FIELD OF INVENTION

The present invention generally relates to herbal medicinal formulations. More specifically it pertains to an oral composition consisting of enteric coated HPMC based capsules containing a synergistic combination of just two herbal ingredients viz, neem seed oil and peppermint oil, for the treatment of gastrointestinal disordersin particular, IBS (Irritable Bowel Syndrome).

BACKGROUND OF THE INVENTION

Definition

Gastrointestinal disorders is a term used to define any condition or disease that occur within gastrointestinal tract or digestive track. Organs that make up the gastrointestinal tract are the mouth, esophagus, stomach, small intestine, large intestine and anus. (https://www.drugs.com/article/gastrointestinal-disorders.ht mr) Certain nerves, hormones and enzymes work together to regulate the functioning of digestive system. In addition, certain bacteria known as gut flora or micro-biome which reside within the gastrointestinal tract, also play an important role in digestion, immunity and overall health.

Diseases affecting the GI Tract

Common diseases affecting the gastrointestinal tract are constipation, irritable bowel syndrome (IBS), nausea, food poisoning, gas, bloating, gastro esophageal reflux disease, hemorrhoids, fissures, lactose intolerance, celiac disease etc. Thesediseases usually impart negative impacts on digestion and overall health. Qw$£p!/m£.d£yela^^ diseases

Irritable Bowel Syndrome (IBS) Irritable Bowel syndrome is a common disorder of lower gastrointestinal tract i.e., large intestine. According to American college of Gastroenterology, IBS is defined as “Abdominal discomfort associated with altered bowel habits

Symptoms of IBS include constipation, diarrhea or both constipation and diarrhea at different times, this situation is also termed as mixed diarrhea. Other symptoms associated with IBS are abdominal pain, cramping, bloating, changes in appearance of bowel movement, increased gas etc.

Existing treatments and their limitations

Diet based treatments - involve increased intake of fiber rich diet, which helps in stretching of the bowel walls, decreases the tension and provides relief in constipation and also reduces diarrhea. But these treatment plans do not help in sudden improvement and sudden pain relief. The effects are imparted slowly, due to which patient continues to suffer.

Drug based treatments- involve the utilization of various chemical based medications such as anticholinergic agents and antispasmodic agents including dicyclomine, clidinium etc. According to National Institute of Health (NIH), the medicines which are prescribed for the treatment of IBS associated diarrhea are loperamide, rifaximin, eluxadilone, alosetron etc. and medication prescribed for treatment of IBS associated constipation include use of laxatives, lubiprotone, linelotide, piecantide etc. (https://www.niddk.nih.^ov/health-information/di^estive- diseases/irritable-bowel- syndrome/treatment). Chemical based treatments though fast acting suffer from the limitations of negative side-effects such as insomnia, nausea, heart burn, constipation, dry mouth etc. and effect the overall health pattern.

Herbal treatments- Herbs have been indicated for usefulness in treatment of IBS.

Hence there is an unmet need for the development of formulation comprising herbalingredients for the treatment of irritable bowels syndrome which if taken orally gives magical results.

Problem addressed and Technologically Advancement achieved The invention represents a major technological advancement in the treatment of IBS by overcoming the limitations of existing approaches viz. diet based changes, synthetic drugs and herbal medicines, none of which were able to address the problem in a holistic manner and therapeutically effective manner, as has been done by present invention. The invention offers an oral composition which when taken at a dose of just two capsules per day for 28 days, gives significant relief to patients, without any side effects, which none of the existing treatments is able to do. Out of the hundreds of phytochemicals and natural compounds available, the inventors by considerable research efforts narrowed down on a biocompatible and synergistic combination of just two easily available herbal ingredients viz. neem oil and mint oil.

However, in mere admixture form, the two when taken orally directly, would not have resulted in IBS treatment as is heing achieved in nresent oral composition. This is because anything which is taken orally, passes through the stomach, where digestion and thus changes in the composition take place.

