Smokeless green chewable formulation and method of preparation thereof

Abstract

The present disclosure relates to smokeless green chewable formulation comprising: 80 to 98 % w / w of a base product comprising at least one herb; 0.2 to 10 % w / w of nicotine; and 1 to 10 % w / w of a pH regulator. The present disclosure also relates to a method of preparation of a smokeless green chewable formulation comprising: a) processing by collecting, washing, cleaning and drying of a plant foliage material from at least one herb; b) cutting the plant foliage material of step a) followed by drying to obtain a dried foliar plant material small pieces; c) cutting the dried foliar plant material small pieces of step b) to obtain a course or flakes foliar powder; d) processing by sterilization the foliar powder of step c) to obtained a sterilized foliar powder; e) formulating the sterilized foliar powder to obtain a base product; and f) processing by fortification of 80 to 98 % w / w of the base product by 0.2 to 10 % of nicotine suspension in glycerol, and 1 to 10% w / w of a pH regulator to obtain a smokeless green chewable formulation, wherein the nicotine is induced in the base product. The formulations of the present disclosure are free from tobacco, efficient and sustained release of nicotine along with antioxidant activity and are safe, ecofriendly and have no toxicity and free of side effects.

Description

SMOKELESS GREEN CHEWABLE FORMULATION AND METHOD OF PREPARATION THEREOFFIELD OF INVENTION

[0001] The present disclosure relates to a chewable smokeless green product without any use of tobacco leaves for nicotine delivery useful for smoking cessation and carving as nicotine replacement therapy (NRT). More particularly, the present disclosure relates to a smokeless green chewable formulation. The present disclosure also relates to a method of preparation of a smokeless green chewable formulation and its application related to smoking cessation syndromes.BACKGROUND OF THE INVENTION

[0002] Background description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.

[0003] Smoking is a well-established health hazards that deliver nicotine with higher, danger to heart, lungs and causes several health related problems to body than that of chewable products. Therefore, Nicotine Replacement Therapy (NRT) for tobacco cessation to the patient with a safer and more therapeutically manageable form that directly alleviates the signs and symptoms of withdrawal and craving. Nicotine chewing gum is a very common and other available nicotine delivery systems are transdermal patches, nasal nicotine solution, vapor inhalers, spray, nicotine lozenge and sub-lingual tablets (smokeless tobacco) are existing for NRT. Smokeless tobacco products for oral use are made from tobacco leaves, such as lamina and stem of the tobacco leaf. The disadvantages of such chewable products may make them unappealing to users as an alternative to smoking.

[0004] The oral use of smokeless tobacco (SLT), chewing the tobacco-specific nitrosamines (TSNAs) are most potent among 28 known carcinogens in SLT (National Cancer Institute, 1992). The mixture of SLT is identified to enhance wrinkling in oral mucosa responsible to create oral injury, inflammation and oral tissue damage.

[0005] Chewers have compromised antioxidant status: The antioxidant defence status in SLT-user by measuring thiobarbituric acid reactive substance (TBARS) showed higher level of malonaldehyde (MDA an end product of lipid peroxidation) formation and lower value of reduced glutathione (GSH) as compared to non-user group. In SLT chewers the ingredientsor metabolic derivatives perturb the cellular metabolism leading to alteration of shape, morphology and cellular DNA damage. Nicotine and TSNA induced toxicity and production of reactive oxygen species (ROS) which in turn, cause the generation of lipid peroxidation (LPO). It is directly proportional to oxidative stress, in which defence mechanism is weakened and higher LPO is also an indicator of membrane damage, oral cancer and malignant lymphoma.

[0006] Nicotine pouches and lozenges are increasingly available in the United States, and sales are growing. The market leaders and highest-spending brands, ZYN and Velo. Nicotine pouches are available in a variety of flavors (mango, black cherry, citrus, and dragon fruit) gum or lozenges approved by Food and Drug Administration (FDA) as nicotine replacement therapy.

[0007] Hukkanen, et al. [Pharmacol Rev., 2005, 57, 79-115] discloses that smoking has enormous negative health consequences worldwide, and the use of tobacco is still rising globally. Nicotine is not a direct cause of most tobacco-related diseases, but it is highly addictive. The addictiveness of nicotine is the cause of continuing use of tobacco products, which in turn results in exposure to the diverse array of carcinogens and other bioactive compounds in tobacco. Tobacco is the single greatest preventable cause of death due to cancer. The vast majority of smokers want to quit, but due to nicotine addiction only a few percent quit successfully. Nicotine medications are widely used as NRT to assist smoking cessation and more recently have been proposed for use concurrently with smoking as part of a risk reduction strategy.

[0008] Biswas et al. [Sci. Rep., 2015, 5, 18284] disclose that nicotine is absorbed from SLT in chewer at alkaline pH to facilitate its absorption through oral mucosa and about 69% is ionized and 31% unionized binding to plasma proteins is less than 5%. Chronic systemic exposure to nicotine may contribute to accelerated coronary and peripheral vascular disease, acute cardiac ischemic events, delayed wound healing, reproductive disturbances, peptic ulcer and esophageal reflux.

[0009] Benowitz et al. [Exp Pharmacol., 2009, 192, 29-60] disclose that chewing tobacco and snuff are buffered to alkaline pH to facilitate absorption of nicotine through oral mucosa. Concentrations of nicotine in the blood rise gradually with the use of SLT and plateau at 30 min with levels persisting and declining slowly over 2 h or more. The various formulations of NRT, such as nicotine gum, transdermal patch, nasal spray, inhaler, sublingual tablets and lozenges, are buffered to alkaline pH to facilitate theabsorption of nicotine through cell membranes. Absorption of nicotine from all NRTs is slower and the increase in nicotine blood levels more gradual than from smoking.

