composition

Abstract

A composition comprising a soy protein isolate, a soy fibre, a phospholipid, and a carbohydrate for use in the treatment or prevention of obesity, type 2 diabetes or cardiovascular disorders, wherein the composition is administered together with a first pharmaceutical composition comprising an appetite suppressant agent.

Description

[0001] COMPOSITION

[0002] Field of the Invention

[0003] The present invention relates to a composition comprising a soy protein isolate, a soy fibre, a phospholipid and a carbohydrate, for use in the treatment or prevention of obesity, type 2 diabetes or cardiovascular disorders. The present invention also relates to a kit comprising a composition comprising a soy protein isolate, a soy fibre, a phospholipid and a carbohydrate; and a first pharmaceutical composition comprising an appetite suppressant agent.

[0004] Background

[0005] Appetite suppressant agents are a type of weight-loss medication often taken by people who are overweight with comorbidities or have obesity. They can affect how the human body and brain experience appetite and hunger. Patients taking appetite suppressant agents may experience feeling less hungry or feeling full faster after eating less food. As a result, fewer calories may be consumed and the patient loses weight.

[0006] GLP-1 receptor agonists (GLP-1 RAs) are a class of drugs that mimic the effects of GLP-1 and may be used as an appetite suppressant agent. Glucagon-like peptide-1 (GLP-1) is an important hormone that plays a key role in blood sugar regulation, by stimulating the release of insulin and reducing the release of glucagon, a hormone that raises blood sugar. It has also been known to help slow down digestion, promoting a feeling of fullness.

[0007] A number of GLP-1 receptor agonists are currently on the market for the treatment of type 2 diabetes and obesity. Medications such as Wegovy® and Ozempic®, which both contain the active ingredient semaglutide, have become especially popular as an appetite suppressant agent. Other appetite suppressant agents include GIP receptor agonists, glucagon receptor agonists and cannabinoid receptor 1 (CB1) inverse agonists.

[0008] However, these medications can be expensive and are often associated with a number of adverse side effects. Such side effects may include eyesight problems including blindness, loss of muscle mass, thyroid cancer, fatigue and gastrointestinal side effects.

[0009] Another way to assist with weight management and combat obesity is by triggering the release of GLP-1 by consuming certain foods that are high in protein, fibre, healthy fats and carbohydrates. Various foods have been reported to promote the release of GLP-1 , and most notably, eggs, nuts, high fibre grains, olive oil, seeds, legumes and avocados. However, given the extensive list of food types that potentially promote GLP-1 release, a challenge still remains to identify specific food ingredients that may maximise these effects.

[0010] In addition, those suffering with weight gain issues or obesity may experience cardiovascular complications, and therefore, a need remains to provide a safe and effective treatment which can reduce or avoid such cardiovascular events.

[0011] Accordingly, there remains a need to develop an improved composition which can be taken together with an appetite suppressant agent which is not only safe but reduces or avoids side effects whilst also improving the efficacy of preventing or treating obesity, type 2 diabetes and / or cardiovascular disorder.

[0012] Detailed Description

[0013] The present invention relates to a composition comprising a soy protein isolate, a soy fibre, a phospholipid, and a carbohydrate for use in the treatment or prevention of obesity, type 2 diabetes or cardiovascular disorders, wherein the composition is administered together with a first pharmaceutical composition comprising an appetite suppressant agent.

[0014] Accordingly, the composition according to the present invention comprises two different components of a soybean, namely a soy protein isolate and a soy fibre. The composition further comprises a phospholipid and a carbohydrate.

[0015] The composition of the present invention comprises proteins, phospholipids, fibres and carbohydrates as macro nutrients. In certain embodiments, the composition may be in the form of a meal replacement. In such an embodiment, the intake of macro nutrients (i.e. proteins, phospholipids, fibres and carbohydrates), 3-6 times per day, releases with each meal replacement the natural GLP-1 , GIP, glucagon and other gastrointestinal hormones which increase satiety (via effect on the hypothalamus). The intake of the essential nutrients avoids too much lean body mass including muscle mass being lost, as well as the lowering of metabolism and energy consumption.

[0016] The release of the natural gastrointestinal hormones may significantly reduce the dosage needed of an appetite suppressant agent such as GLP-1 receptor agonist and increase the efficacy of weight loss, with no observed side effects. The composition according to the present invention may therefore provide the possibility for longer term treatment of obesity, which is important since obesity is a chronic disorder, and rebound of weight loss can better be prevented. Accordingly, both safety and efficacy may be improved.

[0017] Furthermore, the regular daily releases of natural GLP-1 , GIP, glucagon and other Gl- hormones with shorter half-lives of 1-30 minutes, combined with mimicking GLP-1 and other gastrointestinal receptor agonists with slower release and longer term half-lives of 7-30 days, may reduce the dosage needed of the appetite suppressant agent and thereby significantly reduce the associated serious side effects.

[0018] The present invention also relates to a first pharmaceutical composition comprising an appetite suppressant agent for use in the treatment or prevention of obesity, type 2 diabetes or cardiovascular disorders, wherein the first pharmaceutical composition is administered together with a composition comprising a soy protein isolate, a soy fibre, a phospholipid, and a carbohydrate.

[0019] Soy protein isolate

[0020] As used herein, a soy protein isolate refers to a soy protein containing material that contains at least 85%, preferably 90% soy protein by weight on a moisture free basis. The soy protein isolate may be present in the composition in an amount of 20% to 50%, preferably in an amount of 25% to 45%, preferably in an amount of 30% to 40%, by weight, based on the total weight of the composition. The inclusion of a soy protein isolate may improve gut health by increasing probiotics in the intestines, thereby improving the gut microbiome, which in turn may lead to improvement in cardiovascular health and the immune system. It may also demonstrate anti-inflammatory effects. A soy protein isolate is also important to build or rebuild muscles and other tissues.

