Synergistic nutraceutical composition to improve calcium absorption

Abstract

The present invention relates to the field of nutraceutical compositions aimed at enhancing calcium absorption. More particularly, the invention provides a bioactive composition comprising a synergistic combination of casein phosphopeptides and Parmelia perlata, in conjunction with pharmaceutically acceptable excipients. The unique formulation of these components synergistically promotes improved calcium absorption, thereby offering enhanced nutritional and therapeutic benefits.

Description

[0001] SYNERGISTIC NUTRACEUTICAL COMPOSITION TO IMPROVE CALCIUM ABSORPTION

[0002] RELATED APPLICATION:

[0003] The present application claims benefit of the Indian Provisional Application No. IN202421066041 filed on, August 31st, 2024 the entire contents of which are hereby incorporated by reference.

[0004] FIELD OF THE INVENTION

[0005] The present invention relates to the field of nutraceutical compositions designed to enhance calcium absorption. Specifically, this invention pertains to a potent bioactive composition comprising a synergistic combination of casein phosphopeptides and Parmelia perlata, along with pharmaceutically acceptable excipients. Casein phosphopeptides, is derived or isolated or extracted from milk or synthesized through fermentation processes or chemically process. This lichen exhibits astringent, carminative, demulcent, bitter, emollient, laxative, soporific, sedative, and diuretic properties, and is traditionally used to treat a variety of conditions such as sores, bronchitis, excessive salivation, vomiting, toothache, boils, and inflammation. The innovative combination of these ingredients results in a nutraceutical composition that can effectively enhances calcium absorption.

[0006] BACKGROUND OF THE INVENTION

[0007] Calcium is an essential mineral that plays a vital role in several biological processes. It is necessary for building and maintaining strong bones and teeth, muscle function, nerve transmission, blood clotting, and various other critical functions. Calcium is a mineral that the body needs in significant amounts, with approximately 99% stored in the bones and teeth and the remaining 1% utilized for essential bodily functions. Adequate calcium is crucial for muscle function, including the contraction and relaxation of muscles.

[0008] Calcium deficiency leads to severe health problems, including osteoporosis, osteoporotic fractures, dental issues, muscle cramps and spasms, numbness and tingling, fatigue, increased risk of cardiac disease, and mood changes. Several factors contribute to poor calcium absorption, such as poor calcium solubility, interactions with other components in the food matrix, higher parathyroid hormone levels, vitamin D deficiency, and age. Poor calcium absorption interferes with maintaining normal blood calcium levels, necessitating improvements in calcium absorption methods.

[0009] High calcium intake with poor absorption also leads to nutrient deficiencies by interfering with the absorption of other minerals like zinc, copper, and magnesium, and cause gastrointestinal side effects such as constipation, gas, flatulence, and bloating. Given that calcium is the most abundant mineral in the body and essential for muscle contraction, oocyte activation, building strong bones and teeth, blood clotting, nerve impulse transmission, regulating heartbeat, and fluid balance within cells, it is particularly important during periods of growth, pregnancy, and breastfeeding. Long-term calcium deficiency leads to osteoporosis, where bone deterioration increases the risk of fractures.

[0010] Simple calcium salts, such as phosphates and carboxylates, are only slightly soluble in water. In the stomach, calcium ions are released through acid dissolution. However, when the chyme (partially digested food) moves from the stomach into the more alkaline environment of the intestine, these calcium ions may precipitate as insoluble salts. This precipitation process, driven by supersaturated solutions formed during acid neutralization and rising pH, can reduce calcium bioavailability. The decreased bioavailability of calcium — and its associated health consequences — appears to be linked to calcium precipitation at this stage of digestion, possibly due to the absence of inhibitors that prevent calcium salt precipitation. EP1528864 discloses a calcium absorption enhancer comprising as an active ingredient calcium and at least one of the components selected from the group of egg white, egg white proteins and isoflavones, as well as to an orally ingestible composition comprising it. There is no mention of combination with Parmelia perlata.

[0011] JP3993907 discloses a calcium absorption promoter with thermally clottable P-1, 3- glucan, particularly curdlan, to enhance calcium absorption. The invention addresses the issue of insufficient calcium intake leading to diseases like osteoporosis, hypertension, and colorectal cancer. The use of thermally clottable - 1,3-glucan like curdlan restrict formulation options and dietary preferences.

[0012] US9138414 discloses a bioavailable calcium supplement containing USP grade calcium carbonate powder with specific particle size distribution and vitamin D.

[0013] EP2179659 discloses a calcium absorption enhancer utilizing water-soluble calcium particles for sustained-release calcium ion delivery. It addresses efficient calcium absorption in humans and domestic animals, particularly enhancing bone health and calcium fortification. The invention overcomes drawbacks of conventional calcium additives by providing sustained-release benefits. The emphasis on water-soluble calcium particles for sustained-release delivery complicate the formulation and production process.

[0014] CN104605347 discloses a calcium absorption accelerant and a preparation method thereof and simultaneously discloses a calcium supplement containing the accelerant. The calcium absorption accelerant disclosed by the invention is mainly prepared by adding a folia perillae acutae extract and resveratrol in a raw material to improve the absorption rate of an intestinal tract for calcium and adding an elderberry flower extract to prolong the absorption time of the intestinal tract for the calcium and can effectively improve the absorption rate and the absorption quantity of the intestinal tract for the calcium.