[0010] Murphy SE [J. Biol. Chem., 2021, 296, 100722] discloses that nicotine is the key addictive constituent of tobacco it is not a carcinogen, but it drives smoking and continued exposure to the many carcinogens present in tobacco. The investigation into nicotine biotransformation in humans is the formation of cotinine, which occurs in two steps. The first step is cytochrome P450 (P450, CYP) 2A6-catalyzed 50-oxidation to an iminium ion, and the second step is oxidation of the iminium ion to cotinine.

[0011] US 20200383372 discloses a nicotine pouch composition containing a free-base nicotine mixture and sugar alcohol, water content of at least 15% by weight mixed with ion exchange resin, water-soluble fiber, selected from the list of inulin, polydextrose including refined polydextrose, dextrin, maltodextrin, and mixtures, sugar alcohol selected from the group consisting of sorbitol, erythritol, xylitol, lactitol, maltitol, mannitol, hydrogenated starch hydrolyzates, isomalt, a pH-regulating, a humectant, water-insoluble composition.

[0012] US 15 / 255,163 discloses sting free pouches for a technology that makes snus and other nicotine pouch products more accessible to adult consumers by eliminating the stinging sensation associated with their use. Snus is considered less risky to health than smoking, and many tobacco users, particularly in Sweden, have used the product to reduce or eliminate their exposure to the harmful by products of combustion.

[0013] WO 2020 / 187812 discloses a packaging material and an oral pouched nicotine product. The invention relates to a packaging material for use in an oral pouched nicotine product and to an oral pouched nicotine product.

[0014] WO 2018 / 2333795A1 discloses a pouch comprising a matrix of nicotine and water soluble composition product oral pouched nicotine product. Particularly, this disclosure relates to chewable pouch products comprising nicotine in free base and salt form, together with methods of making and using the same. The chewable nicotine product, comprising nicotine base, nicotine salt, flavor, and binder in a water-permeable, waterinsoluble pouch, wherein nicotine and flavor are released when the pouch is chewed, and wherein the product provides good nicotine release, flavor, mouthfeel, and shelf-stability. The formulation comprising nicotine, an orally-acceptable nicotine salt, an orally-acceptable alcohol, flavor and binder in a water-permeable, water-insoluble pouch.

[0015] These methods of nicotine products face challenges in manufacturing, shelf stability, efficient nicotine delivery and consumer acceptance. Nicotine may be stabilized in a polymer or gum matrix or provided in salt form and pH-adjusting agents. High pH mayhave undesirable biter or soapy flavors, and / or poor mouth feel, while products where nicotine is polymer-stabilized may release nicotine relatively slowly and inefficiently.

[0016] The disadvantages of these chewable products may make them unpleasant to users as an alternative to smoking, as chewable products. There is a need for chewable nicotine delivery products, which release nicotine quickly and efficiently, have good flavor and mouth feel, and which are stable for long-term storage.

[0017] Thus, there is a need for chewable nicotine delivery products, with quick and efficient release of nicotine, good flavor and mouthfeel, stable and least possible detriment.OBJECTS OF THE INVENTION

[0018] The primary objective of the present disclosure is to provide a smokeless green chewable formulation.

[0019] Another objective of the present disclosure is to provide a method of preparation of a smokeless green chewable formulation.

[0020] Another objective of the present disclosure is to provide a herbal product composition and process for preparation of NRT for tobacco cessation with a safer and more therapeutically manageable form that directly alleviates the signs and symptoms of smoking withdrawal and craving.

[0021] Still another object of the present invention is to develop a herbal supplement that exerts potent effect for use as NRT for tobacco cessation and carving to the patient with a safer and more manageable form that alleviates the signs and symptoms of smoking withdrawal and craving.

[0022] Yet another object of the present invention is to provide a process for the preparation of a synergistic herbal antioxidant composition for NRT intended for tobacco cessation to the patient with a safer and manageable form to improve directly alleviates the signs and symptoms of smoking withdrawal and craving which acts as preventive to ameliorate the general health of smoker.SUMMARY

[0023] This summary is provided to introduce a selection of concepts in a simplified form that are further described below in Detailed Description section. This summary is not intended to identify key features or essential features of the claimed subject mater, nor is it intended to be used as an aid in determining the scope of the claimed subject mater.

[0024] The present disclosure relates to a chewable smokeless green product without any use of tobacco leaves for nicotine delivery useful for smoking cessation and carving as nicotine replacement therapy (NRT). More particularly, the present disclosure also relates to a smokeless green chewable formulation. The present disclosure also relates to a method of preparation of a smokeless green chewable formulation and its application related to smoking cessation syndromes.

[0025] Accordingly, in one aspect, the present disclosure relates to a smokeless green chewable formulation comprising: 80 to 98 % w / w of a base product comprising at least one herb; 0.2 to 10 % w / w of nicotine; and 1 to 10 % w / w of a pH regulator, wherein the nicotine is induced in the base product.

[0026] Another aspect of the present disclosure relates to a method of preparation of a smokeless green chewable formulation comprising: a) processing by collecting, washing, cleaning and drying of a plant foliage material from at least one herb; b) cutting the plant foliage material of step a) followed by drying to obtain a dried foliar plant material small pieces; c) cutting the dried foliar plant material small pieces of step b) to obtain a course or flakes foliar powder; d) processing by sterilization the foliar powder of step c) to obtained a sterilized foliar powder; e) formulating the sterilized foliar powder to obtain a base product; and f) processing by fortification of 80 to 98 % w / w of the base product by 0.2 to 10 % of nicotine suspension in glycerol, and 1 to 10% w / w of a pH regulator to obtain a smokeless green chewable formulation, wherein the nicotine is induced in the base product.

