DESC:TECHNICAL FIELD:
The present disclosure relates to the development of an Oral Nutritional Supplement (ONS) for reducing gut inflammation and to improve gut immunity in the patients with advanced cancers, for example gastric cancer. More particularly, the present disclosure relates to a composition or formulation comprising of Es-Fortitude GH, an Oral Nutritional Supplement (ONS) product containing liposomal curcumin (HYDROCURC) and Bacillus coagulans (Ganeden BC30) which helps in providing immunomodulatory effect to improve gut immunity as well as to reduce gut inflammation in patients with advanced cancers, for example gastric cancer. Suitable additives, pharmaceutically acceptable excipients and carriers can be present in said composition or formulation.

BACKGROUND:

Gastrointestinal (GI) cancer, the 5th most common malignancy involving epigenetic, genetic, and environmental factors with high rate of human demise (8.8 % of total cancer deaths) still remains a daunting challenge to be circumvented. Of many, Microsatellite Instability (MSI) triggered by DNA mismatch repair deficiency is a crucial prognostic as well as predictive biomarker in GI cancers. Moreover, tumour genotyping and activation of signalling pathways like RAS/BRAF, PI3K, WNT, and ß-catenin stat3 also play significant roles in progression of the disease. Epigenetic regulation of MYC-mediated differentially expressed genes in gastric cancer cell lines has also shed some light developing new therapeutic targets in GI cancers. When validated adequately, sentinel lymph node (SLN) navigation surgery can substantially influence the treatment of gastric cancer giving rise to the conditions for targeted and effective lymphadenectomies.
Nonetheless, this is closely associated with gut inflammation and weight loss. Malnutrition in gastric cancer patients is associated with a poor prognosis and is an important predictor of mortality. Approximately half of the patients has malnutrition and the mortality rate varies from 30%-50%, reaching 80% in cases with advanced pancreatic cancer. Patients with GI malignancy undergoing major elective procedures have a higher risk of postoperative complications, particularly for surgical stress, immune suppression induced by cancer or by blood transfusion. Malnourished patients are always at a greater risk of adverse clinical outcomes and higher incidence of complications like wound / infectious complications. Malnutrition is commonly found in advanced gastric cancer patients due to poor absorption of essential nutrients. Avoidance of gastric cancer, thus, has become a priority in the present time. However, patients with higher risk should be screened for early detection and chemoprevention.
Environmental and nutritional factors have been implicated in the development of the disease. Consumption of salt and salt-preserved food, nitrates, and smoked or pickled foods have been associated with increased risk of developing gastric cancer. Much of the evidence about salt and food preservation, however, is indirect and is based on time trend comparisons.

According to the World Health Organization guidelines, Gastric Cancer can be classified as adenocarcinoma, signet ring-cell carcinoma, and undifferentiated carcinoma. However, it is not as widely used as the Lauren classification, which distinguishes two major subtypes of GC, intestinal and diffuse types. The Lauren classification contains microscopic and macroscopic differences. It has been postulated that intestinal types of GC are associated with chronic atrophic gastritis and intestinal metaplasia, whereas diffuse types originate from normal gastric mucosa. The ratio of intestinal and diffuse types varies between countries and continents. In European countries, intestinal type is currently more common. It tends to occur
more often in the distal stomach, in high-risk areas, and it is often preceded by a long-standing precancerous lesion. The diffuse type prevails among young patients. The extent of the surgical resection depends on the Lauren’s histological subtype of GCs.

