Compositions And Methods For Fat Reduction

Generally, compositions effective for the reduction of fat deposition and/or enhancement of muscle mass. In particular, compositions including admixtures of dry ingredients or admixtures of dry ingredients combined with a carrier composition to aid delivery of constituents of the admixture of dry ingredients.

I. FIELD OF THE INVENTION

Generally, compositions that are effective for the reduction of fat deposition and/or to preserve or enhance muscle mass. In particular, compositions including admixtures of dry ingredients or admixtures of dry ingredients combined with a carrier composition to aid delivery of constituents of the admixture of dry ingredients.

Sarcopenic obesity is characterized by the coexistence of obesity, characterized as >35 percent body fat, and sarcopenia, determined by low skeletal muscle mass and function. Donini L. et al. Definition and diagnostic criteria for sarcopenic obesity: ESPEN and EASO Consensus Statement. Obes Facts. 15 (3) (2022), pp. 321-335. <doi.org/10.1159/000521241>.

However, the condition can be difficult to attribute an exact definition due to the varying norms of different cultures. In the United States, the prevalence of sarcopenic obesity is reported at about 18.1% in women over 60 and about 42.9% in similarly aged men. Shafiee G., Keshtkar A., Soltani A., Ahadi Z., Larijani B., Heshmat R. Prevalence of sarcopenia in the world: a systematic review and meta-analysis of general population studies.J. Diabetes Metab Disord.16 (2017), pp. 16:21. <doi: 10.1186/s40200-017-0302-x>.

Basal metabolic rate can decline by over 4% per decade after age 50. Zoico E., Di Francesco V., Mazzali G., Vettor R., Fantin F. et al. Adipocytokines, fat distribution, and insulin resistance in elderly men and women.J Gerontol A Biol Sci Med Sci59 (2004), pp. 935-939.

The rate of skeletal muscle loss can vary between 3% to 8% every ten years after skeletal muscle mass peaks in early adulthood. Sarcopenic obesity is frequently observed among the elderly population, with both its risk and prevalence rising as individuals age. Johnson Stoklossa C. A. et al. Prevalence of Sarcopenic Obesity in Adults with Class II/III Obesity Using Different Diagnostic Criteria [online].J Nutr Metab(2017) [retrieved on Jul. 18, 2023]. Retrieved from Internet: <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380855/><doi: 10.1155/2017/7307618>.

In subjects older than 65, the rate of loss can accelerate with a range of 6% to 15% prevalence of clinical sarcopenia. Vincent H. K., Raiser S. N., Vincent K. R. The aging musculoskeletal system and obesity-related considerations with exercise.Ageing Res Rev.11 (3) (2012 Mar. 15), pp. 361-373. <doi: 10.1016/j.arr.2012.03.002>.

The general deterioration of the musculoskeletal system leads to negative consequences, including increased likelihood of falls, reduced functionality, increased frailty, and mortality. These outcomes can be associated with a decrease in quality of life and an elevated risk of cardiometabolic conditions such as diabetes and hypertension. Baumgartner R. N., Wayne S. J., Waters D. L., Janssen I., Gallagher D., Morley J. E. Sarcopenic obesity predicts instrumental activities of daily living disability in the elderly.Obes. Res.12 (2004), pp. 1995-2004.

Visceral fat area greater than 100 cm2in both women and men characterizes visceral obesity. Lim S., Kim J. H. et al. Sarcopenic obesity: prevalence and association with metabolic syndrome in the Korean Longitudinal Study on Health and Aging (KLOSHA).Diabetes Care33 (2010), pp. 1652-1654.

A centralization of fat from the subcutaneous to visceral deposition peaks between the ages of 60 and 75. Excess calories previously converted to subcutaneous fat are then stored in the intra-abdominal space. Proinflammatory cytokines and free fatty acids released from VAT cause dyslipidemia and insulin resistance. Stenholm S. et al. Sarcopenic obesity: definition, cause and consequences.Curr Opin Clin Nutr Metab Care,11 (2008), pp. 693-700.

A downward metabolic spiral nicknamed the “metabaging cycle” describes an aging process influenced by hyperlipidemia and fat deposition into muscle, further worsening sarcopenia. Li C. et al. Pathogenesis of sarcopenia and the relationship with fat mass: descriptive review.J Cachexia Sarcopenia Muscle,13 (2) (2022), pp. 781-794. <doi: 10.1002/jcsm.12901>.

Excess serum lipids generate an inflammatory cycle, including fat deposition intramuscularly, including an increase in reactive oxygen species, and production of adipokines and inflammatory cytokines. “Inflammaging” then results, causing less fat to be stored, and a relative excess of circulating free fatty acid). Lackey D., Olefsky M. et al. Regulation of metabolism by the innate immune system.Nat Rev Endocrinol.,12 (1) (2016), pp. 15-28.

Kob et al. note that obesity can predispose progenitor cells to differentiate into adipose rather than muscle cells, when given a paracrine signal to do so from inflammatory cytokines. Kob R. et al. Sarcopenic obesity: molecular clues to a better understanding of its pathogenesis?Biogerontology,16 (2015), pp. 15-29.

Several studies have indicated that obesity can worsen sarcopenia, leading to increased fat infiltration into the muscles, diminished physical function, and a higher mortality risk. Kalinkovich A, Livshits G. (2017). Sarcopenic obesity or obese sarcopenia: A cross talk between age-associated adipose tissue and skeletal muscle inflammation as a main mechanism of pathogenesis.Ageing research reviews.35, 200-221. http://doi: 10.1016/j.arr.2016.09.008; Barbat-Artigas S., Pion H., Leduc-Gaudet P., Rolland Y., Aubertin-Leheudre M. Exploring the role of muscle mass, obesity, and age in the relationship between muscle quality and physical function.J Am Med Dir Assoc.,15 (4) (2014), pp. 303.e313-320. <doi: 10.1016/j.jamda.2013.12.008>.

Resistance training is recognized as an effective method for mitigating the symptoms of sarcopenia and osteoporosis. Avila J., Gutierres A., Sheehy E., Lofgren E., Delmonico J. (2010). Effect of moderate intensity resistance training during weight loss on body composition and physical performance in overweight older adults.Eur. J. Appl. Physiol.,109 (2010), pp. 517-525.

Nevertheless, the dropout rate from such training programs among older adults can reach as high as 33%. Katz B, Duncan D. Lifting and Toning of Arms and Calves Using High-Intensity Focused Electromagnetic Field (HIFEM) Procedure Documented by Ultrasound Assessment.J Drugs Dermatol,20 (7) (2021), pp. 755-759.

