Search

US-12616651-B2 - Topical lipolysis composition and methods

US12616651B2US 12616651 B2US12616651 B2US 12616651B2US-12616651-B2

Abstract

A method for non-surgically reducing localized adipose tissue in a patient is provided. The method comprises topically administering to a site at or proximate adipose tissue, with massage at the site of administration, a composition comprising: at least one biologically compatible pharmacologically active detergent selected from the group consisting of a lipophilic detergent, a hydrophilic detergent, an ionic detergent, a non-ionic detergent, a zwitterionic detergent, a glyceride and a bile acid or salt thereof in a concentration ranging from about 0.5% to about 30% by wt of the composition and at least one phospholipid. In one embodiment, a novel composition comprising deoxycholic acid or a salt thereof at a concentration ranging from about 0.5% to about 30% by wt, and phosphatidylcholine at a concentration ranging from about 0.1% to about 2% by wt, in a cream base is also provided.

Inventors

  • Pankaj Modi

Assignees

  • Lipodissolve Therapeutics Inc.

Dates

Publication Date
20260505
Application Date
20211007

Claims (11)

  1. 1 . A composition in the form of a cream comprising: deoxycholic acid or salt thereof in a concentration ranging from 0.5% to 30% by wt of the composition, phosphatidylcholine in an amount in the range of 0.1-5% by wt, one or more micelle-forming compounds comprising sodium lauryl sulfate, and an Azelaic-Kojic acid mixture, a hyaluronidase-collagenase-artichoke mixture, a (L)-carnitine-aminophylline mixture, thiamine, riboflavin, niacin, pantothenic acid, pyridoxine, and caffeine, combined in a cream base, wherein the composition reduces adipose tissue.
  2. 2 . The composition of claim 1 , wherein the composition comprises sodium deoxycholate.
  3. 3 . The composition of claim 1 , comprising 10% by wt sodium deoxycholate and 5% by weight phosphatidylcholine.
  4. 4 . A method for non-surgically reducing localized adipose tissue in a patient, the method comprising topically administering to a site at or proximate to adipose tissue, a composition as defined in claim 1 , 1-2 times daily for at least 30 days.
  5. 5 . The method of claim 4 , wherein the composition is applied with massage.
  6. 6 . A composition in the form of a cream or emulsion comprising: i) as PHASE A, water, 0.75% sodium lauryl sulfate, 3.0% Azelaic-Kojic Acid mixture (50/50), 3.0% artichoke extract, 3.0% (L)-carnitine-aminophylline mixture (50/50) and 5.0% isopropyl alcohol; ii) as PHASE B, 12% stearic acid, 3.0% glyceryl stearate se, 3.0% niacin, 1.0 olive oil, 4.0% dimethicone, 3.5% 2-hydroxyethyl octadecanoate, and 4.0% ethyl alcohol; iii) as PHASE C, 5.0% linoleic acid, 0.5% tocopherol acetate, 5.5% lactic acid, 5.0% niacinamide, 0.5% evening primrose oil; iv) as PHASE D, 0.5% lecithin, 9.0% sodium deoxycholate, and 0.75% polyoxyethylene lauryl ether and 0.50% phenoxyethanol; and vi) as PHASE E, 0.5% triethanolamine and 5.0% caffeine, 2.5% bitter orange extract, 1.0% glycyrrhetinic acid, 0.25% Ginkgo biloba, 1.0% Aloe Barbadensis leaf extract, 1.0% L-carnitine and 0.5% Nelumbo nucifera leaf extract, combined in order.
  7. 7 . A method for non-surgically reducing localized adipose tissue in a patient, the method comprising topically administering to a site at or proximate to adipose tissue, a composition as defined in claim 6 , 1-2 times daily for at least 30 days.
  8. 8 . The method of claim 7 , wherein the composition is applied with massage.
  9. 9 . A composition in the form of a cream comprising: deoxycholic acid or salt thereof in a concentration ranging from 0.5% to 30% by wt of the composition; phosphatidylcholine in an amount in the range of 0.1-5% by wt.; one or more micelle-forming compounds selected from sodium lauryl sulfate, polyoxyethylene lauryl ether, 2-hydroxyethyl octadecanoate, olive oil, stearic acid, and evening primrose oil; an Azelaic-Kojic acid mixture; an (L)-carnitine-aminophylline mixture; linoleic acid, tocopherol acetate, niacinamide and triethanolamine, wherein the composition reduces adipose tissue.
  10. 10 . The composition of claim 9 , additionally comprising one or more agents that supplement lipolysis selected from the group consisting of caffeine, bitter orange extract, glycyrrhetinic acid, Ginkgo biloba , aloe barbadensis leaf extract, L-carnitine and Nelumbo nucifera leaf extract.
  11. 11 . The composition of claim 10 , wherein the deoxycholic acid or salt thereof is in an amount of less than 10% by weight of the composition.