[0021] The soy protein isolate may comprise one or more isoflavones. The soy protein isolate may contain any suitable isoflavone. In a preferred embodiment, the one or more isoflavones may be selected from the group consisting of daidzein, glycitein, genistein, daidzin, glycitin, genistin, malonylglucosides, 6-O-malonyl-7-O-p-D-daidzin, 6-O-malonyl-7-O-p-D-glycitin, 6- O-malonyl-7-O-p-D-genistin, acetylglucosides, 6-O-acetyl-7-O-p-D-daidzin, 6-O-acetyl-7-O-p- D-glycitin, 6-O-acetyl-7-O-p-D-genistin and combinations thereof. In a further preferred embodiment, the soy protein isolate may contain daidzein, glycitein, genistein and combinations thereof. The soy protein isolate may comprise one or more isoflavones in an amount of 0.01 % to 0.5%, preferably in an amount of 0.03% to 0.25%, and preferably in an amount of 0.05% to 0.2% by weight, based on the total weight of the soy protein isolate.

[0022] The one or more isoflavones may be present in an amount of 0.001% to 0.2%, preferably in an amount of 0.005% to 0.15%, and preferably in an amount of 0.01% to 0.1 % by weight, based on the total weight of the composition.

[0023] The soy protein isolate may contain all nine essential amino acids, namely histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine.

[0024] The soy protein isolate may comprise arginine.

[0025] The soy protein isolate may comprise arginine in an amount of 1% to 15%, preferably in an amount of 3% to 12%, and preferably in an amount of 5% to 10% by weight, based on the total weight of the soy protein isolate.

[0026] Arginine may be present in an amount of 0.2% to 5%, preferably in an amount of 0.5% to 4%, preferably in an amount of 1 % to 4% and preferably in an amount of 2% to 4% by weight, based on the total weight of the composition.

[0027] The presence of arginine and isoflavones may have a number of health benefits. For example, arginine and isoflavones are known to release nitric oxide (NO), which relaxes muscle cells in blood vessels whereby the blood vessels dilate and provide more blood flow, oxygen and nutrients to all tissues and organs. The dilatation of blood vessels is important since this normalises blood pressure, particularly in cases of high blood pressures. Furthermore, this reduces the risk of eyesight problems related to certain appetite suppressant agents such as GLP-1 receptor agonists.

[0028] Soy fibre

[0029] The composition according to the present invention comprises soy fibre. Soy fibre as used herein refers to macromolecular sugars present in soybeans that cannot be digested by human digestive enzymes. Such sugars include cellulose, pectin, xylan and mannose. Soy fibre may increase satiety, and may also act as a prebiotic by increasing healthy bacteria / probiotics to improve the gut microbiome. A prebiotic as used herein refers to a non- digestible compound that, through its metabolization by microorganisms in the gut, modulates the composition and / or activity of the gut microbiota, thus conferring a beneficial physiologic effect on the host.

[0030] In a preferred embodiment, soy fibre is cotyledon soy fibre.

[0031] The soy fibre may be present in an amount of 2% to 10%, preferably in an amount of 3% to 9%, preferably in an amount of 3% to 8%, preferably in an amount of 4% to 7% by weight, based on the total weight of the composition.

[0032] The composition according to the present invention further comprises a phospholipid. Any suitable phospholipid may be used. In one embodiment, the phospholipid may comprise essential polyunsaturated fatty acids.

[0033] In an embodiment, the phospholipid may be selected from the group consisting of phosphatidylcholine, phosphatidylinositol, phosphatidylethanolamine, phosphatidylserine, and phosphatidic acid.

[0034] In a further preferred embodiment, the phospholipid may be a soy phospholipid.

[0035] The phospholipid may be present in an amount of 1% to 15%, preferably in an amount of 3% to 13%, preferably in an amount of 5% to 11%, preferably in an amount of 7% to 9% by weight, based on the total weight of the composition.

[0036] The presence of phospholipids may have a number of advantages including the maintenance of the cell membrane structure, protecting organelles, supporting mitochondrial function, supporting brain health, enhancing acetylcholine, facilitating early brain development, strengthening the gut lining and supporting healthy liver function.

[0037] The combination of the soy protein isolate, soy fibre and phospholipids present in the composition is considered to improve the cholesterol lowering effect, and even double the lipid lowering effect compared to soy protein alone. For example, an intake of a minimum of 25 g of soy protein daily have been reported to reduce cholesterol and protect against heart disease.

[0038] Carbohydrates

[0039] The composition according to the present invention further comprises a carbohydrate. As used herein, the term carbohydrate refers to any natural or synthetic monosaccharide, disaccharide, oligosaccharide or polysaccharide. Any suitable carbohydrate may be used. In an embodiment, the carbohydrate is selected from the group consisting of fructose, sucrose, glucose, galactose, maltose, sorbital, dextrose, other simple sugars, glycogen, soluble starches, and combinations thereof. In a preferred embodiment, the carbohydrate is fructose.

[0040] The carbohydrates may be present in an amount of 10% to 60%, preferably in an amount of 20% to 50%, preferably in an amount of 25% to 45%, preferably in an amount of 30% to 40% by weight, based on the total weight of the composition.

[0041] The presence of carbohydrates provide glucose to both the central nervous system and the muscles, which use glucose as its energy source. Without sufficient amount of carbohydrates, the body may start to break down protein from muscle to release glucose, and lean body mass may thereby be lost. Accordingly, the presence of a carbohydrates may mitigate such effects.