[0015] JP6872699 discloses a composition that shows excellent calcium absorption while containing a dietary fiber derived from a barley stem and / or leaf. The composition containing a barley stem and / or leaf, lactic acid bacteria, calcium, and at least one selected from the group consisting of cabbage fermentation extract, kudzu flower processed material, folic acid, vitamin C and vitamin D.

[0016] CN112471520 discloses a calcium gluconate preparation for promoting calcium absorption comprising calcium gluconate, zinc gluconate, calcium hydroxide, sucrose, butter essence, whole milk, acidity regulator and diluent.

[0017] Based on the above observations, the inventors of the present invention felt that there is an unmet need of the new formulations in the field of nutraceutical compositions which enhance calcium absorption. Specifically, the present invention pertains to a potent bioactive composition comprising a synergistic combination of casein phosphopeptides and Parmelia perlata, along with pharmaceutically acceptable excipients.

[0018] The inventors of the present invention surprisingly found that nutraceutical composition comprising Casein phosphopeptides and Parmelia perlata provides a synergistic nutraceutical composition and enhance calcium absorption effectively.

[0019] OBJECTIVE OF THE INVENTION

[0020] The primary objective of the present invention is to provide a synergistic nutraceutical composition designed to enhance calcium absorption in the body.

[0021] Another objective of the present invention is to provide a synergistic nutraceutical composition comprising Casein phosphopeptides and Parmelia perlata. Another objective of the present invention is to provide a synergistic nutraceutical composition comprising Casein phosphopeptides and Parmelia perlata to enhance calcium absorption in the body.

[0022] Another objective of the present invention is to provide a synergistic nutraceutical composition comprising Casein phosphopeptides and Parmelia perlata along with pharmaceutically acceptable excipients to enhance calcium absorption in the body.

[0023] Another objective of the present invention is to develop a bioactive composition comprising casein phosphopeptides and Parmelia perlata, along with pharmaceutically acceptable excipients.

[0024] One more objective of the present invention is to provide a composition comprising casein phosphopeptides and Parmelia perlata, wherein the casein phosphopeptides and Parmelia perlata are present in a ratio of 1 :0.003 to 1:80.

[0025] Further one more objective of the present invention is to formulate the composition with pharmaceutically acceptable excipients such as diluents, binders, lubricants, glidants, disintegrant, surfactants, additives, solvents, or mixtures thereof.

[0026] Another objective of the present invention is to demonstrate that oral administration of the composition effectively improves calcium absorption in the body.

[0027] Yet Another objective of the present invention is to address calcium deficiency- related health issues by enhancing calcium bioavailability through the synergistic combination of casein phosphopeptides and Parmelia perlata.

[0028] SUMMARY OF THE INVENTION

[0029] The present invention relates to the field of nutraceutical compositions designed to enhance calcium absorption. Specifically, this invention pertains to a potent bioactive composition comprising a synergistic combination of casein phosphopeptides and Parmelia perlata, along with pharmaceutically acceptable excipients.

[0030] The principle aspect of the invention is to provide a synergistic nutraceutical composition aimed at enhancing calcium absorption in the body. The composition includes casein phosphopeptides, which is derived or isolated or extracted from milk through enzymatic hydrolysis or fermentation processes or chemically synthesized. These peptides play a crucial role in the formulation by reducing interactions between calcium and other minerals, preventing the formation of insoluble calcium salts, keeping calcium in a soluble form, and enhancing calcium absorption or incorporation into bones.

[0031] In another aspect of the present invention, the nutraceutical composition provided is designed for oral administration, providing an effective dose that significantly improves calcium absorption in the body. By enhancing calcium absorption, the composition addresses calcium deficiency-related health issues such as osteoporosis, osteoporotic fractures, dental problems, muscle cramps, and spasms, numbness, tingling, fatigue, increased risk of cardiac disease, and mood changes.

[0032] Yet another aspect of the present invention is to provide a combination of Casein phosphopeptides and Parmelia perlata in the composition results in a potent bioactive nutraceutical product that effectively enhances calcium absorption, promoting better bone health and overall calcium balance.

[0033] In one more aspect of the present invention, the nutraceutical composition is particularly beneficial for individuals with poor calcium absorption due to factors such as poor calcium solubility, interactions with other components in the food matrix, higher parathyroid hormone levels, vitamin D deficiency, and age-related issues. It offers a therapeutic solution to improve calcium absorption and maintain normal blood calcium levels. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 : Change in serum total calcium levels

[0035] Figure 2: Change in serum total calcium AUC Figure 3: Change in serum PTH levels

[0036] DETAILED DESCRIPTION OF THE INVENTION

[0037] The following detailed description of the present subject matter the various embodiments. These embodiments are described in sufficient detail to enable those skilled in the art to practice the present subject matter. Other embodiments may be utilized and changes may be made without departing from the scope of the present subject matter.

[0038] References to “an”, “one”, or “various” embodiments in this disclosure are not necessarily to the same embodiment, and such references contemplate more than one embodiment. The following detailed description is, therefore, not to be taken in a limiting sense, and the scope is defined only by the appended claims, along with the full scope of legal equivalents to which such claims are entitled.

[0039] The present invention provides a nutraceutical composition designed to enhance calcium absorption in the body. This composition is formulated to maximize the bioavailability of calcium by leveraging the synergistic effects of casein phosphopeptides and Parmelia perlata.