Figure 1. Classification of Gastric Cancers

Impeccable investigations have demonstrated that, owing to inflammation, there is an approximately 25% increase in colorectal cancer risk due to ulcerative colitis, and a 10-20-fold increase in the risk of pancreatic cancer for patients who have experienced pancreatitis. As we behold, anti-inflammatory agents have increasingly been used as effective adjuvants for conventional therapies and three mechanisms have been proposed: chemo-protection, alterations in pharmacokinetics or metabolism, and chemo-sensitization.
It is found that administration of anti-inflammatory agents can decrease the toxicity of conventional chemotherapeutic agents, thus, protect the normal host cells from the lethal effects. Much to our intrigue, numerous functional foods have exhibited their potential to protect against or increase risk for gastrointestinal (GI) cancers, including their methods of preparation and habits of consumption. The chemopreventive mechanisms by which fruits and vegetables (~400 g/day) reduce esophageal and stomach cancer risk might be attributed to the presence of high levels of micronutrients including antioxidants (vitamin C and E, ß-carotene, a-tocopherol, selenium, and others) which can decrease DNA damage by scavenging reactive oxygen species (ROS) and flavones which inhibit carcinogenesis by decreasing focal adhesion kinases and metalloproteinases. It turns out that plant polyphenols have become a part of the zeitgeist due to their ability to sensitize drug-resistant cancer cells towards chemotherapeutics as well as protect non-target tissues from damage due to their antioxidant and anti-inflammatory properties. The most popular among these polyphenols is, indubitably, curcumin – which is extracted from the rhizomes of Curcuma longa (known as turmeric) and has a multitude of therapeutic effects in various cancers. Mechanistically, it is suggested that anti-inflammatory agents exert their influence on apoptosis by NF-?B signalling, caspase activation, PARP cleavage, targeting p27, p21, p53, E2F, ATM, ERK/MAPK, ß-catenin, etc. On the other hand, consumption of red or processed meat has been linked to increased risk of GI cancers. Consumption of extremely hot beverages is associated with esophageal cancer risk. Abusive consumption of alcoholic beverages leads to public health problems that include direct effects on the consumer (liver disease, motor vehicle accidents, increased cancer risk) albeit the association between alcohol consumption and cancer risk is complex. A wide range of controversial evidences are available for vitamin D intake and risk of GI cancers. Therefore, prospective, controlled trials are needed to study the effects of diets on GI cancers (1, 2).
Bacillus coagulans, a spore forming probiotic, has been reported to have a good regulatory effect on dysbacteriosis caused by various factors. Several beneficial effects of B. coagulans have been reported. Firstly, B. coagulans can promote intestinal digestion. For example, B. coagulans strains can produce various enzymes that facilitate excretion and digestion. Secondly, B. coagulans can regulate host symbiotic microbiota and inhibit the growth of pathogenic bacteria. Lastly, due to its ability to normalize both the quantitative parameters of the immune system and immune cells’ functional activity, B. coagulans can significantly benefit the host immune system. Due to the evidence supporting various probiotic effects of B. coagulans, many B. coagulans strains have been studied in the management and alleviation of several human diseases. B. coagulans can help create an anaerobic and acidic intestinal environment, which is not hospitable to various pathogens, thereby promoting the growth of some probiotics. As facultative anaerobic bacteria, B. coagulans strains can consume free oxygen in the intestine and stomach and reduce redox reactions. This has been proved to be beneficial to the growth of anaerobic microorganisms such as Lactobacillus and Bifidobacterium. Therapeutic benefits of B. coagulans may be related to its ability to produce antimicrobial compounds, thereby hindering pathogenic bacterial growth and balancing microbiota populations. B. coagulans can alter the production of immune activating, anti-inflammatory cytokines, chemokines and growth factors. can act as an adjuvant in the treatment of inflammatory diseases, the underlying mechanism of which is thought to be through Th1\Th2 cell mediated immune responses (3, 4).
The components of the compositions/formulations for Oral Nutritional Supplement (ONS) act synergistically with acceptable pharmaceutically excipients and such composition/formulations have never been reported for reducing gut inflammation and to improve gut immunity in the patients with advanced cancers with greatly enhanced efficacy.

SUMMARY:
The present disclosure relates to the development of an Oral Nutritional Supplement (ONS) for reducing gut inflammation and to improve gut immunity in the patients with advanced cancers, for example gastric cancer. More particularly, the present disclosure relates to a composition or formulation comprising of Es-Fortitude GH, an Oral Nutritional Supplement (ONS) product containing liposomal curcumin (HYDROCURC) and Bacillus coagulans (Ganeden BC30) which helps in providing immunomodulatory effect to improve gut immunity as well as to reduce gut inflammation in patients with advanced cancers, for example gastric cancer. Suitable additives, pharmaceutically acceptable excipients and carriers can be present in said composition or formulation.

OBJECTIVES:

Accordingly, an object of the present invention is to provide new synergistic composition(s) or formulation comprising a nutritional supplement product which will help in the process of reducing the gut inflammation in the patients with advanced cancers, for example gastric cancer. Yet another objective is that, how this product aids in improving the gut immunity in the patients with advanced cancers, for example gastric cancer.
Another object of the present invention is to provide new synergistic composition(s) comprising Es-Fortitude GH, an Oral Nutritional Supplement (ONS) product containing liposomal curcumin (HYDROCURC) and Bacillus coagulans (Ganeden BC30) and pharmaceutically acceptable excipients and carriers which helps in providing immunomodulatory effect to improve gut immunity as well as to reduce gut inflammation in patients with advanced cancers, for example gastric cancer.
Yet another objective of the present invention, is to provide new synergistic composition(s) comprising a composition or formulation comprising Es-Fortitude GH, an Oral Nutritional Supplement (ONS) product containing liposomal curcumin (HYDROCURC) and Bacillus coagulans (Ganeden BC30) and pharmaceutically acceptable excipients and carriers wherein the pharmaceutical composition is useful in the treatment of advanced cancers and other related acute and chronic diseases.

