoms can include red, extremely itchy rashes, fluid filled blisters and swelling.
  • Sea water extract which is prepared from sea water foam generated by friction of sea water and cuttlefish bone is traditionally used since long for many health conditions including otorrhea, skin disease and eye disease but not much studied for chronic skin disease. Further there is no any information how to incorporate sea water extract in palatable formulation.
  • the stable topical formulation of the present invention provides viable and safe and effective treatment of chronic skin diseases as described above.
  • the very first aspect of the present invention is to provide a topical formulation comprising Vitamin D and one or more inactive excipients with another topical formulation comprising sea water extract which comprises elemental calcium in range 0.01 to 10 gm/kg, elemental Lead in range 0.000057 to 0.0057 mg/kg, elemental Iron in the range 0.0385 to 3.85 mg/kg, elemental Zinc in the range 0.01 to 1.03 mg /kg and one or more inactive excipients.
  • Yet another aspect of the present invention is to provide a topical formulation which is to be used for the treatment of chronic skin disease including but not limited to alopecia, eczema, psoriasis, vitiligo and leucoderma in human and animals.
  • One more aspect of the present invention is to provide a topical formulation comprising 200 IU of Vitamin D and one or more inactive excipients with another topical formulation comprising 0.25 % w/w of sea water extract and one or more inactive excipients.
  • One more aspect of the present invention is to provide a topical gel formulation comprising Vitamin D, Sea water extract and one or more inactive excipients selected from cholesterol, buffering agent, chelating agent, anti oxidant
  • sea water extract comprises elemental calcium in range 0.01 to 10 gm/kg, elemental Lead in range 0.000057 to 0.0057 mg/kg, elemental Iron in the range 0.0385 to 3.85 mg/kg, elemental Zinc in the range 0.01 to 1.03 mg /kg.
  • topical formulation of the present invention formulation is to be applied topically on affected area for once or twice daily wherein gel part is applied first and then after oil formulation is applied on affected area of the body.
  • the present invention is all about a stable topical formulation comprising sea water extract and Vitamin D and one or more inactive excipients.
  • the topical formulation as per the present invention is prepared by using vitamin D and one or more inactive excipients and sea water extract and one or more inactive excipients.
  • topical formulation one comprising vitamin D and one or more inactive excipients and another comprising sea water extract which comprises elemental calcium in range 0.01 tolOgm/kg, elemental Lead in range 0.000057 to 0.0057mg/kg, elemental Iron in the range 0.0385 to 3.85mg/kg, elemental Zinc in the range 0.01 to 1.03mg /kg and one or more inactive excipients.
  • Vitamin D and sea water extract can be formulated in a single formulation in the form of emulsion or gel by combining oil part and water part using one or more inactive excipients.
  • the present invention can be formulated as single gel formulation containing Vitamin D and sea water extract and other excipients. To prepare gel formulation, gelling agent is required.
  • a gelling agent can be selected from the group comprising carbomers like carbopol, cellulosic polymers such as hydro xypropyl cellulose, hydroxy ethyl cellulose, methyl cellulose, and hydro xypropylmethyl cellulose; polyvinylalcohol; polyquaternium-10; natural and synthetic gums such as guar gum, hydroxypropyl guar gum, xanthan gum, acacia, and tragacanth; modified starch; acrylic acid/ethyl aery late copolymers; maleic anhydride - alkyl methylvinylethers and copolymers; polymethacrylate copolymers; oleogels.
  • carbomers like carbopol cellulosic polymers such as hydro xypropyl cellulose, hydroxy ethyl cellulose, methyl cellulose, and hydro xypropylmethyl cellulose
  • polyvinylalcohol polyquaternium-10
  • carbopol of carbomer group Preferably carbopol of carbomer group to be used.
  • Carbopol is available as Lubrizol Brand and available with different grades like Ultrez 10, Ultrez 20 etc.
  • present invention provides a topical gel formulation comprising Vitamin D, Sea water extract and one or more inactive excipients selected from cholesterol, buffering agent, chelating agent, anti oxidant.
  • the topical formulation of the present invention remains stable means the final formulation remains stable in term of visible appearance, color uniformity and consistency of the formulation and does not get changed on storage for longer time.
  • Topical formulation as used herein means a formulation intended for topical or local application to an affected region of a subject in need thereof, and includes such formulation forms as gel, cream, ointment, emulsion, suspension, solution, drops, lotion, douche, suppository, troche paint, pessary, spray, sponge, film, or foam.
  • the topical formulation is in the form of a cream, ointment, gel or lotion.
  • the present invention represents certain types of the topical formulations that include shampoo preparations; preparations for nail (like lacquers, paints, varnishes, top coats, base coats, nail hardeners and ridge fillers); vaginal and rectal formulations (like tablet, tampon, ovule, soft gelatin capsule, and ring); and mouth paints.
  • topical formulation means singe topical formulation or more than one topical formulation like one topical formulation contains Vitamin D and another topical formulation contains sea water extract.
  • the term “about” or “approximately” means within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, “about” can mean within 1 or more than 1 standard deviation, per the practice in the art. Alternatively, “about” can mean a range of up to 20%, preferably up to 10%, more preferably up to 5%.
  • % w/w as used herein means the % w/w to be calculated based in weight of the final formulation except where specifically defined. IU or International Unit as used herein for the measurement of Vitamin D is to be considered per gram of the final formulation.
  • Sea water extract as used herein means the dried foam of sea water. More specifically, the dried extract of sea water foam which gets produced after continuous friction of cuttlefish bone with sea water. In the sea when there is continuous friction between the waves of sea and cuttlefish bone floating on water, it produces the thick foam. This foam is collected and dried naturally under sunlight which produces the dried powder form which is to be used for the preparation of the present invention and is also termed as sea water extract herein.
  • Sea water extract contains minerals like Calcium, Ferrous(iron), Copper, Manganese and Zinc, lead, cadmium.
  • Sea water extract as used herein can provide elemental elemental calcium in range 0.01 to 10 gm/kg, elemental Lead in range 0.000057 to 0.0057 mg/kg, elemental Iron in the range 0.0385 to 3.85 mg/kg, elemental Zinc in the range 0.01 to 1.03 mg /kg.
  • the formulation when prepared with sea water extract it means the presence of elemental minerals and metals like elemental calcium in range 0.01 to 10 gm/kg, elemental Lead in range 0.000057 to 0.0057 mg/kg, elemental Iron in the range 0.0385 to 3.85 mg/kg, elemental Zinc in the range 0.01 to 1.03 mg /kg is to be considered.
  • Sea water extract as used herein can be used in the range from about 0.02 to 10% w/w of the formulation, preferably 0.25%w/w to get all elemental minerals mentioned above.
  • Vitamin D is a fat soluble vitamin produced from ergosterol and 7-dehydrocholesterol following exposure to sunlight and is responsible for enhancing intestinal absorption of calcium, iron, magnesium, phosphate and zinc. It is essential for the prevention of rickets, a disease in which the matrix of new bone is not mineralized.
  • Vitamin D3 also known as cholecalciferol
  • vitamin D2 ergocalciferol
  • Cholecalciferol and ergocalciferol can be ingested from the diet and from supplements.
  • Very few foods contain vitamin D; synthesis of vitamin D (specifically cholecalciferol) in the skin is the major natural source of the vitamin. Dermal synthesis of vitamin D from cholesterol is dependent on sun exposure (specifically UVB radiation).
  • Vitamin D The most common biologically active forms of Vitamin D are previtamin D2 and D3, and vitamin D2 and D3.
  • Previtamin D2 and vitamin D2 are produced from ergosterol and are biologically active in humans, cattle, swine and other mammals, but not in poultry.