[0042] The composition according to the present invention may increase metabolism, by commencing the digestive processes, nutrient uptake and rebuilding bodily tissues, which all cost energy. The composition according to the present invention may also provide all essential macro and micro nutrients, thus minimising the loss of lean body mass including muscle mass. In addition, patients who may be undergoing treatment with an appetite suppressant agent alone may lose their appetite and may not be provided with all essential nutrients through diet and exercise. Such patients may develop a serious problem once they enter into starvation (cachexia). The term cachexia refers to a condition which is characterised by muscle mass loss with or without fat mass loss that is often associated with anorexia, an inflammatory process, insulin resistance, and increased protein turnover. Therefore, the present composition aims to mitigate these problems.

[0043] As such, a further aspect of the present invention may relate to a composition comprising a soy protein isolate, a soy fibre, a phospholipid and a carbohydrate, for use in the treatment or prevention of cachexia or muscle atrophy. In a preferred embodiment, the present invention may relate to a composition comprising a soy protein isolate, a soy fibre, a phospholipid and a carbohydrate, for use in the treatment or prevention of cachexia or muscle atrophy, wherein the composition is administered together with a first pharmaceutical composition comprising an appetite suppressant agent.

[0044] First Pharmaceutical composition

[0045] The composition according to the present invention is administered together with a first pharmaceutical composition comprising an appetite suppressant agent.

[0046] The term “together with” can refer to, but is not limited to a situation where the composition and the first pharmaceutical composition comprising an appetite suppressant agent are administered at once at the same time. Therefore, the composition may be administered concurrently (i.e. at the same time as or simultaneously) with a first pharmaceutical composition comprising an appetite suppressant agent. Alternatively, the composition may be administered consecutively or at a different time from the first pharmaceutical composition comprising an appetite suppressant agent. Accordingly, the composition and the first pharmaceutical composition may be administered at any suitable timeframe as long as the composition is administered while the patient is undergoing treatment with the first pharmaceutical composition comprising an appetite suppressant agent. For example, a patient may be given a single dose of an appetite suppressant agent once weekly whilst being administered the composition according to the present invention 3 to 6 times a day.

[0047] An appetite suppressant agent refers to any compound or substance which limits appetite and / or increase the sense of satiety. Any suitable appetite suppressant agent may be used in the first pharmaceutical composition. In a preferred embodiment, the appetite suppressant agent is selected from the group consisting of GLP-1 receptor agonists, GIP receptor agonists, glucagon receptor agonists, cannabinoid receptor 1 (CB1) inverse agonists and combinations thereof. In a further preferred embodiment, the appetite suppressant agent may be a GLP-1 receptor agonist.

[0048] A GLP-1 receptor agonist as used herein refers to a class of drugs that reduce blood sugar and energy intake by activating the GLP-1 receptor. They mimic the actions of the endogenous incretin hormone GLP-1 that is released by the gut after eating. GLP-1 receptor agonists work by activating the GLP-1 receptor. They slow gastric emptying, inhibit the release of glucagon, and stimulate insulin production, therefore reducing hyperglycaemia in people with type 2 diabetes. They also reduce appetite and food intake and therefore body weight, making them an effective treatment for obesity.

[0049] According to the present invention, any suitable GLP-1 receptor agonist may be used in the first pharmaceutical composition. In a preferred embodiment, the GLP-1 receptor agonist may be selected from the group consisting of dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, tirzepatide, retatrutide, pemvidutide, mazdutide, efpeglenatide and albiglutide. In a more preferred embodiment, the GLP-1 receptor agonist is semaglutide. Whilst these active ingredients have been listed as examples of GLP-1 receptor agonists, some of these active ingredients may act as dual or triple receptor agonists. For example, tirzepatide may act as a dual GIP / GLP-1 receptor agonist, pemvidutide may act as a dual GIP / glucagon receptor agonist and retatrutide may act as a triple GLP-1 / GIP / glucagon receptor agonist.

[0050] The GLP-1 receptor agonist may be administered once a week as a single dose in an amount of between 0.01 mg to 10 mg, preferably 0.05 mg to 9 mg, preferably 0.1 mg to 8 mg, preferably 0.1 mg to 7 mg, preferably 0.1 mg to 6 mg, preferably 0.2 mg to 5 mg, preferably 0.2 mg to 4 mg, preferably 0.25 mg to 3 mg, preferably 0.25 mg to 2.5 mg, and preferably 0.25 mg or 0.5 mg.

[0051] In an embodiment according to the present invention, the GLP-1 receptor agonist may be administered for at least 4 weeks. In another embodiment, the GLP-1 receptor agonist may be administered between 4 weeks to 5 years, preferably between 4 weeks to 4 years, preferably between 4 weeks to 3 years, and preferably between 4 weeks to 2 years.

[0052] In an embodiment, the appetite suppressant agent may be a glucose-dependent insulinotropic polypeptide (GIP) receptor agonist. Any suitable GIP receptor agonist may be used in the first pharmaceutical composition.

[0053] In a further embodiment, the appetite suppressant agent may be a glucagon receptor (GCGR) agonist. Glucagon receptor agonists are a class of drugs that treat obesity, non-alcoholic fatty liver disease, and congenital hyperinsulinism. GCGRs are peptide hormones that are secreted by pancreatic alpha cells. They have been shown to increase metabolic rate, increase oxygen consumption, increase energy expenditure, and have anorexigenic effects. Any suitable glucagon receptor agonist may be used in the first pharmaceutical composition. In another embodiment, the appetite suppressant agent may be a cannabinoid receptor 1 (CB1) inverse agonist. CB1 inverse agonist is a type of cannabinoidergic drug that binds to cannabinoid receptor 1 and prevents their activation by endocannabinoids. Any suitable CB1 inverse agonist may be used in the first pharmaceutical composition. In a preferred embodiment, the CB1 inverse agonist may be selected from the group consisting of monlunabant, rimonabant and taranabant.

