Toothpaste for body disorders

Abstract

The present invention relates to a formulation of toothpaste for the treatment of various disorders or diseases in the human body by incorporating or adding appropriate active ingredients in therapeutic amount or pharmaceutically effective amount for a particular disorder or disease intended to be treated. In particular, the present invention relates to a toothpaste formulation comprising of one or more active ingredients, oral mucosal absorption enhancers, gelling agents, preservatives, and one or more inactive agents. The present invention provides a novel toothpaste formulation and the process of preparing the same. Oral cavity offers relatively consistent and friendly physiological conditions for drug delivery or drug absorption. Thus, absorption through oral buccal mucosa in the toothpaste under invention by-passes the undesirable first-pass effects in the liver ensuring rapid and better bioavailability and greater efficacy.

Description

[0001] Title of the invention - TOOTHPASTE FOR BODY DISORDERS

[0002] FIELD OF THE INVENTION:

[0003] The present invention relates to a novel toothpaste formulation. More particularly, the present invention also relates to the process for preparing the novel toothpaste formulation. The present invention relates to a formulation of toothpaste for the treatment of various disorders or diseases in the human body by incorporating or adding appropriate pharmaceutically and medicinally active ingredients in therapeutic amounts for the treatment of diseases or disorders for which these active ingredients are intended for. The formulation may comprise of one or more active ingredients for a particular disease or disorder, nutrients, oral mucosal absorption enhancers, gelling agents, preservatives, chelating agents, and one or more inactive agents.

[0004] BACKGROUND OF THE INVENTION:

[0005] The absorption of drugs through oral buccal mucosa improves bioavailability of drugs that might otherwise be metabolised during their passage through gastrointestinal tract (g.i. tract) or the liver where the undesired first-pass effects occur. The oral buccal mucosa consists of stratified squamous epithelium. Its thickness and degree of keratinization vary from one region to another and may affect the permeability of a drug. Permeability between the different regions of the oral cavity varies greatly because of the diverse structures and functions. In general, the permeability is based on the relative thickness and degree of keratinization of these tissues in the order of SUBLINGUAL > BUCCAL > PALATAL.

[0006] The permeability of oral buccal mucosa is estimated to be 4 - 4000 times greater than that of skin. In addition to circumventing first-pass metabolism, an advantage of the buccal route is its accessibility. Some anti-microbial and anti-inflammatory agents, some local anaesthetics, and some conventional pharmaceuticals, including mouth washes, oral gels, lozenges, and sublingual tablets are among the few examples of oral buccal route administration.

[0007] The present invention uses the same principle and concept of oral buccal route administration of pharmaceutically active ingredients for the treatment of various disorders or diseases in the human body by incorporating or adding in the toothpaste, appropriate active ingredients for the disease or disorder for which they are intended. CN105125445A describes a new dentifrice composition, characteristic combination thing adds in toothpaste by it, and combined usage has synergistic function, has anti-inflammatory, analgesic, and promotes effect of oral ulcer healing.

[0008] US20200138703A1 describes dietary supplement non-fluoride toothpaste and methods of making and using the same. The non-fluoride toothpaste of the cited document includes a dietary supplement carried in an oral vehicle and is suitable for ingestion.

[0009] Published paper of the “Inventors R. Sinclair, L. Trindade de Carvalho, F. Ferial Ismail and N. Meah for Treatment of male and female pattern hair loss conducted a retrospective analysis of all 64 patients diagnosed with Male Pattern Hair Loss (MPHL) and Female Pattern Hair Loss (FPHL) in Journal of the European Academy of Dermatology and Venereology / 2020 Dec; 34(12):e795-e796” who were treated with sublingual minoxidil monotherapy for a duration exceeding six months.

[0010] The published paper in 2021 in Journal of the European Academy of Detmatology and Venereology / Volume 36, Issue 1 / pp. e62-e66 disclosed sublingual minoxidil for men and women with pattern hair loss: a randomized, placebo-controlled; double -blind dose escalation Phase IB clinical trial.

[0011] The aforementioned literatures or existing formulations do not disclose or suggest the development of a novel toothpaste -based drug delivery system comprising minoxidil in combination with oral mucosal absorption enhancers and complementary formulation excipients. Specifically, no prior art describes a synergistic formulation integrating minoxidil with mucosal permeation enhancers such as bile salts, medium-chain fatty acids, or pharmaceutical-grade surfactants, alongside humectants, abrasives, and rheology modifiers within a dentifrice matrix intended for systemic therapeutic application. The current approach introduces a unique composition wherein minoxidil is effectively solubilized and stabilized within a mucoadhesive toothpaste base, facilitating transmucosal absorption through the oral cavity. This design not only maintains oral hygiene but also enables controlled systemic delivery of minoxidil without eliciting significant alterations in blood pressure, thereby representing a novel, safe, and patient-compliant alternative for the management of systemic body disorders. Thus, the cited documents show use of toothpaste formulations in treatment of various disorders or diseases as the oral buccal mucosal absorption is proved to be a more effective way of improving bioavailability of drugs.

[0012] OBJECTIVE OF THE INVENTION:

[0013] The main objective of the present invention is to provide a novel toothpaste formulation for the treatment of various diseases or disorders in the human body by using appropriate pharmaceutically or medicinally active ingredients for a particular disease or disorder for which these ingredients are intended for.

[0014] One more objective of the present invention is to give the active ingredients to the patient bypassing the undesired first-pass effects in the liver.