  • Previtamin D3 and vitamin D3 are biologically active and are produced in the skin of many animals following irradiation of 7-dehydrocholesterol.
  • the other isomeric forms of vitamin D show no significant biological activity.
  • Vitamin D from the diet or dermal synthesis from sunlight is biologically inactive; activation requires enzymatic conversion (hydroxylation) in the liver and kidney.
  • Evidence indicates the synthesis of vitamin D from sun exposure is regulated by a negative feedback loop that prevents toxicity, but because of uncertainty about the cancer risk from sunlight, no recommendations are issued by the Institute of Medicine (US), for the amount of sun exposure required to meet vitamin D requirements.
  • US Institute of Medicine
  • Vitamin D is to be used in the range from 100 IU to 2000 IU per gram of the final formulation, preferably 200 IU per gram.
  • Vitamin D the source can be natural or synthetic.
  • the Vitamin D can be obtained from Tuna fish liver oil, cod liver oil, Albacore, calciferol, calcitriol and ergo calciferol.
  • Vitamin D can be used in the form of calciferol, calcitriol, ergocalciferol or mixture thereof.
  • Vitamin D the international unit or IU to be calculated based on weight of final formulation. Whenever value of IU is mentioned is per gram of the final formulation and not the actual IU of that formulation. For actual IU of Vitamin D, one has to calculate accordingly based on total weight of final formulation.
  • optionally saffron or magnesium chloride can be added in to the formulation.
  • Saffron is a spice derived from the flower of Crocus sativus, commonly known as the saffron crocus.
  • Crocus is a genus in the family Iridaceae.
  • Saffron crocus grows to 20-30 cm (8-12 in) and bears up to four flowers, each with three vivid crimson stigmas, which are the distal end of a carpel.
  • the styles and stigmas are collected and dried to be used mainly as a seasoning and colouring agent in food.
  • Saffron's taste and iodoform- or hay-like fragrance result from the chemicals picrocrocin and safranal. It also contains a carotenoid pigment, crocin, which imparts a rich golden-yellow hue to dishes and textiles.
  • Saffron contains minerals like Calcium, Fe(iron), Magnesium, phosphorus, Potassium, Sodium, Manganese, Selenium.
  • Formulation may further comprise Acid hydrolyzed Saffron.
  • Acid hydro lyzed Saffron can be taken from any known source and can be taken in the range from 0.25 to 25.0 gm/kg of formulation, preferably 0.5-10g/Kg of formulation and most preferably Acid hydrolyzed Saffron can be taken 2.5 g/Kg.
  • saffron may help alleviate the symptoms of major depressive disorder. Preclinical studies indicate that saffron could be a promising candidate for cancer chemoprevention studies.
  • the saffron is to be used in the form of extract of saffron or saffron powder.
  • the acid hydro lyzed saffron to be used.
  • the extract of saffron can be derived from any organic solvent known in the art with preference to methanol and ethanol either alone or in combination.
  • To prepare saffron extract take 3 gm of saffron buds and extract it out with 50 ml organic solvent and then evaporate the organic solvent to dryness to get saffron extract.
  • Magnesium chloride is a supplement version of magnesium, a mineral found naturally in the body. Certain foods, such as nuts, whole grains, beans and spinach, are rich sources of magnesium. Magnesium chloride supplements are not necessary unless you're deficient in the mineral.
  • Formulation may further comprise elemental Magnesium optionally.
  • Elemental magnesium can be taken from any known source and can be taken in the range from 0.11-11.0 g/Kg of formulation, preferably 0.5-2 g/Kg of formulation and most preferably Elemental magnesium can be taken 1.1 g/Kg.
  • Topical formulation as per the present invention can be selected from the formulation including but not limited to oil, gel, cream, ointment, emulsion, suspension, solution, drops, lotion, douche, suppository, troche paint, pessary, spray, sponge, film, or foam.
  • the topical formulation also contains one or more inactive excipients selected from group consisting of vehicle, vehicle base, solvent, surfactant, emulsifying agent, preservatives, anti oxidants, colorant, buffering agent, anti coagulant, fragrance and any other acceptable inactive ingredients based on the final formulation can be added based on the list of known inactive ingredients available in the art.
  • inactive excipients selected from group consisting of vehicle, vehicle base, solvent, surfactant, emulsifying agent, preservatives, anti oxidants, colorant, buffering agent, anti coagulant, fragrance and any other acceptable inactive ingredients based on the final formulation can be added based on the list of known inactive ingredients available in the art.
  • Emulsifying agent is to be used for the preparation of different type of emulsion for the preparation final topical formulation.
  • Emulsifying agent or emulsifier which may be used in the preparation of the present topical formulations include borax, carbomers, polyoxyethylene castor oil derivatives, sorbitan fatty acid esters, polyoxyethylenesorbitan fatty acid esters, polyoxyethylene alkyl ethers, emulsifying wax, caprylic and capric triglycerides, polyethylene glycol esters and others belonging to the class of non-ionic surfactants.
  • the amount of emulsifying agent or emulsifier which may be used in the present invention ranges from about 0.1% to about 10% by weight of the formulation.
  • Preservatives The main purpose of addition of preservatives is to prevent or inhibit the growth of microorganisms, which could result in to a risk of infection or degradation of the therapeutically active ingredient.
  • the preservatives used in the present invention of topical formulation include but are not limited to Sodium methyl paraben, Sodium Propyl paraben, sodium iso propyl paraban, Benzyl alcohol, Benzoic acid, Chlorocresol, Bronopol, phenoxy ethyl hexyl glycerin, phenoxy ethanol etc.
  • phenoxy ethyl hexyl glycerin and/or sodium methyl paraben, sodium propyl paraben and sodium iso propyl paraban and phenoxy ethanol are used as antimicrobial preservatives in the concentration range from 0.02% to 0.3 % w/w & 0.01 to 0.6 respectively.
  • Antioxidant The main role of antioxidant is to reduce the oxidation of active substances and excipients in the final product. Oxidative degradation can be accelerated by light and by the presence of mineral impurities, due to the formation of free radicals.
  • the antioxidants used in the preparation of topical formulation of the present invention include but are not limited to the following: ButylatedHydroxy Anisole, ButylatedHydroxyToulene, Ascorbic acid, Alpha tocopherol etc.
  • Colorant is to be added to give aesthetic look to the final topical formulation.
  • Colorants used for the present invention are those commonly known in the art. Specific colorants include, for example, dyes, an aluminum lake, caramel, colorant based upon iron oxide or a mixture of any of the foregoing. Especially preferred are organic dyes and titanium dioxide. Preferred ranges include from about 0.1% to about 15%.
  • Buffering agent Buffering agent is included in the topical formulation of the present invention to maintain the pH in a certain range to maximize the stability of the final formulation.
  • Suitable buffering agents can include, but are not limited to, acetate buffers, citrate buffers, phosphate buffers, lactic acid buffers, malic acid buffers, succinic acid buffers, borate buffers, sodium hydroxide, potassium hydroxide, and ammonium hydroxide.
  • Phosphate salts such as monosodium phosphate (NaH2P04; also known as monobasic sodium phosphate), disodium hydrogen phosphate (Na2HP04; also known as dibasic sodium phosphate), Potassium dihydrogen phosphate, Disodium hydrogen phosphate dihydrate, monopotassium phosphate (KH2P0), dipotassium phosphate (K2HP04), and mixtures thereof can also be used.
  • Cholesterol is to be used in the formulation for dissolving Vitamin D to get clear solution without any undissolved matter.
  • Lecithin is to be used to improve texture and to prevent rancidity in to the formulation on storage.
  • Sodium gluconate is to be used as a chelating agent.