[0040] Casein phosphopeptides are derived from casein, the main protein found in milk. They are obtained through the enzymatic hydrolysis of casein, which releases peptide fragments that contain phosphorylated serine residues. These residues have a high affinity for calcium ions, preventing the formation of insoluble calcium salts and keeping calcium in a soluble form. This enhances calcium absorption in the intestine and facilitates its incorporation into bones.

[0041] Casein phosphopeptides perform several critical functions that make them ideal for enhancing calcium absorption. Firstly, they enhance calcium solubility. This is crucial because the bioavailability of calcium in the gastrointestinal tract depends significantly on its solubility. When calcium is in a soluble form, it is more easily absorbed by the intestinal cells and transported into the bloodstream. By preventing the formation of insoluble calcium salts, casein phosphopeptides ensure that calcium remains in a form that is readily absorbed.

[0042] Secondly, casein phosphopeptides prevents the precipitation of calcium. In the digestive system, calcium form complexes with other dietary minerals and components, leading to the formation of insoluble salts. These salts are poorly absorbed, reducing the overall bioavailability of calcium. Casein phosphopeptides binds to calcium ions, preventing these interactions and ensuring that calcium remains available for absorption.

[0043] Thirdly, casein phosphopeptides reduces interactions between calcium and other minerals. In the diet, calcium interacts with other minerals such as magnesium, zinc, and iron, forming insoluble complexes that are difficult to absorb. By binding to calcium, casein phosphopeptides minimizes these interactions, enhancing the absorption of not only calcium but potentially other essential minerals as well.

[0044] Finally, casein phosphopeptides improves bone health by enhancing the incorporation of calcium into the bone matrix. Bones are constantly being remodeled, with old bone tissue being replaced by new tissue. This process requires a steady supply of calcium. By increasing the bioavailability of calcium, casein phosphopeptides help ensure that there is enough calcium available to support healthy bone formation and maintenance. As used herein, the term casein phosphopeptides (CPP) may also be referred to by various names, including but not limited to casein-derived peptides, phosphorylated casein peptides, casein-derived phosphorylated peptides, and casein tryptic hydrolysate . All these terms are used interchangeably and carry the same meaning in the context of the present invention.

[0045] Parmelia perlata, also known as stone flower, is a lichen that belongs to the family Parmeliaceae. It exhibits astringent, carminative, demulcent, bitter, emollient, laxative, soporific, sedative, and diuretic effects. By incorporating Parmelia perlata, the composition not only enhances calcium absorption but also provides additional health benefits that support overall well-being.

[0046] The innovative combination of casein phosphopeptides and Parmelia perlata results in a synergistic effect that significantly enhances calcium absorption. This synergy is critical for addressing calcium deficiency-related health issues, such as osteoporosis, osteoporotic fractures, dental problems, muscle cramps and spasms, numbness, tingling, fatigue, increased risk of cardiac disease, and mood changes.

[0047] By enhancing calcium absorption, the composition helps maintain normal blood calcium levels, which is essential for various physiological functions. Calcium plays a crucial role in muscle contraction and relaxation, nerve transmission, blood clotting, and hormone secretion. Adequate calcium levels are also necessary for maintaining the structural integrity of bones and teeth. The synergistic effect of casein phosphopeptides and Parmelia perlata ensures that the body efficiently absorb and utilize calcium, promoting overall health and well-being.

[0048] In principle embodiment of the present invention, synergistic nutraceutical composition as per the present invention comprising of casein phosphopeptides and Parmelia perlata. One embodiment of the present invention provides a synergistic bioactive composition comprising Casein phosphopeptides, Parmelia perlata, or pharmaceutically acceptable salts, isolates, derivatives, or isomers or combination thereof.

[0049] In another embodiment of the present invention, casein phosphopeptides is obtained / isolated / derived from either milk or produced through fermentation or chemical process.

[0050] Parmelia perlata is a species of lichen that belongs to the family Parmeliaceae and is generally referred to as a litho lichen. Parmelia perlata can be prepared by fermentation and extraction.

[0051] According to the present invention, the synergistic bioactive composition comprising Casein phosphopeptides, Parmelia perlata, wherein Casein phosphopeptides and Parmelia perlata are present in a ratio of 1:0.003 to 1:80, 1:0.004 to 1:70, 1:0.005 to 1:60, 1:0.006 to 1:50, 1:0.007 to 1:40, 1:0.008 to 1:30 or 1:0.009 to 1: 15.

[0052] According to the present invention, the amount of Casein phosphopeptides or pharmaceutically acceptable salts, isolates, derivatives, or isomers or combination thereof is present in the range of 0.1 to 99 % w / w, 1 to 90 % w / w, 1 to 80 % w / w, 1 to 70 % w / w, 1 to 60 % w / w , 1 to 50 % w / w, 1 to 40 % w / w, 1 to 99 % w / w, 5 to 99 % w / w, 10 to 99 % w / w, 20 to 99 % w / w, 30 to 99 % w / w, 40 to 99 % w / w, 50 to 99 % w / w, 60 to 99 % w / w, 70 to 99 % w / w of the total composition. The % w / w of the total composition shall be calculated based total weight of Casein phosphopeptides, Parmelia perlata and excipients.

