DESC:
FIELD OF THE INVENTION
[0001] The present disclosure pertains to a medicinal formulation for use as a laxative. In particular, the present disclosure pertains to a laxative formulation comprising a combination of a laxative, a probiotic and an antispasmodic agent, which provides an improved treatment and/or prevention of constipation.

BACKGROUND OF THE INVENTION
[0002] The 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] A normal pattern of stool evacuation is thought to be a sign of health for all ages. Due to drastic changes in diet and lifestyle, constipation is a common problem, with an estimated prevalence of 3% worldwide for functional constipation in children and approximately 20% in the general population. Since constipation is a symptom-based disorder, and its definition is mainly subjective, it is generally characterized by infrequent bowel movements, hard and/or large stools, painful defecation, and fecal incontinence, and is often accompanied by abdominal pain. These symptoms can have a significant impact on a person’s well-being and health related quality of life. Most childhood constipation results from intentional withholding of stool following a painful experience with defecation.
[0004] Treatment for constipation usually includes evacuation of rectum with oral or rectal laxatives and behaviour modification. Even though rectal approach is comparatively faster than oral laxatives which may be stimulant or osmotic, it tends to have relatively low patient compliance, especially among children.
[0005] The use of senna and sennosides as natural laxatives is known in the art. Negative side effects and performance attributes are recognized with using senna based laxative products. US Patent No. 4511561 indicates that the active sennosides contained in senna fruits are sensitive to oxidation and are easily oxidized to the rhein, which has a certain convulsant and pain producing action.
[0006] Significant and continuous efforts have been made to develop improved senna-containing compositions for treating constipation and/or improving stool consistency. For example, JP Patent No. 6116174 B2 discloses an oral composition for improving bowel movement without significant abdominal pain, wherein the composition comprising a combination of senna extract, water-soluble dietary fiber, lactic acid bacteria and insoluble dietary fiber.
[0007] US Patent Application No. 2012/0156143 A1 discloses oral dosage formulations of plant-derived laxatives, which improve palatability and bioavailability of active components. Specifically, this published application discloses a laxative effervescent formulation that contains standardized senna extract (10% w/w sennosides), NaHCO3, citric acid, flavors, fragrance, colors and sweeteners. This document also describes a method for administering plant-derived laxative to an individual in conjunction with probiotic microorganisms.
[0008] Probiotics are known to have health benefits as supplements in restoring and improving the composition of intestinal microflora. The most commonly used probiotics in this context are lactic acid generating bacteria that is lactobacilli and bifidobacteria. PCT Patent Publication No. WO 2005/055934 A2 describes methods for treating irritable bowel syndrome by increasing carbohydrate absorption by administering a composition containing a Bacillus coagulans bacterium (a lactic acid-forming bacterial species). This reference also provides a method for improving stool consistency in a patient afflicted with non-constipated irritable bowel syndrome, by administering an effective amount of a Bacillus coagulans bacteria provided at a concentration of from about l x l08 to about l x l010 viable bacteria.
[0009] Probiotics are available to consumers primarily in the form of fermented dairy products, dietary supplements, and probiotic fortified foods. Probiotic preparations that allow for administration of probiotic with a carrier liquid at the point of consumption have also been reported in the art. For example, PCT Patent Publication No. WO 2010/054439 A1 discloses a probiotic composition in pellet form comprising a core bead and a probiotic microorganism embedded within a matrix, said matrix substantially maintaining the viability of said microorganisms, wherein the matrix is disposed on or in the core bead and whereby said matrix releases said microorganisms into and upon contact with a liquid carrier. However, products containing probiotic bacteria do suffer from a lack of overall desirable enzyme activities and/or from relatively short shelf-lives.
[00010] In spite of the efforts to develop laxative products, there still remains a need in the art for new laxative formulations that exhibit improved characteristics such as improved efficacy, reduced undesirable side effects, and improved consumer/patient comfort and compliance. It is also essential to address abdominal pain and/or replenishment of gut flora, generally associated with assisted clearing of bowel using stimulant laxative. The present disclosure satisfies the existing needs, as well as others, and generally overcomes the deficiencies found in the prior art.
[00011] 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 incorporated reference 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.
[00012] 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.