[0015] One more objective of the present invention is to provide a toothpaste formulation with an increased bioavailability of drugs.

[0016] One more objective of the present invention is to provide a toothpaste formulation which is convenient to use so that better patient compliance is ensured.

[0017] SUMMARY OF THE INVENTION:

[0018] The main object of the present invention is to provide novel toothpaste formulation for body disorders.

[0019] The main object of the present invention is to provide novel toothpaste formulation for body disorder comprises: a) minoxidil is in range of 0.025% to 0.475% w / w; b) one or more oral mucosal absorption enhancers is in range of 0.05% to 3.00% w / w; c) a humectants is in range of 7.50% to 40.00% w / w; d) an abrasives is in range of 20.00% to 40.0% w / w; e) a surfactant is in range of 1.00 to 5.00% w / w; and f) formulation excipients.

[0020] Another object of the present invention is to provide a novel toothpaste formulation and the process for preparing the novel toothpaste formulation.

[0021] Another object of the present invention is to provide a toothpaste formulation containing an oral mucosal absorption enhancers which are selected from the group of bile salts and derivative such as rage or z / sodium glycocholate; or ionic surfactants such as sodium lauryl sulfate; or non-ionic surfactants such as tween 80, polysorbate; or fatty acid such as oleic acid, acylcamitine; or chelating agent such as EDTA, citric acid; or sulfoxides such as dimethyl sulfoxide [DMSO]; or polyols such as glycerol, propanediol; or monohydric alcohols such as ethanol; or choline esters such as palmitoyl choline, decanoyl choline; or natural origin such as quercetine, genistein; or cyclodextrins such as a- cyclodextrin, P- cyclodextrin, y-cyclodextrin; or positively charged polymers such as chitosan.

[0022] Another object of the present invention is providing toothpaste formulation containing active ingredients in therapeutic amounts for the treatment of various diseases or disorders in human body with suitable excipients.

[0023] Another object of the invention is to provide a novel toothpaste formulation for body disorders comprising of one or more active ingredients for a particular disease or disorder, nutrients, oral mucosal absorption enhancers, gelling agents, antioxidants, preservatives, surfactant, chelating agents, and one or more inactive excipients.

[0024] Another object of the present invention is to provide a toothpaste formulation that is prepared for the treatment of various diseases or disorders in human body by incorporating or adding appropriate pharmaceutically or medicinally active ingredients in therapeutic amounts for a particular disease or disorder intended to be treated.

[0025] DETAILED DESCRIPTION OF THE INVENTION:

[0026] In the following detailed description, reference is made to the accompanying drawings, which form a part hereof. In the drawings, similar symbols typically identify similar components, unless context dictates otherwise. The illustrative embodiments described in the detailed description, drawings, and claims are not meant to be limiting. Other embodiments may be utilized, and other changes may be made, without departing from the spirit or scope of the subject matter presented here. The present technology is also illustrated by the examples herein, which should not be construed as limiting in any way.

[0027] As used herein, the terms below have the meanings indicated.

[0028] The singular forms "a," "an," and "the" may refer to plural articles unless specifically stated otherwise. rage 4 or z / The term "about," as used herein, is intended to qualify the numerical values which it modifies, denoting such a value as variable within a margin of error. When no particular margin of error, such as a standard deviation to a mean value given in a chart or table of data, is recited, the term "about" should be understood to mean that range which would encompass the recited value and the range which would be included by rounding up or down to that figure as well, taking into account significant figures.

[0029] The embodiments, illustratively described herein may suitably be practiced in the absence of any element or elements, limitation or limitations, not specifically disclosed herein. Thus, for example, the terms “comprising,” “including,” “containing,” etc. shall be read expansively and without limitation. Additionally, the terms and expressions employed herein have been used as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the claimed technology. Additionally, the phrase “consisting essentially of’ will be understood to include those elements specifically recited and those additional elements that do not materially affect the basic and novel characteristics of the claimed technology. The phrase “consisting of’ excludes any element not specified.

[0030] The main embodiment of the present invention is to provide a novel toothpaste formulation comprising one or more active ingredients for a particular disease or disorder, oral mucosal absorption enhancers, antioxidants, flavouring agents, preservatives, humectants, and one or more inactive excipients.

[0031] The main object of the present invention is to provide novel toothpaste formulation for body disorder comprises: a) minoxidil is in range of 0.025% to 0.475% w / w; b) one or more oral mucosal absorption enhancers is in range of 0.05% to 3.00% w / w; c) a humectants is in range of 7.50% to 40.00% w / w; d) an abrasives is in range of 20.00% to 40.0% w / w; e) a surfactant is in range of 1.00 to 5.00% w / w; and f) formulation excipients.

[0032] According to the embodiment of the present invention is to provide one or more oral mucosal absorption enhancers are selected from the group of bile salts and derivative, ionic surfactants, non-ionic surfactants, fatty acid, chelating agent, sulfoxides, polyols, monohydric alcohols, monohydric alcohols, choline esters, natural origin, cyclodextrins and positively charged polymers.