DETAILED DESCRIPTION:
For the purpose of promoting an understanding of the principles of the invention, reference will now be made to the embodiments and specific language will be used to describe the same. It will nevertheless be understood that no limitation of the scope of the invention is thereby intended, such alterations and further modifications in the illustrated system, and such further applications of the principles of the invention as illustrated therein being contemplated as would normally occur to one skilled in the art to which the invention relates.

It will be understood by those skilled in the art that the foregoing general description and the following detailed description are explanatory of the invention and are not intended to be restrictive thereof.

Unless otherwise defined, all terms, and especially any technical and/or scientific terms, used herein may be taken to have the same meaning as commonly understood by one having an ordinary skill in the art.
Reference throughout this specification to “an aspect”, “another aspect” or similar language means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrase “in an embodiment”, “in another embodiment” and similar language throughout this specification may, but do not necessarily, all refer to the same embodiment.

The terms "comprises", "comprising", or any other variations thereof, are intended to cover a non-exclusive inclusion, such that a process or method that comprises a list of steps does not include only those steps but may include other steps not expressly listed or inherent to such process or method. Similarly, one or more devices or sub-systems or elements or structures or components proceeded by "comprises... a" does not, without more constraints, preclude the existence of other devices or other sub-systems or other elements or other structures or other components or additional devices or additional sub-systems or additional elements or additional structures or additional components.

In an embodiment of the present disclosure, composition or formulation for an Oral Nutritional Supplement (ONS) to diminish gut inflammation and to improve gut immunity in the patients with advanced cancers (Es-FORTITUDE GH) comprising:
a) liposomal curcumin (HYDROCURC) in the range of 40 to 80 weight %; and
b) Bacillus coagulans (Ganeden BC30) in the range of 20 to 40 weight %.

In yet another embodiment of the present disclosure, the composition or formulation, further comprising additives, pharmaceutically acceptable excipients and carriers in the range of 5 to 20 weight %.

In an embodiment of the present disclosure, the composition or formulation further comprising additives including surfactants, preservatives, viscosity modifiers, emulsion stabilizers and additives to modify the color or aroma of the compositions or formulations in the range of 5 to 20 weight %.

In yet another embodiment of the present disclosure, the composition or formulation further comprising piperine (bioperine), prebiotic FOS (Fructooligosaccharide), maltodextrin, silicon dioxide and magnesium stearate in the range of 5 to 20 weight %.

In an embodiment of the present disclosure, the composition or formulation, comprising:
Liposomal Curcumin (water soluble) : 500 mg or more
Piperine (Bioperine) : 5 mg or more
Prebiotic FOS (Fructooligosaccharide) : 100 mg or more
Bacillus Coagulans (Ganaden BC30) : 2 billion CFU or more
Total Carbohydrates : 0.2 gm or more
Total Calories (Less than 1% RDA) : 1 Kcal or more
Less than 1% RDA.

In yet another embodiment of the present disclosure, the composition or formulation, comprising Liposomal Curcumin CWD, Piperine (Bioperine), FOS (Fructooligosaccharide), Bacillus coagulans, Maltodextrin, Silicon Dioxide and Magnesium Stearate.

In an embodiment of the present disclosure, the composition or formulation as and when used reduces gut inflammation, improve gut immunity through Immunomodulatory response triggered through Gut-Brain Axis and reduces muscle fatigue in patients with advanced cancers, acute and chronic diseases.

In yet another embodiment of the present disclosure, Percent Daily Allowance is based on a 2,200 Calorie diet and Per serving (1 capsule) of the composition or formulation.

In an embodiment of the present disclosure, the composition as and when used reduces gut inflammation, improve gut immunity in patients with gut cancer, Gastrointestinal cancers comprising esophageal cancers, stomach cancers and small intestinal cancers.