OBJECTS OF THE INVENTION
[00013] It is an object of the present disclosure to provide a new and improved laxative formulation which is highly effective in the treatment of constipation.
[00014] It is another object of the present disclosure to provide a laxative formulation that provides improved laxative effect while avoiding occurrence of undesirable side effects such as abdominal pain and cramping.
[00015] It is another object of the present disclosure to provide a laxative formulation that has improved consumer acceptability to encourage regular compliance for treating constipation.
[00016] It is another object of the present disclosure to provide a laxative formulation that is capable of restoring healthy gut flora lost during constipation episode.
[00017] It is another object of the present disclosure to provide a laxative formulation that is suitable for administration to children and adults.
[00018] It is yet another object of the present disclosure to provide a laxative formulation in an oral dosage form that enables ease of administration and improved dosing compliance and consistency of the laxative formulation.

SUMMARY
[00019] According to one aspect of the present disclosure there is provided a laxative formulation for oral use comprising a combination of senna extract, a probiotic and an antispasmodic agent. The disclosed laxative formulation stimulates bowel movement naturally and ensures smooth passage of faeces without undesirable gastrointestinal side effects such as abdominal pain and cramping. The disclosed laxative formulation also supports restoration of healthy balance of gut microflora lost during constipation episode, and assists in compliance especially with children.
[00020] In one embodiment, the probiotic used in the laxative formulation of the present disclosure is lactic acid producing bacteria. In a more preferred embodiment, Bacillus coagulans is used as a probiotic in the formulation of the present disclosure. In one embodiment of the present disclosure, the antispasmodic agent is black salt.
[00021] In one particularly preferred embodiment, the formulation disclosed herein includes 1.60% by weight of senna extract, 0.68% by weight of Bacillus coagulans and 0.52% by weight of black salt, with the rest being pharmaceutically acceptable excipients. Pharmaceutical excipients suitable for use in the formulation disclosed herein can include, but not limited to, sweeteners, bulking agents, flavouring agents, coloring agents, coating agents, fillers and binders.
[00022] In one exemplary embodiment, the formulation of the present disclosure includes senna extract, Bacillus coagulans, black salt, at least one bulking agent, at least one sweetener, at least one flavouring agent and at least one coloring agent. In one embodiment, the at least one bulking agent is maltodextrin. In one embodiment, the at least one sweetener comprises sugar, steviol glycoside or a combination thereof. In one embodiment, the at least one flavouring agent can be a nature identical flavouring substance. In one embodiment, the at least one coloring agent can be turmeric E100.
[00023] In one particularly preferred embodiment, the laxative formulation disclosed herein includes senna extract, encapsulated Bacillus coagulans, black salt, maltodextrin, sugar, steviol glycoside, nature identical flavour and turmeric E100.
[00024] According to another aspect of the present disclosure, there is provided a method for treating constipation comprising orally administering to a human subject in need of such treatment, an effective amount of the formulation of the present disclosure.
[00025] The present disclosure provides a laxative formulation comprising: senna extract in an amount ranging from 0.5% to 5.0% by weight of the formulation; Bacillus coagulans in an amount ranging from 0.05 to 3.0% by weight of the formulation; black salt in an amount ranging from 0.05% to 2.0% by weight of the formulation; and rest being one or a plurality of pharmaceutically acceptable excipients.
[00026] In an embodiment, the Bacillus coagulans comprises encapsulated Bacillus coagulans. In an embodiment, the formulation is in form of any or a combination of beads or pellets. In an embodiment, the formulation is enclosed in an elongated tube. In an embodiment, the formulation is in form of powder. In an embodiment, the formulation is filled in a sachet. In an embodiment, the formulation comprises, by weight of the formulation: senna extract in an amount ranging from 0.5% to 5.0%; encapsulated Bacillus coagulans in an amount ranging from 0.05 to 3.0%; black salt in an amount ranging from 0.05% to 2.0%; maltodextrin in an amount ranging from 30% to 40%; sugar in an amount ranging from 40% to 50%; and rest being coloring, flavouring and sweetening agent(s). In an embodiment, the formulation comprises 1 billion CFU of encapsulated Bacillus coagulans and wherein said formulation comprises senna extract in an amount equivalent to 7.5 mg of sennosides. In an embodiment, the formulation comprises, by weight of the formulation: senna extract in an amount of 1.60%; encapsulated Bacillus coagulans in an amount of 0.68%; black salt in an amount of 0.52%; maltodextrin in an amount of 36.80%; sugar in an amount of 47.00%; steviol glycoside in an amount of 0.80%; flavouring agent in an amount of 12.48%; and coloring agent in an amount of 0.12%.
[00027] The present disclosure further provides an elongated tube, having enclosed therewithin, a laxative formulation in form of beads or pellets, said elongated tube effective to deliver said laxative formulation to a user upon drawing a carrier liquid therethrough, wherein said laxative formulation comprises: senna extract in an amount ranging from 0.5% to 5.0%; encapsulated Bacillus coagulans in an amount ranging from 0.05 to 3.0%; black salt in an amount ranging from 0.05% to 2.0%; maltodextrin in an amount ranging from 30% to 40%; sugar in an amount ranging from 40% to 50%; and rest being coloring, flavouring and sweetening agent(s). In an embodiment, the formulation comprises, by weight of the formulation: senna extract in an amount of 1.60%; encapsulated Bacillus coagulans in an amount of 0.68%; black salt in an amount of 0.52%; maltodextrin in an amount of 36.80%; sugar in an amount of 47.00%; steviol glycoside in an amount of 0.80%; flavouring agent in an amount of 12.48%; and coloring agent in an amount of 0.12%.
[00028] Various objects, features, aspects and advantages of the inventive subject matter will become more apparent from the following detailed description of preferred embodiments.