[0027] Various objects, features, aspects and advantages of the present disclosure will become more apparent from the following detailed description of preferred embodiments, along with the accompanying drawing figures in which like numerals represent like features.DETAILED DESCRIPTION OF THE INVENTION

[0033] The following is a detailed description of embodiments of the disclosure. The embodiments are in such detail as to clearly communicate the disclosure. However, the amount of detail offered is not intended to limit the anticipated variations of embodiments; on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the present disclosure as defined by the appended claims.

[0034] All publications herein are incorporated by reference to the same extent as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. Where a definition or use of a term in an incorporatedreference is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies and the definition of that term in the reference does not apply.

[0035] Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.

[0036] In some embodiments, numbers have been used for quantifying weights, percentages, ratios, and so forth, to describe and claim certain embodiments of the invention and are to be understood as being modified in some instances by the term “about.” Accordingly, in some embodiments, the numerical parameters set forth in the written description and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by a particular embodiment. In some embodiments, the numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as practicable.

[0037] The numerical values presented in some embodiments of the invention may contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements.

[0038] Unless the context requires otherwise, throughout the specification which follows, the word “comprise” and variations thereof, such as “comprises” and “comprising” are to be construed in an open, inclusive sense that is as “including, but not limited to.”

[0039] As used in the description herein and throughout the claims that follow, the meaning of “a,” “an,” and “the” includes plural reference unless the context clearly dictates otherwise. Also, as used in the description herein, the meaning of “in” includes “in” and “on” unless the context clearly dictates otherwise.

[0040] The recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as ifit were individually recited herein. Furthermore, the ranges defined throughout the specification include the end values as well, i.e., a range of 1 to 10 implies that both 1 and 10 are included in the range. For the avoidance of doubt, the applicant shall be entitled to any equivalents according to applicable law.

[0041] All methods described herein can be performed in a suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples or exemplary language (e.g., “such as”) provided with respect to certain embodiments herein is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention.

[0042] Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member can be referred to and claimed individually or in any combination with other members of the group or other elements found herein. One or more members of a group can be included in, or deleted from, a group for reasons of convenience and / or patentability. When any such inclusion or deletion occurs, the specification is herein deemed to contain the group as modified.

[0043] The description that follows, and the embodiments described therein, is provided by way of illustration of an example, or examples, of particular embodiments of the principles and aspects of the present disclosure. These examples are provided for the purposes of explanation, and not of limitation, of those principles and of the disclosure.

[0044] It should also be appreciated that the present disclosure can be implemented in numerous ways, including as a system, a method or a device. In this specification, these implementations, or any other form that the invention may take, may be referred to as processes. In general, the order of the steps of the disclosed processes may be altered within the scope of the invention.

[0045] The headings and abstract of the invention provided herein are for convenience only and do not interpret the scope or meaning of the embodiments.

[0046] The following discussion provides many example embodiments of the inventive subject matter. Although each embodiment represents a single combination of inventive elements, the inventive subject matter is considered to include all possible combinations of the disclosed elements. Thus, if one embodiment comprises elements A, B, and C, and a second embodiment comprises elements B and D, then the inventive subject matter is alsoconsidered to include other remaining combinations of A, B, C, or D, even if not explicitly disclosed.

[0047] The term “or”, as used herein, is generally employed in its sense including “and / or” unless the content clearly dictates otherwise.

[0048] Various terms are used herein to the extent a term used is not defined below, it should be given the broadest definition persons in the pertinent art have given that term as reflected in printed publications and issued patents at the time of filing.

[0049] Smoking is a health hazards that deliver nicotine and effect lungs and causes several health related problems. Safer Nicotine Replacement Therapy (NRT) for tobacco cessation that directly alleviates the signs and symptoms of withdrawal and craving. The available nicotine delivery systems are nicotine transdermal patches, inhalers, nasal spray, nicotine lozenge and sub-lingual tablets. The disadvantages of high pH in such chewable products may make them unappealing to users as an alternative to smoking. Therefore, there is a need for chewable nicotine delivery products, with quick-efficient and sustained release of nicotine, good flavor and mouthfeel, stable and least possible detriment.

[0050] The present disclosure relates to a chewable smokeless green product without any use of tobacco leaves for nicotine delivery useful for smoking cessation and carving as NRT. More particularly, the present disclosure relates to a smokeless green chewable formulation. The present disclosure also relates to a method of preparation of a smokeless green chewable formulation and its application related to smoking cessation syndromes.

[0051] An embodiment of the present disclosure is to provide a smokeless green chewable formulation comprising: 80 to 98 % w / w of a base product comprising at least one herb; 0.2 to 10 % w / w of nicotine; and 1 to 10% w / w of a pH regulator, wherein the nicotine is induced in the base product.

[0052] In an embodiment, the herb is selected from a group consisting of Aegle marmelos (Bael), Syzygium cumini (Jamun), Amaranthus cruentus (Chaulai), Trigonella foenum- graecum (Methi), Brassica campestris (Mustard), Centella asiatica (Manduk Pami), Cinnamomum tamala (Tejpatra), Citrus Union (Lemon), Eucalyptus globulus (Sugandhapatra), Foeniculum vulgare (Saunf), Mentha arvensis (Peppermint), Moringa oelifera (drumstick), Murraya koenigii (Meethi Neem), Psidium guajava (Guava), Mangifera indica (Mango), Cassia angustifolia (Senna) and combination thereof.