[0033] According to the embodiment of the present invention is to provide one or more oral mucosal absorption enhancers are selected from the group of bile salts and derivative such as sodium glycocholate; or ionic surfactants such as sodium lauryl sulfate; or non-ionic surfactants such as tween 80, polysorbate; or fatty acid such as oleic acid, acylcarnitine; or chelating agent such as EDTA, citric acid; or sulfoxides such as dimethyl sulfoxide [DMSO]; or polyols such as glycerol, propanediol; or monohydric alcohols such as ethanol; or choline esters such as palmitoyl choline, decanoyl choline; or natural origin such as quercetine, genistein; or cyclodextrins such as a- cyclodextrin, P- cyclodextrin, y-cyclodextrin; or positively charged polymers such as chitosan.

[0034] According to the embodiment of the present invention is to formulate the toothpaste under invention is to provide appropriate and necessary pharmaceutically active ingredients in therapeutic amounts for the treatment of diseases or disorders for which these active ingredients are intended for.

[0035] According to another embodiment, the present invention can also be formulated for eye relating disorders using eye nourishing nutrients like Astaxanthin, Zeaxanthin, Pine Bark extract, Bilberry extract, Lutein, Vitamin A, Vitamin C, Vitamin E acetate, zinc oxide, cupric oxide, sodium selenite, etc.

[0036] According to another embodiment, the present invention can also be formulated for heart relating disorders using heart nourishing nutrients like Folate, Coenzyme Q10, Antioxidants, Magnesium, Resveratrol, Omega-3s, plant sterols and stands, Lcamitine, Quercetin, Lycopene, etc. that are absorbed better through oral mucosal membrane, eliminating first-pass effect, than through gastrointestinal tract.

[0037] According to another embodiment, the present invention can also be formulated for brain relating disorders using brain nourishing nutrients like Boron, Tryptophan, Tyrosine, Valine, Phenylalanine etc. that are better absorbed through oral mucosal membrane.

[0038] According to another embodiment, the present invention can also be formulated for bone relating disorders using bone nourishing nutrients like Boron, Lysine etc. that are better absorbed through oral mucosal membrane. rage t> or z / According to another embodiment, the present invention can also be formulated for immunity boosting using immunity boosting nutrients to boost the immunity like Threonine, Vitamin B6, Vitamin C, Vitamin E, Magnesium, Zinc ,etc. that are better absorbed through oral mucosal membrane.

[0039] According to one embodiment of the present invention, the novel toothpaste formulation is useful in hair therapy, promoting hair growth, or reducing hair loss, or treating hair disorder, or providing nourishment to hair with nutrients.

[0040] The invention is further illustrated by the following examples which are provided to be exemplary of the invention and do not limit the scope of the invention. While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.

[0041] Hence, toothpaste containing active ingredients for hair growth like Minoxidil can be formulated. The following table shows one such example of the toothpaste under invention. The ratio of the active ingredients is in range of 0.025% to 0.475% w / w.

[0042] Minoxidil:

[0043] Conventional topical solutions for hair problems available in market contain 2% w / w minoxidil, 3% w / w minoxidil or 5% w / w minoxidil or 10% w / w minoxidil.

[0044] Minoxidil is a piperidine- pyrimidine derivative with the chemical structure: 2, 6- diamino-4- piperidino-pyrimidine [C9H15N5O]. Pharmacokinetically, approximately 1.4% of topical minoxidil is absorbed through a normal scalp. The positive effect of the minoxidil on hair growth is mainly due to its metabolites, minoxidil sulfate and the enzyme responsible for this conversion is sulfotransferase, which is located in hair follicles. Minoxidil does not bind to plasma proteins or crosses the blood- brain barrier. Approximately, 95% of systemically absorbed drug and its metabolites are excreted via the kidneys within 4 days. Topical minoxidil has been approved by the U.S. food and drug administration (U.S.F.D.A.) for the treatment of androgenic alopecia (AGA). It has been approved by FDA for the treatment of FPHE (Female pattern hair loss). Minoxidil is also used antihypertensive medication. But, its dosage is higher. Antihypertensive dose of minoxidil is from 10 mg to 40 mg per day. While in the toothpaste under invention minoxidil is used in the range between 0.25 mg to 4.75 mg, per serving of toothpaste. Therefore, it is LDOM (Low dose of oral minoxidil) which is < 5 mg.

[0045] As one embodiment the minoxidil is used in the range of 0.01% w / w to 0.50% w / w, more preferably in the range of 0.025% w / w to 0.475% w / w.

[0046] In another embodiment of the present invention, the abrasives are selected from the group of abrasives such as calcium carbonate, sodium metaphosphate, zirconium silicate and calcium pyrophosphate, ceramic, ceramic iron oxide, dry ice, silicon carbide, boron carbide, iron oxide and diamond dust. The ratio of the abrasives is in range of 20.0% w / w to 40.0% w / w.

[0047] In another embodiment of the present invention, the humectants are selected from the group of humectants such as sorbitol, glycerin, hyaluronic acid, propylene glycol, aloe vera, honey, alpha hydroxycarboxylic acid, urea, panthenol, peptides and amino acids. The ratio of the humectant is in range of 7.5% w / w to 40.0% w / w.

[0048] In another embodiment of the present invention, the flavoring agent are selected from the group of flavoring agent such as caraway, clove oil, lemon, fennel, spearmint, rose, peppermint, ginger, raspberry, maltol, sarsaparilla cherry, glycerin, cocoa, licorice, vanillin, ethyl vanillin, menthol and camphor. The ratio of the flavoring agent is in range of 0.10% w / w to 2.7% w / w.

