DESC:FIELD OF THE INVENTION
The present invention relates, in general, to the pharmaceutical field, and more precisely it relates to a medical device containing pharmaceutical composition comprising one or more fat removing agent. In particular, the present invention relates to an injection device, preferably a pen containing pharmaceutical composition comprising bile acid, derivative thereof or pharmaceutically acceptable salt thereof for the subcutaneous administration.

BACKGROUND OF THE INVENTION
“Cholanology”, the study of bile acids, and particularly bile acid chemistry has been of interest for the better part of a century. Although much is known, bile acid chemistry involves a wide variety of chemical entities, many with surprising properties. Mukhopadhyay, S and U. Maitra have published a review on chemistry and biology of the bile acids (Current Science, 2004, 87, 1666-1683). The same is incorporated herein by reference.

Bile acids are characterized by two connecting units, a rigid steroid nucleus and a short aliphatic side chain as shown in Figure 1. Hofmann et al. proposed nomenclature for bile acids (J. Lipid Res, 1992, 33, 599-604). Both the nucleus and the side chain have a large number of possible steric arrangements. The nucleus can be altered by expansion or contraction of individual rings, and the side chain can be shortened or lengthened. In addition, both parts of the bile acid molecule have a large number of possible polar substituents. Ionizing groups may be present on the nucleus or the side chain. Finally, conjugating groups may be present on the nucleus (e.g., sulfate, glucuronate, phosphate) or on the side chain (glycine or taurine or other amino acids, or even sugars). The side chain structure determines the class of the compound (bile acids or bile salts).

Figure 1
Bile acids are amphiphiles, having both an amphiphilic and amphipathic “face”: By convention, the hydrophobic surface is called the “ß-face” and the hydrophilic surface is called the “a-face”. The ß-face is lipid soluble and the a-face is relatively polar, in general. There are bile acids, such as those having polar groups (hydroxyl groups, in naturally occurring bile acids) on the hydrophobic face as well as on the hydrophilic face, e.g., ursodeoxycholic acid. The amphipathic nature of the molecule is responsible for its forming mixed micelles with amphipathic but water-insoluble lipids, such as phosphatidylcholine. Bile acids will not solubilize dietary lipids in the form of mixed micelles unless bile acids are above a critical concentration, termed the critical micellization concentration.

The bile acids found in greatest proportion in humans are chenodeoxycholic acid and deoxycholic acid. Deoxycholic acid is also known as deoxycholate, cholanoic acid, and 3a, 12a-dihydroxy-5ß-cholanate. In the human body deoxycholic acid is used in the emulsification of fats for the absorption in the intestine. In research, deoxycholic acid is used as a mild detergent for the isolation of membrane associated proteins. When substantially pure, deoxycholic acid is a white to off-white crystalline powder form. Deoxycholic acid is one of the four main acids produced by the liver. It is soluble in alcohol and acetic acid. The CAS number for deoxycholic acid is [83-44-3]. Deoxycholic acid can be isolated from the animal origin as well as can be prepared by following synthetic routes.

Rapid removal of body fat is an age-old ideal, and many substances have been claimed to accomplish such results, although few have shown results. “Mesotherapy”, or the use of injectables for the removal of fat, is not widely accepted among medical practitioners due to safety and efficacy concerns, although homeopathic and cosmetic claims have been made since the 1950's. Mesotherapy was originally conceived in Europe as a method of utilizing cutaneous injections containing a mixture of compounds for the treatment of local medical and cosmetic conditions. Although mesotherapy was traditionally employed for pain relief, its cosmetic applications, particularly fat and cellulite removal, have recently received attention in the United States. One such reported treatment for localized fat reduction, which was popularized in Brazil and uses injections of phosphatidylcholine, has been erroneously considered synonymous with mesotherapy. Despite its attraction as a purported “fat-dissolving” injection, the safety and efficacy of these cosmetic treatments remain ambiguous to most patients and physicians. For details see a review, “Mesotherapy and Phosphatidylcholine Injections: Historical Clarification and Review” published by Rotunda, A. M. and M. Kolodney (Dermatologic Surgery, 2006, 32, 465-480).

