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1. (WO2019030772) AN OIL BASED FORMULATION FOR CURE/PAIN MANAGEMENT
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AN OIL BASED FORMULATION FOR CURE/PAIN MANAGEMENT

FIELD OF THE INVENTION

The present invention relates to an oil based formulation for rapid tissue healing progressing to cure and resulting in rapid and lasting pain relief in musculoskeletal injuries and disease, cough and sore throat. More particularly, this invention relates to a composition/formulation comprising of vitamin D derivatives/analogues, vitamin E, vitamin A and vitamin K dissolved in a mixture of suitable oils, ethanol/propanol and pharmaceutically acceptable excipients and carriers. The invention also provides various formulations and methods of preparing the same.

BACKGROUND OF THE INVENTION

All journal articles, other references, patents, and patent applications that are identified in this patent application are incorporated by reference in their entirety.

Damaged tissue results from age, nutritional deficiencies, wear & tear and injury. Pain is generally classified by multiple types and includes, but is not limited to: acute pain and chronic pain caused by damage to tissue such as bone, muscle, or organs. The onset of pain is often accompanied by anxiety or emotional distress and follows damaged tissue/nerve damage.

Pain results from the noxious stimulation of nerve endings. Nociceptive pain is caused by noxious stimulation of nociceptors (e.g., a needle stick or skin pinch), which then transmit impulses over intact neural pathways to the spinal neurons and then to the brain. Neuropathic pain is caused by damage to neural structures, such as damage to peripheral nerve endings or nociceptors, which become extremely sensitive to stimulation and can generate impulses in the absence of stimulation.

Oral/subcutaneous ways for pain relievers are typically prescribed for treatment of acute and chronic pain, including arthritic pain, musculoskeletal pain and neuropathic pain. Oral medicines presently in use may have various side effects including suitability, compatibility to patients, allergies, liver damage and also the amount of drug to be reached at the affected area through systemic circulation for efficacy of the drug and acts for few hours and require frequent repeat doses.

Compositions such as creams, gels, liniments, ointments, balm, lotion, emulsion, suspension, transdermal patch, dermal patch, liquid solution, powder and the like are useful in topical application for pain management. Compositions that readily coat the skin and at the same time provide effective adhesion to the skin surface are preferred.

Further, it is useful to have a composition that provides soothing relief to the skin as well as healing activity and less amount of drug enters the body and it minimizes side effects, however the exiting topical applications available provide relief for few hours only and do not provide lasting relief/cure.

Oral or subcutaneous vitamin D is quite effective in disease and resultant pain associated with vitamin D deficiencies, but it takes longer to heal and provide relief or remove pain and may take months. This route does not provide immediate relief especially in joint disease, spinal disease, skin conditions related to vitamin D deficiencies and wounds. Surprisingly the topical/local vitamin D application provides immediate and lasting relief in all indicated conditions.

There is a need for alternative topical composition/formulation that heals for effective relief, pain management progressing to lasting & fast relief and cure which can be applied over perforated or torn skin with minimum or no side effects, irritation and also to have optimum efficacy and that can provide fast/lasting relief and cure.

Vitamin D is a steroid hormone that plays a vital role in calcium and phosphate absorption and tissue healing. It participates in and influences many biological reactions in body directly or indirectly. In recent studies, several associations between low levels of vitamin D and neuropsychiatric disorders have begun to surface. These disorders include, but are not limited to: Alzheimer's disease, Parkinson's disease, multiple sclerosis, epilepsy, schizophrenia, and autism and many more.

Vitamin D includes Vitamin D-2 (ergocalciferol) and Vitamin D-3 (cholecalciferol). Vitamin D-3 is produced in human skin when it is exposed to ultraviolet B radiation present in sunlight. Vitamin D is known to regulate calcium and phosphorus levels in the blood. Vitamin D contributes to bone growth by helping bones with calcium supplies from food. Lack of adequate Vitamin D can result in bone softening diseases, including rickets and osteomalacia. Even in the absence of osteomalacia, persons with inadequate vitamin D intake may experience osteoporosis, also associated with joint pain, loss of bone density, increased bone fragility and muscular weakness. Vitamin D, in adequate quantities, is also believed to exhibit anti-tumor activity and prevents diabetes. As D-3 is produced in the skin, it can regulate skin cell proliferation and nourishes organs through which it passes on its journey to blood stream.