  • Other ingredients that can be used as chelating agent are ethylene diamine tetracetic acid (EDTA), di-ethylene-triamine penta-acetic acid (DTPA), pyridoxal isonicotinoyl hydrazone, rhodotorulic acid, picolinic acid, nicotinic acid, neoaspergillic acid, methionine and lactic acid.
  • EDTA ethylene diamine tetracetic acid
  • DTPA di-ethylene-triamine penta-acetic acid
  • pyridoxal isonicotinoyl hydrazone pyridoxal isonicotinoyl hydrazone
  • rhodotorulic acid picolinic acid
  • nicotinic acid neoaspergillic
  • Formulation of the present invention can be prepared by the process known in the art based on the selection of final product and accordingly the inactive ingredients can be selected.
  • the topical formulation of the present invention is used for the treatment of chronic skin disease including but not limited to alopecia, eczema, psoriasis, vitiligo and leucoderma in human and animals.
  • topical bioavailability of the active constituents from formulation depends on the inactive ingredients used in the final formulation.
  • topical formulation of the present invention formulation is to be applied topically on affected area for once or twice daily wherein gel part is applied first and then after oil formulation is applied on affected area of the body.
  • the formulation is in single gel form, it can be used to apply once or twice a day on affected area.
  • topical formulation of the present invention is also stable in term of consistency, color and appearance. On storage at room temperature as well as harsh condition, the formulation remains stable without ant degradation or color change or unacceptable changes at room temperature.
  • topical formulation comprising vitamin D can be in the form of oil, emulsion or suspension, preferably in the form of oil.
  • Oil is used for preparation for topical formulation comprising Vitamin D.
  • Oil as used here can be one or combination of different oils.
  • Oils to be used for vehicle for formulation can be selected from coconut, sarso oil, olive oil, carrot seed oil, jojoba oil, tea tree oil, almond oil or mixture thereof.
  • the blend of coconut oil, sarso oil, olive oil, carrot seed oil, jojoba oil, tea tree oil, almond oil to be used as vehicle for preparing formulation of Vitamin D in the form of oil.
  • the oil formulation of Vitamin D contains cholesterol, vehicle, preservative and anti oxidant.
  • topical formulation comprising sea water extract can be in the form of gel, cream, ointment, emulsion, suspension, solution, lotion, spray, sponge, film, or foam, preferably in the form of gel.
  • Inactive excipients for topical gel formulation comprising sea water extract are selected from vehicle base, preservative, anti-oxidant, chelating agent and buffering agent.
  • Vehicle base for topical formulation comprising sea water extract
  • Vehicle base can be selected from the group consisting of petrolatum, cetyl alcohol, acrylic polymers and cellulosic polymers.
  • Ingredients that can be used as vehicle base can be alone or in combination with other.
  • Petrolatum is a pale yellow to yellow -colored, translucent, soft unctuous mass. It is odorless, tasteless, and not more than slightly fluorescent by daylight, even when melted.
  • Petrolatum is a purified mixture of semisolid saturated hydrocarbons having the general formula CnH2n+2, and is obtained from petroleum. The hydrocarbons consist mainly of branched and un- branched chains although some cyclic alkanes and aromatic molecules with paraffin side chains may also be present.
  • Petrolatum is mainly used in topical pharmaceutical formulations as an emollient- vehicle base; it is poorly absorbed by the skin.
  • Cetyl alcohol occurs as waxy, white flakes, granules, cubes, or castings. It has a faint characteristic odor and bland taste. Cetyl alcohol, used in pharmaceutical preparations, is a mixture of solid aliphatic alcohols comprising mainly 1-hexadecanol (C16H340). In lotions, creams, and ointments Cetyl alcohol is used because of its emollient, water- absorptive, and emulsifying properties. It enhances stability, improves texture, and increases consistency.
  • the emollient properties are due to absorption and retention of Cetyl alcohol in the epidermis, where it lubricates and softens the skin while imparting a characteristic 'velvety' texture.
  • Cetyl alcohol is also used for its water absorption properties in water-in-oil emulsions. For example, a mixture of petrolatum and Cetyl alcohol (19: 1) will absorb 40-50% of its weight of water. Cetyl alcohol has also been reported to increase the consistency of water-in-oil emulsions. In oil-in-water emulsions, Cetyl alcohol is reported to improve stability by combining with the water-soluble emulsifying agent. The combined mixed emulsifier produces a close packed, monomolecular barrier at the oil- water interface which forms a mechanical barrier against droplet coalescence.
  • Water soluble polymers such as hydroxyalkyl cellulose polymers (e.g. hydro xymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose and hydroxypropylmethylcellulose), carboxymethyl cellulose, methylhydroxyethyl cellulose and methyl cellulose, acrylic acid polymers or carbomer (e.g. carbopol); sodium alginate and carrageenans. Water soluble polymers are used for the preparation of different type of topical formulation as described herein.
  • hydroxyalkyl cellulose polymers e.g. hydro xymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose and hydroxypropylmethylcellulose
  • carboxymethyl cellulose methylhydroxyethyl cellulose and methyl cellulose
  • acrylic acid polymers or carbomer e.g. carbopol
  • sodium alginate and carrageenans sodium alginate and carrageenans. Water soluble polymers are used for the preparation of different type of topical formulation as described herein.
  • Preservative, anti-oxidant, and buffering agent are described above and the same can be used for preparing formulation of sea water extract.
  • Chelating agent for the use in present invention can be selected from sodium gluconate, ethylenediamine tetracetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), pyridoxal isonicotinoyl hydrazone, rhodotorulic acid, picolinic acid, nicotinic acid, neoaspergillic acid, methionine and lactic acid.
  • the topical gel formulation of sea water extract is having below composition:
  • Example 1 Topical formulation of Vitamin D in oil form:
  • Vitamin D is to be mixed with cholesterol with heating at 50-70°C.
  • Example 2 Topical formulation of sea water extract as gel formulation
  • step 2) solution to step 1) with stirring.
  • Example 3 Efficacy trial for treatment of eczema, psoriasis and alopecia
  • Vitamin D and Sea For alopecia 180 days eczema and psoriasis.
  • Example 4 Single formulation containg vitamin D and Sea water extract
  • Vitamin D Vitamin D
  • Lecithin Soya hydrogenated
  • cholesterol Alpha tocoferol to be dissolved in ethanol with stirring at 50-70 °C.
  • step 2) Mixture of step 2) to be added in mixture of step 1) with siring.

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Abstract

The present invention relates to a topical formulation comprising Vitamin D and sea water extract. The present invention also relates to topical formulation for the treatment of chronic skin and hair disease of mammals like human and animals and process for preparing the same.

Description

Description
Title of Invention : A TOPICAL FORMULATION FOR CHRONIC SKIN AND HAIR
DISEASE FIELD OF THE INVENTION:
The present invention contemplates a topical formulation of sea water extract and Vitamin D and one or more inactive excipients. The present invention also relates to a topical formulation for the treatment of chronic skin and hair disease of mammals like human and animals. BACKGROUND OF THE INVENTION
The human body's largest organ is the integumentary system, which includes the skin, hair, nails, glands and nerve receptors. Skin weighs about 6 lbs. (2.7 kilograms) and sheds itself about once every 27 days, according to the Cleveland Clinic. In adults, skin covers a surface area of 18 square feet (1.7 square meters), according to the University of Pennsylvania Health System (Penn Medicine).
Most skin is waterproof because of keratin, a fibrous protein, and it also is made up of water, other proteins, lipids and different minerals and chemicals.