WO 2006/133160 (incorporated herein by reference in its entirety) describes methods for lipomodeling, e.g., reduction of a fat depot, by administering a neuropeptide Y receptor antagonist to the site of the fat depot. Kolonin M. G. et al. (Nat. Med. June 2004, 10(6), 625-32) describes fat selective pro-apoptotic peptides having potent fat cell killing effects. The described pro-apoptotic peptides require access to the vasculature to kill.

Recently published literature reports that deoxycholic acid has fat removing properties when injected into fatty deposits in vivo. See, WO 2005/117900 and WO 2005/112942, as well as US 2005/0261258; US 2005/0267080; US 2006/127468; and US 2006/0154906 (All incorporated herein by reference in their entirety). Deoxycholate injected into fat tissue has two effects: 1) it kills fat cells via a cytolytic mechanism; and 2) it causes skin tightening. Both of these effects are required to mediate the desired aesthetic corrections (i.e., body contouring). Because deoxycholate injected into fat is rapidly inactivated by exposure to protein and then rapidly returns to the intestinal contents, its effects are spatially contained. As a result of this attenuation effect that confers clinical safety, fat removal therapies typically require 4-6 sessions. This localized fat removal without the need for surgery is beneficial not only for therapeutic treatment relating to pathological localized fat deposits (e.g., dyslipidemias incident to medical intervention in the treatment of HIV), but also for cosmetic fat removal without the attendant risk inherent in surgery (e.g., liposuction). See, Rotunda et al., Dermatol. Surgery, 2004, 30, 1001-1008 (“Detergent effects of sodium deoxycholate are a major feature of an injectable phosphatidylcholine formulation used for localized fat dissolution”) and Rotunda et al., J. Am. Acad. Dermatol., 2005, 973-978 (“Lipomas treated with subcutaneous deoxycholate injections”), both incorporated herein by reference.

Deoxycholic acid or salt thereof (“Deoxycholate”) is also known to be used for non-surgical removal of a localized fat deposit. US 7622130 & US 7754230 discloses method for non-surgical removal of a localized fat deposit in a patient having such a deposit and desiring to remove such a deposit, wherein the deposit is contacted with a composition consisting essentially of an effective amount of deoxycholic acid or salt thereof wherein the composition does not include phosphatidylcholine. Further, US 8298556 discloses a non-liposuction method for treating unwanted localized fat accumulation in a subject having and desiring removal of said localized fat accumulation, which method comprises contacting said accumulation with a composition comprising a deoxycholate salt and a pharmaceutically acceptable excipient wherein said composition does not contain phosphatidylcholine for use as an active ingredient for said treating. US 9636349 discloses a method for reducing a subcutaneous fat deposit in a subject in need thereof, the method comprising administering locally to a subcutaneous fat deposit in the subject a composition comprising: a fat-dissolving effective amount of deoxycholic acid (DCA) or a salt thereof, a pharmaceutically acceptable excipient; and optionally a lipid. All incorporated herein by references in their entirety.

US 8101593, US 8367649 & US 8461140 discloses an aqueous pharmaceutical formulation consisting deoxycholate and at least one pharmaceutically acceptable excipient and/or carrier. All incorporated herein by references in their entirety.

US 8242294 discloses a deoxycholic acid (DCA) or a pharmaceutically acceptable salt thereof wherein the DCA has a 14C content of less than 1 ppt. US 8546367 discloses a composition comprising deoxycholate and at least one pharmaceutically acceptable excipient and/or carrier, wherein the deoxycholate has a 14C content of less than 1 ppt. All incorporated herein by references in their entirety.