[0053] According to the present invention, the amount of Parmelia perlata or pharmaceutically acceptable salts, isolates, derivatives, or isomers or combination thereof is present in the range of 0.0003 to 99.3371 % w / w, 0.06 to 98 % w / w, 0. 1 to 99 % w / w, 1 to 90 % w / w, 1 to 80 % w / w, 1 to 70 % w / w, 1 to 60 % w / w , 1 to 50 % w / w, 1 to 40 % w / w, 1 to 99 % w / w, 5 to 99 % w / w, 10 to 99 % w / w, 20 to 99 % w / w, 30 to 99 % w / w, 40 to 99 % w / w, 50 to 99 % w / w, 60 to 99 % w / w, 70 to 99 % w / w of the total composition. The % w / w of the total composition shall be calculated based total weight of Casein phosphopeptides, Parmelia perlata and excipients.

[0054] In one more embodiment of the present invention, the pharmaceutically acceptable excipients are selected from a diluent, a binder, a surfactant, a lubricant, a glidant an additive, a solvent or mixtures thereof.

[0055] In another embodiment of the present invention, oral administration of an effective dose of the composition improves calcium absorption.

[0056] In yet another embodiment of the present invention, the nutraceutical composition is designed for oral administration. This route of administration is convenient, non- invasive, and suitable for long-term use.

[0057] In one more embodiment of the present invention, the nutraceutical composition is formulated into various dosage forms, such as tablets, capsules, powders, or liquids, depending on the preferences and needs of the target population.

[0058] The composition of the present invention maintains a specific ratio of casein phosphopeptides to Parmelia perlata, ranging from 1:0.003 to 1:80. This ratio is critical to achieving the desired synergistic effect, maximizing calcium absorption.

[0059] This precise ratio ensures that the bioactive properties of both components are harnessed to their fullest potential, enhancing calcium absorption without causing adverse effects.

[0060] In another embodiment the present invention provides a synergistic bioactive composition comprising Casein phosphopeptides, Parmelia perlata, or pharmaceutically acceptable salts, isolates, derivatives, or isomers or combination thereof, wherein Casein phosphopeptides is present in the range of 0.2 to 99.5% w / w of the total composition, and Parmelia perlata is present in the range of 0.02 to 99.8% w / w of the total composition.

[0061] In another embodiment the present invention provides a synergistic bioactive composition comprising Casein phosphopeptides, Parmelia perlata, or pharmaceutically acceptable salts, isolates, derivatives, or isomers or combination thereof, wherein Casein phosphopeptides is present in the range of 10 mg to 500 mg, and Parmelia perlata is present in the range of 1.5 mg to 800 mg.

[0062] In another embodiment the present invention provides a synergistic bioactive composition comprising Casein phosphopeptides, Parmelia perlata, or pharmaceutically acceptable salts, isolates, derivatives, or isomers or combination thereof; wherein a casein phosphopeptides and Parmelia perlata are present in a specific ratio ranging from 1:0.003 to 1:80. The amount of casein phosphopeptides in the composition ranges from 0.2 to 99.5% w / w, while the amount of Parmelia perlata ranges from 0.02 to 99.8% w / w, The composition includes pharmaceutically acceptable excipients.

[0063] According to present invention, the composition can be a two separate composition, wherein one composition comprises Casein phosphopeptides, or pharmaceutically acceptable salts, isolates, derivatives, or isomers or combination thereof and another composition comprises Parmelia perlata, or pharmaceutically acceptable salts, isolates, derivatives, or isomers or combination thereof and the both separate composition are for simultaneous administration to the person in need thereof.

[0064] According to present invention, the present is fixed dose combination, wherein the composition comprising Casein phosphopeptides, Parmelia perlata, or pharmaceutically acceptable salts, isolates, derivatives, or isomers or combination thereof. The fixed dose combination of present invention contains at least two active ingredients wherein the active ingredients are Casein phosphopeptides and Parmelia perlata. The fixed dose combination composition according to present invention is for administration along with Calcium, wherein calcium component can be added into the composition of present invention or calcium component can be coadministered with composition of the present invention. The fixed dose combination composition according to present invention is for administration along with Calcium and vitamin D, wherein Calcium and vitamin D can be added into the composition of present invention Calcium and vitamin D can be co-administered with composition of the present invention.

[0065] In another embodiment the present invention provides a synergistic bioactive composition comprising Casein phosphopeptides, Parmelia perlata, or pharmaceutically acceptable salts, isolates, derivatives, or isomers or combination thereof, wherein the composition further comprises one or more pharmaceutically acceptable excipients selected from a diluent, a binder, a lubricant, a glidant, disintegrant, Surfactant or mixtures thereof. The synergistic bioactive composition of the present invention may contain additional pharmaceutically acceptable excipients.

[0066] Pharmaceutically acceptable excipients are included in the composition to ensure stability, efficacy, and ease of administration.