In present case also if direct oral consumption of neem oil or mint oil is taken, it leads to degradation of the same in stomach, causing gas formation and other undesirable effects, rendering the formulation less useful. Therefore the inventors thought of overcoming this drawback by putting the formulation in “enteric coated HPMC based capsule” and this drug delivery mechanism results in enhancing the efficacy of the formulation as enteric coating permits transit through the stomach to the small intestine hefore the medication is released. The term "enteric" means "of or relating to the small intestine." In other words since the formulation of neem seed oil and mint oil in enteric coated capsule form reaches small intestine and none of these is released in stomach itself, the overall efficacy of the formulation improves drastically as well as the side effects are reduced to nil or minimal. The results are clearly visible in clinical trials and study conducted by the applicant on 15 patients. The important results of this study are described in proceeding description.

Neem also known as Indian lilac and Azadirachta indica is a medicinal plant belong to Meliaceae family. It is commonly known for its medicinal and therapeutic properties. Neem possesses medicinal properties such as antibacterial, antiviral, antifungal, immunomodulatory, antioxidant, anti-mutagenic, anti-cancerous, antiulcer properties etc. These therapeutic properties are present due to the presence of rich amount of antioxidants and other valuable components such as Azadirachtin, nimbolinin, nimbin, nimibidol, salanin and quercitin etc. Peppermint oil is derived from the leaves or flowers peppermint plant, which is ahybrid between water mint and spearmint. Peppermint oil is most commonly used for the treatment of gastrointestinal disorders including irritable bowel syndrome, constipation, diarrhea, bloating, muscle pain, headache etc. and possesses antimicrobial, antibacterial, antifungal, antiviral and antiinflammatory properties. Peppermint oil basically act as a muscle relaxant and decreases visceral pain when administered orally or intrapertoneally.

Most of the prior studies disclose the utilization of formulations in the form of tablets or capsules comprising peppermint oil for the treatment of gastrointestinal disorders including irritable bowel syndrome. But present invention discloses enteric coated HPMC hased capsule comprising a hlend of hoth neem seed oil and peppermint oil for the treatment of Irritable bowel syndrome, which is not disclosed in any of the prior art studies. The capsule disclosed in present invention basically provides effect of both neem seed oil and peppermint oil together in single formulation for relief in IBS associated diarrhea, constipation and other associated symptoms with almost no side effects.

Before going into the details of the invention, the related prior arts are stated below:

Prior art Patents

PATENT APPLICATION NO: US20150044312A1 Discloses “Composition Comprising allium extracts and Neem oil”

The above cited patent discloses a composition of an extract derived from Allium Porum L, genus plant, vegetable oil and neem oil having anti-microbial, anti-bacterial, anti-septic, anti-fungal, repellent, healing and tissue regenerating activity. The preparation steps comprises of: procurement of fresh Allium Porrum , preferably using the bulbs, Grinding of bulbs into small pieces, Insertion of oily matrix in a closed vessel, heating up to 100° C., equipped with motorized blades, In this case, the extraction is achieved in Neem oil (oily matrix), Pre-heating of the Neem oil UP to a temperature range between 70-85° C.. rotation between the range of 30 and 50 rpm, mixing of Allium Porrum pieces in the oily matrix within the vessel for a time range between 50 and 70 min, After the extraction process, solid part is subjected to pressing: the resulting liquid will be added to the oily matrix and everything will be filtered: 1 to 50 pm, After cooling down the liquid ina natural way and it is ready for use or further processing for further packaging.

In the above cited patent, the composition disclosed is in the form of liquid derivedfrom the mixtures of Allium Porum L species, vegetable oil and neem oil which consists of antimicrobial, anti- bacterial, anti-septic, anti-fungal, anti-repellant properties whereas in the present invention, inventors have prepared Hydroxy Propyl Methyl Cellulose (HPMC) based enteric coated capsules containing only two ingredients neem seed oil and peppermint oil for the treatment of abdominal disorders. Lesser ingredients with a synergistic effect and a simple process, is the crux of the present invention. Hence, the present invention differs from the above cited invention as cited invention uses multiple ingredients including neem seed oil and the extraction process followed by manufacturing process is not simple.