[0053] In an embodiment, the pH regulator is selected from a group consisting of sodium bicarbonate, potassium bicarbonate, calcium carbonate, magnesium carbonate and combination thereof.

[0054] In an embodiment, the base product is present in an amount ranging between 81 to98% w / w or 82 to 98% w / w or 83 to 98% w / w or 84 to 98% w / w or 85 to 98% w / w or 86 to98% w / w or 87 to 98% w / w or 88 to 98% w / w or 89 to 98% w / w or 90 to 98% w / w or 91 to98% w / w or 92 to 98% w / w or 93 to 98% w / w or 94 to 98% w / w or 95 to 98% w / w or 96 to98% w / w or 97 to 98% w / w.

[0055] In an embodiment, the nicotine is present in an amount ranging between 0.2 to 9% w / w or 0.2 to 8% w / w or 0.2 to 7% w / w or 0.2 to 6% w / w or 0.2 to 5% w / w or 0.2 to 4% w / w or 0.2 to 3% w / w or 0.2 to 2% w / w or 0.2 to 1% w / w or 0.2 to 0.5% w / w or 0.2 to 0.4% w / w or 0.2 to 0.3% w / w.

[0056] In an embodiment, the pH regulator is added in an amount ranging between 1 to 9% w / w or 1 to 8% w / w or 1 to 7% w / w or 1 to 6% w / w or 1 to 5% w / w or 1 to 4% w / w or 1 to 3% w / w or 1 to 2% w / w.

[0057] In an embodiment, the formulation has a dosage form selected from a group consisting of flakes, course powder, or granules.

[0058] In an embodiment, the formulation includes active antioxidant constituents present naturally in base material.

[0059] In an embodiment, the formulation has optionally 0.1 to 1 % w / w of a natural flavor. The natural flavor is selected from a group consisting of banana, pineapple, orange, strawberry, cinnamon, peppermint, vanilla, raspberry, cherry, apricot and combination thereof.

[0060] In an embodiment, the formulation is free of tobacco leaves, tobacco stem and fibers derived from tobacco.

[0061] In an embodiment, the formulation is as and when used as nicotine replacement therapy (NRT) in tobacco cessation to alleviate the signs and symptoms of withdrawal and craving.

[0062] Another embodiment of the present disclosure is to provide a method of preparation of a smokeless green chewable formulation comprising: a) processing by collecting, washing, cleaning and drying of a plant foliage material from at least one herb; b) cutting the plant foliage material of step a) followed by drying to obtain a dried foliar plant material small pieces; c) cutting the dried foliar plant material small pieces of step b) to obtain a course or flakes foliar powder; d) processing by sterilization the foliar powder of step c) to obtained a sterilized foliar powder; e) formulating the sterilized foliar powder to obtain a base product; and f) processing by fortification of 80 to 98 % w / w of the base product by 0.2 to 10 % of nicotine suspension in glycerol, and 1 to 10% w / w of a pHregulator to obtain a smokeless green chewable formulation, wherein the nicotine is induced in the base product.

[0063] In an embodiment, the washing in step a) is carried out with a solvent selected from a group consisting of water, ethanol and combination thereof. Preferably, the solvent is water.

[0064] In an embodiment, the drying is step a) is carried out at a temperature in the range of 25 to 50 °C for a period in the range of 2 to 8 hrs. Preferably, the temperature is in the range of 25 to 45 °C for a period in the range of 3 to 6 hrs.

[0065] In an embodiment, the plant foliage material of step b) is cut in the range of 1 to 20 mm, preferably in the range of 1 to 10 mm, more preferably in the range of 1 to 4 mm.

[0066] In an embodiment, the drying in step b) is carried out at a temperature in the range of 30 to 50 °C for a period in the range of 2 to 8 hrs Preferably, temperature in the range of 35 to 50 °C for a period in the range of 3 to 6 hrs.

[0067] In an embodiment, the course or flakes foliar powder in step c) has a size in the range of 0.2 to 5 mm, preferably in the range of 0.2 to 3 mm, more preferably in the range of 0.2 to 2 mm.

[0068] In an embodiment, the sterilization in step d) is carried out by steam, UV or gamma-ray radiation. Preferably, the sterilization is carried out by steam sterilization.

[0069] In an embodiment, the sterilization by steam is carried out at a temperature in the range of 120 to 180 °C for a period in the range of 10 second to 3 min at a pressure in the range of 2 to 10 bar. Preferably, the temperature is in the range of 120 to 150°C for a period in the range of 30 second to 3 min at a pressure in the range of 2 to 5 bar.

[0070] In an embodiment, the base product, nicotine, the natural flavor; the pH regulator in step f) are mixed for a period in the range of 10 min to 60 min, preferably 20 to 60 min, at a speed in the range of 1500 to 3500 rpm, preferably at 1500 to 2500 rpm, followed by drying at a temperature in the range of 25 to 40 °C, preferably 25 to 35 °C, for a period in the range of 30 min to 2 hr, preferably 30 min to 1.5 hr.