An intact and properly functioning gastrointestinal (GI) system is of paramount importance in the maintenance of optimal human health. The gastrointestinal (GI) tract plays important roles in nutrient absorption and assimilation, providing a protective barrier against invasion by harmful organisms, and training the immune system to distinguish between harmful and harmless substances. To maximize the absorption of nutrients obtained from the diet, the luminal side of the GI tract is organized into finger-like projections called villi. As a protective barrier against abrasion and to minimize contact of this epithelium by harmful organisms the GI tract is lined by a mucus layer consisting of polysaccharides. The immune system and the GI system are integrally connected. It is at this interface between the lumen of the gut and the lamina propria that the immune system must make decisions regarding which substances are harmless and which are potentially deleterious. The foods we consume as well as opportunistic and beneficial microbes that occupy our gut are full of antigenic peptides and proteins capable of inducing immune responses. In order for the immune system to provide meaningful protection, it needs to be able to carefully discriminate between a large number and variety of antigens (proteins capable of inducing an immune response) that the GI tract is exposed to. The GI tract is populated by as many as 1014 microbes, which is many times greater than the entire number of cells comprising the human body. Probiotics are microorganisms that performs an effective tole in maintaining the health of GI system by altering the environment of GI system, limiting the growth of pathogenic organisms, synthesise nutrients etc. Species such as lactobacillus, bifidobacteria and bacillus coagulans are lactic acid producing bacteria, which can lower the pH, creating an environment that is not hospitable to many yeasts and bacterial species. Probiotic bacteria affect the adaptive and innate immune system by interacting with numerous cell types along the mucosa including B cells, T cells, regulatory T cells, monocytes, macrophages, NK cells and dendritic cells. The immune response is determined by the environment, including cytokines, as well as the absence versus presence of inflammatory mediators. some strains of Bacillus coagulans are able to survive the extremes of heat, acidity of the stomach and bile acids. Bacillus coagulans occupies the gut for just a few days without repeated oral consumption. These characteristics make it an ideal probiotic due to the greater shelf-life stability and survivability to the intestines when consumed.

Nanotechnology provides a compelling medicinal platform with the potential to greatly impact the delivery of a plethora of active ingredients, encompassing small molecule therapeutics, genes, RNAs, peptides, and diagnostic imaging agents, as well as holding great promise for improving the therapeutic index and pharmacokinetics of several drugs under systemic settings. The plausible advantages of nanocarriers are summarized as follows: 1) improvement of a active’s overall pharmacokinetic and pharmacodynamic properties without alteration of its molecular structure; 2) enhanced effective tissue targeting, cellular targeting, and molecular targeting; 3) the ability to circumvent many inherent biological impediments; 4) targeted and nontargeted drug delivery to their respective site of action (cytosol, nucleus, etc) and enhanced therapeutic index of the drug; 5) delivery of multiple drugs with differing chemical properties. Liposomes are artificial “fat bubbles”, ie, vesicles, characterized by having one or more bilayers spontaneously achieved by dispersal of natural or synthetic amphiphatic lipids in water. Since their discovery, they have largely been exploited as delivery vehicles because of their biocompatibility and advantageous safety profile. Their surface can be modified by attaching polyethylene glycol (PEG) which, in turn, prolongs circulation half-life. Doxil and Myocet, two leading doxorubicin liposomes, received Food and Drug Administration (FDA) approval in 1995 and 1999, respectively, followed later by others of the same category. To date, around 17 liposomal drugs are clinically approved and marketed, such as AmBisome (amphotericin B), DaunoXome (daunorubicin), DepoCyt (cytarabine), DepoDur (morphine), and Visudyne (verteporfin). In a 2017 study, phase III outcomes of liposomal combination drugs such as cytarabine–daunorubicin (Vyxeos; CPX-351), as contrasted with their individual counterpart cytarabine and daunorubicin (“7+3”) in 60- to 75-year-old patients with high-risk acute myeloid leukemia, revealed enhanced overall survival of 9.56 vs 5.95 months.
To reduce the gut inflammation in the patients with advanced cancers, for example gut cancer, the present invention provides new synergistic composition(s) or formulation(s) comprising a nutritional supplement product which will help in the process of reducing the gut inflammation in the patients with advanced cancers, for example gastric cancer. In another embodiment, the synergistic composition(s) or formulation(s) aids in improving the gut immunity in the patients with advanced cancers, for example gastric cancer. In yet another embodiment, it provides new synergistic composition(s) or formulation(s) comprising Es-Fortitude GH, an Oral Nutritional Supplement (ONS) product containing liposomal curcumin (HYDROCURC) and Bacillus coagulans (Ganeden BC30) and pharmaceutically acceptable excipients and carriers which helps in providing immunomodulatory effect to improve gut immunity as well as to reduce gut inflammation in patients with advanced cancers, for example gastric cancer.
In another embodiment in accordance with the present invention, it provides new synergistic composition(s) or formulation(s) comprising Es-Fortitude GH, an Oral Nutritional Supplement (ONS) product containing liposomal curcumin (HYDROCURC) and Bacillus coagulans (Ganeden BC30) and pharmaceutically acceptable excipients and carriers wherein the pharmaceutical composition is useful in the treatment of advanced cancers and other related acute and chronic diseases.