PATENT APPLICATION NO. US8808736B2 discloses “Enteric coated multi particulate controlled release peppermint oil composition and related methods”

The above cited invention relates to enteric coated multi-particulate compositions and, more particularly, to enteric coated multi-particulate compositions containing peppermint oil. A multiparticulate composition comprising a plurality of individual enteric coated cores, the cores including a hydrophobic phase containing peppermint oil dispersed in a microcrvstalline cellulose-hased gel and a hvdronhilic containing a hvdrogel.

Above cited invention discloses enteric coated multi-particulate composition comprising peppermint oil whereas in the present invention, inventors are preparing Hydroxy Propyl Methyl Cellulose (HPMC) based enteric coated capsules containing neem oil and peppermint oil for treating abdominal, GI and IBS disorders. Also, the present invention is not a hydrogel. Hence, the present invention differs from the above cited patent. Patent Application No: US20170295801A1 discloses “Oil Based Organic and All Natural Pest

Repellent for Humans and Pets”

The above invention discloses a natural pest repellent composition. The composition comprises a mixture of herb oils, citrus oils, and wood oils safe for human and pet topical use to repel pests. The composition includes organic and natural materials and is capable of repelling pests such as insects, fleas, flies, mosquitoes, bed bugs, and ticks. The natural pest repellent without limitation consists essentially of: Neem oil, peppermint oil, coconut oil, clove oil, basil oil andlavender oil and other oils in combination.

In the above cited paper, an insect repellent comprising neem oil, peppermint oil, and herb oil, citrus oils which is safe for human and pet topical use whereas present invention discloses a combination of neem oil and peppermint oil HPMC based capsules prepared for treatment of GI, IBS and abdominal disorders. The aim of the present invention totally different from that of the above invention. In the present invention capsules are prepared whereas in the above invention pest repellent cream is prepared. Hence, present invention differs from the above cited patent.

Indian Patent Application No. 202141009822 discloses “Neem oil based bilayer tablet and method of preparation thereof’

The above invention discloses a method of preparation of neem based bilayer tablet for aquatic nest management. A method of preparing bilayer tablets comprises of an immediate release layer, wherein the immediate release layer is composed of a powder admixture consisting of an active ingredient, a carrier material and a coating material; a super disintegrants agent; an ultra-violet protectant; a granulating agent; a lubricating agent; and a glidant; and an extended release layer, comprises of (ingredients: wt/wt%) neem oil (10,000ppm), microcrystalline cellulose and colloidal silicon dioxide powder blend equivalent to 60 mg of Azadirachtin, Hydroxypropyl methyl cellulose (HPMC 5 K100 M) (40-90%), sodium alginate (10-20%), ethyl cellulose (18-22CPS) (20- 80%), para amino benzoic acid (1-5%), 95% v/v ethanol (quantity sufficient), magnesium stearate (1-5%) and talc (1-5%).

The above cited invention is different from the present invention, as in the present invention a HPMC based enteric coated capsule is prepared comprising neem and peppermint oil for treating GI, IBS and Abdominal disorders whereas in the above invention bilayer tablets are prepared by utilizing neem which is effective in aquatic pest management. Hence, the present invention is different from the above cited invention.

Journals and Publications

Abdel Rahman Hussein Amin, Alaa El Din Bayoumi, Nadia Zikry Dimetry, Dalia Abdellah Youssef: Efficiency of Nano-formulations of Neem and Peppermint Oils on the Bionomics and Enzymatic Activities of Agrotis ipsilonLarvae (Lepidoptera: Noctuidae): International Journal of Natural Resource Ecology and Management, August 2019; 4(5): 102-llldoi: 10,11648/j,ijnrem,20190405,ll

In the above cited paper, an investigation was carried out to study the role of nano and loaded nanoformulations of neem and pepper mint oil in comparison to bulk form of these oils against the different biological parameters of A. ivsilon larvae. The nano- emulsions were prepared by using neem oil and peppermint oil with 2% Tween 80 as emulsifier and were sonicated using ultrasonic cleanser.