Vitamin D-3 synthesis is of high importance for the prevention of a broad variety of diseases, including various deficiencies and malignancies. Vitamin D-3 is produced in the epidermal skin layer during sun exposure by conversion of 7 -dch yd roch o lc sterol . 7- Dehydrocholesterol, a cholesterol-like molecule present in the skin, is the precursor of Vitamin D-3 and forms cholecalciferol after being exposed to sunlight. Cholecalciferol is the inactive, unhydroxylated form of Vitamin D-3.

Cholecalciferol is thereafter hydro xylated in the liver to become calcidiol (25-hydroxyvitamin D-3). Calcidiol is further hydro xylated in the kidney to become calcitriol (1, 25- dihydroxy vitamin D-3). Calcitriol is the active hormone form of Vitamin D-3. Furthermore, some vitamin D-3 metabolites have themselves been used as chemotherapeutic agents with anti-proliferative effects against several types of cancer including breast, colon, and prostate tumors, leukemia and lymphomas.

Vitamin D is crucial for musculoskeletal health, maintenance, and function. Vitamin

D insufficiency is common among patients undergoing spine surgery. There is a high prevalence of hypo-vitaminosis D in patients with musculoskeletal pain regardless of surgical intervention.

With the frequency and costs of spinal surgery increasing, it is imperative that efforts are continued to reduce the impact on patients and healthcare services. Studies into vitamin D and its associations with orthopedic surgery have yielded alarming findings with regards to the prevalence of vitamin D deficiency. Importantly, altered vitamin D status also contributes to a wide range of diseased conditions.

The components of the present invention act synergistically with acceptable pharmaceutically excipients and such composition/formulations have never been reported for topical applications with greatly enhanced efficacy.

OBJECTIVES OF THE INVENTION

in accordance with the present invention, it has been discovered that vitamin D can be applied topically in certain formulations that make the vitamin D bioavailable. Surprisingly, when this formulation is topically applied for spinal disorders, spinal disc compressions, sciatica, cervical spondylitis, damaged tissues due to injuries/ageing/nutritional deficiencies, cartilage damages, degraded/painful joints, injuries, wounds, sprains, penile fracture, thrombophlebitis, cough, sore throat, cracks and skin dryness etc. it provides immediate relief from pain and burning. It immediately results in tissue healing and pain & distress relief in around 15-20 minutes (the time taken for penetration of oil to reach affected area) along with removal of associated weakness. By setting in rapid healing/cure and lasting pain relief in injuries, wounds, damaged tissue, sciatica, cervical spondylitis, sprains, backache, joint disease & degradation, cartilage damage, dry skin, cracked skin, acne, boils, abscess, cough, sore throat etc. and removes numbness & pain in affected limbs like legs/feet/arms/hands due to nerve compressions in spine by healing the tissues damaged due to ageing, nutritional deficiencies or injuries, the vitamin D becomes therapeutically effective.

This topical application improves skin quality, skin tone, removes cracks, removes skin dryness, improves hair health, hair quality, hair tone and greatly reduces hair loss. It alleviates the need for pain killers, antibiotics and microbicidal. It delivers Vitamin D through topical route and removes vitamin D deficiency.

Accordingly, an object of the present invention, is to provide new synergistic composition(s) comprising a composition or formulation comprising of a vitamin D derivative or analogues, vitamin E. vitamin A and vitamin K dissolved in a mixture of suitable oil, ethanol/propanol and pharmaceutically acceptable excipients and carriers wherein the pharmaceutical composition is useful in the treatment of spinal disorders, spinal disc compressions, damaged tissues due to injuries/ageing/nutritional deficiencies, cartilage damages, degraded/painful joints, injuries, wounds, sprains, penile fracture, thrombophlebitis, boils, acne or abscess, cough, sore throat, cracks and skin dryness etc. and provides immediate relief from pain and burning.

It immediately results in tissue healing and pain/distress relief in around 15-20 minutes (the time taken for penetration of oil to reach affected area) along with removal of associated weakness and it sets rapid cure and lasting pain relief in injuries, wounds, damaged tissue, sciatica, cervical spondylitis, sprains etc. and cures numbness and pain in affected limbs due to nerve compressions in spine by healing the tissues damaged due to ageing, nutritional deficiencies or injuries, cough and sore throat, the vitamin D becomes therapeutically effective.