[0054] The appetite suppressant agent may be provided in the first pharmaceutical composition in a free form or as a pharmaceutically acceptable salt. The term “salt” as used herein refers to a salt of an appetite suppressant agent that is derived from suitable inorganic and organic acids and bases. Examples of salts of a basic group include those formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid or with organic acids such as trifluoroacetic acid, acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid or by using other methods used in the art such as ion exchange. Other salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate salts, and the like. Salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium and N+(CI-C4 alkyl)4 salts. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further salts include, when appropriate, nontoxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, alkyl sulfonate and aryl sulfonate.

[0055] In some aspects, the appetite suppressant agent may exist in an unsolvated form as well as the solvated form, including the hydrated form. “Hydrate” refers to a complex formed by combination of water molecules with molecules or ions of the solute. “Solvate” refers to a complex formed by combination of solvent molecules with molecules or ions of the solute. The solvent may be an organic compound, an inorganic compound, or a mixture of both. Solvate is meant to include hydrate. Some examples of solvents include, but are not limited to, methanol, acetonitrile, N,N-dimethylformamide, tetrahydrofuran, dimethylsulfoxide, and water. In general, the solvated forms are equivalent to unsolvated forms and are encompassed within the scope of the present invention.

[0056] Second

[0057] The composition and the first pharmaceutical composition according to the present invention may further be administered together with a second pharmaceutical composition comprising an appetite suppressant agent. In such an embodiment, the second pharmaceutical composition may comprise the same or different appetite suppressant agent to that contained in the first pharmaceutical composition. In a preferred embodiment, the second pharmaceutical composition may comprise a different appetite suppressant agent to that contained in the first pharmaceutical composition.

[0058] The second pharmaceutical composition may comprise any suitable appetite suppressant agent, such as those described above in connection with the first pharmaceutical composition.

[0059] In a preferred embodiment, the second pharmaceutical composition comprising an appetite suppressant agent may be administered separately from the first pharmaceutical composition comprising appetite suppressant agent.

[0060] The appetite suppressant agent may be provided in the second pharmaceutical composition in a free form or as a pharmaceutically acceptable salt. Suitable salt forms include those as described in connection with the appetite suppressant agent of the first pharmaceutical composition.

[0061] The appetite suppressant agent may exist in an unsolvated form as well as the solvated form. Suitable solvates include those as described in connection with the appetite suppressant agent of the first pharmaceutical composition.

[0062] Methods of Administration

[0063] The first and second pharmaceutical compositions may be administered by any suitable method. Suitable methods include oral administration, administration as a suppository, topical contact, intravenous, intraperitoneal, intramuscular, intralesional, intranasal or subcutaneous administration. Administration is by any route, including parenteral and transmucosal (e.g., buccal, sublingual, palatal, gingival, nasal, vaginal, rectal, or transdermal). Parenteral administration includes, e.g., intravenous, intramuscular, intra-arteriole, intradermal, subcutaneous, intraperitoneal, intraventricular, and intracranial. Other modes of delivery include, but are not limited to, the use of liposomal formulations, intravenous infusion, transdermal patches, etc.).

[0064] In a preferred embodiment, the first and second pharmaceutical compositions are independently administered by oral, intravenous or subcutaneous administration.

[0065] Forms and administration of the composition

[0066] The composition according to the present invention may be in the form of a low calorie or very low calorie meal replacement. As used herein, a low or very low calorie meal replacement refers to a food product that substitutes for a meal and has fewer calories than a typical meal. A very low calorie meal replacement product may provide less than 800 kcal / day, and a low calorie meal replacement product may provide between 800 to 1500 kcal / day. The composition may be taken as a partial meal replacement product or as a total meal replacement product. In the case that the composition is taken as a partial or total meal replacement, a lower dosage of the appetite suppressant agent may be administered.

[0067] The total calorific value of the composition may be less than 800 kcal / day. Alternatively, the total calorific value of the composition may be between 800 kcal / day and 1500 kcal / day, preferably 800 kcal / day and 1400 kcal / day, preferably 800 kcal / day and 1300 kcal / day, and preferably 800 kcal / day and 1200 kcal / day.

[0068] The composition according to the present invention may be provided in the form of a powder, and preferably in the form of a powder that may be blended with a liquid such as milk or water to make a beverage such as a shake. The composition may also be provided in the form of a beverage.

[0069] The composition according to the present invention may be administered between 3 to 6 times daily, preferably between 3 to 5 times daily. In an embodiment, the composition according to the present invention may be administered between 3 to 6 times daily for men, and between 3 to 5 times daily for women. In an embodiment, the composition according to the present invention may be administered every 2 to 8 hours, preferably every 3 to 7 hours, preferably every 4 to 6 hours, and more preferably every 3 to 4 hours. In a further embodiment, when the composition according to the present invention is administered together with a first pharmaceutical composition comprising an appetite suppressant agent, a lower dosage of the appetite suppressant agent than the prescribed amount may be administered. The dosage of the appetite suppressant agent in the first pharmaceutical composition may be reduced by 1 wt.% to 80 wt.%, preferably 1 wt.% to 70 wt.%, preferably 1 wt.% to 60 wt.%, preferably 1 wt.% to 50 wt.%, preferably 5 wt.% to 40 wt.%, more preferably 10 wt.% to 30 wt.%, and yet more preferably 15 wt.% to 25 wt.% compared to the prescribed amount. Accordingly, when the composition according to the present invention is administered together with a first pharmaceutical composition comprising an appetite suppressant agent, a lower dosage of the appetite suppressant agent may be administered compared to a treatment where an appetite suppressant agent alone is administered.

[0070] Appetite suppressant agents such as GLP-1 receptor agonists may cause adverse side effects. Such side effects include nausea, vomiting, diarrhoea, abdominal pain or bloating, constipation, headache, fatigue, indigestion, nasopharyngitis, dyspepsia, flatulence, upper respiratory tract infection, eructation, back pain, dizziness, allergic reaction, pancreatitis, hypoglycaemia, thyroid cancer, eyesight problems including blindness, loss of muscle mass and increased heart rate. Accordingly, by reducing the dosage of an appetite suppressant agent in the pharmaceutical composition, the present invention can substantially reduce, minimise or avoid the side effects associated with appetite suppressant agents to provide a safer treatment.