[0071] In an embodiment of the present disclosure provides the nicotine product composition is free of tobacco, tobacco leaves, stem and fibers not derived from tobacco and relate to the smokeless herbal composition of nicotine (NRT) for tobacco cessation which is more safer to alleviates the signs and symptoms of withdrawal and craving. The product comprising scientifically processed and validated foliage fibers of Aegle marmelos (Bael, family Rutaceae), Syzygium cumini (Jamun, family Myrtaceae), Amaranthus cruentus (Chaulai, family Amaranthaceae). The product comprising scientifically validated andprocessed foliage fibers obtained by process ranging from 80 to 98 % fortified with 0.2 to 10% of nicotine and 1 to 10% of a pH regulator. In some embodiment, the product comprising scientifically processed and validated foliage fibers of Aegle marmelos (Bael, family Rutaceae), Syzygium cumini (Jamun, family Myrtaceae), Amaranthus cruentus (Chaulai, family Amaranthaceae) and Trigonella foenum-graecum (Methi, Fabaceae). The product comprising scientifically validated and processed foliage fibers obtained by process ranging from 80 to 98 % fortified with 0.2 to 10% of nicotine and 1 to 10% of a pH regulator. In another some embodiment, the product comprising scientifically processed and validated foliage fibers of Amaranthus cruentus (Chaulai, family Amaranthaceae), Trigonella foenum-graecum (Methi, Fabaceae) and Brassica campestris (Mustard, Brassicaceae). The product comprising scientifically validated and processed foliage fibers obtained by process ranging from 80 to 98 % fortified with 0.2 to 10% of nicotine and 1 to 10% of a pH regulator.

[0072] In a preferred embodiment of the present provides the nicotine product composition is free of tobacco, tobacco leaves, stem and fibers not derived from tobacco and relate to the smokeless herbal composition of nicotine (NRT) for tobacco cessation which is more safer to alleviates the signs and symptoms of withdrawal and craving. The product comprising scientifically processed and validated foliage fibers selected group of Aegle marmelos (Bael, family Rutaceae), Syzygium cumini (Jamun, family Myrtaceae), Amaranthus cruentus (Chaulai, family Amaranthaceae), Trigonella foenum-graecum (Methi, Fabaceae), Brassica campestris (Mustard, Cruciferae), Centella asiatica, (Manduk Pami, Asiatic pennywort or gotu kola, Apiaceae) Cinnamomum tamala (Tejpatra, Lauraceae), Citrus, genus family (Rutaceae), lemon (C. limori), lime (C. aurantiifolia), sweet orange (C. sinensis), citron (C. medica), Eucalyptus globulus (Sugandhapatra, Myrtaceae), Foeniculum vulgare (Saunf, Umbelliferae), Mentha arvensis (Peppermint, Labiatae), Moringa oelifera (drumstick tree, Moringaceae) Murraya koenigii (Meethi Neem, Rutaceae) Psidium guajava (Guava, Myrtaceae) Mangifera indica (Mango, Anacardiaceae), Cassia angustifolia (Senna, Fabaceae). The product comprising scientifically validated and processed selected from foliage fibers obtained by process ranging from 80 to 98 % fortified with 0.2 to 10% of nicotine and 1 to 10% of a pH regulator.

[0073] In another embodiment of the present invention provides the herbal composition wherein the said composition comprises scientifically processed and validated foliage fibers from Aegle marmelos (Bael) in the range of 5-10%, Syzygium cumini (Jamun) in the range of 2-10%, Amaranthus cruentus (Chaulai) in the range of 2-10%, Trigonella foenum-graecum (Methi) in the range of 2-10%, Brassica campestris (Mustard) in the range of 4- 10%, Centella asiatica, (Manduk Pami) in the range of 5-10%, Cinnamomum tamala (Tejpatra) in the range of 3-7%, Citrus limon (Lemon) in the range of 5-15%, Eucalyptus globulus (Sugandhapatra) in the range of 2-10%, Foeniculum vulgare (Saunf) in the range of 5 2-10%, Mentha arvensis (Peppermint) in the range of 5-15%, Moringa oelifera (drumstick) in the range of 2-15%, Murray a koenigii (Meethi Neem) in the range of 2-15%, Psidium guajava (Guava) in the range of 2-10%, Mangifera indica (Mango) in the range of 2-10%, and Cassia angustifolia (Senna) in the range of 2-5%.

[0074] In another embodiment of the present invention, the product comprising 0 scientifically processed and validated from selected foliage fibers as flakes base obtained by process ranging from 80 to 98 % fortified with 0.2 to 10% of nicotine and pH regulator ranging from 1 to 5.0 %.

[0075] In still another embodiment of the present disclosure provides the product which is derived from herbal sources fortified active constituents and are thus safe, ecofriendly and 5 have no toxicity and free of side effects.

[0076] In accordance with an embodiment, the authorized person to collect the biological material is Dr. Dhan Prakash, Scientific & Technical Consultant. His contact details is 402 Vivek Vihar, Sector-82, Noida-201304; Mob: 8860068363; e-mail: dprakash_in@yahoo.com; GSTIN 09ADUPP9734H1ZN. The ingredients of the 0 composition of the present disclosure were procured from the following source:

[0077] While the foregoing describes various embodiments of the disclosure, other and further embodiments of the disclosure may be devised without departing from the basic scope thereof. The invention is not limited to the described embodiments, versions or examples, which are included to enable a person having ordinary skill in the art to make and use the invention when combined with information and knowledge available to the person skilled in the art.EXAMPLES

[0078] The present invention is further explained in the form of following examples. However, it is to be understood that the following examples are merely illustrative and are not to be taken as limitations upon the scope of the invention.Example 1

[0079] All the plant parts as mentioned were collected from authentic plant foliage material from different natural sources in India, washing, cleaning and shade drying of each foliar plant material separately and cut into small pieces 5 cm, dried at the temperature of50° C and coarsely powdered to 10 mesh, the powdered foliage were mixed in the quantities as given in Table 1. The composition of coarsely powder was followed by sterilization of thefoliar small pieces flakes under steam, or any other suitable UV, gamma-ray radiation safe process.