Skin excretes wastes, regulates temperature and prevents dehydration by controlling the level of perspiration. It also houses sensory receptors that detect pain, sensation and pressure. The skin is also the body's initial defense against bacteria, viruses and other microbes. Skin and hair provide protection from harmful ultraviolet radiation, and the skin guards against sunburn by secreting melanin, according to the American Academy of Dermatology (AAD). Human skin color is determined by the interaction of melanin, carotene and hemoglobin. Human body is a large quantity of cells in the range of 1012 to 1016. New production and removal of cells is a Continues process for human health. But some time there is disturbance in cells production and removal. The reason behind it is lack of minerals and vitamin, which are an essential for production of enzymes and hormones which are having different function and one of them is cells production and removal of cells by producing enzymes, hormone and antioxidants. Antioxidants remove hazardous by the way a urinal, perspiration as well as solid waste. In normal condition human body gets vitamin D3 from sunlight which converts in vitamin D by kidney and liver after metabolism. Then it converts in 1.25 dihydroxy vitamin D by lead (pb). It is steroid hormone resulting in intentional absorption of minerals and vitamins resulting in cell production by cell division and growth. In the same manner antioxidants are also produced. So lack of sunlight is one cause for deficiency of vitamin D.
Currently prevailing chronic skin and hair disease is the result of deficiency of minerals, water and fat soluble vitamins and anti oxidants.
Further deficiency of minerals and vitamins have so many reasons like; (l)Ulcerative, (2) digesting problem (3) injury, (4) infection, (5) tense life (6) improper diet (fast food, junk food) (7) lack of nutrients in food (8) drinking of water which is demineralized or having less minerals.
As per ayurveda, human body is made up of earth, gas, fire, water and sky that is also called as "Panchmahabhoota" and therefore the supply of all molecules are required for the proper health and functioning of the body system. All these molecules should be made available to the body in proper proportion and proper time. If the proportion is not proper it may adversely affect the function of other elements.
In all minerals, calcium is directly responsible for production of vitamin D. if calcium is not available in human body resulting in deficiency of vitamin D, which is most important for mammals. Developed countries like U.S. A and Canada provides vitamin D fortified milk, which indicates the importance of vitamin D. so deficiency of vitamin D is resulting in deficiency of other minerals and vitamins, so it ends with nutrition deficiency which is directly responsible for production of enzymes and hormones resulting in cell division, cell production, cell growth and production of antioxidants. However now a day these diseases are increases, Because of life style and dieting manner, stressful life and use of processed drinking water. Today urban people are working in absence of sun light. Sun light is most important source of vitamin D3. The ultraviolet sun rays of 280 to 315 nanometers provide vitamin D3. This vitamin D3 reaches to kidney and liver, after metabolism vitamin D3 converts in vitamin-D. Then it reacts with lead (pb) and converts in 1.25 dihydroxy vitamin-D which is hormonal form of vitamin-D, hence vitamin-D is not a vitamin but it is a steroid hormone. Diet is second most important reason. Fast food doesn't have sufficient minerals and vitamins. Due to crop pattern (same crop in same land for several years) not using secondary elements like calcium and magnesium as well as trace elements like zinc, ferrous, copper, boron and molybdenum are not used so food grains vegetables and fruits doesn't having sufficient nutrients as the human body requires. The processed drinking water contains approximate 400 to 600 total dissolve solids which are not sufficient minerals for in drinking water. Due to these reasons, normal person doesn't get sufficient minerals and vitamin D and ultimately invites chronic diseases which further increase complications and invite other health conditions.
All this factors lead to chronic skin disease in one or another way and attack on one or another part of skin with different symptoms and such disease can be alopecia, eczema, psoriasis, leucoderma, hydrocele in human and animals. Majority of such diseases are called un-cured and could be managed only by way of some surgical treatment or very high cost therapy.
Currently available treatments include application of steroids, vitamin D and other pain killers. However these treatment options are not complete and effective as the main reason for chronic disease are free radicals which after treatments gets circulated in to the blood stream and remains circulated there. However after stopping or completion of treatment, the free radicals once again come to the site and result in the one or another chronic disease of skin or hair. For the better and complete treatment of chronic disease removal of free radicals from body system is compulsory and for that free radicals need to be come in such a particle size that it gets out from body in form of solid and liquid waste gives complete cure.
There are some medicines available in market, but not resulting in expected results. Those treatments are costly as well as having many side effects. Further available treatments needs to be continued for very long time which may affect body system by one or another way and if patient stop the treatment in between the symptoms starts appearing again and these medicines work as only symptom suppression treatment and not for complete cure.
US6495174 discloses a composition comprising alcoholic extracts of herbs RhizomaZinziberisRecens, Rhizomapinelliae, Floscarthami, Radix rehmanniae, Radix angelicaesinensis, Radixpaenoiaerubra, Cacumenbiotae, Semensesaminigruin,
Radixpolydonimultiflori, Fructusmori combined with Tincture Capsicum, Tincture Cantharidinate and OleumRicini for direct application to scalp for the treatment of all kinds of alopecia in humans. US6447762 describes the preparation of a hair lotion for hair protecting action and prevention of hair loss comprising extracts of herbs Humuluslupulus, Rosmarinusofficinalis and Swertia japonica and Silanodiol salicylate and other pharmaceutically acceptable carriers.
US6365199 discribes a hair growth formulation comprising of lemon peel extract including bioflavonoids membrane and castor oil.
US6451777 discloses a composition containing a compound from the group consisting of lupanetriterpenes, derivatives of lupane, oleanane, ursanetriterpenes and salts thereof for regulating hair growth and loss of hair.
US6358541 disclosed improved compositions comprising saw palmetto berry extract containing phyto sterols and one or more low irritability constituents that enhance penetration of the extract into hair follicular pores, for the treatment of androgenetic alopecia. US6203782 discloses methods and compositions for promoting hair growth, preventing or minimizing hair loss, enhancing or restoring hair color or remelanization and treating other hair and skin conditions. The compositions include as an essential component a treatment agent in an amount effective for treating the condition, preferably selected from the class of herbs consisting of Foeniculumvulgares (fennel seed), Pimpinellaanisum (anise), Carumcarvi (caraway seeds) and mixtures thereof with each other and/or other herbs.
US5000949 discloses a hair grooming composition, which promotes scalp and hair health and growth, comprising petroleum jelly, an oil extract of cactus, glycerin and oil of clover or other odorant and method of producing the composition.
T. Takahashi et. al., reported that Procynidin B-2 isolated from Apple juice acts as growth promoting factor on murine hair epithelial cells. Procyanidin B-2 therapy showed potential as promising cure for male pattern baldness (Phytother. Res. 15, 331-36, 2001). US20100081637 discloses an eczema treatment method comprises application of a therapeutically effective composition in the form of an aqueous topical cream to an affected area of an exterior skin region of a patient, the aqueous topical cream comprising water, a water-soluble organic liquid, a surface active agent, and vitamin D3 compound.
US5834016 relates to a liposome based topical formulation, particularly a formulation providing good penetration of biological active substances into the skin, and being particularly suitable for the treatment of psoriasis. In particular, the invention relates to a liposome based formulation for the topical treatment of psoriasis containing Vitamin D, or a derivative thereof, particularly calcitriol, as an active ingredient.
US20110076328 describes a composition for the treatment or prevention of a disorder resulting in hair loss comprises a cardiac glycoside as active principal. US20120199152 discloses a composition for topical treatment of hair loss/alopecia including three natural, active ingredients, caffeine, saw palmetto berry extract, and epigallocatechin-3-gallate (EGCG). The invention also provides methods for using this composition to treat hair loss.
US20130078301 describes method for stimulating hair growth includes providing a topical composition including a purified oil extract from Melaleucaalternifolia, also known as tea tree. The method may further include applying the topical composition to the skin surrounding the follicles of the human hair at least once a day. A method for preventing the loss of human hair includes providing a topical composition including a purified oil extract from Melaleucaalternifolia, also known as tea tree. The method may further include applying the topical composition to the skin surrounding the follicles of the human hair at least once a day.
