Description:DESCRIPTION:
Field of the invention:
[0001] The present disclosure generally relates to the technical field of a composition for treating pancreatic cancer and, in specific, relates to the preparation of an herbal composition that acts as an alternative chemotherapeutic agent for controlling pancreatic cancer through its action against oxidative stress, inflammation, metastasis, invasion, and proliferation.
Background of the invention:
[0002] Pancreatic cancer is the fourth leading cause of cancer mortality, with a poor prognosis and an overall 5-year survival rate of less than 5%. Even patients who have undergone complete resection, chemotherapy, and radiation have a 5-year survival rate of only 20%. The causes of pancreatic cancer are smoking, diabetes, and pancreatitis. The existing chemotherapeutic drugs were largely ineffective against the pancreatic cancer.

[0003] Gemcitabine is the most commonly used anticancer agent in pancreatic cancer, but its usage can cause pale skin, easy bruising or bleeding, numbness or tingly feeling, weakness, nausea, vomiting, upset stomach, diarrhea, constipation, headache, swelling in your hands, ankles, or feet, skin rash, drowsiness, or hair loss up to 30%. In order to overcome such adverse events, many physicians and patients look into herbal drug-based treatment due to their lesser events of adverse effects.

[0004] Epidemiological studies have demonstrated that the consumption of fruit and vegetables rich in polyphenols is associated with a reduced risk of cancer, particularly anthocyanins. Anthocyanins are a class of water-soluble flavonoids that show a range of pharmacological effects, such as the prevention of cardiovascular disease, obesity control, and antitumor activity.

[0005] Their potential antitumor effects are reported to be based on a wide variety of biological activities including antioxidant; anti-inflammation; anti-mutagenesis; induction of differentiation; inhibiting proliferation by modulating signal transduction pathways, inducing cell cycle arrest and stimulating apoptosis or autophagy of cancer cells; anti-invasion; anti-metastasis; reversing drug resistance of cancer cells and increasing their sensitivity to chemotherapy with low cytotoxicity and safe consumption. However, there are numerous treatment processes for pancreatic cancer and a number of medications used to control pancreatic cancer. The following existing medications are not much effective and they cause various adverse effects.

[0006] The anthocyanins present in punica granatum are mono and diglucosides of cyanidin, pelargonidin, and delphinidin; Litchi chinensis are cyanidin-3-rutinoside, cyanidin-3-glucoside, malvidin-3-glucoside; vitis vinifera are malvidin-3-glucoside and peonidin-3-glucoside, delphinidin -3- glucoside; Hylocereus undatus contains cyanidin 3-O-glucoside, cyanidin 3,5 O-glucoside and pelargonidin 3,5 O-glucoside and garcinia indica are cyanidin-3-glucoside and cyanidin-3-sambubioside. Hence, there is the possibility of the protective effect of herbal fruit peel mixture in pancreatic cancer due to the wide source of anthocyanins in the herbal mixture.

[0007] By addressing all the above mentioned problems, there is a need for an effective herbal composition to overcome the various adverse effects associated with existing medications for treating the pancreatic cancer. There is also a need for an herbal fruit peel mixture that acts as an alternative chemotherapeutic agent for pancreatic cancer through its action against oxidative stress, inflammation, metastasis, invasion, and proliferation. There is also a need for an herbal fruit peel mixture with a cytoprotective activity. There is also a need for an herbal fruit peel mixture that reverts back to the digestive enzymes those involved in the food digestion and controls oxidative stress. There is also a need for an herbal fruit peel mixture with an anti-inflammatory activity that reduces the growth and development of the pancreatic cancer.
Objectives of the invention:
[0008] The primary objective of the present invention is to provide a safe, effective herbal fruit peel mixture to overcome the various adverse effects associated with existing medications for treating a pancreatic cancer.

[0009] Another objective of the present invention is to provide an herbal fruit peel mixture that acts as an alternative chemotherapeutic agent for controlling the pancreatic cancer through its action against oxidative stress, inflammation, metastasis, invasion, and proliferation.

[0010] Yet another objective of the present invention is to provide an herbal fruit peel mixture that is made with fruit peels.

[0011] Another objective of the present invention is to provide an herbal fruit peel mixture with a cytoprotective activity.

[0012] Another objective of the invention is to provide an herbal fruit peel mixture that reverts back to the digestive enzymes involved in the food digestion.