US 8653058, incorporated herein by reference in its entirety, discloses a composition consisting of a salt of deoxycholic acid and a pharmaceutically acceptable excipient, wherein said composition does not comprise phosphatidylcholine.

US 8846066, incorporated herein by reference in its entirety, discloses a method for treating a benign, isolated collection of adipose tissue which method comprises injection of an effective amount of a composition comprising deoxycholate in the absence of phosphatidylcholine into the tissue under conditions wherein the size of said tissue is reduced.

US 9050349 discloses a syringe or syringe-loadable container comprising a composition comprising a deoxycholate salt and at least one pharmaceutically acceptable excipient and/or carrier, wherein the deoxycholate has a 14C content of less than 1 ppt. US 2011/0002896 discloses a syringe for subcutaneous injection wherein said syringe comprises a sterile aqueous composition comprising a fat removing effective amount of up to 5% (w/v) of a detergent which is deoxycholic acid or a salt thereof, and phosphatidylcholine, wherein the detergent is contained in excess of phosphatidylcholine by mass. Similarly, US 9522155, US 2006/0127468 and US 2015/0051182 discloses a syringe or syringe-loadable container comprising a composition comprising a deoxycholic acid or salt thereof. These prior art documents disclose conventional syringe for subcutaneous injection and incorporated herein by references in their entirety.

Deoxycholic acid, now a days, is useful for the removal of localized fat and especially for cosmetic surgery, e.g. removing fat below the chin (often called as “double chin”). Deoxycholic acid for the treatment of double chin is commercially available as Kybella® marketed by Allergan. Kybella® is a prescription medicine used in adults to improve the appearance and profile of moderate to severe fat below the chin (submental fat).

Kybella® (Deoxycholic acid) is available as 10mg/mL sterile solution, supplied in 2mL vials. Each vial is for single patient use. Kybella® is injected into subcutaneous fat tissue in the submental area using an area-adjusted dose of 2 mg/cm2. A single treatment consists of up to a maximum of 50 injections, 0.2 mL each (up to a total of 10 mL), spaced 1-cm apart. Up to 6 single treatments may be administered at intervals no less than 1 month apart.

Using a large bore needle, 1 mL of Kybella® is drawn into a sterile 1 mL syringe and any air bubbles in the syringe barrel is expelled. Have the patient tense the platysma, the submental fat is pinched and, using a 30 gauge (or smaller) 0.5-inch needle, 0.2 mL of Kybella® is injected into the pre-platysmal fat next to each of the marked injection sites by advancing the needle perpendicular to the skin. Injections those are too superficial (into the dermis) may result in skin ulceration. During injection the needle should not be withdrawn from the subcutaneous fat as this could increase the risk of intradermal exposure and potential skin ulceration. If at any time resistance is met as the needle is inserted, indicating the possibility of contact with fascial or nonfat tissue, the needle must be withdrawn to an appropriate depth before the injection is administered. Thus, an intensive care should be taken while administering Kybella® to a patient subcutaneously using a conventional subcutaneous syringe.

Kybella® is injected subcutaneously into the submental fat. A subcutaneous injection is administered as a bolus into the subcutis, the layer of skin directly below the dermis and epidermis, collectively referred to as the cutis. Subcutaneous injections are highly effective in administering vaccines and medications such as insulin, morphine, diacetylmorphine and goserelin. Subcutaneous, as opposed to intravenous, injection of recreational drugs is referred to as “skin popping”. Subcutaneous administration may be abbreviated as SC, SQ, sub-cu, sub-Q, SubQ, or subcut. Subcut is the preferred abbreviation for patient safety. A 25 to 31 gauge thick, 3/8" to 1" long needle can be used. The size is determined by the amount of subcutaneous tissue present, which is based on patient build. The 3/8" and 5/8" needles are most commonly used. Usually, no more than 1 mL of solution is given, compared to intradermal injections, where no more than 0.5 mL is usually given. Subcutaneous injections are inserted at 45 to 90 degree angles, depending on amount of subcutaneous tissue present and length of needle- a shorter, 3/8" needle is usually inserted 90 degrees and a 5/8" needle is usually inserted at 45 degrees. Medication is administered slowly, about 10 seconds/milliliter.