BRIEF DESCRIPTION OF DRAWINGS
[00029] FIG. 1 illustrates an exemplary perspective cutaway view of the elongated tube with laxative formulation contained therewith in, in accordance with embodiment of the present disclosure.

DETAILED DESCRIPTION
[00030] The following is a detailed description of embodiments of the present 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.
[00031] Unless the context requires otherwise, throughout the specification which follow, 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.”
[00032] 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.
[00033] 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.
[00034] In some embodiments, the numbers expressing quantities of ingredients, properties such as concentration, and so forth, used to describe and claim certain embodiments of the invention 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 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.
[00035] The recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein.
[00036] All methods described herein can be performed in 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.
[00037] The headings and abstract of the invention provided herein are for convenience only and do not interpret the scope or meaning of the embodiments.
[00038] Various terms are used herein. To the extent a term used in a claim 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.
[00039] As used herein, the term “effective amount” refers to an amount that is sufficient to yield a desired therapeutic response.
[00040] As used herein, the term “senna extract” refers to a standardized extract of senna leaves and/or pods, isolated as a powder by evaporation of the extract.
[00041] As used herein, the term “constipation” refers to acute constipation and/or chronic constipation including conditions/disorders associated with irregular bowel movements.
[00042] Embodiments of the present disclosure relate to a laxative formulation for oral use comprising a synergistic combination of senna extract, a probiotic and an antispasmodic agent. The laxative formulation disclosed herein stimulates bowel movement naturally and ensures smooth passage of faeces without undesirable gastrointestinal side effects such as abdominal pain and cramping. The disclosed laxative formulation also supports restoration of healthy balance of gut microflora lost during constipation episode, and assists in compliance especially with children.
[00043] In one embodiment, senna extract having 20% sennosides can be used in the laxative formulation of the present disclosure. The anthraquinone component of senna extract known as sennoside works as a pro-drug and passes unchanged until intestinal bacterial flora metabolizes it into active compound. The senna extract thus provides a targeted therapeutic effect, thereby eliminating the problem of drug loss in clinical use.
[00044] In one embodiment, the probiotic used in the laxative formulation of the present disclosure can be lactic acid producing bacteria. According to embodiments of the present disclosure, the probiotic can work synergistically with senna extract and restore healthy gut flora lost during constipation episode. Further, the probiotic produces lactic acid and short-chain fatty acids (SCFAs) that lower pH in colon which heightens muscle contractions hence, decreases abdominal pain and flatulence. In a preferred embodiment, Bacillus coagulans can be used as a probiotic in the laxative formulation of the present disclosure.
[00045] In an embodiment, the antispasmodic agent used in the laxative formulation of the present disclosure can be black salt. The antispasmodic properties of black salt can prevent and/or ease abdominal spasms associated with constipation and/or the constipation therapy.
[00046] In a particularly preferred embodiment, the laxative formulation of the present disclosure includes a combination of senna extract, Bacillus coagulans and black salt. These individual components when used in combination as a ternary mixture in quantities that, if used alone or in a binary mixture would be ineffective, show unexpected synergistic laxative effect.
[00047] In preferred embodiments, the laxative formulation of the present disclosure can include 0.5% to 5.0% by weight of senna extract, 0.05 to 3.0% by weight of Bacillus coagulans and 0.05% to 2.0% by weight of black salt, based on a total weight of the laxative formulation.