WO2014027363 describes an invention relates to an intra-dermally, sub-dermally or topically administrable growth factor concentrate derived from approximately 500 x 106 to 1500 [chi] 106 human platelets per ml for treating hair loss. The concentrate comprises approximately 800 to 1200 pg/ml of Epidermal growth factor (EGF), 20 to 80 pg/ml of Vascular Endothelial growth factor (VEGF), 15 to 30 pg/ml of Basic fibroblast growth factor (b-FGF), 30000 to 40000 pg/ml of Transforming growth factor- [beta] (TGF- [beta]) and 100000 to 200000 pg/ml of Platelet Derived growth factor- AB (PDGF- AB). In present days common treatments for alopecia include hair transplantation, oral, and topical application of drugs and in some case natural solutions. Hair transplantation methods are usually painful, costly, and frequently result in an undesirable, unnatural appearance. The predominant oral as well as topical preparations are chemical products such as Rogaine® and Regaine®, Propecia® and Proscar®' Andolactone®, Androcur®, Eulexin®. Additionally, oral contraceptives (containing estrogens and/or estradiol), tretinoin, and azelaic acid are drugs that have been the subject of scientific studies for their potential to enhance hair growth. There are also a variety of other products on the market today that claim to aid in the growth of hair and effective for alopecia. However most of these treatments may have undesirable side effects or may result in re-occurrence of the condition if application is discontinued.
Psoriasis is very well known and can be defined as an inflammatory skin disease of unknown cause which is usually chronic, frequently recurrent and acute in nature. This skin disease produces lesions that occur predominantly at certain sites, such as elbows, knees and scalp, although other areas of the body may be also inflamed. Psoriasis consists of dull, red, well-defined patches that are usually covered by distinctive silvery scales which, when removed, disclose tiny capillary bleeding points. These lesions spread by peripheral extension and may involve huge areas of the body. The patches are not constant in size, shape and location. Recent studies have shown that psoriasis can have a substantial impact on quality of life, even in patients with low severity psoriasis.
Psoriasis affects an estimated 2-3 percent of the world's population.125 million people worldwide have psoriasis, according to the World Psoriasis Day consortium. According to the US National Institutes of Health (NIH), between 5.8 and 7.5 million Americans have psoriasis, a prevalence of over 2%. A prevalence of 1.5% has been identified in the UK (Gelfand et al, 2005).
Eczema is the term used to describe a number of skin conditions including contact dermatitis, atopic dermatitis and seborrhoeic dermatitis. These conditions are characterized by pruritus (itchiness), erythema (redness), excoriation (scratches, scabs), induration (swelling) and papulation (bumpiness) of the skin. Causes can range from allergic reactions to external substances, as in contact dermatitis, to internal causes as in atopic dermatitis or a yeast infection as in seborrhoeic dermatitis. Symptoms can include red, extremely itchy rashes, fluid filled blisters and swelling. Sea water extract which is prepared from sea water foam generated by friction of sea water and cuttlefish bone is traditionally used since long for many health conditions including otorrhea, skin disease and eye disease but not much studied for chronic skin disease. Further there is no any information how to incorporate sea water extract in palatable formulation.
Thus there is a need in the society for some stable formulation which contains sea water extract, Vitamin D which is for topical application and has no or less side effects and provides effective result against the chronic skin disease mentioned above.
The stable topical formulation of the present invention provides viable and safe and effective treatment of chronic skin diseases as described above.
SUMMARY OF THE INVENTION
Above discussed problems is overcome by inventors of the present invention by providing topical formulation as described herein. The very first aspect of the present invention is to provide a topical formulation comprising Vitamin D and one or more inactive excipients with another topical formulation comprising sea water extract which comprises elemental calcium in range 0.01 to 10 gm/kg, elemental Lead in range 0.000057 to 0.0057 mg/kg, elemental Iron in the range 0.0385 to 3.85 mg/kg, elemental Zinc in the range 0.01 to 1.03 mg /kg and one or more inactive excipients..
Yet another aspect of the present invention is to provide a topical formulation which is to be used for the treatment of chronic skin disease including but not limited to alopecia, eczema, psoriasis, vitiligo and leucoderma in human and animals. One more aspect of the present invention is to provide a topical formulation comprising 200 IU of Vitamin D and one or more inactive excipients with another topical formulation comprising 0.25 % w/w of sea water extract and one or more inactive excipients. One more aspect of the present invention is to provide a topical gel formulation comprising Vitamin D, Sea water extract and one or more inactive excipients selected from cholesterol, buffering agent, chelating agent, anti oxidant wherein sea water extract comprises elemental calcium in range 0.01 to 10 gm/kg, elemental Lead in range 0.000057 to 0.0057 mg/kg, elemental Iron in the range 0.0385 to 3.85 mg/kg, elemental Zinc in the range 0.01 to 1.03 mg /kg.
The application of the topical formulation of the present invention formulation is to be applied topically on affected area for once or twice daily wherein gel part is applied first and then after oil formulation is applied on affected area of the body.
DETAILED DESCRIPTION OF THE INVENTION
The present invention is all about a stable topical formulation comprising sea water extract and Vitamin D and one or more inactive excipients.
The topical formulation as per the present invention is prepared by using vitamin D and one or more inactive excipients and sea water extract and one or more inactive excipients. As per one embodiment topical formulation of Vitamin D and one or more inactive excipients with another topical formulation comprising sea water extract which comprises elemental calcium in range 0.01 to lOgm/kg, elemental Lead in range 0.000057 to 0.0057 mg/kg, elemental Iron in the range 0.0385 to 3.85mg/kg, elemental Zinc in the range 0.01 to 1.03 mg/kg and one or more inactive excipients.
As per one embodiment of the invention, there are two different topical formulation, one comprising vitamin D and one or more inactive excipients and another comprising sea water extract which comprises elemental calcium in range 0.01 tolOgm/kg, elemental Lead in range 0.000057 to 0.0057mg/kg, elemental Iron in the range 0.0385 to 3.85mg/kg, elemental Zinc in the range 0.01 to 1.03mg /kg and one or more inactive excipients.
As per another embodiment of the invention, Vitamin D and sea water extract can be formulated in a single formulation in the form of emulsion or gel by combining oil part and water part using one or more inactive excipients. In one embodiment the present invention can be formulated as single gel formulation containing Vitamin D and sea water extract and other excipients. To prepare gel formulation, gelling agent is required. For the present invention as a gelling agent can be selected from the group comprising carbomers like carbopol, cellulosic polymers such as hydro xypropyl cellulose, hydroxy ethyl cellulose, methyl cellulose, and hydro xypropylmethyl cellulose; polyvinylalcohol; polyquaternium-10; natural and synthetic gums such as guar gum, hydroxypropyl guar gum, xanthan gum, acacia, and tragacanth; modified starch; acrylic acid/ethyl aery late copolymers; maleic anhydride - alkyl methylvinylethers and copolymers; polymethacrylate copolymers; oleogels. Preferably carbopol of carbomer group to be used. Carbopol is available as Lubrizol Brand and available with different grades like Ultrez 10, Ultrez 20 etc. As per one embodiment, present invention provides a topical gel formulation comprising Vitamin D, Sea water extract and one or more inactive excipients selected from cholesterol, buffering agent, chelating agent, anti oxidant.
The topical formulation of the present invention remains stable means the final formulation remains stable in term of visible appearance, color uniformity and consistency of the formulation and does not get changed on storage for longer time.