[0067] Diluent is selected from one or more of calcium carbonate, dicalcium phosphate, tricalcium phosphate, magnesium carbonate, calcium sulfate, magnesium oxide, microcrystalline cellulose, cellulose powder, maltodextrin, lactose anhydrous, lactose monohydrate, sucrose, mannitol, sorbitol, xylitol, starch, pregelatinized starch, hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyethylene glycol, polyvinylpyrrolidone, xanthan gum, or a mixture thereof. According to the present invention, the composition may comprise a diluent in an amount ranging from 1% to 98% by w / w of the total composition. Binder is selected from one or more of microcrystalline cellulose, carboxymethylcellulose sodium, hydroxypropyl cellulose, hydroxypropyl methylcellulose, Hypromellose, low-substituted hydroxypropyl cellulose, methylcellulose, pregelatinized starch, starch, povidone, Polyvinylpyrrolidone, copovidone, carbomer, sodium alginate, acacia, agar, guar gum, maltodextrin, pectin, tragacanth, or a mixture thereof. According to the present invention, the composition may comprise a binder in an amount ranging from 0.1% to 12% by w / w of the total composition.

[0068] Lubricant is selected from one or more of magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, talc, polyethylene glycol, colloidal silicon dioxide, or glyceryl behenate, zinc stearate or a mixture thereof. According to the present invention, the composition may comprise a lubricant in an amount ranging from 0.5% to 10% by w / w of the total composition.

[0069] Glidant is selected from one or more of colloidal silicon dioxide, hydrophobic colloidal silica, silicon dioxide, talc, tribasic calcium phosphate, or a mixture thereof. According to the present invention, the composition may comprise a glidant in an amount ranging from 0.5% to 10% by w / w of the total composition.

[0070] Disintegrant is selected from one or more of alginic acid, calcium alginate, carboxymethylcellulose calcium, carboxymethylcellulose sodium, microcrystalline cellulose, chitosan, com starch, pregelatinized starch, croscarmellose sodium, crospovidone, docusate sodium, low-substituted hydroxypropyl cellulose, methylcellulose, povidone, sodium alginate, sodium starch glycolate, cross-linked hydroxypropyl cellulose, or a mixture thereof. According to the present invention, the composition may comprise a disintegrant in an amount ranging from 0.4% to 15% by w / w of the total composition. Surfactant is selected from one or more of polysorbates, sorbitan esters, polyethylene glycol esters, polyoxyethylene stearates, polyoxyethylene castor oil derivatives, poloxamers, sodium lauryl sulfate, sodium dodecyl sulfate, sodium stearate, sodium dioctyl sulfosuccinate, benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, lecithin, phosphatidylcholine, lauryl betaine, or a mixture thereof.

[0071] The composition of the present invention can be prepared using conventional methods known in the art for formulating oral dosage forms. Depending on the desired final product, the formulation may be prepared through direct compression, wherein the active pharmaceutical ingredient is blended with suitable excipients such as fillers, binders, disintegrants, and lubricants, followed by compression into tablets. Alternatively, the composition may be processed through granulation techniques, including wet or dry granulation, to enhance flow properties and compressibility. The prepared formulation can be filled into sachets or capsules for ease of administration. Additionally, the composition can be supplied as a powder or granules for reconstitution into an oral suspension. Other suitable processes may also be employed to achieve the desired dosage form while ensuring stability, efficacy, and patient compliance. The processes for the preparation of nutraceutical compositions are well known in the art.

[0072] In another embodiment the present invention provides a synergistic bioactive composition comprising Casein phosphopeptides, Parmelia perlata, or pharmaceutically acceptable salts, isolates, derivatives, or isomers or combination thereof, wherein the composition is in the form of tablets, capsules, powder, pill, hard capsule filled with liquid or solids, soft capsules, granules, pellets, caplets, mini-tablets, syrup, suspension, sachet, modified release formulations, gummies or any other oral dosage form. The preferred dosage for is oral dosage form.

[0073] In another embodiment the present invention provides a synergistic bioactive composition comprising Casein phosphopeptides, Parmelia perlata, or pharmaceutically acceptable salts, isolates, derivatives, or isomers or combination thereof, wherein after oral administration, the composition improves serum total calcium levels by at least 23.84% more than the combined individual effects of Casein phosphopeptides and Parmelia perlata at 5 hours.

[0074] In another embodiment the present invention provides a synergistic bioactive composition comprising Casein phosphopeptides, Parmelia perlata, or pharmaceutically acceptable salts, isolates, derivatives, or isomers or combination thereof, after oral administration, the composition improves serum total calcium AUC (0 to 5 hours) by at least 19.17% more than the combined individual effects of Casein phosphopeptides and Parmelia perlata.

[0075] In another embodiment the present invention provides a synergistic bioactive composition comprising Casein phosphopeptides, Parmelia perlata, or pharmaceutically acceptable salts, isolates, derivatives, or isomers or combination thereof, wherein after oral administration, the composition reduces serum PTH levels by at least 24.26% more than the combined individual effects of Casein phosphopeptides and Parmelia perlata at 5 hours.

[0076] In another embodiment the present invention provides a synergistic bioactive composition comprising Casein phosphopeptides, Parmelia perlata, or pharmaceutically acceptable salts, isolates, derivatives, or isomers or combination thereof, wherein the composition enhances calcium absorption.