[0071] The composition according to the present invention is therefore considered to provide one or more of the following health benefits: Secures lower dosage of an appetite suppressant agent such as GLP-1 receptor agonists, with fewer side effects. Secures vasodilatation with increased blood flow. Secures reduced risk for eyesight problems including blindness associated with appetite suppressant agents such as GLP-1 receptor agonists. Secures increased weight loss compared to an appetite suppressant agent alone. Secures essential nutritional need / nutrients for all bodily functions, and preservation of lean body mass including muscle mass, bone mass and organ tissue. Secures cardiovascular health benefits, including improved blood circulation in blood vessels, anti-atherosclerotic effect on the arterial wall and significant reductions of blood pressure and blood lipids (LDL and total cholesterol, homocysteine, Apolipoprotein B (ApoB), and coagulation factors).

[0072] Additional components

[0073] The composition according to the present invention may further comprise vitamins, minerals, electrolytes and trace elements which may support vital functions in the body. Such additional components may be selected from the group consisting of vitamin A, vitamin D, vitamin E, vitamin C, thiamine, riboflavin, niacin, vitamin B6, folic acid, vitamin B12, biotin, pantothenic acid, vitamin K, calcium, phosphorus, iron, magnesium, zinc, iodine, potassium, chloride, copper, manganese, selenium, molybdenum, chromium, and combinations thereof. The inclusion of thiamine, niacin, vitamin B6, vitamin B12, vitamin D3, vitamin K2-7, and / or magnesium in particular may all support cardiovascular function.

[0074] The components of the composition may provide sufficient amount of the essential nutrients the body requires to build and replace new cells. They may also support the cardiovascular functions of the body.

[0075] The composition according to the present invention may consist of plant-based ingredients. Accordingly, the composition may consist of foods or ingredients derived solely from plants. When the composition consists of plant-based ingredients, it was found to increase the feeling of fullness for up to 4 hours, and sometimes longer, from each meal replacement sachet comprising the composition according to the present invention.

[0076] Medical Use

[0077] The composition according to the present invention may be used in the treatment of obesity, type 2 diabetes or cardiovascular disorder. The composition according to the present invention may also be used for the prevention of obesity, type 2 diabetes or cardiovascular disorder.

[0078] In an embodiment, the composition according to the present invention may be used in the prevention of obesity. Prevention of obesity may include administering the composition for weight maintenance rather than weight loss, and in particular for longer term weight maintenance. Longer term may refer to any reasonable length of time of treatment, for example, for more than 2 years, preferably more than 5 years, and preferably more than 10 years. Accordingly, in an embodiment, the composition comprising a soy protein isolate, a soy fibre, a phospholipid and a carbohydrate, may be used for weight maintenance, and in particular, longer term weight maintenance, wherein the composition is administered together with a first pharmaceutical composition comprising an appetite suppressant agent. In a preferred embodiment, the appetite suppressant agent may be administered at the lowest prescribed dose (e.g. 0.25 mg / week or 0.5 mg / week). Such an embodiment may provide all essential nutrients whilst minimising or avoiding side effects associated with an appetite suppressant agent.

[0079] The composition according to the present invention may further be used in the prevention and / or treatment of cachexia or muscle atrophy. Accordingly, the composition comprising a soy protein isolate, a soy fibre, a phospholipid and a carbohydrate, may be used for the treatment or prevention of cachexia or muscle atrophy. In a preferred embodiment, the composition comprising a soy protein isolate, a soy fibre, a phospholipid and a carbohydrate, may be used in the treatment or prevention of cachexia or muscle atrophy, wherein the composition is administered together with a first pharmaceutical composition comprising an appetite suppressant agent.

[0080] In an embodiment, the present invention relates to a method for treating or preventing obesity, type 2 diabetes or cardiovascular disorder in a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising a soy protein isolate, a soy fibre, a phospholipid, and a carbohydrate, together with a first pharmaceutical composition comprising an appetite suppressant agent.

[0081] The present invention also relates to the use of a composition comprising a soy protein isolate, a soy fibre, a phospholipid, and a carbohydrate, for the manufacture of a medicament for the therapeutic and / or prophylactic treatment of obesity, type 2 diabetes or cardiovascular disorder, wherein the composition is administered together with a first pharmaceutical composition comprising an appetite suppressant agent.

[0082] As used herein, the terms “treating” and “treatment” and like terms refer to the administration of the composition or active ingredient (e.g. GLP-1 receptor agonist and / or GIP receptor agonist and / or glucagon receptor agonist) in an amount effective to prevent, alleviate, or ameliorate one or more symptoms of a disease or condition, i.e., indication, and / or to prolong the survival of the patient being treated. The term “obesity” as used herein is defined in the WHO classifications of weight (Kopelman (2000) Nature 404:635643). Underweight refers to a body mass index or BMI of less than 18.5 kg / m2(thin); healthy refers to a BMI of 18.5-24.9 kg / m2(normal); grade 1 overweight refers to a BMI of 25.0-29.9 kg / m2(overweight); grade 2 overweight refers to a BMI of 30.0-39.0 kg / m2(obesity); grade 3 overweight is greater than or equal to a BMI of 40.0 kg / m2(morbid obesity).

[0083] The term cardiovascular disorder as used herein refers to any abnormal function of the heart, particularly, abnormal functions or deficiency of the myocardium. In an embodiment, the cardiovascular disorder may be selected from the group consisting of coronary heart disease, cardiomyopathy, hypertrophy, ischemic heart disease, heart failure, inflammatory heart disease, small vessels disease, fibrosis, valvular heart disease, aneurysm, atherosclerotic disease, dyslipidaemia, hypercholesterolemia, hypertension, coronary artery disease, myocarditis, amyloidosis, and combinations thereof.