[0049] In another embodiment of the present invention, the preservatives are selected from the group of preservatives such as benzalkonium chloride, benzoic acid, benzyl alcohol, parabens, Sodium propylparaben, Sodium methylparaben, chlorobutanol, phenol, sodium benzoate and EDTA. The ratio of the preservatives is in range of 0.05% w / w to 0.10% w / w.

[0050] In another embodiment of the present invention, the oral mucosal absorption enhancers are selected from one or more groups of oral mucosal absorption enhancers such as oleic acid, tween 80, lauric acid, acylcarnitine, sodium salicylate, linoleic acid, polyethylene glycol 400, poly sorbate 80, propanediol and sodium glycocholate. The ratio of the Absorption Enhancers is in range of 0.05% w / w to 3.0% w / w. In another embodiment of the present invention, the sweetener is selected from the group of sweetener such as sodium saccharin, sorbitol, Xylitol, sucralose and glycerol. The ratio of the sweetener is in range of 0.01% w / w to 40.0% w / w.

[0051] In another embodiment of the present invention, the thickening agent is selected from the group of thickening agent such as sodium carboxymethyl cellulose, hydroxypropyl methylcellulose and natural gums. The ratio of the thickening agent is in range of 0.01% w / w to 6.0% w / w.

[0052] In another embodiment of the present invention, the antioxidants are selected from the group of antioxidants such as sodium bisulfite, sodium metabisulfite, sodium thiosulfate, citric acid, sodium nitrite. The ratio of the antioxidants is in range of 0.01% w / w to 5.0% w / w.

[0053] In another embodiment of the present invention, the surfactant is selected from the group of surfactant such as sodium lauryl sulphate, coc amidopropyl betaine and sodium methyl cocoyl taurate (adinol). The ratio of the surfactant is in range of 0.01% w / w to 4.0% w / w.

[0054] In another embodiment of the present invention, the solvent / vehicle is selected from the group of solvent / vehicle such as Ethanol, water, PEG 300, PEG 400, propylene glycol, glycerin and acetone. The solvent / vehicle is used in sufficient quantity.

[0055] In present invention sorbitol used as a natural sweetener that doesn't cause tooth decay like sugar does. It encourages saliva production, a natural defense against cavities and plaque. This makes sorbitol-based chewing gum an effective tool in oral hygiene. Also used as a humectant, an ingredient that prevents loss of water in the toothpaste. A humectant traps water in the toothpaste so that when you squeeze the tube, you get a nice, smooth substance.

[0056] In present invention protect cells from damage caused by free radicals, potentially reducing the risk of chronic diseases and promoting overall health.

[0057] Table 1: Formulation of Toothpaste

[0058] Above table shows the quantity of ingredients required for preparing a 3.5 kg of hair growth toothpaste. The quantity of active ingredient Minoxidil is calculated considering 1 gm per serving of the toothpaste. And, the active ingredient Minoxidil is in the concentration of 0.025% w / w to 0.475 % w / w.

[0059] EXAMPLES:

[0060] Example 1: PREPARATION OF TOOTHPASTE

[0061] Manufacturing process for 3.5 kg batch size of hair growth toothpaste

[0062] Weighing the raw materials according to the batch size as follows: Step 1: Dissolve 1400 gm. of sorbitol in demineralised water sufficient to make 70 % w / w solution.

[0063] Step 2: prepared solution 3.5 gm. of sodium benzoate, 3.5 gm of E.D.T.A., 3.5 gm. of sodium methyl parabene, 1.75 gm. of sodium propyl parabene with stirring in about 40 ml. of demineralised water. Add the prepared solution to the sorbitol solution.

[0064] Step 3: Mix 270 gm of glycerine and 52.5 gm of sodium C.M.C. and mix well to form a homogeneous gel. And, then add half the quantity of it to the previously prepared solution of sorbitol, sodium benzoate, E.D.T.A., sodium methyl parabene and sodium propyl parabene.

[0065] Step 4: Take the 15.8 gm. of active ingredient Minoxidil and mix well to make homogeneous dispersion further add 1050 gm. Of calcium carbonate and mix well with continuous stirring and add 35 gm. Of oleic acid and mix well.

[0066] Step 5: Add previously prepared mixture of 24 gm. of menthol and 14 gm of camphor and mix well. Add 5.25 gm of clove oil and 10.5 gm of spearmint flavour and mix well with stirring.

[0067] Step 6: Add previously prepared solution of sucralose in 70 ml of demineralised water and mix well and add the remaining quantity of glycerine- sodium C.M.C. dispersion and mix well.

[0068] Step 7: Add 94.5 gm of citric acid solution prepared in 100 ml. of demineralised water to above prepared paste and mix well and add gently previously prepared solution of 70 gm of sodium lauryl sulphate (S.L.S.) in 210 ml of hot demineralised water, and mix slowly in a way so that the bubble formation is avoided.

[0069] Step 8: Add sufficient quantity of demineralised water to make the entire bulk 3.5 kg of total weight, and stir gently for 1 hour.

[0070] Example 2: PREPARATION OF TOOTHPASTE

[0071] Manufacturing process for 3.5 kg batch size of hair growth toothpaste

[0072] Weighing the raw materials according to the batch size as follows:

[0073] Step 1: Dissolve 1300 gm. of sorbitol in demineralised water sufficient to make 70 % w / w solution.

[0074] Step 2: prepared solution 3.5 gm. of sodium benzoate, 3.5 gm of E.D.T.A., 3.5 gm. of sodium methyl parabene, 1.75 gm. of sodium propyl parabene with stirring in about 40 ml. of demineralised water. Add the prepared solution to the sorbitol solution.