The present invention differs from the above cited paper, as the present invention involves the combination of neem and peppermint oil HPMC based capsules AND NOT NANO FORMULATIONS. Moreover the present invention has been clinically tested to be effective and beneficial for treating GI, IBS and Abdominal disorders whereas in the above cited paper they are utilizing neem and peppermint oil for the preparation of nano-emulsions effective against enzymatic activities of Agrotis ipsilon Larvae and not for GI/ABS. Hence, the present invention is totally differentfrom the above cited paper. Rakesh K. Mansi Chitkara, Gagandeep Kaur, Arashmeet Kaur, Sandeep Arora and I.S. Sandhu: formulation development and antimicrobial evaluation of polyherbal soap: Chitkara College of Pharmacy, Chitkara University: Plant Archives Vol. 19, Supplement 2, 2019 pp. 1342-1346

The above cited study was conducted to develop the polyherbal hygienic soap by using cold process method and evaluate antimicrobial potential by agar welldiffusion method. Soap was prepared using coconut oil, castor oil, Neem oil, Mentha oil, rose petals extract and NaOH (lye) and the different extracts were incorporated into the basic saponification reaction.

The present invention differs from the above cited paper, as in the above invention a polyherbal soap is prepared by utilizing combinations of oil such as coconut oil, castor oil, neem oil and mentha oil whereas in the present invention, HPMC based enteric coated capsules are prepared by utilizing neem and peppermint oil for treating GI, IPS and Abdominal disorders. Hence, the present invention is totally different from the above cited paper.

Brooks D. Cash, Michael S. Epstein, and Syed M. Shah: A Novel Delivery System of Peppermint Oil Is an Effective Therapy for Irritable Bowel Syndrome Symptoms: Dig Dis Sci (2016) 61:560-571, DOI 10.1007/sl0620- 015-3858-7

The above cited study was done to evaluate the efficacy and tolerability of a novel formulation of peppermint oil capsules for treating IBS-M and IBS-D symptoms. The peppermint oil was extracted from mentha plant. The site-specific targeting (SST) technology used for the Peppermint Oil evaluated in this trial consists of a triple-coated microsphere formulation designed to promote sustained release of PO in the small intestine. This controlled release is designed to overcome unpredictable delivery and tolerability issues with older PO technology and is implemented by converting PO into a solid-state matrix with microcrystalline cellulose as a spherical core. A seal coat surrounds the core to trap the terpenes, themiddle coat is an enteric polymer that dissolves at the intestinal pH and is insoluble at the gastric pH, and the external coat contains a non- mucoadhesive polymer, which facilitates transit through the stomach. The microspheres have an average diameter of less than 1.5 mm to allow rapid transit through the pylorus irrespective of the digestive stage of the stomach. The present invention is different from the above cited invention, as in the above invention they are only utilizing peppermint oil for the treatment of IBS symptoms and also preparing triple coated micro-sphere formulation in the form of capsules whereas in the present invention HPMC based enteric coated capsules are prepared with the combination of peppermint and neem oil for treating GI, IBS and Abdominal disorders.

Most of the prior studies disclose the utilization of formulations in the form of tablets or capsules comprising peppermint oil for the treatment of gastrointestinal disorders including irritable bowel syndrome. But present invention discloses enteric coated HPMC based capsule comprising a blend of neem seed oil and peppermint oil for the treatment of Irritable bowel syndrome, which is not disclosedin any of the prior art studies.

None of the prior art citations provide a solution to a problem of Irritable bowel syndrome in most efficacious manner without any side effects as is disclosed in thepresent invention.

OBJECT OF THE PRESENT INVENTION

The main object of the present invention is to disclose a herbal formulation which is efficacious and quick in treatment of irritable bowel syndrome.

Another object of the present invention is to disclose a herbal formulation for treatment of Irritable bowel syndrome, which is free from side effects.

One more object of the present invention is to disclose a herbal formulation in whichthe ingredients are in a synergistic combination and give magical results in treatment of Irritable bowel syndrome.