This topical application improves skin quality, skin tone, removes cracks, removes skin dryness, improves hair health, hair quality, hair tone and greatly reduces hair loss. It alleviates the need for pain killers and/or antibiotics and/or microbicidals. It delivers vitamin D through topical route and removes vitamin D deficiency.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is thus based upon the discovery that vitamin D can effectively treat and heal spinal disorders, disc compressions, sciatica, cervical spondylitis, resultant numbness and/or weakness in legs or feet or shoulders or arms or hands, damaged tissues, multiple injuries, wounds, sprains, cartilage damage, damaged or degraded or painful joints, penile fracture, boils, acne, abscess, thrombophlebitis, cough and sore throat, dry skin, cracked skin, hair loss in a short duration by healing damaged tissues due to ageing, deficiencies or injuries when administered topically in a therapeutically effective formulation. It provides rapid, lasting and permanent cure, it is found to heal wounds in less than two days, provide pain relief in 15-20 minutes, autocorrects spinal disc compressions, cures chronic trouble in few days, time taken is proportional to the duration (length) of chronic illness. By a therapeutically effective formulation it is meant that the active substance is bioavailable, which is able to exert a biological activity when administered in that formulation. Such formulations effectively exhibit the biological activity of vitamin D in diminishing or completely alleviating the distress involved in such conditions. The formulation is also pharmaceutically acceptable for topical application.

The Vitamin D3 or D2 or their derivatives or analogues along with vitamins A, E and K dissolved in ethanol/propanol oils and pharmaceutically accepted excipients are effective in healing, providing cure and pain relief through topical application in injured or degraded tissues/body parts due to age, nutritional deficiencies or diseases, such as Thrombophlebitis, Cervical spondylitis, pain in neck, backache, spine, shoulders, arms, hands, associated numbness and removal of spinal disc compressions.

Also effective in lower spinal disc compressions resulting in local pain, sciatica pain and numbness in lower limbs includes backache.

For wounds, it heals in around 40 hrs. and also removes associated pain in 20 minutes. For muscle and tissue injuries, it heals injuries and torn muscle and tissues very fast and removes the associated pain and distress in around 20 minutes. Heals and regenerates degraded tissues due to age or injuries, it also heals and regenerates cartilage and removes associated joint pain, inflammation, stiffness and weakness in joints and lubricate them. Heals fast sprains, their inflammation and provides associated pain relief in 20 minutes and very effective in multiple and sports injuries involving soft tissue, muscles, cuts or bruises etc.

It acts on abscess, heals it and provides relief in associated pain, burning, itching and dryness. Heals acne, boils and provides immediate relief from pain, itching and burning. Heals and provides immediate pain relief in cracks. Removes skin dryness, improves skin tone, and heals cracked skin. It also alleviates need for pain killers and/or antibiotics and/or microbicidals.

Vitamin D is essential in many biological processes and involved in biological reactions directly or indirectly. Vitamin D deficiency causes gap in these processes and healing does not take place effectively and immediately. When Vitamin D is delivered

locally by topical application body's natural healing and defense mechanism is activated locally which also results in immediate pain relief. Since the topical application follows natural route of vitamin D so it provides healing and relief naturally (vitamin D is synthesized in skin upon exposure to ultraviolet rays mainly from sun, gets dissolved in skin oil and is transported to bloodstream. Following this route it nourishes and heals organs through which it passes during its journey to blood stream).

This invention alleviates and eliminates the need for pain killers, antibiotics and microbicidals etc. wherever required. Healing process takes appreciably short time. Also included within the scope of this invention and within the meaning of the term vitamin D are analogs of vitamin D. Analogs of vitamin D are well known in the ait and such compounds can have modifications in the side ch ain and/or changes in the nuclear part of the secosteroid molecule. Vitamin D analogs can contain side chain modify cations involving introduction of unsaturation; transposing, adding, removing or substituting hydroxyl groups; substituting hydrogens; forming carbocyclic structure; introducing a heteroatom link; inverting stereo chemically; removing or adding a Iky I groups and changing the number of links in the side chain.

The present invention relates to novel synergistic composition); s ) comprising new synergistic composition); s ) comprising vitamin D, its derivative or analogue, vitamin E, vitamin K and vitamin A and Alcohols.

As used herein, the term "topical administration" or "topical delivery" means intradermal administration of a pharmaceutical by administration of the pharmaceutical or a composition comprising the pharmaceutical to intact/perforated skin. For instance, applying or rubbing a composition of the present invention onto an area of intact/perforated skin or by placing an intradermal patch comprising a composition of the invention onto an area of intact/perforated skin for desired effect .

The term "topical composition" means a pharmaceutical composition designed for topical administration and containing a pharmaceutical.

As used herein, the phrase "intradermal ly-acceptable" means any pharmaceutical, excipient or other component of a topical formulation that is safe, non-irritating or approved for intradermal or topical administration in mammals.