[0084] Appetite suppressant and a low calorie or very low calorie meal replacement product

[0085] A further aspect of the present invention relates to a first pharmaceutical composition comprising an appetite suppressant agent for use in the treatment or prevention of obesity, type 2 diabetes or cardiovascular disorders, wherein the first pharmaceutical composition is administered together with a low calorie meal replacement product or a very low calorie meal replacement product.

[0086] A very low calorie meal replacement product may provide less than 800 kcal / day, and a low calorie meal replacement product may provide between 800 to 1500 kcal / day. The total calorific value of the low calorie meal replacement product may be less than 800 kcal / day. Alternatively, the total calorific value of the low calorie meal replacement product may be between 800 kcal / day and 1500 kcal / day, preferably 800 kcal / day and 1400 kcal / day, preferably 800 kcal / day and 1300 kcal / day, and preferably 800 kcal / day and 1200 kcal / day.

[0087] The low calorie meal replacement product or very low calorie meal replacement product may be taken as a partial meal replacement product or as a total meal replacement product. In the case that the low calorie meal replacement product or very low calorie meal replacement product is taken as a partial or total meal replacement, a lower dosage of the appetite suppressant agent may be administered. This aspect of the present invention may further comprise a second pharmaceutical composition comprising a further appetite suppressant agent.

[0088] This aspect of the present invention may further comprise any of the features of the pharmaceutical composition as described herein.

[0089] Combination

[0090] A further aspect of the present invention relates to a combination (i.e. , a combination therapy) for use in the treatment or prevention of obesity, type 2 diabetes or cardiovascular disorders, the combination comprising a composition and a first pharmaceutical composition; wherein the composition comprises a soy protein isolate, a soy fibre, a phospholipid, and a carbohydrate; and the first pharmaceutical composition comprises an appetite suppressant agent.

[0091] The composition and the first pharmaceutical composition comprising an appetite suppressant agent may be administered at once at the same time. Therefore, the composition may be administered concurrently (i.e. at the same time as or simultaneously) with a first pharmaceutical composition comprising an appetite suppressant agent. Alternatively, the composition may be administered consecutively or at a different time from the first pharmaceutical composition comprising an appetite suppressant agent. Accordingly, the composition and the first pharmaceutical composition may be administered at any suitable timeframe as long as the composition is administered while the patient is undergoing treatment with the first pharmaceutical composition comprising an appetite suppressant agent. For example, a patient may be given a single dose of an appetite suppressant agent once weekly whilst being administered the composition according to the present invention 3 to 6 times a day.

[0092] The combination according to the present invention may further comprise a second pharmaceutical composition comprising a further appetite suppressant agent.

[0093] The combination may further comprise any of the features of the composition, first pharmaceutical composition and second pharmaceutical composition as described herein.

[0094] Kit A further aspect of the present invention relates to a kit comprising: a composition comprising a soy protein isolate, a soy fibre, a phospholipid, and a carbohydrate; and a first pharmaceutical composition comprising an appetite suppressant agent.

[0095] The kit according to the present invention may further comprise a second pharmaceutical composition comprising a further appetite suppressant agent.

[0096] The kit may further comprise any of the features of the composition, first pharmaceutical composition and second pharmaceutical composition as described herein.

[0097] Benefits

[0098] It has surprisingly been found that the combination of the composition and the first pharmaceutical composition comprising an appetite suppressant agent demonstrates a number of benefits.

[0099] It has been found that the dose of the appetite suppressant agent may be substantially reduced when it is administered together with the present composition, thereby reducing or avoiding the associated side effects as well as improving the safety of the treatment.

[0100] The combination of the composition and the first pharmaceutical composition comprising an appetite suppressant agent has further been found to improve the efficacy of the treatment of obesity, wherein an increased weight loss was observed compared to a treatment with an appetite suppressant agent alone. Therefore, the applicant has found that the combination of the composition and the first pharmaceutical composition comprising an appetite suppressant agent leads to a synergistic effect.

[0101] The combined treatment is also considered to reduce the loss of lean body mass including muscle.

[0102] The combined treatment may further improve longer term weight maintenance following weight loss by extending the treatment with the composition according to the present invention.

[0103] Specific embodiments of the invention will now be described by way of examples, with reference to the accompanying drawings, in which: Figure 1 shows the weight loss by patient after 1 week of consuming the composition according to the present invention (e.g. composition of Example 1) as a total meal replacement, five times a day, together with a GLP-1 agonist, as described in Example 5.

[0104] Examples

[0105] Example 1 - composition The nutritional information of an example of a composition comprising a soy protein isolate, a soy fibre, a phospholipid and a carbohydrate according to the present invention is set out below:

[0106] • Reference intake of an average adult (8400 kj 12000 kcal)

[0107] Example 2 - composition used as a partial meal replacement together with GLP-1 reception agonist

[0108] A female patient was placed on a combination treatment of Ozempic® and a composition according to the present invention (composition of Example 1) as follows:

[0109] • The patient was administered the composition of Example 1 , 3 days a week, for breakfast, lunch and evening meal, while eating a calorie restricted dinner with smaller portion.

[0110] • During the 4 days per week she did exercise, a fourth meal comprising a composition of Example 1 was added before each training session.

[0111] • As such the female patient was given a composition of Example 1 , 3-4 times / day, and had a smaller portion dinner.

[0112] Age: 38 years. Initial weight: 88 kg. Height: 165cm. BMI: 32 kg / m2.

[0113] Ozempic®: 0.25 mg injection first week, thereafter 0.5 mg injection weekly (i.e. lowest drug dosage).