SUMMARY OF THE INVENTION

The present invention discloses oral composition in enteric coated HPMC based capsule form for the treatment of gastrointestinal disorders in particular, IBS (Irritable Bowel Syndrome). The composition contains a synergistic combination of just two herbal ingredients viz, neem seed oil and peppermint oil, as active ingredients. The process of preparation of HPMC (Hydroxy Propyl Methyl Cellulose) based enteric coated capsules consists of blending of essential oils i.e., neem seed oil and peppermint oil followed by dispensing the blended oils into HPMC capsule shell. Color and binding solutions (HPMC) are added and emulsifiers like Tween 80, PEG 6000 and Ecopol L 100 are mixed, followed by enteric coating of capsules. Finally the capsules are sorted and packed. The efficacyand safety parameters of the prepared capsules are determined.

The idea behind the formulation of present invention is to provide enhancedeffectiveness of both the ingredients i.e., Neem seed oil and peppermint oil due to the formulation being in the form of a single enteric coated HPMC capsule. It is a natural, effective and low cost treatment of Irritable bowel syndrome.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1: Graphical representation of mean total GSRS score

Figure 2: Graphical representation of mean GSRS scores for diarrhea beforeand after 28 days treatment.

Figure 3: Graphical representation of mean GSRS scores for constipationbefore and after 28 days treatment.

Figure 4: Graphical representation of mean GSRS scores for abdominal pain before and after 28 days treatment.

Figure 5: Graphical representation of mean GSRS scores for pain or discomfort in abdominal relieved by bowel action before and after 28 days treatment.

Figure 6: Graphical representation of mean GSRS scores for passing gas before and after 28 days treatment.

Figure 7: Graphical representation of mean GSRS scores for feeling ofbloating before and after 28 days treatment. Figure 8: Graphical representation of mean GSRS scores for loose bowelmovement before and after 28 days treatment.

Figure 9: Graphical representation of mean GSRS scores for Hard stoolbefore and after 28 days treatment.

Figure 10: Graphical representation of mean GSRS scores for urgent need togo to toilet to empty bowel before and after 28 days of treatment.

Figure 11: Graphical representation of mean GSRS scores for feeling that bowel was not empty before and after 28 days of treatment.

Figure 12: Graphical representation of mean GSRS scores for feeling offullness shortly after starting meal before and after 28 days treatment.

Figure 13: Graphical representation of mean GSRS scores for feeling full evenafter one stopped eating before and after 28 days treatment.

Figure 14: Graphical representation of mean GSRS scores for visible swellingof abdomen before and after 28 days treatment.

DETAILED DESCRIPTION OF THE INVENTION

The following description is of best-contemplated mode of carrying out the invention. The description is made for the purpose of illustrating the general principles of the invention and should not be taken in a limiting sense.

The present invention discloses polyherbal enteric coated HPMC based capsule comprising both Neem seed oil and Peppermint oil for the treatment of gastrointestinal disorder including irritable bowel syndrome (IBS). None of the prior art studies discloses a synergistic combination of neem seed oil and peppermint oil for the treatment of IBS and the use of enteric coated HPMC capsule form for drug delivery. The main idea behind the present invention is to provide the effectiveness of both ingredients against irritable bowel syndrome. Choice of HPMC capsule shells in the present invention has a strong rationale.

The HPMC capsule shell is natural and the use of HPMC capsules is preferred in the present invention as it is easy to manufacture without using glue, binders, fillers, and coating as is required in making tablets. HPMC capsule shell can be filed withjust the active ingredients and thus minimize the number of additional ingredients required. HPMC is vegan and vegetarian friendly and is thus preferred over gelatin capsules these days. HPMC capsule shell has no natural taste, smell or colour. HPMC capsule is easy to swallow and also dissolves in the stomach quite quickly, often in just 5-10 minutes. Other capsules such as Bovine gelatin capsules take more like 20 minutes. Tablets take hours to dissolve completely. This makes HPMC capsules an ideal delivery method.

Choice of enteric coated HPMC capsules has also been made after careful consideration.