[0080] Formulating the coarsely powders to arrive at the composition into base product for use as excipient and carrier of active ingredient as natural fiber, flavor and antioxidant. This base product was passed through very short period 1 minute of high pressure steam at a temperature 120°C that makes it possible to decontaminate without adverse effect on quality. Further, fortification of base product 96% by 1.5% nicotine suspension in glycerol and 1% sodium bicarbonate, 0.8% potassium bicarbonate, 0.5% calcium carbonate and 0.2% magnesium carbonate as pH regulator and mixed properly in a mixer blander for 30 minutes and kept at room temperature (about 15-30°C) for 1 hour. The end product thus obtained was ready to fill in pouches of desired quantities. The pouches were finally exposed through gamma irradiation at the dose of 10 kGy toxicologically and nutritionally confirmed maximum safe dose to eliminate microbial load of spices without causing any significant organoleptic or chemical alterations. This radiation does not cause any toxicological changes or activation of irradiated food products, therefore, toxicological tests for food treated by this method are not needed.

[0081] The end product is suitable to formulate into dosage forms selected from a group comprising flakes, course powder, or granules as most of the constituents derived from herbal sources and are thus safe, eco friendly and have no toxicity and free of side effects. The process for preparing the nicotine product composition is free of tobacco, tobacco fibers and fibers derived from tobacco and relate to the smokeless herbal composition of nicotine (NRT) for tobacco cessation to the patient which is safer to alleviate the signs and symptoms of withdrawal and craving. The combination of the present formulation is not a mere admixture of the ingredients used resulting in aggregation of their properties but a mixture having synergistically enhanced properties as shown in (Table 2).Example 2:

[0082] All the plant parts as mentioned were collected from authentic plant foliage material from different natural sources in India, washing, cleaning and shade drying of each foliar plant material separately and cut into small pieces 2 cm, dried at the temperature of 40° C and coarsely powdered flakes to 8 mesh, the powdered foliage were mixed in the quantities as given in Table 1. The composition of coarsely powder was followed by sterilization of the foliar small pieces under steam, or any other suitable UV, gamma-ray radiation safe process.

[0083] Formulating the coarsely powders to arrive at the composition into base product for use as excipient and carrier of active ingredient as natural fiber, flavor and antioxidant. This base product was passed through very short period 90 seconds of high pressure steam at a temperature 120°C that makes it possible to decontaminate without adverse effect on quality. Further, fortification of base product 96% by 0.2% nicotine suspension in glycerol and 1.8% potassium bicarbonate, 1.0% calcium carbonate and 1.0% magnesium carbonate as pH regulator and mixed properly in a mixer blander for 45 minutes and kept at room temperature (about 15-30 °C) for 1 hour. The end product thus obtained was ready to fill in pouches of desired quantities. The pouches were finally exposed through gamma irradiation at the dose of 5 kGy toxicologically and nutritionally confirmed safe dose to eliminate microbial load of spices without causing any significant chemical alterations and does not cause any toxicological changes or activation of irradiated products, therefore, toxicological tests for food treated by this method are not needed.

[0084] The end product is suitable to formulate into dosage forms selected from a group comprising flakes, course powder, or granules. As most of the constituents derived from herbal sources and are thus safe, eco friendly and have no toxicity and free of side effects. The process for preparing the nicotine product composition is free of tobacco, tobacco fibers and fibers derived from tobacco and relate to the smokeless herbal composition of nicotine (NRT) for tobacco cessation to the patient which is safer to alleviate the signs and symptoms of withdrawal and craving. The combination of the present formulation is not a mere admixture of the ingredients used resulting in aggregation of their properties but a mixture having synergistically enhanced properties as shown in Table 2.Example 3:

[0085] All the plant parts as mentioned were collected from authentic plant foliage material from different natural sources in India, washing, cleaning and shade drying of each foliar plant material separately and cut into small pieces 2 cm, dried at the temperature of 30° C and coarsely powdered flakes to 10 mesh, the powdered foliage were mixed in the quantities as given in Table 1. The composition of coarsely powder was followed by sterilization of the foliar small pieces under steam, or any other suitable UV-ray radiation safe process.

[0086] Formulating the coarsely powders to arrive at the composition into base product for use as excipient and carrier of active ingredient as natural fiber, flavor and antioxidant. This base product was passed through very short period 45 seconds of high pressure steam at a temperature 130°C to decontaminate without adverse effect on quality. Further,fortification of base product 94% by 2.0% nicotine suspension in glycerol and 1.0% sodium bicarbonate, 1.5% calcium carbonate and 1.5% magnesium carbonate as pH regulator and mixed properly in a mixer blander for 60 minutes and kept at room temperature (about 15- 30°C) for 1 hour. The end product thus obtained was ready to fill in pouches of desired quantities. The pouches were finally exposed through gamma-ray irradiation at the dose of 8 kGy toxicologically and nutritionally confirmed safe dose to eliminate microbial load of spices without causing any significant organoleptic or chemical alterations that radiation does not cause any toxicological changes or activation of irradiated food products, therefore, toxicological tests for food treated by this method are not needed.