[0013] Other objective of the invention is to provide an herbal fruit peel mixture that controls oxidative stress.

[0014] Another objective of the invention is to provide an herbal fruit peel mixture with anti-inflammatory activity and controls the growth and development of the pancreatic cancer.

Summary of the invention:
[0015] The present disclosure proposes an herbal fruit peel mixture. The following presents a simplified summary in order to provide a basic understanding of some aspects of the claimed subject matter. This summary is not an extensive overview. It is not intended to identify key/critical elements or to delineate the scope of the claimed subject matter. Its sole purpose is to present some concepts in a simplified form as a prelude to the more detailed description that is presented later.

[0016] In order to overcome the above deficiencies of the prior art, the present disclosure is to solve the technical problem to provide an herbal fruit peel composition that acts as an alternative chemotherapeutic agent for controlling pancreatic cancer through its action against oxidative stress, inflammation, metastasis, invasion, and proliferation.

[0017] According to one aspect, the invention provides an herbal fruit peel mixture composition of Litchi chinensis, Punica granatum, Vitis vinifera, Hylocereus undatus, and Garcinia indica. The oral dosage of the composition can be used as a remedy for the prevention of oxidative stress, inflammation and metastasis, and associated tumerogenesis.

[0018] In one embodiment, the composition includes 20 to 40 weight percent of a Litchi chinensis (lychee), 20-40 weight percent of a Punica granatum (pomegranate), 10-20 weight percent of a Vitis vinifera (grapes), 10-20 weight percent of a Hylocereus undatus (dragon fruit), and 20-40 weight percent of a Garcinia indica (kokum).

[0019] In one embodiment, the invention provides a safe herbal fruit peel mixture for oral usage in pancreatic cancer. The herbal mixtures show significant cytoprotective activity. In one embodiment, the invention provides the herbal fruit peel mixture which shows pancreoprotective and liver protective activity by controlling the levels of pancreatic and liver enzymes.

[0020] In one embodiment, the herbal fruit peel mixture shows control activity over oxidative stress by enhancing the antioxidant enzymes and by depleting the Malondialdehyde MDA. In one embodiment, the herbal fruit peel mixture shows anti-inflammatory properties by reducing the levels of inflammatory markers in the pancreas.

[0021] According to another aspect, the invention provides a method for preparing an herbal fruit peel mixture for controlling pancreatic cancer. At one step, the fruit peels are separated from the one or more collected ripened fruits. At another step, the fruit peels are subjected to shade drying. At another step, the coarse powder is prepared from the dried fruit peels. In one exemplary embodiment, at another step, an aqueous suspension of the coarse powder is prepared. At another step, the aqueous extract of the coarse powder is distilled or concentrated by a vacuum evaporation. Further, at another step, the excess solvent is removed from the aqueous extract by a lyophilization process. The aqueous extract of the fruit peels is concentrated/ distilled by vacuum evaporation at a temperature varies between 30°C and 50°C.

[0022] Further, objects and advantages of the present invention will be apparent from a study of the following portion of the specification, the claims, and the attached drawings.
Detailed description of drawings:
[0023] The accompanying drawings, which are incorporated in and constitute a part of the specification, illustrate an embodiment of the invention, and, together with the description, explain the principles of the invention.

[0024] FIG. 1 illustrates an exemplary flowchart of a method for preparing an herbal fruit peel mixture for controlling pancreatic cancer, in accordance to the exemplary embodiment of the invention.
Detailed invention disclosure:
[0025] Various embodiments of the present invention will be described in reference to the accompanying drawings. Wherever possible, same or similar reference numerals are used in the drawings and the description to refer to the same or like parts or steps.

[0026] The present disclosure has been made with a view towards solving the problem with the prior art described above, and it is an object of the present invention to provide an herbal fruit peel composition that acts as an alternative chemotherapeutic agent for controlling pancreatic cancer through its action against oxidative stress, inflammation, metastasis, invasion, and proliferation.

[0027] According to one exemplary embodiment of the invention, a composition of herbal fruit peels comprises Litchi chinensis, Punica granatum, Vitis vinifera, Hylocereus undatus, and Garcinia indica. The oral dosage of the composition can be used as a remedy for the prevention of oxidative stress, inflammation and metastasis, and associated tumerogenesis. The composition provides a safe, effective herbal fruit peel mixture to overcome the various adverse effects associated with existing medications for pancreatic cancer.