In accordance with an embodiment of the present disclosure, an Oral Nutritional Supplement (ONS) formulation is provided.
In yet another embodiment of the present disclosure, new synergistic composition(s) or formulation(s) or the Oral Nutritional Supplement (ONS) formulation is augmented with liposomal curcumin (HYDROCURC) and Bacillus coagulans (Ganeden BC30).
In yet another embodiment, to reduce the gut inflammation in the patients with advanced gastric cancer, new synergistic composition(s) or formulation(s) comprising Es-Fortitude GH, an Oral Nutritional Supplement (ONS) product is augmented with liposomal curcumin (HYDROCURC) having 4x bioavailability when compared to USP grade curcumin. It also contains Bacillus coagulans (Ganeden BC30) which is known to reduce gut inflammation and improve gut immunity, blended with piperine (bioperine), prebiotic FOS (Fructooligosaccharide), maltodextrin, silicon dioxide, magnesium stearate. This serves the purpose of nutritional supplement product for gastric cancer (Es-Fortitude GH).

In accordance with an embodiment of the present disclosure, new synergistic composition(s) or formulation(s) or the Oral Nutritional Supplement (ONS) comprises the liposomal curcumin (HYDROCURC) provides four times more bioavailability compared to USP grade curcumin.
In yet another embodiment of the present disclosure, the Bacillus coagulans (Ganeden BC30) is blended with piperine (bioperine), prebiotic FOS (Fructooligosaccharide), maltodextrin, silicon dioxide and magnesium stearate to prepare new synergistic composition(s) or formulation(s) or the Oral Nutritional Supplement (ONS).

In accordance with an embodiment of the present disclosure, the Bacillus coagulans (Ganeden BC30) in the new synergistic composition(s) or formulation(s) or the Oral Nutritional Supplement (ONS) helps to reduce gut inflammation and improve gut immunity through immunomodulatory response triggered through Gut Brain Axis.

In yet another embodiment of the present disclosure, the said formulation is a powder blend.

In accordance with an embodiment of the present disclosure, the Oral Nutritional Supplement (ONS) formulation is for use in reducing gut inflammation and also to improve gut immunity in the patients with advanced gastric cancer.
In yet another embodiment, new synergistic composition(s) or formulation(s) comprising the Oral Nutritional Supplement (ONS) may be in form of dry powder, liquid, syrup or any other form as required by patients having advanced cancers.
In yet another embodiment of the present invention, new synergistic composition(s) or formulation(s) comprising the Oral Nutritional Supplement (ONS) may include other additives including surfactants, preservatives, viscosity modifiers, and emulsion stabilizers, as per requirements.
In yet another embodiment of the present invention, new synergistic composition(s) or formulation(s) comprising the Oral Nutritional Supplement (ONS) may include other additives to modify the color or aroma of the compositions or formulations described herein.

EXAMPLES:
The present invention illustrated with the help of following examples, which are not intended to limit the scope of the invention and any such modification therein falls within the scope of this invention. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are intended to provide further explanation of the subject matter. Those skilled in the art will appreciate that many modifications may be made in the invention without changing the essence of the invention.

Example 1:
Composition or Formula 1:
Liposomal Curcumin (HYDROCURC)
Bacillus coagulans (Ganaden BC30)

Example 2:
Composition or Formula 2:
Liposomal Curcumin (water soluble) : 500 mg or more
Piperine ( Bioperine) : 5 mg or more
Prebiotic FOS(Fructooligosaccharide) : 100 mg or more
Bacillus coagulans (Ganaden BC30) : 2 billion CFU or more
Total Carbohydrates : 0.2 gm or more
Total Calories (Less than 1% RDA) : 1 Kcal or more
Less than 1% RDA
* Percent Daily Allowance are based on a 2,200 Calorie diet.

Example 3:
Composition or Formulation 3:
Liposomal Curcumin CWD
Piperine (Bioperine)
FOS (Fructooligosaccharide)
Bacillus coagulans
Maltodextrin
Silicon Dioxide
Magnesium Stearate.