Topical formulation as used herein means a formulation intended for topical or local application to an affected region of a subject in need thereof, and includes such formulation forms as gel, cream, ointment, emulsion, suspension, solution, drops, lotion, douche, suppository, troche paint, pessary, spray, sponge, film, or foam. Preferably, the topical formulation is in the form of a cream, ointment, gel or lotion. The present invention represents certain types of the topical formulations that include shampoo preparations; preparations for nail (like lacquers, paints, varnishes, top coats, base coats, nail hardeners and ridge fillers); vaginal and rectal formulations (like tablet, tampon, ovule, soft gelatin capsule, and ring); and mouth paints. Further for the purpose of present invention topical formulation means singe topical formulation or more than one topical formulation like one topical formulation contains Vitamin D and another topical formulation contains sea water extract. The term "about" or "approximately" means within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, "about" can mean within 1 or more than 1 standard deviation, per the practice in the art. Alternatively, "about" can mean a range of up to 20%, preferably up to 10%, more preferably up to 5%.
% w/w as used herein means the % w/w to be calculated based in weight of the final formulation except where specifically defined. IU or International Unit as used herein for the measurement of Vitamin D is to be considered per gram of the final formulation.
Sea water extract
Sea water extract as used herein means the dried foam of sea water. More specifically, the dried extract of sea water foam which gets produced after continuous friction of cuttlefish bone with sea water. In the sea when there is continuous friction between the waves of sea and cuttlefish bone floating on water, it produces the thick foam. This foam is collected and dried naturally under sunlight which produces the dried powder form which is to be used for the preparation of the present invention and is also termed as sea water extract herein.
Sea water extract contains minerals like Calcium, Ferrous(iron), Copper, Manganese and Zinc, lead, cadmium.
Sea water extract as used herein can provide elemental elemental calcium in range 0.01 to 10 gm/kg, elemental Lead in range 0.000057 to 0.0057 mg/kg, elemental Iron in the range 0.0385 to 3.85 mg/kg, elemental Zinc in the range 0.01 to 1.03 mg /kg.
As per present invention when the formulation is prepared with sea water extract it means the presence of elemental minerals and metals like elemental calcium in range 0.01 to 10 gm/kg, elemental Lead in range 0.000057 to 0.0057 mg/kg, elemental Iron in the range 0.0385 to 3.85 mg/kg, elemental Zinc in the range 0.01 to 1.03 mg /kg is to be considered.
Sea water extract as used herein can be used in the range from about 0.02 to 10% w/w of the formulation, preferably 0.25%w/w to get all elemental minerals mentioned above. Vitamin D
Vitamin D is a fat soluble vitamin produced from ergosterol and 7-dehydrocholesterol following exposure to sunlight and is responsible for enhancing intestinal absorption of calcium, iron, magnesium, phosphate and zinc. It is essential for the prevention of rickets, a disease in which the matrix of new bone is not mineralized. In humans, the most important compounds in this group are vitamin D3 (also known as cholecalciferol) and vitamin D2 (ergocalciferol). Cholecalciferol and ergocalciferol can be ingested from the diet and from supplements. Very few foods contain vitamin D; synthesis of vitamin D (specifically cholecalciferol) in the skin is the major natural source of the vitamin. Dermal synthesis of vitamin D from cholesterol is dependent on sun exposure (specifically UVB radiation).
The most common biologically active forms of Vitamin D are previtamin D2 and D3, and vitamin D2 and D3. Previtamin D2 and vitamin D2 are produced from ergosterol and are biologically active in humans, cattle, swine and other mammals, but not in poultry. Previtamin D3 and vitamin D3 are biologically active and are produced in the skin of many animals following irradiation of 7-dehydrocholesterol. The other isomeric forms of vitamin D show no significant biological activity.
Vitamin D from the diet or dermal synthesis from sunlight is biologically inactive; activation requires enzymatic conversion (hydroxylation) in the liver and kidney. Evidence indicates the synthesis of vitamin D from sun exposure is regulated by a negative feedback loop that prevents toxicity, but because of uncertainty about the cancer risk from sunlight, no recommendations are issued by the Institute of Medicine (US), for the amount of sun exposure required to meet vitamin D requirements.
For the preparation of the topical formulation of the present invention, Vitamin D is to be used in the range from 100 IU to 2000 IU per gram of the final formulation, preferably 200 IU per gram.
For Vitamin D, the source can be natural or synthetic. The Vitamin D can be obtained from Tuna fish liver oil, cod liver oil, Albacore, calciferol, calcitriol and ergo calciferol. For the purpose of present invention Vitamin D can be used in the form of calciferol, calcitriol, ergocalciferol or mixture thereof.
For calculation of Vitamin D, the international unit or IU to be calculated based on weight of final formulation. Whenever value of IU is mentioned is per gram of the final formulation and not the actual IU of that formulation. For actual IU of Vitamin D, one has to calculate accordingly based on total weight of final formulation.
Further as per one aspect of the present invention, optionally saffron or magnesium chloride can be added in to the formulation.
Saffron powder
Saffron is a spice derived from the flower of Crocus sativus, commonly known as the saffron crocus. Crocus is a genus in the family Iridaceae. Saffron crocus grows to 20-30 cm (8-12 in) and bears up to four flowers, each with three vivid crimson stigmas, which are the distal end of a carpel. The styles and stigmas are collected and dried to be used mainly as a seasoning and colouring agent in food. Saffron's taste and iodoform- or hay-like fragrance result from the chemicals picrocrocin and safranal. It also contains a carotenoid pigment, crocin, which imparts a rich golden-yellow hue to dishes and textiles.
Saffron contains minerals like Calcium, Fe(iron), Magnesium, phosphorus, Potassium, Sodium, Manganese, Selenium.
Saffron also contains vitamins like Riboflavin (vitamin B l), Niacin and Vitamin A (carotinoid) and Vitamin E. As per one embodiment, Formulation may further comprise Acid hydrolyzed Saffron. Acid hydro lyzed Saffron can be taken from any known source and can be taken in the range from 0.25 to 25.0 gm/kg of formulation, preferably 0.5-10g/Kg of formulation and most preferably Acid hydrolyzed Saffron can be taken 2.5 g/Kg. There is some evidence to suggest that saffron may help alleviate the symptoms of major depressive disorder. Preclinical studies indicate that saffron could be a promising candidate for cancer chemoprevention studies. Early studies suggest that it may protect the eye from the direct effects of bright light, and from retinal stress in additional to slowing down macular degeneration and retinitis pigmentosa. Some studies suggest that saffron may help relieve the symptoms of premenstrual syndrome.
For the purpose of the preparation of topical formulation of present invention the saffron is to be used in the form of extract of saffron or saffron powder. Preferably the acid hydro lyzed saffron to be used.
The extract of saffron can be derived from any organic solvent known in the art with preference to methanol and ethanol either alone or in combination. To prepare saffron extract, take 3 gm of saffron buds and extract it out with 50 ml organic solvent and then evaporate the organic solvent to dryness to get saffron extract.
Magnesium chloride
Magnesium chloride is a supplement version of magnesium, a mineral found naturally in the body. Certain foods, such as nuts, whole grains, beans and spinach, are rich sources of magnesium. Magnesium chloride supplements are not necessary unless you're deficient in the mineral.
Widespread acknowledgements of the depletion of magnesium in human diets have made it one of the most important nutrients to supplement in the diet. Recognition of low magnesium intake across all industrialized nations has led to an exponential growth of magnesium research. Magnesium's potent activities as a healing agent are part of a diverse history in traditional medicine around the world, and have been studied actively by medical practitioners as early as the 1600's. A 2006 report from the World Health Organization estimated that 75% of adults consume a diet that is deficient in magnesium.