Increased age and poorer physical performance have been linked to a greater likelihood of discontinuation. Rosado H., Bravo J., Raimundo A., Carvalho J., Marmeleira J., Pereira C. Effects of two 24-week multimodal exercise programs on reaction time, mobility, and dual-task performance in community-dwelling older adults at risk of falling: a randomized controlled trial.BMC Public Health,10: 21 (Suppl 2) (2021), p. 408. <doi: 10.1186/s12889-021-10448-x>.

Consequently, there is a long felt but unresolved need for alternative approaches to enhance body composition and mitigate muscle and bone loss, as well as total body fat reduction. There would be a substantial advantage in embodiments of a solid composition for oral delivery, or a topical composition for application to an area of the skin, each of the dosage forms effective to reduce visceral fat deposition and/or preserving or enhancing skeletal muscle mass.

II. SUMMARY OF THE INVENTION

Accordingly, a broad object of particular embodiments of the invention can be provide an admixture of dry ingredients useful in the preparation of solid dosage forms which by oral delivery, or topical dosage forms which by application to the skin, can be effective in the reduction of visceral fat deposition and/or preserving or enhancing skeletal muscle mass. In particular embodiments, the admixture of dry ingredients can comprise, consist essentially of, or consist of, one or more of: Gynostemma Powder Extract, Mulberry Leaf Extract, Goji Berry Powder Extract, Sage Extract, CoffeeRobustaExtract, Cardamom Seed Extract,AstragalusRoot Extract, andPanax notoginsengRoot Extract.

Another broad object of particular embodiments of the invention can be to provide a method of admixing dry ingredients useful in the preparation of solid dosage forms which by oral delivery, or topical dosage forms which by application to the skin, can be effective in the reduction of visceral fat deposition and/or preserving or enhancing skeletal muscle mass, wherein the method comprises, consists essentially, or consists of admixing one or more of:GynostemmaPowder Extract, Mulberry Leaf Extract, Goji Berry Powder Extract, Sage Extract, CoffeeRobustaExtract, Cardamom Seed Extract,AstragalusRoot Extract, andPanax NotoginsengRoot Extract.

Another broad object of particular embodiments of the invention can be to provide a carrier composition adapted to blend with an admixture of dry ingredients to provide a topical composition effective in the reduction of visceral fat deposition and/or preserving or enhancing skeletal muscle mass, wherein the dry ingredients blended with the carrier composition can comprise, consist essentially of, or consist of one or more of:GynostemmaPowder Extract, Mulberry Leaf Extract, Goji Berry Powder Extract, Sage Extract, CoffeeRobustaExtract,CardamomSeed Extract,AstragalusRoot Extract, andPanax NotoginsengRoot Extract.

Another broad object of the invention can be to provide a topical composition applied to the skin effective to reduce visceral fat deposition and/or preserve or enhance skeletal muscle mass, wherein the topical composition includes one or more dry ingredients comprising, consisting essentially of, or consisting of, one or more of:GynostemmaPowder Extract, Mulberry Leaf Extract, Goji Berry Powder Extract, Sage Extract, CoffeeRobustaExtract,CardamomSeed Extract,AstragalusRoot Extract, andPanax NotoginsengRoot Extract, blended into a carrier composition.

Another broad object of the invention can be to provide a method of making a topical composition applied to the skin effective to reduce visceral fat deposition and/or preserve or enhance skeletal muscle mass, wherein the topical composition includes one or more dry ingredients comprising, consisting essentially of, or consisting of, one or more of:GynostemmaPowder Extract, Mulberry Leaf Extract, Goji Berry Powder Extract, Sage Extract, CoffeeRobusta Extract, CardamomSeed Extract,AstragalusRoot Extract, andPanax NotoginsengRoot Extract, blended into a carrier composition.

Naturally, further objects of the invention are disclosed throughout other areas of the specification, drawings, photographs, and claims.

IV. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Compositions and methods of preparing and using such compositions to reduce fat deposition and/or preserve or enhance muscle mass. Embodiments of the composition for reduction of fat deposition can comprise, consist essentially of, or consist of an admixture of dry ingredients as described herein or equivalents thereof. In particular embodiments, the composition can comprise, consist essentially of, or consist of an admixture of dry ingredients combined with a carrier composition to aid delivery of the constituents of the admixture of dry ingredients and/or the constituents of the carrier composition. The carrier composition can, as illustrative examples, comprise an ointment, a gel, a lotion, a cream, or other topical carrier adapted to aid delivery of constituents of the admixture of dry ingredients and constituents of the carrier composition, including the active agents therein, to or through the skin by transepidermal route, transappendageal route, or combinations thereof.

In particular embodiments, the delivery system can employ reversible electroporation, in which electrostatic repulsion creates short-lived but high voltage pulses in order to open ionic channels on the skin allowing delivery of constituents of the admixture of dry ingredients and/or constituents of the carrier composition, including the active agents therein, within a topical composition through the skin. Application and delivery of the constituents of the admixture of dry ingredients and/or the constituents of carrier composition within a topical composition can result in a cascade of physiologic triggers that can enhance lipid metabolism.

One target of the active agents in the topical composition can be transcription factor SREBP-1 which regulates the conversion of glucose into fatty acids. Transcription factor SREBP-1 can be inhibited by a polysaccharide included in particular embodiments of the topical composition. Chen M., Xu J., Wang Y., Wang Z., Guo L., Li X., Huang L.,Arctium lappaL. The polysaccharide can regulate lipid metabolism in type 2 diabetic rats through the SREBP-1/SCD-1 axis.Carbohydr Res.,494 (2020), p. 108055. <doi: 10.1016/j.carres.2020.108055>. Inhibiting this protein can limit lipogenesis and can reduce, substantially reduce, or prevent long-term energy storage in the form of fat deposition.

Another target of the active agents in the topical composition can be adenosine monophosphate activated protein kinase (“AMPK”) which when stimulated can be an important regulator of cellular metabolism. Li Y., Xu S., Mihaylova M., Zheng B., Hou X., Jiang B., Park O., Luo Z., Lefai E., Shyy Y., Gao B., Wierzbicki M., Verbeuren J., Shaw J., Cohen A., Zang M. AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice.Cell Metab.,13 (4) (2011), pp. 376-388. <doi: 10.1016/j.cmet.2011.03.009>. AMPK, which declines with advancing age, can be found in every cell in the body. It is essential for energy production and utilization of fat for fuel, especially visceral fat. Particular embodiments of the topical composition can act to increase expression of AMPK.