[0075] Step 3: Mix 270 gm of glycerine and 52.5 gm of sodium C.M.C. and mix well to form a homogeneous gel. And, then add half the quantity of it to the previously prepared solution of sorbitol, sodium benzoate, E.D.T.A., sodium methyl parabene and sodium propyl parabene.

[0076] Step 4: Take the 15.8 gm. of active ingredient Minoxidil and mix well to make homogeneous dispersion further add 1050 gm. of calcium carbonate and mix well with continuous stirring and add 35 gm. of oleic acid and 26.25 gm of tween 80 mix well.

[0077] Step 5: Add previously prepared mixture of 24 gm. of menthol and 14 gm of camphor and mix well. Add 5.25 gm of clove oil and 10.5 gm of spearmint flavour and mix well with stirring. Step 6: Add previously prepared solution of sucralose in 70 ml of demineralised water and mix well and add the remaining quantity of glycerine- sodium C.M.C. dispersion and mix well.

[0078] Step 7: Add 1.75 gm of sodium bisulphite and 1.75 gm of sodium hiosulphate solution prepared in 100 ml. of demineralised water to above prepared paste and mix well and add gently previously prepared solution of 70 gm of sodium lauryl sulphate (S.L.S.) in 210 ml of hot demineralised water, and mix slowly in a way so that the bubble formation is avoided.

[0079] Step 8: Add sufficient quantity of demineralised water to make the entire bulk 3.5 kg of total weight, and stir gently for 1 hour.

[0080] Example 3: PREPARATION OF TOOTHPASTE

[0081] Manufacturing process for 3.5 kg batch size of hair growth toothpaste Weighing the raw materials according to the batch size as follows: Step 1: Dissolve 1300 gm. of sorbitol in demineralised water sufficient to make 70 % w / w solution.

[0082] Step 2: prepared solution 3.5 gm. of sodium benzoate, 3.5 gm of E.D.T.A., 3.5 gm. of sodium methyl parabene, 1.75 gm. of sodium propyl parabene with stirring in about 40 ml. of demineralised water. Add the prepared solution to the sorbitol solution.

[0083] Step 3: Mix 270 gm of glycerine and 52.5 gm of sodium C.M.C. and mix well to form a homogeneous gel. And, then add half the quantity of it to the previously prepared solution of sorbitol, sodium benzoate, E.D.T.A., sodium methyl parabene and sodium propyl parabene.

[0084] Step 4: Take the 0.875 gm. of active ingredient Minoxidil and mix well to make homogeneous dispersion further add 1050 gm. of calcium carbonate and mix well with continuous stirring and add 35 gm. of oleic acid and 26.25 gm of tween 80 and 26.25 gm of lauric acid mix well.

[0085] Step 5: Add previously prepared mixture of 24 gm. of menthol and 14 gm of camphor and mix well. Add 5.25 gm of clove oil and 10.5 gm of spearmint flavour and mix well with stirring.

[0086] Step 6: Add previously prepared solution of 1.75 gm of sucralose in 70 ml of demineralised water and mix well and add the remaining quantity of glycerine- sodium C.M.C. dispersion and mix well.

[0087] Step 7: Add 94.5 gm of citric acid and 3.5 gm of sodium meta-bisulphate solution prepared in 100 ml. of demineralised water to above prepared paste and mix well and add gently previously prepared solution of 70 gm of sodium lauryl sulphate (S.L.S.) in 210 ml of hot demineralised water, and mix slowly in a way so that the bubble formation is avoided.

[0088] Step 8: Add sufficient quantity of demineralised water to make the entire bulk 3.5 kg of total weight, and stir gently for 1 hour.

[0089] Example 4: PREPARATION OF TOOTHPASTE

[0090] Manufacturing process for 3.5 kg batch size of hair growth toothpaste

[0091] Weighing the raw materials according to the batch size as follows:

[0092] Step 1: Dissolve 1400 gm. of sorbitol in demineralised water sufficient to make 70 % w / w solution. (If ready solution is available it can be used directly).

[0093] Step 2: prepared solution 3.5 gm. of sodium benzoate, 3.5 gm of E.D.T.A., 3.5 gm. of sodium methyl parabene, 1.75 gm. of sodium propyl parabene with stirring in about 40 ml. of demineralised water. Add the prepared solution to the sorbitol solution.

[0094] Step 3: Mix 270 gm of glycerine and 52.5 gm of sodium C.M.C. and mix well to form a homogeneous gel. And, then add half the quantity of it to the previously prepared solution of sorbitol, sodium benzoate, E.D.T.A., sodium methyl parabene and sodium propyl parabene.

[0095] Step 4: Take the 16.62 gm of active ingredient Minoxidil and mix well to make homogeneous dispersion further add 1050 gm. Of calcium carbonate and mix well with continuous stirring and add 1.75 gm. of acylcamitine and mix well.

[0096] Step 5: Add previously prepared mixture of 21 gm. of menthol and 14 gm of camphor and mix well. Add 5.25 gm of clove oil and 10.5 gm of spearmint flavour and mix well with stirring. Step 6: Add previously prepared solution of sucralose in 70 ml of demineralised water and mix well and add the remaining quantity of glycerine- sodium C.M.C. dispersion and mix well. Step 7: Add 1.75 gm of sodium thiosulphate solution prepared in 100 ml. of demineralised water to above prepared paste and mix well and add gently previously prepared solution of 70 gm of sodium lauryl sulphate (S.L.S.) in 210 ml of hot demineralised water, and mix slowly in a way so that the bubble formation is avoided. Step 8: Add sufficient quantity of demineralised water to make the entire bulk 3.5 kg of total weight, and stir gently for 1 hour.