[0077] In another embodiment the present invention provides a synergistic bioactive composition comprising Casein phosphopeptides, Parmelia perlata, or pharmaceutically acceptable salts, isolates, derivatives, or isomers or a combination thereof can be provided as a kit. In the kit, both the active ingredients can be present as a separate composition intended to administrate simultaneously. The kit may comprise calcium composition. In addition to calcium, the kit may further comprise vitamin D. In another embodiment the present invention provides a kit comprising Casein phosphopeptides, and Parmelia perlata, optionally further comprising a Calcium and vitamin D supplement, wherein the combination of Casein phosphopeptides and Parmelia perlata enhances calcium absorption upon oral administration, wherein oral administration of combination of Casein phosphopeptides and Parmelia improves serum total calcium by at least 23.84% and reduces serum PTH levels by at least 24.26% more than the combined individual effects of Casein phosphopeptides and Parmelia perlata at 5 hours.

[0078] In another embodiment the present invention provides a synergistic bioactive composition comprising Casein phosphopeptides, Parmelia perlata, or pharmaceutically acceptable salts, isolates, derivatives, or isomers or a combination thereof, wherein Casein phosphopeptides is present in an amount ranging from 10 mg to 500 mg, Parmelia perlata is present in an amount ranging from 1.5 mg to 800 mg; wherein the composition is for oral administration; wherein the composition enhances calcium absorption upon oral administration; and wherein oral administration of the composition improves serum total calcium by at least 23.84% and reduces serum PTH levels by at least 24.26% more than the combined individual effects of Casein phosphopeptides and Parmelia perlata at 5 hours.

[0079] The composition of the present invention remains stable at room temperature.

[0080] Oral administration of the composition ensures that the active ingredients are delivered directly to the gastrointestinal tract, where calcium absorption primarily occurs. The presence of casein phosphopeptides ensures that calcium remains in a soluble form, facilitating its uptake by the intestinal cells. Meanwhile, the bioactive compounds in Parmelia perlata support the overall absorption process and provide additional health benefits. The effective dose of the composition is designed to significantly improve calcium absorption in the body. This is particularly beneficial for individuals with poor calcium absorption due to factors such as poor calcium solubility, interactions with other components in the food matrix, higher parathyroid hormone levels, vitamin D deficiency, and age-related issues. By improving calcium absorption, the composition helps maintain normal blood calcium levels, reducing the risk of calcium deficiency-related health problems.

[0081] The present invention provides a synergistic bioactive composition comprising Casein phosphopeptides, Parmelia perlata, or pharmaceutically acceptable salts, isolates, derivatives, or isomers or combination thereof, wherein Casein phosphopeptides is present in the range of 10 mg to 500 mg, 10 mg to 450 mg, 10 mg to 400 mg, 10 mg to 350 mg, 10 mg to 300 mg, 10 mg to 250 mg, 10 mg to 240 mg, 10 mg to 230 mg, 10 mg to 220 mg, 10 mg to 200 mg, 20 mg to 200 mg, 25 mg to 200 mg.

[0082] The present invention provides a synergistic bioactive composition comprising Casein phosphopeptides, Parmelia perlata, or pharmaceutically acceptable salts, isolates, derivatives, or isomers or combination thereof, wherein Parmelia perlata is present in the range of 1.5 mg to 800 mg, 1.5 mg to 700 mg, 2 mg to 600 mg, 2 mg to 500 mg, 2 mg to 400 mg, 2 mg to 300 mg, 2 mg to 200 mg, 2 mg to 150 mg, 2 mg to 100 mg.

[0083] The synergistic nutraceutical composition of as per the present invention offers a comprehensive solution for enhancing calcium absorption and addressing calcium deficiency-related health issues. The primary applications and benefits of the composition include:

[0084] Bone Health: The composition as per the present invention supports bone health by enhancing calcium absorption and incorporation into bones. This is particularly important for individuals at risk of osteoporosis and osteoporotic fractures. By ensuring adequate calcium intake and absorption, the composition helps maintain bone density and strength, reducing the risk of fractures and bone-related diseases.

[0085] Dental Health: Calcium is essential for the development and maintenance of healthy teeth. The composition as per the present invention helps ensure that sufficient calcium is available for the formation of strong tooth enamel and dentin, reducing the risk of dental problems such as cavities and tooth decay.

[0086] Muscle Function: Calcium plays a critical role in muscle contraction and relaxation. The composition as per the present invention supports muscle health by ensuring adequate calcium levels, reducing the risk of muscle cramps, spasms, and weakness.

[0087] Nerve Transmission: Calcium is involved in nerve transmission, facilitating the communication between nerve cells. The composition as per the present invention also helps maintain normal calcium levels, supporting proper nerve function and reducing the risk of neurological issues.

[0088] Cardiovascular Health: Adequate calcium levels are necessary for the proper functioning of the cardiovascular system. The composition as per the present invention helps reduce the risk of cardiac diseases by ensuring that calcium is efficiently absorbed and utilized by the body.

[0089] Overall Well-being: The composition as per the present invention provides additional health benefits through the bioactive compounds found in Parmelia perlata. These compounds have various medicinal properties, supporting overall health.

[0090] EXAMPLES

[0091] The invention described herein comprises in various objects and their description as mentioned above, with respect to characteristics and processes adopted. While these aspects are emphasized in the invention, any variations of the invention described above are not to be regarded as departure from the spirit and scope of the invention as described.

[0092] EXAMPLE-1: COMPOSITION Following is a general composition formula as per the present invention:

[0093] Process for preparation:

[0094] 1. Accurately weigh each ingredient in separate containers.

[0095] 2. Sift the previously weighed active ingredients and excipients through a sieve.

[0096] 3. Combine the contents from step 2 to prepare suitable oral dosage form.