[00048] Accordingly, the present disclosure provides a laxative formulation comprising: senna extract in an amount ranging from 0.5% to 5.0% by weight of the formulation; Bacillus coagulans in an amount ranging from 0.05 to 3.0% by weight of the formulation; black salt in an amount ranging from 0.05% to 2.0% by weight of the formulation; and rest being one or a plurality of pharmaceutically acceptable excipients. In an embodiment, the Bacillus coagulans comprises encapsulated Bacillus coagulans. In an embodiment, the formulation is in form of any or a combination of beads or pellets. In an embodiment, the formulation is enclosed in an elongated tube. In an embodiment, the formulation is in form of powder. In an embodiment, the formulation is filled in a sachet. In an embodiment, the formulation comprises, by weight of the formulation: senna extract in an amount ranging from 0.5% to 5.0%; encapsulated Bacillus coagulans in an amount ranging from 0.05 to 3.0%; black salt in an amount ranging from 0.05% to 2.0%; maltodextrin in an amount ranging from 30% to 40%; sugar in an amount ranging from 40% to 50%; and rest being coloring, flavouring and sweetening agent(s). In an embodiment, the formulation comprises 1 billion CFU of encapsulated Bacillus coagulans and wherein said formulation comprises senna extract in an amount equivalent to 7.5 mg of sennosides. In an embodiment, the formulation comprises, by weight of the formulation: senna extract in an amount of 1.60%; encapsulated Bacillus coagulans in an amount of 0.68%; black salt in an amount of 0.52%; maltodextrin in an amount of 36.80%; sugar in an amount of 47.00%; steviol glycoside in an amount of 0.80%; flavouring agent in an amount of 12.48%; and coloring agent in an amount of 0.12%.
[00049] The present disclosure further provides an elongated tube, having enclosed therewithin, a laxative formulation in form of beads or pellets, said elongated tube effective to deliver said laxative formulation to a user upon drawing a carrier liquid therethrough, wherein said laxative formulation comprises: senna extract in an amount ranging from 0.5% to 5.0%; encapsulated Bacillus coagulans in an amount ranging from 0.05 to 3.0%; black salt in an amount ranging from 0.05% to 2.0%; maltodextrin in an amount ranging from 30% to 40%; sugar in an amount ranging from 40% to 50%; and rest being coloring, flavouring and sweetening agent(s). In an embodiment, the formulation comprises, by weight of the formulation: senna extract in an amount of 1.60%; encapsulated Bacillus coagulans in an amount of 0.68%; black salt in an amount of 0.52%; maltodextrin in an amount of 36.80%; sugar in an amount of 47.00%; steviol glycoside in an amount of 0.80%; flavouring agent in an amount of 12.48%; and coloring agent in an amount of 0.12%.
[00050] In one preferred embodiment, the formulation disclosed herein can include 1.60% by weight of senna extract, 0.68% by weight of Bacillus coagulans and 0.52% by weight of black salt, with the rest being suitable pharmaceutical excipients. Pharmaceutical excipients suitable for use in the laxative formulation of the present disclosure can include, but not limited to, sweeteners, bulking agents, flavouring agents, coloring agents, coating agents, fillers and binders.
[00051] In one exemplary embodiment, the formulation of the present disclosure can include senna extract, Bacillus coagulans, black salt, at least one bulking agent, at least one sweetener, at least one flavouring agent and at least one coloring agent. In one embodiment, the at least one bulking agent can be maltodextrin. In one embodiment, the at least one sweetener comprises sugar, steviol glycoside or a combination thereof. In one embodiment, the at least one flavouring agent can be a nature identical flavouring substance. The flavouring agent imparts to the laxative formulation a pleasant flavour which encourages consumers, especially children, to adhere to treatment regimen and therefore provides better compliance. In one embodiment, the at least one coloring agent can be turmeric E100. Although embodiments of the present disclosure disclose utilization of specific embodiments, it should be appreciated that any other pharmaceutically acceptable excipients, as known to or appreciated by a person skilled in the pertinent art, can be utilized, to sub-serve its intended purpose and to realize the formulation of the present disclosure as laid down in the present disclosure without departing from the spirit and scope of the present invention.
[00052] In one particularly preferred embodiment, the laxative formulation disclosed herein can include senna extract, encapsulated Bacillus coagulans, black salt, maltodextrin, sugar, steviol glycoside, nature identical flavour and turmeric E100.
[00053] In one preferred embodiment, the laxative formulation comprises:

Ingredient Function Weight (mg) % w/w
Senna extract 20%
(7.5 mg Sennoside) Active ingredient 40 1.60%
Encapsulated Bacillus coagulans Active ingredient 17 0.68%
Black salt Active ingredient 13 0.52%
Maltodextrin Bulking agent 920 36.80%
Sugar Sweetener 1175 47.00%
Steviol Glycoside Sweetener 20 0.80%
Nature Identical Flavour Flavouring agent 312 12.48%
Turmeric color (E100) Coloring agent 3 0.12%
Total 2500 100.00%