Subcutaneous injections are very well known in the medical treatments whereas in some of the medical treatments administration of drug through injections are frequent and sometimes even on daily basis. The injection should be given under the skin, into the fat layer. It is therefore difficult for a patient to administer drug subcutaneously by himself using conventional syringe and vial which requires training, accuracy and proficiency. It also becomes very difficult for a patient to visit doctor every time he/she is in need of the treatment and thereby increases numbers of visits of the doctor. For such a treatment it is always a convenient option for a patient if he/she could take that particular treatment by himself at home and at a convenient time. In order to overcome such a problem, an auto-injector or an injection-pen has been introduced which is easy to use and easy to handle for a patient.

Auto-injector or injection-pen have several advantages over the traditional vial-and-syringe method of drug delivery including improved patient satisfaction and adherence, greater ease of use, superior accuracy for delivering small doses of drug, greater social acceptability, and less reported injection pain. In recent years, pens have become increasingly user-friendly, and some models are highly intuitive to use, requiring little or no instruction.

The traditional route of subcutaneous administration has been the vial and syringe. However, this method of administration has many disadvantages, including fear of injections, poor dose accuracy, lack of social acceptance, lengthy training time, and difficulty of transportation. These factors can all act as barriers to therapy, impacting on lifestyle flexibility and negatively influencing treatment adherence, patient self-management behavior. Injection pens have been developed to help address these issues, with resulting improvements in portability, dosing accuracy, and convenience of delivery. Increased patient preference, treatment satisfaction, and quality of life have been reported for pen devices compared with the vial and syringe; these benefits may be particularly important due to their demonstrated impact on patient adherence. Other studies have shown that pen devices are associated with improved costs of care, less reported injection pain, and improved patient self-management behaviors, including adherence to treatment, compared with the vial and syringe. Because of the greater ease of use of injection pens, people with visual impairment or reduced dexterity may especially benefit from using an injection pen rather than a vial and syringe.

In view of the above mentioned disadvantages of the conventional subcutaneous injection syringe and care to be taken while administering Kybella® subcutaneous injection to a patient even by a trained practitioner, there is a need for such a solution which can overcome problems being faced even by the trained practitioners while administering the drug as well as by patients while taking the drug during the treatment using Kybella® subcutaneous injection. Unlike other injection-pens where the patient has to take higher dose of drug through one or two injections in a day, using the injection-pen of the present invention a patient can take up to 50 doses (as per Kybella® prescribing information) in one sitting with ease and convenience and with accurate amount of drug even at low dose. Thus, the injection-pen of the present invention improves patient compliance, patient satisfaction and increases patient’s willingness as well as acceptability for the treatment. Further, the injection-pen of the present invention differs from other injection-pen in a way that a patient or a doctor need not to change needle every time administering the drug. Thus, a single injection-pen can be used multiple times unlike known Kybella® subcutaneous injection-syringe. Further, during the treatment if the patient feels discomfort the treatment can be stopped for a day or two when injection-pen of the present invention is used whereas in the current treatment of Kybella® once a syringe has been filled up with Kybella® drug-formulation, the treatment cannot be interrupted and has to be finished even if the patient is feeling discomfort during the treatment. There is also no fear of contamination of the remaining drug in the pen due to design of the pen which enhances the safety and effectiveness of the drug in the injection-pen.

OBJECTS OF THE INVENTION
It is therefore one of the principal object of the present invention to provide a medical device containing pharmaceutical composition comprising an effective amount of one or more fat removing agent.