As per one embodiment, Formulation may further comprise elemental Magnesium optionally. Elemental magnesium can be taken from any known source and can be taken in the range from 0.11-11.0 g/Kg of formulation, preferably 0.5-2 g/Kg of formulation and most preferably Elemental magnesium can be taken 1.1 g/Kg. Topical formulation as per the present invention can be selected from the formulation including but not limited to oil, gel, cream, ointment, emulsion, suspension, solution, drops, lotion, douche, suppository, troche paint, pessary, spray, sponge, film, or foam. As per one aspect the topical formulation also contains one or more inactive excipients selected from group consisting of vehicle, vehicle base, solvent, surfactant, emulsifying agent, preservatives, anti oxidants, colorant, buffering agent, anti coagulant, fragrance and any other acceptable inactive ingredients based on the final formulation can be added based on the list of known inactive ingredients available in the art.
Emulsifying agent is to be used for the preparation of different type of emulsion for the preparation final topical formulation.
Emulsifying agent or emulsifier which may be used in the preparation of the present topical formulations include borax, carbomers, polyoxyethylene castor oil derivatives, sorbitan fatty acid esters, polyoxyethylenesorbitan fatty acid esters, polyoxyethylene alkyl ethers, emulsifying wax, caprylic and capric triglycerides, polyethylene glycol esters and others belonging to the class of non-ionic surfactants. The amount of emulsifying agent or emulsifier which may be used in the present invention ranges from about 0.1% to about 10% by weight of the formulation.
Preservatives: The main purpose of addition of preservatives is to prevent or inhibit the growth of microorganisms, which could result in to a risk of infection or degradation of the therapeutically active ingredient. The preservatives used in the present invention of topical formulation include but are not limited to Sodium methyl paraben, Sodium Propyl paraben, sodium iso propyl paraban, Benzyl alcohol, Benzoic acid, Chlorocresol, Bronopol, phenoxy ethyl hexyl glycerin, phenoxy ethanol etc. Preferably, in the present invention phenoxy ethyl hexyl glycerin and/or sodium methyl paraben, sodium propyl paraben and sodium iso propyl paraban and phenoxy ethanol are used as antimicrobial preservatives in the concentration range from 0.02% to 0.3 % w/w & 0.01 to 0.6 respectively.
Antioxidant: The main role of antioxidant is to reduce the oxidation of active substances and excipients in the final product. Oxidative degradation can be accelerated by light and by the presence of mineral impurities, due to the formation of free radicals. The antioxidants used in the preparation of topical formulation of the present invention include but are not limited to the following: ButylatedHydroxy Anisole, ButylatedHydroxyToulene, Ascorbic acid, Alpha tocopherol etc.
Colorant: Colorant is to be added to give aesthetic look to the final topical formulation. Colorants used for the present invention are those commonly known in the art. Specific colorants include, for example, dyes, an aluminum lake, caramel, colorant based upon iron oxide or a mixture of any of the foregoing. Especially preferred are organic dyes and titanium dioxide. Preferred ranges include from about 0.1% to about 15%. Buffering agent: Buffering agent is included in the topical formulation of the present invention to maintain the pH in a certain range to maximize the stability of the final formulation. Suitable buffering agents can include, but are not limited to, acetate buffers, citrate buffers, phosphate buffers, lactic acid buffers, malic acid buffers, succinic acid buffers, borate buffers, sodium hydroxide, potassium hydroxide, and ammonium hydroxide. Phosphate salts such as monosodium phosphate (NaH2P04; also known as monobasic sodium phosphate), disodium hydrogen phosphate (Na2HP04; also known as dibasic sodium phosphate), Potassium dihydrogen phosphate, Disodium hydrogen phosphate dihydrate, monopotassium phosphate (KH2P0), dipotassium phosphate (K2HP04), and mixtures thereof can also be used. Cholesterol is to be used in the formulation for dissolving Vitamin D to get clear solution without any undissolved matter.
Lecithin is to be used to improve texture and to prevent rancidity in to the formulation on storage. Sodium gluconate is to be used as a chelating agent. Other ingredients that can be used as chelating agent are ethylene diamine tetracetic acid (EDTA), di-ethylene-triamine penta-acetic acid (DTPA), pyridoxal isonicotinoyl hydrazone, rhodotorulic acid, picolinic acid, nicotinic acid, neoaspergillic acid, methionine and lactic acid. The topical formulation of present invention acts by converting the free radicals in such a particle size that after going in to the blood stream they gets exited totally from either solid waste or liquid waste. Further with this process, simultaneously the production of new cells by cell division and cell growth starts parallel. Therefore after removal of free radical from the body site, the new cells get generated quickly and therefore the effect can be seen very quickly on the affected area of skin. Further as free radicals are totally removed from body, chances of reoccurrence of disease are very negligible.
Formulation of the present invention can be prepared by the process known in the art based on the selection of final product and accordingly the inactive ingredients can be selected.
The topical formulation of the present invention is used for the treatment of chronic skin disease including but not limited to alopecia, eczema, psoriasis, vitiligo and leucoderma in human and animals.
Further the topical bioavailability of the active constituents from formulation depends on the inactive ingredients used in the final formulation.
The application of the topical formulation of the present invention formulation is to be applied topically on affected area for once or twice daily wherein gel part is applied first and then after oil formulation is applied on affected area of the body.
As per one embodiment, if the formulation is in single gel form, it can be used to apply once or twice a day on affected area.
Further the topical formulation of the present invention is also stable in term of consistency, color and appearance. On storage at room temperature as well as harsh condition, the formulation remains stable without ant degradation or color change or unacceptable changes at room temperature.
As per one embodiment of the present invention topical formulation comprising vitamin D can be in the form of oil, emulsion or suspension, preferably in the form of oil.
As a vehicle mainly oil is used for preparation for topical formulation comprising Vitamin D. Oil as used here can be one or combination of different oils. Oils to be used for vehicle for formulation can be selected from coconut, sarso oil, olive oil, carrot seed oil, jojoba oil, tea tree oil, almond oil or mixture thereof. Preferably the blend of coconut oil, sarso oil, olive oil, carrot seed oil, jojoba oil, tea tree oil, almond oil to be used as vehicle for preparing formulation of Vitamin D in the form of oil. As per one embodiment, the oil formulation of Vitamin D contains cholesterol, vehicle, preservative and anti oxidant.
As per another embodiment the oil formulation of vitamin D is having below composition:
As per one embodiment of the present invention topical formulation comprising sea water extract can be in the form of gel, cream, ointment, emulsion, suspension, solution, lotion, spray, sponge, film, or foam, preferably in the form of gel.
Inactive excipients for topical gel formulation comprising sea water extract are selected from vehicle base, preservative, anti-oxidant, chelating agent and buffering agent.
Vehicle base for topical formulation comprising sea water extract can be Vehicle base can be selected from the group consisting of petrolatum, cetyl alcohol, acrylic polymers and cellulosic polymers.
Ingredients that can be used as vehicle base can be alone or in combination with other.
Petrolatum: Petrolatum is a pale yellow to yellow -colored, translucent, soft unctuous mass. It is odorless, tasteless, and not more than slightly fluorescent by daylight, even when melted. Petrolatum is a purified mixture of semisolid saturated hydrocarbons having the general formula CnH2n+2, and is obtained from petroleum. The hydrocarbons consist mainly of branched and un- branched chains although some cyclic alkanes and aromatic molecules with paraffin side chains may also be present. Petrolatum is mainly used in topical pharmaceutical formulations as an emollient- vehicle base; it is poorly absorbed by the skin.