Active agents in particular embodiments of the topical composition can increase expression of ursolic acid which can act to reduce inflammation caused by proinflammatory cytokines released by visceral fat. Katashima K., Silva R., Gomes L., Pichard C., Pimentel D. Ursolic acid and mechanisms of actions on adipose and muscle tissue: a systematic review.Obes Rev.,18 (6) (2017), pp. 700-711. <doi: 10.1111/obr.12523>.

Ursolic acid can also act to increase the body's levels of uncoupling proteins, both UCP-1 and UCP-3. These proteins are responsible for generating thermogenesis in a non-shivering manner within brown adipose tissue. Overexpression of these uncoupling proteins can also transform white adipose tissue (WAT) into beige adipose tissue, which increases utilization of fat tissue for heat and energy generation. Bargut L., Souza-Mello V., Aguila B., Mandarim-de-Lacerda A. Browning of white adipose tissue: lessons from experimental models [online].Horm Mol Biol Clin Investig. (2017), 31 (1)/j/hmbci.2017.31.issue-1/hmbci-2016-0051/hmbci-2016-0051.xml. [retrieved Jun. 2, 2023]. Retrieved from Internet: <https://pubmed.ncbi.nlm.nih.gov/28099124/><doi: 10.1515/hmbci-2016-0051>.

Illustrative embodiments of an inventive composition comprising, consisting essentially of, or consisting of an admixture of dry ingredients are set forth in the Tables that follow. In particular embodiments, the relationship between the ingredients is further defined as percent by weight (“w/w %”).

In particular embodiments, an inventive admixture of dry ingredients effective to reduce visceral fat deposition and/or preserve or enhance muscle mass can comprise, consist essentially of, or consist of the dry ingredients set forth in Table 1. The relative weight percent can be adjusted based on the dosage form and delivery route.

In particular embodiments, an inventive admixture of dry ingredients effective to reduce visceral fat deposition and/or preserve or enhance muscle mass can be produced in batches scaled by use of the range of percents by weight set forth in Table 2. The resulting batch can then be divided into dosage amounts of about 0.1 grams to about 0.2 grams. As a further illustrative example, an effective topical composition for the reduction of visceral fat deposition can include about 0.1 grams to about 0.5 grams of the inventive admixture of dry ingredients per milliliter of a topical composition. As a further illustrative example, a particular embodiment of a topical composition of 50 milliliters can include about 5 grams to about 10 grams of the inventive admixture of dry ingredients blended with a carrier composition suitable for application to the skin.

In particular embodiments, an inventive admixture of dry ingredients effective to reduce visceral fat deposition and/or preserve or enhance muscle mass can comprise, consist essentially of, or consist of the dry ingredients set forth in Table 3 with the relative weight percent adjusted based on the dosage form and delivery route.

In particular embodiments, an inventive admixture of dry ingredients effective to reduce visceral fat deposition can be produced in batches scaled by use of the range of weight percents set forth in Table 4. The resulting batch can then be divided into dosages of about 0.1 grams to about 0.2 grams each. As a further illustrative example, an effective topical composition for the reduction of visceral fat deposition and/or preserve or enhance muscle mass can include about 0.1 grams to about 0.2 grams of the inventive admixture of dry ingredients per milliliter of the topical composition. As a further illustrative example, a particular embodiment of a topical composition of 50 milliliters can include about 5 grams to about 10 grams of the inventive admixture of dry ingredients blended with a carrier composition suitable for application to the skin. In particular embodiments, the inventive admixture of dry ingredients in the amount of about 5.5 grams to about 6.5 grams can be blended with 50 mL of a carrier composition to produce a topical composition effective upon application to reduce visceral fat deposition and/or preserve or enhance muscle mass.

As an illustrative example, an inventive admixture of dry ingredients effective to reduce visceral fat deposition and/or preserve or enhance muscle mass can be produced in batches scaled by use of the weight percents set forth in Table 5. The resulting batch can then be divided into dosages of about 0.1 grams to about 0.2 grams each. As a further illustrative example, an effective topical composition for the reduction of visceral fat deposition can include about 0.1 grams to about 0.2 grams of the inventive admixture of dry ingredients per milliliter of the topical composition. As a further illustrative example, a particular embodiment of a topical composition of 50 milliliters can include about 5 grams to about 10 grams of the inventive admixture of dry ingredient blended with a carrier composition suitable for application to the skin. In particular embodiments, the inventive admixture of dry ingredients in the amount of about 5.5 grams to about 6.5 grams can be blended with 50 mL of a carrier composition to produce a topical composition effective upon application to reduce visceral fat deposition and/or preserve or enhance muscle mass.

The ingredients can be further described as follows:

GynostemmaPowder Extract (CAS #80321-63-7):Gynostemmapentaphyllum is a climbing vine found in South and East Asia primarily. It is in the family Cucurbitaceae which includes cucumbers, gourds, and melons.GynostemmaPowder Extract can be an excellent source of saponins, chemicals that the body uses to create several compounds including steroidal hormones. A key saponin inGynostemmaare gypenosides. Gypenosides confer several documented benefits including reducing anxiety, decreasing mast cell production, thereby benefitting allergies, and regulating deposition of body fat. Studies have shown that gypenosides can increase the body's production of AMPK. Choi E. et al. Supplementation with extract ofGynostemma pentaphyllumleaves can reduce anxiety in healthy subjects with chronic psychological stress: A randomized, double-blind, placebo-controlled clinical trial.Phytomedicine.52 (2019), pp. 198-205. <doi: 10.1016/j.phymed.2018.05.002>; Nguyen P. et al. New dammarane-type glucosides as potential activators of AMP-activated protein kinase (AMPK) fromGynostemma pentaphyllum. Bioorg Med Chem.19 (21) (2011), pp. 6254-6260. <doi: 10.1016/j.bmc.2011.09.013>.

AMPK, an enzyme found in all cells regulates lipid metabolism and energy production. AMPK declines with advancing age. One of the key actions of AMPK is to trigger burning of stored fat for energy. Anaerobic glycolysis and metabolism, inducing energy conservation, can reduce circulating AMPK, which is a major contributor to abdominal fat formation and storage. Hardie G. AMPK: a key regulator of energy balance in the single cell and the whole organism.Int J Obes(Lond). 32 (Suppl 4) (2008), pp. S7-S12.

Increased AMPK production can support body fat reduction by promoting utilization and oxidation of glucose while decreasing appetite. AMPK can increase fatty acid oxidation (burning fat for energy) while simultaneously reducing fatty acid synthesis. AMP-activated protein kinase [online]. Wikipedia [retrieved Jun. 2, 2023]. Retrieved from Internet: <https://en.wikipedia.org/wiki/AMP-activated_protein kinase>.