[0097] Example 5: PREPARATION OF TOOTHPASTE Manufacturing process for 3.5 kg batch size of hair growth toothpaste Weighing the raw materials according to the batch size as follows:

[0098] Step 1: Dissolve 1400 gm. of sorbitol in demineralised water sufficient to make 70 % w / w solution. (If ready solution is available it can be used directly).

[0099] Step 2: prepared solution 3.5 gm. of sodium benzoate, 3.5 gm of E.D.T.A., 3.5 gm. of sodium methyl parabene, 1.75 gm. of sodium propyl parabene with stirring in about 40 ml. of demineralised water. Add the prepared solution to the sorbitol solution.

[0100] Step 3: Mix 270 gm of glycerine and 52.5 gm of sodium C.M.C. and mix well to form a homogeneous gel. And, then add half the quantity of it to the previously prepared solution of sorbitol, sodium benzoate, E.D.T.A., sodium methyl parabene and sodium propyl parabene.

[0101] Step 4: Take the 15.8 gm. of active ingredient Minoxidil and mix well to make homogeneous dispersion further add 1050 gm. Of calcium carbonate and mix well with continuous stirring and add 17.5 gm. of sodium salicylate and 3.5 gm of linoleic acid and mix well.

[0102] Step 5: Add previously prepared mixture of 21 gm. of menthol and 14 gm of camphor and mix well. Add 5.25 gm of clove oil and 10.5 gm of spearmint flavour and mix well with stirring.

[0103] Step 6: Add previously prepared solution of sucralose in 70 ml of demineralised water and mix well and add the remaining quantity of glycerine- sodium C.M.C. dispersion and mix well.

[0104] Step 7: Add 1.75 gm og sodium nitrite and 52.5 gm of citric acid solution prepared in 100 ml. of demineralised water to above prepared paste and mix well and add gently previously prepared solution of 70 gm of sodium lauryl sulphate (S.L.S.) in 210 ml of hot demineralised water, and mix slowly in a way so that the bubble formation is avoided.

[0105] Step 8: Add sufficient quantity of demineralised water to make the entire bulk 3.5 kg of total weight, and stir gently for 1 hour.

[0106] Example 6: PREPARATION OF TOOTHPASTE

[0107] Manufacturing process for 3.5 kg batch size of hair growth toothpaste

[0108] Weighing the raw materials according to the batch size as follows: Step 1: Dissolve 1400 gm. of sorbitol in demineralised water sufficient to make 70 % w / w solution.

[0109] Step 2: prepared solution 3.5 gm. of sodium benzoate, 3.5 gm of E.D.T.A., 3.5 gm. of sodium methyl parabene, 1.75 gm. of sodium propyl parabene with stirring in about 40 ml. of demineralised water. Add the prepared solution to the sorbitol solution.

[0110] Step 3: Mix 270 gm of glycerine and 52.5 gm of sodium C.M.C. and mix well to form a homogeneous gel. And, then add half the quantity of it to the previously prepared solution of sorbitol, sodium benzoate, E.D.T.A., sodium methyl parabene and sodium propyl parabene. Step 4: Take the 15.8 gm. of active ingredient Minoxidil and mix well to make homogeneous dispersion further add 1050 gm. Of calcium carbonate and mix well with continuous stirring and add 1.75 gm. of polyethylene glycol 400 and 1.75 gm of poly sorbate 80 and mix well. Step 5: Add previously prepared mixture of 21 gm. of menthol and 14 gm of camphor and mix well. Add 5.25 gm of clove oil and 10.5 gm of spearmint flavour and mix well with stirring.

[0111] Step 6: Add previously prepared solution of sucralose in 70 ml of demineralised water and mix well and add the remaining quantity of glycerine- sodium C.M.C. dispersion and mix well.

[0112] Step 7: Add 1.75 gm og sodium nitrite solution prepared in 100 ml. of demineralised water to above prepared paste and mix well and add gently previously prepared solution of 70 gm of sodium lauryl sulphate (S.L.S.) in 210 ml of hot demineralised water, and mix slowly in a way so that the bubble formation is avoided.

[0113] Step 8: Add sufficient quantity of demineralised water to make the entire bulk 3.5 kg of total weight, and stir gently for 1 hour. Example 7: PREPARATION OF TOOTHPASTE Step 1: Dissolve 1400 gm. of sorbitol in demineralised water sufficient to make 70 % w / w solution.

[0114] Step 2: prepared solution 3.5 gm. of sodium benzoate, 3.5 gm of E.D.T.A., 3.5 gm. of sodium methyl parabene, 1.75 gm. of sodium propyl parabene with stirring in about 40 ml. of demineralised water. Add the prepared solution to the sorbitol solution.

[0115] Step 3: Mix 270 gm of glycerine and 52.5 gm of sodium C.M.C. and mix well to form a homogeneous gel. And, then add half the quantity of it to the previously prepared solution of sorbitol, sodium benzoate, E.D.T.A., sodium methyl parabene and sodium propyl parabene.