In one of the embodiment, capsule shell containing the composition or formulation of the present invention is made of HPMC.
In one of the embodiment, compositions or formulations of the present invention comprises Liposomal curcumin (HYDROCURC) having four times bioavailability when compared to USP grade curcumin.
In another embodiment, compositions or formulations of the present invention comprises Ganeden BC30 which reduces gut inflammation and improve gut immunity through Immunomodulatory response triggered through Gut-Brain Axis.
In yet another embodiment, compositions or formulations of the present invention comprises Hydrocurc which reduces muscle fatigue which is a very common symptom in cancer patients.
In one of the embodiment, the composition or formulation is in capsule form and 1 or 2 capsule per day or as required by the patient can be given. In one of the embodiment, 30 or more capsules can be packed in one packet. In another embodiment, less than 30 capsules are packed in one packet.

Example 4

Evidences from Case Studies with Es-Fortitude-GH:
Esperer Onco Nutrition has come up with an innovative nutritional supplements (Es-Fortitude-GH) that help cancer patients take the rigours of cancer therapy via an anti-inflammatory intervention with better absorption of the nutrients towards improving gut health thereby improving prognosis and Quality of Life (QoL). Below we are providing case studies of 6 volunteers during post-marketing surveillance (PMS) in Indo-American Hospital, Hyderabad which assessed the safety and efficacy of the aforementioned product to ameliorate gut health of patients. The body weights of the patients were carefully measured during each cycle of the therapy, which was accompanied by measurement of BMI. Alongside, several biochemical parameters (viz., blood profile, liver profile, renal profile, PT INR, etc.) were also measured across the prognosis. Volunteers were given a questionnaire to assess the impact on QoL and were monitored for adverse events of supplementation.
Table 1 provides the general description of the patients, with tumor site, treatment, safety of nutritional intervention Es-Fortitude-GH.
Table 2 summarizes the body weight gain that was observed in patients over six visits and average weight at end of 6 visits was higher than initial average weight. Changes in BMI were also recorded.
Table 3 depicts the biochemical parameters which showed improvement or remained almost same (haemoglobin, WBC, platelets, SGOT, SGPT, serum creatinine, PT/INR). The QoL analysis indicated a marked improvement in physical and mental wellness of the volunteers and no adverse effects were reported.
Please find below Tables 1, 2 and 3 (see next page):

Patient name Age Weight/Height/Sex Site of the Tumor Type of Treatment Side effects of the treatment Nutritional Intervention Es-Fortitude-GH Dose Diet Adverse Effect
Patient 1 45 39 kg/ 165 cm/ Female Gastrointestinal Cancer Chemotherapy, Radiotherapy, Immunotherapy Mucositis, Dysphagia, Neutropenia Es-Fortitude-GH 4 capsules/ day Liquid to soft diet, oral fluid None
Patient 2 53 56 kg /167 cm/ Male Esophageal Cancer Chemotherapy, Radiotherapy Mucositis, Dysphagia, Neutropenia Es-Fortitude-GH 4 capsules/ day Liquid to soft diet, oral fluid None
Patient 3 53 57 kg/ 165.1 cm/ Male Stomach Cancer Chemotherapy, Radiotherapy Mucositis, Dysphagia, Neutropenia Es-Fortitude-GH 4 capsules/ day Liquid to soft diet, oral fluid None
Patient 4 55 75 kg/173 cm/ Male Small intestine Chemotherapy, Radiotherapy Mucositis, Dysphagia, Neutropenia Es-Fortitude-GH 4 capsules/ day Liquid to soft diet, oral fluid None
Patient 5 48 80 kg/ 152 cm/ Female Gastrointestinal Cancer Chemotherapy, Radiotherapy Mucositis, Dysphagia, Neutropenia Es-Fortitude-GH 4 capsules/ day Liquid to soft diet, oral fluid None
Patient 6 58 95 kg/ 158 cm/ Male Stomach Cancer Chemotherapy, Radiotherapy, Immunotherapy Mucositis, Dysphagia, Neutropenia Es-Fortitude-GH 4 capsules/ day Liquid to soft diet, oral fluid None

Table 1: General description of the patients, with tumor site, treatment, safety of nutritional intervention Es-Fortitude-GH