[00054] According to embodiments of the present disclosure, the laxative formulation can be formulated into any suitable oral dosage form. Preferred oral dosage forms include, but not limited to, oral tablets, capsules, powders, chewable tablets, orally disintegrating tablets, dispersible tablets, soluble tablets, sublingual tablets, buccal tablets, troches, effervescent formulations, syrups, and oral liquid preparations.
[00055] In one embodiment, the laxative formulation of the present disclosure can be produced in the form of beads or pellets which can be used within a drinking straw, elongated tube or the like such that when a user draws liquid (alternatively and synonymously referred to as “carrier liquid” or “carrier fluid”) through the drinking straw or elongated tube, the laxative formulation can be delivered to the user.
[00056] In an embodiment, the elongated tube defines a proximal end and a distal end with a filter/retainer disposed at or adjacent to each of the proximal and distal ends so as to define an enclosure/space therebetween. The laxative formulation of the present disclosure can be contained in the enclosure/space. The filter/retainer may be in form of an end cap, with one or a plurality of through-holes/perforations defined thereon, that can be retained at each end of the elongated tube. In an embodiment, the tube defines a sieve portion and a mounting portion. In an embodiment, the sieve portion includes one or a plurality of perforations. In an embodiment, the sieve portion includes one or a plurality of elongated slots. The elongated slots, preferably, are sufficiently small to retain the pellets/beads within the tube and sufficiently large enabling relatively unimpeded passage of carrier liquid through the tube. In an embodiment, the tube has an internal diameter of about 8 mm. In an embodiment, the elongated slots are about 1 mm in width. In an embodiment, the sieve portion defines an inwardly extending conical surface with one or a plurality of elongated slots and/or perforations defined thereon. This configuration allows for increased surface area for elongated slots and/or perforations, and hence, greater cross-sectional flow area for the carrier liquid to pass through the tube.
[00057] In one embodiment, the formulation of the present disclosure is prepared in the form of small dissolvable beads and incorporated in an elongated tube (alternatively and synonymously referred to as “drinking straw” or “straw”) so that when a liquid, such as for example water, milk or fruit juice, is sucked/drawn through the straw by a user, the beads comprising the laxative formulation are progressively dissolved or otherwise dispersed in the carrier liquid, effectively delivering the laxative formulation to the user. The laxative formulation delivered through the elongated tube significantly improves the patient compliance, in particular, amongst the paediatric patients. Preferably, the pellets or beads are spherical in shape with diameters of 25% to 75% of internal diameter of the elongated tube. Preferably, diameter of the pellets/beads is around 2-3 mm. The pellets/beads may be formed layer by layer, which enables dissolution characteristics of the pellets/beads to be controlled so that as each of the pellet dissolves and its size reduces, shape thereof is retained.
[00058] FIG. 1 illustrates an exemplary perspective cutaway view of the elongated tube with laxative formulation contained therewithin, in accordance with an embodiment of the present disclosure. As can be seen from the figure, the elongated tube 100 defines a proximal end 102 and a distal end 104 with a filter/retainer 106a and 106b disposed at or adjacent to each of the proximal and distal ends so as to define an enclosure/space 110 therebetween. The laxative formulation of the present disclosure (shown as 120) can be contained in the enclosure/space 110. The filter/retainer (106a, 106b) may be in form of an end cap, with one or a plurality of through-holes/perforations defined thereon, that can be retained at each end of the elongated tube. In an embodiment, the filter/retainer (106a, 106b) defines a sieve portion 108a and a mounting portion 108b. In an embodiment, the sieve portion 108a includes one or a plurality of perforations. In an embodiment, the sieve portion 108a includes one or a plurality of elongated slots 112. The elongated slots, preferably, are sufficiently small to retain the pellets/beads within the tube and sufficiently large enabling relatively unimpeded passage of carrier liquid through the tube. As can also be seen from the figure, the sieve portion 108a defines an inwardly extending conical surface 114 with one or a plurality of elongated slots and/or perforations (shown as 112) defined thereon. This configuration allows for increased surface area for elongated slots and/or perforations, and hence, greater cross-sectional flow area for the carrier liquid to pass through the tube.
[00059] In an embodiment, each elongated tube is configured to contain about 2.5 g of the laxative formulation. In an embodiment, the elongated tube serves the need of a single oral dosage delivery system. Effectively, the elongated tube containing laxative formulation therewithin can deliver about 7.5 mg of sennosides, 1 billion CFU of Bacillus coagulans and black salt in an amount of about 0.5% by weight of the formulation.
[00060] In another aspect, the present disclosure provides a method for treating constipation comprising orally administering to a human subject in need of such treatment an effective amount of the laxative formulation of the present disclosure.
[00061] While the foregoing description discloses various embodiments of the disclosure, other and further embodiments of the invention may be devised without departing from the basic scope of the disclosure. 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 having ordinary skill in the art.