[0116] Step 4: Take the 15.8 gm. of active ingredient Minoxidil and mix well to make homogeneous dispersion further add 1050 gm. Of calcium carbonate and mix well with continuous stirring and add 2.62 gm of propanediol and 1.75 gm of sodium glycocholate and mix well.

[0117] Step 5: Add previously prepared mixture of 21 gm. of menthol and 14 gm of camphor and mix well. Add 5.25 gm of clove oil and 10.5 gm of spearmint flavour and mix well with stirring.

[0118] Step 6: Add previously prepared solution of sucralose in 70 ml of demineralised water and mix well and add the remaining quantity of glycerine- sodium C.M.C. dispersion and mix well.

[0119] Step 7: Add 35 gm of citric acid and 1.75 gm of sodium thio sulphate solution prepared in 100 ml. of demineralised water to above prepared paste and mix well and add gently previously prepared solution of sodium lauryl sulphate (S.L.S.) in 210 ml of hot demineralised water, and mix slowly in a way so that the bubble formation is avoided.

[0120] Step 8: Add sufficient quantity of demineralised water to make the entire bulk 3.5 kg of total weight, and stir gently for 1 hour.

[0121] While the present invention has been described in terms of its specific embodiments, certain modification and equivalents will be apparent to those skilled in the art and are intended to be included with in the scope of the present invention. The basic principle and concept of the hair growth toothpaste is active ingredients like minoxidil are absorbed through oral mucosal membrane in oral cavity whereas most absorption takes place sublingually. Also, buccal cavity absorption as well as palatal absorption plays an important role.

[0122] All formulation can be formulated in gel form also using appropriate excipients.

[0123] BENEFITS OF ABSORPTION THROUGH ORAL BUCCAL MUCOSA:

[0124] 1. Absorption of drugs through oral buccal mucosa improves bioavailability of drugs.

[0125] 2. Another advantage of oral buccal mucosal absorption of active ingredients is it by-passes the first-pass effects in the liver where the undesired first-pass effects may occur, decreasing the efficacy of active ingredients if taken through gastrointestinal tract.

[0126] Advantages of toothpaste over topical minoxidil formulation:

[0127] 1. Convenience: It is easier to use it as it does not required extra time or extra efforts for its use. During morning tooth brushing of the mouth in a routine way, toothpaste under invention can be conveniently used by a patient. Hence, strict patient compliance is easy.

[0128] 2. Cosmesis: There is no residue or colour change on scalp as it happens with topical minoxidil formulation.

[0129] Sinclair scale is a new 5 - point photographic grading system that has been embraced in clinical dermatology practices to evaluate and monitor the progress of FPHL (female pattern hair loss).

[0130] Sinclair scale for female pattern hair loss: i. Stage 1 is normal. ii. Stage 2 shows the widening of the central part. iii. Stage 3 shows the widening of the central part and loss of volume lateral to the part line. iv. Stage 4 shows the development of a bald spot anteriorly. v. Stage 5 shows the advanced hair loss.

[0131] Table 2 illustrated that active ingredient Minoxidil is calculated considering serving of the toothpaste was administered daily over a 24-week period to evaluate its systemic efficacy in promoting hair regrowth. Hair density was assessed at two scalp regions frontal and vertex at baseline (week 0) and after 24 weeks of treatment. These findings suggest that the transmucosal delivery of minoxidil via the toothpaste base successfully enhanced systemic bioavailability, leading to a measurable increase in terminal hair density. Importantly, no significant alterations in blood pressure or systemic side effects were observed, underscoring the safety and therapeutic potential of this novel formulation for managing androgenic alopecia and other hair loss disorders.

[0132] Table 2: The frontal and vertex hair density

[0133] An increase in terminal hair reflects a significant change in the hair growth pattern where finer, shorter vellus hairs are replaced by thicker, longer, and more pigmented terminal hairs. This transition is often influenced by particularly elevated levels of androgens, which can stimulate hair follicles to shift from producing vellus hair to terminal hair. This process is commonly observed in various conditions such as androgenic alopecia, where an increase in terminal hair can indicate the progression of hair regrowth or the effectiveness of certain treatments.

[0134] Table 5: Improvement in the frontal and vertex hair count using sublingual minoxidil

[0135] The administration of sublingual minoxidil at a dose of 0.025% resulted in a mean increase in terminal hair count / cm of 6 for the frontal scalp and 12 for the vertex scalp. The 0.45% dose produced mean increases of 20 for the frontal scalp and 35 for the vertex scalp. At the 0.475% dose, the mean increase in terminal hair count / cm was 45 for the frontal scalp and 90 for the vertex scalp.

[0136] MEAN PEAK PLASMA CONCENTRATION:

[0137] As the invention result used on 4 healthy adult participants using 0.45% minoxidil one time daily for 7 days, the mean peak plasma concentrations were observed as shown in below table 6. Minoxidil used 1 gm per serving of the toothpaste under the invention with 0.45% w / w. Hence, each participant was given 4.5 mg of sublingual minoxidil per serving once daily for 7 days. The dose was below the LDOM [Low dose oral minoxidil] dose which is less than 5 mg of the daily dose. All participants were instructed to brush their teeth in a normal usual way. The result observed is given in below table:

[0138] Table-6:

[0139] Plasma concentration threshold for the development of any hemodynamic effect is (20 ng / ml), and our invention results are below that level indicating that the toothpaste under invention is safe. EFFECT ON BLOOD PRESSURE [B.P.]:

[0140] As per above results in table-6, no significant alterations in the blood pressure level were observed as per the results indicating that the toothpaste under invention is safe.