Patient Diagnosis Treatment types Body weight in Kgs (1-6 visits) BMI in Kg/m2 (1-6 visits)
1st visit 2nd visit 3rd visit 4th visit 5th visit 6th visit 1st visit 2nd visit 3rd visit 4th visit 5th visit 6th visit
Patient 1
Ca Small Intestine Chemotherapy, Radiotherapy, Immunotherapy 39.0 39.3 40 40.6 41.4 41.9 14.3 14.4 14.7 14.9 15.22 15.4
Patient 2
Esophageal Cancer Chemotherapy, Radiotherapy 56 56.2 56.5 56.7 57 57.7 20.7 20.8 20.9 21 21.1 21.3
Patient 3
Stomach Cancer Chemotherapy, Radiotherapy 57 57.2 57.5 57.5 57.8 58 21.1 21.1 21.2 21.2 21.4 21.4
Patient 4
Small intestinal cancer Chemotherapy, Radiotherapy 75 75 76 76 77 77 25.8 25.8 26.5 26.5 26.8 26.8
Patient 5
Small intestinal cancer Chemotherapy, Radiotherapy 80 80 80 81 82 83.5 36.9 35.2 34.7 35.2 35.6 35.8
Patient 6
Stomach Cancer Chemotherapy, Radiotherapy 95 95 90 90 91 91 39.5 39.5 37.5 37.5 37.8 37.8

Table 2: Changes in Body weight and BMI of the patients over six cycles of the treatment

Biochemical Parameters
Hb WBC Platelets SGOT SGPT Cr PT/INR
Patient 1 1st cycle 14 4.3 1.1 35 25 2 3
2nd cycle 13 4.3 1.1 37 27 1.7 2.5
3rd cycle 12 3.7 1.1 33 18 1.5 1.2
4th cycle 12 3.7 1.1 36 19 0.8 1.2
5th cycle 12 3.7 1.1 20 14 0.9 1.1
6th cycle 12 3.7 1.1 17 12 0.8 1.2
Patient 2 1st cycle 11.0 3.0 1.2 22 30 1.5 1.1
2nd cycle 11.2 3.5 1.5 20 31 1.0 1.1
3rd cycle 11.5 3.8 1.7 25 27 0.9 1.1
4th cycle 11.8 4.0 1.7 20 28 0.9 1.1
5th cycle 11.9 4.2 1.8 20 26 0.8 1.1
6th cycle 11.9 4.2 1.8 21 25 0.8 1.1
Patient 3 1st cycle 10.0 3.0 1.0 30 30 0.9 1.1
2nd cycle 10.5 3.5 1.5 28 25 1.0 1.1
3rd cycle 10.5 3.9 1.7 27 26 1.0 1.1
4th cycle 11.0 4.0 1.8 27 26 1.0 1.1
5th cycle 11.2 4.5 1.8 26 26 1.0 1.1
6th cycle 11.2 4.5 1.8 26 26 1.0 1.1
Patient 4 1st cycle 11.2 4.5 2.0 15 23 0.8 1.1
2nd cycle 12.0 4.5 2.0 10 18 0.5 1.2
3rd cycle 12.0 4.8 2.0 10 18 0.5 1.1
4th cycle 12.5 4.8 1.5 7 15 0.4 1.1
5th cycle 13.5 4.8 1.7 7 15 0.5 1.1
6th cycle 13.5 4.8 1.8 7 15 0.4 1.1
Patient 5 1st cycle 11 4.0 1.5 12 40 0.8 1.1
2nd cycle 10 6.5 1.5 10 35 0.9 1.1
3rd cycle 9 6.0 1.5 10 30 0.9 1.1
4th cycle 12 6.0 2.0 10 20 0.8 1.1
5th cycle 12 6.0 2.0 10 20 0.8 1.1
6th cycle 12 6.0 2.0 10 20 0.8 1.1
Patient 6 1st cycle 9.5 11.0 1.0 35 11 1.7 1.1
2nd cycle 9.3 7.5 1.25 47 12 1.9 1.1
3rd cycle 10 6.5 1.5 25 10 0.9 1.1
4th cycle 11 6.0 2.0 25 10 0.8 1.1
5th cycle 11 6.0 2.0 25 10 0.8 1.1
6th cycle 11 6.0 2.0 25 10 0.8 1.1

Table 3: Monitoring biochemical parameters (Blood, liver, renal profiles, PT/INR) of the patients over six cycles of the treatment

STORAGE
In one of the embodiment, composition(s) or formulation(s) of the present invention for Oral Nutritional Supplement is packed in suitable bottles for storage, for example HDPE Bottle. The shelf life of the compositions or formulations of the present invention for Oral Nutritional Supplement is at least 24 months from the date of manufacture, when stored at ambient conditions. The package or the bottle should be stored at ambient conditions, in a clean, dry place and away from direct sunlight.