Mulberry Leaf Extract (CAS #94167-5-2): Mulberry (Morus alba) is a shrub or tree native to Asia. One of the constituent compounds in the Mulberry Leaf Extract, 1-deoxynojirimycin, inhibits the breakdown of ingested sugars and starches into glucose. This inhibition translates into less insulin output and ultimately into reduced fatty acid synthesis and fat deposition. Mulberry Leaf Extract also contains chlorogenic acid and its related chemicals (isomers), rutin, quercetin, resveratrol, quercetin, p-hydroxycinnamic acid, and caffeic acid. Mulberry Leaf Extract can activate UCP-1, AMPK, PPAR alpha, and PGC 1 alpha. Lim H., Lee O., Kim Y., Yang J, Lim Y. Anti-inflammatory and anti-obesity effects of mulberry leaf and fruit extract on high fat diet-induced obesity.Exp Biol Med.238 (2013), pp. 1160-1169. <doi: 10.1177/1535370213498982>. Mulberry Leaf Extract can activate brown adipose tissue and can induce browning of inguinal white adipose tissue in type 2 diabetic rats through regulating the AMP-activated protein kinase signaling pathway. Cheng L. et al. Mulberry leaf activates brown adipose tissue and induces browning of inguinal white adipose tissue in type 2 diabetic rats through regulating AMP-activated protein kinase signalling pathway [online]. Br J Nutr. (2022) 127 (6), pp. 810-822 [retrieved Jun. 2, 2023]. Retrieved from Internet: <https://pubmed.ncbi.nlm.nih.gov/33971987/>.

Goji Berry Powder Extract (CAS #85085-46-7): Goji Berry, also known as Wolfberry, is a bright red fruit native to Asia. Goji Berries offer a wide range of nutrients including vitamins, minerals and anti-oxidants. A constituent of Goji Berry Powder Extract comprises a water-soluble polysaccharide fraction (glycoconjugates) clinically demonstrated to have beneficial effects on blood sugar metabolism and body composition. Masci A., Carradori S., Casadei M. A., Paolicelli P., Petralito S., Ragno R., Cesa S.Lycium barbarumpolysaccharides: Extraction, purification, structural characterisation and evidence about hypoglycaemic and hypolipidaemic effects. A review.Food Chem.254 (2018), pp. 254: 377-389. <doi: 10.1016/j.foodchem.2018.01.176>[retrieved Jun. 2, 2023]. Retrieved from Internet: <https://www.sciencedirect.com/journal/food-chemistry>.

Polysaccharides contained in Goji Berry Powder Extract can activate AMPK and suppress sterol regulatory element-binding protein-1c (SREBP-1c). SREBP-1c is a transcription factor required for glucose utilization and fatty acid and lipid production. SREBP-1c activated in the liver by insulin results in insulin output and ultimately produces excessive fat storage. Inhibition of SREB-1c has been clinically shown to reduce fat deposition. Lee W., Lee Y., Wang Q., Yang Y. Crude extracts fromLycium barbarumcan suppress SREBP-1c expression and prevent diet-induced fatty liver through AMPK activation.Biomed Res Int. (2014) p. 196198. <doi: 10.1155/2014/196198>; Samar E., Beyleroglu M. The effect of goji berry consumption on weight loss in boxers [online]. Progress in Nutrition 22 (1-S) (2020), pp. 103-110 [retrieved on Jun. 2, 2023]. Retrieved from Internet: <https://www.mattioli1885journals.com/index.php/progressinnutrition/issue/view/750><doi.org/10.23751/pn.v22i1-S.9799>.

Sage Extract (CAS #84082-79-1): Sage is a well-known and commonly used herb for both culinary and medicinal uses.Sage officinaliscontains several bioactive compounds including tannins (salviatannin), essential oils including one or more of alpha-thujone, beta-thujone, cineole, camphor, flavones, phenolic acids, and various terpenes. Sage can be a source of ursolic acid which, as above described, can increase the expression of AMPK and irisin in skeletal muscles. This directly leads to improved lipid metabolism and increase in lean tissue synthesis. Seo D. et al. Ursolic acid in health and disease.Korean J Physiol Pharmacol.22 (3) (2018), pp. 235-248.

Additionally, ursolic acid can increase levels of Uncoupling Protein 1 (UPC1). UPC1 can be a respiration uncoupler responsible for generating non-shivering thermogenesis in brown fat tissue. Upon activation it stimulates the production of heat rather than ATP within brown adipose tissue. It is also thought to occur in beige adipocytes. Ursolic Acid has also been proven to upregulate Uncoupling Protein 3 (UPC 3). Specifically, UCP1 and UCP3 expression affects free fatty acid catabolismas a downstream target of AMPK activation in skeletal muscle. Chu X. et al. Ursolic acid increases energy expenditure through enhancing free fatty acid uptake and β-oxidation via an UCP3/AMPK-dependent pathway in skeletal muscle.Mol Nutr Food Res.59 (8) (2015), pp. 1491-503. <doi: 10.1002/mnfr.201400670>.

CoffeeRobustaExtract (CAS #97593-13-0): CoffeeRobustaaccounts for about 40% of global coffee production. It is grown in Africa, Indonesia, with the largest producer being Vietnam. CoffeeRobustaExtract is derived from unroasted coffee bean to retain heat sensitive compounds. CoffeeRobustaExtract can be standardized to 50% chlorogenic acid. Chlorogenic acid can improve cardiovascular health, normalize blood pressure, balance blood sugar, reduce inflammation, and reduce fatty liver disease. Tajik N., Tajik M., Mack I., Enck P. The potential effects of chlorogenic acid, the main phenolic components in coffee, on health: a comprehensive review of the literature.Eur J Nutr.56 (7) (2017), pp. 2215-2244. <doi: 10.1007/s00394-017-1379-1>. Chlorogenic acid can increase browning of adipocytes by increasing expression of UCP1 and peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC 1A). PGC 1A is a member of a family of transcription coactivators that plays a central role in the regulation of cellular energy metabolism. Sudhakar M. et al. Chlorogenic acid promotes development of brown adipocyte-like phenotype in 3T3-LI adipocytes. [online].Journal of Functional Foods(74) (2020) [retrieved on Jun. 2, 2023]. Retrieved from Internet: https://www.sciencedirect.com/science/article/pii/S1756464620303856.

PGC 1A can be involved in disorders such as obesity, diabetes, and cardiomyopathy. PGC1A was originally described as a coactivator of PPARy that modulated expression of uncoupling protein 1 (UCP1) and thermogenesis in brown fat. It has also been shown to control mitochondrial biogenesis and oxidative metabolism in many cell types. PGC1A can be induced in muscle by exercise and can stimulate beneficial effects of exercise in muscle.