A gelling agent is incorporated in HPMC capsules to achieve enteric properties. This allows the protection of sensitive active ingredients from the acidic environment of the stomach to result in complete dissolution in the intestine only. They also provide sufficient taste-masking and acidresistance to prevent gastric reflux.

The problem of poor bioavailability is also suitably addressed by using HPMC based enteric coated capsules in the present invention. These capsules can interact with poorly soluble APIs, leading to a lower crystallisation rate in the GI tract, which can be important in situations when there are supersaturated APIs in theintestine or when dosing either a high-energy salt form or a weakly basic API.

Therefore the HPMC capsules are Enteric coated to prevent disintegration in the stomach to prevent partial neutralisation of the anti- microbial properties of the active ingredients and also peppermint oil if released in the stomach can lead to burps and discomfort to the consumer. Hence enteric coated capsules disintegrate in the small intestine to produce best results. Because of the coated capsules the active material is completely available for the action. Method of preparation

The method used for the preparation of enteric coated HPMC Based neem seed and peppermint oil capsules comprises of following steps:

Procurement of ingredients:

The active ingredients used in present invention are Neem seed oil and Peppermint oil and packed forms of these two are procured from M/s. Immuno Natural Oils Pvt.Ltd., Mandsaur, Madhya Pradesh and other inactive ingredients such as HPMC shells, Titanium dioxide, Ecopol L 100, PEG 100, PEG 6000, Tween 80, Talc, IPA, Apple green and water were procured from routine vendors.

Table 1: List of Ingredients used:

Filling of capsules: Dispense Neem seed oil, Peppermint oil and empty capsule shells. Loaded the blend of neem seed oil and peppermint oil and empty HPMC shells in Liquid filling machine. Oil capsules are filled using automatic liquid filling machine. Preparation of banding solution: Hydroxypropyl cellulose (HPMC), Isopropyl alcohol, water and apple green color are dispensed for the preparation of banding solution. Further the prepared banding solution is fed in the bath of the band sealing machine along with that capsules are added to the hopper of the band sealing machine. The capsules are band sealed, dried in the drying chamber of the band sealing machine and ejected through the chute.

Coating with coating solution: The oil filled capsules are further coated with coating solution consisting of Ecopol L 100, IPA, Talc & Tween 80 in coating pan.These seed oil filled capsules are further sealed and packed.

CLINICAL TRIALS AND EFFICACY ANALYSIS:

The prepared capsules are further analyzed for the efficacy and safety. The efficacyand safety analysis were conducted on 15 patients with irritable bowel syndrome (IBS). The patients were administered two capsules in the morning for a duration of 28 days. After the duration of 28 days, no capsule is required and the course canbe repeated only after few months if the problem recurs.

Demographics and measurements at baseline:

Total 15 patients received the treatment. Most of the subjects were male (86.6%), having a mean age 35.2±14.2 years, mean height and weight 168.46±4.631 cm and 67.3±6.46 kg respectively. Among these, 66.66% were married and 86.66% were living with families. 33.3% and 13.33% of subjects were having the habit of drinking and smoking.

Vital signs of the subjects:

Vital signs such as body temperature, Blood pressure, respiration rate and pulse rate of the subjects were determined at the time of screening. Mean body temperature was recorded as 36.92±0.3, Blood pressure was 127.2/81.3 mm hg, Mean respiration rate was 81.6±4.55 cpm and pulse rate was 18.2± 0.54 bpm. (Table 2)

Table 2: Vital signs of the subjects

Measurement of GI Symptoms by Gastrointestinal symptom rating scale (GSRS):

GSRS was measured on 7 scale questionnaire which comprises of 13 questions, in which score of 13 was considered as normal condition and score of 91 was considered as most severe condition. After treatment with Neem seed oil and peppermint oil capsules, 25.18, 45.32 and 65.46% decline in GI symptoms after 1,2 and 4 weeks of treatment respectively was observed. (Table 3)

Table 3: Mean total GSRS Scale

Improvement in GSRS Score after treatment:

Mean GSRS values were determined after 28 days of treatment with Neem seed oil and peppermint oil capsules. It was observed that, baseline for diarrhea was 4.93, which was declined to 2 after treatment and percentage improvement was 59.43%. 48.1% improvement in constipation, 68% improvement in abdominal pain, 70.45% improvement in pain and discomfort in abdominal relieved by bowel action, 50% improvement in passing gas symptom, 71.67% improvement in the feeling of bloating symptom, 68.44% improvement in loose bowel symptom, 57.08 % improvement in hard stool symptom, 64.2% improvement in urgent need to go to toilet to empty bowel symptom, 68.6% improvement in feeling that bowel was not empty symptom, 66.32% improvement in feeling of fullness shortly after starting meal symptom, 73.02% improvement in feeling full even after you stopped eating symptom and 71.09% improvement in visible swelling of abdomen symptom was observed after 28 days of treatment with capsule disclose in present invention. (Table 4)

Table 4: Percentage (%) improvement in mean GSRS scores of study subjects after treatment

IBS-QOL (Irritable bowel syndrome quality of life) Questionnaire:

Each patient completed IBS-QOL questionnaire developed by Patrick et.al. It comprises of 34 IBS-specific items with high internal consistency and reproducibility. Five point likert scale was used to access degree of QOL. The statements used were 1 = not at all, 2 = slightly, 3 = moderately, 4 = quite a bit, 5= extremely or great deal. Final raw scores are transformed into 0 (Poor quality life) to 100 (Max. quality of life) using formula:

Scale score = (The sum of items - lowest possible score)/ Possible raw score range x 100

The IBS-QOL instrument and scoring programs have used this transformation to provide comparative data for interpretation. All these were sum scored to calculate overall score, which was also transferred into 0-100 scale.

Table 5: IBS Quality of life total mean score Global Assessment of Symptoms:

Global assessment was measured using 3 (0-3) scale evaluation method, in which 0 indicate nil symptoms, 1 indicate mild, 2 is moderate and 3 is severe symptoms. According to Global assessment score after treatment, it was observed that there was a significant decline in symptoms after 28 days of treatment. The level of significance was found < 0.05. (Table 6)

Table 6: Global assessment of symptoms before and after treatment

Safety analysis:

No severe adverse events were evaluated during the study. Further, all the vital signs such as temperature, blood pressure, pulse rate and respiration rate were in normal range. The laboratory data hematology and Biochemistry was foundnormal at the screening visit and end of the study.

From the above, it can be concluded that the present invention is better in efficacy due to synergistic effect of both the ingredients taken together in the form of single enteric coated HPMC capsule.

Novelty of the present invention lies in the disclosure of a single HPMC based enteric coated capsule comprising the blend of neem seed oil and peppermint oil forthe treatment of Irritable bowel syndrome. Most of the prior art studies discloses the use of peppermint oil in the form of tablets or capsules for the treatment of IBSbut none of the prior art indicates REDUCTION OF SIDE EFFECTS TO ALMOST NIL NOR DOES ANY PRIOR ART FORMULATION SHOWS EFFICACY discloses a single HPMC based enteric coated capsule comprising the blend of neem seed oil and peppermint oil. Hence the present invention is NOVEL.

Inventive step by way of technological advancement lies in formulation of a single enteric coated HPMC capsule comprising both neem seed oil and peppermintoil for treatment of IBS which is not disclosed in any of the prior art studies.

Moreover as the capsules comprises of natural ingredients including the shell and hence possesses almost no side effects.

Further inventive step by way of economic advancement lies in disclosure of enteric coated HPMC based Neem seed oil and peppermint oil capsules which are very efficacious and possesses almost No side effects, thus the intake is not required on DAILY BASIS FOR LONG TERM as with other formulations directed for suchkind of abdominal problems. The quality of life of such patients is drastically improved with the help of these two capsules taken only for 28 days.

Industrial application is duly clear as the present invention is formulation for treatment of GI, IBS disorders. The problem of IBS is very common so formulation which is highly efficacious, easy to take and has minimal side effects will attract the medicine manufacturers.