Cetyl alcohol: Cetyl alcohol occurs as waxy, white flakes, granules, cubes, or castings. It has a faint characteristic odor and bland taste. Cetyl alcohol, used in pharmaceutical preparations, is a mixture of solid aliphatic alcohols comprising mainly 1-hexadecanol (C16H340). In lotions, creams, and ointments Cetyl alcohol is used because of its emollient, water- absorptive, and emulsifying properties. It enhances stability, improves texture, and increases consistency. The emollient properties are due to absorption and retention of Cetyl alcohol in the epidermis, where it lubricates and softens the skin while imparting a characteristic 'velvety' texture. Cetyl alcohol is also used for its water absorption properties in water-in-oil emulsions. For example, a mixture of petrolatum and Cetyl alcohol (19: 1) will absorb 40-50% of its weight of water. Cetyl alcohol has also been reported to increase the consistency of water-in-oil emulsions. In oil-in-water emulsions, Cetyl alcohol is reported to improve stability by combining with the water-soluble emulsifying agent. The combined mixed emulsifier produces a close packed, monomolecular barrier at the oil- water interface which forms a mechanical barrier against droplet coalescence.
Water soluble polymers such as hydroxyalkyl cellulose polymers (e.g. hydro xymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose and hydroxypropylmethylcellulose), carboxymethyl cellulose, methylhydroxyethyl cellulose and methyl cellulose, acrylic acid polymers or carbomer (e.g. carbopol); sodium alginate and carrageenans. Water soluble polymers are used for the preparation of different type of topical formulation as described herein.
Preservative, anti-oxidant, and buffering agent are described above and the same can be used for preparing formulation of sea water extract.
Chelating agent for the use in present invention can be selected from sodium gluconate, ethylenediamine tetracetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), pyridoxal isonicotinoyl hydrazone, rhodotorulic acid, picolinic acid, nicotinic acid, neoaspergillic acid, methionine and lactic acid.
As per one embodiment, the topical gel formulation of sea water extract is having below composition:
Ingredients %w/w Sea water extract 0.25
DM Water Qs
Lubrizol Ultrez 20 1
Alpha tocoferol 0.01
Ethanol 8
Lecithin (Soya hydrogenated) 5
Potassium dihydrogen phosphate 0.025
Disodium hydrogen phosphate 0.145
dihydrate
phenoxy ethyl hexyl glycerin 0.2
Sodium gluconate 0.05
NAOH Qs to adjust pH 7.4
The disclosure described above will enable any person having ordinary skill in the art to practice the invention. In order to better enable the reader to understand specific and different embodiments and the advantages thereof, reference to the following non-limiting examples is suggested. However, the following examples should not be read to limit the scope of the invention. Further based on the knowledge of above teaching and practical example, a person skilled in the art can do minor changes and prepare other form of topical formulation which is also covered in the scope of present invention. EXAMPLES
Example 1: Topical formulation of Vitamin D in oil form:
Figure imgf000020_0001
Procedure:
1) Vitamin D is to be mixed with cholesterol with heating at 50-70°C.
2) Coconut oil was added in water bath with continuous stirring; 3) Coconut oil of step 3) was cooled down to room temperature and to it olive oil, caroot seed oil, jojoba oil, almond oil, carrot seed oil, tea tree oil were added with continuous stirring;
4) Phenoxy ethyl hexyl glycerin and Alpha tocopherol was added to step 4) with stirring;
5) Sarso oil was added to step 5) to get final volume.
Example 2: Topical formulation of sea water extract as gel formulation
Figure imgf000021_0001
Procedure:
1) Sea water extract, Sodium gluconate and phenoxy ethyl hexyl glycerin was added to DM water with stirring and filtered by watmann filter;
2) Take Lecithin (Soya hydrogenated), Apha tocoferol to ethanol and dissolve at
temperature of 50-70 °C seperately.
3) Add step 2) solution to step 1) with stirring.
4) Lubrizol Ultrez 20 was added to step 3) with stirring and allowed to settle for 10 minutes;
5) 5% NaOH solution were added to step 4) to adjust pH 7.4
6) Potassium dihydrogen phosphate and Disodium hydrogen phosphate dihydrate to be added to mixture of step 5).
Example 3: Efficacy trial for treatment of eczema, psoriasis and alopecia
Number of patient: eczema (20), psoriasis (20) and Alopecia (15)
Age: 12 to 65 years
Figure imgf000021_0002
Combination of 60-90 days 70 to 80% have got complete cure in
Vitamin D and Sea For alopecia: 180 days eczema and psoriasis.
water extract 60 to 70% have got complete cure in alopecia.
Example 4: Single formulation containg vitamin D and Sea water extract
Figure imgf000022_0001
Procedure:
1) Sea water extract, sodium gluconate, Phenoxy ethyl hexyl glycerin to be dissolved in purified water with stirring and filter the mixture.
2) Vitamin D, Lecithin (Soya hydrogenated), cholesterol, Alpha tocoferol to be dissolved in ethanol with stirring at 50-70 °C.
3) Mixture of step 2) to be added in mixture of step 1) with siring.
4) Add Lubrizol Ultrez 20 to mixture of step 3) to obtain gel formulation and keep for 10 minutes.
5) Add NaOH solution to gel of step 4) to achieve pH of 7.4.
6) Potassium dihydrogen phosphate and Disodium hydrogen phosphate dihydrate to be added to mixture of step 5).

Claims

I/We claim;
1) A topical formulation comprising Vitamin D and one or more inactive excipients with another topical formulation comprising sea water extract which comprises elemental calcium in range 0.01 to 10 gm/kg, elemental Lead in range 0.000057 to 0.0057 mg/kg, elemental Iron in the range 0.0385 to 3.85 mg/kg, elemental Zinc in the range 0.01 to 1.03 mg /kg and one or more inactive excipients.
2) The topical formulation according to claim 1, wherein vitamin D is present in the range from 100 to 2000 IU.
3) The topical formulation according to claim 1, wherein the topical formulation comprising vitamin D is selected form of oil, emulsion, suspension.
4) The topical formulation according to claim 3, wherein the formulation is in the form of oil.
5) The topical formulation according to claim 4, contains Vitamin D, cholesterol, vehicle, preservative and anti oxidant.
6) The topical formulation according to claim 1, wherein topical formulation comprising sea water extract in the form of gel, cream, ointment, emulsion, suspension, solution, lotion, spray, sponge, film, or foam.
7) The topical formulation according to claim 6, wherein topical formulation comprising sea water extract is in the form of gel.
8) A topical gel formulation comprising Vitamin D, Sea water extract and one or more inactive excipients selected from cholesterol, buffering agent, chelating agent, anti oxidant wherein sea water extract comprises elemental calcium in range 0.01 to 10 gm/kg, elemental Lead in range 0.000057 to 0.0057 mg/kg, elemental Iron in the range 0.0385 to 3.85 mg/kg, elemental Zinc in the range 0.01 to 1.03 mg /kg.
9) The topical formulation comprising according to claim 1, wherein formulation comprising 200 IU of vitamin D and one or more inactive excipients and another formulation comprising 0.25% w/w of sea water extract and one or more inactive excipients.
10) The topical formulation comprising according to claim 1, is used for the treatment of chronic skin disease including but not limited to alopecia, eczema, psoriasis, vitiligo and leucoderma in human and animals.
PCT/IN2016/050236 2015-07-13 2016-07-12 A topical formulation for chronic skin and hair disease WO2017009870A1 (en)

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EP3441062A1 (en) * 2017-08-07 2019-02-13 Corbinos Pubill, Maria Teresa Seawater and salt powder balancing formulations and nutritional and pharmaceutical compositions

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WO2007099396A2 (en) * 2005-06-07 2007-09-07 Foamix Ltd. Antibiotic kit and composition and uses thereof

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WO2007099396A2 (en) * 2005-06-07 2007-09-07 Foamix Ltd. Antibiotic kit and composition and uses thereof

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3441062A1 (en) * 2017-08-07 2019-02-13 Corbinos Pubill, Maria Teresa Seawater and salt powder balancing formulations and nutritional and pharmaceutical compositions

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