Description

Pharmacologically active compositions and methods using the compositions for topical, i.e., non-surgical administration to patients in need thereof with demonstrated efficacy in reducing or removing localized adipose tissue, i.e., a deposit of fat cells including but not limited to lipomas. In one embodiment, administration is by application to a skin surface at or proximate to a localized adipose tissue site. In one embodiment, administration is subcutaneous at or proximate to localized adipose tissue. In one embodiment, administration is percutaneous, i.e., absorption through the skin from topical application at or proximate to localized adipose tissue. Percutaneous administration may be directly to a skin surface, i.e., to the skin itself, or indirectly, e.g., to a surface such as a pad that then contacts the skin. All such administration methods are topical administration. The method results in clinically demonstrated decreased localized deposits of adipose tissue, i.e., fat, for cosmetic improvement. Exemplary uses include but are not limited to therapy for lower eyelid fat herniation, on the neck, under the chin, lipodystrophy, and fat deposits associated with cellulite. The compositions are provided into or proximal to adipose tissues after penetration of the superficial skin layers into subcutaneous layers. The compositions include detergents and can also include other agents such as anti-inflammatory agents, analgesics, dispersion or anti-dispersion agents and pharmaceutically acceptable excipients and drugs of high or low molecular weight. There is increased prevalence of both surgical and non-surgical procedures for improving appearance with a population that is aging and gaining weight. Liposuction, also known as lipoplasty or suction lipectomy, is a popular procedure that removes fat through an incision in the skin through which a cannula is inserted, optionally with solutions to assist the process. The cannula is connected to a suction source and the fat is aspirated through the cannula and discarded. Liposuction is performed under general or local anesthesia, depending on the amount and location of the fat to be removed. It is an expensive and painful procedure. The most commonly used forms of liposuction additionally use fluid injection methodologies where a medicated solution of a mixture of salts, an anesthetic, and a vasoconstrictor is infused into the treatment site prior to fat aspiration. The medicated solution helps the fat be removed more easily, reduces blood loss, and provides anesthesia both during and after surgery. However, liposuction and other surgical methods of fat removal are associated with significant adverse events. These include bruising, swelling, numbness, soreness, burning sensation, risk of infection, pigmentation changes, formation of fat clots or blood clots that can migrate to the lungs and can cause death, excessive fluid loss leading to shock or fluid accumulation that must be drained, friction burns or other damage to the skin or nerves, or perforation of vital organs. Liposuction requires a recovery time of one to two weeks where the patient cannot work or perform certain daily activities. Because liposuction requires local and occasionally general anesthesia, there are significant anesthesia-related risks. Such surgical procedures are expensive, time consuming, very painful, require hospitalization, and can led to serious side effects and scars if performed improperly. Formulations containing phosphatidyicholine and bile salts (PBFs) are used to treat localized fat accumulation. Open label clinical studies reported promising results using PBF injections for treatment of localized fat accumulation, including lower eyelid fat herniation and “buffalo hump” lipodystrophy, cellulites, etc. Phosphatidylcholine (PPC) is a natural phospholipid that is an essential component of normal cell membranes and is important for cell membrane repair. Phosphatidylcholine is also the major delivery form of the essential nutrient choline. Choline is a precursor in the synthesis of the neurotransmitter acetylcholine, the methyl donor betaine and phospholipids, including phosphatidylcholine and sphingomyelin among others. Phosphatidylcholine is also involved in the hepatic export of very-low-density lipoproteins. Bile salts have been used to improve the aqueous solubility of phosphatidylcholine and more recently medications like amphotericin B, Taxol®, diazepam, antipain medications, anti-inflammatory drugs, several anticancer and antitumor compounds, some proteins such as insulin, heparin, neurotoxins, vaccines, etc. In one embodiment the inventive composition with demonstrated clinical efficacy combines highly purified phosphatidylcholine with the secondary bile salt sodium deoxycholate, an antimicrobial, alcohol, and water to form a stable mixed micelle preparation that can be rapidly sterilized and used for topical administration. Pharmaceutical preparations of this compositio