[0141] As sublingual dosing bypasses hepatic first pass metabolism sublingual minoxidil would be anticipated to increase follicular minoxidil sulphate bioavailability and consequently hair growth. As hepatic sulfation of minoxidil enhances the hemodynamic effect, sublingual minoxidil would also be anticipated to reduce hemodynamic side effect and consequently improve safety.

[0142] Conclusion:

[0143] Minoxidil has shown therapeutic potential beyond its traditional use in treating hypertension and androgenetic alopecia. Its integration into a transmucosal drug delivery platform specifically a medicated toothpaste presents an innovative approach for the systemic management of body disorders. The oral mucosa provides an advantageous route for systemic drug delivery due to its rich vascularization and the ability to bypass hepatic first-pass metabolism. To enhance the permeability of minoxidil across the mucosal barrier the formulation used absorption enhancers. These compounds work by transiently loosening tight junctions or modulating membrane fluidity, thereby facilitating greater transmucosal transport of the active compound. Additionally, humectants are employed to retain mucosal hydration, improve the solubility of minoxidil, and prolong its contact time with the oral mucosa.

[0144] The formulation also integrates functional excipients that support both therapeutic delivery and oral hygiene. Abrasives in mechanical plaque removal while ensuring uniform dispersion of the drug throughout the oral cavity. Surfactants are included to improve foaming and enhance the wetting of mucosal surfaces, further promoting drug bioavailability. And other formulation excipients incorporated to optimize viscosity and mucoadhesion, enabling sustained drug release and improved mucosal residence time. This approach offers a non-invasive, patient-compliant alternative to traditional systemic drug delivery, enabling daily administration with minimal risk. Importantly, due to controlled, low-dose transmucosal absorption, the formulation significantly reduces systemic exposure and has shown to cause no clinically significant alterations in blood pressure, thereby maintaining cardiovascular safety while delivering therapeutic benefit for chronic body disorders.

Claims

Claims:I / We claim,1. A toothpaste formulation for body disorders comprises: a. minoxidil is in range of 0.025% to 0.475% w / w; b. one or more oral mucosal absorption enhancers is in range of 0.05% to 3.00% w / w; c. a humectants is in range of 7.50% to 40.00% w / w; d. an abrasives is in range of 20.00% to 40.0% w / w; e. a surfactant is in range of 1.00 to 5.00% w / w; and f. formulation excipients.

2. The toothpaste formulation as claimed in claim 1, wherein one or more the oral mucosal absorption enhancers are selected from the groups of bile salts and derivative, ionic surfactants, non-ionic surfactants, fatty acid, chelating agent, sulfoxides, polyols, monohydric alcohols, monohydric alcohols, choline esters, natural origin, cyclodextrins and positively charged polymers.

3. The toothpaste formulation as claimed in claim 1, wherein the oral mucosal absorption enhancers are selected from sodium glycocholate, sodium lauryl sulfate, tween 80, polysorbate, oleic acid, acylcarnitine, EDTA, citric acid, dimethyl sulfoxide [DMSO], glycerol, propanediol, ethanol, palmitoyl choline, decano yl choline, quercetine, genistein, a- cyclodextrin, P- cyclodextrin, y-cyclodextrin and chitosan.

4. The toothpaste formulation as claimed in claim 1, wherein formulation excipients are selected from preservative, sweetener, thickening agent, antioxidants, flavoring agent and vehicle.

5. The toothpaste formulation as claimed in claim 1 & 4, wherein flavoring agent is selected from caraway, clove oil, lemon, fennel, spearmint, rose, peppermint, ginger, raspberry, maltol, sarsaparilla cherry, glycerin, cocoa, licorice, vanillin, ethyl vanillin, menthol and camphor.

6. The toothpaste formulation as claimed in claim 1 & 4, wherein one or more preservatives are selected from benzalkonium chloride, benzoic acid, benzyl alcohol, parabens, Sodium propylparaben, Sodium methylparaben, chlorobutanol, phenol, sodium benzoate and EDTA.

7. The toothpaste formulation as claimed in claim 1, wherein one or more humectants are selected from sorbitol, glycerin, hyaluronic acid, propylene glycol, aloe vera, honey, alpha hydroxycarboxylic acid, urea, panthenol, peptids and amino acids.

8. The toothpaste formulation as claimed in claim 1 & 4, wherein one or more sweetener is selected from sodium saccharin, sorbitol, Xylitol, sucralose and glycerol.

9. The toothpaste formulation as claimed in claim 1, wherein one or more abrasives are selected from calcium carbonate, sodium metaphosphate, zirconium silicate and calcium pyrophosphate, ceramic, ceramic iron oxide, dry ice, silicon carbide, boron carbide, iron oxide and diamond dust.

10. The toothpaste formulation as claimed in claim 1 & 4, wherein one or more thickening agent is selected from sodium carboxymethyl cellulose, hydroxypropyl methylcellulose and natural gums.

11. The toothpaste formulation as claimed in claim 1 & 4, wherein one or more antioxidants are selected from sodium bisulfite, sodium metabisulfite, sodium thiosulfate, citric acid, sodium nitrite or combination thereof.

12. The toothpaste formulation as claimed in claim 1, wherein one or more surfactant is selected from sodium lauryl sulphate, cocamidopropyl betaine and sodium methyl cocoyl taurate (adinol).

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