EXAMPLES
[00062] A laxative formulation was prepared, composition for which is as provided in Table 1a and Table 1b below –
Ingredient Function Weight (mg) % w/w
Senna extract 20%
(7.5 mg Sennoside) Active ingredient 40 1.60%
Encapsulated Bacillus coagulans Active ingredient 17 0.68%
Black salt Active ingredient 13 0.52%
Maltodextrin Bulking agent 920 36.80%
Sugar Sweetener 1175 47.00%
Steviol Glycoside Sweetener 20 0.80%
Nature Identical Flavour Flavouring agent 312 12.48%
Turmeric color (E100) Coloring agent 3 0.12%
Total 2500 100.00%

Average serving size: 2.5 g per straw (Straw weight may vary, packed by volume and not by weight) Average quantity per straw
Protein (g) 0.020
Fat, total (g) 0.005
- saturated (g) 0.0
- trans (g) 0.0
Cholesterol (mg) 0.0
Carbohydrate, total (g) 2.4
- sugars (g) 1.2
Dietary Fibre (g) 0.0
Sodium (mg) 52.5
Potassium (mg) 0.3
Calcium (mg) 0.0
Sennosides (mg) 7.5
Bacillus coagulans (billion CFU) 1.0

[00063] Some of the aforesaid ingredients are mixed with requisite amount of water to prepare a syrup. The bead formulation was then prepared by taking seed sugar in a heated pan (rotating pan coater) and adding syrup onto the seed sugar while maintaining requisite temperature and humidity conditions and mixing for a time sufficient to produce beads. Beads that are larger than required are removed by passing the pan’s contents through an aperture sieve
[00064] THERAPEUTIC EFFICACY AND SAFETY STUDY
[00065] Open labeled, non comparative, prospective efficacy and safety study was carried out to evaluate the therapeutic efficacy of straw containing sennoside with probiotic in treating functional constipation in children with age group 5 to 12 years.
[00066] STUDY DESIGN
• Name of test product - Straw containing laxative formulation (of Table 1)
• Dose - One straw of Sennoside with probiotic per night for 3 consecutive nights
• 15 patients enrolled
• 3 visits
• Day 0 - Screening and enrolment visit, checking inclusion/exclusion criteria. Dispensing of Investigational Product
• Day 3 ± 1 – Post treatment: Checking stool, adverse event monitoring etc.
• Day 6/7 - Follow-up: Checking stool, adverse event monitoring etc.
• Inclusion criteria
• Children between the age group 5-12 years of age.
• Children suffering from functional constipation diagnosed with Rome III criteria.
• Except functional constipation disorders patients were judged to be in general good health based on medical history, physical examination and Rome III test as assessed by the Investigator.
• Efficacy endpoints
• Rome III criteria assessment was done at visit 1 (Day 0), Visit 2 (Day 3/4) and visit 3 (Day 6 or Day 7) to see the improvement in constipation symptoms.
• Bristol stool grading assessment for type of stool was done in all 3 visits.
• Subjective global assessment of child patient status regarding their constipation on visual analogue scale was performed on all 3 visits.
• Efficacy assessment was done at the end of study treatment (visit 2) and at the end of post treatment follow up (visit 3) and
• Assessment of overall clinical condition of patient was done with the help of 5-point scale at all 3 visits.
• The global assessment of efficacy of treatment – was conducted by the physicians and child patient at the end of the study.
• Safety
• Proportion of children in each treatment group experiencing 1) Adverse Event 2) Drug Related Adverse Event (Related, Unrelated) was not compared as no adverse events were reported.
• Incidence of treatment to overcome adverse events - there were no incidences to overcome AE since no AE were reported.
• Changes in the vital parameters - body temperature, pulse rate, respiratory rate from baseline to the end of treatment.
• Global Assessment of tolerability
[00067] ROME III CRITERIA BASELINE ASSESSMENT
[00068] Table 2a below provides the symptoms that were verified and documented for each patient. Table 2b below provides results of the Rome III criteria baseline assessment.
Symptoms Y/N
3 or less bowel movements per week
At least one episode of faecal incontinence per week after child has acquired complete bowel control
History of extensive faecal retention or withholding behaviour by the child
having hard and painful stools
Large fecal mass on digital rectal examination
Large in diameter stools that cause rectal outlet obstruction

Laxative Formulation in straw (N=15) Observed
(Mean ± SD)
Screening (Visit 1, Day 0) 4.00 ± 0.00
Visit 2 (Day 3±1) 0.80 ± 1.21
Visit 3 (Day 6 or 7) 2.53 ± 1.41
P value for before treatment vs. after treatment p<0.05

[00069] Effect on Total Visual Analogue Scale – Subjective Global Assessment of patients status regarding their constipation
[00070] Description of the face that best described the patient’s general status regarding incontinence was documents at each visit. The Score was given depending on the face expression as provided in the Table 3a below. Table 3b below provides results of the total visual analogue scale - subjective global assessment of patients status regarding their constipation.