ADVANTAGES:

The following are the technical advantages of the invention:

• Composition(s) or formulation(s) for Oral Nutritional Supplement for Gastrointestinal GI Cancer comprises all the required nutrients for reducing gut inflammation and improve gut immunity.
• It also contains liposomal curcumin (HYDROCURC) which provides 4 times more bioavailability compared to USP grade curcumin.
• It contains Ganeden BC30 which is clinically proven to reduce gut inflammation and improve gut immunity through immunomodulatory response triggered through Gut-Brain Axis.
• The liposomal curcumin (HYDROCURC) is clinically proven to reduce muscle fatigue which is a very common symptom in cancer patients.
• It is a gluten and lactose free product.

While the invention has been described and illustrated with reference to certain particular embodiments thereof, those skilled in the art will appreciate that various adaptations, changes, modifications, substitutions, deletions, or additions of procedures and protocols may be made without departing from the spirit and scope of the invention. For example, effective dosages other than the particular dosages as set forth herein above may be applicable as a consequence of variations in responsiveness of the mammal being treated for any of the indications with the compounds of the invention indicated above. The specific pharmacological responses observed may vary according to and depending upon the particular active compounds selected or whether there are present pharmaceutical carriers, as well as the type of formulation and mode of administration employed, and such expected variations or differences in the res tills arc contemplated in accordance with the objects and practices of the present invention. It is intended, therefore, that the invention be defined by the scope of the claims which follow and that such claims be interpreted as broadly as is reasonable.

While specific language has been used to describe the present subject matter, any limitations arising on account thereto, are not intended. As would be apparent to a person in the art, various working modifications may be made to the method in order to implement the inventive concept as taught herein.

References:
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4. Jiang Cao, Zhiming Yu, Wenyin Liu, Jianxin Zhao, Hao Zhang, Qixiao Zhai, Wei Chen. Probiotic characteristics of Bacillus coagulans and associated implications for human health and diseases. Journal of Functional Foods, Volume 64, 2020,103643, ISSN 1756-4646, https://doi.org/10.1016/j.jff.2019.103643. ,CLAIMS:We Claim:

1. Composition or formulation for an Oral Nutritional Supplement (ONS) to diminish gut inflammation and to improve gut immunity in the patients with advanced cancers (Es-FORTITUDE GH) comprising:
a) liposomal curcumin (HYDROCURC) in the range of 40 to 80 weight %; and
b) Bacillus coagulans (Ganeden BC30) in the range of 20 to 40 weight %.

2. The composition or formulation as claimed in claim 1, further comprising additives, pharmaceutically acceptable excipients and carriers in the range of 5 to 20 weight %.

3. The composition or formulation as claimed in preceding claims, comprising additives including surfactants, preservatives, viscosity modifiers, emulsion stabilizers and additives to modify the color or aroma of the compositions or formulations in the range of 5 to 20 weight %.

4. The composition or formulation as claimed in preceding claims, comprising piperine (bioperine), prebiotic FOS(Fructooligosaccharide), maltodextrin, silicon dioxide and magnesium stearate in the range of 5 to 20 weight %.

5. The composition or formulation as claimed in as claimed in preceding claims, comprising:
Liposomal Curcumin (water soluble) : 500 mg or more
Piperine ( Bioperine) : 5 mg or more
Prebiotic FOS (Fructooligosaccharide): 100 mg or more
Bacillus Coagulans (Ganaden BC30) : 2 billion CFU or more
Total Carbohydrates : 0.2 gm or more
Total Calories (Less than 1% RDA) : 1 Kcal or more
Less than 1% RDA.

6. The composition or formulation as claimed in as claimed in preceding claims, comprising Liposomal Curcumin CWD, Piperine (Bioperine), FOS(Fructooligosaccharide), Bacillus coagulans, Maltodextrin, Silicon Dioxide and Magnesium Stearate.

7. The composition or formulation as claimed in preceding claims, wherein the composition as and when used reduces gut inflammation, improve gut immunity through Immunomodulatory response triggered through Gut-Brain Axis and reduces muscle fatigue in patients with advanced cancers, acute and chronic diseases.

8. The composition or formulation as claimed in preceding claims, wherein Percent Daily Allowance is based on a 2,200 Calorie diet and Per serving (1 capsule).

9. The composition or formulation as claimed in in preceding claims, wherein the composition as and when used reduces gut inflammation, improve gut immunity in patients with gut cancer, Gastrointestinal cancers comprising esophageal cancers, stomach cancers and small intestinal cancers.