[0097] EXAMPLE-2A: TABLET COMPOSITION

[0098] EXAMPLE-2B: TABLET COMPOSITION Manufacturing process of tablet composition of example 2A - 2B:

[0099] 1. Accurately weigh each ingredient in separate containers.

[0100] 2. Sift the previously weighed active ingredients, diluent(s), and disintegrating agent(s) separately through a #40 sieve. 3. Combine the contents from step 2 in a rapid mixer granulator (RMG) using a slow-speed impeller. 4. Binder solution preparation: Weigh the binding agent(s) and solubilizing agent(s) in a separate container, dissolve them in the solvent(s), and then add the anthocyanin(s) to the same solution.

[0101] 5. Add the binder solution to the mixture from step 3 in the RMG, using a slow impeller speed.

[0102] 6. Sift and dry the granulated wet mass in a fluid bed dryer at 50°C ± 5 °C until the blend's level of dryness (LOD) is reduced to below 1.5% w / w.

[0103] 7. Sift the semi-dried granules through sieve #20, followed by sieve #30.

[0104] 8. Sift the previously weighed lubricant(s) or glidant(s) separately through sieve #40, then mix them with the material from Step 7.

[0105] 9. Compress the blend from Step 8 to form tablets

[0106] EXAMPLE-2C: CAPSULE COMPOSITION

[0107] Manufacturing process of capsule composition of example 2C:

[0108] 1. Accurately weigh each ingredient in separate containers.

[0109] 2. Sift the previously weighed active ingredients, diluent(s), and disintegrating agent(s) separately through a #40 sieve.

[0110] 3. The active ingredient(s) and excipients are blended to create a uniform powder or granulate (Formulation preparation).

[0111] 4. The empty hard gelatin or HPMC capsule is separated into two halves — the body and the cap (Capsule separation).

[0112] 5. The capsule body is filled with the prepared uniform blend (Filling). 6. The filled body is rejoined with the cap to close the capsule (Capsule joining)

[0113] 7. The filled capsules are cleaned to remove any powder residue and are inspected for quality (e.g., weight, integrity, and fill consistency) (Polishing and Inspection).

[0114] 8. Final capsules are packaged in suitable containers (e.g., bottles or blister packs) for distribution (Packaging).

[0115] EXAMPLE-2D: SACHET COMPOSITION

[0116] Manufacturing process of Sachet composition of example 2D:

[0117] 1. Accurately weigh each ingredient in separate containers.

[0118] 2. Sift the previously weighed active ingredients and excipients through a sieve.

[0119] 3. Combine the contents from step 2.

[0120] 4. Fill the mixture of step 3 into a Sachet. EXAMPLE 3: ANIMAL STUDY

[0121] Objective of the animal study: To evaluate the synergistic efficacy of casein phosphopeptides and Parmelia perlata on serum calcium absorption and parathyroid hormone (PTH) levels in rats.

[0122] Materials and Method: Male wistar rats, aged 8-9 weeks and weighing 230-270 g at the start of the experiments, were divided into different groups, each containing 5 rats.

[0123] All the animals were provided with a calcium restricted diet for 3 weeks prior to the starting of the treatments.

[0124] Animal grouping: Group Std. served as a standard group whereas all the remaining groups (Tl, T2 and T3) received the respective treatments as per the table mentioned below.

[0125] Table 1: b.wt.: Body weight OD : Once daily Evaluation parameters:

[0126] Serum total calcium levels: Serum total calcium levels were measured by Clinchem multi control level 1 Mindray using Calcium assay kit (of Shenzhen Mindray Biomedical).

[0127] Serum PTH levels: Serum PTH levels were measured by Multimode Reader (Biotek Instruments), Cytation 5 model Serial no. 1909161E using respective ELISA kit (of Krishgen Biosystems) leaflet under biosafety cabinet.

[0128] Serum total calcium Area Under Curve (AUC): It is calculated through graphPad prism based on serum total calcium levels.

[0129] Tests parameters:

[0130] Serum Calcium: Calcium is a mineral that the body needs in significant amounts. It is essential for bone health, with about 99% of the body's calcium stored in the bones and teeth. The remaining 1% is used for various essential functions throughout the body. Calcium is crucial for muscle function, including the contraction and relaxation of muscles. It also helps with the transmission of nerve impulses, blood clotting, and the secretion of various hormones and enzymes. Additionally, calcium plays a critical role in cell signaling and communication. It helps regulate the heartbeat, maintain healthy blood pressure, and keep the body's pH levels balanced. Calcium deficiency can have severe consequences on the body. It can lead to a range of health problems, including osteoporosis, dental issues, muscle cramps and spasms, fatigue, and numbness or tingling. Calcium supplementation is often necessary to address calcium deficiency, but its effectiveness is limited by poor intestinal absorption. The study results are provided in table 2 and figure 1 (Change in serum total calcium levels).

[0131] Calcium Area Under the Curve: Calcium Area Under the Curve (AUC) represents the area under the blood concentration-time curve of calcium, also known as the blood concentration-time profile. It is defined by the blood concentration curve on the top and the x-axis (time) on the bottom. The AUC is a measure of the total systemic exposure to calcium. It reflects both the dose of calcium and the rate at which calcium is cleared from the body. The higher the AUC, the greater the absorption. The study results are provided in table 3 and figure 2 (Change in serum total calcium AUC).