In one embodiment, the present invention relates to novel synergistic composition(s) or formulations comprising a vitamin D derivatives or analogues, vitamin E, vitamin A and vitamin K dissolved in a mixture of suitable oil including medicinal oils, ethanol/propanol and pharmaceutically acceptable excipients and carriers.

If desired, other additives including surfactants, penetration enhancers, preservatives, viscosity modifiers, and emulsion stabilizers may be included in the invented compositions. Suitable surfactants include sodium lauryl sulfate, cetostearyl alcohol, ceteareth 12, cet caret h 20, cetearyl alcohol, Cetomacrogol 1000, stearic acid, and poloxamer.

Suitable penetration enhancers include propylene glycol.

Suitable preservatives include mcthylparaben. propylparaben, ethylhexylglycerin, phenoxyethanol/propanoL chlorocresol, potassium sorbate, sorbic acid, bronopol, methychloroisothiazolinone, and methylisothiazolinone.

If desired, other additives may be included to modify the colour or aroma of the topical compositions described herein.

In a preferred aspect, the application provides a process for preparing the formulation of the present invention. The process comprises weighing individual ingredients and mixing with suitable oil base to obtain a stable solution. The solution obtained was kept in closed container and advised to shake well before application.

The present invention is described with reference to the following representative examples, which are given by way of illustration and should not be construed to limit the scope of the present invention.

Exemplary formulations are given below:

Example:

The composition is prepared by dissolving vitamin D in oil base along with pharmaceutically acceptable excipients.

Formula 1: An example of formulation comprises Cholecalciferol as 1 gm in 3300 gms (0.03%)

Formula 2: An example of formulation comprises Cholecalciferol as 1 gm in

2200gms (0.045%)

Formula 3: An example of formulation comprises Cholecalciferol as 1 gm in 2500gms (0.04%)

Formula 4: An example of formulation comprises Cholecalciferol as 1 gm in 330gms (0.3%)

Formula 5: An example of formulation comprises Cholecalciferol as 1 gm in 100 gms (0.1%)

Formula 6: An example of formulation comprises Cholecalciferol as 1 gm in 33000 gms (0.003%)

Carrier medium / solvent base:

Oil (Coconut, Sesame, Flax Seed, olive oil, peanut oil, almond oil, soya bean oil, mustard oil. sunflower oil. cod liver oil. medicinal oil or a mixture thereof.) q.s

Ethanol/propanol 0.1 - 2%

Vitamin E 0.1 - 5%

Vitamin A 0.1 - 5%

Vitamin K 0.001 - 1 %

Excipients and preservative: Quantity sufficient

The preferable ratio of vitamin D in oil base is 1: 3000 w/v.

Other compositions of vitamin D in oil base are prepared with different ratios, wherein the ratio of vitamin D in oil is 1:2200 w/v, 1:3300 w/v and 1 :2500 w/v, 1:330 w/v, 1 : 100 w/v. 1:33000 w/v

in another embodiment composition of vitamin D with different oil base are prepared.

In another embodiment it includes a process for preparation of a composition comprising :- (a) Individually weighing all the ingredients in separate containers,

(b) Mixing vitamin D in suitable oil base,

(c) Mixing of all ingredients with suitable excipients and preservatives to obtain the stable formulation.

Examples of Efficacy:

Sample Examples

Patient 1— History: N. K. Chaudhary, age-45, Male, Executive with 4 years history of Slip disc in L4. L5 causing back pain.

The patient applied the test formulation with vitamin D3 by massaging oil for 10 minutes twice a day into the painful area and after any activity. In 15 days felt completely relieved without the use of any other medication or exercise. It is notable that the patient has since continued to work and is pain-free.

Patient 2— History: Geeta, Age-35, female, Office Assistant, Foot sprain with swelling and pain.

Applied test formulation twice a day got pain free in 20 minutes and was completed relieved in two days without the use of any other medication.

Patient 3— History: William, age-50, Male, Security Guard had sudden back ache followed by severe pain in thighs. Complaining of inability to walk or stand.

After one month of his trouble the patient applied the test formulation with vitamin D3 by massaging the oil in spinal area twice a day. The patient got completely relieved in 20 days of his backache and pain in thighs. It is mentioned that patient did not apply test formulation on his thighs and the pain in thighs went away because of spinal disc corrections. And there was no use of any other medication or exercise during period of treatment.

Patient 4— History: Abhay S harm a. age-50, Male, Govt. Executive with 8 years history of slip disc had various types of treatment except surgery. Used test formulation for one month applied once every third day got 95% improvement and relief. The patient had recently developed knee joint pain and was total relieved of his ailment in one month without use of any other medicine or therapy.