[0114] Weight Loss after 5 months: 8 kg

[0115] Weight Loss after 10 months: 11 kg, i.e. 12.5% weight loss of initial body weight.

[0116] The female patient reported increased energy, better wellbeing and did not increase the dosage of Ozempic® during the treatment. The female patient reported better skin quality with less wrinkles, developed no “Ozempic face” and had no saggy skin after her weight loss. Ozempic face refers to the gaunt, sagging appearance of the face that can occur when someone loses weight quickly while taking Ozempic® or other GLP-1 receptor agonists. In addition, no side effects were reported.

[0117] As such, a safer weight loss result was achieved by using an appetite suppressant such as Ozempic® when this was combined with the composition according to the present invention. The dosage of Ozempic® could be kept at a lower dosage with no side effects reported, and an increased weight loss above what could be expected using Ozempic® alone. The composition according to the present invention provided nutritional support, whereby too much loss of muscle mass and fatigue were avoided. No negative changes were observed in any of the blood tests taken. Example 3 - composition as a total meal replacement

[0118] Previous data indicate that by using the composition according to the present invention (e.g. composition of Example 1) as a total meal replacement to exchange all meals, the weight loss after 8 weeks was 15% weight loss of initial body weight for men and 12% weight loss of initial body weight for women, which is more weight loss in a shorter time compared to an appetite suppressant product

[0119] Reference Example 4 - administration of Ozempic® without the composition according to the present invention

[0120] A 70 year old male patient taking Ozempic® injections once weekly, achieved a 10% body weight loss during 12 months of treatment. The dosage of Ozempic® had to be increased from 0.5 mg to a much higher dose weekly, and the last few months of treatment resulted in no further weight loss. The musculature became so weak that the patient had to use crutches when walking after weight loss, developed a heart infarction, heavy breathing and a sense of his blood circulation not being sufficient.

[0121] Example 5 - a 4-week pilot study investigating short-term weight loss and tolerability of low- dose GLP-1 agonists with the composition according to the present invention

[0122] Methods

[0123] Four adults (BMI > 28 kg / m2) were enrolled onto a 4-week, non-blinded, randomised pilot study. Each patient was randomized egually to tirzepatide 2.5 mg weekly (Arm A) or semaglutide 0.25 mg weekly (Arm B). Patients consumed a composition according to the present invention (e.g. composition of Example 1) as a total meal replacement (7 days a week for 4 weeks, five times a day), with non-starchy vegetables and >2 L of fluids permitted. Body weight and waist circumference were measured at baseline and week 4. Weekly assessments recorded adherence, adverse effects, and patient-reported outcomes.

[0124] Patient Characteristics

[0125] The characteristics of the four patients (P01 to P04) are set out below:

[0126] Results

[0127] Body Weight Reduction

[0128] The results of the weight loss of each patient after 1 week are shown in Figure 1 .

[0129] Waist Circumference Reduction Three patients completed the study, achieving mean weight loss of 6.5% (5-7.1 kg) and waist reductions of 6-9 cm. Adverse effects were mild except one semaglutide-related withdrawal (P04) highlighting the importance of early tolerability management of semaglutide. Tirzepatide was found to be more tolerable than semaglutide, consistent with reports of reduced Gl side effects at lower doses.

[0130] Conclusions

[0131] Based on the 4-week weight loss results, it is estimated that the average weight loss will be approximately 11-13 % after 8 weeks, 17-19% after 12 weeks, and 22-24% after 16 weeks. This weight loss is significantly more compared to administration of an appetite suppressant agent alone.

[0132] The observed 5-7 kg weight loss (-6.5%) exceeds typical early-phase results for pharmacotherapy (i.e., appetite suppressant agents) alone, suggesting synergy between appetite suppressant agents and nutritional control using the composition according to the present invention (e.g. composition of Example 1).

[0133] Therefore, the combination of the composition according to the present invention (e.g. composition of Example 1) and an appetite suppressant agent (e.g., tirzepatide, e.g., semaglutide) may improve the efficacy of the treatment of obesity, in which an increased weight loss is observed compared to a treatment with an appetite suppressant agent alone.

[0134] The typical starting dose of semaglutide is 0.25 mg once weekly. This dose is gradually increased every 4 weeks until a maintenance dose is reached (approximately -1.5 mg). The applicants have surprisingly found that the dose of the appetite suppressant agent may be kept at the lowest dose (e.g., the starting dose) or substantially reduced, when it is administered together with the present composition, thereby reducing or avoiding the associated side effects as well as improving the safety of the treatment.

[0135] The applicants have found that combining low-dose GLP-1 therapy with the composition according to the present invention (e.g. composition of Example 1), as a complete meal replacement, yields clinically meaningful short-term weight loss with high satiety and minimal side effects.

[0136] The composition according to the present invention (e.g. composition of Example 1) may also be used as a partial meal replacement. Therefore, improved weight maintenance results are also expected in patients treated with the composition according to the present invention alone and with an appetite suppressant agent, as compared to treatment with an appetite suppressant agent alone.

Claims

- 23 -CLAIMS1. A composition comprising a soy protein isolate, a soy fibre, a phospholipid and a carbohydrate, for use in the treatment or prevention of obesity, type 2 diabetes or cardiovascular disorder, wherein the composition is administered together with a first pharmaceutical composition comprising an appetite suppressant agent.

2. The composition for use according to claim 1 , wherein the appetite suppressant agent is selected from the group consisting of GLP-1 receptor agonists, GIP receptor agonists, glucagon receptor agonists, cannabinoid receptor 1 (CB1) inverse agonists and combinations thereof.

3. The composition for use according to claim 1 , wherein the composition is further administered together with a second pharmaceutical composition comprising a further appetite suppressant agent.