[0132] Serum parathyroid hormones: Parathyroid hormone (PTH) plays critical roles in calcium homeostasis and bone biology. First discovered as a calcium-regulating hormone in the 1920s, PTH is secreted by the parathyroid glands and is the primary regulator of blood calcium concentration in all terrestrial vertebrate species. The synthesis and secretion of PTH are stimulated by any decrease in blood calcium, while secretion of the hormone is inhibited by an increase in blood calcium. This rapid negative feedback regulation of PTH production, along with the biological actions of the hormone on different target tissues, represents the most important homeostatic mechanism for minute-to-minute control of calcium concentration in the extracellular fluid (ECF). PTH increases the release of calcium from bone and reduces the renal clearance of calcium. Higher and lower serum parathyroid hormone levels indicate lower and higher serum calcium levels, respectively. The study results are provided in table 4 and figure 3.

[0133] Animal study results:

[0134] Table 2:

[0135] * in combination group (T3) compared to the sum of change in individual Test groups (T1+T2)

[0136] Table 3:

[0137] * in combination group (T3) compared to the sum of change in individual Test groups (T1+T2)

[0138] Table 4:

[0139] * in combination group (T3) compared to the sum of change in individual Test groups (T1+T2)

[0140] The results of the study, as presented in the foregoing tables, clearly establish that the composition of the present invention provides a significant improvement in calcium absorption efficacy. The experimental design and selected efficacy parameters were structured to closely replicate the physiological conditions associated with calcium absorption, thereby enabling accurate and reliable evaluation based on scientifically accepted criteria. The recorded data demonstrate enhanced calcium absorption in test subjects administered with the composition comprising ingredients Casein Phosphopeptides and Parmelia perlata. This substantiates the synergistic effect of the composition of the present invention in promoting calcium uptake. Accordingly, the composition of the present invention presents a promising therapeutic and / or prophylactic solution for the management of calcium deficiency. Enhanced calcium absorption, as facilitated by the composition, helps in the prevention and / or treatment of calcium deficiency-related disorders, including but not limited to osteoporosis, osteoporotic fractures, dental disorders, muscle cramps and spasms, numbness, tingling sensations, fatigue, increased susceptibility to cardiac conditions, and mood disturbances.

Claims

WE CLAIM:

1. A synergistic bioactive composition comprising:(a) Casein phosphopeptides,(b) Parmelia perlata or pharmaceutically acceptable salts, isolates, derivatives, or isomers or combination thereof.

2. The synergistic bioactive composition as claimed in claim 1, wherein Casein phosphopeptides and Parmelia perlata is in a ratio of 1:0.003 to 1:80.

3. The synergistic bioactive composition as claimed in claim 1, wherein;(a) Casein phosphopeptides is present in the range of 0.2 to 99.5 % w / w of the total composition,(b) Parmelia perlata is present in the range of 0.02 to 99.8% of the total composition.

4. The synergistic bioactive composition as claimed in claim 1, wherein;(a) Casein phosphopeptides is present in the range of 10 mg to 500 mg.(b) Parmelia perlata is present in the range of 1.5 mg to 800 mg.

5. The synergistic bioactive composition as claimed in claim 1, wherein the composition further comprises one or more pharmaceutically acceptable excipients selected from a diluent, a binder, a lubricant, a glidant, or mixtures thereof.

6. The synergistic bioactive composition as claimed in claim 1, wherein the composition is in the form of tablets, capsules, powder, pill, hard capsule fdled with liquid or solids, soft capsules, granules, pellets, caplets, mini-tablets, syrup, suspension, sachet, modified release formulations, gummies or any other oral dosage form.

7. The synergistic bioactive composition as claimed in claim 1, wherein;(a) After oral administration, the composition improves serum total calcium levels by at least 23.84% more than the combined individual effects of Casein phosphopeptides and Parmelia perlata at 5 hours; or(b) After oral administration, the composition improves serum total calcium AUC (0 to 5 hours) by at least 19.17% more than the combined individual effects of Casein phosphopeptides and Parmelia perlata.(c) after oral administration, the composition reduces serum PTH levels by at least 24.26% more than the combined individual effects of Casein phosphopeptides and Parmelia perlata at 5 hours.

8. The synergistic bioactive composition as claimed in claim 1, wherein the composition enhances calcium absorption.

9. A kit comprising:(a) Casein phosphopeptides, and(b) Parmelia perlata, optionally comprising a calcium, vitamin D supplement or both, wherein the combination of Casein phosphopeptides and Parmelia perlata enhances calcium absorption upon oral administration, wherein oral administration of combination of Casein phosphopeptides and Parmelia improves serum total calcium by at least 23.84% and reduces serum PTH levels by at least 24.26% more than the combined individual effects of Casein phosphopeptides and Parmelia perlata at 5 hours.

10. The synergistic bioactive composition comprising:(a) Casein phosphopeptides in an amount ranging from 10 mg to 500 mg,(b) Parmelia perlata in an amount ranging from 1.5 mg to 800 mg; wherein the composition is for oral administration; wherein the composition enhances calcium absorption upon oral administration; and wherein oral administration of the composition improves serum total calcium by at least 23.84% and reduces serum PTH levels by at least 24.26% more than the combined individual effects of Casein phosphopeptides and Parmelia perlata at 5 hours.

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