[0028] In one embodiment herein, the composition includes 20 to 40 weight percent of a Litchi chinensis (lychee), 20-40 weight percent of a Punica granatum (pomegranate), 10-20 weight percent of a Vitis vinifera (grapes), 10-20 weight percent of a Hylocereus undatus (dragon fruit), and 20-40 weight percent of a Garcinia indica (kokum). In one embodiment, the composition of the herbal fruit peel mixture is carried out twice as herbal mixture 1 and herbal mixture 2.

[0029] In one embodiment herein, the effect of the herbal fruit peel mixture on human pancreatic cell lines using in vitro Cell viability assay (MTT assay) IC50 values (in μg) of the herbal mixtures is shown in table 1.
Table- 1
Compound BxPC-3 PANC-1
Herbal Mixture1 47.42±2.87 55.56±2.54
Herbal fruit peel mixture2 23.60±2.76 29.16±1.33
Doxorubicin 2.41±0.35 2.70±0.49

[0030] In one embodiment herein, table 1 describes the effect of the herbal fruit peel mixture on human cell lines such as BxPC3 & PANC1 using cell viability assay using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide). The herbal mixtures show significant inhibition of BxPC3 & PANC1 cell lines growth.

[0031] In one embodiment herein, the effect of the herbal fruit peel mixture on pancreatic and hepatic enzymes in azaserine induced pancreatic cancer.
Table- 2
Groups Control Azaserine Control Standard Herbal fruit peel mixture1 Herbal fruit peel mixture2
Amylase 230.56±4.26 453.56±3.94# 259.32±5.64* 272.94±4.44* 246.94±4.23*
Lipase 24.23±6.13 82.16±5.61# 29.64±3.49* 27.94±3.97* 25.64±5.09*
SGOT 71.17±2.68 115.50±2.6# 75.50±2.93* 91.33±3.68* 75.33±4.22*
SGPT 39.50±1.80 73.83±1.56# 41.50±2.00* 55.83±2.56* 43.67±2.58*
ALP 174.83±3.0 240.83±3.9# 186.67±3.81* 204.33±5.7* 182.50±3.9*
LDH 355.65±5.5 484.85±6.4# 385.76±11.95* 392.26±3.8* 364.48±7.5*
GGT 2.35±0.03 4.76±0.13# 2.92±0.07* 3.06±0.07** 2.72±0.07*

[0032] In one embodiment herein, table 2 describes the effect of herbal mixtures on pancreatic and liver enzymes in azaserine induced mice. The azaserine induced mice show significant elevation of Amylase, lipase, SGOT (Glutamic-oxalacetic transaminase), SGPT (glutamic-pyruvic transaminase), ALP (alkaline phosphatase), LDH (Lactate dehydrogenase) and GGT (gamma-glutamyl transferase) in a significant manner compared to that of control. Treatment with the herbal mixtures shows a significant reduction of elevated pancreatic and liver enzymes in azaserine induced pancreatic cancer mice.

[0033] In one embodiment herein, the amylase and lipase expressed in U/L; SGOT, SGPT, and ALP were expressed in IU/dL; LDH was expressed in mU/ml and GGT was expressed in IU/ml. P<0.05* significance followed by one-way ANOVA followed by DUNNETT’s multiple comparison tests when compared with the azaserine control group. In one embodiment herein, the DUNNETT’s can be used after the ANOVA has been run to identify the pairs with significant differences. P<0.05# significance followed by one-way ANOVA followed by DUNNETT’s comparison test when comparing the azaserine control group with the control.