CardamomPowder Extract (CAS #8000-66-6):Cardamomis a spice native to the Indian subcontinent and Indonesia. It is commonly used in Indian dishes and is a member of the Ginger family.Cardamomis a rich source of several terpenes including α-terpineol, myrcene and limonene. Clinical studies evidence that ingestion of cardamom can increase serum irisin levels as well as improve fasting blood sugar (FBS), insulin (FBI), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c). Daneshi-Maskooni M. et al. Green cardamom supplementation improves serum irisin, glucose indices, and lipid profiles in overweight or obese non-alcoholic fatty liver disease patients: a double-blind randomized placebo-controlled clinical trial.BMC Complement Altern Med.19 (1) (2019), p. 59. <doi: 10.1186/s12906-019-2465-0>. Even moderately increased levels of circulating irisin can increase energy expenditure, reduce body weight and improves diet-induced insulin resistance. Zhang Y. et al. Irisin stimulates browning of white adipocytes through mitogen-activated protein kinase p38 MAP kinase and ERK MAP kinase signaling. Diabetes, 63 (2) (2014), pp. 514-525. <doi: 10.2337/db13-1106>.

AstragalusRoot Extract (CAS #94166-93-5):Astragalusis a genus comprised of over 3000 herbs and shrubs. It is in the legume family and grown in climates in the northern hemisphere. It has been used for centuries in and considered one of the most useful herbs in traditional Chinese medicine.Astragalus's constituents include astragalosides. Astragalosides are terpene glycoside compounds that have a wide range of action including anti-oxidant, anti-cancer, immune enhancement, improved digestion, increased energy while reducing fatigue, and can also be used to protect cellular integrity during chemotherapy.

Recent evidence shows thatAstragaluscan improve leptin sensitivity. Leptin is essential for appetite control, but leptin resistance is a common problem with overweight individuals. Consequently, reestablishing leptin sensitivity can act to reduce excess weight, and adipose tissue.Astragalusroot can increase the transport of leptin across the blood brain barrier, thereby inhibiting obesity. Blood leptin concentration can be up to three times higher in people with obesity than in lean people, but the blood leptin concentration in the cerebrospinal fluid of people with obesity can be only 30% of that of lean people.Astragalusalso helps to reduce inflammation, a major contributing factor to visceral fat chronicity. Shao J. et al. Recent evidence in support of traditional Chinese medicine to restore normal leptin function in simple obesity [online].Heliyon(2022 May 19 [retrieved Jun. 2, 2023]. Retrieved from on Internet: <https://pubmed.ncbi.nlm.nih.gov/35620623/><doi: 10.1016/j.heliyon.2022.e09482>. Another component ofAstragalusis formononetin. Formononetin can upregulate UCP1 and PPARy. Formononetin regulates adipocyte thermogenesis as a non-classical PPARy agonist. Nie T. et al. The natural compound, formononetin, extracted fromAstragalus membranaceusincreases adipocyte thermogenesis by modulating PPARγ activity.Br J Pharmacol.175 (9) (2018), pp. 1439-1450. <doi: 10.1111/bph.14139>.

Panax NotoginsengExtract (CAS #94279-78-4):Panax Notoginsengis a species ofPanaxthat grows naturally in China. It is also known as Chinese or TienchiGinseng. Panax Notoginsengcontains several dammarane type ginsenosides. Zhang X. et al. Effect ofPanax notoginsengSaponins and Major Anti-Obesity Components on Weight Loss [online].Pharmacol.11 (2020), p. 601751 [retrieved on Jun. 2, 2023]. Retrieved from Internet: <https://www.frontiersin.org/articles/10.3389/fphar.2020.601751/full><doi: 10.3389/fphar.2020.601751>. Dammarane type ginsenosides are tetracyclic triterpenes and form triterpene saponins such as those found in certain Ginsengs. Dammaranes are known for improving energy, immunity, lowering lipid levels and blood pressure, reducing osteoporosis, protecting the liver, and increasing longevity. Dammaranes are also neuroprotective, cardioprotective, and have exhibited anti-cancer potential. Yoshikawa M. et al. Bioactive saponins and glycosides. XIX.Notoginseng(3): immunological adjuvant activity of notoginsenosides and related saponins: structures of notoginsenosides-L, -M, and -N from the roots ofPanax notoginseng. Chem Pharm Bull(Tokyo) 49 (11) (2001), pp. 1452-1456. <doi: 10.1248/cpb.49.1452>.Notoginsengcan affect weight through a number of pathways. The ginsenosides impact UCP1 and AMPK which help to increase the browning of white adipose tissue.Notoginsengcan also improve glucose metabolism by stimulating Insulin Receptor Substrate-1 (IRS1) to increase insulin sensitivity, and improve skeletal muscle glucose uptake through its effect on Glucose transporter 4 (GLUT4). T. C. Chang, et al. Effect of ginsenosides on glucose uptake in human Caco-2 Cells is mediated through altered Na+/glucose cotransporter 1 expression.Journal of Agricultural Food Chemistry55 (2007), pp. 1993-1998. Additional benefits include upregulating AMPK, PGC 1A and Sirtuin1 (SIRT1). SIRT1 is a cellular energy sensor involved in glucose and lipid metabolism, browning of white fat, and mitochondrial biogenesis. Y. C. Huang, et al. Effect and mechanism of ginsenosides CK and Rgl on stimulation of glucose uptake in 3T3-L1 Adipocytes.Journal of Agricultural Food Chemistry58 (2010), pp. 6039-6047. <doi: 10.1021/jf9034755>; Y. C. Huang, et al. An essential role of cAMP response element binding protein in ginsenoside Rg1-mediated inhibition of Na/glucose cotransporter 1 gene expression.Molecular Pharmacology88 (6) (2015), pp. 1072-83. <doi: 10.1124/mol.114.097352>; W. L. Chang, et al. The inhibitory effect of ginsenoside Rgl on glucose and lipid production in human HepG2 Cells.Adaptive Medicine5 (4) (2013), pp. 181-188. <doi: 10.4247/AM.2013.ABD068>.