[0087] The end product is suitable to formulate into dosage forms selected from a group comprising flakes, course powder, or granules as most of the constituents derived from herbal sources and are thus safe, eco friendly and have no toxicity and free of side effects. The process for preparing the nicotine product composition is free of tobacco, tobacco fibers and fibers derived from tobacco and relate to the smokeless herbal composition of nicotine (NRT) for tobacco cessation to the patient which is safer to alleviate the signs and symptoms of withdrawal and craving. The combination of the present formulation is not a mere admixture of the ingredients used resulting in aggregation of their properties but a mixture having synergistically enhanced properties as shown in (Table 2).Example 4:

[0088] All the plant parts as mentioned were collected from authentic plant foliage material from different natural sources in India, washing, cleaning and shade drying of each foliar plant material separately and cut into small pieces 3 cm, dried at the temperature of 30° C and coarsely powdered to 10 mesh, the powdered foliage were mixed in the quantities as given in Table 1. The composition of coarsely powder was followed by sterilization of the foliar small pieces under steam, or any other suitable UV, X-ray, gamma-ray radiation safe process.

[0089] Formulating the coarsely powders to arrive at the composition into base product for use as excipient and carrier of active ingredient as natural fiber, flavor and antioxidant. This base product was passed through very short period 60 seconds of high pressure steam at a temperature 120°C that makes it possible to decontaminate without adverse effect on quality. Further, fortification of base product 90% by 6.0% nicotine suspension in glycerol and 1.5% sodium bicarbonate, 1.0% calcium carbonate and 1.5% magnesium carbonate as pH regulator and mixed properly in a mixer blander for 45 minutes and kept at room temperature (about 15-30 °C) for 1.5 hour. The end product thus obtained is ready to fill inpouches of desired quantities. The pouches are finally exposed through X-ray irradiation at the dose of 5 kGy toxicologically and nutritionally confirmed safe dose to eliminate microbial load of spices without causing any significant organoleptic or chemical alterations that radiation does not cause any toxicological changes or activation of irradiated food products, therefore, toxicological tests for food treated by this method are not needed.

[0090] The end product is suitable to formulate into dosage forms selected from a group comprising course flakes, powder, or granules. As most of the constituents derived from herbal sources and are thus safe, ecofriendly and have no toxicity and free of side effects of tobacco. The process for preparing the nicotine product composition is free of tobacco, tobacco fibers and fibers derived from tobacco and relate to the smokeless herbal composition of nicotine (NRT) for tobacco cessation to the patient which is safer to alleviate the signs and symptoms of withdrawal and craving. The combination of the present formulation is not a mere admixture of the ingredients used resulting in aggregation of their properties but a mixture having synergistically enhanced properties as shown in (Table 2). Table 1: The % foliar composition used in different examples.Example 5:

[0091] Estimation of Total Phenolic Content (TPC), Antioxidant Activity, Free radical scavenging activity (FRSA) and Release of nicotine in saliva.

[0092] Total Phenolic Content (TPC): TPC in different extracts were measured as described by Ragazzi & Veronese (1973). The 10 mg extract was dissolved in 10 ml of 50% MeOH: H2O (1: 1), and in 1.0 ml, 1.0 ml of Folin's Reagent (IN) and 2.0 ml of Na2CO2(20%) were added subsequently mixed properly, left at room temperature for 30 min and added water to 25 ml absorbance was measured at Xmax725 nm on UV Spectrophotometer and TPC were expressed as gallic acid equivalent (GAE) mg / g on dry weight basis. The results of formulations 1 to 4 as given in Table 2.

[0093] Antioxidant Activity: Estimated as described by Emmons & Peterson (1999) by monitoring the coupled autoxidation of p-carotene and linoleic acid. 10 mg extract was dissolved in 10ml of 50% methanol / water, filtered through a 0.2 pm. 2mg p-carotene was dissolved in 20 ml chloroform and 3.0ml of this solution was added to 40mg of linoleic acid and 400 mg of Tween-40. The chloroform was removed under a stream of Nitrogen gas followed by the addition of 100ml water and the solution was mixed well. Aliquots (3ml) of the P-carotene and linoleic acid emulsion were mixed with 40pl of plant extracts in methanol to the equivalent of 2.0mg / ml and incubated at 50° C. Oxidation of this emulsified reaction mixture was measuring absorbance at AII|;|X470 nm Antioxidant activity was expressed as % inhibition relative to control after a 60-minute incubation. The results of formulations 1 to 4 as given in Table 2.

[0094] Free radical scavenging activity (FRSA): The hydrogen donating or radical scavenging ability was evaluated by the DPPH radical scavenging method using the stable radical DPPH (2,2-diphenyl-l-picrylhydrazyl), which is reduced in presence of antioxidant active substances. DPPH as stable free radical accepts an electron or hydrogen radical to become a stable diamagnetic molecule. For the analysis, 0.1ml of lOmg / lOml of sample in methanol was added to 2.9 ml freshly prepared l,l-diphenyl-2-picryl- hydrazil (DPPH) solution (6 x 10'5M in MeOH). The reduction of the DPPH radical was measured continuously, absorbance was recorded at ZII|;|X517 nm after 1 hour of incubation. The FRSA was calculated according to the method of Yen & Duh (1995). The inhibitory concentration (IC50) and anti radical power (ARP) were estimated and calculated as described by Kroyer(2004). The efficient concentration IC50 which represents the amount of antioxidant necessary to decrease the initial DPPH concentration by 50%, widely used to measure the antioxidant activity. The lower the IC50, the higher the antioxidant capacity. The results of formulations 1 to 4 as given in Table 2.

[0095] The herbs used for the base product have medicinal values which are beneficial for the human being. The present formulations able to produce sustain release of nicotine along with antioxidant activity. Further, in absence of the herbal base product, the antioxidant activity will not be obtained which also suggest the synergistic effect of the present formulation. Table 2: Results of TPC, AOA and IC50 (mg / ml) of the formulations 1 to 4.