[0034] In one embodiment herein, the effect of the herbal fruit peel mixture on oxidative stress markers in azaserine induced pancreatic cancer is shown in table 3 below.
Table- 3
Groups Control Azaserine Control Standard Herbal fruit peel mixture1 Herbal fruit peel mixture2
Total protein 53.26±0.51 33.23±0.87# 47.00±0.77* 47.69±0.92* 52.22±0.82*
SOD 3.12±0.04 1.06±0.09# 2.94±0.06* 2.70±0.02* 3.06±0.06*
CAT 1.42±0.04 0.22±0.04# 1.32±0.03* 1.29±0.02* 1.36±0.04*
GSH 22.94±0.60 14.26±0.14# 21.30±0.46* 20.00±0.57* 21.69±0.72*
GPx 31.08±0.57 23.52±0.35# 28.14±0.60* 25.61±0.41* 29.86±0.40*
GST 3.12±0.10 5.56±0.14# 3.41±0.13* 3.92±0.06* 3.20±0.06*
MDA 78.44±2.71 133.89±3.31# 93.16±2.48* 98.64±3.84* 82.99±4.39*

[0035] In one embodiment herein, table 3 describes the effect of herbal mixtures on oxidative stress parameters in azaserine induced mice. The cancer control group show a significant reduction in protein, SOD (Superoxide dismutase), CAT (catalase), GSH (glutathione), and GPx (glutathione peroxidase) and an elevation of GST (Glutathione S-transferases), and MDA (malondialdehyde). Treatment with herbal mixtures shows a significant elevation of protein, SOD, CAT, GSH, and GPx and a significant reduction of GST and MDA in azaserine induced pancreatic cancer mice.

[0036] In one embodiment herein, SOD, CAT was expressed as IU/min/mg of protein, GSH is expressed as ɳmol/mg of protein MDA is expressed as Umol/g, and GST are expressed as μg/min/ mg of protein. P<0.05* significance followed by one-way ANOVA followed by DUNNETT’s multiple comparison tests when compared with the azaserine control group. P<0.05# significance followed by one-way ANOVA followed by DUNNETT’s comparison test when comparing the azaserine control group with the control.

[0037] In one embodiment herein, the effect of the herbal fruit peel mixture on inflammatory markers in azaserine induced pancreatic cancer is shown in table 4 below.
Table- 4
Groups TNFα (pg/mg of protein) IL6 (pg/mg of protein) CRP (ng/mg of protein)
Normal Control 25.83±1.66 28.00±1.00 4.53±0.35
Azaserine control 62.16±2.42# 46.66±1.27# 9.09±0.26#
Standard (Galcitabine) 31.66±2.17* 32.33±1.40* 4.92±0.21*
Herbal fruit peel mixture1 36.83±1.13* 34.16±1.42* 6.25±0.12*
Herbal fruit peel mixture2 29.33±1.45* 31.00±1.15* 4.98±0.19*

[0038] In one embodiment, the table 4 describes the effect of herbal mixtures on inflammatory markers in azaserine induced mice. The azaserine control group showed a significant elevation of TNFα, IL6, and CRP in mice. Treatment with herbal mixtures showed a significant reduction of TNFα, IL6, and CRP in azaserine induced cancer in mice. P<0.05* significance followed by one-way ANOVA followed by DUNNETT’s multiple comparison tests when compared with the azaserine control group. P<0.05# significance followed by one-way ANOVA followed by DUNNETT’s comparison test when comparing the azaserine control group with the control. P<0.05* significance followed by one-way ANOVA followed by DUNNETT’s multiple comparison tests when compared with the azaserine control group. P<0.05# significance followed by one-way ANOVA followed by DUNNETT’s comparison test when comparing the azaserine control group with the control.

[0039] In one embodiment herein, the comprised herbal fruit peel mixture subjected to cytotoxicity studies using BxPC3 and PANC1 human cell lines. In one embodiment herein, the studies are divided into number of groups. In one embodiment herein, group 1 describes control rats received distilled water, group 2 describes Azaserine control rats received 5mg/kg bd.wt, i.p (once week for 3 weeks), group 3 served with Azaserine along with Gemcitabine (10mg/kg), group 4 served with azaserine along with the herbal fruit peel mixture1 (200mg/kg), group 5 served with azaserine along with the herbal fruit peel mixture2 (200mg/kg).

[0040] In one embodiment herein, the pancreatic cancer is induced with azaserine at the dose rate of 5 mg/kg body weight intraperitoneal by dissolving it in distilled water, once in a week for 3 weeks and then after 1 h all those mice are administered with test compounds. The treatment and supply of food to mice are stopped six hours before the sacrifice. Blood was drawn using retroorbitol puncture and serum was separated at 3000rpm. All the animals are sacrificed and pancreas was separated for further estimations.