Now with primary reference toFIGS.1through3, illustrating particular embodiments of a carrier composition (1) and methods of making a carrier composition comprising, consisting essentially of, or consisting of an admixture of one or more of Phase A ingredients (2) (as shown in the illustrative examples of Tables 6 through 7 and described within Blocks A through E of the block flow diagram ofFIG.1), or an admixture of one or more of Phase B ingredients (3) (as shown in the illustrative example of Table 8 and described within Blocks F through L of the block flow diagram ofFIG.2), or an admixture of one or more of Phase A ingredients (2) and one or more of Phase B ingredients (3) (as shown in the illustrative examples ofFIGS.1and2), and illustrating particular embodiments of a topical composition (5) and methods of making a topical composition (5) comprising, consisting essentially of, or consisting of Phase C ingredients (4) (as shown in the illustrative examples of Tables 1 through 5 and described within Bock M ofFIG.3) blended with a carrier composition (1) which topical composition (5) can be applied to the skin for effective reduction in visceral fat deposition and/or to preserve or enhance muscle mass.

The Carrier Composition.

Now, with primary reference toFIGS.1and2, illustrating particular embodiments of a carrier composition (1) and methods of making and using particular embodiments of a carrier compositions (1). Illustrative examples of the carrier composition (1) can comprise, consist essentially of, or consist of a Phase A carrier composition (6) including one or more Phase A ingredients (2) and/or comprise, consist essentially of, or consist of a Phase B carrier composition (7) including one or more Phase B ingredients (3). In particular embodiments, each of Phase A carrier composition (6) and Phase B carrier composition (7) can be prepared separate from the other as discrete inventive formulations, while in other embodiments the Phase A carrier composition (6) and Phase B carrier composition (7) can be prepared separately and then subsequently combined to produce embodiments of inventive carrier compositions (1). In particular embodiments the Phase A carrier composition (6) and/or Phase B carrier composition (7) can be combined with a Phase C (8) including an admixture of one or more Phase C ingredients (4) to produce embodiments of a topical compositions (5) which can be applied to the skin to effect reduction of fat deposition and/or preserve or enhance muscle mass.

Phase A Carrier Composition. Now, with primary reference toFIG.1, the Phase A carrier composition (6) can comprise, consist essentially of, or consist of, one or more of the following Phase A ingredients (2) set forth in Table 6.

Illustrative embodiments of the Phase A carrier composition (6) can be produced by varying the weight percent (“w/w %”) of each ingredient within the specified range relative to the weight of water as set forth in Table 7.

The Phase A ingredients (2) can be further described as follows:

Water (CAS #7732-18-5) is an ACS Reagent Grade Water which meets ASTM Type I and/or ASTM Type II specifications and may otherwise be referred to as purified water, ultratrace water, HPLC grade water, deionized water, injection quality water, sterile purified water, molecular biology grade water, or equivalents thereof.

Carbomer (CAS #76050-42-5) is poly(acrylic acid) a white powder that is a high molecular weight polymer cross-linked by acrylic acid and allyl sucrose ether or allyl pentaerythritol ether, or equivalents thereof. Carbomer 940 can be used in embodiments as a thickening, suspending, and emulsifying agent.

Polysorbate 20 (CAS #9005-64-5) is 2-[2-[3,4-bis(2-hydroxyethoxy)oxolan-2-yl]-2-(2-hydroxyethoxy) ethoxy]ethyldodecanoate a non-toxic, nonionic surfactant/emulsifier and dispersing agent which can be used in embodiments to allow oil and water to mix without the use of alcohol.

Now, with primary reference toFIG.1, an illustrative example of a Phase A carrier composition (6) including one or more of the Phase A ingredients (2), set out in Tables 6 and 7, can be produced by a method comprising one or more of: transfer of a measured amount of water (CAS: #7732-18-5) to a mixing vessel of a mixing device (Block A). Sprinkle Carbomer (CAS #76050-42-5) onto the surface of the water, and in particular embodiments about 2% to about 6% (w/w %) (Block B). Mix the carbomer and water admixture at low speed (about 2,000 rpm to about 5,000 rpm) until the carbomer is thoroughly wetted (Block C). Add glycerin (CAS #56-81-5), and in particular embodiments about 5% to about 15% (w/w %), and polysorbate 20 (CAS #9005-64-5), and in particular embodiments about 1% to about 4% (Block D). Bring the temperature of the admixture to about 55° C. to about 60° C. and mix until uniform (Block E).

Phase B Carrier Composition. Now, with primary reference toFIG.2, Phase B carrier compositions (7) can comprise, consist essentially of, or consist of, one or more of the following Phase B ingredients (3) set forth in Table 8.

Particular illustrative embodiments of the Phase B carrier composition (7) can be produced by varying the weight percent (“w/w %”) of each Phase B ingredient (3) within the specified range as set forth in Table 9.

The ingredients can be further described as follows:

Cetearyl Alcohol (CAS #67762-27-0) is Cetostearyl Alcohol (CH3(CH2)nOH) a mixture of cetyl and stearyl alcohols or equivalents thereof which can function as an emulsion stabilizer, opacifying agent; surfactant-foam booster, and/or viscosity increasing agent.

PEG-20 Stearate (CAS #9004-99-3) is polyethylene glycol C2nH4n+2On+1or equivalent thereof which can be useful as one or more of a penetration enhancer, surfactant, emulsifier, or humectant.

Grape Seed oil (CAS #8024-22-4) is an oil pressed from seeds ofVitis vinifera, or an equivalent thereof.

Jojoba Esters (CAS #85186-93-2) is hydrolyzed jojoba esters produced as hydrogenation or transesterification product of Jojoba oil, or equivalents thereof.

Helianthus AnnuusSeed Wax (CAS #68937-99-5) is the residue from the expression of oil from the seedcake of sunflower.

Acacia decurrensFlower Wax (CAS #98903-76-5) is the flower wax from the flowers ofAcacia decurrens.

Cetyl Alcohol (CAS #36653-82-4) is cetyl alcohol formula CH3(CH2)15OH or equivalent thereof.

Jojoba Esters (CAS #85186-93-2) is hydrolyzed jojoba esters produced as hydrogenation or transesterification product of Jojoba oil.

Helianthus AnnuusSeed Wax (CAS #68937-99-5) is the residue from the expression of oil from the seedcake of sunflower.

Water (CAS #7732-18-5) is ACS Reagent Grade Water which meet ASTM Type I or ASTM Type II specifications and may otherwise be referred to as purified water, ultratrace water, HPLC grade water, deionized water, injection quality water, sterile purified water, molecular biology grade water.

Jojoba Esters (CAS #85186-93-2) means hydrolyzed jojoba esters produced as hydrogenation or transesterification product of Jojoba oil.

Polyglyceryl-3 Beeswax (CAS #136097-93-3) means a polar beeswax derivative in which the free fatty acids of beeswax have been converted to polyglycerol esters.