[0096] Release of nicotine in saliva: six replicates of 0.5g of product was mixed with 10 ml of artificial saliva with continuous sonication at room temperature. Samples were drawn after 0, 5, 10, 15, 30, 45 and 60 minutes followed by centrifugation and supernatant was processed and nicotine contents were estimated by GC-MS as shown in Table 3. Results showed efficient and sustained release of nicotine for a longer period of time.Table 3: Release of nicotine from the Product after 5, 15, 30, 45 and 60 minutes.

[0097] Further, testing of the formulation was carried out to evaluate mouth feel, organoleptic effect and satisfaction as sustained release of active ingredient in different 5 people of different age group and results are specified in Table 4. Number of volunteers were10 in each group and age group was 30 - 60 years.Table 4. Feed back after chewing the Product: after 5, 15, 30 and 45 minutes.NS = non-significant, cannot say; *Number of persons who remarked out of ten;Satisfactory, good, very good and excellent stands for the efficacy of the product (s) as mouth 0 feel, organoleptic effect and sustained release of active ingredient.

[0098] It is to be understood that the above description is intended to be illustrative, and not restrictive. For example, the above-discussed embodiments may be used in combination with each other. Many other embodiments will be apparent to those of skill in the art upon reviewing the above description. 5 ADVANTAGES OF THE PRESENT INVENTION

[0099] The formulations of the present disclosure are free from tobacco.

[0100] The formulations of the present disclosure able to produce efficient and sustained release of nicotine for a longer period of time.

[0101] The formulations of the present disclosure show antioxidant activity. 0

[0102] The presence of herbal composition shows good flavor and mouth feel.

[0103] The formulations of the present disclosure are derived from herbal sources fortified active constituents and are thus safe, ecofriendly and have no toxicity and free of side effects.

Claims

We Claim:

1. A smokeless green chewable formulation comprising:80 to 98 % w / w of a base product comprising at least one herb;0.2 to 10 % w / w of nicotine; and1 to 10 % w / w of a pH regulator, wherein the nicotine is induced in the base product.

2. The formulation as claimed in claim 1, wherein the herb is selected from a group consisting of Aegle marmelos (Bael), Syzygium cumini (Jamun), Amaranthus cruentus (Chaulai), Trigonella foenum-graecum (Methi), Brassica campestris (Mustard), Centella asiatica, (Manduk Pami), Cinnamomum tamala (Tejpatra), Citrus limon (Lemon), Eucalyptus globulus (Sugandhapatra), Foeniculum vulgare (Saunf), Mentha arvensis (Peppermint), Moringa oelifera (drumstick), Murraya koenigii (Meethi Neem), Psidium guajava (Guava), Mangifera indica (Mango), Cassia angustifolia (Senna) and combination thereof.

3. The formulation as claimed in claim 1, wherein the pH regulator is selected from a group consisting of sodium bicarbonate, potassium bicarbonate, calcium carbonate, magnesium carbonate and combination thereof.

4. The formulation as claimed in claim 1, wherein the formulation has a dosage form selected from a group consisting of flakes, course powder, or granules.

5. The formulation as claimed in claim 1, wherein the formulation includes active antioxidant constituents present naturally in base material.

6. The formulation as claimed in claim 1, wherein the formulation has optionally 0.1 to 1 % w / w of a natural flavor.

7. The formulation as claimed in claim 1, wherein the formulation is free of tobacco leaves, tobacco stem and fibers derived from tobacco.

8. The formulation as claimed in claim 1, wherein the formulation is as and when used as nicotine replacement therapy (NRT) in tobacco cessation to alleviate the signs and symptoms of withdrawal and craving.

9. A method of preparation of a smokeless green chewable formulation comprising: a) processing by collecting, washing, cleaning and drying of a plant foliage material from at least one herb; b) cutting the plant foliage material of step a) followed by drying to obtain a dried foliar plant material small pieces;c) cutting the dried foliar plant material small pieces of step b) to obtain a course or flakes foliar powder; d) processing by sterilization the foliar powder of step c) to obtained a sterilized foliar powder; e) formulating the sterilized foliar powder to obtain a base product; and f) processing by fortification of 80 to 98 % w / w of the base product by 0.2 to 10 % of nicotine suspension in glycerol, and 1 to 10% w / w of a pH regulator to obtain a smokeless green chewable formulation, wherein the nicotine is induced in the base product.

10. The method as claimed in claim 9, wherein the washing in step a) is carried out with a solvent selected from a group consisting of water, ethanol, and combination thereof.

11. The method as claimed in claim 9, wherein the drying is step a) is carried out at a temperature in the range of 25 to 50 °C for a period in the range of 2 to 8 hrs.

12. The method as claimed in claim 9, wherein the plant foliage material of step b) is cut in the range of 1 to 20 mm.

13. The method as claimed in claim 9, wherein the drying in step b) is carried out at a temperature in the range of 25 to 50 °C for a period in the range of 2 to 8 hrs.

14. The method as claimed in claim 9, wherein the course or flakes foliar powder in step c) has a size in the range of 0.2 to 5 mm.

15. The method as claimed in claim 9, wherein the sterilization in step d) is carried out by stream, UV or gamma-ray radiation.

16. The method as claimed in claim 9, wherein the sterilization by steam is carried out at a temperature in the range of 120 to 180 °C for a period in the range of 10 second to 3 min at a pressure in the range of 2 to 10 bar.

17. The method as claimed in claim 9, wherein the base product, nicotine, the natural flavor; the pH regulator in step f) are mixed for a period in the range of 10 min to 60 min at a speed in the range of range of 1500 to 3500 rpm followed by drying at a temperature in the range of 25 to 40 °C for a period in the range of 30 min to 2 hr.

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