[0041] In one embodiment herein, the comprised herbal mixtures show significant Inhibition of BxPC3 & PANC1. The comprised herbal mixtures show significant reduction of α amylase, Lipase, Lactate dehydrogenase, gamma glutamyl transfererase, SGOT, SGPT and ALP in azaserine induced pancreatic mice (shown in Table 2). The comprised herbal mixtures show significant elevation of pancreatic protein, SOD, CAT, GSH and GPx and significant reduction of GST and MDA significantly in azaserine induced pancreatic mice (shown in Table 3). The comprised herbal mixtures show significant reduction of TNF-α, IL6 and CRP significantly in azaserine induced pancreatic mice (as shown in Table 4).

[0042] According to one exemplary embodiment of the invention, FIG. 1 refers to the exemplary flowchart of a method 100 for preparing an herbal fruit peel mixture for controlling pancreatic cancer. At step 102, peels are separated from the one or more collected ripened fruits. At step 104, the peels are subjected to shade drying. At step 106, the coarse powder is prepared from the dried fruit peels. In one exemplary embodiment, at step 108, an aqueous suspension of the coarse powder is prepared. At step 110, the aqueous extract of the coarse powder is distilled or concentrated by a vacuum evaporation. Further, at step 112, the excess solvent is removed from the aqueous extract by a lyophilization process. The aqueous extract of the fruit peels is concentrated/ distilled by vacuum evaporation at a temperature varies between 30°C and 50°C.

[0043] Numerous advantages of the present disclosure may be apparent from the discussion above. In accordance with the present disclosure, an herbal fruit peel mixture is disclosed which acts as an alternative chemotherapeutic agent for controlling pancreatic cancer through its action against oxidative stress, inflammation, metastasis, invasion, and proliferation. The proposed invention provides a safe and effective herbal fruit peel mixture to overcome the various adverse effects associated with existing medications for pancreatic cancer. The herbal fruit peel mixture is made with fruit peels. The herbal fruit peel mixture has cytoprotective activity. The herbal fruit peel mixture controls oxidative stress. The herbal fruit peel mixture controls the growth and development of pancreatic cancer.

[0044] It will readily be apparent that numerous modifications and alterations can be made to the processes described in the foregoing examples without departing from the principles underlying the invention, and all such modifications and alterations are intended to be embraced by this application.
, Claims:CLAIMS:
I/We Claim:
1. A composition of a herbal fruit peel mixture for treating a pancreatic cancer, comprising:
Lychee peel, Pomegranate peel, Grapes peel, Dragon Fruit peel, and Kokum peel,
whereby the composition of the herbal fruit peel mixture acts as an alternative chemotherapeutic agent for treating the pancreatic cancer and acts against oxidative stress, inflammation, metastasis and invasion and proliferation.
2. The composition of the herbal fruit peel mixture as claimed in claim 1, wherein
the Lychee peel is present at 20 to 40 weight percent of the composition;
the Pomegranate peel is present at 20 to 40 weight percent of the composition;
the Grapes peel is present at 10 to 20 weight percent of the composition;
the Dragon peel is present at 10 to 20 weight percent of the composition; and
the Kokum peel is present at 20 to 40 weight percent of the composition.
3. The composition of the herbal fruit peel mixture as claimed in claim 1, wherein the composition of the herbal fruit peel mixture is administered orally.
4. The composition of the herbal fruit peel mixture as claimed in claim 1, wherein the composition of the herbal fruit peel mixture is formulated as capsules, tablets, soft gels, gummies, chocolates, oral dispersible strips and beverages.
5. A method for preparing a composition of an herbal fruit peel mixture for treating a pancreatic cancer, comprising:
separating peels from one or more collected ripened fruits;
subjecting the separated peels to shade drying;
preparing a coarse powder by grinding the dried fruit peels;
preparing an aqueous suspension of the coarse powder;
distilling the aqueous extract of the coarse powder by a vacuum evaporation; and
removing the excess solvent from the aqueous extract by a lyophilization process, thereby obtaining the composition of the herbal fruit peel mixture.
6. The method as claimed in claim 5, wherein the peels of the one or more collected ripened fruits include Lychee peel, Pomegranate peel, Grapes peel, Dragon Fruit peel, and Kokum peel.
7. The method as claimed in claim 5, the aqueous extract of the fruit peels is concentrated by the vacuum evaporation at a temperature varies between 30°C and 50°C.