It is one of the further object of the present invention to provide a medical device containing pharmaceutical composition comprising an effective amount of bile acid, derivative thereof or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipient and/or carrier that improves patient satisfaction and adherence, has greater ease of use, has superior accuracy for delivering small doses of drug, has greater social acceptability, and has less injection pain and thereby increases patient’s acceptability for the treatment.

It is one of the further object of the present invention to use the medical device in the method of a non-surgical removal of a localized fat deposit in a subject in need thereof.

It is one of the further object of the present invention to use the medical device in the non-liposuction method for treating/dissolving/removing unwanted localized fat accumulation in a subject in need thereof.

It is one of the further object of the present invention to use the medical device in the method for reducing a subcutaneous fat deposit in a subject in need thereof.

It is one of the further object of the present invention to provide a method of removing fat deposit in a subject comprising administration of an effective amount of one or more fat removing agent using medical device of the present invention.

It is one of the further object of the present invention to provide a method of a non-surgical removal of a localized fat deposit in a subject, non-liposuction method for treating/dissolving/removing unwanted localized fat accumulation in a subject and method for reducing a subcutaneous fat deposit in a subject comprising administration of an effective amount of one or more fat removing agent using medical device of the present invention.

DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to the medical device containing pharmaceutical composition comprising fat removing agent and one or more pharmaceutically acceptable excipient and/or carrier.

In one of the preferred embodiments of the present invention, the medical device is a syringe, a syringe loadable container or an auto-injector device.

As used herein, the term “syringe” includes but not limited to pre-filled syringes suitable for injecting effective amount of the pharmaceutical composition comprising fat removing agent to the patient. Pre-filled syringes according to the present invention may look like for example that shown in Figure 2 but cannot be considered as the exact illustration for the invention. Pre-filled syringe shown in Figure 2 is for illustration purpose only and actual pre-filled syringes of the present invention may differ from the illustration.

Figure 2
As used herein, the term “syringe-loadable container” includes but not limited to an ampoule or vial or cartridge containing pharmaceutical composition comprising fat removing agent. Syringe-loadable containers according to the present invention may look like for example those shown in Figure 3 but cannot be considered as the exact illustration for the invention. Syringe-loadable containers shown in Figure 3 are for illustration purpose only and actual syringe-loadable containers of the present invention may differ from the illustration.


Figure 3
As used herein, the term “auto-injector” is a medical device designed to deliver a dose of a particular drug. Most auto-injectors are spring-loaded syringes. By design, auto-injectors are easy to use and are intended for self-administration by patients, or administration by untrained personnel refers to the practice where the patient or a doctor need not to withdraw drug from the ampoule and fill the syringe manually. Doses in the auto-injectors can also be adjusted using a simple knob. Auto-injectors according to the present invention include but not limited to pre-filled syringes and injection-pens. Injection-pens are one-time use pens or multiple-time use pens. One-time use pens contain pharmaceutical composition comprising fat removing agent and one or more pharmaceutically acceptable excipient and/or carrier whereas the multiple-time use pens has reservoir for drug, e.g. cartridge containing pharmaceutical composition comprising fat removing agent and one or more pharmaceutically acceptable excipient and/or carrier.

As used herein, the term “injection-pen” includes but not limited to all those injection-pens useful for similar use as intended by the present invention. Further, with the help of such injection-pens of the present invention 1-50 accurate dosing of 10µl to 500µL can be done depending upon the cartridge used in the injection-pens. Injection-pens according to the present invention may look like for example those shown in Figure 4 but cannot be considered as the exact illustration for the invention. Injection-pens shown in Figure 4 are for illustration purpose only and actual injection-pens of the present invention may differ from the illustration.


Figure 4
In one of the further embodiments of the present invention, the pharmaceutical composition comprising fat removing agent is a liquid formulation comprising an effective amount of a drug and one or more pharmaceutically acceptable excipient and/or carrier.