Patient 5— History: Om Prakash, age-25, Male. Masson met with an accident on his motorcycle was severely injured having deep and long cut near his elbow and large bruised area over his shoulder with blue color and was unable to lift his arm. He was having severe pain. Applied test formulation on second day. In 20 minutes he experienced no pain and was able to lift his arm freely. Oil was applied for three days three times a day. His bruises dried in forty hours and his deep cut healed in three days. No other pain killer, antibiotic or microbicidal was used during period of treatment with test formulation and patient felt no pain during this period.

Patient 6— History: Ramesh Kumar, age -46. Male, Gardner, got his tow crushed by-concrete stone had severe pain and bleeding. Applied test formulation after 15 minutes of injury the pain stopped in 15 minutes. Test formulation was applied for three days three times a day and the wound completely healed in 3 days. No other pain killer, antibiotic or microbicidal was used during period of treatment with test formulation and patient felt no pain during this period.

Patient 7— History: Jameela, age-55, Female, Canteen employee, had severe knee pain for last one year, was not able to walk and the life was difficult for her. Her mobility was restricted. Started using test formulation in 1 t week of February 2018, applied it once a daily and she was completely relived of her pain in 15 days. No other medicine and pain killers were used during this period. She applies test formulation around seven times per month and is leading trouble free and pain free life since then.

Surprisingly the composition prepared with ratio of vitamin D in oil base 1:3000 w/v have shown better efficacy.

The oil used in preparing the formulation is selected from suitable and compatible oil selected from the organic oils, vegetable oils and medicinal oils. The specific oils are selected among the oils from but not limited to the Coconut. Sesame, Flax Seed, olive oil. peanut oil, almond oil, soya bean oil, mustard oil, sunflower oil, cod liver oil, medicinal oil or a mixture thereof.

Vitamin D is synthesized in skin by action of UV (295-315) on 7-dehydrocholestrol and performs autocrine and paracrine functions in skin. Vitamin D in blood nourishes organs and heals the malfunctions/deficiencies in various organs including spine, muscles and other tissues. The same natural path is utilized in this innovation of vitamin D oil application to provide similar benefits. Based on the application following the natural path, the formulation is applied topically and it is found to affect cure in the organs beneath area of application and relieves pain as immediately when it reaches the affected tissue normally in 15 to 20 minutes of application.

Advantages:

It heals and cures sprains and removes associated pain and distress.

Provides relief in multiple injuries and heals sports injuries in very short time.

It regenerates cartilage, lubricates joints and found to drastically reduce their pain and inflammation. It cures joint disease.

It effectively heals penile fracture.

The topical pharmaceutical composition may be used in the treatment of backache, spinal disorders, disc compressions and damaged tissue due to ageing, deficiencies or injuries. It corrects spinal disorders, removes pain and heals tissues, and is able to cure sciatica and associated pain & numbness in lower limbs, cervical spondylitis and associated pain and numbness in shoulders, arms or hands, when applied over spine only.

It also promotes and expedites wound healing and removes associated pain, itching, inflammation and distress immediately.

It is found to heal boils and acne.

It is found to heal abscess.

It is also found to heal cracks, remove skin dryness and improves skin tone.

It improves hair health & tone and stops hair loss.

It heals thrombophlebitis and immediately removes pain.

It provides relief in cough and sore throat.

The topical pharmaceutical composition may be used in the treatment of spinal disorders, disc compressions, sciatica, cervical spondylitis, resultant numbness of

associated limbs, boils, acne, dry or cracked skin, wounds, sprains, injuries and joint disease etc.

The topical formulation is also useful for the conditions wherein cutaneous nerves may be involved.

The present invention also relates to process of preparation of the compositions or formulations of the present invention.

While the invention has been described and illustrated with reference to certain particular embodiments thereof, those skilled in the art will appreciate that various adaptations, changes, modifications, substitutions, deletions, or additions of procedures and protocols may be made without departing from the spirit and scope of the invention. For example, effective dosages other than the particular dosages as set forth herein above may be applicable as a consequence of variations in responsiveness of the mammal being treated for any of the indications with the compounds of the invention indicated above. The specific pharmacological responses observed may vary according to and depending upon the particular active compounds selected or whether there are present pharmaceutical carriers, as well as the type of formulation and mode of administration employed, and such expected variations or differences in the res tills arc contemplated in accordance with the objects and practices of the present invention. It is intended, therefore, that the invention be defined by the scope of the claims which follow and that such claims be interpreted as broadly as is reasonable.