Now, with primary reference toFIG.2, the illustrative example of the Phase B carrier composition (7) including one or more of the Phase B ingredients (3) set out in Tables 8 and 9 can be produced by a method comprising one or more of: admixing (w/w %) in a mixing vessel of a mixing device the emulsifying wax (cetearyl alcohol and PEG-20 stearate) (in particular embodiments emulsifying wax of about 2% to about 5%) (Block F) with grape seed oil (in particular embodiments grape seed oil of about 3% to about 5%) (as shown in Block G), Acticire® MB (Jojoba Esters,Helianthus annuusseed wax,Acacia Decurrensflower wax,Acacia decurrensflower wax, and polyglycerin-3) (in particular embodiments Acticire® MB of about 2% to about 7%) (Block H), Emulium® Dolcea (Cetyl Alcohol, Glyceryl Stearate, Jojoba EstersHelianthus annuusSeed Wax, Sodium Stearoyl Glutamate, water, Polyglycerin-3) (and in a particular embodiments Emulium® Dolcea of about 1% to about 6%) (Block I), Polysorbate 80 (and in particular embodiments Polysorbate 80 of about 1% to about 5%) (Block J), Emulium®Mellifera(Polyglyceryl-6 Distearate, Jojoba Esters, Polyglyceryl-3 Beeswax, Cetyl Alcohol) (and in particular embodiments Emulium®Melliferaof about 0.5% to about 5%) (Block K). Mix until uniform.

Again, with primary reference toFIG.2, the invention can include embodiments in which the Phase A carrier composition (6) can be admixed to Phase B carrier composition (7) until uniform (as shown by the illustrative example of Block L). In particular embodiments the mixture of Phase A carrier composition (6) and Phase B carrier composition (7) can be cooled to room temperature.

Now, with primary reference toFIG.3, in particular embodiments, the method can further include a Phase C composition (8) in which the mixture of Phase A (6) and Phase B (7) can be cooled to about 35° C. to about 45° C. (Block L) and Phase C ingredient(s) (4) can be admixed into the combination of Phase A (2) combined with Phase B (7) and mixed at low speed (about 2000 rpm to about 5,000 rpm) until obtaining a uniform mixture of Phase A ingredients (2), Phase B ingredients (3), and Phase C ingredients (4) (Block M) to produce a topical composition (5) containing Phase C ingredients (4) within the range of weight percent set forth in Table 10.

A further illustrative embodiment of the topical composition (5) includes Phase C ingredients (4) by weight percent in a carrier composition (1) as set forth in Table 11, which can, but need not necessarily be, the Phase A carrier composition (6), the Phase B carrier composition (7), or the combination thereof, and in particular embodiments, the carrier composition (6) can comprise can be an equivalent to the Phase A carrier composition (6), the Phase B carrier composition (7), or the combination thereof, or another carrier composition (1) capable of or adapted to blend with Phase C ingredients and suitable for application to the skin.

An embodiment of the inventive topical composition (5) obtained by the method of illustrated byFIGS.1through3was employed in a study to evaluate efficacy of the topical composition (5) to reduce visceral fat deposition and/or preserve or enhance muscle mass.

The Study. Eligible subjects (21-80 yrs., BMI<33 kg/m2) were included in a study after reviewing inclusion and exclusion criteria. Study subjects accepted into the study expressed a desire to improve their body composition, with willingness to apply the inventive topical composition (5) for transcutaneous delivery twice a day. Exclusion criteria were cardiac disorders requiring medication or treatment, immunosuppressive diseases, poorly controlled endocrine disorders, recent abdominal surgeries, pregnancy, breast feeding, and the use of weight loss medications or testosterone. Fifteen eligible study subjects (9 women and 6 men, 30 to 80 years old, BMI 21 to 33 kg/m2) were enrolled in the study. All participants received treatment instructions and provided written informed consent.

The treatment protocol included application of three pumps of the topical composition (5) (about 3 milliliters to about 5 milliliters) to the abdominal skin twice daily, once in the morning and again at night. Study subjects were strictly instructed to maintain their regular routine diet and exercise program, and to avoid weight gain or loss of over 5 lb from baseline for the study duration. Evaluation parameters included 2D and 3D photographs that were taken in a standardized studio setting before treatment with the topical composition (5), and again at one month, and again two months following treatment inception with the topical composition (5).

The gold standard for biometric analysis is the dual-energy X-ray absorptiometry (DEXA). HF-BIA, such as InBody®, has been shown to be highly correlated with the DEXA for assessing skeletal muscle mass (standard coefficient beta (β)≥0.95) and percent body fat (β≥0.94, R2 ≥0.89). Jensky-Squires E. et al. (2008). Validity and reliability of body composition analysers in children and adults.Br J Nutr.100 (4), 859-65. https://doi: 10.1017/S0007114508925460. Epub 2008-3-18. PMID: 18346304. Other biometric indices available through this device include weight, BMI, visceral adipose area in cm2, and calculated basal metabolic rate. Basal metabolic rate (BMR) is the amount of energy expended during rest in a neutral environment over a 24-hour period. The InBody® 770 utilizes John J. Cunningham's equation which uses lean body mass (LBM, kg) to estimate BMR (43):

The factors in determining BMR among body composition measures are lean body mass, body fat mass, levels of physical activity, and nutrition are also significant determinants. Konarzewski M., Książek A. (2013). Determinants of intra-specific variation in basal metabolic rate.J Comp Physiol B.183 (1), 27-41. https://doi: 10.1007/s00360-012-0698-z. Epub 2012-7-31. PMID: 22847501; PMCID: PMC3536993. As SMM is a component of LBM, it can be expected that an increase in BMR is correlated with increased SMM and decreased PBF. The transcutaneous topical composition (5) tested showed improvement in study subjects SMM and BMR in conjunction with reduced PBF and VAT following treatment.

HF-BIA, such as InBody®, has been shown to be highly correlated with the DEXA for assessing skeletal muscle mass (standard coefficient beta (B) ≥0.95) and percent body fat (β≥0.94, R2 ≥0.89) (15). Thus, the InBody® 770 was deemed an appropriate instrument to measure body biometrics for this study. Biometric index measurements were taken at the same time points using the InBody® 770, including weight (lb), percent body fat (PBF, %), skeletal muscle mass (SMM, 1b), visceral fat area (VAT, cm2), and basal metabolic rate (BMR, kcal). Fasting liver enzyme panel and lipid panels were drawn from each study subject prior to the start of the study, and again at one month and 2 months post inception.