In one of the further embodiments of the present invention, fat removing agent includes but not limited to bile acid, a derivative thereof or a pharmaceutically acceptable salt thereof. Suitable examples of bile acid or derivative thereof according to the present invention includes but not limited to deoxycholic acid, ursodeoxycholic acid, taurocholic acid, glycocholic acid, chenodeoxycholic acid, taurochenodeoxycholic acid, glycochenodeoxycholic acid, lithocholic acid or pharmaceutically acceptable salts thereof.

In one of the further embodiments of the present invention, one or more pharmaceutically acceptable excipient and/or carrier is selected from the group comprising, one or more vehicle, one or more solvent/co-solvent and one or more pH adjusting agents including buffers and combination thereof.

In one of the preferred embodiments of the present invention, the fat removing agent is a derivative of bile acid, i.e. deoxycholic acid or a salt thereof. The amount of the Deoxycholic acid or pharmaceutically acceptable salt thereof in the pharmaceutical composition of the present invention is about 20% w/v, preferably about 5% w/v, more preferably about 0.05% w/v to about 5% w/v, more preferably about 2.5% w/v, 1.5% w/v, 1.0% w/v or 0.5% w/v.

Using injection-pen of the present invention desired dose of the drug can be divided into 1 to 50 injections, preferably from 10 to 50 injections, more preferably from 25 to 50 injections depending upon the total amount of drug to be administered. Further, using injection-pen of the present invention desired dose of drug can be divided into 1µl to 500µl and administered accurately depending upon the total amount of drug to be administered. Using the injection-pen of the present invention desired amount of drug can be administered even at as low as 1µl dose.

In one of the preferred embodiments of the present invention, the liquid pharmaceutical composition of the present invention is suitable for parenteral administration, preferably as an injection and more preferably as subcutaneous injection.

As used herein, “pharmaceutically acceptable excipient” means a compound that is useful in preparing a pharmaceutical composition that is generally safe, non-toxic and neither biologically nor otherwise undesirable, and includes excipients that are acceptable for veterinary use or human pharmaceutical use. A pharmaceutically acceptable excipient as used in the specification and claims includes both one and more than one such excipient. Some examples of suitable excipients include without limitation lactose, dextrose, sucrose, sorbitol, mannitol, starches, gum acacia, calcium phosphate, alginates, tragacanth, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, phosphatidylcholine, cellulose, sterile water, syrup, and methyl cellulose. The formulations can additionally include: lubricating agents such as talc, magnesium stearate, and mineral oil; wetting agents; emulsifying and suspending agents; and preserving agents such as methyl- and propylhydroxy-benzoates and benzyl alcohol. The compositions of the present invention can be formulated so as to provide quick, sustained or delayed release of the active ingredient after administration to the patient by employing procedures known in the art.

As used herein, the term “vehicle” refers to pharmacologically acceptable aqueous vehicles for the compositions. Pharmacologically acceptable aqueous vehicles for the compositions can include, for example, any liquid solution that is capable of dissolving the drug and is not toxic to the particular individual receiving the formulation. Examples of pharmaceutically acceptable aqueous vehicles include, without limitation, saline, water and acetic acid. Typically, pharmaceutically acceptable aqueous vehicles are sterile.

As used herein, the term “pH adjusting agent” refers to an agent that helps adjusting and achieving desired pH of the composition. pH adjusting agents include but are not limited to acids, bases and buffers.

As used herein, the term “buffer” refers to an aqueous solution comprising a mixture of a weak acid and its conjugate base or a weak base and its conjugate acid. A buffer has the property that the pH of the solution changes very little when a small amount of acid or base is added to it. Buffer solutions are used as a means of keeping pH at a nearly constant value in a wide variety of chemical applications. Examples of suitable buffers include phosphate buffers and those known in the literature (see, for example, Troy, D. B., ed. (2005) Remington: The Science and Practice of Pharmacy, 21st ed., Lippincott Williams & Wilkins).