Visual Analogue Scale
Screening (Visit 1, Day 0) 4.80 ± 1.01
Visit 2 (Day 3±1) 2.40 ± 0.83
Visit 3 (Day 6 or 7) 3.47 ± 1.19
P value for before treatment vs. after treatment p<0.05

[00071] Effect On Total Overall Clinical Condition Of Children
[00072] Assessment of overall clinical condition of patient was done on 5 point scale as represented in table 4a below. Table 4b provides results of total overall clinical condition of children.
1 Much Worse
2 Worse
3 No Change
4 Improved
5 Much Improved

Overall Clinical Condition Of Children
Screening (Visit 1, Day 0) 1.87 ± 0.35
Visit 2 (Day 3±1) 4.47 ± 0.74
Visit 3 (Day 6 or 7) 3.40 ± 0.99
P value for before treatment vs. after treatment p<0.05

[00073] Investigator’s Assessment Regarding Treatment with Laxative Formulation Contained In a Straw
[00074] Table 5 below provides results of investigator’s assessment regarding treatment with laxative formulation contained in a straw.

Grading Laxative Formulation in Straw (N=15)
% of patients No. of patients
Excellent 86.67% 13
Good 13.33% 2
Satisfactory or Fair 0.00% 0
Poor 0.00% 0
Total 100% 15

[00075] Patient’s Assessment Regarding Treatment with Laxative Formulation Contained In a Straw
[00076] Table 6 below provides results of patient’s assessment regarding treatment with laxative formulation contained in a straw

Grading Laxative Formulation in Straw (N=15)
% of patients No. of patients
Very Good Improvement 86.67% 13
Good Improvement 13.33% 2
Moderate Improvement 0.00% 0
Negligible Improvement 0.00% 0
Worse 0.00% 0
Total 100% 15

[00077] Investigator’s Assessment Regarding Efficacy of Treatment with Laxative Formulation Contained In a Straw
[00078] Table 7 below provides results of investigator’s assessment regarding efficacy of treatment with laxative formulation contained in a straw

Grading Laxative Formulation in Straw (N=15)
% of patients No. of patients
Very Good Improvement 60% 9
Good Improvement 40% 6
Moderate Improvement 0.00% 0
Negligible Improvement 0.00% 0
Worse 0.00% 0
Total 100% 15

[00079] Patient’s Assessment Regarding Efficacy of Treatment with Laxative Formulation Contained In a Straw
[00080] Table 8 below provides results of patient’s assessment regarding efficacy of treatment with laxative formulation contained in a straw

Grading Laxative Formulation in Straw (N=15)
% of patients No. of patients
Very Good Improvement 46.67% 7
Good Improvement 53.33% 8
Moderate Improvement 0.00% 0
Negligible Improvement 0.00% 0
Worse 0.00% 0
Total 100% 15

[00081] Following conclusions were drawn from the clinical trial (study to evaluate therapeutic efficacy of the laxative formulation contained in an elongated tube) –
• Average Rome III criteria at the 3 visits were 4.00, 0.80, 2.53 indicating a reduction in symptoms of functional constipation;
• Average Visual Analogue Scale, where 0 is Happy and 10 is Crying, at the 3 visits were 4.80, 2.40, 3.47;
• Average Overall Clinical Condition of Children, where 1 is Much Worse and 5 is Much Improved, at the 3 visits were 1.87, 4.47, 3.40;
• Investigator’s Assessment of Tolerability
• 13 patients graded as Excellent
• 2 patients graded as Good
• Patient’s Assessment of Tolerability
• 13 patients graded as Excellent
• 2 patients graded as Good
• Investigator’s Assessment of Efficacy
• 9 patients graded as Excellent
• 6 patients graded as Good
• Patient’s Assessment of Efficacy
• 7 patients graded as Excellent
• 8 patients graded as Good
[00082] It can be concluded from the study that the laxative formulation of the present disclosure including a combination of senna extract, a probiotic and an antispasmodic serves as an improved method for treatment and/or prevention of constipation as it stimulates bowel movement naturally and ensures smooth passage of faeces without abdominal pain or cramps (undesirable side effects common with known laxative formulations) while restoring healthy gut flora lost during constipation episode. Further, delivery of laxative formulation of the present disclosure in form of an elongated tube/drinking straw (wherein the laxative formulation is enclosed therewithin in form of pellets/beads) drastically improves the patient compliance, especially in children.