The primary outcomes and evaluation method assessed body biometrics including weight (lb), percent body fat (PBF, %), skeletal muscle mass (SMM, lb), visceral adipose tissue (VAT, cm2), and (BMR, kcal). The InBody® 770 (Cerritos, CA, USA) was used to measure the changes of these variables, and standardized photographs were taken at baseline, at 1-month, and 2-month follow-up visits. Additionally, as a secondary primary evaluation, blind reviewers assessed study subjects aesthetic improvement including overall abdominal contour, degree of abdominal protuberance, periumbilical skin laxity, and apparent muscle tone using the 5-point Likert scale. The statistical significance was tested by the RStudio and MS Excel utilizing the paired sample t-test with the significance level, a, set at 5% and the null hypothesis set to 0.

The secondary outcomes focused on the complete metabolic panel blood values, specifically the lipid profile and liver metabolism values. Parameters such as triglycerides, cholesterol, HDL, LDL, alanine aminotransferase, alkaline phosphatase, and aspartate aminotransferase were assessed through blood tests. The liver function tests were conducted to ensure the safety of the topical composition (5) regarding its impact on liver function. And lipid metabolism. Measurements were taken at baseline, 1-month, and 2-month follow-up visits.

All fifteen study subjects completed the treatment regime and attended follow-up appointments. No adverse events or significant expected sequelae were reported. Participants did not experience any discomfort or difficulties during the at-home application of the topical composition (5) and were able to resume their daily activities after treatment. The weight of the subjects did not significantly change throughout the study, as their weight remained within a 51b range of baseline (p-value>0.05).

Now, with primary reference toFIG.4, biometric analysis showed that at baseline, mean weight measured 162.96 lb. The average percent body fat was 29.22%. Mean skeletal muscle mass (SMM) measured 64.42 lb. Mean visceral adipose tissue (VAT) value was 110.03 cm2, with a normal value of <100 cm2. Basal metabolic rate (BMR) averaged 1519.70 kcal. At the conclusion of the study, the average PBF was lowered to 27.95% (p-value<0.05), a decrease of 1.27%, which translates to a 4.2% lowering of this biometric index. SMM increased to 65.37 lb (p-value<0.05), an increase of 0.95 pounds, without any change in diet or exercise regimes. VAT decreased to 103.51 cm (p-value<0.05), a 5.9% improvement. There was an increase in the average BMR by 14.42 kcal (p-value<0.05). Average weight at baseline was 162.96 lb, and the mean weight decreased slightly to 162.14 lb at the conclusion of the study with a change of −0.82 lb (p-value>0.05).

Now, with primary reference toFIG.5, overall, blinded reviewers evaluating the body morphology improvement in the study subjects observed positive scores for improvement across all categories. No ratings were given by the reviewers to indicate any worsening of appearance.

ILLUSTRATIVE EXAMPLES

Now, with reference toFIG.6, depicting a 39-year-old female following childbirth and four pregnancies before treatment (left image), and two months following twice daily application of the topical composition (5) (right image), there was a noted improvement in abdominal contour.

Now, with reference toFIG.7, depicting a 41-year-old male (subject SS010) with central abdominal protuberance before treatment (left image) and following twice daily application of the topical composition (right image), the epigastric and periumbilical region showed significant improvement in both abdominal protuberance and apparent muscle tone.

Now, with primary reference toFIG.8, which illustrates the improvement in biometric measurement index changes of subject SS010. PBF decreased by 2.80 percent, with a loss of VAT by 13.00 cm2(−16.31%). SMM improved by 1.80 lb (+2.11%) and achieved a 27.00 kcal improvement in BMR and lost 3.00 lb.

Now, with primary reference toFIG.9, subject SS010 images shown inFIG.7were evaluated by three blinded reviewers. The assessment shows an aesthetic improvement over all categories.

Now, with primary reference toFIG.10, depicting a 78-year-old-female (SS012) before treatment (left image), and two months following twice daily application of topical composition (right image). The subject body morphology type and age group are clinically difficult to improve.

Now, with primary reference toFIG.11, SS012 body biometrics showed improvement after two months with a decrease in PBF by 2.10%, reduction in VAT by 8.60 cm2(−6.88%), an increase in SMM by 2.60 lb (+3.49%), and a 44.00 kcal improvement in BMR. SS012 weight stayed within 2.0 lb (p-value>0.05) of baseline.

Now, with primary reference toFIG.12, SS012 images were evaluated by three blinded reviewers. The assessment shows an aesthetic improvement over all categories.

Now, with primary reference toFIG.13, depicting an 80-year-old male (SS016) before treatment (left image), and two months following twice daily application of topical composition (right image).

Now, with primary reference toFIG.14, subject SS016 had significant reduction of visceral fat. Biometric indices showed improvement with a decrease in PBF by 5.20%, reduction in VAT by 16.00 cm2(−16.04%), an increase in SMM by 3.40 lb (+4.77%), and a 66.00 kcal improvement (−3.95%) in BMR. SS016 weight stayed within the required 5.0 lb weight change limit required by the study (p-value>0.05) of baseline.

Now, with reference toFIG.15, overall, of the 15 subject population treated in the study, the majority showed reduction in triglycerides while the others remained within their pre-treatment normal limits. There was an average decrease in triglycerides of 28.64 mg/dL across the patient population (p-value<0.05). There was also a decrease in average cholesterol and LDL across the patient population by 19.27 mg/dL (p-value<0.05) and 14.00 mg/dL (p-value<0.05), respectively. HDL values increased slightly but stayed within the normal range of 35.0 to 65.0 mg/dL for men, 35.0 to 80.0 mg/dL for women. Results of the lipid metabolism evaluation are portrayed inFIG.12.

Now, with reference toFIGS.16A,16B, and16C, liver function studies including alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (ASTZ) across the 15 subjects in the study population over the two month treat period changed very minimally (p-value>0.05) and stayed within the normative range.

There were no adverse events. No patient experienced nausea, diarrhea, abdominal cramping, or pain. One patient reported transient tingling upon application. There were no instances of skin rash, erythema, itching, or hives. No patient reported an allergic reaction.

As can be easily understood from the foregoing, the basic concepts of the present invention may be embodied in a variety of ways. The invention involves numerous and varied embodiments of a topical composition and methods for making and using such topical composition including the best mode.

It should be understood that each element of an apparatus or each step of a method may be described by an apparatus term or method term. Such terms can be substituted where desired to make explicit the implicitly broad coverage to which this invention is entitled.

In addition, as to each term used it should be understood that unless its utilization in this application is inconsistent with such interpretation, common dictionary definitions should be understood to be included in the description for each term as contained in Merriam-Webster's Collegiate Dictionary, each definition hereby incorporated by reference.