4. The composition for use according to any one of the preceding claims, wherein the soy protein isolate is present in an amount of 20% to 50%, preferably in an amount of 25% to 45%, preferably in an amount of 30% to 40%, by weight, based on the total weight of the composition.

5. The composition for use according to any one of the preceding claims, wherein the soy protein isolate comprises one or more isoflavones, preferably wherein the one or more isoflavones is selected from the group consisting of daidzein, glycitein, genistein, daidzin, glycitin, genistin, malonylglucosides, 6-O-malonyl-7-O-p-D-daidzin, 6-O- malonyl-7-O-p-D-glycitin, 6-O-malonyl-7-O-p-D-genistin, acetylglucosides, 6-O-acetyl- 7-O-p-D-daidzin, 6-O-acetyl-7-O-p-D-glycitin, 6-O-acetyl-7-O-p-D-genistin and combinations thereof.

6. The composition for use according to any one of the preceding claims, wherein the soy protein isolate comprises arginine, preferably in an amount of 1% to 15%, preferably in an amount of 3% to 12%, and preferably in an amount of 5% to 10% by weight, based on the total weight of the soy protein isolate.

7. The composition for use according to any one of the preceding claims, wherein the soy fibre is present in an amount of 2% to 10%, preferably in an amount of 3% to 9%,preferably in an amount of 3% to 8%, preferably in an amount of 4% to 7% by weight, based on the total weight of the composition.

8. The composition for use according to any one of the preceding claims, wherein the phospholipid is present in an amount of 1 % to 15%, preferably in an amount of 3% to 13%, preferably in an amount of 5% to 11%, preferably in an amount of 7% to 9% by weight, based on the total weight of the composition.

9. The composition for use according to any one of the preceding claims, wherein the phospholipid is selected from the group consisting of phosphatidylcholine, phosphatidylinositol, phosphatidylethanolamine, phosphatidylserine, and phosphatidic acid.

10. The composition for use according to any one of the preceding claims, wherein the carbohydrate is selected from the group consisting of fructose, sucrose, glucose, galactose, maltose, sorbital, dextrose, other simple sugars, glycogen, soluble starches, and combinations thereof.

11. The composition for use according to any one of the preceding claims, wherein the carbohydrate is present in an amount of 10% to 60%, preferably in an amount of 20% to 50%, preferably in an amount of 25% to 45%, preferably in an amount of 30% to 40% by weight, based on the total weight of the composition.

12. The composition for use according to any one of the preceding claims, wherein the appetite suppressant agent is a GLP-1 receptor agonist and is administered once a week as a single dose in an amount of between 0.01 mg to 10 mg, preferably 0.05 mg to 9 mg, preferably 0.1 mg to 8 mg, preferably 0.1 mg to 7 mg, preferably 0.1 mg to 6 mg, preferably 0.2 mg to 5 mg, preferably 0.2 mg to 4 mg, preferably 0.25 mg to 3 mg, preferably 0.25 mg to 2.5 mg, and preferably 0.25 mg or 0.5 mg.

13. The composition for use according to claim 12, wherein the GLP-1 receptor agonist is administered for at least 4 weeks, preferably between 4 weeks to 5 years, preferably between 4 weeks to 4 years, preferably between 4 weeks to 3 years, and preferably between 4 weeks to 2 years.

14. The composition for use according to any one of the preceding claims, wherein the appetite suppressant agent is a GLP-1 receptor agonist selected from the groupconsisting of dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, tirzepatide, retatrutide, pemvidutide, mazdutide, efpeglenatide and albiglutide.

15. The composition for use according to any one of the preceding claims, further comprising vitamin A, vitamin D, vitamin E, vitamin C, thiamine, riboflavin, niacin, vitamin B6, folic acid, vitamin B12, biotin, pantothenic acid, vitamin K, calcium, phosphorus, iron, magnesium, zinc, iodine, potassium, chloride, copper, manganese, selenium, molybdenum, chromium, or combinations thereof.

16. The composition for use according to any one of the preceding claims, wherein the appetite suppressant agent is administered by oral, intravenous or subcutaneous administration.

17. The composition for use according to any one of the preceding claims, wherein the composition is administered between 3 to 6 times daily, preferably between 3 to 5 times daily.

18. The composition for use according to claim 17, wherein the total calorific value of the composition is less than 800 kcal / day.

19. The composition for use according to claim 17, wherein the total calorific value of the composition is between 800 kcal / day and 1500 kcal / day, preferably 800 kcal / day and 1400 kcal / day, preferably 800 kcal / day and 1300 kcal / day, and preferably 800 kcal / day and 1200 kcal / day.

20. The composition for use according to any one of the preceding claims, wherein the composition is provided in the form of a powder.

21. The composition for use according to any one of the preceding claims, wherein the composition is provided in the form of a beverage.

22. A kit comprising: a composition comprising a soy protein isolate, a soy fibre, a phospholipid, and a carbohydrate; and a first pharmaceutical composition comprising an appetite suppressant agent.

23. The kit according to claim 22, further comprising a second pharmaceutical composition comprising a further appetite suppressant agent.

24. The kit according to claim 22 or 23, further comprising any one of the features of claims 3 to 21.

25. A composition comprising a soy protein isolate, a soy fibre, a phospholipid and a carbohydrate, for use in the treatment or prevention of cachexia or muscle atrophy.

26. A combination for use in the treatment or prevention of obesity, type 2 diabetes or cardiovascular disorders, the combination comprising a composition and a first pharmaceutical composition; wherein the composition comprises a soy protein isolate, a soy fibre, a phospholipid, and a carbohydrate; and the first pharmaceutical composition comprises an appetite suppressant agent.

27. A first pharmaceutical composition comprising an appetite suppressant agent for use in the treatment or prevention of obesity, type 2 diabetes or cardiovascular disorders, wherein the first pharmaceutical composition is administered together with a low calorie meal replacement product or a very low calorie meal replacement product.

Images