ADVANTAGES OF THE INVENTION
[00083] The present disclosure provides a laxative formulation including a synergistic combination of senna extract, a probiotic and an antispasmodic, which provides an improved method for treatment and/or prevention of constipation.
[00084] The present disclosure provides a new and improved laxative formulation which stimulates bowel movement naturally and ensures smooth passage of faeces without abdominal pain.
[00085] The present disclosure provides a laxative formulation which is capable of restoring healthy gut flora lost during constipation episode.
[00086] The present disclosure provides a laxative formulation in an oral dosage form that enhances patient compliance, especially in children.
[00087] The present disclosure provides a laxative formulation which is suitable for oral administration to children, adults, aged patients, or other patients suffering from constipation.
[00088] The present disclosure provides a laxative formulation that provides improved laxative effect while minimizing potential undesirable side effects such as abdominal pain and cramping.
[00089] The present disclosure provides a laxative formulation which induces bowel movement within 6-8 hours, thereby avoiding excessive repeated dosing of the medication.
[00090] The present disclosure provides a laxative formulation in an oral dosage form which enables ease of administration, improved dosing compliance and consistency of the laxative formulation.

,CLAIMS:
1. A laxative formulation comprising:
senna extract in an amount ranging from 0.5% to 5.0% by weight of the formulation;
Bacillus coagulans in an amount ranging from 0.05 to 3.0% by weight of the formulation;
black salt in an amount ranging from 0.05% to 2.0% by weight of the formulation; and
rest being one or a plurality of pharmaceutically acceptable excipients.
2. The formulation as claimed in claim 1, wherein the Bacillus coagulans comprises encapsulated Bacillus coagulans.
3. The formulation as claimed in claim 1, wherein said formulation is in form of any or a combination of beads or pellets.
4. The formulation as claimed in claim 1, wherein said formulation is enclosed in an elongated tube.
5. The formulation as claimed in claim 1, wherein said formulation is in form of powder.
6. The formulation as claimed in claim 1, wherein said formulation comprises, by weight of the formulation:
senna extract in an amount ranging from 0.5% to 5.0%;
encapsulated Bacillus coagulans in an amount ranging from 0.05 to 3.0%;
black salt in an amount ranging from 0.05% to 2.0%;
maltodextrin in an amount ranging from 30% to 40%;
sugar in an amount ranging from 40% to 50%; and
rest being coloring, flavouring and sweetening agent(s).
7. The formulation as claimed in claim 5, wherein said formulation comprises 1 billion CFU of encapsulated Bacillus coagulans and wherein said formulation comprises senna extract in an amount equivalent to 7.5 mg of sennosides.
8. The formulation as claimed in claim 1, wherein said formulation comprises, by weight of the formulation:
senna extract in an amount of 1.60%;
encapsulated Bacillus coagulans in an amount of 0.68%;
black salt in an amount of 0.52%;
maltodextrin in an amount of 36.80%;
sugar in an amount of 47.00%;
steviol glycoside in an amount of 0.80%;
flavouring agent in an amount of 12.48%; and
coloring agent in an amount of 0.12%.
9. An elongated tube, having enclosed therewithin, a laxative formulation in form of beads or pellets, said elongated tube effective to deliver said laxative formulation to a user upon drawing a carrier liquid therethrough, wherein said laxative formulation comprises:
senna extract in an amount ranging from 0.5% to 5.0%;
encapsulated Bacillus coagulans in an amount ranging from 0.05 to 3.0%;
black salt in an amount ranging from 0.05% to 2.0%;
maltodextrin in an amount ranging from 30% to 40%;
sugar in an amount ranging from 40% to 50%; and
rest being coloring, flavouring and sweetening agent(s).
10. The elongated tube as claimed in claim 10, wherein said formulation comprises, by weight of the formulation:
senna extract in an amount of 1.60%;
encapsulated Bacillus coagulans in an amount of 0.68%;
black salt in an amount of 0.52%;
maltodextrin in an amount of 36.80%;
sugar in an amount of 47.00%;
steviol glycoside in an amount of 0.80%;
flavouring agent in an amount of 12.48%; and
coloring agent in an amount of 0.12%.