In one of the further embodiments of the present invention, the pH of the pharmaceutical composition is in the range of 6.0 to 8.5, preferably in the range of 7.5 to 8.5 and more preferably in the range of 8.0 to 8.5.

Pharmacologically active compositions useful in the preferred embodiments of the present invention are formulated for the non-surgical removal of localized fat deposits. As used herein, “non-surgical” refers to medical procedures that do not require an incision. Injections are examples of non-surgical procedures. Liposuction is a surgical procedure.

In one of the preferred embodiments of the present invention, the pharmacologically active composition is administered by injection, for example, by bolus injection. In order to be effective, the pharmaceutical composition must have direct contact with the fat tissue regardless of how it is infused. The pharmaceutical formulations can be injected subcutaneously or infused directly into the fat. Formulations for injection can be presented in unit dosage form, for example, in ampoules or in multi-dose containers, with an added preservative. The compositions can take such forms as suspensions, solutions, or emulsions in oily or aqueous vehicles, and can contain formulatory agents such as suspending, stabilizing and/or dispersing agents.

In one of the further embodiments of the present invention, the pharmaceutical composition further comprises one or more therapeutically active agents. Such other therapeutically active agents are those having similar therapeutic indication intended to have by means of the present invention and can be used for the purposes of the present invention.

In one of the preferred embodiments of the present invention, the pharmaceutical composition comprises an effective amount of the Deoxycholic acid or pharmaceutically acceptable salt thereof, one or more pharmacologically acceptable vehicle and one or more pH adjusting agent having pH in the range of 8.0 to 8.5 wherein the pharmaceutical composition is contained in an injection-pen.

In one of the further embodiments of the present invention, a medical device is such that it improves patient satisfaction and adherence, has greater ease of use, has superior accuracy for delivering small doses of drug, has greater social acceptability, and has less injection pain and thereby increases patient’s acceptability for the treatment.

In one of the further embodiments of the present invention, a medical device is used in the method of a non-surgical removal of a localized fat deposit in a subject having need thereof.

In one of the further embodiments of the present invention, a medical device is used in the non-liposuction method for treating/dissolving/removing unwanted localized fat accumulation in a subject having need thereof.

In one of the further embodiments, the present invention provides a method of removing fat deposit in a subject comprising administration of an effective amount of one or more fat removing agent using medical device of the present invention. In one of the preferred embodiments, the present invention provides a method of removing fat deposit in a subject comprising administration of an effective amount of a bile acid, a derivative thereof, a pharmaceutically acceptable salt thereof using medical device of the present invention.

In one of the further embodiments, the present invention provides a method of a non-surgical removal of a localized fat deposit in a subject, non-liposuction method for treating/dissolving/removing unwanted localized fat accumulation in a subject and method for reducing a subcutaneous fat deposit in a subject comprising administration of an effective amount of one or more fat removing agent using medical device of the present invention. In one of the preferred embodiments, the present invention provides a method of a non-surgical removal of a localized fat deposit in a subject, non-liposuction method for treating/dissolving/removing unwanted localized fat accumulation in a subject and method for reducing a subcutaneous fat deposit in a subject comprising administration of an effective amount of a bile acid, a derivative thereof, a pharmaceutically acceptable salt thereof using medical device of the present invention. ,CLAIMS:WE CLAIM,
1. A medical device containing pharmaceutical composition comprising an effective amount of one or more fat removing agent and one or more pharmaceutically acceptable excipient and/or carrier.
2. A medical device according to claim 1 is an auto-injector device.
3. A medical device according to claim 2 wherein an auto-injector device is an injection-pen or a pre-filled syringe.
4. An auto-injector device containing pharmaceutical composition comprising an effective amount of a bile acid, a derivative thereof or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipient and/or carrier.
5. An auto-injector device according to claim 4 is an injection-pen or a pre-filled syringe.

Dated this 2nd day of October 2018

[KETANA BABARIA]
IN/PA-660
ATTORNEY FOR THE APPLICANTS